Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Tomoharu Yoshizumi Last modified date:2023.09.28

Professor / Department of Surgery and Science / Department of Clinical Medicine / Faculty of Medical Sciences


Papers
1. Toru Ikegami, Jong Man Kim, Dong-Hwan Jung, Yuji Soejima, Dong-Sik Kim, Jae-Won Joh, Sung-Gyu Lee, Tomoharu Yoshizumi, Masaki Mori, Conceptual changes in small-for-size graft and small-for-size syndrome in living donor liver transplantation., Korean journal of transplantation, 10.4285/jkstn.2019.33.4.65, 33, 4, 65-73, 2019.12, Early series in living donor liver transplantation (LDLT) in adults demonstrated a lower safe limit of graft volume standard liver volume ratio 25%-45%. A subsequent worldwide large LDLT series proposed a 0.8 graft recipient weight ratio (GRWR) to define small-for-size graft (SFSG) in adult LDLT. Thereafter, researchers identified innate and inevitable factors including changes in liver volume during imaging studies and graft shrinkage due to perfusion solution. Although the definition of small-for-size syndrome (SFSS) advocated in the 2000s was mainly based on prolonged cholestasis and ascites output, the term SFSS was inadequate to describe clinical manifestations possibly caused by multiple factors. Thus, the term "early allograft dysfunction (EAD)," characterized by total bilirubin >10 mg/dL or coagulopathy with international normalized ratio >1.6 on day 7, has become prevalent to describe graft dysfunction including SFSS after LDLT. Although various efforts have been made to overcome EAD in LDLT, graft selection to maintain an expected GRWR >0.8 and full venous drainage, as well as inflow modulation using splenic artery ligation, have become standard in recent LDLT..
2. Takeo Toshima, Tomoharu Yoshizumi, Noboru Harada, The authors' reply: Indispensable discrepancy between predicted graft "volume" and actual graft "weight" in clinical practice in living-donor liver transplantation., Annals of gastroenterological surgery, 10.1002/ags3.12492, 5, 6, 867-868, 2021.11, We would like to respond to the Letter to the Editor "'GRWR' or 'GV/SLV' in clinical practice in living donor liver transplantation" by Haruki et al, that is a comment on our original article "Which is better to use 'body weight' or 'standard liver weight,' for predicting small-for-size graft syndrome after living-donor liver transplantation?" in Annals of Gastroenterological Surgery..
3. 渡辺 亮, 播本 憲史, 新木 健一郎, 塚越 真梨子, 石井 範洋, 萩原 慶, 星野 弘毅, 村主 遼, 関 貴臣, 吉住 朋晴, 山下 洋市, 馬場 秀夫, 樋口 徹也, 調 憲, 進行再発大腸がんに対する効果的な外科治療介入を考える 大腸がん肝転移切除症例に対する早期再発とoverall survivalに基づいた切除戦略, 日本癌治療学会学術集会抄録集, 60回, OWS28-3, 2022.10.
4. Tomonari Shimagaki, Tomoharu Yoshizumi, Shinji Itoh, Norifumi Iseda, Takahiro Tomiyama, Akinari Morinaga, Huanlin Wang, Takeshi Kurihara, Yoshihiro Nagao, Takeo Toshima, Noboru Harada, Nao Kinjo, Takashi Maeda, Masaki Mori, The ratio of serum des-gamma-carboxy prothrombin to tumor volume as a new biomarker for early recurrence of resected hepatocellular carcinoma., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13750, 52, 4, 381-389, 2022.04, BACKGROUND: Early recurrence (ER) of hepatocellular carcinoma (HCC) (within 1 year after resection) is known to be a poor prognostic factor. The aim was to identify the risk factors associated with ER after HCC resection. METHODS: Data were analyzed retrospectively from patients who underwent primary resection for HCC from two hospitals. For cross-validation, HCC resection cases were divided into the training and testing cohort. The clinicopathological factors between the ER and non-ER groups and factors for predicting ER and prognosis after HCC resection were compared. RESULTS: Out of 173 patients in the training dataset, 33 patients had ER and the ER group showed larger tumor size, more intrahepatic metastasis (IM), and a higher ratio of serum des-gamma-carboxy prothrombin (DCP) to tumor volume (TV) (DCP/TV) than the non-ER group. Out of 203 patients in the testing dataset, 30 patients had ER and the ER group demonstrated larger tumor size, more IM, and higher serum alpha-fetoprotein, AFP/TV, DCP/TV, AFP/tumor maximum diameter (TMD), and DCP/TMD than the non-ER group. The patients were divided into high and low DCP/TV groups and high serum DCP/TV was associated with unfavorable overall survival in the training and testing dataset. Multivariate analysis confirmed that high serum DCP/TV and IM were independently associated with ER. CONCLUSION: Preoperative high serum DCP/TV may be useful for stratifying patients at risk of early HCC recurrence after curative resection..
5. Yumiko Kinoshita, Rieko Izukura, Junji Kishimoto, Maki Kanaoka, Hayato Fujita, Koji Ando, Shuntaro Nagai, Sayuri Akiyoshi, Tetsuzo Tagawa, Makoto Kubo, Junichi Inokuchi, Kenoki Ohuchida, Eiji Oki, Kentaro Tanaka, Masatoshi Eto, Tomoharu Yoshizumi, Masafumi Nakamura, Akiko Chishaki, Reliability, validity, and responsiveness of the Japanese version of the EORTC QLQ-ELD14 in evaluating the health-related quality of life of elderly patients with cancer., Journal of cancer research and clinical oncology, 10.1007/s00432-022-04414-2, 1-16, 2022.10, PURPOSE: This study evaluated the reliability, validity, and responsiveness of the Japanese version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-ELD14 and measured the health-related quality of life (HRQOL) of elderly Japanese patients with cancer aged ≥ 60 and ≥ 70 years. METHODS: The study recruited elderly Japanese patients with cancer aged ≥ 60 (≥ 70) years (n = 1803 [n = 1236]). The EORTC QLQ-ELD14 was evaluated for reliability, validity, responsiveness, and correlations of changes in score between the EORTC QLQ-ELD14 and the EORTC QLQ-C30 before and after the commencement of the COVID-19 pandemic. RESULTS: In both age groups, the proportion of missing items was low (< 3%). Cronbach's α was good at ≥ 0.70, except for two of the seven items. All the intraclass coefficient constants were good at ≥ 0.70. The concurrent validity was good but correlation with the EORTC QLQ-C30 was not strong, except for the hypothesis items. Regarding the assessment of responsiveness, only one item ("maintaining purpose") of the EORTC QLQ-ELD14 worsened (- 6.14 ± 29.20, standard response of mean > 0.2) after the commencement of the COVID-19 pandemic. The changes in score between the EORTC QLQ-ELD14 and the "global health status/QOL" and "summary score" of the EORTC QLQ-C30 had moderate-to-high negative correlations for all items, except two. Hypotheses to evaluate construct validity were accepted at 90%, while responsiveness was accepted at 80%. CONCLUSION: The Japanese version of the EORTC QLQ-ELD14 questionnaire appears to have acceptable reliability, validity, and responsiveness to evaluate HRQOL in elderly Japanese people with cancer..
6. Tomonari Shimagaki, Shinji Itoh, Katsuya Toshida, Takahiro Tomiyama, Akinari Morinaga, Yukiko Kosai, Takahiro Tomino, Takeshi Kurihara, Yoshihiro Nagao, Kazutoyo Morita, Noboru Harada, Tomoharu Yoshizumi, Prevention of bile duct injury using indocyanine green fluorescence in laparoscopic liver cyst fenestration for giant liver cyst: a case report., Journal of surgical case reports, 10.1093/jscr/rjac479, 2022, 10, rjac479, 2022.10, The case is a 78-year-old female. A giant liver cyst was pointed out by abdominal echo from 7 years ago, but because the size of the cyst tended to increase, it was decided to operate taking into account the risk of the cyst rupturing. Laparoscopic surgery was started, and the cyst contents did not fluorescent when observed by the indocyanine green (ICG) fluorescence method. Laparoscopic liver cyst fenestration was performed using the ICG fluorescence method, paying attention to the damage to the bile duct excluded by the cyst. The opened cyst was filled with the greater omentum. In this report, we describe that the ICG fluorescence method can evaluate the presence or absence of bile leakage from the hepatic dissection and the running of the bile duct on the inner wall of the cyst, and is considered to contribute to safer laparoscopic liver cyst fenestration..
7. Kyoto Matsudo, Naoki Haratake, Yuki Ono, Mikihiro Kohno, Tomoyoshi Takenaka, Tomoharu Yoshizumi, Multiple systemic artery to pulmonary vessel fistulas (SAPVFs) completely resected by video-assisted thoracoscopic surgery: a case report., Surgical case reports, 10.1186/s40792-022-01540-4, 8, 1, 184-184, 2022.09, BACKGROUND: Systemic artery to pulmonary vessel fistula (SAPVF) is an uncommon abnormal vascular communication between systemic arteries and the lung parenchyma. It has been reported that the appropriate treatment for SAPVF is embolization or surgical resection. However, in patients such as ours, who have many aberrant vessels or multiple lesions, surgery should be considered as the first-choice treatment. CASE PRESENTATION: This case report describes multiple SAPVFs and huge bullae at the apex of the left lung in a 43-year-old man that were resected completely with the video-assisted thoracoscopic surgery (VATS). The patient had an uneventful postoperative recovery without any complications and was discharged 9 days postoperatively. He had heavy smoking history, and the giant bullae and the diffuse emphysematous change were found in the lung. Therefore, the chronic inflammation may have been present in the thoracic cavity, which caused multiple SAPVFs. CONCLUSIONS: We describe the clinical course and management of the patient with multiple SAPVFs who had no obvious history of surgery, trauma, or various inflammatory or infection diseases. VATS should be the first-choice treatment in patients with many abnormal vessels or multiple lesions..
8. Asato Hashinokuchi, Naoki Haratake, Tomoyoshi Takenaka, Kyoto Matsudo, Taichi Nagano, Kenji Watanabe, Keisuke Kosai, Yuka Oku, Yuki Ono, Shinkichi Takamori, Mikihiro Kohno, Shingo Baba, Kousei Ishigami, Tomoharu Yoshizumi, Clinical significance of the combination of preoperative SUVmax and CEA in patients with clinical stage IA lung adenocarcinoma., Thoracic cancer, 10.1111/1759-7714.14599, 13, 18, 2624-2632, 2022.09, BACKGROUND: Preoperative maximum standardized uptake value (SUVmax) of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography and serum carcinoembryonic antigen (CEA) have been reported as prognostic factors for lung adenocarcinoma. However, the significance of combined SUVmax and CEA in early-stage lung adenocarcinoma is not well known. METHODS: We retrospectively evaluated the relationship between the combination of SUVmax and CEA and the prognosis of 410 patients with clinical stage IA lung adenocarcinoma who underwent resection. The cutoff values for SUVmax and CEA were determined by receiver operating characteristic curve analysis, and patients were categorized into high SC (SUVmax and CEA) group (SUVmax ≥2.96 and CEA ≥5.3), moderate SC group (either SUVmax <2.96 and CEA ≥5.3 or SUVmax ≥2.96 and CEA <5.3) and low SC group (SUVmax <2.96 and CEA <5.3). RESULTS: Kaplan-Meier curve analysis showed that patients with clinical stage IA lung adenocarcinoma in the high SC group had significantly shorter overall survival (OS) and recurrence-free survival (RFS) than the other groups (p = 0.011 and p < 0.0001, respectively). Multivariate analysis showed that high SC was an independent prognostic factor of OS (p = 0.029) and RFS (p < 0.0001). CONCLUSIONS: High values of SUVmax and CEA were associated with poor OS and RFS in patients with stage IA lung adenocarcinoma. Simultaneous evaluation of SUVmax and CEA may be an effective prognostic marker to determine the optimal treatment strategy of early-stage lung adenocarcinoma..
9. Shinji Itoh, Takahiro Tomiyama, Akinari Morinaga, Takeshi Kurihara, Yoshihiro Nagao, Takeo Toshima, Kazutoyo Morita, Noboru Harada, Masaki Mori, Tomoharu Yoshizumi, Clinical effects of the use of the indocyanine green fluorescence imaging technique in laparoscopic partial liver resection., Annals of gastroenterological surgery, 10.1002/ags3.12563, 6, 5, 688-694, 2022.09, AIM: This study aimed to clarify the clinical effects of the indocyanine green (ICG)-fluorescence imaging (FI) technique for determination of liver transection lines during laparoscopic partial liver resection for liver tumors. METHODS: This was a retrospective study including 112 patients who underwent laparoscopic partial liver resection for liver tumors. These enrolled patients were divided into an ICG-FI group (n = 55) and a non-ICG-FI group (n = 57) according to the availability of the ICG-FI. The clinicopathological characteristics of patients between two groups were compared before and after propensity score matching. RESULTS: The ICG-FI and non-ICG-FI groups differed at baseline in terms of ICG retention rate at 15 min. After propensity score matching, two comparable groups of 32 patients each were obtained. The negativity rated of the pathological surgical margins were comparable between the two groups before and after propensity score matching. However, the surgical margins were significantly wider in the ICG-FI group before and after propensity score matching (P = .039 and P = .047, respectively). CONCLUSION: The ICG-fluorescence imaging technique may offer clinical benefits in terms of a secure surgical margin in laparoscopic partial liver resection..
10. Shinji Itoh, Katsuya Toshida, Kazutoyo Morita, Takeshi Kurihara, Yoshihiro Nagao, Takahiro Tomino, Takeo Toshima, Noboru Harada, Masaki Mori, Tomoharu Yoshizumi, Clinical effectiveness of surgical treatment after lenvatinib administration for hepatocellular carcinoma., International journal of clinical oncology, 10.1007/s10147-022-02229-2, 27, 11, 1725-1732, 2022.11, BACKGROUND: There is little evidence concerning survival after surgery in patients with hepatocellular carcinoma who have received lenvatinib treatment. The aim of this study was to evaluate whether post-lenvatinib surgical treatment in patients with hepatocellular carcinoma improves overall survival. METHODS: The cohort of this retrospective study comprised 55 patients with hepatocellular carcinoma who had undergone lenvatinib treatment. We classified them into two groups according to post-lenvatinib surgical treatment status and compared clinicopathologic factors and prognosis between the two groups with the aim of identifying predictors of overall survival. RESULTS: The median duration of lenvatinib administration was 5.8 months (range, 0.4-24.0 months). Twelve of the 55 patients underwent surgery after receiving lenvatinib. There was no significant difference in assessed clinicopathological factors between patients who did and did not undergo surgery after being treated with lenvatinib. Multivariate analysis revealed that older age was associated with a significantly worse overall survival (hazard ratio: 2.332; 95% confidence interval 1.062-5.168; P = 0.0369) and that surgery after treatment with lenvatinib achieved better overall survival than other forms of treatment (hazard ratio: 0.121; 95% confidence interval 0.016-0.901; P = 0.0393). CONCLUSIONS: Surgical treatment after lenvatinib administration may be a useful therapeutic option for select patients with hepatocellular carcinoma..
11. Satomi Tanaka, Kimie Fujita, Kanako Yakushiji, Noboru Harada, Tomoharu Yoshizumi, Changes in Physical Activity Due to Fear of COVID-19 and Its Impact on Depression Among Post-Liver Transplant Patients in Japan: A Longitudinal Survey Study., Annals of transplantation, 10.12659/AOT.938239, 27, e938239, 2022.12, BACKGROUND Regular physical activity (PA) is important for maintaining mental and physical health after liver transplantation (LT); however, the fluctuations in routine PA during COVID-19 and its putative impacts are currently unknown. This study examined the changes in PA during the COVID-19 pandemic and explored its association with fear and depression during the pandemic. MATERIAL AND METHODS This longitudinal study included 83 LT patients whose PA was measured using the short form of the International Physical Activity Questionnaire before and during COVID-19. Fear of COVID-19 was estimated based on previous studies, and depression was assessed using the Patient Health Questionnaire-9. Participants were also asked about important sources of information on COVID-19. PA was classified as inactive or active depending on the changes in PA, and logistic regression analyses with PA as a dependent variable were conducted to explore the associations among PA, depression, and fear of COVID-19. RESULTS Moderate and high PA exhibited decreasing trends before and during the COVID-19 pandemic, especially in males. Fear of being infected with SARS-CoV-2, the virus that causes COVID-19, while shopping was significantly higher in females and was significantly independent of inactivity during the COVID-19 pandemic. Only 1 patient reported that their transplant center was their main source of information about COVID-19. Only 4.9% of the LT participants were depressed. CONCLUSIONS Our study results indicate the need to support the provision of accurate information about COVID-19 by health care professionals in transplant centers, especially for patients with low PA, to prevent PA decline in LT patients..
12. Yoshihiro Nagao, Katsuya Toshida, Akinari Morinaga, Takahiro Tomiyama, Yukiko Kosai, Tomonari Shimagaki, Takahiro Tomino, Huanlin Wang, Takeshi Kurihara, Takeo Toshima, Kazutoyo Morita, Shinji Itoh, Noboru Harada, Tomoharu Yoshizumi, Caution for living donor liver transplantation with congenital portosystemic shunt: a case report., Surgical case reports, 10.1186/s40792-022-01533-3, 8, 1, 190-190, 2022.10, BACKGROUND: Congenital portosystemic shunt is an infrequent abnormal connection between the portal vascular system and the systemic circulation. Portosystemic shunts are common findings in patients with cirrhosis, causing gastroesophageal varices, hepatic encephalopathy, and others. However, there is no consensus or literature describing how to manage asymptomatic patients with portosystemic shunts and normal liver. CASE PRESENTATION: The patient was a 39-year-old female who underwent donor right hepatectomy for living donor liver transplantation. The patient was healthy by nature, however, developed hepatic encephalopathy after the surgery due to a development of portosystemic shunt. Portosystemic shunt stole portal blood flow, and imaging modalities revealed narrowing of the portal trunk, representing prolonged depletion of portal blood flow. Balloon-occluded retrograde transvenous obliteration (B-RTO) was performed for occlusion of the portosystemic shunt. B-RTO increased portal blood flow, and hepatic encephalopathy with hyperammonemia was successfully resolved without the outbreak of any other symptom of portal hypertension. CONCLUSIONS: A congenital portosystemic shunt itself is not a contraindication for donor hepatectomy, but perioperative endovascular shunts occlusion or intraoperative ligature of these shunts should be considered..
13. Katsuya Toshida, Takeo Toshima, Noboru Harada, Yuki Nakayama, Takahiro Tomiyama, Akinari Morinaga, Yukiko Kosai-Fujimoto, Takahiro Tomino, Takeshi Kurihara, Yoshihiro Nagao, Kazutoyo Morita, Shinji Itoh, Tomoharu Yoshizumi, Autoimmune Hepatitis in an Immunosuppression-Free Patient Who Underwent Living Donor Liver Transplantation From an Identical Twin: A Case Report., Transplantation proceedings, 10.1016/j.transproceed.2022.09.022, 54, 10, 2791-2793, 2022.12, Although there have been a few liver transplantations (LTs) between identical twins, to our knowledge hepatic damage after LT in an immunosuppressant-free patient has not been reported. Autoimmune liver disease recurrence after LT is also a postoperative problem. In this follow-up to our previous report, we present the case of a 57-year-old man with acute liver failure who underwent living donor liver transplantation (LDLT) from an identical twin. Six months after LDLT, the patient was free from immunosuppressive medication and showed good liver function. However, 1 year after LDLT, he developed liver damage and was diagnosed with autoimmune hepatitis by liver biopsy. His liver function was improved with steroid pulse therapy and the resumption of immunosuppressive medications. Even after LDLT from an identical twin, careful management is required for patients to remain free of immunosuppressive medications, considering the background liver disease..
14. Hiroyuki Suzuki, Hideki Iwamoto, Takahiro Seki, Toru Nakamura, Atsutaka Masuda, Takahiko Sakaue, Toshimitsu Tanaka, Yasuko Imamura, Takashi Niizeki, Masahito Nakano, Shigeo Shimose, Tomotake Shirono, Yu Noda, Naoki Kamachi, Miwa Sakai, Kazutoyo Morita, Masamichi Nakayama, Tomoharu Yoshizumi, Ryoko Kuromatsu, Hirohisa Yano, Yihai Cao, Hironori Koga, Takuji Torimura, Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors., Cancer communications (London, England), 10.1002/cac2.12411, 43, 4, 415-434, 2023.04, BACKGROUND: Antiangiogenic tyrosine kinase inhibitors (TKIs) provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma (HCC). However, patients with HCC often develop resistance toward antiangiogenic TKIs, and the underlying mechanisms are not understood. The aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in HCC. METHODS: We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC patients. We evaluated the prognosis, therapeutic response, and serum insulin-like growth factor-binding protein-1 (IGFBP-1) levels of 31 lenvatinib-treated HCC patients. Based on the array of results, a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were conducted. Additionally, in vivo genetic and pharmacological gain- and loss-of-function experiments were performed. RESULTS: In the patient cohort, IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall survival. Mechanistically, antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor signaling. IGFBP-1 stimulated angiogenesis through activation of the integrin α5β1-focal adhesion kinase pathway. Consequently, loss of IGFBP-1 and integrin α5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib treatment. CONCLUSIONS: Together, our data shed light on mechanisms underlying acquired resistance of HCC to antiangiogenic TKIs. Antiangiogenic TKIs induced an increase of tumor IGFBP-1, which promoted angiogenesis through activating the IGFBP-1-integrin α5β1 pathway. These data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors..
15. Gouji Toyokawa, Francesca Bersani, Paolo Bironzo, Francesca Picca, Fabrizio Tabbò, Naoki Haratake, Tomoyoshi Takenaka, Takashi Seto, Tomoharu Yoshizumi, Silvia Novello, Giorgio V Scagliotti, Riccardo Taulli, Tumor plasticity and therapeutic resistance in oncogene-addicted non-small cell lung cancer: from preclinical observations to clinical implications., Critical reviews in oncology/hematology, 10.1016/j.critrevonc.2023.103966, 184, 103966-103966, 2023.04, The identification of actionable targets in oncogene-addicted non-small cell lung cancer (NSCLC) has fueled biomarker-directed strategies, especially in advanced stage disease. Despite the undeniable success of molecular targeted therapies, duration of clinical response is relatively short-lived. While extraordinary efforts have defined the complexity of tumor architecture and clonal evolution at the genetic level, not equal interest has been given to the dynamic mechanisms of phenotypic adaptation engaged by cancer during treatment. At the clinical level, molecular targeted therapy of EGFR-mutant and ALK-rearranged tumors often results in epithelial-to-mesenchymal transition (EMT) and histological transformation of the original adenocarcinoma without the acquisition of additional genetic lesions, thus limiting subsequent therapeutic options and patient outcome. Here we provide an overview of the current understanding of the genetic and non-genetic molecular circuits governing this phenomenon, presenting current strategies and potentially innovative therapeutic approaches to interfere with lung cancer cell plasticity..
16. Shohei Yoshiya, Noboru Harada, Takeo Toshima, Katsuya Toshida, Yukiko Kosai, Takahiro Tomino, Yoshihiro Nagao, Hiroto Kayashima, Shinji Itoh, Tomoharu Yoshizumi, Treatment strategy for hepatocellular carcinoma recurrence in the transplant era: Focusing on the Japan criteria., Surgery today, 10.1007/s00595-023-02710-z, 2023.06, PURPOSE: To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria. METHODS: The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging. RESULTS: Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging. CONCLUSION: Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes..
17. Koichi Morisaki, Daisuke Matsuda, Atsushi Guntani, Yutaka Matsubara, Go Kinoshita, Shogo Kawanami, Sho Yamashita, Kenichi Honma, Tadashi Furuyama, Terutoshi Yamaoka, Shinsuke Mii, Kimihiro Komori, Tomoharu Yoshizumi, Treatment outcomes between bypass surgery and endovascular therapy in patients with chronic limb-threatening ischemia classified as bypass-preferred category based on Global Vascular Guidelines., Journal of vascular surgery, 10.1016/j.jvs.2023.04.006, 2023.04, OBJECTIVE: The aim of this study was to examine outcomes between bypass surgery and endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI), classified as bypass-preferred according to the Global Vascular Guidelines (GVG). METHODS: We retrospectively analyzed the multi-center data of patients who underwent infrainguinal revascularization for CLTI with Wound, Ischemia, and foot Infection (WIfI) Stage 3 to 4 and Global Limb Anatomical Staging System (GLASS) Stage III, which is classified as bypass-preferred category by the GVG between 2015 and 2020. The endpoints were limb salvage and wound healing. RESULTS: We analyzed 301 patients and 339 limbs following 156 bypass surgeries and 183 EVTs. The 2-year limb salvage rates were 92.2% in the bypass surgery group and 76.3% in the EVT group, respectively (P < .01). The 1-year wound healing rates were 86.7% in the bypass surgery group and 67.8% in the EVT group (P < .01). Multivariate analysis shows decreased serum albumin level (P < .01), increased wound grade (P = .04), and EVT (P < .01) were risk factors for major amputation. Decreased serum albumin level (P < .01), increased wound grade (P < .01), GLASS infrapopliteal grade (P = .02), inframalleolar (IM) P grade (P = .01), and EVT (P < .01) were risk factors for impaired wound healing. Subgroup analysis of limb salvage in patients after EVT, decreased serum albumin level (P < .01), increased wound grade (P = .03), increased IM P grade (P = .04), and congestive heart failure (P < .01) were risk factors for major amputation. According to scoring by existence of these risk factors, 2-year limb salvage rates following EVT were 83.0% and 42.8% for the total score of 0 to 2 and of 3 to 4, respectively (P < .01). CONCLUSIONS: Bypass surgery provides better limb salvage and wound healing in patients with WIfI Stage 3 to 4 and GLASS Stage III, which is classified as bypass-preferred category by the GVG. In patients after EVT, serum albumin level, wound grade, IM P grade, and congestive heart failure were related to major amputation. Although bypass surgery may be considered as initial revascularization procedure in patients classified as bypass-preferred category, in case that EVT has to be selected, relatively acceptable outcomes can be expected in patients with less of these risk factors..
18. Katsuya Toshida, Shinji Itoh, Hiroto Kayashima, Yoshihiro Nagao, Shohei Yoshiya, Takahiro Tomino, Yukiko Kosai Fujimoto, Yuriko Tsutsui, Yuki Nakayama, Noboru Harada, Tomoharu Yoshizumi, The hemoglobin, albumin, lymphocyte, and platelet score is a prognostic factor for Child-Pugh A patients undergoing curative hepatic resection for single and small hepatocellular carcinoma., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13885, 53, 6, 522-530, 2023.06, AIM: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score reflects the immune system and the nutritional status of patients, and prognosis in various cancers. However, the HALP score in hepatocellular carcinoma has not been reported. METHODS: Data were analyzed retrospectively from Child-Pugh A patients undergoing hepatic resection for single hepatocellular carcinoma ≤5 cm. For cross-validation, patients were divided into the training (332 patients) and validation cohort (210 patients). In the training cohort, we divided patients into two groups by appropriate cut-off value of the HALP score, and univariable and multivariable analyses were conducted for disease-free and overall survival (OS) between two groups. In the validation cohort, we examined OS by Kaplan-Meier analysis in the same cut-off value of the HALP score in the training cohort. RESULTS: The HALP-low group was significantly older (p = 0.0003), had fewer hepatitis B surface antigen-positive patients (p = 0.0369), higher prothrombin time (p = 0.0141), lower fibrosis-4 index (p = 0.0206), bigger maximum tumor size (p = 0.0196), and less histological liver fibrosis (p = 0.0077). Multivariate analysis showed that the independent prognostic factors for disease-free survival were fibrosis-4 index ≥2.67 (p = 0.0008), simple nodular type with extranodular growth or confluent multinodular type (p = 0.0221), and intrahepatic metastasis (p = 0.0233), and that for OS were fibrosis-4 index ≥2.67 (p = 0.0020), HALP ≤45.6 (p = 0.0228), and poor differentiation (p = 0.0305). In the validation cohort, Kaplan-Meier analysis revealed the trend toward significantly impaired OS (p = 0.0220) in the HALP-low group. CONCLUSION: We showed that a low HALP score is the independent prognostic factor for Child-Pugh A patients undergoing curative hepatic resection for single and small hepatocellular carcinoma..
19. Eiji Oki, Mitsuhiko Ota, Tomonori Nakanoko, Yasushi Tanaka, Satoshi Toyota, Qingjiang Hu, Yu Nakaji, Ryota Nakanishi, Koji Ando, Yasue Kimura, Yuichi Hisamatsu, Koshi Mimori, Yoshiya Takahashi, Hajime Morohashi, Takahiro Kanno, Kotaro Tadano, Kenji Kawashima, Hironobu Takano, Yuma Ebihara, Masaki Shiota, Junichi Inokuchi, Masatoshi Eto, Tomoharu Yoshizumi, Kenichi Hakamada, Satoshi Hirano, Masaki Mori, Telesurgery and telesurgical support using a double-surgeon cockpit system allowing manipulation from two locations., Surgical endoscopy, 10.1007/s00464-023-10061-6, 1-8, 2023.05, BACKGROUND: Although several studies on telesurgery have been reported globally, a clinically applicable technique has not yet been developed. As part of a telesurgical study series conducted by the Japan Surgical Society, this study describes the first application of a double-surgeon cockpit system to telesurgery. METHODS: Surgeon cockpits were installed at a local site and a remote site 140 km away. Three healthy pigs weighing between 26 and 29 kg were selected for surgery. Non-specialized surgeons performed emergency hemostasis, cholecystectomy, and renal vein ligation with remote assistance using the double-surgeon cockpits and specialized surgeons performed actual telesurgery. Additionally, the impact of adding internet protocol security (IPsec) encryption to the internet protocol-virtual private network (IP-VPN) line on communication was evaluated to address clinical security concerns. RESULTS: The average time required for remote emergency hemostasis with the double-surgeon cockpit system was 10.64 s. A non-specialized surgeon could safely perform cholecystectomy or renal vein ligation with remote assistance. Global Evaluative Assessment of Robotic Skills and System Usability Scale scores were higher for telesurgical support-assisted surgery by a non-specialized surgeon using the double-surgeon cockpits than for telesurgery performed by a specialized surgeon without the double-cockpit system. Adding IPsec encryption to the IP-VPN did not have a significant impact on communication. CONCLUSION: Telesurgical support through our double-surgeon cockpit system is feasible as first step toward clinical telesurgery..
20. Shotaro Kinoshita, Yo-Ichi Yamashita, Yuki Kitano, Hiromitsu Hayashi, Keishi Sugimachi, Takashi Nishizaki, Kengo Fukuzawa, Kiyoshi Kajiyama, Nobutomo Miyanari, Tomoharu Yoshizumi, Hiroshi Takamori, Hideo Baba, Survival impact of pancreatic resection for metastases in the pancreas: A retrospective multi-center study., Surgical oncology, 10.1016/j.suronc.2023.101942, 48, 101942-101942, 2023.06, BACKGROUND: Pancreatic metastases from other primary malignancies are rare. There is no clear evidence for a treatment strategy for this condition. The purpose of this study was to assess the clinical outcomes, including prognostic factors for pancreatic resection of metastatic tumors in the pancreas, through a retrospective review. METHODS: Data of 35 patients who underwent pancreatic resection for pancreatic metastasis between 2005 and 2020 in eight Japanese institutions were included in this study. Survival analyses were performed using the Kaplan-Meier method, and comparisons were made using the Cox proportional hazards model. RESULTS: The median follow-up period was 35 months (range, 5-102 months). Median duration from resection for primary tumor to resection for metastatic pancreatic tumor was 10.6 years (range, 0.6-29.2 years). The 3- and 5-year survival rates after resection for metastatic tumors in the pancreas were 89% and 69%, respectively. In contrast, the 3- and 5-year disease-free survival rates after resection for metastatic tumors in the pancreas were 48% and 21%, respectively. Performance status ≥1 at the time of resection for metastatic tumors in the pancreas (HR: 7.56, p = 0.036) and pancreatic metastasis tumor diameter >42 mm (HR: 6.39, p = 0.02) were significant poor prognostic factors only in the overall survival. CONCLUSIONS: The prognosis of pancreatic resection for metastatic tumors in the pancreas is relatively good for selected patients. However, because it is prone to recurrence after radical surgery, it should only be considered in patients with good PS..
21. Jin Shiraishi, Shinji Itoh, Takahiro Tomino, Shohei Yoshiya, Yoshihiro Nagao, Hiroto Kayashima, Noboru Harada, Ichiro Sakamoto, Hiroyuki Tsutsui, Tomoharu Yoshizumi, Surgical treatment of hepatocellular carcinoma after Fontan operation: three case reports and review of the literature., Clinical journal of gastroenterology, 10.1007/s12328-023-01795-w, 2023.04, We herein describe three patients with Fontan-associated liver disease who developed hepatocellular carcinoma (HCC). The first patient was a 28-year-old woman who had undergone the Fontan operation (FO) at the age of 4 years. She was diagnosed with HCC (cT4aN0M0, Stage IVA, UICC 8th edition), for which she underwent extended posterior right sectionectomy and partial hepatectomy of S2. She developed recurrence of peritoneal dissemination after 12 months, and she was alive 18 months after surgery. The second patient was a 43-year-old man who had undergone the FO at the age of 3 years. He was diagnosed with HCC (cT2N0M0, Stage II), for which he underwent laparoscopic-assisted partial hepatectomy of S3. He remained free from recurrent HCC for 17 months. The third patient was a 21-year-old woman who had undergone the FO at the age of 3 years. She was diagnosed with HCC (cT3N0M0, Stage III), for which she underwent laparoscopic-assisted partial hepatectomy of S2 and S4. She remained free from recurrent HCC for 30 months. We reviewed 18 surgical cases of HCC arising from Fontan-associated liver disease, including our 3 cases, and found that a high preoperative alpha-fetoprotein concentration might be a predictor of HCC recurrence..
22. Masaki Kaibori, Kengo Yoshii, Yuzo Umeda, Takahito Yagi, Takehiro Okabayashi, Kenta Sui, Akira Mori, Yuhei Hamaguchi, Kiyoshi Kajiyama, Daisuke Hokuto, Kazuteru Monden, Tomoharu Yoshizumi, Yoriko Nomura, Kan Toriguchi, Jong Man Kim, Gi Hong Choi, Je Ho Ryu, Yangseok Koh, Koo Jeong Kang, Young Kyoung You, Kwang-Sik Chun, Young Seok Han, Chan Woo Cho, Young Il Choi, Dong-Sik Kim, Jae Do Yang, Keita Mori, Atsushi Hiraoka, Hiroki Yamaue, Masafumi Nakamura, Masakazu Yamamoto, Itaru Endo, Surgical Outcomes of Laparoscopic versus Open Hepatectomy for Left Hepatocellular Carcinoma: Propensity Score Analyses Using Retrospective Japanese and Korean Individual Patient Data., Liver cancer, 10.1159/000527294, 12, 1, 32-43, 2023.02, INTRODUCTION: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC). METHODS: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups. RESULTS: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group. CONCLUSIONS: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver..
23. Sachie Omori, Tomoko Shigechi, Kana Kawaguchi, Hideki Ijichi, Eiji Oki, Tomoharu Yoshizumi, Successful Prevention of Tumour Lysis Syndrome in HER2-positive Breast Cancer: Case Report and Literature Review., Anticancer research, 10.21873/anticanres.16403, 43, 5, 2371-2377, 2023.05, BACKGROUND/AIM: Tumour lysis syndrome (TLS) is a life-threatening oncological emergency. TLS is rare and associated with a higher mortality rate in solid tumours than in haematological malignancies. Our case report and literature review aimed to identify the distinctive features and hazards of TLS in breast cancer. CASE REPORT: A 41-year-old woman complained of vomiting and epigastric pain and was diagnosed with HER2-positive, hormone-receptor-positive breast cancer with multiple liver and bone metastases and lymphangitis carcinomatosis. She had several risk factors for TLS: high tumour volume, high sensitivity to antineoplastic treatment, multiple liver metastases, high lactate dehydrogenase levels, and hyperuricaemia. To prevent TLS, she was treated with hydration and febuxostat. One day after the first course of trastuzumab and pertuzumab, she was diagnosed with disseminated intravascular coagulation (DIC). After 3 further days of observation, she was relieved of DIC and administered a reduced dose of paclitaxel without life-threatening complications. The patient achieved a partial response after four cycles of anti-HER2 therapy and chemotherapy. CONCLUSION: TLS in solid tumours is a lethal situation and can be complicated by DIC. Early recognition of patients who are at risk of TLS and initiation of therapy is essential to avoid fatal situations..
24. Kenji Watanabe, Fumihiko Kinoshita, Tomoyoshi Takenaka, Taichi Nagano, Yuka Oku, Keisuke Kosai, Yuki Ono, Naoki Haratake, Mikihiro Kohno, Takeshi Kamitani, Tadamasa Yoshitake, Tatsuro Okamoto, Mototsugu Shimokawa, Kousei Ishigami, Tomoharu Yoshizumi, Skeletal muscle area predicts the outcomes of non-small-cell lung cancer after trimodality therapy., Interdisciplinary cardiovascular and thoracic surgery, 10.1093/icvts/ivad020, 36, 2, 2023.02, OBJECTIVES: Sarcopenia correlates with poor prognosis in various malignancies. However, the prognostic significance of sarcopenia remains to be determined in patients with non-small-cell lung cancer who undergo surgery after receiving neoadjuvant chemoradiotherapy (NACRT). METHODS: We retrospectively reviewed the patients with stage II/III non-small-cell lung cancer who underwent surgery following NACRT. The paravertebral skeletal muscle area (SMA) (cm2) at the 12th thoracic vertebra level was measured. We calculated the SMA index (SMAI) as SMA/squared height (cm2/m2). Patients were divided into low and high SMAI groups, and the association of SMAI with clinicopathological factors and prognosis was assessed. RESULTS: The patients' [men, 86 (81.1%)] median age was 63 (21-76) years. There were 106 patients including 2 (1.9%), 10 (9.4%), 74 (69.8%), 19 (17.9%) and 1 (0.9%) patients with stage IIA, IIB, IIIA, IIIB and IIIC, respectively. Of the patients, 39 (36.8%) and 67 (63.2%) were classified in the low and the high SMAI groups, respectively. Kaplan-Meier analysis showed that the low group had a significantly shorter overall survival and disease-free survival than the high group. Multivariable analysis identified low SMAI as an independent poor prognostic factor for overall survival. CONCLUSIONS: Pre-NACRT SMAI correlates with poor prognosis; therefore, assessing sarcopenia based on pre-NACRT SMAI may help determine optimal treatment strategies and suitable nutritional and exercise interventions..
25. Fumihiko Kinoshita, Mototsugu Shimokawa, Tomoyoshi Takenaka, Tatsuro Okamoto, Kenichi Taguchi, Yoshinao Oda, Tomoharu Yoshizumi, Prognostic impact of noninvasive areas in resected pathological stage IA lung adenocarcinoma., Thoracic cancer, 10.1111/1759-7714.14910, 2023.04, MAIN PROBLEMS: In non-small-cell lung cancer, ground-glass opacity on computed tomography imaging reflects pathological noninvasiveness and is a favorable prognostic factor. However, the significance of pathological noninvasive areas (NIAs) has not been fully revealed. In this study, we aimed to elucidate the prognostic impact of NIAs on lung adenocarcinoma. METHODS: We analyzed 402 patients with pathological stage (p-Stage) IA lung adenocarcinoma who underwent surgery in 2013-2016 at two institutions and examined the association of the presence of NIAs with clinicopathological factors and prognosis. Furthermore, after using propensity-score matching to adjust for clinicopathological factors, such as age, sex, smoking history, pathological invasive area size, pathological T factor (p-T), p-Stage, and histological subtype (lepidic predominant adenocarcinoma [LPA] or non-LPA), the prognostic impact of NIAs was evaluated. RESULTS: Patients were divided into NIA-present (N = 231) and NIA-absent (N = 171) groups. Multivariable analysis showed that NIA-present was strongly associated with earlier p-T, earlier p-Stage, LPA, and epidermal growth factor receptor mutation. Kaplan-Meier survival analysis showed that the NIA-present group displayed a better prognosis than the NIA-absent group in disease-free survival (DFS) and overall survival (OS) (5-year DFS 94.6% vs. 87.2%, 5-year OS 97.2% vs. 91.1%). However, after adjusting for clinicopathological factors by propensity score matching, no significant differences in prognosis were identified between the NIA-present and NIA-absent groups (5-year DFS 92.4% vs 89.6%, 5-year OS 95.6% vs 94.3%). CONCLUSIONS: Our current study suggests that the prognostic impact of the presence of NIAs on lung adenocarcinoma is due to differences in clinicopathological factors..
26. Taichi Nagano, Fumihiko Kinoshita, Asato Hashinokuchi, Kyoto Matsudo, Kenji Watanabe, Shinkichi Takamori, Mikihiro Kohno, Naoko Miura, Mototsugu Shimokawa, Tomoyoshi Takenaka, Tomoharu Yoshizumi, Prognostic Impact of C-Reactive Protein-to-Lymphocyte Ratio in Non-small Cell Lung Cancer: A Propensity Score-Matching Analysis., Annals of surgical oncology, 10.1245/s10434-023-13250-8, 30, 6, 3781-3788, 2023.06, BACKGROUND: Many inflammatory and nutritional markers have been used to predict prognosis in lung cancer. The C-reactive protein (CRP)-to-lymphocyte ratio (CLR) is a useful prognostic factor in various cancers. However, the prognostic value of preoperative CLR in patients with non-small cell lung cancer (NSCLC) remains to be established. We examined the significance of the CLR compared with known markers. METHODS: A total of 1380 surgically resected NSCLC patients treated at two centers were recruited and divided into derivation and validation cohorts. After CLRs were calculated, patients were classified into high and low CLR groups based on the cutoff value determined by receiver operating characteristics curve analysis. Subsequently, we determined the statistical associations of the CLR with clinicopathological factors and prognosis and further analyzed its prognostic impact by propensity-score matching. RESULTS: Of all the inflammatory markers examined, CLR yielded the highest area-under-the-curve value. The prognostic impact of CLR remained significant after propensity-score matching. Prognosis was significantly worse in the high-CLR group than in the low-CLR group (5-year, disease-free survival [DFS]: 58.1% vs. 81.9%, P < 0.001; 5-year overall survival [OS]: 72.1% vs. 91.2%, P < 0.001). The results were confirmed in the validation cohorts. Multivariable analysis also showed high CLR as an independent factor for both DFS and OS (DFS: hazard ratio [HR] 1.42, P = 0.027; OS: HR 1.95, P = 0.0037). CONCLUSIONS: Preoperative CLR is a useful marker for predicting the prognosis of NSCLC patients who have undergone surgery..
27. Katsuya Toshida, Shinji Itoh, Yuki Nakayama, Yuriko Tsutsui, Yukiko Kosai-Fujimoto, Takahiro Tomino, Shohei Yoshiya, Yoshihiro Nagao, Noboru Harada, Kenichi Kohashi, Yoshinao Oda, Tomoharu Yoshizumi, Preoperative HALP score is a prognostic factor for intrahepatic cholangiocarcinoma patients undergoing curative hepatic resection: association with sarcopenia and immune microenvironment., International journal of clinical oncology, 10.1007/s10147-023-02358-2, 2023.05, BACKGROUND: The hemoglobin-albumin-lymphocyte-platelet (HALP) score is a combination index that assesses nutritional status and systemic inflammatory response and is reported to predict prognosis in several cancer types. However, researches about the usefulness of the HALP score in intrahepatic cholangiocarcinoma (ICC) are limited. METHODS: This was a single-center, retrospective study of 95 patients who underwent surgical resection for ICC between 1998 and 2018. We divided patients into two groups by calculating the cutoff value of the HALP score and examined clinicopathological characteristics, prognosis, and sarcopenia. Tumor-infiltrating lymphocytes (TILs), CD8 + TILs, and FOXP3 + TILs were evaluated by immunohistochemical staining of resected tumors. RESULTS: Of 95 patients, 22 were HALP-low. The HALP-low group had significantly lower hemoglobin (p = 0.0007), lower albumin (p = 0.0013), higher platelet counts (p < 0.0001), fewer lymphocytes (p < 0.0001), higher CA19-9 levels (p = 0.0431), and more lymph node metastasis (p = 0.0013). Multivariate analysis revealed that the independent prognostic factors for disease-free survival were maximum tumor size (≥ 5.0 cm) (p = 0.0033), microvascular invasion (p = 0.0108), and HALP score (≤ 25.2) (p = 0.0349), and that factors for overall survival were lymph node metastasis (p = 0.0020) and HALP score (≤ 25.2) (p = 0.0014). The HALP-low group contained significantly more patients with sarcopenia (p = 0.0015). Immunohistochemistry showed that counts of CD8 + TILs were significantly lower in the HALP-low group (p = 0.0075). CONCLUSIONS: We demonstrated that low HALP score is an independent prognostic factor for ICC patients undergoing curative hepatic resection and is associated with sarcopenia and the immune microenvironment..
28. Nao Nishida, Jun Ohashi, Goki Suda, Takehiro Chiyoda, Nobuharu Tamaki, Takahiro Tomiyama, Sachiko Ogasawara, Masaya Sugiyama, Yosuke Kawai, Seik-Soon Khor, Masao Nagasaki, Akihiro Fujimoto, Takayo Tsuchiura, Miyuki Ishikawa, Koichi Matsuda, Hirohisa Yano, Tomoharu Yoshizumi, Namiki Izumi, Kiyoshi Hasegawa, Naoya Sakamoto, Masashi Mizokami, Katsushi Tokunaga, Prediction Model with HLA-A*33:03 Reveals Number of Days to Develop Liver Cancer from Blood Test., International journal of molecular sciences, 10.3390/ijms24054761, 24, 5, 2023.03, The development of liver cancer in patients with hepatitis B is a major problem, and several models have been reported to predict the development of liver cancer. However, no predictive model involving human genetic factors has been reported to date. For the items incorporated in the prediction model reported so far, we selected items that were significant in predicting liver carcinogenesis in Japanese patients with hepatitis B and constructed a prediction model of liver carcinogenesis by the Cox proportional hazard model with the addition of Human Leukocyte Antigen (HLA) genotypes. The model, which included four items-sex, age at the time of examination, alpha-fetoprotein level (log10AFP) and presence or absence of HLA-A*33:03-revealed an area under the receiver operating characteristic curve (AUROC) of 0.862 for HCC prediction within 1 year and an AUROC of 0.863 within 3 years. A 1000 repeated validation test resulted in a C-index of 0.75 or higher, or sensitivity of 0.70 or higher, indicating that this predictive model can distinguish those at high risk of developing liver cancer within a few years with high accuracy. The prediction model constructed in this study, which can distinguish between chronic hepatitis B patients who develop hepatocellular carcinoma (HCC) early and those who develop HCC late or not, is clinically meaningful..
29. Mitsuhiko Ota, Hiroshi Saeki, Hideo Uehara, Yoshiko Matsuda, Satoshi Tsutsumi, Tetsuya Kusumoto, Hisateru Yasui, Yasunari Ubukata, Shohei Yamaguchi, Hiroyuki Orita, Naoki Izawa, Saburo Kakizoe, Mototsugu Shimokawa, Tomoharu Yoshizumi, Yoshihiro Kakeji, Masaki Mori, Eiji Oki, Phase II clinical trial to study the safety and efficacy of combined S-1 + oxaliplatin therapy as neoadjuvant chemotherapy for locally advanced gastric cancer in older patients., International journal of clinical oncology, 10.1007/s10147-023-02373-3, 2023.06, BACKGROUND: Gastrectomy with D2 dissection and adjuvant chemotherapy is the standard treatment for locally advanced gastric cancer (LAGC) in Asia. However, administering chemotherapy with sufficient intensity after gastrectomy is challenging. Several trials demonstrated the efficacy of neoadjuvant chemotherapy (NAC). However, limited studies explored the feasibility of NAC-SOX for older patients with LAGC. This phase II study (KSCC1801) evaluated the safety and efficacy of NAC-SOX in patients with LAGC aged ≥ 70 years. METHODS: Patients received three cycles of SOX130 (oxaliplatin 130 mg/m2 on day 1, oral S-1 40-60 mg twice daily for two weeks every three weeks) as NAC, followed by gastrectomy with lymph node dissection. The primary endpoint was the dose intensity (DI). The secondary endpoints were safety, R0 resection rate, pathological response rate (pRR), overall survival, and relapse-free survival. RESULTS: The median age of 26 enrolled patients was 74.5 years. The median DI in NAC-SOX130 was 97.2% for S-1 and 98.3% for oxaliplatin. Three cycles of NAC were administered in 25 patients (96.2%), of whom 24 (92.3%) underwent gastrectomy with lymphadenectomy. The R0 resection rate was 92.3% and the pRR (≥ grade 1b) was 62.5%. The major adverse events (≥ grade 3) were neutropenia (20.0%), thrombocytopenia (11.5%), anorexia (11.5%), nausea (7.7%), and hyponatremia (7.7%). Postoperative complications of abdominal infection, elevated blood amylase, and bacteremia occurred in one patient each. Severe diarrhea and dehydration caused one treatment-related death. CONCLUSIONS: NAC-SOX130 is a feasible therapy for older patients, although systemic management and careful monitoring of adverse events are necessary..
30. Yutaka Matsubara, Shogo Kawanami, Go Kinoshita, Shun Kurose, Yoshino Shinichiro, Koichi Morisaki, Tadashi Furuyama, Tomoharu Yoshizumi, Perioperative therapeutic antibiotics are beneficial to prevent exacerbation of limb-associated infection after bypass surgery in patients with critical limb-threatening ischemia and foot infection score of ≥1., Vascular, 10.1177/17085381231154608, 17085381231154608-17085381231154608, 2023.01, OBJECTIVE: Postoperative limb infection is associated with a poor prognosis and a low amputation-free survival rate after surgical revascularization in patients with critical limb-threatening ischemia. The Global Vascular Guidelines 2019 recommend antibiotic therapy for patients with deep space foot infection or wet gangrene; however, no study is cited as evidence for this recommendation. The present study was performed to offer new evidence supporting the use of perioperative therapeutic antibiotics in patients with critical limb-threatening ischemia (CLTI) undergoing surgical revascularization. METHODS: This single-center retrospective study was performed in Kyushu University Hospital and involved patients with CLTI who underwent surgical revascularization from 2003 to 2021. Ampicillin/sulbactam and cefazolin were defined as preventive antibiotics, and other types were defined as therapeutic antibiotics. Postoperative limb-associated infection was defined as an increased foot infection (fI) score in the Wound, Ischemia, and foot Infection (WIfI) classification system after surgical revascularization. The association between perioperative antibiotic therapy and postoperative limb-associated infection was assessed. RESULTS: Among 286 limbs of 263 patients with CLTI, 27 (9%) limbs developed postoperative limb-associated infection after surgical revascularization. The fI scores were significantly higher in the patients with than without postoperative limb-associated infection (1.0 ± 0.2 vs 0.4 ± 0.1, respectively; p = 0.0033), indicating that an fI score of ≥1 was a risk factor for postoperative limb-associated infection. Perioperative therapeutic antibiotics significantly reduced the incidence of postoperative limb-associated infection compared with preventive antibiotics (0.0% vs. 44.8%, respectively; p = 0.0028) in the patients with CLTI who had an fI score of ≥1 after bypass surgery, although perioperative therapeutic antibiotics were not effective for patients with an fI score of 0. CONCLUSION: Perioperative therapeutic antibiotics for patients with an fI score of ≥1 are beneficial for reducing the incidence of postoperative limb-associated infection after surgical revascularization..
31. Takayuki Nakanishi, Yasuto Yoneshima, Koji Okamura, Toyoshi Yanagihara, Mikiko Hashisako, Takeshi Iwasaki, Naoki Haratake, Shun Mizusaki, Keiichi Ota, Eiji Iwama, Tomoyoshi Takenaka, Kentaro Tanaka, Tomoharu Yoshizumi, Yoshinao Oda, Isamu Okamoto, MicroRNA-326 negatively regulates CD155 expression in lung adenocarcinoma., Cancer science, 10.1111/cas.15921, 2023.08, Treatment with immune checkpoint inhibitors induces a durable response in some patients with non-small-cell lung cancer, but eventually gives rise to drug resistance. Upregulation of CD155 expression is implicated as one mechanism of resistance to programmed death receptor-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors, and it is therefore important to characterize the mechanisms underlying regulation of CD155 expression in tumor cells. The aim of this study was to identify microRNAs (miRNAs) that might regulate CD155 expression at the posttranscriptional level in lung cancer. Comprehensive miRNA screening with target prediction programs and a dual-luciferase reporter assay identified miR-346, miR-328-3p, miR-326, and miR-330-5p as miRNAs that bind to the 3'-UTR of CD155 mRNA. Forced expression of these miRNAs suppressed CD155 expression in lung cancer cell lines. Immunohistochemical staining of CD155 in tissue specimens from 57 patients with lung adenocarcinoma revealed the median tumor proportion score for CD155 to be 68%. The abundance of miR-326 in these specimens with a low level of CD155 expression was significantly greater than in specimens with a high level (p < 0.005). Our results thus suggest that miR-326 negatively regulates CD155 expression in lung adenocarcinoma and might therefore play a role in the development of resistance to PD-1/PD-L1 inhibitors..
32. Shinichiro Yoshino, Yutaka Matsubara, Shun Kurose, Sho Yamashita, Koichi Morisaki, Tadashi Furuyama, Tomoharu Yoshizumi, Left Renal Vein Division during Open Surgical Repair for Abdominal Aortic Aneurysm May Cause Long-Term Kidney Remodeling., Annals of vascular surgery, 10.1016/j.avsg.2023.03.035, 2023.04, BACKGROUND: Left renal vein division (LRVD) is a maneuver performed during open surgical repair for abdominal aortic aneurysms. Even so, the long-term effects of LRVD on renal remodeling are unknown. Therefore, we hypothesized that interrupting the venous return of the left renal vein might cause renal congestion and fibrotic remodeling of the left kidney. METHODS: We used a murine left renal vein ligation model with 8-week-old to 12-week-old wild-type male mice. Bilateral kidneys and blood samples were harvested postoperatively on days 1, 3, 7, and 14. We assessed the renal function and the pathohistological changes in the left kidneys. In addition, we retrospectively analyzed 174 patients with open surgical repairs between 2006 and 2015 to assess the influence of LRVD on clinical data. RESULTS: Temporary renal decline with left kidney swelling occurred in a murine left renal vein ligation model. In the pathohistological assessment of the left kidney, macrophage accumulation, necrotic atrophy, and renal fibrosis were observed. In addition, Myofibroblast-like macrophage, which is involved in renal fibrosis, was observed in the left kidney. We also noted that LRVD was associated with temporary renal decline and left kidney swelling. LRVD did not, however, impair renal function in long-term observation. Additionally, the relative cortical thickness of the left kidney in the LRVD group was significantly lower than that of the right kidney. These findings indicated that LRVD was associated with left kidney remodeling. CONCLUSIONS: Venous return interruption of the left renal vein is associated with left kidney remodeling. Furthermore, interruption in the venous return of the left renal vein does not correlate with chronic renal failure. Therefore, we suggest careful follow-up of renal function after LRVD..
33. Tomoyoshi Takenaka, Tokujiro Yano, Koji Yamazaki, Tatsuro Okamoto, Motoharu Hamatake, Shinkichi Takamori, Mikihiro Kohno, Naoko Miura, Mototsugu Shimokawa, Tomoharu Yoshizumi, Is radical local therapy effective in postoperative recurrent EGFR-mutated non-small cell lung cancer?, Thoracic cancer, 10.1111/1759-7714.14911, 2023.05, BACKGROUND: Long-term survival can be achieved with radical local therapy in some cases of postoperative recurrence of non-small cell lung cancer (NSCLC). Here, we evaluated post-recurrence survival (PRS) after treatment of postoperative recurrent epidermal growth factor receptor (EGFR) mutated NSCLC and examined the effectiveness of radical local therapy. METHODS: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data (e.g., treatment and survival outcomes) were obtained and analyzed. RESULTS: From 2010 to 2015, 505 patients with recurrent NSCLC were enrolled into the study, and 154 EGFR mutation-positive cases were included. As the initial treatment for recurrence, 111 patients (72%) received chemotherapy, 14 (9%) received chemoradiotherapy, 14 (9%) received definitive radiotherapy, and seven (5%) received surgical resection. The remaining eight patients (5%) received supportive care. The median PRS and 5-year survival rates for all cases were 64 months and 53.2%, respectively. The 5-year survival rate according to the initial treatment was as follows: supportive care, 0%; chemotherapy, 53.3% and radical local therapy, 60.1%. The six patients who received radical local treatment remained recurrence-free for more than 3 years after recurrence with only initial treatment. CONCLUSIONS: Although radical local therapy may be curative in some patients, chemotherapy including EGFR-TKI treatment is expected to provide long-term survival comparable to that of radical local therapy..
34. Shun Kurose, Yutaka Matsubara, Shinichiro Yoshino, Keiji Yoshiya, Koichi Morisaki, Tadashi Furuyama, Tomoaki Hoshino, Tomoharu Yoshizumi, Interleukin-38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2-p38 pathway-dependent manner., Physiological reports, 10.14814/phy2.15581, 11, 2, e15581, 2023.01, Macrophages play crucial roles in abdominal aortic aneurysm (AAA) formation through the inflammatory response and extracellular matrix degradation; therefore, regulating macrophages may suppress AAA formation. Interleukin-38 (IL-38) is a member of the IL-1 family, which binds to IL-36 receptor (IL1RL2) and has an anti-inflammation effect. Because macrophages express IL1RL2, we hypothesized that IL-38 suppresses AAA formation by controlling macrophages. We assessed a C57BL6/J mouse angiotensin II-induced AAA model with or without IL-38 treatment. RAW 264.7 cells were cultured with tumor necrosis factor-α and treated with or without IL-38. Because p38 has important roles in inflammation, we assessed p38 phosphorylation in vitro and in vivo. To clarify whether the IL-38 effect depends on the p38 pathway, we used SB203580 to inhibit p38 phosphorylation. IL1RL2+ macrophage accumulation along with matrix metalloproteinase (MMP)-2 and -9 expression was observed in mouse AAA. IL-38 reduced the incidence of AAA formation along with reduced M1 macrophage accumulation and MMP-2 and -9 expression in the AAA wall. Macrophage activities including inducible nitric oxide, MMP-2, and MMP-9 production and spindle-shaped changes were significantly suppressed by IL-38. Furthermore, we revealed that inhibition of p38 phosphorylation diminished the effects of IL-38 on regulating macrophages to reduce AAA incidence, indicating the protective effects of IL-38 depend on the p38 pathway. IL-38 plays protective roles against AAA formation through regulation of macrophage accumulation in the aortic wall and modulating the inflammatory phenotype. Using IL-38 may be a novel therapy for AAA patients..
35. Yuka Oku, Gouji Toyokawa, Sho Wakasu, Fumihiko Kinoshita, Shinkichi Takamori, Kenji Watanabe, Naoki Haratake, Taichi Nagano, Keisuke Kosai, Kazuki Takada, Airi Fujimoto, Kodo Higashijima, Yoshimasa Shiraishi, Kentaro Tanaka, Hiroaki Takeoka, Masaki Okamoto, Takanori Yamashita, Mototsugu Shimokawa, Fumihiro Shoji, Koji Yamazaki, Tatsuro Okamoto, Takashi Seto, Hitoshi Ueda, Sadanori Takeo, Naoki Nakashima, Isamu Okamoto, Tomoyoshi Takenaka, Tomoharu Yoshizumi, Impact of the pretreatment prognostic nutritional index on the survival after first-line immunotherapy in non-small-cell lung cancer patients., Cancer medicine, 10.1002/cam4.6110, 2023.05, BACKGROUND: Immunotherapy has become a standard-of-care for patients with non-small-cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death-1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first-line ICI combined with or without chemotherapy. MATERIALS AND METHODS: Two-hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first-line therapy. Cutoff value of the pretreatment PNI was set as 42.17. RESULTS: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression-free survival (PFS; hazard ratio [HR] =  0.67, 95% confidence interval [CI]: 0.51-0.88, p =  0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32-0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p =  0.0011) and OS (p  < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). CONCLUSION: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first-line ICI therapy..
36. Koichi Morisaki, Atsushi Guntani, Go Kinoshita, Shogo Kawanami, Sho Yamashita, Yutaka Matsubara, Tadashi Furuyama, Shinsuke Mii, Kimihiro Komori, Tomoharu Yoshizumi, Impact of ambulatory status change on survival in patients with chronic limb-threatening ischemia undergoing infrainguinal surgical or endovascular revascularization., Journal of vascular surgery, 10.1016/j.jvs.2023.03.024, 2023.03, OBJECTIVE: This study aimed to evaluate the influence of change in ambulatory status on the prognosis of patients with chronic limb-threatening ischemia (CLTI) undergoing infrainguinal bypass surgery or endovascular therapy (EVT). METHODS: We retrospectively analyzed data from two vascular centers for patients who underwent revascularization for CLTI between 2015 and 2020. The primary endpoint was overall survival (OS), and the secondary endpoints were changes in ambulatory status and postoperative complications. RESULTS: Throughout the study, 377 patients and 508 limbs were analyzed. In the preoperative nonambulation cohort, the average body mass index (BMI) was lower in the postoperative nonambulatory group than in the postoperative ambulatory group (P < .01). The percentage of cerebrovascular disease (CVD) was higher in the postoperative nonambulatory group than in the postoperative ambulatory group (P = .01). In the preoperative ambulation cohort, the average controlling nutritional status (CONUT) score was higher in the postoperative nonambulatory group than in the postoperative ambulatory group (P < .01). There was no difference in the bypass percentage and the EVT in the preoperative nonambulation (P = .32) and ambulation (P = .70) cohorts. According to the change in ambulatory status before and after revascularization, the 1-year OS rates were 86.8% in the ambulatory → ambulatory group, 81.1% in the nonambulatory → ambulatory group, 54.7% in the nonambulatory → nonambulatory group, and 23.9% in the ambulatory → nonambulatory group (P < .01). On multivariate analysis, increased age (P = .04), higher Wound, Ischemia, and foot Infection stage (P = .02), and increased CONUT score (P < .01) were independent risk factors for the decline in ambulatory status in patients with preoperative ambulation. In patients with preoperative nonambulation, increased BMI (P < .01) and absence of CVD (P = .04) were independent factors related to the improved ambulatory status. The percentages of postoperative complications were 31.0% and 17.0% in the preoperative nonambulation and the preoperative ambulation in the overall cohort (P < .01). Preoperative nonambulatory status (P < .01), CONUT score (P < .01), and bypass surgery (P < .01) were risk factors for postoperative complications. CONCLUSIONS: Improved ambulatory status is associated with better OS in patients with preoperative nonambulatory status after infrainguinal revascularization for CLTI. Although patients with preoperative nonambulatory status have a risk of postoperative complication, some may benefit from revascularization if they have no factors such as low BMI and CVD, improving their ambulatory status..
37. Toshio Ichiki, Yuichi Yamada, Takamichi Ito, Takeshi Nakahara, Yasuharu Nakashima, Masafumi Nakamura, Tomoharu Yoshizumi, Akira Shiose, Koichi Akashi, Yoshinao Oda, Histological and immunohistochemical prognostic factors of primary angiosarcoma., Virchows Archiv : an international journal of pathology, 10.1007/s00428-023-03572-z, 483, 1, 59-69, 2023.06, Angiosarcoma is a malignant vascular endothelial neoplasm with various histological patterns. Despite its highly malignant potential, histological prognostic prediction has not been adopted for angiosarcoma. This study aimed to establish a method of predicting the prognosis of primary angiosarcoma. Formalin-fixed, paraffin-embedded samples from 104 primary angiosarcomas were prepared. All the cases were reviewed based on histological examinations with H&E staining. Because the French Fédération Nationale des Centres de Lutte Contre Le Cancer system (FNCLCC) is not adopted for angiosarcoma, we experimentally established a modified version of FNCLCC. Immunohistochemical staining for ERG, CD31, CD34, D2-40, HHV-8, p16, C-MYC, and p53 was performed. Fluorescence in situ hybridization (FISH) was performed for 31 cases to assay c-MYC gene amplification. Multivariate analysis revealed that age (> 70 years old) (p = 0.0011), non-cutaneous angiosarcoma (p = 0.0265), metastasis on diagnosis (p < 0.0001), size ≥ 5 cm (p = 0.0388), no taxane chemotherapy (p = 0.0388), strong nuclear atypia (p = 0.0087), and the presence of luminal structure in ≥ 50% of the tumor volume (p = 0.0009) were independent poor prognostic factors. Among angiosarcomas with luminal formation, mFNCLCC scores were significantly correlated with a poorer prognosis. The overexpression of p16 was associated with less luminal formation (p = 0.0192). Immunohistochemical analysis of C-MYC showed a moderate level of concordance with FISH (Kappa value = 0.45). This study suggested that luminal formation and nuclear atypia may be poor histological prognostic factors of angiosarcoma and that mFNCLCC would be useful for predicting the prognosis of angiosarcoma with luminal formation..
38. Koichi Morisaki, Daisuke Matsuda, Yutaka Matsubara, Shun Kurose, Shinichiro Yoshino, Go Kinoshita, Kenichi Honma, Terutoshi Yamaoka, Tadashi Furuyama, Tomoharu Yoshizumi, Global Limb Anatomic Staging System Inframalleolar Modifier Predicts Limb Salvage and Wound Healing in Patients with Chronic Limb Threatening Ischaemia Undergoing Endovascular Infrainguinal Revascularisation., European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery, 10.1016/j.ejvs.2022.11.023, 65, 3, 391-397, 2023.03, OBJECTIVE: This study aimed to analyse the influence of the Global Anatomic Staging System (GLASS) and inframalleolar (IM) disease on the treatment outcomes of patients with chronic limb threatening ischaemia (CLTI) who undergo endovascular treatment (EVT) METHODS: Data of patients who underwent infrainguinal endovascular therapy (EVT) for CLTI between 2015 and 2019 at two centres were analysed retrospectively. The endpoints were major amputation, major adverse limb events (MALE), and wound healing. RESULTS: Overall, 276 patients and 340 limbs were analysed. The number of revascularisations for an infrapopliteal lesion was 48 (70.6%), 63 (63.0%), and 142 (82.6%) in the GLASS I, GLASS II, and GLASS III stages, respectively (p < .001). There was no statistically significant difference in limb salvage among the GLASS stages (p = .78). The limb salvage rates at one year were 94.6%, 88.0%, and 70.0% in the IM P0 P1, and P2 groups, respectively (p < .001). Multivariable analysis showed that Wound, Ischemia, and foot Infection (WIfI) stage, and IM grade were risk factors for major amputation. The freedom from MALE rates at two years were 60.5%, 45.3%, and 41.1% in the GLASS I, II, and III stages, respectively (p = .003) and 64.1%, 43.5%, and 18.4% in the IM P0, P1, and P2 groups, respectively (p < .001). Multivariable analysis demonstrated that WIfI stage, GLASS stage, IM grade, and infrapopliteal revascularisation were risk factors for MALE. There was no significant difference in wound healing among GLASS I - III (p = .75). The wound healing rates at 365 days were 78.6%, 68.6%, and 42.0% in the IM P0, P1, and P2 groups, respectively (p = .065). Multivariable analysis showed that WIfI stage and IM P2 were risk factors for incomplete wound healing. CONCLUSION: GLASS IM was associated with major amputation, MALE, and wound healing, while GLASS stage was associated with only MALE..
39. Yukio Tokumitsu, Hiroaki Nagano, Yo-Ichi Yamashita, Tomoharu Yoshizumi, Toru Hisaka, Atsushi Nanashima, Tamotsu Kuroki, Takao Ide, Yuichi Endo, Tohru Utsunomiya, Kenji Kitahara, Yota Kawasaki, Masahiko Sakota, Kohji Okamoto, Yuko Takami, Masatoshi Kajiwara, Mitsuhisa Takatsuki, Toru Beppu, Susumu Eguchi, Efficacy of laparoscopic liver resection for small hepatocellular carcinoma located in the posterosuperior segments: A multi-institutional study using propensity score matching by the Kyushu Study Group of Liver Surgery., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13929, 2023.05, AIM: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. METHODS: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. RESULTS: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. CONCLUSIONS: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS..
40. Hiroto Kayashima, Shinji Itoh, Mototsugu Shimokawa, Hiromitsu Hayashi, Hiroshi Takamori, Kengo Fukuzawa, Mizuki Ninomiya, Kenichiro Araki, Yo-Ichi Yamashita, Keishi Sugimachi, Hideaki Uchiyama, Yuji Morine, Tohru Utsunomiya, Tadashi Uwagawa, Takashi Maeda, Hideo Baba, Tomoharu Yoshizumi, Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial., International journal of clinical oncology, 10.1007/s10147-023-02399-7, 2023.08, BACKGROUND: Six-month adjuvant chemotherapy with S-1 is standard care for resected pancreatic cancer in Japan; however, the optimal duration has not been established. We aimed to evaluate the impact of duration of adjuvant chemotherapy with S-1. METHODS: We performed a multicenter, randomized, open-label, phase II study. Patients with histologically proven invasive pancreatic ductal carcinoma, pathological stage I-III, and no local residual or microscopic residual tumor were eligible. Patients were randomized 1:1 to receive 6- or 12-month adjuvant chemotherapy with S-1. The primary endpoint was 2-year overall survival (OS). Secondary endpoints were disease-free survival (DFS) and feasibility. RESULTS: A total of 170 patients were randomized (85 per group); the full analysis set was 82 in both groups. Completion rates were 64.7% (6-month group) and 44.0% (12-month group). Two-year OS was 71.5% (6-month group) and 65.4% (12-month group) (hazard ratio (HR): 1.143; 80% confidence interval CI 0.841-1.553; P  =  0.5758). Two-year DFS was 46.4% (6-month group) and 44.9% (12-month group) (HR: 1.069; 95% CI 0.727-1.572; P = 0.6448). In patients who completed the regimen, 2-year DFS was 56.5% (6-month group) and 75.0% (12-month group) (HR: 0.586; 95% CI 0.310-1.105; P  = 0.0944). Frequent (≥ 5%) grade ≥ 3 adverse events comprised anorexia (10.5% in the 6-month group) and diarrhea (5.3% vs. 5.1%; 6- vs. 12-month group, respectively). CONCLUSIONS: In patients with resected pancreatic cancer, 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS..
41. Koichi Morisaki, Daisuke Matsuda, Yutaka Matsubara, Terutoshi Yamaoka, Tadashi Furuyama, Tomoharu Yoshizumi, Editor's Choice - Bypass Surgery Provides Better Wound Healing than Endovascular Treatment in Global Limb Anatomic Staging System Inframalleolar Modifier P1., European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery, 10.1016/j.ejvs.2023.01.048, 65, 5, 758-759, 2023.05.
42. Taichi Nagano, Naoki Haratake, Kyoto Matsudo, Asato Hashinokuchi, Kenji Watanabe, Shinkichi Takamori, Mikihiro Kohno, Naoko Miura, Tomoyoshi Takenaka, Tomoharu Yoshizumi, Conservative treatment for residual lung congestion after left upper trisegmentectomy: a case report., Translational cancer research, 10.21037/tcr-22-2104, 12, 2, 421-426, 2023.02, BACKGROUND: Currently, segmentectomy is the procedure of choice in approximately 10% of lung cancer surgeries in Japan. However, complications are often observed in that procedure. In particular, residual pulmonary congestion after segmentectomy often leads to surgical intervention. CASE DESCRIPTION: We report a case of improved congestion in the residual lung after left upper trisegmentectomy (LUTS) with conservative treatment under careful observation. A 65-year-old man was diagnosed with bilateral lung cancer and initially underwent LUTS. On the next day after surgery, blood sputum was observed. Computed tomography (CT) showed consolidation in the lingual region of the left lung and stenosis of V4+5 in the left lung. The cause of the congestion was thought to be an isolated segment with part of the remaining S3 and a thin V4+5 with poor flow. Because pulmonary torsion or necrosis of the residual lung was not observed, conservative treatment with antibiotics under careful follow-up by CT was chosen. The pulmonary congestion and inflammatory reaction gradually improved, and the patient was discharged home on the 26th day after surgery. CONCLUSIONS: We experienced a case of residual pulmonary congestion after LUTS that resolved with conservative treatment. Careful follow-up of the patient's general condition and imaging studies are considered to be important..
43. Atsushi Fukunaga, Kazuhide Takata, Shinji Itoh, Ryo Yamauchi, Takashi Tanaka, Keiji Yokoyama, Satoshi Shakado, Kenichi Kohashi, Tomoharu Yoshizumi, Fumihito Hirai, Complete tumor necrosis confirmed by conversion hepatectomy after atezolizumab-bevacizumab treatment for advanced-stage hepatocellular carcinoma with lung metastasis., Clinical journal of gastroenterology, 10.1007/s12328-022-01744-z, 16, 2, 224-228, 2023.04, A combined therapy of atezolizumab and bevacizumab (atezo/bev) is used as the first-line treatment for unresectable hepatocellular carcinoma (HCC). In this study, we report the case of curative hepatic resection in a 77-year-old man who initially had unresectable advanced-stage HCC with lung metastases. This rare hepatectomy conversion was owing to the administration of atezo/bev. Notwithstanding the side effects of immune-related adverse event hepatitis and intratumoral hemorrhage developed during atezo/bev treatment; after seven treatment cycles, the patient's tumor markers normalized, the tumor shrank markedly, and the metastasis disappeared. Subsequently, conversion therapy with hepatic resection was performed, and pathology confirmed complete tumor necrosis. No cancer recurrence was observed at the 8-month postoperative follow-up, and the patient remained drug free..
44. Taichi Nagano, Shinkichi Takamori, Asato Hashinokuchi, Kyoto Matsydo, Mikihiro Kohno, Naoko Miura, Tomoyoshi Takenaka, Takeshi Kamitani, Mototsugu Shimokawa, Kousei Ishigami, Yoshinao Oda, Tomoharu Yoshizumi, Comparison of radiological and pathological tumor sizes in resected non-small cell lung cancer., General thoracic and cardiovascular surgery, 10.1007/s11748-023-01938-3, 2023.05, OBJECTIVES: In non-small cell lung cancer (NSCLC), T factor plays an important role in determining staging. The present study aimed to determine the validity of preoperative evaluation of clinical T (cT) factor by comparing radiological and pathological tumor sizes. METHODS: Data for 1,799 patients with primary NSCLC who underwent curative surgery were investigated. The concordance between cT and pathological T (pT) factors was analyzed. Furthermore, we compared groups with an increase or decrease of ≥ 20% and groups with an increase or decrease of < 20% in the size change between preoperative radiological and pathological diameters. RESULTS: The mean sizes of the radiological solid components and the pathological invasive tumors were 1.90 cm and 1.99 cm, respectively, correlation degree = 0.782. The group with increased pathological invasive tumor size (≥ 20%) compared with the radiologic solid component was significantly more likely female, consolidation tumor ratio (CTR) ≤ 0.5, and within cT1. Multivariate logistic analysis identified CTR < 1, cT ≤ T1, and adenocarcinoma as independent risk factors for increased pT factor. CONCLUSION: The radiological invasive area of tumors with cT1, CTR < 1, or adenocarcinoma on preoperative CT may be underestimated compared with pathological invasive diameter..
45. Katsuya Toshida, Takeo Toshima, Shinji Itoh, Shohei Yoshiya, Takahiko Mukaino, Takayuki Fujii, Mitsuru Watanabe, Ryo Yamasaki, Noriko Isobe, Tomoharu Yoshizumi, Caution to Poor Adherence With Immunosuppressant Medication That Causes Coma-Onset Autoimmune Encephalitis: A Case Report and Literature Review., Transplantation proceedings, 10.1016/j.transproceed.2023.07.005, 2023.07, Autoimmune encephalitis after liver transplantation (LT) is a rare disorder. This is because patients are usually in an immunosuppressed state after LT. Here, we report a rare case of autoantibody-negative autoimmune-encephalitis-induced coma after living-donor (LD) LT. A 45-year-old woman who underwent LDLT for primary biliary cholangitis (PBC) was brought to our hospital with the chief complaint of cognitive deficiency and an episode of memory loss. Physical examination, laboratory tests, and cerebrospinal fluid analysis revealed no significant findings. However, diffusion-weighted magnetic resonance imaging showed hyperintensity in the bilateral hippocampus. No autoantibodies associated with autoimmune encephalitis were detected. The diagnosis of antibody-negative autoimmune encephalitis was made on the basis of low immunosuppressive drug levels in the blood (indicative of poor adherence) and the presence of PBC as the autoimmune disease. The patient regained consciousness after intravenous methylprednisolone pulse therapy and plasma exchange. This case highlights that when examining patients with impaired consciousness after LDLT, it is important to consider autoimmune encephalitis as a potential diagnosis..
46. Shinichiro Yoshino, Koichi Morisaki, Daisuke Matsuda, Atsushi Guntani, Go Kinoshita, Yutaka Matsubara, Shogo Kawanami, Sho Yamashita, Kenichi Honma, Tadashi Furuyama, Terutoshi Yamaoka, Shinsuke Mii, Kimihiro Komori, Tomoharu Yoshizumi, Bypass Surgery Provides Better Outcomes Compared with Endovascular Therapy in Patients with Chronic Limb-Threatening Ischemia Classified as Indeterminate Category According to the Global Vascular Guidelines., Annals of vascular surgery, 10.1016/j.avsg.2023.05.014, 2023.05, BACKGROUND: The present study aimed to determine the preferred initial revascularization procedure between bypass surgery and endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI) categorized as indeterminate according to the Global Vascular Guidelines (GVG). METHODS: We retrospectively analyzed the multicenter data of patients who underwent infrainguinal revascularization for CLTI categorized as indeterminate according to the GVG between 2015 and 2020. The end point was the composite of relief from rest pain, wound healing, major amputation, reintervention, or death. RESULTS: A total of 255 patients with CLTI and 289 limbs were analyzed. Of the 289 limbs, 110 (38.1%) and 179 (61.9%) underwent bypass surgery and EVT, respectively. The 2-year event-free survival rates with respect to the composite end point were 63.4% and 28.7% in the bypass and EVT groups, respectively (P < 0.01). Multivariate analysis revealed that increased age (P = 0.03); decreased serum albumin level (P = 0.02); decreased body mass index (P = 0.02); dialysis-dependent end-stage renal disease (P < 0.01); increased Wound, Ischemia, and foot Infection (WIfI) stage (P < 0.01); Global Limb Anatomic Staging System (GLASS) III (P = 0.04); increased inframalleolar grade (P < 0.01); and EVT (P < 0.01) were independent risk factors for the composite end point. In the WIfI-GLASS 2-III and 4-II subgroups, bypass surgery was superior to EVT with regard to 2-year event-free survival (P < 0.01). CONCLUSIONS: Bypass surgery is superior to EVT in terms of the composite end point in patients classified as indeterminate according to the GVG. Bypass surgery should be considered an initial revascularization procedure, especially in the WIfI-GLASS 2-III and 4-II subgroups..
47. Hirofumi Hasuda, Tetsuo Ikeda, Yutaka Makizaki, Haruka Yokota, Yoshiki Tanaka, Hiroshi Ohno, Mototsugu Shimokawa, Hiroya Matsuoka, Yasue Kimura, Eiji Oki, Tomoharu Yoshizumi, Alterations in the gut microbiome in patients with esophageal carcinoma in response to esophagectomy and neoadjuvant treatment., Surgery today, 10.1007/s00595-022-02607-3, 53, 6, 663-674, 2023.06, PURPOSE: Analyzing the gut microbiome is essential for planning treatment strategies to manage esophageal squamous cell carcinoma. This study aimed to characterize the gut microbiome of patients with esophageal squamous cell carcinoma and to identify alterations in its composition during treatment. METHODS: We observed alterations in the gut microbiome in 21 consecutive patients with esophageal squamous cell carcinoma at five different time points, from neoadjuvant treatment to postoperative surgery. Ten healthy individuals were used as a non-cancer control group. Fecal samples were collected and analyzed using 16S ribosomal ribonucleic acid sequencing. RESULTS: Before treatment, participants with esophageal squamous cell carcinoma had different alpha and beta diversity in comparison to healthy controls. The number of Streptococcus, a facultative anaerobic bacterium, was significantly higher, whereas that of Faecalibacterium, an obligate anaerobic bacterium, was significantly lower. Both alpha and beta diversity remained unchanged during neoadjuvant treatment, but the alterations were pronounced after surgery. The increase in the relative abundance of Streptococcus and the decrease in that of Faecalibacterium also tended to be more pronounced after surgery. CONCLUSIONS: The gut microbiome in patients with esophageal squamous cell carcinoma is altered with surgical intervention..
48. Taichi Nagano, Fumihiko Kinoshita, Asato Hashinokuchi, Kyoto Matsudo, Kenji Watanabe, Shinkichi Takamori, Mikihiro Kohno, Naoko Miura, Mototsugu Shimokawa, Tomoyoshi Takenaka, Tomoharu Yoshizumi, ASO Visual Abstract: Prognostic Impact of C-Reactive Protein-to-Lymphocyte Ratio in Non-small Cell Lung Cancer-A Propensity Score Matching Analysis., Annals of surgical oncology, 10.1245/s10434-023-13396-5, 30, 6, 3789-3789, 2023.06.
49. Expression of hypoxia-inducible factor-1 alpha, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma : correlation with poor prognosis with possible regulation.
50. N. Harimoto, Y. Yoshida, T. Kurihara, K. Takeishi, S. Itoh, N. Harada, E. Tsujita, Y. -I. Yamashita, H. Uchiyama, Y. Soejima, T. Ikegami, T. Yoshizumi, H. Kawanaka, T. Ikeda, K. Shirab'e, H. Saeki, E. Oki, Y. Kimura, Y. Maehara, Prognostic Impact of Des-gamma-carboxyl Prothrombin in Living-Donor Liver Transplantation for Recurrent Hepatocellular Carcinoma, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2014.09.178, 47, 3, 703-704, 2015.04, Background. Although the Milan criteria are widely accepted for liver transplantation (LT) in patients for hepatocellular carcinoma (HCC), they have not been fully evaluated for salvage LT in patients with recurrent HCC. We have previously reported outcomes of living-donor LT (LDLT) for HCC and identified 2 risk factors affecting recurrence-free survival (RF'S): tumor size >5 cm and des-gamma-carboxyl prothrombin (DCP) concentration >300 mAU/mL (Kyushu University criteria). This study was designed to clarify risk factors for tumor recurrence after LDLT in patients with recurrent HCC.
Methods. Outcomes in 114 patients who underwent LDLT for recurrent HCC were analyzed retrospectively. RFS rates after LDLT were calculated, and risk factors for tumor recurrence were identified.
Results. The 1-, 3-, and 5-year RFS rates after LDLT were 90.6%, 80.4%, and 78.8%, respectively. Univariate analysis showed that tumor recurrence was associated with alpha-fetoprotein concentration >= 300 ng/mL, DCP concentration >300 mAU/mL, tumor number >= 4, tumor size >= 5 cm, transarterial chemotherapy before LDLT, duration of last treatment of HCC to LDLT <3 months, bilobar distribution, exceeding Milan criteria, exceeding Kyushu University criteria, poor differentiation, and histologic vascular invasion. Multivariate analysis showed that DCP >= 300 mAU/mL (P = .03) and duration from last treatment to LDLT <3 months (P = .01) were independent predictors of RFS.
Conclusions. DCP concentration and time between last treatment and LDLT are prognostic of RFS in patients undergoing LDLT for HCC..
51. 下川 雅弘, 吉住 朋晴, 伊藤 心二, 間野 洋平, 本村 貴志, 戸島 剛男, 原田 昇, 播本 憲史, 池上 徹, 副島 雄二, 前原 喜彦, 酸化ストレス応答因子Nrf2の肝細胞癌における発現の臨床的および生物学的意義, 日本癌学会総会記事, 76回, J-3046, 2017.09.
52. 伊藤 心二, 吉住 朋晴, 下川 雅弘, 間野 洋平, 本村 貴志, 戸島 剛男, 原田 昇, 播本 憲史, 池上 徹, 副島 雄二, 前原 喜彦, 肝細胞癌におけるリンパ球/単球比とPD-L1発現の関連に関する検討, 日本癌学会総会記事, 76回, J-3047, 2017.09.
53. 池上 徹, 吉住 朋晴, 大平 将史, 本村 貴志, 間野 洋平, 戸島 剛男, 伊藤 心二, 原田 昇, 播本 憲史, 副島 雄二, 前原 喜彦, 全肝移植における死体肝移植ドナー移植片のサイズ不適合を解決する方法(How to overcome graft-body size mismatching in deceased donor whole liver transplantation), 日本外科学会定期学術集会抄録集, 118回, 1069-1069, 2018.04.
54. S Itoh, K Yugawa, M Shimokawa, S Yoshiya, Y Mano, K Takeishi, T Toshima, Y Maehara, M Mori, T Yoshizumi, Prognostic significance of inflammatory biomarkers in hepatocellular carcinoma following hepatic resection., BJS open, 10.1002/bjs5.50170, 3, 4, 500-508, 2019.08, Background: Cancer-related inflammation has been correlated with cancer prognosis. This study evaluated inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), programmed death ligand (PD-L) 1 expression, and tumour microenvironment in relation to prognosis and clinicopathological features of patients with hepatocellular carcinoma (HCC) undergoing curative hepatic resection. Methods: Patients who had liver resection for HCC in 2000-2011 were analysed. Univariable and multivariable analyses were conducted for overall (OS) and recurrence-free (RFS) survival. Immunohistochemical analyses of PD-L1, CD8 and CD68 expression were performed. HCC cell lines were evaluated for PD-L1 expression. A subgroup analysis was conducted to determine patient features, survival and the tumour microenvironment. Results were validated in a cohort of patients with HCC treated surgically in 2012-2016. Results: Some 281 patients who underwent hepatic resection for HCC were included. Multivariable analysis showed that low LMR was an independent prognostic factor of OS (hazard ratio (HR) 1·59, 95 per cent c.i. 1·00 to 2·41; P = 0·045) and RFS (HR 1·47, 1·05 to 2·04; P = 0·022) after resection. Low preoperative LMR values were correlated with higher α-fetoprotein values (P < 0·001), larger tumour size (P < 0·001), and high rates of poor differentiation (P = 0·035) and liver cirrhosis (P = 0·008). LMR was significantly lower in PD-L1-positive patients than in those with PD-L1 negativity (P < 0·001). Results were confirmed in the validation cohort. PD-L1 expression was upregulated in HCC cell lines treated with interferon-γ and co-cultured with THP-1 monocyte cells. Conclusion: LMR is an independent predictor of survival after hepatic resection in patients with HCC. Modulation of the immune checkpoint pathway in the tumour microenvironment is associated with a low LMR..
55. 山下 洋市, 木下 翔太郎, 北野 雄希, 林 洋光, 杉町 圭史, 西崎 隆, 福澤 謙吾, 梶山 潔, 宮成 信友, 吉住 朋晴, 高森 啓史, 馬場 秀夫, 転移性膵腫瘍に対する膵切除の臨床成績に関する多施設共同研究, 日本癌治療学会学術集会抄録集, 59回, O44-2, 2021.10.
56. 山下 洋市, 木下 翔太郎, 北野 雄希, 林 洋光, 杉町 圭史, 西崎 隆, 福澤 謙吾, 梶山 潔, 宮成 信友, 吉住 朋晴, 高森 啓史, 馬場 秀夫, 転移性膵腫瘍に対する膵切除の臨床成績に関する多施設共同研究, 日本癌治療学会学術集会抄録集, 59回, O44-2, 2021.10.
57. Yuji Soejima, Tomoaki Taguchi, Toshiharu Matsuura, Makoto Hayashida, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Rex Shunt for Portal Vein Thrombosis After Pediatric Living Donor Liver Transplantation., Annals of transplantation, 26, e909493, 2021.12, BACKGROUND Portal vein thrombosis (PVT) after pediatric liver transplantation (LT) is a common but grave complication which could eventually result in life-threatening portal hypertension. A "Rex" shunt between the superior mesenteric vein and the Rex recess of the liver has been reported to be a treatment option for extrahepatic portal vein obstruction; however, its application to living donor liver transplantation (LDLT) is limited due to the availability of appropriate vein grafts. In this study, we retrospectively evaluated the effectiveness of Rex shunt as an option for the treatment of PVT after pediatric LDLT. CASE REPORT Three children underwent the Rex shunt for early (n=2) and late (n=1) PVT after LDLT using the greater saphenous vein (n=2) and the external iliac vein (n=1) from the parents who previously donated their livers. Two of the 3 children are free from symptoms with patent shunt grafts at 14 years after the procedures. One child died at 30 days after LDLT due to repeated episodes of PVT, which finally led to hepatic infarction. CONCLUSIONS The Rex shunt is feasible to treat PVT after LDLT. However, additional surgical insults to the living donor need further discussion..
58. Junichi Takahashi, Takaaki Masuda, Akihiro Kitagawa, Taro Tobo, Yusuke Nakano, Tadashi Abe, Yuki Ando, Keisuke Kosai, Yuta Kobayashi, Yoshihiro Matsumoto, Tomoharu Yoshizumi, Masaki Mori, Koshi Mimori, Fanconi Anemia Complementation Group E (FANCE), a DNA Repair-Related Gene, Is a Potential Marker of Poor Prognosis in Hepatocellular Carcinoma., Oncology, 10.1159/000520582, 100, 2, 101-113, 2021.11, INTRODUCTION: Fanconi anemia complementation group E (FANCE) is a Fanconi anemia (FA) pathway gene that regulates DNA repair. We evaluated the clinical relevance of FANCE expression in hepatocellular carcinoma (HCC). METHODS: First, the associations between the expression of FA pathway genes including FANCE and clinical outcomes in HCC patients were analyzed in two independent cohorts: The Cancer Genome Atlas (TCGA, n = 373) and our patient cohort (n = 53). Localization of FANCE expression in HCC tissues was observed by immunohistochemical staining. Gene set enrichment analysis (GSEA) and gene network analysis (SiGN_BN) were conducted using the TCGA dataset. Next, an in vitro proliferation assay was performed using FANCE-knockdown HCC cell lines (HuH7 and HepG2). The association between mRNA expression of FANCE and that of DNA damage response genes in HCC was analyzed using TCGA and Cancer Cell Line Encyclopedia datasets. Finally, the association between FANCE mRNA expression and overall survival (OS) in various digestive carcinomas was analyzed using TCGA data. RESULTS: FANCE was highly expressed in HCC cells. Multivariate analysis indicated that high FANCE mRNA expression was an independent factor predicting poor OS. GSEA revealed a positive relationship between enhanced FANCE expression and E2F and MYC target gene expression in HCC tissues. FANCE knockdown attenuated the proliferation of HCC cells, as well as reduced cdc25A expression and elevated histone H3 pSer10 expression. SiGN_BN revealed that FANCE mRNA expression was positively correlated with DNA damage response genes (H2AFX and CHEK1) in HCC tissues. Significant effects of high FANCE expression on OS were observed in hepatobiliary pancreatic carcinomas, including HCC. CONCLUSIONS: FANCE may provide a potential therapeutic target and biomarker of poor prognosis in HCC, possibly by facilitating tumor proliferation, which is mediated partly by cell cycle signaling activation..
59. Ryota Nakanishi, Eiji Oki, Hirofumi Hasuda, Eiki Sano, Yu Miyashita, Akihiro Sakai, Naomichi Koga, Naotaka Kuriyama, Kentaro Nonaka, Yoshiaki Fujimoto, Tomoko Jogo, Kentaro Hokonohara, Qingjiang Hu, Yuichi Hisamatsu, Koji Ando, Yasue Kimura, Tomoharu Yoshizumi, Masaki Mori, ASO Author Reflection: Radiomics-Based Prediction for the Responder to First-Line Oxaliplatin-Based Chemotherapy in Patients with Colorectal Liver Metastasis., Annals of surgical oncology, 10.1245/s10434-020-09584-2, 28, 6, 2986-2987, 2021.06.
60. Tetsuya Yasunaka, Yasuto Takeuchi, Akinobu Takaki, Fukuo Kondo, Tomoharu Yoshizumi, Kenichi Kohashi, Atsushi Oyama, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Hiroyuki Okada, A case of focal nodular hyperplasia with hepatic failure treated with liver transplantation., Clinical journal of gastroenterology, 10.1007/s12328-021-01529-w, 15, 1, 171-176, 2021.11, Focal nodular hyperplasia (FNH) is a benign nodular lesion, but because of its feature of portal tract vessel abnormality, it may induce portal hypertension. A 27-year-old woman was admitted with a fever. A large nodule with satellite lesions was found in the liver and cotton wool-like feature of arteries were detected on angiography. Technetium galactosyl serum albumin scintigraphy and diagnostic laparoscopy showed that the tumor site was functional, while the surrounding area was a non-functional fibrotic area. A biopsy specimen indicated that the nodular lesion was an FNH-like lesion. She experienced several instances of variceal rupture and suffered liver failure, receiving liver transplantation. The excised liver showed a centrally scarred area in the nodule, indicating that the diagnosis was FNH. We herein report this case as a rare case of FNH that progressed to liver failure..
61. Takahiro Tomiyama, Takuya Yamamoto, Shokichi Takahama, Takeo Toshima, Shinji Itoh, Noboru Harada, Mototsugu Shimokawa, Daisuke Okuzaki, Masaki Mori, Tomoharu Yoshizumi, Up-regulated LRRN2 expression as a marker for graft quality in living donor liver transplantation., Hepatology communications, 10.1002/hep4.2033, 6, 10, 2836-2849, 2022.07, The quality and size of liver grafts are critical factors that influence living-donor liver transplantation (LDLT) function and safety. However, the biomarkers used for predicting graft quality are lacking. In this study, we sought to identify unique graft quality markers, aside from donor age, by using the livers of non-human primates. Hepatic gene microarray expression data from young and elderly cynomolgus macaques revealed a total of 271 genes with significantly increased expression in the elderly. These candidate genes were then narrowed down to six through bioinformatics analyses. The expression patterns of these candidate genes in human donor liver tissues were subsequently examined. Importantly, we found that grafts exhibiting up-regulated expression of these six candidate genes were associated with an increased incidence of liver graft failure. Multivariable analysis further revealed that up-regulated expression of LRRN2 (encoding leucine-rich repeat protein, neuronal 2) in donor liver tissue served as an independent risk factor for graft failure (odds ratio 4.50, confidence interval 2.08-9.72). Stratification based on graft expression of LRRN2 and donor age was also significantly associated with 6-month graft survival rates. Conclusion: Up-regulated LRRN2 expression of liver graft is significantly correlated with graft failure in LDLT. In addition, combination of graft LRRN2 expression and donor age may represent a promising marker for predicting LDLT graft quality..
62. Masahito Nakano, Hiroshi Yatsuhashi, Shigemune Bekki, Yuko Takami, Yasuhito Tanaka, Yoko Yoshimaru, Koichi Honda, Yasuji Komorizono, Masaru Harada, Michihiko Shibata, Shotaro Sakisaka, Satoshi Shakado, Kenji Nagata, Tomoharu Yoshizumi, Shinji Itoh, Tetsuro Sohda, Satoshi Oeda, Kazuhiko Nakao, Ryu Sasaki, Tsutomu Yamashita, Akio Ido, Seiichi Mawatari, Makoto Nakamuta, Yoshifusa Aratake, Shuichi Matsumoto, Tatsuji Maeshiro, Takashi Goto, Takuji Torimura, Trends in hepatocellular carcinoma incident cases in Japan between 1996 and 2019., Scientific reports, 10.1038/s41598-022-05444-z, 12, 1, 1517-1517, 2022.01, We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996-2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60-69 years, 70-79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease..
63. Asato Hashinokuchi, Mikihiro Kohno, Keisuke Kosai, Yuki Ono, Naoki Haratake, Daiki Shibata, Hidetaka Yamamoto, Tomoyoshi Takenaka, Tomoharu Yoshizumi, Surgical resection of a tuberculoma in the diaphragm: a case report., Surgical case reports, 10.1186/s40792-022-01554-y, 8, 1, 198-198, 2022.10, BACKGROUND: Extrapulmonary tuberculosis commonly affects the lymphatic system, nervous system, and gastrointestinal system. Tuberculous infection in the muscle is very rare. Moreover, tuberculous infection in the diaphragm is extremely rare. We herein report a case of tuberculomas in the diaphragm and posterior mediastinum that were successfully diagnosed and treated. CASE PRESENTATION: We encountered a 62-year-old woman with a tuberculoma in the diaphragm. The patient presented with mild dyspnea. Computed tomography showed a mass in the left diaphragm, focal thickening of the posterior mediastinum, and multiple nodules in the lungs. Positron emission tomography-computed tomography showed increased uptake in the left diaphragm mass and thickening of the posterior mediastinum; therefore, we considered the masses to be malignant and planned surgical resection. However, the patient was diagnosed with tuberculosis from a sputum culture, and she was treated with anti-tuberculous therapy. The masses in the diaphragm and posterior mediastinum had become enlarged after 6 months of anti-tuberculous therapy; therefore, the patient underwent resection of both masses. Tuberculous infection was histologically confirmed in each lesion. She was pathologically diagnosed with tuberculous abscesses in the diaphragm and posterior mediastinum and began treatment with anti-tuberculosis drugs. CONCLUSIONS: Preoperative diagnosis of a tuberculoma in the diaphragm is usually difficult, and surgical intervention is important for both diagnosis and treatment..
64. Rigel Suzuki, Yuki Ono, Koji Noshita, Kwang Su Kim, Hayato Ito, Yuhei Morioka, Tomokazu Tamura, Daisuke Okuzaki, Tetsuzo Tagawa, Tomoyoshi Takenaka, Tomoharu Yoshizumi, Teppei Shimamura, Shingo Iwami, Takasuke Fukuhara, Smoking enhances the expression of angiotensin-converting enzyme 2 involved in the efficiency of severe acute respiratory syndrome coronavirus 2 infection., Microbiology and immunology, 10.1111/1348-0421.13034, 67, 1, 22-31, 2022.10, Smoking is one of the risk factors most closely related to the severity of coronavirus disease 2019 (COVID-19). However, the relationship between smoking history and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is unknown. In this study, we evaluated the ACE2 expression level in the lungs of current smokers, ex-smokers, and nonsmokers. The ACE2 expression level of ex-smokers who smoked cigarettes until recently (cessation period shorter than 6 months) was higher than that of nonsmokers and ex-smokers with a long history of nonsmoking (cessation period longer than 6 months). We also showed that the efficiency of SARS-CoV-2 infection was enhanced in a manner dependent on the angiotensin-converting enzyme 2 (ACE2) expression level. Using RNA-seq analysis on the lungs of smokers, we identified that the expression of inflammatory signaling genes was correlated with ACE2 expression. Notably, with increasing duration of smoking cessation among ex-smokers, not only ACE2 expression level but also the expression levels of inflammatory signaling genes decreased. These results indicated that smoking enhances the expression levels of ACE2 and inflammatory signaling genes. Our data suggest that the efficiency of SARS-CoV-2 infection is enhanced by smoking-mediated upregulation of ACE2 expression level..
65. Yuki Ono, Tetsuzo Tagawa, Fumihiko Kinoshita, Naoki Haratake, Kazuki Takada, Mikihiro Kohno, Tomoyoshi Takenaka, Takeshi Kamitani, Mototsugu Shimokawa, Yoshinao Oda, Masaki Mori, Tomoharu Yoshizumi, Relationship between consolidation tumor ratio and tumor-infiltrating lymphocytes in small-sized lung adenocarcinoma., Thoracic cancer, 10.1111/1759-7714.14524, 13, 15, 2134-2141, 2022.07, BACKGROUND: Consolidation tumor ratio (CTR) is associated with cancer progression and histological invasiveness in lung adenocarcinoma (LAD). However, little is known about the association between CTR and immune-related factors, including tumor-infiltrating lymphocytes (TILs) density or tumor expression of programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) in small-sized LAD. METHODS: This study included 258 patients with LAD (<3 cm) who underwent surgery. Patients were assigned to four groups: CTR = 0; 0 < CTR <0.5; 0.5 ≤ CTR <1 (ground-glass opacity [GGO] group); and CTR = 1 (pure-solid group). CD4+ , CD8+ , and FoxP3+ TIL density and PD-L1 and IDO1 tumor expression were assessed by immunohistochemistry. RESULTS: Among the GGO group, CD8+ and FoxP3+ TIL density increased significantly with increasing CTR (p < 0.001 and p < 0.001, respectively). Moreover, PD-L1 and IDO1 expression was significantly higher in the pure-solid group than in the GGO group (p < 0.001 and p < 0.001, respectively). CONCLUSIONS: CTR was correlated with the abundance of CD8+ and FoxP3+ TILs in the GGO group. PD-L1 and IDO1 positivity rates were significantly higher in the pure-solid group than in the GGO group. Increased CTR may be correlated with immunosuppressive condition..
66. Katsuya Toshida, Shinji Itoh, Kyohei Yugawa, Yukiko Kosai, Takahiro Tomino, Shohei Yoshiya, Yoshihiro Nagao, Hiroto Kayashima, Noboru Harada, Kenichi Kohashi, Yoshinao Oda, Tomoharu Yoshizumi, Prognostic significance for recurrence of fibroblast growth factor receptor 2 in intrahepatic cholangiocarcinoma patients undergoing curative hepatic resection., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13875, 53, 5, 432-439, 2022.12, AIMS: The fibroblast growth factor receptor 2 (FGFR2) fusion gene is frequently found as a genetic abnormality in the FGFR pathway in patients with intrahepatic cholangiocarcinoma (ICC). The FGFR fusion protein, produced from the FGFR fusion gene, is thought to cause tumor cell growth. To date, there have been few reports on the relationship between pathologic FGFR2 expression and prognosis in patients who have undergone hepatectomy for ICC, and on the relationship between FGFR2 and tumor-infiltrating lymphocytes (TILs). METHODS AND RESULTS: We enrolled 92 patients who underwent hepatectomy for ICC and performed immunohistochemical staining for FGFR2 and cluster of differentiation 8, and hematoxylin and eosin staining for evaluating TILSs. The relationships between the FGFR2 and clinicopathological characteristics and outcomes were analyzed, and patients were classified into positive (n = 18) and negative (n = 74) FGFR2 groups. The FGFR2-positive group contained more men (p < 0.0001) and had lower serum albumin (p = 0.0355) and higher carcinoembryonic antigen (p = 0.0099). Furthermore, multivariable analyses revealed that the FGFR2-positive group had worse disease-free survival (DFS) (p = 0.0002). Multivariate analysis showed that the independent prognostic factors for DFS were maximum tumor size (≥5 cm) (p = 0.0011), tumor localization (perihilar type) (p = 0.0180), and FGFR2 positivity (p = 0.0029). There was no significant difference in TILs count between the two groups. CONCLUSION: We showed that FGFR2 high expression was an independent prognostic factor for recurrence of resected ICC..
67. Keishi Sugimachi, Hiromitsu Araki, Hideyuki Saito, Takaaki Masuda, Fumihito Miura, Kentaro Inoue, Tomonari Shimagaki, Yohei Mano, Tomohiro Iguchi, Masaru Morita, Yasushi Toh, Tomoharu Yoshizumi, Takashi Ito, Koshi Mimori, Persistent epigenetic alterations in transcription factors after a sustained virological response in hepatocellular carcinoma, JGH Open, 10.1002/jgh3.12833, 6, 12, 854-863, 2022.10, BACKGROUND AND AIM: The risk of hepatocellular carcinoma (HCC) persists in a condition of sustained virologic response (SVR) after hepatitis C virus (HCV) eradication. Comprehensive molecular analyses were performed to test the hypothesis that epigenetic abnormalities present after an SVR play a role in hepatocarcinogenesis. METHODS: Whole-genome methylome and RNA sequencing were performed on HCV, SVR, and healthy liver tissue. Integrated analysis of the sequencing data focused on expression changes in transcription factors and their target genes, commonly found in HCV and SVR. Identified expression changes were validated in demethylated cultured HCC cell lines and an independent validation cohort. RESULTS: The coincidence rates of the differentially methylated regions between the HCV and SVR groups were 91% in the hypomethylated and 71% in the hypermethylated regions in tumorous tissues, and 37% in the hypomethylated and 36% in the hypermethylated regions in non-tumorous tissues. These results indicate that many epigenomic abnormalities persist even after an SVR was achieved. Integrated analysis identified 61 transcription factors and 379 other genes that had methylation abnormalities and gene expression changes in both groups. Validation cohort specified gene expression changes for 14 genes, and gene ontology pathway analysis revealed apoptotic signaling and inflammatory response were associated with these genes. CONCLUSION: This study demonstrates that DNA methylation abnormalities, retained after HCV eradication, affect the expression of transcription factors and their target genes. These findings suggest that DNA methylation in SVR patients may be functionally important in carcinogenesis, and could serve as biomarkers to predict HCC occurrence..
68. Takeo Toshima, Noboru Harada, Shinji Itoh, Kazutoyo Morita, Yoshihiro Nagao, Takeshi Kurihara, Takahiro Tomino, Yukiko Kosai-Fujimoto, Akinari Morinaga, Takahiro Tomiyama, Tomoharu Yoshizumi, Outcomes of living-donor liver transplantation for acute-on-chronic liver failure based on newly proposed criteria in Japan., Clinical transplantation, 10.1111/ctr.14739, 36, 8, e14739, 2022.06, AIM: Recently, new diagnostic criteria for acute-on-chronic liver failure (ACLF) were established in Japan. However, there is little evidence regarding the feasibility of classifying patients undergoing living-donor liver transplantation (LDLT). The aim was to re-evaluate the impact of these new diagnostic criteria on ACLF and the severity classification of patients undergoing LDLT. METHODS: We collected data of 82 recipients who underwent LDLT for liver failure between 1997 and 2020 and reviewed it retrospectively. RESULTS: Of the 82 patients with liver failure, 31 (37.8%) were diagnosed with ACLF; Grade 0 (n = 6), Grade 1 (n = 7), Grade 2 (n = 9), and Grade 3 (n = 9). There was no substantial difference in overall survival (OS) and the occurrence of postoperative complications between liver failure patients with and without ACLF. The OS after LDLT was significantly different among the four groups of ACLF patients (P = .036). Interestingly, ACLF Grade 3 patients had substantially lower OS compared to other ACLF groups even after LDLT (P = .006; 5-year OS rates, 33.3% vs. 85.9%). CONCLUSION: Proper use of the new diagnostic criteria for ACLF in Japan demonstrated that the presence and severity of ACLF, especially the presence of multiple organ failures, leads to morbidity and mortality even in an LDLT setting. Considering that the patients with ACLF Grade 3 do not have the favorable outcomes of LDLT, deceased-donor liver transplantation usage, or LDLT before reaching the severity of Grade 3 may be suitable for further research..
69. Takahiro Tomiyama, Shinji Itoh, Norifumi Iseda, Katuya Toshida, Akinari Morinaga, Kyohei Yugawa, Yukiko Kosai Fujimoto, Takahiro Tomino, Takeshi Kurihara, Yoshihiro Nagao, Kazutoyo Morita, Noboru Harada, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Tomoharu Yoshizumi, Myeloid-derived suppressor cell infiltration is associated with a poor prognosis in patients with hepatocellular carcinoma., Oncology letters, 10.3892/ol.2022.13213, 23, 3, 93-93, 2022.03, The clinicopathological features of myeloid-derived suppressor cell (MDSC) and CD8+ T-cell infiltration in hepatocellular carcinoma (HCC) are poorly understood. The present study examined MDSC and CD8+ T-cell infiltration in surgically resected primary HCC specimens and investigated the association of MDSC and CD8+ T-cell infiltration with clinicopathological features and patient outcomes. Using a database of 466 patients who underwent hepatic resection for HCC, immunohistochemical staining of CD33 (an MDSC marker) and CD8 was performed. High infiltration of MDSCs within the tumor was observed in patients with a poorer Barcelona Clinic Liver Cancer stage, larger tumor size, more poorly differentiated HCC, and greater presence of portal venous thrombosis, microscopic vascular thrombosis and macroscopic intrahepatic metastasis. MDSC infiltration and CD8+ T-cell infiltration were independent predictors of recurrence-free survival and overall survival, respectively. Stratification based on the MDSC and CD8+ T-cell status of the tumors was also associated with recurrence-free survival (10 year-recurrence-free survival; MDSChighCD8+ T-cellLow, 3.68%; others, 25.7%) and overall survival (10 year-overall survival; MDSChighCD8+ T-cellLow, 12.0%; others, 56.7%). In conclusion, the present large cohort study revealed that high MDSC infiltration was associated with a poor clinical outcome in patients with HCC. Furthermore, the combination of the MDSC and tumor-infiltrating CD8+ T-cell status enabled further classification of patients based on their outcomes..
70. Mamoru Morimoto, Kazuteru Monden, Taiga Wakabayashi, Naoto Gotohda, Yuta Abe, Goro Honda, Mohammed Abu Hilal, Takeshi Aoki, Horacio J Asbun, Giammauro Berardi, Albert C Y Chan, Rawisak Chanwat, Kuo-Hsin Chen, Yajin Chen, Daniel Cherqui, Tan To Cheung, Ruben Ciria, David Fuks, David A Geller, Ho-Seong Han, Kiyoshi Hasegawa, Etsuro Hatano, Osamu Itano, Yukio Iwashita, Hironori Kaneko, Yutaro Kato, Ji Hoon Kim, Rong Liu, Santiago López-Ben, Fernando Rotellar, Yoshihiro Sakamoto, Atsushi Sugioka, Tomoharu Yoshizumi, Keiichi Akahoshi, Felipe Alconchel, Shunichi Ariizumi, Andrea Benedetti Cacciaguerra, Manuel Durán, Alain García Vázquez, Nicolas Golse, Yoshihiro Miyasaka, Yasuhisa Mori, Satoshi Ogiso, Chikara Shirata, Federico Tomassini, Takeshi Urade, Hitoe Nishino, Filipe Kunzler, Shingo Kozono, Hiroaki Osakabe, Chie Takishita, Daisuke Ban, Taizo Hibi, Norihiro Kokudo, Masayuki Ohtsuka, Yuichi Nagakawa, Takao Ohtsuka, Minoru Tanabe, Masafumi Nakamura, Masakazu Yamamoto, Akihiko Tsuchida, Go Wakabayashi, Minimally invasive anatomic liver resection: Results of a survey of world experts., Journal of hepato-biliary-pancreatic sciences, 10.1002/jhbp.1094, 29, 1, 33-40, 2022.01, BACKGROUND: Although the number of minimally invasive liver resections (MILRs) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR. METHOD: We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs). RESULTS: All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green negative staining method, and intraoperative ultrasound. CONCLUSION: Minimally invasive anatomic liver resection remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons..
71. Norifumi Harimoto, Shinji Itoh, Takahiro Yamanaka, Kei Hagiwara, Norihiro Ishii, Mariko Tsukagoshi, Akira Watanabe, Kenichiro Araki, Tomoharu Yoshizumi, Ken Shirabe, Mac-2 Binding Protein Glycosylation Isomer as a Prognostic Marker for Hepatocellular Carcinoma With Sustained Virological Response., Anticancer research, 10.21873/anticanres.15479, 42, 1, 245-251, 2022.01, BACKGROUND/AIM: Mac2-binding protein glycosylation isomer (M2BPGi) is a non-invasive marker for assessing liver fibrosis. This was a retrospective study investigating whether M2BPGi predicts recurrence of hepatocellular carcinoma (HCC) after hepatectomy in patients with HCC who achieved a sustained virological response (SVR). PATIENTS AND METHODS: We retrospectively reviewed the clinicopathological factors from 60 patients who underwent hepatectomy for HCC after achieving a SVR. We divided all patients into high M2BPGi and low M2BPGi groups and analyzed the clinicopathological and surgical outcomes. RESULTS: High M2BPGi (>1.54, n=23) was significantly associated with lower serum albumin, higher ICGR15, higher Fib-4 index, large blood loss, and worse recurrence-free survival compared to low M2BPGi (≤1.54, n=37). Multivariate analysis identified high M2BPGi and large tumor size as being associated with reduced recurrence-free survival. Multivariate analysis identified lower serum albumin, larger tumor size and higher DCP as associated with reduced overall survival. There was no difference regarding recurrence pattern. CONCLUSION: Preoperative M2BPGi is a useful biomarker for HCC recurrence after hepatectomy for SVR-HCC..
72. Nami Yamashita, Yoshihiro Morimoto, Atsushi Fushimi, Rehan Ahmad, Atrayee Bhattacharya, Tatsuaki Daimon, Naoki Haratake, Yuka Inoue, Satoshi Ishikawa, Masaaki Yamamoto, Tsuyoshi Hata, Sayuri Akiyoshi, Qiang Hu, Tao Liu, Henry Withers, Song Liu, Geoffrey I Shapiro, Tomoharu Yoshizumi, Mark D Long, Donald Kufe, MUC1-C Dictates PBRM1-Mediate Chronic Induction of Interferon Signaling, DNA Damage Resistance and Immunosuppression in Triple-Negative Breast Cancer., Molecular cancer research : MCR, 10.1158/1541-7786.MCR-22-0772, 21, 3, 274-289, 2022.11, The polybromo-1 (PBRM1) chromatin-targeting subunit of the SWI/SNF PBAF chromatin remodeling complex drives DNA damage resistance and immune evasion in certain cancer cells through mechanisms that remain unclear. STAT1 and IRF1 are essential effectors of type I and II interferon (IFN) pathways. Here, we report that MUC1-C is necessary for PBRM1 expression and that it forms a nuclear complex with PBRM1 in TNBC cells. Analysis of global transcriptional (RNA-seq) and chromatin accessibility (ATAC-seq) profiles further demonstrated that MUC1-C and PBRM1 drive STAT1 and IRF1 expression by increasing chromatin accessibility of promoter-like signatures (PLSs) on their respective genes. We also found that MUC1-C, PBRM1, and IRF1 increase the expression and chromatin accessibility on PLSs of the (i) type II IFN pathway IDO1 and WARS genes and (ii) type I IFN pathway RIG-I, MDA5, and ISG15 genes that collectively contribute to DNA damage resistance and immune evasion. In support of these results, targeting MUC1-C in wild-type BRCA TNBC cells enhanced carboplatin-induced DNA damage and the loss of self-renewal capacity. In addition, MUC1-C was necessary for DNA damage resistance, self-renewal, and tumorigenicity in olaparib-resistant BRCA1-mutant TNBC cells. Analysis of TNBC tumors corroborated that (i) MUC1 and PBRM1 are associated with decreased responsiveness to chemotherapy and (ii) MUC1-C expression is associated with the depletion of tumor-infiltrating lymphocytes (TILs). These findings demonstrate that MUC1-C activates PBRM1, and thereby chromatin remodeling of IFN-stimulated genes that promote chronic inflammation, DNA damage resistance, and immune evasion. Implications: MUC1-C is necessary for PBRM1-driven chromatin remodeling in chronic activation of IFN pathway genes that promote DNA damage resistance and immunosuppression..
73. Takahiro Tomiyama, Masahiro Shimokawa, Noboru Harada, Katsuya Toshida, Akinari Morinaga, Yukiko Kosai-Fujimoto, Takahiro Tomino, Takeshi Kurihara, Yoshihiro Nagao, Takeo Toshima, Kazutoyo Morita, Shinji Itoh, Tomoharu Yoshizumi, Low syntaxin 17 expression in donor liver is associated with poor graft prognosis in recipients of living donor liver transplantation., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13809, 52, 10, 872-881, 2022.07, AIM: Liver transplantation (LT) is the only curative therapy for decompensated liver cirrhosis. For recipients of living donor LT (LDLT), restoration of liver function after transplantation is highly dependent on liver regenerative capacity, which requires large amounts of intracellular energy. Mitochondrial metabolism provides a stable supply of ATP for liver regeneration. Mitophagy is a selective process in which damaged, non-functional mitochondria are degraded and replaced with new functional mitochondria. We investigated the relationship between expression of Syntaxin17 (STX17), a key protein in mitophagy regulation, in donor livers and graft survival. METHODS: We examined STX17 expression in grafts from 143 LDLT donors who underwent right lobe resection and investigated the relationship between STX17 expression and graft function. We investigated the correlations among STX17 expression, mitochondrial membrane potential and cell proliferation, using a STX17-knockdown hepatocyte cell line. RESULTS: Recipients transplanted with low STX17-expression grafts had significantly lower graft survival rates than recipients transplanted with high STX17-expression grafts (88.9% vs. 100%, p<0.01). Multivariate analysis showed that low STX17 expression (HR: 10.7, CI: 1.29-88.0, p<0.05) and the absence of splenectomy (HR: 6.27, CI: 1.59-24.8, p<0.01) were independent predictive factors for small-for-size graft syndrome, which is the severe complication in LDLT. In the vitro experiments, the percentage of depolarized damaged mitochondria was increased in the STX17-knockdown hepatocyte cell line, suggesting decreased mitophagy and ATP synthesis. Cell proliferation was significantly decreased in the STX17-knockdown hepatocyte cell line. CONCLUSION: STX17 contributes to mitophagy and maintenance of mitochondrial function in hepatocytes and may be a predictor of graft dysfunction in LDLT patients. This article is protected by copyright. All rights reserved..
74. Norifumi Iseda, Shinji Itoh, Tomoharu Yoshizumi, Takahiro Tomiyama, Akinari Morinaga, Kyohei Yugawa, Masahiro Shimokawa, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Yoshiyuki Kitamura, Yoshihiro Nagao, Takeo Toshima, Noboru Harada, Kenichi Kohashi, Shingo Baba, Kousei Ishigami, Yoshinao Oda, Masaki Mori, Impact of Nuclear Factor Erythroid 2-Related Factor 2 in Hepatocellular Carcinoma: Cancer Metabolism and Immune Status., Hepatology communications, 10.1002/hep4.1838, 6, 4, 665-678, 2022.04, We examined phosphorylated nuclear factor erythroid 2-related factor 2 (P-NRF2) expression in surgically resected primary hepatocellular carcinoma (HCC) and investigated the association of P-NRF2 expression with clinicopathological features and patient outcome. We also evaluated the relationship among NRF2, cancer metabolism, and programmed death ligand 1 (PD-L1) expression. In this retrospective study, immunohistochemical staining of P-NRF2 was performed on the samples of 335 patients who underwent hepatic resection for HCC. Tomography/computed tomography using fluorine-18 fluorodeoxyglucose was performed, and HCC cell lines after NRF2 knockdown were analyzed by array. We also analyzed the expression of PD-L1 after hypoxia inducible factor 1α (HIF1A) knockdown in NRF2-overexpressing HCC cell lines. Samples from 121 patients (36.1%) were positive for P-NRF2. Positive P-NRF2 expression was significantly associated with high alpha-fetoprotein (AFP) expression, a high rate of poor differentiation, and microscopic intrahepatic metastasis. In addition, positive P-NRF2 expression was an independent predictor for recurrence-free survival and overall survival. NRF2 regulated glucose transporter 1, hexokinase 2, pyruvate kinase isoenzymes L/R, and phosphoglycerate kinase 1 expression and was related to the maximum standardized uptake value. PD-L1 protein expression levels were increased through hypoxia-inducible factor 1α after NRF2 overexpression in HCC cells. Conclusions: Our large cohort study revealed that P-NRF2 expression in cancer cells was associated with clinical outcome in HCC. Additionally, we found that NRF2 was located upstream of cancer metabolism and tumor immunity..
75. Yukiko Kosai-Fujimoto, Shinji Itoh, Kyohei Yugawa, Takasuke Fukuhara, Daisuke Okuzaki, Takeo Toshima, Noboru Harada, Yoshinao Oda, Tomoharu Yoshizumi, Masaki Mori, Impact of JMJD6 on intrahepatic cholangiocarcinoma., Molecular and clinical oncology, 10.3892/mco.2022.2564, 17, 2, 131-131, 2022.08, The association of Jumonji domain-containing 6 (JMJD6) with the prognosis of various types of cancer has been demonstrated, except in intrahepatic cholangiocarcinoma (ICC). The present study aimed to clarify the impact of JMJD6 on ICC. The liver specimens of 51 patients who underwent surgery for ICC were analyzed for JMJD6 expression using immunohistochemistry staining. The relationship between clinicopathological factors and JMJD6 expression was investigated. The cellular activity was also evaluated in JMJD6 knocked down cells with Transwell migration assay and viability assay. In the immunohistochemistry staining of clinical samples, high expression of JMJD6 was seen in 32 of 51 samples. High expression was also associated with improved overall survival (OS) and recurrence-free survival (RFS) (P=0.0033 and 0.048, respectively). Further analyses revealed that higher JMJD6 expression was one of the improved independent prognostic factors of OS and RFS. Expression of JMJD6 was knocked down in commercial culture cell lines of ICC, and RNA and protein were extracted to analyze the downstream gene expression using RNA-sequencing and western blotting. JMJD6 knockdown was associated with higher programmed death-ligand 1 (PD-L1) expression in RNA-sequencing and western blotting. In addition, PD-L1 expression was higher in JMJD6 low expression clinical samples when measured using immunohistochemistry staining. In conclusion, high expression of JMJD6 was an independent favorable prognostic factor of ICC. JMJD6 may influence the prognosis of ICC through the regulation of PD-L1 expression..
76. Kenji Watanabe, Noboru Harada, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Yoshihiro Nagao, Takeo Toshima, Shinji Itoh, Tomoharu Yoshizumi, Masaki Mori, Gastric Tube-Preserving Pancreaticoduodenectomy Using Intraoperative Blood Perfusion Imaging After Esophagectomy., Pancreas, 10.1097/MPA.0000000000001976, 51, 2, e21-e22, 2022.02.
77. Norifumi Iseda, Shinji Itoh, Katsuya Toshida, Takahiro Tomiyama, Akinari Morinaga, Masahiro Shimokawa, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Takeo Toshima, Yoshihiro Nagao, Noboru Harada, Tomoharu Yoshizumi, Masaki Mori, Ferroptosis is induced by lenvatinib through fibroblast growth factor receptor-4 inhibition in hepatocellular carcinoma., Cancer science, 10.1111/cas.15378, 113, 7, 2272-2287, 2022.04, The tyrosine kinase inhibitor lenvatinib is used to treat advanced hepatocellular carcinoma (HCC). Ferroptosis is a type of cell death characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS). Nuclear factor erythroid-derived 2-like 2 (Nrf2) protects HCC cells against ferroptosis. However, the mechanism of lenvatinib-induced cytotoxicity and the relationships between lenvatinib resistance and Nrf2 are unclear. Thus, we investigated the relationship between lenvatinib and ferroptosis and clarified the involvement of Nrf2 in lenvatinib-induced cytotoxicity. Cell viability, lipid ROS levels, and protein expression were measured using Hep3B and HuH7 cells treated with lenvatinib or erastin. We examined these variables after silencing fibroblast growth factor receptor-4 (FGFR4) or Nrf2 and overexpressing-Nrf2. We immunohistochemically evaluated FGFR4 expression in recurrent lesions after resection and clarified the relationship between FGFR4 expression and lenvatinib efficacy. Lenvatinib suppressed system Xc - (xCT) and glutathione peroxidase 4 (GPX4) expression. Inhibition of the cystine import activity of xCT and GPX4 resulted in the accumulation of lipid ROS. Silencing-FGFR4 suppressed xCT and GPX4 expression and increased lipid ROS levels. Nrf2-silenced HCC cells displayed sensitivity to lenvatinib and high lipid ROS levels. In contrast, Nrf2-overexpressing HCC cells displayed resistance to lenvatinib and low lipid ROS levels. The efficacy of lenvatinib was significantly lower in recurrent HCC lesions with low-FGFR4 expression than in those with high-FGFR4 expression. Patients with FGFR4-positive HCC displayed significantly longer progression-free survival than those with FGFR4-negative HCC. Lenvatinib induced ferroptosis by inhibiting FGFR4. Nrf2 is involved in the sensitivity of HCC to lenvatinib..
78. Kaoru Umehara, Yuji Karashima, Tomoharu Yoshizumi, Ken Yamaura, Factors Associated With Postreperfusion Syndrome in Living Donor Liver Transplantation: A Retrospective Study., Anesthesia and analgesia, 10.1213/ANE.0000000000006002, 135, 2, 354-361, 2022.03, BACKGROUND: Postreperfusion syndrome (PRS) after portal vein reperfusion during liver transplantation (LT) has been reported to cause rapid hemodynamic changes and is associated with a prolonged postoperative hospital stay, renal failure, and increased mortality. Although there are some reports on risk factors for PRS in brain-dead donor LT, there are a few reports on those in living donor LT. Therefore, we retrospectively reviewed the factors associated with PRS to contribute to the anesthetic management so as to reduce PRS during living donor LT. METHODS: After approval by the ethics committee of our institution, 250 patients aged ≥20 years who underwent living donor LT at our institution between January 2013 and September 2018 were included in the study. A decrease in mean arterial pressure of ≥30% within 5 minutes after portal vein reperfusion was defined as PRS, and estimates and odds ratio (OR) for PRS were calculated using logistic regression. The backward method was used for variable selection in the multivariable analysis. RESULTS: Serum calcium ion concentration before reperfusion (per 0.1 mmol/L increase; OR, 0.74; 95% confidence interval (CI), 0.60-0.95; P < .001), preoperative echocardiographic left ventricular end-diastolic diameter (per 1-mm increase: OR, 0.90; 95% CI, 0.85-0.95; P < .001, men [versus women: OR, 2.45; 95% CI, 1.26-4.75; P = .008]), mean pulmonary artery pressure before reperfusion (restricted cubic spline, P = .003), anhepatic period (restricted cubic spline, P = .02), and graft volume to standard liver volume ratio (restricted cubic spline, P = .03) were significantly associated with PRS. CONCLUSIONS: In living donor LT, male sex and presence of small left ventricular end-diastolic diameter, large graft volume, and long anhepatic period are associated with PRS, and a high calcium ion concentration and low pulmonary artery pressure before reperfusion are negatively associated with PRS..
79. Yukihisa Takayama, Akihiro Nishie, Keisuke Ishimatsu, Yasuhiro Ushijima, Nobuhiro Fujita, Yuichiro Kubo, Tomoharu Yoshizumi, Ken-Ichi Kouhashi, Junki Maehara, Yuta Akamine, Kousei Ishigami, Diagnostic potential of T1ρ and T2 relaxations in assessing the severity of liver fibrosis and necro-inflammation., Magnetic resonance imaging, 10.1016/j.mri.2022.01.002, 87, 104-112, 2022.04, PURPOSE: To investigate the utility of T1ρ and T2 relaxations for assessing the severity of liver fibrosis (F stage) and necro-inflammation (A stage) in patients with chronic liver disease (CLD). MATERIALS AND METHODS: We calculated T1ρ and T2 relaxations of the liver parenchyma in 82 patients who underwent liver surgery. F and A stages of enrolled patients were assessed by referring to surgically resected specimens. The relationships between T1ρ or T2 relaxation and F or A stage were assessed using one-way analysis of variance followed by Tukey's multiple comparison test, Spearman's rank correlation test and a receiver operating characteristic analysis. RESULTS: The T1ρ and T2 values of the liver parenchyma were significantly increased as the F and A stages progressed. The T1ρ and T2 values showed significant differences between F0 and F4, between F1 and F4, and between F2 and F4. In addition, T1ρ values showed a significant difference between F0 and F3 as well. The highest diagnostic ability for fibrosis was obtained when differentiating ≥F3 from ≤F2 using T1ρ: the sensitivity was 82.8%, the specificity 79.2% and the area under the curve (AUC) 0.87. The sensitivity and AUC of T1ρ relaxation (46.9% and 0.67) were significantly higher than those of T2 relaxation (29.7% and 0.60) for differentiating ≥A1 from A0. CONCLUSION: T1ρ and T2 relaxations have potential as a biochemical marker for assessing the severity of liver fibrosis and necro-inflammation. T1ρ relaxation may be slightly superior to T2 relaxation in terms of diagnostic ability for liver fibrosis and necro-inflammation..
80. Chuan Lan, Yuki Kitano, Yo-Ichi Yamashita, Takanobu Yamao, Kiyoshi Kajiyama, Tomoharu Yoshizumi, Kengo Fukuzawa, Keishi Sugimachi, Yasuharu Ikeda, Hiroshi Takamori, Nobutomo Miyanari, Masahiko Hirota, Hideo Baba, Correction: Cancer-associated fibroblast senescence and its relation with tumour-infiltrating lymphocytes and PD-L1 expressions in intrahepatic cholangiocarcinoma., British journal of cancer, 10.1038/s41416-021-01615-3, 126, 2, 311-312, 2022.02.
81. Katsuya Toshida, Shinji Itoh, Takahiro Tomiyama, Akinari Morinaga, Yukiko Kosai, Takahiro Tomino, Takeshi Kurihara, Yoshihiro Nagao, Kazutoyo Morita, Noboru Harada, Tomoharu Yoshizumi, Comparison of the prognostic effect of sarcopenia on atezolizumab plus bevacizumab and lenvatinib therapy in hepatocellular carcinoma patients., JGH open : an open access journal of gastroenterology and hepatology, 10.1002/jgh3.12777, 6, 7, 477-486, 2022.07, Background and Aim: Sarcopenia has received much attention as a poor prognostic factor in various fields, and has also been reported to worsen prognosis in patients with hepatocellular carcinoma (HCC) treated with sorafenib or lenvatinib (LEN). Atezolizumab/bevacizumab (ATZ/BEV) is recommended as first-line drug therapy for unresectable-HCC, but the effect of sarcopenia on patients treated with ATZ/BEV is unknown. Methods: We enrolled 98 patients treated with ATZ/BEV or LEN. Computed tomography performed before the initiation of drug therapy was used to diagnose sarcopenia in accordance with the criteria proposed by the Japanese Society of Hepatology. Patients were divided into two groups based on the presence or absence of sarcopenia in each regimen, and patient characteristics, adverse events, and prognosis were compared. Results: In ATZ/BEV therapy, 57.1% of patients had sarcopenia. The sarcopenia group had significantly more women (P = 0.0125) and more macroscopic vascular invasion (P = 0.0270). Sarcopenia had no significant effect on progression-free survival (PFS) and overall survival (OS). In LEN therapy, 63.4% of patients had sarcopenia. The sarcopenia group was significantly older (P = 0.0064) and had a higher number of women (P = 0.0003), a higher neutrophil-lymphocyte ratio (P = 0.0222), worse albumin-bilirubin grade (P = 0.0087), and worse best response (P = 0.0255). PFS (P = 0.0091) and OS (P = 0.0006) were worse in the sarcopenia group. In multivariate analysis, age (P = 0.0362), lymphocyte-monocyte ratio (P = 0.0365), and sarcopenia (P = 0.0268) were independent prognostic factors for OS. Conclusion: In ATZ/BEV therapy, sarcopenia does not determine prognosis, and therapeutic efficacy can be expected even in cases of sarcopenia..
82. Takashi Niizeki, Takayuki Tokunaga, Yuko Takami, Yoshiyuki Wada, Masaru Harada, Michihiko Shibata, Kazuhiko Nakao, Ryu Sasaki, Fumihito Hirai, Satoshi Shakado, Tomoharu Yoshizumi, Shinji Itoh, Hiroshi Yatsuhashi, Shigemune Bekki, Akio Ido, Seiichi Mawatari, Koichi Honda, Rie Sugimoto, Takeshi Senju, Hirokazu Takahashi, Takuya Kuwashiro, Tatsuji Maeshiro, Makoto Nakamuta, Yoshifusa Aratake, Tsutomu Yamashita, Yuichiro Otsuka, Shuichi Matsumoto, Tetsuro Sohda, Shigeo Shimose, Kenta Murotani, Yasuhito Tanaka, Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis., Targeted oncology, 10.1007/s11523-022-00921-x, 17, 6, 643-653, 2022.11, BACKGROUND: A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. OBJECTIVE: This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. PATIENTS AND METHODS: This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. RESULTS: After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). CONCLUSIONS: ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN..
83. Ryota Nakanishi, Yoshiaki Fujimoto, Masahiko Sugiyama, Yuichi Hisamatsu, Tomonori Nakanoko, Koji Ando, Mitsuhiko Ota, Yasue Kimura, Eiji Oki, Tomoharu Yoshizumi, Clinical impact of the triple-layered circular stapler for reducing the anastomotic leakage in rectal cancer surgery: Porcine model and multicenter retrospective cohort analysis., Annals of gastroenterological surgery, 10.1002/ags3.12516, 6, 2, 256-264, 2022.03, Aim: To investigate the impact of the triple-layered circular stapler compared with the double-layered circular stapler on anastomotic leakage after rectal cancer surgery. Methods: The bursting pressure was compared between porcine ileocolic anastomoses created using a double- or triple-layered stapler. We also retrospectively analyzed the incidence of severe anastomotic leakage in 194 patients who underwent colorectal anastomosis using a double- or triple-layered circular stapler during rectal cancer resection performed in two cancer centers between January 2015 and April 2021. Results: In the porcine model, the bursting pressure was higher in anastomoses created using the triple-layered stapler than the double-layered stapler (end-to-end anastomosis: 26.4 ± 6.2 mm Hg vs 14.5 ± 4.3 mm Hg, P = .0031; side-to-side anastomosis: 27.7 ± 5.0 mm Hg vs 18.0 ± 2.9 mm Hg, P = .0275). Intersectional leakage occurred in 41% and 83% of anastomoses created using the triple- or double-layered stapler, respectively (P = .0821). In the clinical cohort, the double- and triple-layered stapler was used in 153 and 41 patients, respectively. The incidence of anastomotic leakage was lower for anastomoses created using the triple-layered stapler vs the double-layered stapler (0.0% vs 5.8%, P = .0362). In multivariate analysis, the factors independently associated with a lower incidence of anastomotic leakage were female sex (odds ratio: 0.16, 95% confidence interval: 0.01-0.90, P = .0354) and triple-layered stapler usage (odds ratio: 0.00, 95% confidence interval: 0.00-0.96, P = .0465). Conclusion: Anastomoses created using a triple-layered circular stapler had high bursting pressure, which might contribute to a lower incidence of anastomotic leakage after rectal cancer surgery..
84. Shinji Itoh, Yoshihiro Nagao, Kazutoyo Morita, Takeshi Kurihara, Takahiro Tomino, Yukiko Kosai-Fujimoto, Noboru Harada, Nobuhiro Fujita, Yasuhiro Ushijima, Masaki Mori, Tomoharu Yoshizumi, Association between Sarcopenia and Omega-3 Polyunsaturated Fatty Acid in Patients with Hepatocellular Carcinoma., JMA journal, 10.31662/jmaj.2022-0037, 5, 2, 169-176, 2022.04, Introduction: This study aimed to validate whether preoperative sarcopenia can predict long-term outcomes in patients with hepatocellular carcinoma (HCC) and identify the associations between sarcopenia and polyunsaturated fatty acids (PUFAs). Methods: This large, retrospective study included 353 patients who underwent hepatic resection for HCC and preoperative computed tomography scans. Skeletal muscle mass was measured at the third lumbar vertebrae. The cutoff value for sarcopenia followed the Japan Society of Hepatology's assessment criteria for sarcopenia. Results: Ninety-three patients (26.3%) with preoperative sarcopenia were enrolled. These patients had a significantly lower body mass index (p < 0.0001) and serum albumin level (p = 0.0070) as well as a higher rate of advanced-stage cancer (p = 0.0062) than those without sarcopenia. Patients with sarcopenia had significantly shorter overall survival than the other patients before (p = 0.0001) and after (p = 0.0415) propensity score matching. The sarcopenia group was significantly associated with low levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which were categorized based on omega-3 PUFAs, compared with those in the non-sarcopenia group (p = 0.0030 and p = 0.0135). Conclusions: We demonstrated an association between sarcopenia and the long-term prognosis in patients with HCC. Low EPA and DHA levels were associated with preoperative sarcopenia. Further prospective studies are needed to investigate whether nutritional support using omega-3 PUFAs can prevent and manage skeletal muscle mass depletion..
85. Kazuki Takada, Mototsugu Shimokawa, Fumitaka Mizuki, Shinkichi Takamori, Tomoyoshi Takenaka, Naoko Miura, Yasunori Shikada, Tomoharu Yoshizumi, Association between sex and outcomes in patients with non-small-cell lung cancer receiving combination chemoimmunotherapy as a first-line therapy: a systematic review and meta-analysis of randomized clinical trials., European journal of medical research, 10.1186/s40001-022-00789-7, 27, 1, 157-157, 2022.08, INTRODUCTION: Recently, several meta-analyses have investigated the association between sex and the efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC). However, this issue remains controversial, because the results have been inconsistent. Moreover, the effect of sex on outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy is poorly understood. The aim of this study was to examine the association between sex and outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy. METHODS: We searched PubMed and Scopus from database inception to Feb 18, 2022 and performed a systematic review and meta-analysis of randomized and controlled clinical trials investigating ICI+non-ICI vs non-ICI as a first-line therapy in NSCLC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) in male and female patients were calculated using common and random-effects models. RESULTS: We analyzed 5,830 patients, comprising 4,137 (71.0%) males and 1,693 (29.0%) females, from nine randomized clinical trials. The pooled HR (95%CI) for OS comparing ICI+non-ICI vs non-ICI was 0.80 (0.72-0.87) for males and 0.69 (0.54-0.89) for females. The pooled HR (95%CI) for PFS comparing ICI+non-ICI vs non-ICI was 0.60 (0.55-0.66) for males and 0.56 (0.44-0.70) for females. CONCLUSIONS: In patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy, a greater improvement in OS and PFS was observed in female patients than in male patients..
86. Ryota Nakanishi, Ken’ichi Morooka, Kazuki Omori, Satoshi Toyota, Yasushi Tanaka, Hirofumi Hasuda, Naomichi Koga, Kentaro Nonaka, Qingjiang Hu, Yu Nakaji, Tomonori Nakanoko, Koji Ando, Mitsuhiko Ota, Yasue Kimura, Eiji Oki, Yoshinao Oda, Tomoharu Yoshizumi, Artificial Intelligence-Based Prediction of Recurrence after Curative Resection for Colorectal Cancer from Digital Pathological Images, Annals of Surgical Oncology, 10.1245/s10434-022-12926-x, 30, 6, 3515-3516, 2022.12, BACKGROUND: To develop an artificial intelligence-based model to predict recurrence after curative resection for stage I-III colorectal cancer from digitized pathological slides. PATIENTS AND METHODS: In this retrospective study, 471 consecutive patients who underwent curative resection for stage I-III colorectal cancer at our institution from 2004 to 2015 were enrolled, and 512 randomly selected tiles from digitally scanned images of hematoxylin and eosin-stained tumor tissue sections were used to train a convolutional neural network. Five-fold cross-validation was used to validate the model. The association between recurrence and the model's output scores were analyzed in the test cohorts. RESULTS: The area under the receiver operating characteristic curve of the cross-validation was 0.7245 [95% confidence interval (CI) 0.6707-0.7783; P < 0.0001]. The score successfully classified patients into those with better and worse recurrence free survival (P < 0.0001). Multivariate analysis revealed that a high score was significantly associated with worse recurrence free survival [odds ratio (OR) 1.857; 95% CI 1.248-2.805; P = 0.0021], which was independent from other predictive factors: male sex (P = 0.0238), rectal cancer (P = 0.0396), preoperative abnormal carcinoembryonic antigen (CEA) level (P = 0.0216), pathological T3/T4 stage (P = 0.0162), and pathological positive lymph node metastasis (P < 0.0001). CONCLUSIONS: The artificial intelligence-based prediction model discriminated patients with a high risk of recurrence. This approach could help decision-makers consider the benefits of adjuvant chemotherapy..
87. Kazuki Takada, Sebastiano Buti, Melissa Bersanelli, Mototsugu Shimokawa, Shinkichi Takamori, Taichi Matsubara, Tomoyoshi Takenaka, Tatsuro Okamoto, Motoharu Hamatake, Yuko Tsuchiya-Kawano, Kohei Otsubo, Yoichi Nakanishi, Isamu Okamoto, David J Pinato, Alessio Cortellini, Tomoharu Yoshizumi, Antibiotic-dependent effect of probiotics in patients with non-small cell lung cancer treated with PD-1 checkpoint blockade., European journal of cancer (Oxford, England : 1990), 10.1016/j.ejca.2022.06.002, 172, 199-208, 2022.06, BACKGROUND: We previously validated in European patients with NSCLC treated with programmed death-1 (PD-1) checkpoint inhibitors the cumulative detrimental effect of concomitant medications. MATERIALS AND METHODS: We evaluated the prognostic ability of a "drug score" computed on the basis of baseline corticosteroids, proton pump inhibitors, and antibiotics, in an independent cohort of Japanese patients with advanced NSCLC treated with PD-1 monotherapy. Subsequently, we assessed the impact of baseline probiotics on the score's diagnostic ability and their interaction with antibiotics in influencing survival. RESULTS: Among the 293 eligible patients, good (19.5 months), intermediate (13.4 months), and poor (3.7 months) risk groups displayed a significantly different overall survival (OS) (log-rank test for trend: p = 0.016), but with a limited diagnostic ability (C-index: 0.57, 95%CI: 0.53-0.61), while no significant impact on progression-free survival (PFS) was reported (log-rank test for trend: p = 0.080; C-index: 0.55, 95%CI: 0.52-0.58). Considering the impact of the probiotics∗antibiotics interaction (p-value 0.0510) on OS, we implemented the drug score by assigning 0 points to concomitant antibiotics and probiotics. With the adapted drug score good, intermediate, and poor risk patients achieved a median OS of 19.6 months, 13.1 months, and 3.7 months, respectively, with a similar diagnostic ability (log-rank test for trend: p = 0.006; C-index: 0.58, 95%CI: 0.54-0.61). However, the diagnostic ability for PFS of the adapted score was improved (log-rank test for trend: p = 0.034; C-index: 0.62, 95%CI: 0.54-0.69). CONCLUSIONS: Although we failed to validate the drug score in this independent Japanese cohort, we showed that probiotics may have an antibiotic-dependent impact on its prognostic value. Further investigation looking at the effect of concomitant medications and probiotics across cohorts of different ethnicities is warranted..
88. Noriaki Wada, Nobuhiro Fujita, Keisuke Ishimatsu, Seiichiro Takao, Tomoharu Yoshizumi, Yoshiko Miyazaki, Yoshinao Oda, Akihiro Nishie, Kousei Ishigami, Yasuhiro Ushijima, A novel fast kilovoltage switching dual-energy computed tomography technique with deep learning: Utility for non-invasive assessments of liver fibrosis., European journal of radiology, 10.1016/j.ejrad.2022.110461, 155, 110461-110461, 2022.10, PURPOSE: To investigate whether the iodine density of liver parenchyma in the equilibrium phase and extracellular volume fraction (ECV) measured by deep learning-based spectral computed tomography (CT) can enable noninvasive liver fibrosis staging. METHOD: We retrospectively analyzed 63 patients who underwent dynamic CT using deep learning-based spectral CT before a hepatectomy or liver transplantation. The iodine densities of the liver parenchyma (I-liver) and abdominal aorta (I-aorta) were independently measured by two radiologists using iodine density images at the equilibrium phase. The iodine-density ratio (I-ratio: I-liver/I-aorta) and CT-ECV were calculated. Spearman's rank correlation analysis was used to evaluate the relationship between the I-ratio or CT-ECV and liver fibrosis stage, and receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performances of the I-ratio and CT-ECV. RESULTS: The I-ratio and CT-ECV showed significant positive correlations with liver fibrosis stage (ρ = 0.648, p < 0.0001 and ρ = 0.723, p < 0.0001, respectively). The areas under the ROC curve for the CT-ECV were 0.882 (F0 vs ≥ F1), 0.873 (≤F1 vs ≥ F2), 0.848 (≤F2 vs ≥ F3), and 0.891 (≤F3 vs F4). CONCLUSIONS: Deep learning-based spectral CT may be useful for noninvasive assessments of liver fibrosis..
89. Kei Hagiwara, Norifumi Harimoto, Takahiro Yamanaka, Norihiro Ishii, Takehiko Yokobori, Mariko Tsukagoshi, Akira Watanabe, Kenichiro Araki, Tomoharu Yoshizumi, Ken Shirabe, A new liver regeneration molecular mechanism involving hepatic stellate cells, Kupffer cells, and glucose-regulated protein 78 as a new hepatotrophic factor., Journal of hepato-biliary-pancreatic sciences, 10.1002/jhbp.1183, 30, 2, 165-176, 2022.05, BACKGROUND/PURPOSE: To overcome liver failure, we focused on liver regeneration mechanisms by the activation of hepatic stellate cells (HSCs) and Kupffer cells (KCs). It is known that the HSC-secreted Mac-2-binding protein glycan isomer (M2BPGi) activates KC in the fibrotic liver. However, its importance for liver regeneration of the HSCs/M2BPGi/KCs axis after hepatectomy is still unknown. The aim of this study was to clarify whether the HSC-derived M2BPGi can activate KCs after hepatectomy, and elucidate the new molecular mechanism of liver regeneration. METHODS: We examined the effect of M2BPGi on human hepatocytes and KCs, and explored secretory factors from M2BPGi-activated KCs using proteomics. Furthermore, the effect on liver regeneration of glucose-regulated protein 78 (GRP78) as one of the M2BPGi-related secreted proteins was examined in vitro and in murine hepatectomy models. RESULTS: Although M2BPGi had no hepatocyte-promoting effect, M2BPGi promoted the production of GRP78 in KCs. The KC-driven GRP78 promoted hepatocyte proliferation. GRP78 administration facilitated liver regeneration after 70% hepatectomy and increased the survival rate after 90% hepatectomy in mice. CONCLUSIONS: The M2BPGi-activated KCs secrete GRP78, which facilitates liver regeneration and improves the survival in a lethal mice model. Our data suggest that the new hepatotrophic factor GRP78 may be a promising therapeutic tool for lethal liver failure..
90. Atsushi Nanashima, Susumu Eguchi, Toru Hisaka, Yota Kawasaki, Yo-ichi Yamashita, Takao Ide, Tamotsu Kuroki, Tomoharu Yoshizumi, Kenji Kitahara, Yuichi Endo, Tohru Utsunomiya, Masatoshi Kajiwara, Masahiko Sakoda, Kohji Okamoto, Hiroaki Nagano, Yuko Takami, Toru Beppu, Risk Factors of Complications from Central Bisectionectomy (H458) for Hepatocellular Carcinoma: A Multi-Institutional Single-Arm Analysis, Cancers, 10.3390/cancers15061740, 15, 6, 1740-1740, 2023.03, Background: This study aims to clarify the perioperative risk factors and short-term prognosis of central bisectionectomy (CB) for hepatocellular carcinoma (HCC). Methods: Surgical data from 142 selected patients out of 171 HCC patients who underwent anatomical CB (H458) between 2005 and 2020 were collected from 17 expert institutions in a single-arm retrospective study. Results: Morbidities recorded by the International Study Group of Liver Surgery (ISGLS) from grade BC post-hepatectomy liver failure (PHLF) and bile leakage (PHBL), or complications requiring intervention were observed in 37% of patients. A multivariate analysis showed that increased blood loss (iBL) > 1500 mL from PHLF (risk ratio [RR]: 2.79), albumin level < 4 g/dL for PHBL (RR, 2.99), involvement of segment 1, a large size > 6 cm, or compression of the hepatic venous confluence or cava by HCC for all severe complications (RR: 5.67, 3.75, 6.51, and 8.95, respectively) (p < 0.05) were significant parameters. Four patients (3%) died from PHLF. HCC recurred in 50% of 138 surviving patients. The three-year recurrence-free and overall survival rates were 48% and 81%, respectively. Conclusions: Large tumor size and surrounding tumor involvement, or compression of major vasculatures and the related iBL > 1500 mL were independent risk factors for severe morbidities in patients with HCC undergoing CB..
91. Yuriko Tsutsui, Sachiyo Yoshio, Takahiro Tomiyama, Tomonari Shimagaki, Shinji Itoh, Noboru Harada, Yuichi Yoshida, Shiori Yoshikawa, Eiji Kakazu, Tatsuya Kanto, Tomoharu Yoshizumi, Preoperative serum brain-derived neurotrophic factor as a predictive biomarker for sepsis after living-donor liver transplantation., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13834, 53, 1, 72-83, 2023.01, AIM: Although the survival rate after living-donor liver transplantation (LDLT) is improving, sepsis still limits the prognosis. Immune dysfunction and sarcopenia are often observed in LDLT patients, and increase susceptibility to infection. Brain-derived neurotrophic factor (BDNF) is a myokine produced by immune cells and skeletal muscle. We aimed to determine whether serum BDNF could be a feasible biomarker for sepsis of LDLT patients. METHODS: We measured serum samples from 124 patients who underwent LDLT and 9 healthy volunteers for BDNF. We examined its correlation with incidence rate of sepsis. To clarify the source of BDNF, we examined its expression in lymphocytes, skeletal muscle cells, and hepatocytes. RESULTS: Patients who experienced sepsis showed worse short-term survival. Preoperative serum BDNF was lower in LDLT patients compared with healthy volunteers, and was also lower in Child-Pugh C compared with Child-Pugh A or B. Serum BDNF was inversely correlated with Model for End-Stage Liver Disease and controlling nutritional status (CONUT) scores, but had a weak positive correlation with skeletal muscle mass index (SMI). Multivariate analysis revealed that serum BDNF was independently associated with sepsis. Preoperative serum BDNF was a better predictor of sepsis in LDLT patients than CONUT score or SMI. Serum BDNF was positively correlated with lymphocyte counts, especially T cells. In vitro, T cells and skeletal muscle cells produced BDNF. CONCLUSIONS: Preoperative serum BDNF could be a predictive biomarker for sepsis after LDLT, by reflecting the systemic condition including hepatic function, nutritional status, and immune status..
92. Yoshihiko Maehara, Eiji Oki, Mitsuhiko Ota, Norifumi Harimoto, Koji Ando, Ryota Nakanishi, Tetsuro Kawazoe, Yoshiaki Fujimoto, Kentaro Nonaka, Hiroyuki Kitao, Makoto Iimori, Kunio Makino, Teiji Takechi, Takeshi Sagara, Kazutaka Miyadera, Kazuaki Matsuoka, Hiroshi Tsukihara, Yuki Kataoka, Takeshi Wakasa, Hiroaki Ochiiwa, Yoshihiro Kamahori, Eriko Tokunaga, Hiroshi Saeki, Tomoharu Yoshizumi, Yoshihiro Kakeji, Ken Shirabe, Hideo Baba, Mitsuo Shimada, Lineage of drug discovery research on fluorinated pyrimidines: chronicle of the achievements accomplished by Professor Setsuro Fujii., International journal of clinical oncology, 10.1007/s10147-023-02326-w, 28, 5, 613-624, 2023.03, Prof. Setsuro Fujii achieved significant results in the field of drug discovery research in Japan. He developed nine well-known drugs: FT, UFT, S-1 and FTD/TPI are anticancer drugs, while cetraxate hydrochloride, camostat mesilate, nafamostat mesilate, gabexate mesilate and pravastatin sodium are therapeutic drugs for various other diseases. He delivered hope to patients with various diseases across the world to improve their condition. Even now, drug discovery research based on Dr. Fujii's ideas is continuing..
93. Kozue Kakizoe, Takehiro Torisu, Yutaro Ihara, Noboru Harada, Tomoharu Yoshizumi, Shin Fujioka, Masahiro Kondo, Takanari Kitazono, Gastroduodenal ulcers in liver transplant recipients under immunosuppressive therapy., Digestive diseases (Basel, Switzerland), 10.1159/000530472, 2023.04, Introduction The proportion of gastroduodenal ulcers caused by drugs is increasing. However, the risk of gastroduodenal ulcer from drugs other than non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin (LDA) is unclear. An association between immunosuppressive drugs and gastroduodenal ulcers has been suggested. We aimed to identify the immunosuppressive drugs and clinical characteristics associated with gastroduodenal ulcers in post-liver transplant patients. Methods The study investigated 119 patients who underwent esophagogastroduodenoscopy after liver transplantation and two patients were excluded. Clinical characteristics, medications, and endoscopic images were retrospectively reviewed. Results Among 117 post-living donor liver transplant recipients, gastroduodenal ulcers were found in 10 (9.2%) patients. The ulcer group had endoscopically gastritis more frequently (40%) compared with the non-ulcer group (10%). Logistic regression analysis revealed gastritis, NSAIDs use and mycophenolate mofetil were risk factors in the post-liver transplant patients. Among 103 patients not on NSAIDs, eight (7.8%) had peptic ulcer. The most common ulcer site and ulcer shape were the gastric antrum and a circular shape, respectively. All patients in the ulcer group were taking mycophenolate mofetil, which was the only immunosuppressive drug that showed a significant difference between the two groups. Five out of eight ulcer patients (63%) were taking gastric acid suppressants, and gastroduodenal ulcers in post-liver transplant recipients were suggested to be refractory. Conclusion Patients treated with immunosuppressive drugs after liver transplantation can develop gastroduodenal ulcers, even with gastric acid suppressant medication. Mycophenolate mofetil may increase the risk of gastroduodenal ulcers compared with other immunosuppressive drugs..
94. Kazuhiro Kai, Toshifumi Fujiwara, Yoshihiro Nagao, Eiji Oki, Tomoharu Yoshizumi, Masatoshi Eto, Yasuharu Nakashima, Evaluation of bone density and skeletal muscle mass after sleeve gastrectomy using computed tomography method., Bone reports, 10.1016/j.bonr.2023.101661, 18, 101661-101661, 2023.06, INTRODUCTION: Sleeve gastrectomy is the most common surgical procedure to reduce weight and treat metabolic complications in patients with moderate-to-severe obesity; however, it affects the musculoskeletal system. Dual-energy X-ray absorptiometry (DXA), which is commonly used to measure bone mineral density (BMD), may be affected by excess fat tissue around the bones, interrupting BMD measurement. Due to the strong correlation between DXA and the Hounsfield units (HU) obtained from computed tomography (CT) scans, BMD assessment using clinical abdominal CT scans has been useful. To date, there has been no report of detailed CT evaluation in patients with severe obesity after sleeve gastrectomy. OBJECTIVE: This study investigated the effect of sleeve gastrectomy in severely obese patients on bone and psoas muscle density, and cross-sectional area using retrospective clinical CT scans. METHODS: This was a retrospective observational study that included 86 patients (35 males and 51 females) who underwent sleeve gastrectomy between March 2012 and May 2019. Patients' clinical data (age at the time of surgery, sex, body weight, body mass index (BMI), comorbidities, and preoperative and postoperative blood test results, HU of the lumbar spine and psoas muscle and psoas muscle mass index (PMI)) were evaluated. RESULTS: The mean age at the time of surgery was 43 years, and the body weight and BMI significantly reduced (p < 0.01) after surgery. The mean hemoglobin A1c level showed significant improvement in males and females. Serum calcium and phosphorus levels remained unchanged before and after surgery. In CT analysis, HU of the lumbar spine and psoas muscle showed no significant decrease, but PMI showed a significant decrease (p < 0.01). CONCLUSIONS: Sleeve gastrectomy could dramatically improve anthropometric measures without causing changes in serum calcium and phosphorus levels. Preoperative and postoperative abdominal CT revealed no significant difference in the bone and psoas muscle density, and the psoas muscle mass was significantly decreased after sleeve gastrectomy..
95. Takahiro Tomino, Shinji Itoh, Nobuhiro Fujita, Daisuke Okamoto, Yuki Nakayama, Katsuya Toshida, Takahiro Tomiyama, Yuriko Tsutsui, Yukiko Kosai, Takeshi Kurihara, Yoshihiro Nagao, Kazutoyo Morita, Noboru Harada, Yasuhiro Ushijima, Kenichi Kohashi, Kousei Ishigami, Yoshinao Oda, Tomoharu Yoshizumi, Clinical association between intraoperative indocyanine green fluorescence imaging pattern, preoperative Gd-EOB-DTPA-enhanced magnetic resonance imaging findings, and histological differentiation in hepatocellular carcinoma., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13902, 2023.03, AIM: We aimed to evaluate the association between the intraoperative indocyanine green (ICG) fluorescence imaging (FI) pattern, preoperative magnetic resonance imaging (MRI) findings using gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), preoperative diffusion-weighted imaging (DWI) of MRI, and histological differentiation of hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the data for 80 tumors of 64 patients. Intraoperative ICG FI patterns were classified into cancerous or rim-positive type. We evaluated the signal intensity ratio of the tumor and the surrounding liver tissue in the portal phase (SIRPP) and intensity in the hepatobiliary phase (HBP) of Gd-EOB-DTPA-enhanced MRI, the apparent diffusion coefficient (ADC) in the DWI of MRI, and clinicopathologic factors. RESULTS: In the rim-positive group, the rate of poorly differentiated HCC and hypointensity type in HBP were significantly higher, and SIRPP and ADC were significantly lower than the rim-negative group. In the cancerous group, the rate of well or moderately differentiated HCC and hyperintensity type in HBP, SIRPP, and ADC were significantly higher than the noncancerous group. Multivariate analysis identified low SIRPP, low ADC, and hypointensity type in HBP as the significant predictive factors for rim-positive HCC and high SIRPP, high ADC, and hyperintensity type in HBP as the significant predictive factors for cancerous HCC. The positive rate of programmed cell death 1-ligand 1 and vessels that encapsulate tumor clusters status of the rim-positive HCC and HCC with low SIRPP were significantly higher than the control group. CONCLUSIONS: The intraoperative ICG FI pattern of HCC closely correlated with histological differentiation, preoperative SIRPP and intensity type in the Gd-EOB-DTPA MRI, and preoperative ADC in the DWI of MRI..
96. Takahiro Tomiyama, Shinji Itoh, Norifumi Iseda, Katsuya Toshida, Yukiko Kosai-Fujimoto, Takahiro Tomino, Takeshi Kurihara, Yoshihiro Nagao, Kazutoyo Morita, Noboru Harada, Yu-Chen Liu, Daisuke Ozaki, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Tomoharu Yoshizumi, Clinical Significance of Signal Regulatory Protein Alpha (SIRPα) Expression in Hepatocellular Carcinoma., Annals of surgical oncology, 10.1245/s10434-022-13058-y, 30, 6, 3378-3389, 2023.01, BACKGROUND: Signal regulatory protein alpha (SIRPα), expressed in the macrophage membrane, inhibits phagocytosis of tumor cells via CD47/SIRPα interaction, which acts as an immune checkpoint factor in cancers. This study aimed to clarify the clinical significance of SIRPα expression in hepatocellular carcinoma (HCC). METHODS: This study analyzed SIRPα expression using RNA sequencing data of 372 HCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical staining of our 189 HCC patient cohort. The correlation between SIRPα expression and clinicopathologic factors, patient survival, and intratumor infiltration of immune cells was investigated. RESULTS: Overall survival (OS) was significantly poorer with high SIRPα expression than with low expression in both TCGA and our cohort. High SIRPα expression correlated with lower recurrence-free survival (RFS) in our cohort. High SIRPα expression was associated with higher rates of microvascular invasion and lower serum albumin levels and correlated with greater intratumor infiltration of CD68-positive macrophages and myeloid-derived suppressor cells (MDSCs). Multivariate analysis showed that SIRPα expression and high infiltration of CD8-positive T cells and MDSCs were predictive factors for both RFS and OS. Patients with high SIRPα expression and infiltration of CD8-positive T cells and MDSCs had significantly lower RFS and OS rates. In spatial transcriptomics sequencing, SIRPα expression was significantly correlated with CD163 expression. CONCLUSIONS: High SIRPα expression in HCC indicates poor prognosis, possibly by inhibiting macrophage phagocytosis of tumor cells, promoting MDSC infiltration and inducing antitumor immunity. Treatment alternatives using SIRPα blockage should be considered in HCC as inhibiting macrophage antitumor immunity and MDSCs..
97. Katsuya Toshida, Shinji Itoh, Noboru Harada, Akinari Morinaga, Kyohei Yugawa, Takahiro Tomiyama, Yukiko Kosai-Fujimoto, Takahiro Tomino, Takeshi Kurihara, Yoshihiro Nagao, Kazutoyo Morita, Yoshinao Oda, Tomoharu Yoshizumi, Cancer-associated fibroblasts promote tumor cell growth via miR-493-5p in intrahepatic cholangiocarcinoma., Cancer science, 10.1111/cas.15644, 114, 3, 937-947, 2023.03, The association between tumor microenvironment (TME) and cancer-associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma (ICC) progression is poorly understood. This study aimed to reveal whether specific microRNAs (miRNAs) in extracellular vesicles (EVs) derived from CAFs were involved in ICC progression. Conditioned medium (CM) and EVs in the CM of CAFs and normal fibroblasts (NFs) derived from ICC specimens were used to investigate the effects on tumor cell lines. miRNA microarray assay was used to examine the miRNAs of EVs derived from CAFs and NFs in ICC, and the effects of miR-493-5p on tumor cell lines were examined. Additionally, databases were used to identify miR-493-5p targets, and the relationship between prognosis of ICC patients and cocaine- and amphetamine-regulated transcript propeptide (CARTPT), one of the targets of miR-493-5p, expression in ICC tissues was retrospectively analyzed. Compared with NF-derived CM and EVs, CAF-derived CM and EVs promoted cell lines in proliferation, scratch, migration, and invasion assays. miRNA microarray analysis revealed that miR-493-5p was significantly increased in CAF-derived EVs compared to NF-derived EVs. Tumor cell lines transfected with miR-493-5p were promoted in proliferation and scratch assays. Immunohistochemical staining was performed on 76 ICC specimens; both overall and recurrence-free survival rates were significantly worse in the CARTPT-negative group. Univariate and multivariate analyses showed that low CARTPT expression was an independent poor prognostic factor for overall and recurrence-free survival. Overall, our data suggest that CAFs in the ICC TME suppress CARTPT in tumor cells and promote tumor cells via miR-493-5p in EVs..
98. Takahiro Tomiyama, Shinji Itoh, Norifumi Iseda, Katsuya Toshida, Yukiko Kosai-Fujimoto, Takahiro Tomino, Takeshi Kurihara, Yoshihiro Nagao, Kazutoyo Morita, Noboru Harada, Yu-Chen Liu, Daisuke Okuzaki, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Tomoharu Yoshizumi, ASO Visual Abstract: Clinical Significance of Signal Regulatory Protein Alpha (SIRPα) Expression in Hepatocellular Carcinoma., Annals of surgical oncology, 10.1245/s10434-023-13182-3, 30, 6, 3390-3391, 2023.02.
99. Takahiro Tomiyama, Shinji Itoh, Katsuya Toshida, Akinari Morinaga, Yukiko Fujimoto-Kosai, Takahiro Tomino, Takeshi Kurihara, Yoshihiro Nagao, Kazutoyo Morita, Noboru Harada, Kenichi Kohashi, Yuichiro Eguchi, Yoshinao Oda, Masaki Mori, Tomoharu Yoshizumi, A rare case of unresectable, microsatellite instability-high hepatocellular carcinoma and an examination of the tumor microenvironment., International cancer conference journal, 10.1007/s13691-022-00585-4, 12, 1, 81-86, 2023.01, Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide, and the mortality rate of patients with unresectable HCC is very high. Microsatellite instability (MSI) is an essential biomarker for response to immune checkpoint inhibitors (ICI) in various tumors. However, the frequency of MSI in HCC is low (1.11%). There is only one case report of MSI-high HCC, and it is not well understood how high MSI affects the tumor microenvironment of HCC. Hence, we describe an interesting patient with unresectable MSI-high HCC, including the evaluation of immune status in the tumor microenvironment. A 68-year-old man presented to our department with HCC in liver segment 1. Contrast-enhanced CT revealed a liver tumor of 6.0 cm in maximum size. The patient underwent extended left and caudate lobectomy of the liver for HCC. Four months after surgical resection, contrast-enhanced computed tomography (CECT) detected 13 recurrent nodules. The patient was diagnosed with unresectable hepatocellular carcinoma recurrence, and we decided to administer systematic chemotherapy. Lenvatinib was administered over approximately 2 years as a first-line treatment, which resulted in intrahepatic tumor shrinkage. However, follow-up CECT showed new lesions, hepatogastric mesentery lymph node swelling, and peritoneal dissemination. After MSI-high status was identified, the patient began to receive pembrolizumab (200 mg, every 3 weeks). Eleven cycles of pembrolizumab therapy were administered over approximately 8 months, during which the diameter of the hepatogastric mesentery lymph node swelling and peritoneal dissemination showed shrinkage but later re-increased. As the third- and fourth-line therapy has been administered, the tumors and lymph nodes have shrunk. We report a rare case in which multikinase inhibitors were effectively used to treat MSI-high HCC..
100. Kaori Kuramitsu, Takumi Fukumoto, Hiroto Egawa, Hideki Ohdan, Koji Umeshita, Shinji Uemoto, Taizo Hibi, Mureo Kasahara, Tomoharu Yoshizumi, Koichi Mizuta, Tsuyoshi Shimamura, Hiroyuki Furukawa, A Multicenter Japanese Survey Assessing the Long-term Outcomes of Liver Retransplantation Using Living Donor Grafts., Transplantation, 10.1097/TP.0000000000002958, 104, 4, 754-761, 2020.04, BACKGROUND: Liver transplantation is the most suitable treatment option available for end-stage liver disease. However, some patients require retransplantation, despite medical advances that have led to improved survival. We aimed to compile a definitive, nationwide resource of liver retransplantation data in Japan, seeking to identify the predictors of patient survival posttransplantation. METHODS: Questionnaires were sent to 32 institutions that had conducted 281 retransplantations before 2015. RESULTS: Among the 265 patients included in this study (142 pediatric cases), the average age at primary transplantation was 23 years, and retransplantation was performed after an average of 1468 days. The main indication for retransplantation was graft rejection (95 patients). Living-donor liver transplantation accounted for 94.7% of primary transplantations and 73.2% of retransplantations. Patient survival at 1, 3, or 5 years did not differ by type of transplantation but was better for pediatric (70.8%, 68.3%, and 60.1%, respectively) than for adult (57.2%, 50.4%, and 45.2%, respectively) recipients (P = 0.0003). Small-for-size syndrome, retransplantation within 365 days, and inpatient status at retransplantation were significant predictors of poor survival in pediatric cases. Retransplantation within 365 days and conditions warranting retransplantation were significant predictors of poor survival in adult patients. CONCLUSIONS: In Japan, where >70% of retransplantations are performed using living donors, the indications and timing are different from those in previous reports from other countries, while maintaining comparable survival rates. Considering technical challenges, graft failure within 365 days should be thoroughly restricted to justify the use of living donor..
101. Shohei Yoshiya, Tomoharu Yoshizumi, Norifumi Iseda, Kazuki Takeishi, Takeo Toshima, Yoshihiro Nagao, Shinji Itoh, Noboru Harada, Toru Ikegami, Masaki Mori, Anastomosis of the Common Hepatic Artery and Round Ligament as Portal Vein Arterialization for Hepatic Artery Occlusion After Deceased Donor Liver Transplantation: A Case Report., Transplantation proceedings, 10.1016/j.transproceed.2019.12.003, 52, 2, 641-643, 2020.03, BACKGROUND: Hepatic artery occlusion (HAO) is a life-threatening complication after liver transplantation. We report a case of portal vein arterialization (PVA) with anastomosis of the recipient common hepatic artery (CHA) and a graft of the round ligament to achieve intrahepatic arterial flow. CASE PRESENTATION: A 57-year-old man had a medical history of decompensated liver cirrhosis secondary to cholestatic liver disease owing to biliary anastomotic stricture after living donor liver transplantation and end-stage renal failure. He underwent deceased donor liver and renal transplantation with anastomosis of the recipient proper hepatic artery and the graft CHA. He experience symptoms from HAO on postoperative day 23 and underwent emergency surgery to re-anastomose the hepatic artery. Despite several instances of re-anastomoses, intrahepatic arterial flow was not able to be achieved and therefore PVA with anastomosis of the recipient CHA and the graft round ligament was performed. Although liver enzyme levels rapidly declined after surgery and the finding of liver infarction was not observed, a large amount of watery stool was observed owing to portal hypertension, which was an adverse effect of PVA. As enhanced computed tomography on POD 31 showed a pseudoaneurysm of the anastomotic site, occlusion with coils was performed to arrest hemorrhage, and a contrast study after coil occlusion showed intrahepatic arterial blood flow via collateral arteries. Thereafter, the patient needed treatment for ischemic biliary duct stenosis and was discharged home on POD 98. CONCLUSION: PVA using a round ligament for HAO after liver transplantation might play a role as a bridge treatment until retransplantation or maturation of collaterals..
102. Masafumi Ohira, Tomoharu Yoshizumi, Kyohei Yugawa, Yukiko Kosai-Fujimoto, Shoichi Inokuchi, Takashi Motomura, Yohei Mano, Takeo Toshima, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Masaki Mori, Association of inflammatory biomarkers with long-term outcomes after curative surgery for mass-forming intrahepatic cholangiocarcinoma., Surgery today, 10.1007/s00595-019-01905-7, 50, 4, 379-388, 2020.04, PURPOSE: Inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are reportedly predictive of the long-term outcomes of several cancers. We evaluated their correlations with the post-surgical long-term outcomes of patients with mass-forming (MF) intrahepatic cholangiocarcinoma (ICC). METHODS: The subjects of this study were 52 patients who underwent hepatic resection for MF-ICC at our hospital. We measured the cutoff values of NLR, LMR and PLR, using receiver operating characteristic curves, and compared the survival rates of patients with high vs. those with low values. We also evaluated a prognostic scoring system based on significant inflammatory biomarkers. RESULTS: The cutoff values for NLR, LMR, and PLR were 1.93, 4.78, and 98, respectively. The high-NLR and low-LMR groups had significantly worse prognoses than the low-NLR and high-LMR groups. We designed a scoring system using the inflammation score (IS) based on NLR and LMR values, stratifying patients into three groups with scores of 0, 1, or 2. The IS was significantly correlated with overall survival (OS), with 5-year survival rates by the IS score of 100% for 0, 61% for 1, and 32% for 2 (P = 0.011). The IS was found to be an independent predictor of OS in multivariate analysis. CONCLUSIONS: Our IS scoring system may predict long-term outcomes after surgery for MF-ICC..
103. Takeo Toshima, Tomoharu Yoshizumi, Noboru Harada, Shinji Itoh, Masaki Mori, Authors' Reply: Prognostic Impact of Osteopenia in Patients Who Underwent Living Donor Liver Transplantation for Hepatocellular Carcinoma., World journal of surgery, 10.1007/s00268-020-05639-3, 44, 9, 3184-3185, 2020.09.
104. Yo-Ichi Yamashita, Shinichi Aishima, Yosuke Nakao, Tomoharu Yoshizumi, Hiroaki Nagano, Tamotsu Kuroki, Yuko Takami, Takao Ide, Masayuki Ohta, Mitsuhisa Takatsuki, Atsushi Nanashima, Fuminori Ishii, Kenji Kitahara, Satoshi Iino, Toru Beppu, Hideo Baba, Susumu Eguchi, Clinicopathological characteristics of combined hepatocellular cholangiocarcinoma from the viewpoint of patient prognosis after hepatic resection: High rate of early recurrence and its predictors., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13507, 50, 7, 863-870, 2020.07, AIM: Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a very rare subtype of primary liver carcinoma; therefore, its clinicopathological characteristics have not yet been elucidated in detail. The aim of the study was to reveal the clinicopathological characteristics and prognostic factors of cHCC-CCA after hepatic resection (HR) METHODS: A total of 124 patients who underwent curative HR for cHCC-CCA between 2000 and 2016 were enrolled in this multi-institutional study conducted by the Kyushu Study Group of Liver Surgery. Clinicopathological analysis was performed from the viewpoint of patient prognosis. RESULTS: A total of 62 patients (50%) had early recurrence within 1.5 years after HR, including 36 patients (58%) with extrahepatic recurrence. In contrast, just four patients (3%) had late recurrence occurring >3 years after HR. The independent predictors of early recurrence were as follows: des-gamma carboxyprothrombin >40 mAU/mL (odds ratio 26.2, P = 0.0117), carbohydrate antigen 19-9>37 IU/l (odds ratio 18.0, P = 0.0200), and poorly differentiated HCC or CCA (odds ratio 11.2, P = 0.0259). CONCLUSIONS: Half of the patients with cHCC-CCA had early recurrence after HR. Preoperative elevation of des-gamma carboxyprothrombin or carbohydrate antigen 19-9 and the existence of poorly differentiated components of HCC or CCA in resected specimens are predictors of its early recurrence..
105. Kyohei Yugawa, Kenichi Kohashi, Shinji Itoh, Tomoharu Yoshizumi, Ichiro Sakamoto, Hiroyuki Tsutsui, Masaki Mori, Yoshinao Oda, Combined hepatocellular-cholangiocarcinoma after tetralogy of Fallot repair: a case report and review of literature., Pathology, research and practice, 10.1016/j.prp.2020.152908, 216, 5, 152908-152908, 2020.05, BACKGROUND: Liver fibrosis and cancer are serious hepatic complications for patients with congenital heart diseases. We present a rare case of combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC-CCA) after the repair of tetralogy of Fallot (TOF). CASE PRESENTATION: A 54-year-old Japanese woman had undergone biventricular repair for TOF at 7 years old. She presented with abdominal distension. Abdominal CT revealed ascites and a 90-mm tumor involving the liver's left lobe. Tumor marker values were: alpha-fetoprotein, 16,208 ng/mL and des-gamma-carboxy prothrombin, 33,920 mAU/mL. The preoperative diagnosis was malignant tumor of the liver (e.g., HCC or intrahepatic CCA). We performed a left lobectomy of the liver. Histopathologically, the tumor was composed of two components growing in trabecular and irregular tubular patterns accompanied by a transitional area; the tumor was diagnosed as cHCC-CCA. The non-cancerous area showed fibrous change mainly surrounding a central vein and sinusoid, expanding toward the portal area without inflammation. CONCLUSIONS: We provide the details of our patient's cHCC-CCA that developed from fibrous congestive liver associated with right-sided heart failure after TOF repair, diagnosed based on histopathological features. We discuss liver fibrosis as a hepatic complication and a careful follow-up maneuver for improving the outcomes of patients with chronic hepatic congestion..
106. Tomoharu Yoshizumi, Masaki Mori, Correction to: Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy., Surgery today, 10.1007/s00595-019-01949-9, 50, 4, 423-423, 2020.04, The article Portal flow modulation in living donor liver transplantation: review..
107. Toru Ikegami, Tomoharu Yoshizumi, Takahiro Tomiyama, Shoichi Inokuchi, Masaki Mori, Extensive portal thrombectomy with secure shunt ligation should be more strongly emphasized in the real-world setting., Journal of hepatology, 10.1016/j.jhep.2019.09.009, 72, 1, 199-201, 2020.01.
108. Shinji Itoh, Tomoharu Yoshizumi, Kyohei Yugawa, Daisuke Imai, Shohei Yoshiya, Kazuki Takeishi, Takeo Toshima, Noboru Harada, Toru Ikegami, Yuji Soejima, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Impact of Immune Response on Outcomes in Hepatocellular Carcinoma: Association With Vascular Formation., Hepatology (Baltimore, Md.), 10.1002/hep.31206, 72, 6, 1987-1999, 2020.12, BACKGROUND AND AIMS: We investigated the prognostic value of programmed death ligand 1 (PD-L1) expression, tumor-infiltrating CD8-positive T-cell status, and their combination in hepatocellular carcinoma (HCC). Their association with PD-L1 expression and vascular formation was further explored. APPROACH AND RESULTS: Using a database of 387 patients who underwent hepatic resection for HCC, immunohistochemical staining of PD-L1, CD8, and CD34 was performed. Additionally, we undertook an enzyme-linked immunosorbent assay for soluble PD-L1. Compared with patients with HCC and PD-L1-negative expression (n = 311), patients with HCC and PD-L1-positive expression (n = 76) showed significantly worse overall survival (OS; multivariate hazard ratio, 2.502; 95% confidence interval [CI], 1.716-3.649; P < 0.0001). The presence of tumor-infiltrating CD8-positive T cells was significantly correlated with longer OS (multivariate hazard ratio, 0.383; 95% CI, 0.274-0.537; P < 0.0001). Stratification based on PD-L1 expression in cancer cells and tumor-infiltrating CD8-positive T-cell status was also significantly associated with OS (log-rank, P < 0.0001). HCC with PD-L1-positive expression was significantly correlated with positivity for vessels that encapsulated tumor clusters. Serum PD-L1 levels were significantly higher in the group of patients who had PD-L1-positive expression than in the group of patients who had PD-L1-negative expression (P = 0.0158). CONCLUSIONS: PD-L1 expression in cancer cells was associated with a poor clinical outcome and vascular formation in patients with HCC. Additionally, the combination of PD-L1 expression with tumor-infiltrating CD8-positive T-cell status enabled further classification of patients based on their clinical outcome. Thus, PD-L1 expression in cancer cells and tumor-infiltrating CD8-positive T-cell status might serve as predictive tissue biomarkers..
109. Noboru Harada, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Shinji Itoh, Kazuki Takeishi, Takeo Toshima, Yoshihiro Nagao, Shohei Yoshiya, Masaki Mori, Impact of middle hepatic artery reconstruction after living donor liver transplantation using the left lobe., Clinical transplantation, 10.1111/ctr.13850, 34, 6, e13850, 2020.06, INTRODUCTION: The aim of this study was to clarify the impact of middle hepatic artery reconstruction on the outcomes of duct-to-duct biliary anastomosis after living donor liver transplantation (LDLT) using the left lobe. MATERIALS AND METHODS: Among 258 patients who underwent LDLT using the left lobe, 216 patients who underwent hepatic artery reconstruction and one hepatic duct reconstruction with duct-to-duct interrupted anastomosis were divided into three groups: Group A (n = 123), one arterial stump with left hepatic artery reconstruction; Group B (n = 32), two arterial stumps with only left hepatic artery reconstruction; and Group C (n = 61), two arterial stumps with reconstruction of the left and middle hepatic arteries. The outcomes after LDLT were compared among the three groups. RESULTS: No hepatic artery complications occurred. Group B had a significantly greater incidence of anastomotic biliary stricture than Group C. A multivariate analysis with Cox regression revealed that being in Group B was the only significant independent risk factor for postoperative anastomotic biliary stricture after LDLT. CONCLUSIONS: Middle and left hepatic artery reconstruction is safe in LDLT and may prevent biliary stricture caused by dual hepatic artery reconstruction when the graft has left and middle hepatic artery stumps..
110. Seiichiro Takao, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Kakihara, Tomohiro Nakayama, Nobuhiro Fujita, Koichiro Morita, Keisuke Ishimatsu, Tomoharu Yoshizumi, Toru Ikegami, Masatoshi Kondo, Hiroshi Honda, Improved visualization of a fine intrahepatic biliary duct on drip infusion cholangiography-computed tomography: Impact of knowledge-based iterative model reconstruction., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13477, 50, 5, 629-634, 2020.05, AIM: The purpose of this study was to investigate the visualization of fine biliary ducts with knowledge-based iterative model reconstruction (IMR) in low-dose drip infusion computed tomography (CT) cholangiography (DIC-CT) as compared with filtered back projection (FBP) and hybrid iterative reconstruction (iDose4 ). METHODS: A total of 38 patients underwent DIC-CT for living donor liver transplantation. CT was performed approximately 20 min after the end of the infusion of meglumine iotroxate (100 mL). Images were reconstructed using FBP, iDose4 , and IMR, and 1-mm slice images at fixed window level and width were prepared for assessment. Two reviewers independently evaluated the quality of visualization of the fine biliary ducts of the caudate lobe (B1) using a 5-point scale. The visualization scores of three reconstructed images were compared using the Kruskal-Wallis test and Mann-Whitney U-test. RESULTS: For reviewer 1, the visualization score of IMR was significantly higher than that of FBP (P = 0.012), and tended to be higher than that of iDose4 (P = 0.078). For reviewer 2, the visualization score of IMR was significantly higher than those of both FBP and iDose4 (P < 0.01). CONCLUSIONS: IMR showed better visualization of B1 on DIC-CT than FBP or iDose4 . DIC-CT reconstructed with IMR may be useful to the anatomical grasp of biliary tracts in cases of hepatectomy..
111. Nobuhiro Fujita, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Tomohiro Nakayama, Yasuhiro Ushijima, Daisuke Kakihara, Yukihisa Takayama, Koichiro Morita, Keisuke Ishimatsu, Seiichiro Takao, Tomoharu Yoshizumi, Norihiro Furusyo, Hiroshi Honda, Increased and More Heterogeneous Gadoxetic Acid Uptake of the Liver Parenchyma after Hepatitis C Virus Eradication by Direct Antiviral Agent., Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine, 10.2463/mrms.tn.2019-0183, 19, 4, 389-393, 2020.12, We evaluated the changes of gadoxetic acid uptake of the liver parenchyma after hepatitis C virus (HCV) eradication by direct-antiviral agent (DAA) therapy. The increase rate of the liver-to-muscle signal intensity ratio, the skewness and the kurtosis were calculated in the hepatobiliary phase. After sustained virological response, gadoxetic acid uptake of the liver parenchyma increased, but became heterogeneous. Our study proved that HCV eradication by DAA therapy could significantly affect gadoxetic acid uptake..
112. Takahiro Nakamura, Mio Fukuda, Ryosuke Matsukane, Kimitaka Suetsugu, Noboru Harada, Tomoharu Yoshizumi, Nobuaki Egashira, Masaki Mori, Satohiro Masuda, Influence of POR*28 Polymorphisms on CYP3A5*3-Associated Variations in Tacrolimus Blood Levels at an Early Stage after Liver Transplantation., International journal of molecular sciences, 10.3390/ijms21072287, 21, 7, 2020.03, It is well known that the CYP3A5*3 polymorphism is an important marker that correlates with the tacrolimus dose requirement after organ transplantation. Recently, it has been revealed that the POR*28 polymorphism affects the pharmacokinetics of tacrolimus in renal transplant patients. In this study, we examined whether POR*28 as well as CYP3A5*3 polymorphism in Japanese recipients and donors would be another biomarker for the variation of tacrolimus blood levels in the recipients during the first month after living-donor liver transplantation. We enrolled 65 patients treated with tacrolimus, who underwent liver transplantation between July 2016 and January 2019. Genomic DNA was extracted from whole-blood samples, and genotyping was performed to examine the presence of CYP3A5*3 and POR*28 polymorphisms in the recipients and donors. The CYP3A5*3/*3 genotype (defective CYP3A5) of the recipient (standard partial regression coefficient [median C/D ratio of CYP3A5 expressor vs. CYP3A5 non-expressor, p value]: Pod 1-7, β= -0.389 [1.76 vs. 2.73, p < 0.001]; Pod 8-14, β = -0.345 [2.03 vs. 2.83, p < 0.001]; Pod 15-21, β= -0.417 [1.75 vs. 2.94, p < 0.001]; Pod 22-28, β = -0.627 [1.55 vs. 2.90, p < 0.001]) rather than donor (Pod 1-7, β = n/a [1.88 vs. 2.76]; Pod 8-14, β = n/a [1.99 vs. 2.93]; Pod 15-21, β = -0.175 [1.91 vs. 2.94, p = 0.004]; Pod 22-28, β = n/a [1.61 vs. 2.67]) significantly contributed to the increase in the concentration/dose (C/D) ratio of tacrolimus for at least one month after surgery. We found that the tacrolimus C/D ratio significantly decreased from the third week after transplantation when the recipient carried both CYP3A5*1 (functional CYP3A5) and POR*28 (n = 19 [29.2%], median C/D ratio [inter quartile range] = 1.58 [1.39-2.17]), compared with that in the recipients carrying CYP3A5*1 and POR*1/*1 (n = 8 [12.3%], median C/D ratio [inter quartile range] = 2.23 [2.05-3.06]) (p < 0.001). In conclusion, to our knowledge, this is the first report suggesting that the POR*28 polymorphism is another biomarker for the tacrolimus oral dosage after liver transplantation in patients carrying CYP3A5*1 rather than CYP3A5*3/*3..
113. Shinji Itoh, Tomoharu Yoshizumi, Masaki Mori, Is sarcopenic obesity superior to sarcopenia as a predicting indicator in patients with hepatocellular carcinoma following hepatic resection?, Hepatobiliary surgery and nutrition, 10.21037/hbsn.2019.09.14, 9, 2, 202-204, 2020.04.
114. Yukiko Kosai-Fujimoto, Tomoharu Yoshizumi, Takahiro Tomiyama, Akinari Morinaga, Norifumi Iseda, Shoichi Inokuchi, Kyohei Yugawa, Shohei Yoshiya, Takeo Toshima, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Masaki Mori, Living-Donor Liver Transplantation for Patients With Extrahepatic Malignancy: A Series of 14 Patients in a Single Institution., Transplantation proceedings, 10.1016/j.transproceed.2019.12.041, 52, 3, 889-893, 2020.04, Extrahepatic malignancy is a relative contraindication for liver transplant in many countries. Nevertheless, the indications for living-donor liver transplantation (LDLT) for such patients vary by institution. Our aim was to reevaluate the indications for LDLT in patients with extrahepatic malignancy. We retrospectively reviewed data for 609 patients who underwent adult LDLT from May 1997 to January 2018 and analyzed patients with a history of extrahepatic malignancies or concurrent malignancies. Fourteen patients had extrahepatic malignancies concurrent with or before LDLT. Malignancies in 9 patients were detected during their systematic screening for LDLT. The mean duration between surgeries was 70 days (range, 20-209 days). Five patients had a history of extrahepatic malignancies before considering LDLT. The estimated 5-year survival rate was 100%. Although the risk and long-term prognosis of patients with extrahepatic malignancy are not well known, such patients can be candidates for LDLT if they undergo curative surgery for the malignancy, and if the prognosis of the malignancy is the same or superior to that of LDLT..
115. Masahiro Shimokawa, Tomoharu Yoshizumi, Shinji Itoh, Norifumi Iseda, Kazuhito Sakata, Kyohei Yugawa, Takeo Toshima, Noboru Harada, Toru Ikegami, Masaki Mori, Modulation of Nqo1 activity intercepts anoikis resistance and reduces metastatic potential of hepatocellular carcinoma., Cancer science, 10.1111/cas.14320, 111, 4, 1228-1240, 2020.04, The processing of intracellular reactive oxygen species (ROS) by nuclear factor erythroid-derived 2-like 2 (Nrf2) and NADPH quinone oxidoreductase 1 (Nqo1) is important for tumor metastasis. However, the clinical and biological significance of Nrf2/Nqo1 expression in hepatocellular carcinoma (HCC) remains unclear. We aimed to clarify the clinical importance of Nrf2/Nqo1 expression in HCC and evaluate the association of Nrf2/Nqo1 expression with HCC metastasis. We also evaluated the impact of Nqo1 modulation on HCC metastatic potential. We used spheroids derived from HCC cell lines. In anchorage-independent culture, HCC cells showed increased ROS, leading to the upregulation of Nrf2/Nqo1. Futile stimulation of Nqo1 by β-lapachone induces excessive oxidative stress and dramatically increased anoikis sensitivity, finally diminishing the spheroid formation ability, which was far stronger than depletion of Nqo1. We analyzed 117 cases of primary HCC who underwent curative resection. Overexpression of Nrf2/Nqo1 in primary HCC was associated with tumor size, high α-fetoprotein, and des-γ-carboxy-prothrombin levels. Overexpression of Nrf2/Nqo1 was also associated with multiple intrahepatic recurrences (P = .0073) and was an independent risk factor for poor prognosis (P = .0031). NADPH quinone oxidoreductase 1 plays an important role in anchorage-independent survival, which is essential for survival for circulation and distant metastasis of HCC cells. These results suggest that targeting Nqo1 activity could be a potential strategy for HCC adjuvant therapy..
116. Sachie Omori, Noboru Harada, Takeo Toshima, Kazuki Takeishi, Shinji Itoh, Toru Ikegami, Tomoharu Yoshizumi, Masaki Mori, Multiple liver metastases originating from synchronous double cancer of neuroendocrine tumor and rectal cancer: a case report., Surgical case reports, 10.1186/s40792-020-0800-9, 6, 1, 36-36, 2020.02, BACKGROUND: Neuroendocrine tumor (NET) is a relatively rare tumor and can develop in almost any organ, but primary mesenteric NETs are extremely rare. In addition, liver metastases from synchronous double cancer of neuroendocrine tumor graded as G1 and second primary malignancies (SPMs) have never been reported before. We herein report a case of multiple liver metastases from synchronous double cancer of NET (G1) at the ileal mesentery and rectal cancer. CASE PRESENTATION: A 66-year-old man was identified as having tumors in the rectum and the ileal mesentery by computed tomography (CT). He underwent laparoscopic low anterior resection for rectal cancer and biopsy of the ileal mesentery lymph node and was diagnosed with rectal cancer as pT3 pN1 cM0 (stage IIIB) and NET (G1) of the ileal mesentery. He received oxaliplatin and capecitabine (XELOX) for 3 months as adjuvant chemotherapy for rectal cancer. The NET (G1) of the ileal mesentery was low grade and had not expanded at follow-up. A CT scan performed 4 years after the surgery indicated multiple liver metastases. All the metastases had the same findings on CT and magnetic resonance imaging (MRI). Thus, the patient underwent the first stage of modified associating liver partition and portal vein ligation for staged hepatectomy (modified ALPPS), comprising partial hepatectomies of segments 3 and 4, ligation of the right branch of portal vein, and hepatic partition on the demarcation line, followed by the second stage of modified ALPPS (right lobectomy). Histopathological findings revealed that the 14 nodules were metastatic liver tumors of rectal cancer and the 2 nodules were liver metastases of the NET (G1). CONCLUSIONS: Our findings suggest that synchronous double cancer of NET and gastrointestinal cancer may be indistinguishable in preoperative images. However, curative resection, precise pathological diagnosis, and adequately adjusted treatment may result in a better prognosis..
117. Tomoharu Yoshizumi, Masaki Mori, Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy., Surgery today, 10.1007/s00595-019-01881-y, 50, 1, 21-29, 2020.01, Small-for-size graft (SFSG) syndrome after living donor liver transplantation (LDLT) is the dysfunction of a small graft, characterized by coagulopathy, cholestasis, ascites, and encephalopathy. It is a serious complication of LDLT and usually triggered by excessive portal flow transmitted to the allograft in the postperfusion setting, resulting in sinusoidal congestion and hemorrhage. Portal overflow injures the liver directly through nutrient excess, endothelial activation, and sinusoidal shear stress, and indirectly through arterial vasoconstriction. These conditions may be attenuated with portal flow modulation. Attempts have been made to control excessive portal flow to the SFSG, including simultaneous splenectomy, splenic artery ligation, hemi-portocaval shunt, and pharmacological manipulation, with positive outcomes. Currently, a donor liver is considered a SFSG when the graft-to-recipient weight ratio is less than 0.8 or the ratio of the graft volume to the standard liver volume is less than 40%. A strategy for transplanting SFSG safely into recipients and avoiding extensive surgery in the living donor could effectively address the donor shortage. We review the literature and assess our current knowledge of and strategies for portal flow modulation in LDLT..
118. Takeo Toshima, Tomoharu Yoshizumi, Yukiko Kosai-Fujimoto, Shoichi Inokuchi, Shohei Yoshiya, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Masaki Mori, Prognostic Impact of Osteopenia in Patients Who Underwent Living Donor Liver Transplantation for Hepatocellular Carcinoma., World journal of surgery, 10.1007/s00268-019-05206-5, 44, 1, 258-267, 2020.01, BACKGROUND: Osteopenia, loss of bone mineral density (BMD), was recently identified to be independently associated with early marker of deconditioning that precedes sarcopenia in patients with hepatocellular carcinoma (HCC). The aim of this study was to clarify the impact of osteopenia as the risk factor for mortality after living donor liver transplantation (LDLT) compared with already-reported biological markers. METHODS: Data were collected retrospectively for all consecutive patients who underwent LDLT for HCC at our institution between January 1998 and December 2015. BMD was evaluated with computed tomographic measurement of pixel density in the midvertebral core of the 11th thoracic vertebra. Data related to clinicopathological parameters and prognosis were analyzed. RESULTS: The median value of BMD was 163.6 Hounsfield units and osteopenia was identified in 103 (53.4%) of the 193 recipients, according to the age-specific formula. In addition to the other tumor burdens, such as tumor numbers ≥5 (HR 2.521, P = 0.027), DCP levels >200 mAU/mL (HR 2.678, P = 0.006), and neutrophil-to-lymphocyte ratio ≥3.01 (HR 2.068, P = 0.025), osteopenia (HR 2.106, P = 0.024) was independent risk factor for mortality by multivariate analysis. Overall survival of the patients who met the two risk factors and more was significantly lower than the others (HR 5.382, P < 0.001). Besides, the calibration plot for the 5-year overall survival using nomogram was predicted very well (C-index 0.746). CONCLUSIONS: Preoperative osteopenia was independently associated with post-LDLT mortality among patients with HCC. Moreover, risk score and nomogram with calibration curve were developed to confirm the clinical usefulness of osteopenia for post-LDLT patients..
119. Kyohei Yugawa, Shinji Itoh, Tomoharu Yoshizumi, Shohei Yoshiya, Kazuki Takeishi, Takeo Toshima, Noboru Harada, Toru Ikegami, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Prognostic impact of 8-hydroxy-deoxyguanosine and its repair enzyme 8-hydroxy-deoxyguanosine DNA glycosylase in hepatocellular carcinoma., Pathology international, 10.1111/pin.12952, 70, 8, 533-541, 2020.08, Hepatocellular carcinoma (HCC) has a poor prognosis in the setting of chronic inflammation and fibrosis, both of which promote nuclear DNA oxidative damage. 8-hydroxy-deoxyguanosine (8-OHdG) DNA glycosylase (OGG1) enhances the repair of 8-OHdG, which is the primary oxidative stress-induced mutation that leads to malignant alterations. This study aims to clarify the relationships between oxidative stress-induced factors and HCC progression. The clinicopathological factors were compared with immunohistochemistry OGG1 and 8-OHdG expressions in 86 resected HCC specimens. High 8-OHdG expression was associated with high serum aspartate transaminase and total bilirubin levels, as well as a low platelet count, compared with low 8-OHdG expression. Histological liver cirrhosis and poor differentiation were more frequent in patients with high 8-OHdG expression than in those with low 8-OHdG expression. The 8-OHdG was negatively correlated with OGG1 expression in HCC patients. Therefore, we classified the patients into two groups, low OGG1/high 8-OHdG group and the other group. The patients with low OGG1/high 8-OHdG expressions had worse prognosis than those with the other expressions. Our results showed that low OGG1/high 8-OHdG expressions in nuclei influence HCC patient outcomes. Evaluating the patterns of OGG1 and 8-OHdG expressions might provide pivotal prognostic biomarkers in patients with HCC..
120. Daisuke Imai, Takashi Maeda, Mototsugu Shimokawa, Huanlin Wang, Shohei Yoshiya, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Tomoharu Yoshizumi, Masaki Mori, Prognostic nutritional index is superior as a predictor of prognosis among various inflammation-based prognostic scores in patients with hepatocellular carcinoma after curative resection., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13431, 50, 1, 101-109, 2020.01, AIM: There is increasing evidence that inflammation-based prognostic scores are stage-independent predictors of poor outcome in patients with hepatocellular carcinoma (HCC). However, these findings were observed in a small-sized study comparing the prognostic value of these scores for patients after curative resection for HCC. METHODS: We retrospectively analyzed 717 consecutive patients with HCC who underwent curative liver resection at Hiroshima Red Cross Hospital & Atomic Bomb Survivors Hospital. Clinicopathological variables including preoperative inflammation-based prognostic scores, such as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Controlling Nutritional Status score, prognostic nutritional index (PNI), and Glasgow Prognostic Score were analyzed. The prognostic value of these scores was compared by the time-dependent receiver operating characteristic curve analyses. RESULTS: The integrate area under the curve of PNI, Controlling Nutritional Status score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and Glasgow Prognostic Score were 0.6751, 0.6435, 0.5845, 0.5276, and 0.5351 for overall survival (OS), respectively, and 0.5955, 0.5694, 0.4692, 0.4873, and 0.5272 for disease-free survival, respectively. Multivariate analyses for prognosis factor in HCC patients showed that PNI was an independent predictor of both OS (HR 0.91, P < 0.001) and disease-free survival (HR 0.94, P < 0.001). When the patients were divided into high and low PNI groups, the patients in the low PNI group had significant poorer OS (P < 0.001) and disease-free survival (P < 0.001), even after background factors were matched between these two groups. CONCLUSIONS: PNI is superior to Controlling Nutritional Status score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, or Glasgow Prognostic Score as a predictor of OS and recurrence-free survival in patients with HCC who underwent curative hepatic resection..
121. Kazuki Takeishi, Toru Ikegami, Tomoharu Yoshizumi, Nao Fujimori, Masaki Mori, Reply., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.25725, 26, 5, 727-728, 2020.05.
122. Toru Ikegami, Tomoharu Yoshizumi, Norifumi Iseda, Takeo Toshima, Mohamed Elemam Elshawy, Masaki Mori, Reply., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.25702, 26, 3, 463-464, 2020.03.
123. Takeo Toshima, Tomoharu Yoshizumi, Shoichi Inokuchi, Yukiko Kosai-Fujimoto, Takeshi Kurihara, Shohei Yoshiya, Yohei Mano, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Mototsugu Shimokawa, Yoshihiko Maehara, Masaki Mori, Risk factors for the metabolic syndrome components of hypertension, diabetes mellitus, and dyslipidemia after living donor liver transplantation., HPB : the official journal of the International Hepato Pancreato Biliary Association, 10.1016/j.hpb.2019.08.008, 22, 4, 511-520, 2020.04, BACKGROUND: Metabolic syndrome (MS) is the most common long-term complication after liver transplantation, and it has been increasing in incidence. The aim of this study was to clarify the risk factors for each MS component -hypertension, diabetes mellitus, and dyslipidemia-after living-donor liver transplantation (LDLT), including characteristics of living-donors. METHODS: Data related to clinicopathological parameters including MS components in 461 consecutive patients who underwent LDLT were analyzed retrospectively. RESULTS: Prevalence of all MS components (hypertension, diabetes mellitus, and dyslipidemia) increased from 9.3%, 16.5%, and 7.2% before LDLT to 44.9%, 45.3%, and 50.8% after LDLT, respectively. By multivariate logistic regression analysis, the three factors, cyclosporine use (OR 2.086, P = 0.001), recipient age (OR 1.036, P = 0.001), and BMI (OR 1.072, P = 0.026) were independent predictors for post-LDLT hypertension. Next, the three factors, male recipient (OR 2.471, P < 0.001), recipient age (OR 1.039, P = 0.002), and donor BMI (OR 1.124, P = 0.012) were independent for post-LDLT diabetes mellitus. The four factors, cyclosporine use (OR 2.015, P = 0.001), prolonged prednisolone use (OR 1.928, P = 0.002), recipient age (OR 1.019, P = 0.037), and GRWR (OR 0.316, P = 0.037) were independent for post-LDLT dyslipidemia as well. CONCLUSIONS: Not only recipient-related factors but also donor-related factors were independently associated with each targeted post-LDLT MS component..
124. Kazuki Takeishi, Tomoharu Yoshizumi, Shinji Itoh, Kyohei Yugawa, Shohei Yoshiya, Takeo Toshima, Noboru Harada, Toru Ikegami, Akihiro Nishie, Masaki Mori, Surgical Indications for Hepatocellular Carcinoma with Non-hypervascular Hypointense Nodules Detected by Gd-EOB-DTPA-Enhanced MRI., Annals of surgical oncology, 10.1245/s10434-020-08419-4, 27, 9, 3344-3353, 2020.09, BACKGROUND: The surgical indication for non-hypervascular hypointense nodules (NHVN) detected incidentally on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) for classical hepatocellular carcinoma (HCC) is unknown. Our aim is to clarify the long-term outcomes in patients with this finding. METHODS: We reviewed the cases of 290 HCC patients, including 66 patients with NHVN, who underwent Gd-EOB-MRI prior to hepatectomy, between October 2008 and December 2017 at our center. We divided the patients into three groups: a no-NHVN group, a treated NHVN group, and an untreated NHVN group. RESULTS: There was no significant difference in (RFS) or overall survival (OS) between the no-NHVN and untreated NHVN groups (p = 0.103 and 0.103, respectively). There was no significant difference between these two groups after propensity score matching. Multivariate analyses showed that microscopic intrahepatic metastases and the size of the main classical HCC, the target tumor, were independent prognostic factors of overall survival, but the presence of non-hypervascular hypointense nodules was not. There was no significant difference in RFS or OS between the treated NHVN and untreated NHVN groups (p = 0.158 and 0.109, respectively). CONCLUSIONS: Non-hypervascular hypointense nodules detected incidentally on Gd-EOB-MRI associated with targeted hypervascular HCC did not reflect prognosis of HCC after hepatectomy. Surgical procedures for classical enhancing HCC may be performed even if non-hypervascular hypointense nodules adjacent to the targeted HCC cannot be removed completely..
125. Kazuki Takeishi, Tomoharu Yoshizumi, Toru Ikegami, Shinji Itoh, Noboru Harada, Nao Fujimori, Takamasa Ohno, Masaki Mori, Transgastric Endoscopic Lumen-Apposing Metal Stents for Intra-abdominal Fluid Collections After Living Donor Liver Transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.25707, 26, 4, 598-601, 2020.04.
126. Noboru Harada, Tomoharu Yoshizumi, Shohei Yoshiya, Kazuki Takeishi, Takeo Toshima, Shinji Itoh, Toru Ikegami, Mio Fukuda, Satohiro Masuda, Masaki Mori, Use of Mycophenolate Mofetil Suspension as Part of Induction Therapy After Living-Donor Liver Transplant., Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 10.6002/ect.2020.0041, 18, 4, 485-490, 2020.08, OBJECTIVES: The aim of this study was to evaluate recipient safety, tolerability, and pharmacokinetics of mycophenolate mofetil suspension compared with mycophenolate mofetil capsules as part of induction therapy after living-donor liver transplant. MATERIALS AND METHODS: Between July 2017 and April 2019, we retrospectively enrolled 20 adult primary living-donor liver transplant recipients. Recipients were divided into 3 groups: group 1 received mycophenolate mofetil suspension of 3000 mg (n = 6), group 2 received 3000 mg mycophenolate mofetil via opened capsules (n = 8), and group 3 received mycophenolate mofetil suspension of 2000 mg (n = 6). Administration was started on postoperative day 1, with tacrolimus administered on postoperative day 2 or day 3. RESULTS: The values of area under the plasma concentration time curve for 0 to 12 hours were significantly higher in the 3000 mg/day mycophenolate mofetil suspension group than in the 2000 mg/day mycophenolate mofetil suspension group (P = .024) and in the 3000mg/day mycophenolate mofetil capsule group (P = .013). Significant positive correlations were shown between blood concentration at 8 hours after administration and the plasma concentration time curve for 0 to 12 hours (r2 = 0.96; P < .001) in patients in the suspension group. No patients required mycophenolate mofetil reduction because of leukopenia and diarrhea. Only 1 biopsy-proven acute cellular rejection was recognized in the mycophenolate mofetil suspension group (at 2000 mg/day). There were no significant differences in frequency of opportunistic infections among the 3 groups. CONCLUSIONS: Mycophenolate mofetil suspension is useful as part of immunosuppressive induction therapy after living-donor liver transplant because its concentration increases greater than that of mycophenolate mofetil capsules and because of the low risk of rejection and adverse events..
127. Daisuke Imai, Takashi Maeda, Huanlin Wang, Kensaku Sanefuji, Hiroto Kayashima, Shohei Yoshiya, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Tomoharu Yoshizumi, Masaki Mori, Elevation of Mac-2 binding protein glycosylation isomer after hepatectomy is associated with post-hepatectomy liver failure, total Pringle time, and renal dysfunction., Annals of gastroenterological surgery, 10.1002/ags3.12271, 3, 5, 515-522, 2019.09, Background: Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum glycomarker used to assess liver fibrosis. However, it has been reported that M2BPGi is likely to reflect other factors not limited to liver fibrosis. Methods: We retrospectively analyzed 79 patients with liver tumors who underwent liver resection. M2BPGi was measured within 1 week before operation and almost 1 month after operation. We introduced a value termed the "ΔM2BPGi ratio" (=M2BPGiafter operation/M2BPGibefore operation), and analyzed factors that influenced the ΔM2BPGi ratio. Results: The median value of the ΔM2BPGi ratio was 1.28 (range, 0.36-5.68). In 64 patients (81.0%), the cutoff index values of M2BPGi were elevated approximately 1 month after operation, especially in patients who experienced post-hepatectomy liver failure (PHLF). Multiple linear regression showed total Pringle time, PHLF grade ≥B, and preoperative value of creatinine were significant predictors of the ΔM2BPGi ratio. The mean values of the ΔM2BPGi ratio were 1.37 ± 0.07, 1.52 ± 0.22, and 2.94 ± 0.30 for PHLF grade 0, grade A, and grade B, respectively, resulting in statistically significant differences by the Kruskal-Wallis test (P = 0.022). Conclusions: Total Pringle time, PHLF grade ≥B, and preoperative creatinine significantly influenced the elevation of M2BPGi almost 1 month after liver resection. This study strongly affirms the previous suggestion that M2BPGi is likely to reflect other factors not limited to liver fibrosis..
128. Tomonari Shimagaki, Sachiyo Yoshio, Hironari Kawai, Yuzuru Sakamoto, Hiroyoshi Doi, Michitaka Matsuda, Taizo Mori, Yosuke Osawa, Moto Fukai, Takeshi Yoshida, Yunfei Ma, Tomoyuki Akita, Junko Tanaka, Akinobu Taketomi, Rikinari Hanayama, Tomoharu Yoshizumi, Masaki Mori, Tatsuya Kanto, Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma., Scientific reports, 10.1038/s41598-019-52356-6, 9, 1, 15788-15788, 2019.10, Current serum hepatocellular carcinoma (HCC) biomarkers are insufficient for early diagnosis. We aimed to clarify whether serum MFG-E8 can serve as a diagnostic or prognostic biomarker of HCC. Serum MFG-E8 levels of 282 HCC patients, who underwent primary hepatectomy, were examined by ELISA. We also quantified serum MFG-E8 levels in patients with chronic hepatitis (CH), liver cirrhosis (LC), as well as in healthy volunteers (HVs). Serum MFG-E8 levels were significantly lower in HCC patients than in HVs regardless of the etiology of liver disease (3.6 ± 0.1 vs 5.8 ± 0.2 ng/mL, p < 0.0001), and recovered after treatment of HCC. Serum MFG-E8 levels in CH and LC patients were comparable to those in HVs. Serum MFG-E8 could detect HCCs, even α-fetoprotein (AFP)-negative or des-γ-carboxy prothrombin (DCP)-negative HCCs, in CH and LC patients. Our new HCC prediction model using MFG-E8 and DCP (Logit(p) = 2.619 - 0.809 × serum MFG-E8 + 0.0226 × serum DCP) distinguished HCC patients from CH and LC patients with an area under the curve of 0.923, a sensitivity of 81.1%, and a specificity of 89.8%. Futhermore, low preoperative serum MFG-E8 was an independent predictor of poor overall survival. Thus, serum MFG-E8 could serve as a feasible diagnostic and prognostic biomarker for HCC..
129. Yoshihiko Maehara, Yuji Soejima, Tomoharu Yoshizumi, Naoyuki Kawahara, Eiji Oki, Hiroshi Saeki, Tomohiko Akahoshi, Toru Ikegami, Yo-Ichi Yamashita, Tadashi Furuyama, Keishi Sugimachi, Noboru Harada, Tetsuzo Tagawa, Norifumi Harimoto, Shinji Itoh, Hideto Sonoda, Koji Ando, Yuichiro Nakashima, Yoshihiro Nagao, Nami Yamashita, Yuta Kasagi, Takafumi Yukaya, Takeshi Kurihara, Ryosuke Tsutsumi, Shinkichi Takamori, Shun Sasaki, Tetsuo Ikeda, Yoshikazu Yonemitsu, Takasuke Fukuhara, Hiroyuki Kitao, Makoto Iimori, Yuki Kataoka, Takeshi Wakasa, Masami Suzuki, Koji Teraishi, Yasuto Yoshida, Masaki Mori, The evolution of surgical treatment for gastrointestinal cancers., International journal of clinical oncology, 10.1007/s10147-019-01499-7, 24, 11, 1333-1349, 2019.11, INTRODUCTION: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. MATERIALS AND METHODS, AND RESULTS: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. CONCLUSION: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival..
130. Takeo Toshima, Tomoharu Yoshizumi, Shinji Itoh, Katsuya Toshida, Takahiro Tomiyama, Akinari Morinaga, Yukiko Kosai-Fujimoto, Takahiro Tomino, Takeshi Kurihara, Kazutoyo Morita, Noboru Harada, ASO Author Reflections: Future Perspectives of Novel Prognostic Predictor of Vessels that Encapsulate Tumor Cluster (VETC) for Hepatocellular Carcinoma., Annals of surgical oncology, 10.1245/s10434-021-10546-5, 28, 13, 8196-8197, 2021.07.
131. Shohei Yoshiya, Shinji Itoh, Tomoharu Yoshizumi, Masaki Mori, ASO Author Reflections: A New Prognostic Factor for Pancreatic Cancer., Annals of surgical oncology, 10.1245/s10434-020-09386-6, 28, 6, 3208-3208, 2021.06.
132. Kojiro Hata, Kimitaka Suetsugu, Nobuaki Egashira, Yoko Makihara, Shinji Itoh, Tomoharu Yoshizumi, Masatake Tanaka, Motoyuki Kohjima, Hiroyuki Watanabe, Satohiro Masuda, Ichiro Ieiri, Association of lenvatinib plasma concentration with clinical efficacy and adverse events in patients with hepatocellular carcinoma., Cancer chemotherapy and pharmacology, 10.1007/s00280-020-04178-x, 86, 6, 803-813, 2020.12, PURPOSE: This study aimed to examine the association between the trough plasma concentration of lenvatinib with the objective response rate (ORR) and adverse events in patients with hepatocellular carcinoma (HCC). METHODS: Twenty-one patients with HCC who received lenvatinib were enrolled. We examined the median trough concentration (Ctrough median) of plasma lenvatinib until the first clinical response evaluation. The receiver-operating characteristic curve was drawn to show the discrimination potential of the Ctrough median for the ORR, using the modified Response Evaluation Criteria in Solid Tumors. Adverse events were graded based on the Common Terminology Criteria for Adverse Events (ver. 5.0). RESULTS: The Ctrough median values in the complete response and partial response group were significantly higher than those in the stable disease and progressive disease groups. The ORR was significantly higher in the high-Ctrough median group (≥ 42.68 ng/mL) than in the low-Ctrough median group (< 42.68 ng/mL) (80.0% vs. 18.2%; p = 0.0089). Although there was no difference in the occurrence of most adverse events between the high- and low-Ctrough median groups, the occurrence of any grade anorexia (100.0% vs. 45.5%; p = 0.0124) and grade 3 serious hypertension (70.0% vs. 18.2%; p = 0.0300) was significantly higher in the high-Ctrough median group than in the low-Ctrough median group. Multivariate analysis showed that high-Ctrough median was significantly associated with ORR development (odds ratio, 15.00; 95% confidence interval, 1.63-138.16; p = 0.0168). CONCLUSION: Maintaining Ctrough median above 42.68 ng/mL was crucial for achieving the ORR in patients with HCC..
133. Junji Kawasaki, Takeo Toshima, Tomoharu Yoshizumi, Shinji Itoh, Yohei Mano, Huanlin Wang, Norifumi Iseda, Noboru Harada, Yoshinao Oda, Masaki Mori, ASO Visual Abstract: Prognostic Impact of Vessels that Encapsulate Tumor Cluster (VETC) in Patients who Underwent Liver Transplantation for Hepatocellular Carcinoma., Annals of surgical oncology, 10.1245/s10434-021-10248-y, 2021.07.
134. Junji Kawasaki, Takeo Toshima, Tomoharu Yoshizumi, Shinji Itoh, Yohei Mano, Huanlin Wang, Norifumi Iseda, Noboru Harada, Yoshinao Oda, Masaki Mori, Prognostic Impact of Vessels that Encapsulate Tumor Cluster (VETC) in Patients who Underwent Liver Transplantation for Hepatocellular Carcinoma., Annals of surgical oncology, 10.1245/s10434-021-10209-5, 28, 13, 8186-8195, 2021.06, BACKGROUND: There is limited published information about prognostic value of vessels that encapsulate tumor cluster (VETC) based on their involvement with immune cells in hepatocellular carcinoma (HCC). Our goal was to evaluate prognostic impact of VETC in patients who underwent living-donor liver transplantation (LDLT) for HCC, focusing on the involvement of VETC with immune status in tumor microenvironment (TME). METHODS: Using a database of 150 patients who underwent LDLT for HCC, immunohistochemical staining of CD34 for VETC, angiopoietin-2 (Ang-2), CD3, and CD68, was reviewed with patients' clinicopathological factors. RESULTS: A strong correlation between VETC pattern and malignant potential in HCC was observed; larger tumor size (P < 0.001), more numbers of tumors (P = 0.003), higher α-fetoprotein levels (P = 0.001), higher des-γ-carboxy prothrombin levels (P = 0.022), microvascular invasion (P < 0.001), and poor differentiation (P = 0.010). Overall survival (OS) of patients with VETC(+) was significantly lower than those with VETC(-) (P = 0.021; 5-year OS rates, 72.0% vs. 87.1%). Furthermore, the ratio of CD3(+) cells was significantly lower in VETC(+) group (P = 0.001), indicating that VETC activity may be strongly correlated with lymphocyte activity. Moreover, combination status of VETC(+)/CD3low was an independent risk factor for mortality (hazard ratio 2.760, 95% confidence interval 1.183-6.439, P = 0.019). Additionally, the combination of VETC expression with immune status (low CD3 levels) enabled further classification of patients based on their clinical outcome. CONCLUSIONS: Our results show the prognostic impact of VETC expression, tumor-infiltrating lymphocytes (TILs), and their combination in the setting of LDLT for HCC, which can be a novel prognostic biomarker for mortality after LDLT..
135. Kyohei Yugawa, Shinji Itoh, Tomoharu Yoshizumi, Norifumi Iseda, Takahiro Tomiyama, Takeo Toshima, Noboru Harada, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Prognostic impact of tumor microvessels in intrahepatic cholangiocarcinoma: association with tumor-infiltrating lymphocytes., Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 10.1038/s41379-020-00702-9, 34, 4, 798-807, 2021.04, Tumor microvessel density (MVD) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (ICC). Tumor-infiltrating lymphocytes (TILs) are also key components of the tumor microenvironment that play important roles in ICC progression. This study aimed to clarify the relationships between the MVD and immune status and prognosis in patients with ICC. Immunohistochemical staining for cluster of differentiation 34 (CD34), cluster of differentiation 8 (CD8), forkhead box protein P3 (Foxp3), and programmed death-ligand 1 (PD-L1) was performed. The relationships between the MVD and clinicopathological characteristics and outcomes were analyzed. Additionally, the correlations between the MVD, CD8+ and Foxp3+ TIL counts, and PD-L1 expression were evaluated. One hundred ICC patients were classified into high (n = 50) and low (n = 50) MVD groups. The serum platelet and carbohydrate antigen 19-9 levels were higher in the low MVD group than in the high MVD group (P = 0.017 and P = 0.008, respectively). The low MVD group showed a significantly larger tumor size (P = 0.016), more frequent microvascular invasion (P = 0.001), and a higher rate of intrahepatic (P = 0.023) and lymph node (P < 0.001) metastasis than the high MVD group. Moreover, the MVD showed a high positive correlation with CD8+ TILs (r = 0.754, P < 0.001) and a negative correlation with Foxp3+ TILs (r = -0.302, P = 0.003). In contrast, no significant correlation was observed between the MVD and PD-L1 expression in cancer cells (P = 0.817). Patients with low MVDs had a significantly worse prognosis than those with high MVDs. Furthermore, multivariable analyses revealed that a low MVD influenced recurrence-free survival. A decreased intratumoral MVD might predict ICC patient outcomes. Tumor microvessels might be associated with ICC progression, possibly by altering TIL recruitment..
136. Shinji Itoh, Eiji Tsujita, Kengo Fukuzawa, Keishi Sugimachi, Tomohiri Iguchi, Mizuki Ninomiya, Takashi Maeda, Kiyashi Kajiyama, Eisuke Adachi, Hideaki Uchiyama, Tohru Utsunomiya, Yasuharu Ikeda, Soichirou Maekawa, Takeo Toshima, Noboru Harada, Tomoharu Yoshizumi, Masaki Mori, Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: A multi-institutional retrospective study., Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 10.1016/j.pan.2021.08.003, 21, 7, 1356-1363, 2021.08, BACKGROUND: The aim of this study was to investigate the clinical value of nutritional and immunological prognostic scores as predictors of outcomes and to identify the most promising scoring system for patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-institutional study. METHODS: Data were retrospectively collected for 589 patients who underwent surgical resection for PDAC. Prognostic analyses were performed for overall (OS) and recurrence-free survival (RFS) using tumor and patient-related factors, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), modified GPS, C-reactive protein-to-albumin ratio, Controlling Nutritional Status score, and the Geriatric Nutritional Risk Index. RESULTS: Compared with PDAC patients with high PNI values (≥46), low PNI (<46) patients showed significantly worse overall survival (OS) (multivariate hazard ratio (HR), 1.432; 95% CI, 1.069-1.918; p = 0.0161) and RFS (multivariate HR, 1.339; 95% CI, 1.032-1.736; p = 0.0277). High carbohydrate antigen 19-9 (CA19-9) values (≥450) were significantly correlated with shorter OS (multivariate HR, 1.520; 95% CI, 1.261-2.080; p = 0.0002) and RFS (multivariate HR, 1.533; 95% CI, 1.199-1.961; p = 0.0007). Stratification according to PNI and CA19-9 was also significantly associated with OS and RFS (log rank, P < 0.0001). CONCLUSIONS: Our large cohort study showed that PNI and CA19-9 were associated with poor clinical outcomes in PDAC patients following surgical resection. Additionally, combining PNI with CA19-9 enabled further classification of patients according to their clinical outcomes..
137. Shoichi Inokuchi, Shinji Itoh, Tomoharu Yoshizumi, Akinari Morinaga, Takeo Toshima, Kazuki Takeishi, Yoshihiro Nagao, Noboru Harada, Toru Ikegami, Mototsugu Shimokawa, Masaki Mori, Prognostic significance of systemic inflammation score in patients who undergo hepatic resection for hepatocellular carcinoma., Langenbeck's archives of surgery, 10.1007/s00423-021-02103-1, 406, 3, 773-779, 2021.05, PURPOSE: Systemic inflammation score (SIS) is a novel prognostic score (0, 1, or 2) for various cancers, based on preoperative serum albumin level and lymphocyte-to-monocyte ratio (LMR); modified SIS (mSIS) uses a different LMR cutoff value and was thought to be a more accurate predictor for cancer prognosis. Here, we assessed the prognostic value of SIS and mSIS in patients who receive hepatic resection for hepatocellular carcinoma (HCC). METHODS: We retrospectively evaluated SIS and mSIS of 314 patients after hepatic resection for HCC, against their clinicopathological factors and outcomes, using receiver operating characteristics (ROC) analysis over time. RESULTS: Among patients with preoperative SIS 2, significantly more HCC specimens were poorly differentiated (P = 0.0281), larger (P = 0.0006), and had more microscopic vascular invasion (P = 0.0136) than the SIS 0-1 group; the mSIS 2 group also had significantly larger tumors (P = 0.0039) than the mSIS 0-1 group. In ROC analysis, SIS was a better predictor of overall survival (OS) and recurrence-free survival (RFS) than mSIS. The SIS 2 group had shorter OS (P = 0.0015) and RFS (P = 0.0065) than other patients. In multivariate analysis, SIS 2 was an independent risk factor for shorter OS (hazard ratio (HR) 1.53, P = 0.0497) and RFS (HR 1.58, P = 0.0053). CONCLUSION: SIS is superior to mSIS in predicting prognosis of patients with HCC. mSIS is not a great predictor of prognosis in resected HCC..
138. Ryota Nakanishi, Eiji Oki, Hirofumi Hasuda, Eiki Sano, Yu Miyashita, Akihiro Sakai, Naomichi Koga, Naotaka Kuriyama, Kentaro Nonaka, Yoshiaki Fujimoto, Tomoko Jogo, Kentaro Hokonohara, Qingjiang Hu, Yuichi Hisamatsu, Koji Ando, Yasue Kimura, Tomoharu Yoshizumi, Masaki Mori, Radiomics Texture Analysis for the Identification of Colorectal Liver Metastases Sensitive to First-Line Oxaliplatin-Based Chemotherapy., Annals of surgical oncology, 10.1245/s10434-020-09581-5, 28, 6, 2975-2985, 2021.06, OBJECTIVE: The aim of this study was to develop a radiomics-based prediction model for the response of colorectal liver metastases to oxaliplatin-based chemotherapy. METHODS: Forty-two consecutive patients treated with oxaliplatin-based first-line chemotherapy for colorectal liver metastasis at our institution from August 2013 to October 2019 were enrolled in this retrospective study. Overall, 126 liver metastases were chronologically divided into the training (n = 94) and validation (n = 32) cohorts. Regions of interest were manually segmented, and the best response to chemotherapy was decided based on Response Evaluation Criteria in Solid Tumors (RECIST). Patients who achieved clinical complete and partial response according to RECIST were defined as good responders. Radiomics features were extracted from the pretreatment enhanced computed tomography scans, and a radiomics score was calculated using the least absolute shrinkage and selection operator regression model in a trial cohort. RESULTS: The radiomics score significantly discriminated good responders in both the trial (area under the curve [AUC] 0.8512, 95% confidence interval [CI] 0.7719-0.9305; p < 0.0001) and validation (AUC 0.7792, 95% CI 0.6176-0.9407; p < 0.0001) cohorts. Multivariate analysis revealed that high radiomics scores greater than - 0.06 (odds ratio [OR] 23.803, 95% CI 8.432-80.432; p < 0.0001), clinical non-T4 (OR 6.054, 95% CI 2.164-18.394; p = 0.0005), and metachronous disease (OR 11.787, 95% CI 2.333-70.833; p = 0.0025) were independently associated with good response. CONCLUSIONS: Radiomics signatures may be a potential biomarker for the early prediction of chemosensitivity in colorectal liver metastases. This approach may support the treatment strategy for colorectal liver metastasis..
139. Katsuya Toshida, Shinji Itoh, Tomoharu Yoshizumi, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Takeo Toshima, Yoshihiro Nagao, Noboru Harada, Kojiro Hata, Yoko Makihara, Hiroyuki Watanabe, Masaki Mori, Retrospective evaluation of the effect of Ninjin'yoeito in hepatocellular carcinoma patients treated with lenvatinib., Surgery today, 10.1007/s00595-021-02358-7, 52, 3, 441-448, 2021.08, PURPOSES: Lenvatinib (LEN) is a molecular-target drug, used for unresectable hepatocellular carcinoma (HCC). It is associated with adverse events (AEs), including hypertension, proteinuria, fatigue, and anorexia, which may force dose reduction or discontinuation. Ninjin'yoeito (NYT) is a Chinese-Japanese herbal compound that can effectively treat fatigue and anorexia, and which has been used for chronic liver diseases. NYT reduces AEs and improves the liver function in patients treated with sorafenib but its effect on LEN is unclear. METHODS: The present study included 46 patients (male, n = 32; female, n = 14) who received LEN for HCC at our hospital. Their median age was 70 years (range 36-88 years), and their median body weight was 61.5 kg (range 38.4-97.0 kg). Patients were divided into two groups, depending on whether they received NYT medication. Their AEs and liver function were examined one month after starting LEN. RESULTS: The NYT group suffered less fatigue (63.6% vs. 11.4%, P = 0.0014) and showed elevated aspartate aminotransferase levels (45.5% vs. 14.3%, P = 0.0433) in comparison to the non-NYT group. The non-NYT group also showed a significantly exacerbated albumin-bilirubin (ALBI) grade (P = 0.0342) and ALBI score (average change: + 0.232, P = 0.0001) at 1 month in comparison to baseline. CONCLUSION: NYT apparently suppressed LEN-induced fatigue and helped maintain liver function in patients with HCC..
140. Daisuke Imai, Takashi Maeda, Huanlin Wang, Tomonari Shimagaki, Kensaku Sanefuji, Hiroto Kayashima, Shinichi Tsutsui, Hiroyuki Matsuda, Tomoharu Yoshizumi, Masaki Mori, Risk Factors for and Outcomes of Intraoperative Blood Loss in Liver Resection for Hepatocellular Tumors., The American surgeon, 10.1177/0003134820949995, 87, 3, 376-383, 2021.03, Intraoperative blood loss (IBL) during liver resection is a predictor of morbidity, mortality, and tumor recurrence after hepatectomy; however, there have been few reports on patient factors associated with increased IBL. We enrolled consecutive patients who underwent liver resection for primary liver malignancies, and evaluated the predictors of IBL using a data set in which factors that might influence IBL, such as surgical devices, methods and anesthetic technique, were all standardized. We studied 244 patients. A multivariate analysis revealed that higher IBL was an independent risk factor for post-hepatectomy liver failure grade ≥B and overall survival. Multiple linear regression analyses showed serum creatinine, clinically significant portal hypertension (CSPH), tumor size, and major hepatectomy were all significant predictors of IBL. In conclusion, higher IBL was significantly associated with increased morbidity and mortality in patients with primary HCC who underwent liver resection. The risk of IBL was related to several factors including tumor size, serum creatinine, CSPH, and major hepatectomy..
141. Tomoharu Yoshizumi, Shinji Itoh, Mototsugu Shimokawa, Shoichi Inokuchi, Noboru Harada, Kazuki Takeishi, Yohei Mano, Shohei Yoshiya, Takeshi Kurihara, Yoshihiro Nagao, Toru Ikegami, Yuji Soejima, Masaki Mori, Simultaneous splenectomy improves outcomes after adult living donor liver transplantation., Journal of hepatology, 10.1016/j.jhep.2020.08.017, 74, 2, 372-379, 2021.02, BACKGROUND & AIMS: Small-for-size graft (SFSG) syndrome is a major cause of graft loss after living donor liver transplantation (LDLT). Splenectomy (Spx) is an option to prevent this catastrophic complication, but its effect remains controversial. Herein, we aimed to elucidate the effect of simultaneous Spx on graft function and long-term outcomes after LDLT. METHODS: Three hundred and twenty patients were divided into 2 groups: those undergoing (n = 258) and those not undergoing (n = 62) simultaneous Spx. To overcome selection bias, propensity score matching (PSM) was performed (n = 50 in each group). RESULTS: Before PSM, recipients undergoing simultaneous Spx showed better graft function on post-operative day (POD) 7 and 14, as well as lower sepsis frequency within 6 months after LDLT and better graft survival rates compared to those not undergoing Spx. After PSM, compared to patients not undergoing Spx, those undergoing Spx had a lower frequency of early graft dysfunction on POD 7 (p = 0.04); a lower frequency of SFSG syndrome (p = 0.01), lower serum total bilirubin levels (p = 0.001), and lower international normalized ratio (p = 0.004) on POD 14; lower sepsis frequency within 6 months after LDLT (p = 0.02), and better graft survival rates (p = 0.04). Univariate analysis revealed that not undergoing Spx (hazard ratio 3.06; 95% CI 1.07-11.0; p = 0.037) was the only risk factor for graft loss after LDLT. CONCLUSIONS: Simultaneous Spx may prevent SFSG syndrome and is a predictive factor for graft survival after LDLT. Simultaneous Spx is recommended when a small graft (≤35% of standard liver weight) is predicted preoperatively, or for patients with portal hypertension or high portal pressure (above 20 mmHg) after reperfusion in LDLT. LAY SUMMARY: Living donor liver transplantation (LDLT) for patients with acute or chronic liver failure is an alternative to overcome the deceased donor shortage. The potential mismatch between graft and body size is a problem that needs to be solved for LDLT recipients. Herein, we evaluated the impact of simultaneous splenectomy and showed that it was associated with favorable outcomes in patients undergoing LDLT..
142. Shoichi Inokuchi, Tomoharu Yoshizumi, Takeo Toshima, Shinji Itoh, Kyohei Yugawa, Noboru Harada, Hiroyuki Mori, Takasuke Fukuhara, Yoshiharu Matsuura, Masaki Mori, Suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy., Cancer medicine, 10.1002/cam4.3519, 10, 5, 1501-1514, 2021.03, Autophagy removes damaged organelles to inhibit malignant transformation during tumor initiation. Once a cancer matures, it uses the autophagic pathway as an energy source. Optineurin (OPTN) is an autophagy adaptor protein that recruits microtubule-associated protein 1 light chain 3, an autophagosome marker, to the autophagosome. Despite studies of the relation between cancer progression and autophagy adaptor proteins, there are no reports to our knowledge of a correlation between hepatocellular carcinoma (HCC) and OPTN. We aimed here to investigate the effects of OPTN expression on HCC progression through autophagy. Immunohistochemistry was used to measure the OPTN expression in the tissues of 141 Japanese patients with HCC. The effects of OPTN expression on HCC progression and mitophagy were assessed using an OPTN knockout (KO) cell line in vitro. We used this KO cell line to establish and exploit a mouse model of HCC to determine the effects of OPTN expression on tumor progression. Immunohistochemical analysis showed that patients with elevated expression of OPTN experienced shorter overall survival (OS) and recurrence-free survival (RFS). OPTN KO cells proliferated relatively slower versus wild-type (WT) cells in vitro. Western blot analysis showed that mitophagy was suppressed in OPTN KO cells, and ATP synthesis and beta-oxidation were reduced. The mouse model of HCC showed that OPTN KO cells formed smaller tumors versus WT cells less 10 weeks after implantation. Overall, the present findings suggest that OPTN is a key mediator of mitophagy that contributes to HCC progression through mitochondrial energy production..
143. Huanlin Wang, Shinji Itoh, Yuji Matsumoto, Akihiro Nishie, Takeshi Kurihara, Tomonari Shimagaki, Yoshihiro Nagao, Takeo Toshima, Noboru Harada, Kenichi Kohashi, Yoshinao Oda, Kousei Ishigami, Haruhiko Maruyama, Tomoharu Yoshizumi, Masaki Mori, Surgically resected hepatic mass caused by fascioliasis., Clinical journal of gastroenterology, 10.1007/s12328-021-01339-0, 14, 2, 662-667, 2021.04, Fascioliasis is a parasitic infestation caused by the digenetic trematodes Fasciola hepatica and F. gigantica. It is not commonly seen in developed countries, so diagnosis there is always difficult as a result of confusion with other hepatic or biliary disorders. A 56-year-old man presented at our hospital with a hepatic mass that had been inadvertently discovered by ultrasonography. Abdominal computed tomography revealed a multi-cystic lesion distributed along the branch of the right bile duct. Endoscopic retrograde cholangiopancreatography showed serrated changes ranging from the upper level of the common bile duct to the right hepatic bile duct. Eosinophilia was not observed and tumor marker levels were within normal ranges. Following right lobectomy combined with bile duct reconstruction, a histological examination revealed cholangitis with inflammatory cell infiltration accompanied by parasite egg-like structures and Charcot-Leyden crystals. An additional serologic test was positive for F. hepatica antibodies. A diagnosis of fascioliasis was thus confirmed by histopathology and serology. Fascioliasis should be suspected if imaging findings such as multiple small hypodense lesions in the liver are observed, and serologic tests can be useful for differential diagnosis..
144. Shohei Yoshiya, Noboru Harada, Takahiro Tomiyama, Kazuki Takeishi, Takeo Toshima, Tomohiro Iguchi, Shinji Itoh, Mizuki Ninomiya, Tomoharu Yoshizumi, Masaki Mori, The Significant Prognostic Factors in Prolonged Intensive/High Care Unit Stay After Living Donor Liver Transplantation., Transplantation proceedings, 10.1016/j.transproceed.2021.02.020, 53, 5, 1630-1638, 2021.06, BACKGROUND: Prolonged stay in an intensive/high care unit (ICU/HCU) after living donor liver transplantation (LDLT) is a significant event with possible mortality. METHODS: Adult-to-adult LDLTs (n = 283) were included in this study. Univariate and multivariate analyses were performed for the factors attributed to the prolonged ICU/HCU stay after LDLT. RESULTS: Recipients who stayed in the ICU/HCU 9 days or longer were defined as the prolonged group. The prolonged group was older (P = .0010), had a higher model for end-stage liver disease scores (P < .0001), and had higher proportions of patients with preoperative hospitalization (P < .0001). Delirium (P < .0001), pulmonary complications (P < .0001), sepsis (P < .0001), reintubation or tracheostomy (P < .0001), relaparotomy due to bleeding (P = .0015) or other causes (P < .0001), and graft dysfunction (P < .0001) were associated with prolonged ICU/HCU stay. Only sepsis (P = .015) and graft dysfunction (P = .019) were associated with in-hospital mortality among patients with prolonged ICU/HCU stay or graft loss within 9 days of surgery. Among these patients, grafts from donors aged <42 years and with a graft-to-recipient weight ratio of >0.76% had significantly higher graft survival than grafts from others (P = .0013 and P < .0001, respectively). CONCLUSION: Prolonged ICU/HCU stay after LDLT was associated with worse short-term outcomes. The use of grafts of sufficient volume from younger donors might improve graft survival..
145. Takeo Toshima, Tomoharu Yoshizumi, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Yoshihiro Nagao, Shinji Itoh, Noboru Harada, Masaki Mori, Which is better to use "body weight" or "standard liver weight", for predicting small-for-size graft syndrome after living donor liver transplantation?, Annals of gastroenterological surgery, 10.1002/ags3.12412, 5, 3, 363-372, 2021.05, Aim: Little evidence about whether to apply graft-to-recipient body weight ratio (GRWR) or graft weight to standard liver weight (GW/SLW) for graft selection has been published. The aim of the present study was to clarify the importance of the correct use of GRWR and GW/SLW for selecting graft according to the recipients' physique in living donor liver transplantation (LDLT). Methods: Data were collected for 694 recipients who underwent LDLT between 1997 and 2020. Results: One of the marginal grafts meeting GW/SLW ≥ 35% but GRWR < 0.7% has been used in more recipients with men and higher body mass index (BMI), and the other meeting GRWR ≥ 0.7% but GW/SLW < 35% has been used in more recipients with women with lower BMI. In the cohort of BMI > 30 kg/m2, the recipients with GRWR < 0.7% had a significantly higher incidence of small-for-size graft syndrome (SFSS) compared to those with GRWR ≥ 0.7% (P = 0.008, 46.2% vs 5.9%), and using the cutoff of GW/SLW < 35% could not differentiate. In contrast, in the cohort of BMI ≤ 30 kg/m2, the recipients with GW/SLW < 35% also had a significantly higher incidence of SFSS (P = 0.013, 16.9% vs 9.4%). Multivariate analysis showed that GRWR < 0.7% [odds ratio (OR) 14.145, P = 0.048] was the independent risk factor for SFSS in obese recipients, and GW/SLW < 35% [OR 2.685, P = 0.002] was the independent risk factor in non-obese recipients. Conclusion: Proper use of the formulas for calculating GRWR and GW/SLW in choosing graft according to recipient BMI is important, not only to meet metabolic demand for avoiding SFSS but also to ameliorate donor shortages..
146. Kojiro Hata, Kimitaka Suetsugu, Nobuaki Egashira, Yoko Makihara, Shinji Itoh, Tomoharu Yoshizumi, Masatake Tanaka, Motoyuki Kohjima, Hiroyuki Watanabe, Satohiro Masuda, Ichiro Ieiri, Association of lenvatinib plasma concentration with clinical efficacy and adverse events in patients with hepatocellular carcinoma., Cancer chemotherapy and pharmacology, 10.1007/s00280-020-04178-x, 86, 6, 803-813, 2020.12, PURPOSE: This study aimed to examine the association between the trough plasma concentration of lenvatinib with the objective response rate (ORR) and adverse events in patients with hepatocellular carcinoma (HCC). METHODS: Twenty-one patients with HCC who received lenvatinib were enrolled. We examined the median trough concentration (Ctrough median) of plasma lenvatinib until the first clinical response evaluation. The receiver-operating characteristic curve was drawn to show the discrimination potential of the Ctrough median for the ORR, using the modified Response Evaluation Criteria in Solid Tumors. Adverse events were graded based on the Common Terminology Criteria for Adverse Events (ver. 5.0). RESULTS: The Ctrough median values in the complete response and partial response group were significantly higher than those in the stable disease and progressive disease groups. The ORR was significantly higher in the high-Ctrough median group (≥ 42.68 ng/mL) than in the low-Ctrough median group (< 42.68 ng/mL) (80.0% vs. 18.2%; p = 0.0089). Although there was no difference in the occurrence of most adverse events between the high- and low-Ctrough median groups, the occurrence of any grade anorexia (100.0% vs. 45.5%; p = 0.0124) and grade 3 serious hypertension (70.0% vs. 18.2%; p = 0.0300) was significantly higher in the high-Ctrough median group than in the low-Ctrough median group. Multivariate analysis showed that high-Ctrough median was significantly associated with ORR development (odds ratio, 15.00; 95% confidence interval, 1.63-138.16; p = 0.0168). CONCLUSION: Maintaining Ctrough median above 42.68 ng/mL was crucial for achieving the ORR in patients with HCC..
147. Masatoshi Murakami, Nao Fujimori, Yoshihiro Nagao, Tomoharu Yoshizumi, Kazuhide Matsumoto, Sho Yasumori, Katsuhito Teramatsu, Yu Takamatsu, Takamasa Oono, Yoshihiro Ogawa, Colonic varices: a rare complication of pancreatic cancer., Clinical journal of gastroenterology, 10.1007/s12328-020-01225-1, 13, 6, 1355-1359, 2020.12, A 55-year-old man was diagnosed with pancreatic cancer of the uncus and received chemotherapy (modified FOLFIRINOX). Ten months later, he was admitted to our hospital with massive lower gastrointestinal bleeding. Contrast-enhanced CT showed ascending colon varices caused by the occlusion of the superior mesenteric vein (SMV) due to pancreatic cancer invasion. Colonoscopy revealed tortuous varices with red spots in the ascending colon. The patient received blood transfusions and was discharged; however, he was hospitalized for recurrent massive lower gastrointestinal bleeding 3 months later. During this readmission, we performed the transileocolic vein obliteration method due to SMV stenosis and the absence of an obvious shunt. He experienced an uneventful post-operative recovery, and contrast-enhanced CT after 2 months revealed no recurrence of colonic varices. Ectopic varices are portosystemic venous collaterals resulting from portal hypertension occurring in any locations other than the esophagogastric region. Colonic varices have rarely been reported before. Patients with pancreatic cancer may present with gastrointestinal bleeding caused by tumor bleeding or esophagogastric varices; however, ectopic varices such as colon varices, a rare complication of pancreatic cancer, should be considered in patients with obscure gastrointestinal bleeding..
148. Mohamed Elshawy, Takeo Toshima, Yoshiki Asayama, Yuichiro Kubo, Shinichiro Ikeda, Toru Ikegami, Shingo Arakaki, Tomoharu Yoshizumi, Masaki Mori, Correction to: Post-transplant inflow modulation for early allograft dysfunction after living donor liver transplantation., Surgical case reports, 10.1186/s40792-020-00958-y, 6, 1, 198-198, 2020.08, An amendment to this paper has been published and can be accessed via the original article..
149. Ryoichi Goto, Yukiko Kosai-Fujimoto, Shintaro Yagi, Tsuyoshi Kobayashi, Nobuhisa Akamatsu, Tsuyoshi Shimamura, Satoru Imura, Satoshi Ogiso, Shugo Mizuno, Mitsuhisa Takatsuki, Takasuke Fukuhara, Tatsuya Kanto, Susumu Eguchi, Katsuhiko Yanaga, Yasuhiro Ogura, Takumi Fukumoto, Mitsuo Shimada, Kiyoshi Hasegawa, Hideki Ohdan, Shinji Uemoto, Yuji Soejima, Toru Ikegami, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, De novo hepatocellular carcinoma in living donor liver grafts: A Japanese multicenter experience., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13565, 50, 12, 1365-1374, 2020.12, AIM: Direct-acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post-living donor liver transplantation (LDLT). METHODS: We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post-LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan. RESULTS: Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4-15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus-related cirrhosis, of which two were treated with direct-acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody-positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19-463] days). CONCLUSION: Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody-positive grafts, should be carefully followed by surveillance of the liver graft..
150. Yoshihiro Miyagi, Tatsuya Kinjo, Tomoharu Yoshizumi, Noboru Harada, Shingo Arakaki, Tetsu Kinjo, Akira Hokama, Mitsuhisa Takatsuki, Elective staged proctocolectomy and living donor liver transplantation for colon cancer with sclerosing cholangitis-related ulcerative colitis: a case report., Surgical case reports, 10.1186/s40792-020-01059-6, 6, 1, 278-278, 2020.11, BACKGROUND: Primary sclerosing cholangitis (PSC) is a well-known complication of ulcerative colitis (UC), but it is rare to encounter patients requiring both living donor liver transplantation (LDLT) and proctocolectomy. We report a case of elective two-stage surgery involving proctocolectomy performed after LDLT for a patient with early colon cancer concurrent with PSC-related UC. To our knowledge, this is the first report of concurrent cancer successfully treated with both LDLT and proctocolectomy. CASE PRESENTATION: A 32-year-old Japanese man with colon cancer associated with UC underwent restorative proctocolectomy at 3 months after living donor liver transplantation (LDLT) for PSC. He was diagnosed with PSC and UC when he was a teenager. Conservative therapy was initiated to treat both PSC and UC. He had experienced recurrent cholangitis for years; therefore, a biliary stent was placed endoscopically. However, his liver function progressively deteriorated. Colonoscopic surveillance revealed early colon cancer; hence, surgical treatment was considered. PSC progressed to cirrhosis and portal hypertension; hence, LDLT was performed before restorative proctocolectomy. Three months after LDLT, we performed restorative proctocolectomy with ileal pouch-anal anastomosis. The postoperative course was uneventful. The patient was well, with good liver and bowel functions and without tumor recurrence, more than 1 year after proctocolectomy. CONCLUSIONS: With strict patient selection and careful patient management and follow-up, elective proctocolectomy may be performed safely and effectively after LDLT for concurrent early colon cancer with PSC-related UC. There are no previous reports of the use of both LDLT and proctocolectomy for the successful treatment of PSC-related UC and concurrent cancer..
151. Shoichi Inokuchi, Shinji Itoh, Tomoharu Yoshizumi, Kyohei Yugawa, Shohei Yoshiya, Takeo Toshima, Kazuki Takeishi, Tomohiro Iguchi, Kensaku Sanefuji, Noboru Harada, Keishi Sugimachi, Toru Ikegami, Kenichi Kohashi, Kenichi Taguchi, Hirotoshi Yonemasu, Kengo Fukuzawa, Yoshinao Oda, Masaki Mori, Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma., Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 10.1016/j.pan.2020.07.011, 20, 6, 1175-1182, 2020.09, BACKGROUND/OBJECTIVES: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC). METHODS: Ninety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined. RESULTS: The low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19-9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC. CONCLUSIONS: Low mitochondrial OGG1 expression might aggravate the PDAC prognosis..
152. Mohamed Elshawy, Takeo Toshima, Yoshiki Asayama, Yuichiro Kubo, Shinichiro Ikeda, Toru Ikegami, Shingo Arakaki, Tomoharu Yoshizumi, Masaki Mori, Post-transplant inflow modulation for early allograft dysfunction after living donor liver transplantation., Surgical case reports, 10.1186/s40792-020-00897-8, 6, 1, 164-164, 2020.07, BACKGROUND: To treat small-for-size syndrome (SFSS) after living donor liver transplantation (LDLT), many procedures were described for portal flow modulation before, during, or after transplantation. The selection of the procedure as well as the best timing remains controversial. CASE PRESENTATION: A 43-year-old female with end-stage liver disease underwent LDLT with extended left with caudate lobe graft from her donor who was her 41-year-old brother (graft volume/standard liver volume (GV/SLV), 35.7%; graft to recipient weight ratio (GRWR), 0.67%). During the surgery, splenectomy could not be performed owing to severe peri-splenic adhesions to avoid the ruined bleedings. The splenic artery ligation was not also completely done because it was dorsal to the pancreas and difficult to be approached. Finally, adequate portal vein (PV) inflow was confirmed after portal venous thrombectomy. As having post-transplant optional procedures that are accessible for PV flow modulation, any other procedures for PV modulation during LDLT were not done until the postoperative assessment of the graft function and PV flow for possible postoperative modulation of the portal flow accordingly. Postoperative PV flow kept as high as 30 cm/s. By the end of the 1st week, there was a progressive deterioration of the total bilirubin profile (peak as 19.4 mg/dL) and ascitic fluid amount exceeded 1000 mL/day. Therefore, splenic artery embolization was done effectively and safely on the 10th postoperative day (POD) to reverse early allograft dysfunction as PV flow significantly decreased to keep within 20 cm/s and serum total bilirubin levels gradually declined with decreased amounts of ascites below 500 mL on POD 11 and thereafter. The patient was discharged on POD 28 with good condition. CONCLUSIONS: SFSS can be prevented or reversed by the portal inflow modulation, even by post-transplant procedure. This case emphasizes that keeping accessible angiographic treatment options for PV modulation, such as splenic artery embolization, after LDLT is quite feasible..
153. Yusuke Yonemura, Tomoharu Yoshizumi, Shoichi Inokuchi, Yukiko Kosai-Fujimoto, Noboru Harada, Shinji Itoh, Takeo Toshima, Kazuki Takeishi, Shohei Yoshiya, Masaki Mori, Predictor of outcome after living donor liver transplantation for patients with hepatocellular carcinoma beyond the Japan criteria., Annals of gastroenterological surgery, 10.1002/ags3.12335, 4, 4, 413-421, 2020.07, Background: The Japan criteria (JC, maximum tumor size within 5 cm, within five tumor nodules, AFP within 500 ng/mL or within Milan criteria) have been applied to cadaveric liver transplantation (LT) for hepatocellular carcinoma (HCC) and will be used for living donor LT (LDLT) in Japan. The aim of this study was to verify the JC in LDLT and to clarify the risk factor of HCC recurrence and mortality after LDLT beyond the JC. Patients and methods: Adult patients who underwent LDLT for end-stage liver disease with HCC until October 2019 were reviewed retrospectively (n = 246). Patients were divided into two groups according to whether they were within JC (n = 203) or beyond JC (n = 43). Recurrence-free or overall survival rates after LDLT were compared. Univariate and multivariate analyses were performed to identify risk factors of HCC recurrence and HCC-related mortality after LDLT for patients beyond the JC. Results: Patients beyond the JC had significantly poorer 5-year recurrence-free (50.3% vs 95.9%, P < .001) or overall (61.7% vs 98.1%, P < .001) survival rates compared with patients within the JC. A multivariate analysis revealed that des-gamma-carboxy prothrombin (DCP) ≥ 300 mAU/mL (hazard ratio 9.36, 95% CI; 2.41-36.4, P = .001) was an independent risk factor for HCC recurrence and HCC-related mortality (hazard ratio 13.8, 95% CI; 1.92-98.6, P = .01) after LDLT in patients beyond the JC. Conclusion: The outcome of LDLT for patients within the JC was favorable. Patients beyond the JC with DCP ≥ 300 mAU/mL might be contraindicated for LDLT..
154. Tomohiro Iguchi, Keishi Sugimachi, Yohei Mano, Takashi Motomura, Masahiko Sugiyama, Mitsuhiko Ota, Masahiko Ikebe, Taito Esaki, Tomoharu Yoshizumi, Masaru Morita, Masaki Mori, Yasushi Toh, Prognostic Impact of Geriatric Nutritional Risk Index in Patients With Synchronous Colorectal Liver Metastasis., Anticancer research, 10.21873/anticanres.14416, 40, 7, 4165-4171, 2020.07, BACKGROUND/AIM: The Geriatric Nutritional Risk Index (GNRI) is a prognostic indicator for several cancers; however, the association between the GNRI and colorectal liver metastasis (CRLM) remains unknown. PATIENTS AND METHODS: Eighty patients who underwent hepatectomy for synchronous CRLM were divided into two groups based on the GNRI. RESULTS: The preoperative CA19-9 levels were significantly higher in the low (GNRI ≤98; n=30) than the normal GNRI group (GNRI >98; n=50). Patients in the low GNRI group had poorer outcomes than those in the normal GNRI group. A low GNRI was an independent prognostic factor for recurrence-free survival and overall survival. Among 50 patients who experienced recurrence, only 16 of 22 patients (72.7%) in the low GNRI group could receive intensive treatment and 27 of 28 patients (96.4%) in the normal GNRI group. CONCLUSION: The GNRI is a simplified prognostic factor for patients with CRLM..
155. Satomi Tanaka, Kimie Fujita, Maki Kanaoka, Kiyoko Makimoto, Kanako Yakushiji, Rumi Tanaka, Noboru Harada, Toru Ikegami, Tomoharu Yoshizumi, Prospective study of objective physical activity and quality of life in living donor liver transplant recipients., Japan journal of nursing science : JJNS, 10.1111/jjns.12362, 17, 4, e12362, 2020.10, AIM: The aims of this study were to: (a) describe the physical activity (PA) and quality of life (QOL) in living donor liver transplant (LDLT) recipients pre-operatively and at 3 months and 6 months post-operatively; (b) compare PA and QOL at 6 months post-operatively with a healthy control group; and (c) explore pre-operative factors that predict PA changes. METHODS: Patients over 20 years of age who were undergoing LDLT were recruited. PA was measured based on the number of steps/day and time spent performing moderate-to-vigorous PA (MVPA) during 1 week using an accelerometer. QOL was assessed based on a physical (PCS) and mental (MCS) component summary of the eight-item Short-Form Health Survey. The LDLT and healthy control groups were matched for age (±3 years) and gender. Pre-operative factors predicting a change in PA were calculated using a generalized linear mixed model. RESULTS: Twenty-four patients completed the study. By 6 months post-LDLT, the MCS and PCS were comparable to those in the control group. The number of steps (3,887 steps/day) and MVPA (29.3 min/week) showed significant improvement by 6 months post-operatively, but remained much lower compared with those in the control group. The multivariate analysis showed that younger age (p < .01, p = .04) and higher skeletal muscle mass (SMM; p < .01, p = .03) were predictors of improvement in number of steps and MVPA. CONCLUSION: This study suggests the need for pre-operative interventions by healthcare professionals that focus on outcomes such as improving low SMM to facilitate post-operative PA recovery..
156. Nobuhiro Fujita, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Kakihara, Yukihisa Takayama, Tomoharu Yoshizumi, Tomoyuki Hida, Yoshinao Oda, Tomoyuki Okuaki, Hiroshi Honda, Quantitative evaluation of liver function and pathology with hepatocyte fraction on Gadoxetic acid-enhanced MR imaging., Magnetic resonance imaging, 10.1016/j.mri.2020.08.018, 73, 125-129, 2020.11.
157. Satomi Tanaka, Kimie Fujita, Kiyoko Makimoto, Maki Kanaoka, Kanako Yakushiji, Rumi Tanaka, Noboru Harada, Tomoharu Yoshizumi, Relationships of accelerometer-determined physical activity with obesity, hypertension, diabetes, dyslipidemia, and health-related quality of life in patients after liver transplantation., Clinical transplantation, 10.1111/ctr.14117, 34, 12, e14117, 2020.12, The contribution of physical activity (PA) to the prevention of metabolic abnormalities following liver transplantation (LT) has not been well documented. We aimed to assess PA in post-LT patients and to quantify its relationships with the development of postoperative metabolic abnormalities and health-related quality of life (HRQOL). We recruited 111 patients who had undergone LT ≥ 6 months previously. PA was measured by accelerometry, and HRQOL was evaluated using SF-8. PA was quantified as the number of steps per day, and the time spent performing moderate-to-vigorous PA and light PA per week. The prevalence of hypertension, diabetes, and dyslipidemia increased more than twofold following LT. The proportion of the participants with a sedentary lifestyle (<5000 steps/day) was 36%. Logistic regression analysis showed that postoperative hypertension and obesity were associated with preoperative body mass index and the number of steps taken (in 2000 steps/day increments). Preoperative diabetes was associated with obesity, and PA was associated with physical function-related HRQOL scores. Thus, increasing the number of steps taken per day has the potential to reduce hypertension and obesity, and PA could improve physical function-related HRQOL in patients following LT..
158. Toshiharu Matsuura, Kenichi Kohashi, Yuki Kawano, Yoshiaki Takahashi, Koichiro Yoshimaru, Tomoharu Yoshizumi, Yoshinao Oda, Masaki Mori, Tomoaki Taguchi, Successful management to prevent early graft loss due to Seventh-day Syndrome after liver retransplantation: A case report and literature review., Pediatric transplantation, 10.1111/petr.13907, 25, 5, e13907, 2020.11, Graft loss characterized by sudden deterioration after initial favorable recovery of the allograft function within the first week after liver transplantation was reported as "seventh-day syndrome." The outcome of seventh-day syndrome is extremely poor, and its etiology and management are not still established. We herein reported a seventh-day syndrome case who was successfully managed by immediate desensitization after liver retransplantation and reviewed by English literature. A 19-year-old woman who had underwent the first liver transplantation when she was 2-year-old. She developed graft failure due to chronic rejection and was on the waiting list for retransplantation. An evaluation of panel-reactive antibody showed high positivity, but there were no preformed donor-specific antibodies. Plasma exchange was performed one-time just before retransplantation and the mean fluorescence intensity significantly decreased. The second liver was successfully transplanted, and post-operative course was uneventful. However, on post-operative day 5, her body temperature elevated and thereafter, her liver enzymes dramatically elevated. We immediately started a desensitization consisted of plasma exchange, intravenous immunoglobulin, and anti-CD20 antibody. The peak level of AST and ALT was 5799 IU/L and 3960 IU/L, respectively. The pathological findings of liver biopsy revealed some central venous endotheliitis and massive centrilobular hemorrhagic hepatocellular necrosis. These findings were not typical for antibody-mediated rejection, but the desensitization was effective and liver graft was successfully rescued. The only way to prevent early graft loss due to seventh-day syndrome is thought to be an immediate decision to start intensive desensitization..
159. Katsuya Toshida, Ryosuke Minagawa, Hiroto Kayashima, Shohei Yoshiya, Tadashi Koga, Kiyoshi Kajiyama, Tomoharu Yoshizumi, Masaki Mori, The Effect of Prone Positioning as Postoperative Physiotherapy to Prevent Atelectasis After Hepatectomy., World journal of surgery, 10.1007/s00268-020-05682-0, 44, 11, 3893-3900, 2020.11, BACKGROUND: The incidences of postoperative pulmonary complications (PPCs) such as atelectasis, pneumonia and pleural effusion after major surgery range from <1 to 23%. Atelectasis after abdominal surgery increases the duration of hospitalization and short-term mortality rate, but there are few reports about atelectasis after hepatectomy. The effectiveness of prone position drainage as physiotherapy has been reported, but it remains unclarified whether prone positioning prevents atelectasis after hepatectomy. This study aimed to evaluate the effect of the prone position on the incidence of atelectasis after hepatectomy. METHODS: We retrospectively analyzed the incidence of PPCs after hepatectomy at a single center. Patients were divided into two cohorts. The earlier cohort (n = 165) underwent hepatectomy between January 2016 and March 2018 and was analyzed to identify the risk factors for atelectasis and short-term outcomes; the later cohort (n = 51) underwent hepatectomy between April 2018 and March 2019 and underwent prone position drainage in addition to regular mobilization postoperatively. The incidences of PPCs were compared between the two cohorts. RESULTS: Independent risk factors for atelectasis were anesthetic duration (P = 0.016), operation time (P = 0.046) and open surgery (P = 0.011). The incidence of atelectasis was significantly lower in the later cohort (9.8%) than the earlier cohort (34.5%, P < 0.001). Moreover, the later cohort had a significantly shorter duration of oxygen support (P < 0.001) and postoperative hospitalization (P < 0.001). After propensity score-matching, the incidence of atelectasis remained significantly lower in the later cohort (P = 0.027). CONCLUSION: Prone position drainage may decrease the incidence of atelectasis after hepatectomy and improve the short-term outcomes..
160. Noboru Harada, Tomoharu Yoshizumi, Toshiharu Matsuura, Tomoaki Taguchi, Masaki Mori, Usefulness of microsurgical back-table angioplasty for multiple hepatic arteries in living donor liver transplantation., Annals of gastroenterological surgery, 10.1002/ags3.12370, 4, 6, 735-740, 2020.11, The graft hepatic artery orifice is tiny in living donor liver transplantation, and therefore, it is more difficult to reconstruct the hepatic artery than in deceased donor liver transplantation. In situ, multi-vessel hepatic artery reconstruction in living donor liver transplantation is time-consuming, and reconstructions are often complicated if the hepatic graft has several stumps. We describe two living donor liver transplants using back-table microsurgical angioplasty to combine two hepatic artery stumps to create a single orifice, and sequential single-vessel hepatic artery reconstruction in the recipient. Briefly, we used double-needle interrupted sutures for the two hepatic artery stumps with a biangular stay-suture method in back-table microsurgical angioplasty. Each suture was placed from the inner side of the arterial wall to the outer side, which allowed for safe and reliable suturing. After placing the interrupted sutures in the anterior wall, we turned over the vessels in the cold storage on the back table and placed interrupted sutures in the posterior wall. In the recipient, the single stump of the graft was anastomosed to the recipient's hepatic artery using an interrupted pattern and a surgical microscope. The postoperative courses of the donors and recipients were uneventful. Back-table hepatic artery angioplasty is a feasible option to overcome the complexities of multi-vessel arterial reconstruction in living donor liver transplantation. We recommend performing secure multi-vessel hepatic arterial reconstruction adapted to the clinical scenario. Using simple appropriate anastomosis, back-table microsurgical angiography may provide good results in living donor liver transplantation..
161. 吉住 朋晴, 池上 徹, 原田 昇, 伊藤 心二, 武石 一樹, 戸島 剛男, 間野 洋平, 吉屋 匠平, 栗原 健, 副島 雄二, 森 正樹, がんにまつわる感染症Up to Date HTLV-1陽性者への肝移植後成人T細胞白血病発症の危険因子, 日本癌治療学会学術集会抄録集, 57回, SSY10-3, 2019.10.
162. 渡辺 亮, 播本 憲史, 新木 健一郎, 久保 憲生, 五十嵐 隆通, 塚越 真梨子, 石井 範洋, 吉住 朋晴, 有馬 浩太, 山下 洋市, 馬場 秀夫, 樋口 徹也, 調 憲, 大腸癌肝転移conversion surgeryにおけるSUV変化率に基づいた治療戦略, 日本癌治療学会学術集会抄録集, 57回, RT21-1, 2019.10.
163. 伊藤 心二, 吉住 朋晴, 森 正樹, 肝細胞癌におけるPD-L1発現と浸潤性CD8陽性Tリンパ球の関連(Association of tumor-infiltrating CD8-T cells with programmed cell death-ligand 1 expression in hepatocellular carcinoma), 日本癌学会総会記事, 78回, P-1124, 2019.09.
164. 井口 詔一, 吉住 朋晴, 伊藤 心二, 福澤 謙吾, 吉屋 匠平, 戸島 剛男, 武石 一樹, 原田 昇, 池上 徹, 副島 雄二, 森 正樹, 膵癌におけるDNA修復酵素OGG1発現の意義, 日本癌治療学会学術集会抄録集, 57回, P25-4, 2019.10.
165. Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Masashi Ohira, Yoshihiko Maehara, Appropriate Use of Stents to Prevent Biliary Complications after Living Donor Liver Transplantation, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2017.10.009, 226, 2, 201, 2018.02.
166. Tatsunori Miyata, Yo-ichi Yamashita, Tomoharu Yoshizumi, Masayuki Shiraishi, Masayuki Ota, Susumu Eguchi, Shinichi Aishima, Hideo Baba, Hikaru Fujioka, CXCL12 is involved in liver metastasis of intrahepatic cholangiocarcinoma, CANCER SCIENCE, 109, 864-864, 2018.12.
167. Tatsunori Miyata, Yoichi Yamashita, Tomoharu Yoshizumi, Masayuki Shiraishi, Masayuki Ota, Susumu Eguchi, Shinichi Aishima, Hideo Baba, Hikaru Fujioka, Cxcl12 is involved in liver metastasis of intrahepatic cholangiocarcinoma, CANCER RESEARCH, 10.1158/1538-7445.AM2018-1069, 78, 13, 2018.07.
168. N. Harimoto, K. Yugawa, T. Ikegami, M. Ohira, Y. Mano, T. Motomura, T. Toshima, S. Itoh, N. Harada, Y. Soejima, T. Yoshizumi, Y. Maehara, Y. Oda, Hepatobiliary and Pancreatic: Pregnancy induced hepatic veno-occlusive disease requiring liver transplantation, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.13975, 33, 1, 9, 2018.01.
169. Kazuki Takeishi, Hirofumi Kawanaka, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Impact of Splenic Volume and Splenectomy on Prognosis of Hepatocellular Carcinoma Within Milan Criteria After Curative Hepatectomy., World journal of surgery, 10.1007/s00268-017-4232-z, 42, 4, 1120-1128, 2018.04, BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) with portal hypertension (PH) is very poor. Splenomegaly is considered important evidence of PH. Our aim was to clarify the prognostic value of splenic volume (SV) and the effect of splenectomy on the prognosis of HCC within the Milan criteria after curative hepatectomy. METHODS: In this single-center retrospective study, we reviewed 160 patients with HCC that met the Milan criteria, including 138 who had undergone hepatectomy and 22 who had undergone hepatectomy and splenectomy between July 2004 and December 2010. SV was measured by three-dimensional computed tomography and patients allocated to three groups (high SV ≥300 mL; low <300 mL; and splenectomy) to compare post-hepatectomy survival rates. RESULTS: Multivariate analyses showed that SV is an independent prognostic factor for overall and disease-free survival. The overall survival rates at 5 years in the high SV, low SV, and splenectomy groups were 39, 75, and 88%, respectively. The overall survival rate in the high SV group was significantly worse than in the low SV and splenectomy groups (P < 0.001). There was no significant difference between the low SV and splenectomy groups (P = 0.831). CONCLUSIONS: High SV is an independent predictor of post-hepatectomy HCC recurrence and overall survival. There is no significant difference in prognosis between low SV and splenectomy groups, even though the latter had high SV. Combined splenectomy with hepatectomy for HCC and PH may improve prognosis and be an appropriate alternative when liver transplantation cannot be performed..
170. T. Ikegami, T. Yoshizumi, M. Ohira, N. Harada, Y. Soejima, Y. Maehara, Indication of living donor liver transplantation for septuagenarians from double equipoise theory, American Journal of Transplantation, 10.1111/ajt.14446, 18, 1, 278-279, 2018.01.
171. Watanabe Akira, Araki Kenichirou, Harimoto Norihumi, Yoshizumi Tomoharu, Arima Kouta, Yamashita Youichi, Baba Hideo, Higuchi Tetsuya, Kuwano Hiroyuki, Shirabe Ken, Timing of Liver Surgery for Colorectal Liver Metastasis(Surgery First vs. Chemotherapy First) A new strategy based on FDG-PET for managing liver metastasis from colorectal cancer(和訳中), 日本肝胆膵外科学会・学術集会プログラム・抄録集, 30回, 293-293, 2018.06.
172. 【合併症ゼロを目指した最新の低侵襲内視鏡外科手術】 膵臓・脾臓 腹腔鏡下脾臓摘出術.
173. 【肝】大腸癌多発肝転移に対する手術の工夫 大腸癌肝転移におけるFDG-PETに基づく新たな治療戦略.
174. 【肝】大腸癌多発肝転移に対する手術の工夫 大腸癌肝転移におけるFDG-PETに基づく新たな治療戦略.
175. 【肝癌-診断・治療の最新知見-】 肝癌の治療 肝移植.
176. 周術期管理から退院後のTOTAL SUPPORT~GUT STARVATIONとKAMPO~ 成人肝移植後消化管障害に対するTJ-100ツムラ大建中湯の有効性に関する多施設共同二重盲検無作為化比較試験(DKB14 study).
177. 播本 憲史, 吉住 朋晴, 足立 英輔, 池田 泰治, 内山 秀昭, 宇都宮 徹, 梶山 潔, 木村 光一, 岸原 文明, 杉町 圭史, 二宮 瑞樹, 福澤 謙吾, 前田 貴司, 調 憲, 前原 喜彦, 肝細胞癌切除患者におけるCONUTscoreの意義 多施設共同研究の結果から, 日本癌治療学会学術集会抄録集, 56回, O25-1, 2018.10.
178. 播本 憲史, 吉住 朋晴, 足立 英輔, 池田 泰治, 内山 秀昭, 宇都宮 徹, 梶山 潔, 木村 光一, 岸原 文明, 杉町 圭史, 二宮 瑞樹, 福澤 謙吾, 前田 貴司, 調 憲, 前原 喜彦, 肝細胞癌切除患者におけるCONUTscoreの意義 多施設共同研究の結果から, 日本癌治療学会学術集会抄録集, 56回, O25-1, 2018.10.
179. 門脈圧亢進症に対する腹腔鏡下脾摘術を安全に行うための手技のポイント.
180. Takeshi Kurihara, Tomoharu Yoshizumi, Shinji Itoh, Norifumi Harimoto, Noboru Harada, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, GRAFT SELECTION STRATEGY IN ADULT-TO-ADULT LIVING DONOR LIVER TRANSPLANTATION: WHEN BOTH HEMI-LIVER GRAFTS MEET VOLUMETRIC CRITERIA, TRANSPLANT INTERNATIONAL, 30, 259-259, 2017.09.
181. Tomoharu Yoshizumi, Shinji Itoh, Norifumi Harimoto, Noboru Harada, Takashi Motomura, Yohei Mano, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, IMPACT OF SIMULTANEOUS SPLENECTOMY IN LIVING DONOR LIVER TRANSPLANTATION ANALYZED BY PROPENSITY SCORE MATCHING, TRANSPLANT INTERNATIONAL, 30, 128-128, 2017.09.
182. 【外科手術器具の理論と使用法】III.エネルギーデバイス 肝臓手術で用いるエネルギーデバイス.
183. 【混合型肝癌をめぐる混乱の終焉を目指して】 肝細胞癌の診断で肝移植された混合型肝癌の特徴.
184. 【激変する肝疾患診療の現状】 肝移植の現況と問題点.
185. 【目で見る腹腔鏡下肝切除-エキスパートに学ぶ!】 エキスパートに学ぶ手技 肝後区域切除 体位とエネルギーデバイスの工夫
<ポイント>腹腔鏡下肝切除はその低侵襲性から急速に普及し,2016年4月より亜区域,区域,2区域,3区域切除が保険収載された.特に肝右葉後区域および上前区域切除は,開腹手術では大きな皮膚切開が必要となり,腹腔鏡下肝切除との侵襲の差が大きい.内視鏡下手術の高画質拡大視効果を活かし,肝臓の膜構造を十分考慮した完全腹腔鏡下の右外側領域(後区域)切除を行っており,止血器具の使用方法も工夫している.(著者抄録).
186. 【肝移植手術に学ぶ】 生体および脳死肝移植における肝静脈再建.
187. 【解剖学的変異を考慮した肝胆膵外科手術】 生体肝移植における脈管解剖を考慮したグラフト採取術.
188. リンパ球好中球比(NLR)の生体肝移植予後予測マーカーとしての有用性.
189. 生体肝移植術中脾臓摘出術が術後成績に及ぼす影響に関する検討
初回成人間生体肝移植を施行した482例を対象とし、生体肝移植術中に脾臓摘出を併施した302例(摘出群、男性137名、女性165名、平均54.0歳)と併施しなかった180例(非摘出群、男性85名、女性95名、平均50.4歳)の2群に分けた。術後敗血症と術後6ヵ月以内の急性拒絶反応の頻度は、摘出群でともに低かった。摘出群で術後14日目の総ビリルビン値は低値で、腹水量は少なく、PT%は高値であった。脾臓摘出に起因する術後合併症では、術後膵液瘻を26例(5.4%)認めた。5例(1.0%)に術後門脈血栓を認めた。術後脾門部断端からの出血を5例(1.0%)、脾臓摘出後重症感染症は3例に認めた。6ヵ月グラフト生存率は摘出群で93.4%、非摘出群で84.3%、10年グラフト生存率は摘出群で73.7%、非摘出群で64.9%と、摘出群で有意に良好であった。多変量解析で脾臓摘出非施行とMELD 22以上が、生体肝移植後6ヵ月以内グラフトロスの独立危険因子であった。.
190. 発熱を呈し手術適応に苦慮した出血性肝血管腫の1例
"症例は37歳,女性.39℃を超える発熱を主訴に当科紹介受診となった.血液検査所見ではWBC 8,820/μl,Neut 73.4%,CRP 13mg/dlと炎症反応上昇を認めた.腫瘍マーカー陰性.造影CT,造影MRIでは内部に出血を伴う血管腫の所見であった.PET-CT,ガリウムシンチにて異常集積は認めなかった.感染症内科,血液内科にコンサルトしたところ,血液疾患や膠原病はいずれも否定的で,熱源は肝血管腫以外認めなかった.2週間以上持続する発熱を伴い,腫瘍内部に出血もみられたため,本人と家族に十分なICを行った上,手術を行う方針となった.肝機能温存を考慮し,術式は拡大肝後区域切除術を選択した.術後は4日目に解熱が得られ,術後9日目に自宅退院となった.肉眼所見は海綿状血管腫であった.肝血管腫の手術適応として,破裂の危険のあるものや随伴症状があるものとされているが,発熱のみを主訴とする報告は稀であり手術適応決定に苦慮したが,良好な結果を得たため報告する."(著者抄録).
191. 胆管細胞癌に対する治療戦略 腫瘤形成型胆管細胞癌における炎症因子と予後、炎症指標としてのFDG-PETの有用性に関する検討.
192. 脳死肝移植へのBrigeとしてのHigh-Flow CHDFの有効性.
193. Watanabe Akira, Araki Kenichirou, Kubo Norio, Igarashi Takamichi, Tsukaghoshi Mariko, Ishii Norihiro, Yamanaka Takahiro, Yoshizumi Tomoharu, Kuwano Hiroyuki, Shirabe Ken, 腫瘤形成型肝内胆管癌では炎症と予後との間に関連性があり、炎症予測因子としてFDG-PETが有用である(Mass forming intrahepatic cholangiocarcinoma had relation between inflammation and prognosis, and usefulness of FDG-PET as inflammatory predictive factor), Journal of Hepato-Biliary-Pancreatic Sciences, 24, Suppl.1, A299-A299, 2017.05.
194. Yohei Mano, Sachiyo Yoshio, Hirotaka Shoji, Masaya Sugiyama, Hiroyoshi Doi, Toru Okamoto, Yosuke Osawa, Kiminori Kimura, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Masashi Mizokami, Tatsuya Kanto, Critical roles of bone morphogenetic protein 4 in cirrhotic and cancer-associated fibroblasts that regulates cellar senescence and cancer-supportive phenotype in the human liver, HEPATOLOGY, 64, 86A-86A, 2016.10.
195. Shinji Itoh, Tomoharu Yoshizumi, Koichi Kimura, Hirohisa Okabe, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Ken Shirabe, Akihiro Nishie, Yoshihiko Maehara, Effect of Sarcopenic Obesity on Outcomes of Living-Donor Liver Transplantation for Hepatocellular Carcinoma., Anticancer research, 36, 6, 3029-34, 2016.06, BACKGROUND/AIM: We aimed to evaluate the effect of body composition on the outcome of living-donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We performed LDLT in 153 patients with HCC and divided the patients into two groups based on skeletal muscle mass-to-visceral fat area ratio (SVR), as assessed by computed tomography (CT) measurement, namely a low-SVR group (n=38) and a not-low SVR group (n=112). We compared surgical outcomes between the two groups. RESULTS: A low SVR was significantly correlated with a higher body mass index and male sex. No differences were found between the two groups in terms of other factors. The patients in the low-SVR group had a significantly poorer prognosis than those in the not-low SVR group in terms of recurrence-free (p=0.01) and overall (p=0.03) survival. The results of the multivariate analysis showed low SVR to be an independent and prognostic indicator for patients with HCC who had undergone LDLT. CONCLUSION: Pre-transplant body composition measured by CT is a major determinant of prognosis in LDLT for HCC in Japan..
196. Hideaki Uchiyama, Ryosuke Minagawa, Shinji Itoh, Kiyoshi Kajiyama, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Kenji Takenaka, Yoshihiko Maehara, Favorable Outcomes of Hepatectomy for Ruptured Hepatocellular Carcinoma: Retrospective Analysis of Primary R0-Hepatectomized Patients., Anticancer research, 36, 1, 379-85, 2016.01, BACKGROUND/AIM: The rupture of hepatocellular carcinoma (HCC) is defined as a detrimental staging factor. The aim of the present study was to elucidate whether the prognosis of surgical patients with ruptured HCC was truly appalling. PATIENTS AND METHODS: The data obtained from the medical records of 1,031 patients who underwent primary R0 hepatecomy for HCC between August 2003 and November 2014 at the Department of Surgery and Science, Kyushu University Hospital and its two affiliated hospitals, were retrospectively analyzed. Twenty-seven patients had ruptured HCC. RESULTS: The recurrence-free and overall survival for patients with ruptured HCC were favorable. All 19 patients with ruptured HCC who experienced recurrence had intrahepatic recurrence, while only three had peritoneal recurrence. The multivariate risk factor analyses showed that rupture itself was not relevant to recurrence-free survival nor to overall patient survival. CONCLUSION: Rupture itself does not have much relevance to the outcome for patients who undergo hepatectomy..
197. Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Feasible usage of ABO incompatible grafts in living donor liver transplantation., Hepatobiliary surgery and nutrition, 10.3978/j.issn.2304-3881.2015.06.02, 5, 2, 91-7, 2016.04, BACKGROUND: The use of ABO incompatible (ABOi) graft in living donor liver transplantation (LDLT) has not been an established procedure worldwide. METHODS: Four hundred and eight adult LDLTs, using ABOi (n=19) and non-ABOi (n=389) grafts, were performed as a single center experience. RESULTS: In ABOi-LDLT group (n=19), median isoagglutinin titer before plasma exchange (PE) at LDLT and after LDLT (max) was ×256, ×32 and ×32, respectively. Rituximab was given at 21.8±6.1 days before LDLT and PE was performed 3.7±1.6 times. Although ABOi-LDLTs had increased rate of splenectomy (89.4% vs. 44.7%, P<0.001) and lower portal venous pressure (PVP) at the end of surgery (13.8±1.1 vs. 16.9±0.2 mmHg, P=0.003), other operative factors including graft ischemic time, operative time and blood loss were not different between the groups. Although ABOi-LDLTs had increased incidence of cytomegalovirus infection (52.6% vs. 22.9%, P=0.007), other post-transplant complications including bacterial sepsis and acute rejection were not different between the groups. The 5-year graft survival rate was 87.9% in ABOi-LDLTs and 80.3% in non-ABOi-LDLTs (P=0.373). CONCLUSIONS: ABOi-LDLT could be safely performed, especially under rituximab-based protocol..
198. Yuki Bekki, Toru Ikegami, Yoshihiro Yoshida, Daisuke Imai, Shinji Itoh, Norifumi Harimoto, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara, Graft vs. Systemic Heparinization in Living Donor Liver Transplantation: Risks and Benefits to Recipients and Donors, TRANSPLANTATION, 100, S139-S140, 2016.05.
199. ICG蛍光法による術中肝静脈還流域ナビゲーション.
200. 池田 哲夫, 播本 憲史, 伊藤 心二, 岡部 弘尚, 木村 光一, 池上 徹, 吉住 朋晴, 橋爪 誠, 前原 喜彦, Laparoscopic surgery; Patients protection from laparoscopic major hepato-pancreatic surgery 腹腔鏡下肝切除の安全性を担保するための3Dミクロ立体再構築法による外科解剖の解明(Laparoscopic surgery: Patients protection from laparoscopic major hepato-pancreatic surgery Elucidation of the surgical an, 日本肝胆膵外科学会・学術集会プログラム・抄録集, 28回, 356-356, 2016.06.
201. 池上 徹, 吉住 朋晴, 内山 秀昭, 播本 憲史, 伊藤 心二, 岡部 弘尚, 木村 光一, 山下 洋市, 前原 善彦, Liver transplantation; Liver transplantation for HCC, when and how? Complicated portal vein reconstruction, technical consideration 生体肝移植における門脈血栓賞に対する対策とその成績(Liver transplantation: Liver transplantation for HCC, when and how? Complicated portal vein recon, 日本肝胆膵外科学会・学術集会プログラム・抄録集, 28回, 358-358, 2016.06.
202. 調 憲, 吉住 朋晴, 池上 徹, 内山 秀昭, 前原 喜彦, Liver transplantation; Which is better for living-related liver transplantation,Right lobe graft vs.left lobe graft? 生体肝移植においては左側グラフトが第一選択である(Liver transplantation: Which is better for living-related liver transplantation, Right lobe graft vs. left lobe g, 日本肝胆膵外科学会・学術集会プログラム・抄録集, 28回, 334-334, 2016.06.
203. 伊藤 心二, 吉住 朋晴, 播本 憲史, 木村 光一, 岡部 弘尚, 原田 昇, 池上 徹, 内山 秀昭, 池田 哲夫, 前原 喜彦, Liver2; Multimodality treatment for advanced hepatocellular carcinoma 肉眼的門脈内腫瘍栓を伴う肝細胞癌に対する肝切除を中心とした集学的治療(Liver2: Multimodality treatment for advanced hepatocellular carcinoma Surgical treatment of hepatocellular carcinoma with macroscopic portal venous tu, 日本肝胆膵外科学会・学術集会プログラム・抄録集, 28回, 358-358, 2016.06.
204. Hideaki Uchiyama, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Yoshihiko Maehara, Outcomes of adult-to-adult living donor liver transplantation in 321 recipients., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.24378, 22, 3, 305-15, 2016.03, We conducted a retrospective investigation in order to clarify whether selecting the type of liver graft had an impact on outcomes of adult-to-adult living donor liver transplantation (AALDLT). Data from the medical records of the donors and the recipients of 321 consecutive cases of AALDLT performed between April 2004 and March 2014 were retrospectively analyzed. Our general criteria for selecting the type of liver graft was that a left graft was preferentially selected when the estimated volume of the left graft was ≥35% of the standard liver volume of the recipient, and that a right graft was selected only when the estimated remnant liver volume of the donor was ≥35% of the total liver volume. In this series, 177 left grafts, 136 right grafts, and 8 posterior grafts were used. The left grafts tended to have 2 or more arteries, whereas the right grafts tended to have 2 or more bile duct orifices. The graft survival curves and the incidences of severe complications were comparable between the AALDLT using right grafts and the AALDLT using left grafts. The preoperative estimation of graft size hardly enabled us to predict severe posttransplant complication. Moreover, small-for-size graft syndrome occurred regardless of the estimated graft volumes. Instead, donor age was a significant risk factor for small-for-size graft syndrome. In conclusion, left grafts should be more aggressively used for the sake of donors' safety. The use of hepatic grafts from older donors should be avoided if possible in order to circumvent troublesome posttransplant complications..
205. Kazutoyo Morita, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo-Ichi Yamashita, Keishi Sugimachi, Norifumi Harimoto, Shinji Itoh, Tetsuo Ikeda, Yoshihiko Maehara, Relevance of microRNA-18a and microRNA-199a-5p to hepatocellular carcinoma recurrence after living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.24400, 22, 5, 665-76, 2016.05, There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. First, we performed microarray analyses of samples from a liver with primary HCC, a liver that was noncancerous, and a liver that had recurrence-metastasis from 3 patients with posttransplant recurrence. Then we selected miRNAs with consistently altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous livers was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. MicroRNA-18a (miR-18a) expression was increased, and microRNA-199a-5p (miR-199a-5p) expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor, and insulin-like growth factor 2. In conclusion, increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT. Liver Transplantation 22 665-676 2016 AASLD..
206. Norifumi Harimoto, Tomoharu Yoshizumi, Masahiro Shimokawa, Kazuhito Sakata, Kouichi Kimura, Shinji Itoh, Toru Ikegami, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70 years and older with hepatocellular carcinoma., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12674, 46, 12, 1247-1255, 2016.11, AIM: The present study investigated the effect of sarcopenia on short- and long-term surgical outcomes and identified potential prognostic factors for hepatocellular carcinoma (HCC) following hepatectomy among patients 70 years of age and older. METHODS: Patient data were retrospectively collected for 296 consecutive patients who underwent hepatectomy for HCC with curative intent. Patients were assigned to two groups according to age (younger than 70 years, and 70 years and older), and the presence of sarcopenia. The clinicopathological, surgical outcome, and long-term survival data were analyzed. RESULTS: Sarcopenia was present in 112 of 296 (37.8%) patients with HCC, and 35% of patients aged 70 years and older. Elderly patients had significantly lower serum albumin levels, prognostic nutrition index, percentage of liver cirrhosis, and histological intrahepatic metastasis compared with patients younger than 70 years. Overall survival and disease-free survival rates in patients with sarcopenia correlated with significantly poor prognosis in the group aged 70 years and older. Multivariate analysis revealed that sarcopenia was predictive of an unfavorable prognosis. CONCLUSION: This retrospective analysis revealed that sarcopenia was predictive of worse overall survival and recurrence-free survival after hepatectomy in patients 70 years of age and older with HCC..
207. Yuji Soejima, Tomoaki Taguchi, Maki Sugimoto, Makoto Hayashida, Tomoharu Yoshizumi, Toru Ikegami, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Three-dimensional printing and biotexture modeling for preoperative simulation in living donor liver transplantation for small infants., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.24516, 22, 11, 1610-1614, 2016.11.
208. 【C型肝炎治療における新時代の幕開け】 肝移植症例における抗C型肝炎ウイルス(HCV)治療の今後
わが国における成人間肝移植の最も多い原因疾患は、C型肝炎である。C型肝炎ウイルス(HCV)は肝移植後早期に再感染し、放置すれば肝線維化が進行し、肝硬変ひいてはグラフトロスに至る。従って、肝移植後の抗ウイルス療法は重要である。肝移植に必要な免疫抑制剤の投与も継続しながら、インターフェロン(IFN)を中心とした抗ウイルス治療は、免疫賦活を伴うため、Interferon mediated graft dysfunction(IGD)といった病態にも配慮が必要で、その奏効率は限定的であった。その後、IFNフリーの治療が導入され、肝移植後の抗HCV治療も進歩してきた。本稿では、いわゆる直接作用型ウイルス薬(direct acting agent:DAA)の効果に関する文献的考察を含めて報告する。(著者抄録).
209. 【Stage IV胃癌に対する外科治療戦略】 切除可能なStage IV胃癌に対する外科治療 胃癌肝転移の外科治療
われわれは,胃癌肝転移に対する外科治療の適応を,「単発かつN0/N1」としている.それ以外はすべて化学療法を適応する.胃癌肝転移の外科治療適応のボーダーラインと考えられる症例(肝転移個数が少数かつN2までなど)に対しては,化学療法で病勢コントロールが得られた症例[著効(CR)/有効(PR)/安定(SD)]に対して,R0切除が見込める場合は外科治療が適応されうると考えている.(著者抄録).
210. 【エキスパートに聞く!高難度内視鏡外科手術のコツ】 腹腔鏡下肝切除術(亜区域切除、1区域切除).
211. 【最新 肝胆膵高難度外科手術アトラス】 高難度外科手術手技 肝臓 生体肝移植レシピエント手術.
212. 【肝内胆管癌の新しい規約と治療戦略】 再発肝内胆管癌の治療
肝内胆管癌は予後不良な原発性肝癌である.肝細胞癌に比べ症例数が少ないため,外科切除以外の治療法は確立していない.治癒切除後にも高頻度に再発がみられ,再発部位は肝内,リンパ節転移,肺転移,腹膜播種など多彩で複数の臓器に及ぶ場合も多いため,治療は困難を伴う.本稿では再発病巣に対する外科切除,化学療法,放射線療法,分子標的薬などの現状と成績について最近の文献をもとに紹介する.(著者抄録).
213. 【肝硬変を理解する-分子機構から実臨床に至るまで-】 治療 わが国における肝移植の現況と将来の展望.
214. 【肝胆膵疾患とオートファジー】 オートファジー異常と肝胆膵疾患 肝再生とオートファジー.
215. 【門脈圧亢進症の制御-病態研究と治療の進展】 門脈血栓、門脈圧減圧療法 外科的アプローチによる門脈圧亢進症治療 脾機能制御の意義について.
216. 【高齢者における外科治療の低侵襲化と至適管理】 高齢者に対する肝胆膵外科・肝移植手術の現況
急速な高齢化社会の到来とともに,高齢者に対する肝胆膵外科領域の手術は増加している.高齢者では多臓器にわたる併存疾患や主要臓器の機能低下,栄養不良,免疫能低下などがあるため,手術侵襲に伴うリスクとQOLの低下,癌の根治性を含めた予後とのバランスなどから個別に適切な治療法を選択する必要がある.低侵襲治療である腹腔鏡下手術は高齢者でも安全に施行しうることが報告されている.腹腔鏡下手術により体壁の破壊を最小限にとどめる事で種々の疾患で予後不良因子であるサルコペニアの発生・進展を予防する事は術後のQOL/ADLの維持につながると考えられる.高齢者における術後の特徴としては,術後せん妄が高頻度であり,また誤嚥性肺炎の合併は重篤化する恐れがある.疼痛コントロールと早期離床に向けた,多職種による周術期チーム医療が術後管理の鍵を握る.わが国における原発性肝癌の集計では75歳以上の高齢者が約30%を占める.われわれの経験では主要臓器機能が保たれた症例を適切に選択すれば,75歳以上の高齢者でも安全に肝切除は可能である.生体肝移植希望症例の高齢化も進んでいる.肝臓以外の他臓器の機能が正常でPerformance Status(PS)良好な症例では,肝移植後の成績は若年者と同等である.このため,高齢者でも年齢のみでは生体肝移植の適応外とはならないが,長期生存例ではde novo悪性腫瘍の発生を念頭においた経過観察が必要である.(著者抄録).
217. ここを見て欲しい こだわりの手技 安全・確実な生体肝移植の施行を目指した我々の手術手技.
218. サルコペニアは肝硬変合併肝細胞癌における術後合併症のリスク因子である.
219. サルコペニアと外科.
220. 山下 洋市, 吉住 朋晴, 池上 徹, 内山 秀昭, 辻田 英司, 伊藤 心二, 播本 憲史, 副島 雄二, 武冨 紹信, 馬場 秀夫, 前原 喜彦, プロテインチップアレイを用いた急性肝不全生体肝移植患者におけるバイオマーカーの検討(Inquiries About Biomarkers of Acute Liver Failure in Patients Who Underwent Living Donor Liver Transplantation Using a Protein Chip Array), 福岡医学雑誌, 10.15017/1784634, 107, 7, 131-135, 2016.07, 肝性脳症の原因物質はまだ同定されていない。我々は、肝移植を受けた急性肝不全患者の意識回復が時に劇的である事から、このような患者において肝性脳症の原因物質が周術期に劇的に変化していると考えた。そこで、肝性脳症の原因物質を同定するために、プロテインチップシステム4000(サイファージェンバイオシステムズ、横浜)を用いて、患者血清中のバイオマーカーを検討した。生体肝移植を受けた急性肝不全患者4名より、周術期4ポイント(手術前、術後1日、術後3日、術後7日)で血清を採取して、合計16のサンプルを得た。今回は、Biomek2000ロボットにより作製された3つのチップを使用した。測定はサンプル毎に2回行い、結果はCiphergenExpressTMデータマネージャーを用いて分析した。周術期における発現ピークの変動パターンを7パターンに分割し、周術期に有意に変動した発現ピークとして755個を同定した。もちろん、755個の発現ピーク全ての構造を決定することは困難である。従って、我々は更に検討を重ね、肝性脳症の原因物質の候補を絞り込む必要がある。我々の今回の検討結果は、肝性脳症の原因物質を決定するには多くの困難が待ち受けていることを示唆している。(著者抄録).
221. マージナル・ドナーを用いた生体肝移植の全国集計結果 60歳以上ドナーとHTLV-1陽性ドナーからの生体肝移植成績.
222. 切除不能膵癌に対するFOLFORINOX療法の有効性と安全性の検討.
223. 地方中核都市における我々のリクルート戦略.
224. 外傷外科の修練はどうあるべきか 医療機関の連携による外傷外科修練カリキュラム.
225. 小型(3cm以下)肝細胞癌に対する治療 肝切除、生体肝移植の成績からみた小肝細胞癌の外科治療戦略.
226. 左半腹臥位完全腹腔鏡下肝肝切除の適応と手技のポイント.
227. 慢性肝不全の急性増悪に対する血液型不適合生体ドナー肝移植
68歳女。自己免疫性肝炎にて経過観察中、著明な黄疸と肝機能および凝固因子の悪化を呈した。慢性肝炎の急性増悪による肝不全として集中的治療を行うも急速に状態が悪化したため、ABO血液型不適合生体肝移植(ABOi-LDLT)の適応と判断された。ABOi-LDLTに向けた脱感作としてリツキシマブ500mgを投与し、待機中は連日血漿交換を行ったところ、CD20陽性リンパ球は陰性化し、肝性脳症は認めなかった。リツキシマブ投与2週間後にAB+ドナーからA+レシピエントへのABOi-LDLTを実施し、術後はシクロスポリンを含む免疫抑制療法を行った結果、術後経過中の血液凝集反応は低値で推移した。術後2年経過時点でABOi-LDLT関連の合併症を認めることなく正常肝機能で日常生活を営んでいる。.
228. 成人生体肝移植における長期予後因子の検討.
229. 成人生体肝移植における術後SSIの発症危険因子と予後の検討.
230. 手術手技のスコア化による若手肝臓外科医の手術手技修練法 若手外科医の立場から.
231. 新たな肝星細胞のバイオマーカーである血清糖タンパク質WFA(+)-M2BPの肝線維化進展における役割.
232. 生体肝移植におけるERAS概念を取り入れた術後管理.
233. 生体肝移植におけるグラフトヘパリン化vs.全身ヘパリン化によるドナー・レシピエントへの影響の評価.
234. 吉住 朋晴, 高田 泰次, 調 憲, 池上 徹, 内山 秀昭, 池田 哲夫, 上本 伸二, 武冨 紹信, 前原 喜彦, 日本肝胆膵外科学会プロジェクト委員会, 生体肝移植におけるHTLV-1の及ぼす影響 多施設共同研究(Impact of human T-cell leukemia virus type 1 on living donor liver transplantation: a multi-center study in Japan), 日本肝胆膵外科学会・学術集会プログラム・抄録集, 28回, 293-293, 2016.06.
235. 生体肝移植症例の肺動脈圧に関する検討
生体肝移植症例の肺動脈圧について検討した。生体肝移植を施行した271例中、全身麻酔導入終了後・肝移植前平均動脈圧と手術開始時門脈圧のデータを得た185例(男性88名、女性97名、平均54.5歳)を対象とした。肺高血圧合併群ではレシピエントのChild-Pugh分類Cが有意に多く、MELDスコアが有意に高値であった。また、手術開始時と手術終了時の門脈圧が有意に高値であった。ドナー因子では肺高血圧合併群で女性ドナーが多い傾向にあり、右葉グラフト使用が高頻度であった。手術開始時平均門脈圧と平均肺動脈圧の間には弱い相関を認めた。平均門脈圧、平均肺動脈圧ともにChild C症例でChild AまたはB症例に比べ、有意に高値であった。平均肺動脈圧はMELDスコア20以上群で有意に高値であった。門脈大循環シャントがある症例では、無い症例に比べ、手術開始時心拍出係数が有意に高値であった。生体肝移植後6ヵ月生存率は、肺高血圧非合併群で93.8%、合併群で91.7%と両群間に有意差を認めなかった。.
236. 池上 徹, 吉住 朋晴, 内山 秀昭, 播本 憲史, 伊藤 心二, 岡部 弘尚, 山下 洋市, 原田 昇, 副島 雄二, 前原 善彦, 生着不全に対する肝再移植 最適な選択基準は何か LDLT後の生着不全に対する肝再移植の適応は何か(Liver re-transplantation for graft failure: What are optimal selection criteria? What is the indication of re-liver transplantation for graft failure after LDLT?), 日本消化器外科学会総会, 71回, WS22-3, 2016.07.
237. 癌胎児遺伝子SALL4とヒストン脱アセチル化酵素(HDAC1,2)の共発現による肝細胞癌悪性転化の分子機序.
238. 肝 C型肝炎についてup to date 生体肝移植後C型肝炎再発に対するDAAを用いた治療効果の検討.
239. 伊藤 心二, 吉住 朋晴, 下川 雅弘, 島垣 智成, 吉田 佳弘, 王 歓林, 長津 明久, 本村 貴志, 原田 昇, 播本 憲史, 池上 徹, 副島 雄二, 前原 喜彦, 肝内胆管癌におけるPD-L1発現の生物学的意義, 日本癌学会総会記事, 75回, J-1021, 2016.10.
240. 肝内胆管癌におけるPD-L1発現の生物学的意義に関する研究.
241. 肝星細胞の新しいバイオマーカーWFA+-M2BPの肝臓外科における意義と展望.
242. 肝硬変に伴う脾機能亢進症に対する腹腔鏡下脾臓摘出術における術前脾動脈塞栓術の有用性
肝硬変に伴う脾機能亢進症に対する腹腔鏡下脾臓摘出術(Lap-Sp)における術前脾動脈塞栓術(SAE)の有用性について検討した。SAEを施行せずにLap-Spのみ行った15例(A群)とSAEを行い、Lap-Spを行った12例(B群)を対象とした。摘出脾重量、術中出血量には有意差を認めなかったが、術中の赤血球輸血量、手術時間は有意差にB群で良好であった。術後ドレーン中アミラーゼに有意差はないもののB群で高い傾向にあったが、術後Alb値、T.Bil値、PT値、CRP値に差を認めなかった。術後合併症、術後出血性合併症、術後在院日数に有意差はないが、B群で改善する傾向を認めた。.
243. 肝移植と門脈圧亢進症 生体肝移植術中脾臓摘出術の術後成績に及ぼす影響に関する検討.
244. 肝細胞癌に対する生体肝移植後再発における炎症関連スコアの意義.
245. 岡部 弘尚, 吉住 朋晴, 内山 秀昭, 池上 徹, 播本 憲史, 伊藤 心二, 原田 昇, 山下 洋市, 馬場 秀夫, 前原 喜彦, 肝細胞癌の治癒的治療後の再発に関する予防的管理 肝細胞がんにおける病理学的構造分類の臨床的意義(Preventive management for recurrence after curative treatment of hepatocellular carcinoma Clinical significance of pathological architectural classification in hepatocellular carcinoma), 日本消化器外科学会総会, 71回, WS20-4, 2016.07.
246. 内山 秀昭, 吉住 朋晴, 池上 徹, 播本 憲史, 伊藤 心二, 岡部 弘尚, 木村 光一, 原田 昇, 池田 哲夫, 前原 喜彦, 肝細胞癌の治癒的治療後の再発に関する予防的管理 肝細胞癌に対する生体肝移植 筆者らの選択基準の正当性の評価(Preventive management for recurrence after curative treatment of hepatocellular carcinoma Living-donor liver transplants for hepatocellular carcinoma: validation of our selection criterion), 日本消化器外科学会総会, 71回, WS20-7, 2016.07.
247. 肝細胞癌の発育進展と間葉系形質獲得からみた原発性肝癌取扱い規約の組織構造分類の意義.
248. 肝細胞癌予後不良因子としての癌胎児遺伝子SALL4とヒストン脱アセチル化酵素(HDAC1、2)の重要性に関する検討.
249. 肝細胞癌切除患者におけるInflammation-based prognostic scoreと骨格筋量の相関.
250. 肝胆膵高難度手術に対する腹腔鏡手術のあり方と将来展望 腹腔鏡下肝切除を安全に行うために必要な知識、技術そしてトレーニング これまでに得てきたこと、これから必要なこと.
251. 肝門脈管への正確なアプローチ 組織標本立体再構築とコンピュータ画像解析による肝門部ミクロ立体解剖の解明.
252. 胃静脈瘤に対する腹腔鏡下Hassab術の手技の工夫
2008年4月~2015年3月迄に胃静脈瘤に対し、外科治療を行った肝硬変症27例(男性16例、女性11例、平均58.5±12.7歳)を対象に、腹腔鏡下petit Hassab術が胃静脈瘤に対する治療として許容できるか検討した。27例中24例(88.9%)はHALSを用い手術を行い、開腹移行は脾門部の径6cmの巨大脾動脈瘤症例で膵体尾部切除が必要となった1例のみであった。腹腔鏡下petit Hassab術と腹腔鏡下Hassab術の手術成績に関しては、脾重量の中央値は452g、590gと両群とも巨脾症例が多かったが、手術時間の中央値は313分、345分、出血量は139g、210gと両群に有意差はなくともに安全な手術であった。胃静脈瘤に対する腹腔鏡下手術は有用であり、左胃静脈が関与しない胃静脈瘤に対しては胃小彎側血行郭清を省略する腹腔鏡下petit Hassab術は許容できると考えられた。.
253. 脂肪肝温阻血再灌流傷害におけるNADPH oxidaseシグナルの関与とその制御.
254. 脳死肝移植へのBridgeとしてのHigh-Flow CHDFの有効性に関する検討.
255. 脾摘やPSEは、門脈圧を改善するか 肝硬変症に対する脾摘の長期成績について.
256. 脾臓マクロファージ由来MMP-12による肝星細胞活性化の制御.
257. 伊藤 心二, 吉住 朋晴, 播本 憲史, 木村 光一, 岡部 弘尚, 原田 昇, 池上 徹, 内山 秀昭, 池田 哲夫, 前原 喜彦, 腫瘍血栓を伴う進行性肝細胞癌の集学的治療 肉眼的門脈内腫瘍血栓を伴う肝細胞癌の外科的治療(Multidisciplinary treatment of advanced hepatocellular carcinoma with tumor thrombus Surgical treatment of hepatocellular carcinoma with macroscopic portal venous tumor thrombus), 日本消化器外科学会総会, 71回, WS19-2, 2016.07.
258. 池田 哲夫, 木村 光一, 伊藤 心二, 岡部 弘尚, 播本 憲史, 池上 徹, 吉住 朋晴, 小野木 真哉, 橋爪 誠, 前原 喜彦, 腹腔鏡下肝胆膵手術の最近の改良点と問題点 Orthodox & Serendipity 腹腔鏡下肝切除術の安全性改善と適応拡大のための外科的戦略(Recent refinement and problem of laparoscopic hepato-biliary-pancreatic surgery: Orthodox & Serendipity surgical strategy for improving safety and expanded indication of laparoscopic, 日本消化器外科学会総会, 71回, SY8-7, 2016.07.
259. 池上 徹, 吉住 朋晴, 内山 秀昭, 播本 憲史, 伊藤 心二, 岡部 弘尚, 木村 光一, 調 憲, 前原 善彦, 血液型不適応・クロスマッチ陽性グラフトを用いた生体肝移植の成績, 日本外科学会定期学術集会抄録集, 116回, OP-001, 2016.04.
260. 解剖学的変異症例に対する高難度肝胆膵手術 コツと技 レシピエント内頸静脈グラフトを用いた中肝静脈なし右葉グラフト肝静脈再建法.
261. 門脈内腫瘍栓を有する進行肝癌に対する外科治療成績と分子機序に基づいた新しい治療戦略.
262. 門脈内腫瘍栓を有する進行肝癌に対する外科切除を中心とした治療成績.
263. 門脈血栓症例に対する肝移植の適応と成績 門脈血栓を有する生体肝移植術の予後と手術戦略.
264. 非代償性肝硬変患者の術前運動機能からみた肝移植後の経過.
265. 食道静脈瘤合併肝細胞癌の手術成績の検討.
266. 骨格筋面積と筋力・身体活動性を合わせたサルコペニアの新たな診断基準による生体肝移植後短期治療成績の高精度予測.
267. 高度脈管侵襲を伴った肝癌に対する治療戦略 門脈内腫瘍栓を伴う肝細胞癌に対する外科治療を中心とした治療戦略.
268. 島垣 智成, 吉住 朋晴, 木村 光一, 本村 貴志, 長津 明久, 岡部 弘尚, 伊藤 心二, 原田 昇, 播本 憲史, 池上 徹, 内山 秀昭, 副島 雄二, 前原 喜彦, 高齢者の非代償性肝硬変に対して生体肝移植を施行し得た1例(Living Donor Liver Transplantation in an Elderly Recipient with Preserved Performance Status: A Case Report), 福岡医学雑誌, 107, 6, 115-20, 2016.06, 【はじめに】高齢者に生体肝移植を行うべきかどうかについては、議論のあるところである。【症例】74歳女性。検診で肝機能異常を指摘され、原発性胆汁性肝硬変と診断、経過観察されていた。その後肝予備能が低下し、他院にて生体肝移植が検討されたが、70歳を超えていたため適応外とされた。当院では70歳以上の肝移植症例の経験もあり、レシピエントの全身状態が良好であったこと(PS2)、グラフト条件も満たしていたことから、生体肝移植可能と判断し、生体肝移植術(拡大左葉グラフト)施行。術後経過は概ね良好で、術後35日目退院となった。現在も在宅・生存中であり、非常に良好なQOLを維持している。【考察】生体肝移植は、高齢レシピエントに対してもPSが保たれている場合は、安全に施行出来る可能性が高く、良好な術後成績を得られると考える。(著者抄録).
269. 60歳以上のドナーを用いた生体肝移植 当科の成績と全国集計の検討.
270. B型肝炎治療の課題と将来への展開 生体肝移植後B型肝炎ワクチンの効果とHLA-DPの一塩基多型に関する検討.
271. Kazuki Takeishi, Takashi Maeda, Ken Shirabe, Eiji Tsujita, Yo-Ichi Yamashita, Norifumi Harimoto, Shinji Itoh, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Clinicopathologic Features and Outcomes of Non-B, Non-C Hepatocellular Carcinoma After Hepatectomy., Annals of surgical oncology, 10.1245/s10434-015-4728-4, 22 Suppl 3, 3, S1116-24, 2015.12, PURPOSE: This retrospective study aimed to investigate the clinical characteristics and long-term outcomes after hepatectomy in patients with non-B, non-C (NBNC) hepatocellular carcinoma (HCC) who were negative for hepatitis B virus surface antigen and anti-hepatitis C virus antibody. METHODS: We retrospectively reviewed 666 patients with HCC who underwent hepatectomy. The patients were divided into NBNC-HCC patients [n = 117 (17.6 %)] and hepatitis virus (HV)-HCC patients [n = 547 (82.4 %)]. We compared the clinicopathologic characteristics and long-term outcomes between the 2 groups. Two patients with incomplete virus-marker data were not analyzed. RESULTS: NBNC-HCC patients had better liver function but more advanced and larger HCCs and a high incidence of intrahepatic metastasis compared to HV-HCC patients. Recurrence-free and overall survival were similar in both groups. Multivariate analysis showed that aspartate aminotransferase (AST) and α-fetoprotein were independently associated with disease-free and overall survival in NBNC-HCC patients after hepatectomy. High AST was significantly associated with tumor size and rate of capsule formation with cancer cell infiltration in NBNC-HCC patients, but not with other liver function tests, fibrosis, or necrosis of noncancerous lesions. CONCLUSIONS: NBNC-HCC patients have better liver function than HV-HCC patients, despite having more advanced HCC at diagnosis. There were no differences in long-term outcomes after hepatectomy between NBNC-HCC and HV-HCC patients. Preoperative AST and α-fetoprotein were independently associated with the prognosis of NBNC-HCC after hepatectomy. Serum AST levels might be associated with tumor malignancy in NBNC-HCC patients..
272. Mizuki Ninomiya, Ken Shirabe, Marcelo E Facciuto, Myron E Schwartz, Sander S Florman, Tomoharu Yoshizumi, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Yoshihiko Maehara, Comparative study of living and deceased donor liver transplantation as a treatment for hepatocellular carcinoma., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.12.009, 220, 3, 297-304, 2015.03, BACKGROUND: Living donor liver transplantation (LDLT) is an important treatment option for unresectable hepatocellular carcinoma (HCC), but whether recurrence and survival in LDLT differ from those in deceased donor liver transplantation (DDLT) remains controversial. STUDY DESIGN: A retrospective analysis was performed between patients with HCC who underwent LDLT in a Japanese institute (n = 133) and those who underwent DDLT in a United States institute (n = 362). RESULTS: Although there was a difference in patient background characteristics (eg, body mass index, donor age, Model for End-Stage Liver Disease [MELD] score), tumor aggressiveness represented by Milan criteria and microscopic vascular invasion were comparable between the 2 groups. The cumulative 5-year recurrence rates of the LDLT group and the DDLT group were similar (14.8% vs 19.0%, p = 0.638), but overall survival in the LDLT group was significantly better than that in the DDLT group (84.2% vs 63.5%, p < 0.0001). Separate multivariate analysis identified different preoperative predictive factors for HCC recurrence (salvage transplantation and Des-gamma-carboxy prothrombin >300 in the LDLT group, beyond Milan criteria in the DDLT group). Combined multivariate analysis of the 2 groups identified recipient's body mass image >30 kg/m(2) as an independent risk factor for overall survival; the technique of transplantation (LDLT or DDLT) was not found to be a risk factor. CONCLUSIONS: When compared between the institutes where LDLT or DDLT were the first treatment choices for unresectable HCC, recurrence rates were comparable. Living donor liver trasplantation is a viable treatment option for unresectable HCC, providing recurrence rates similar to those achieved with DDLT..
273. 吉住 朋晴, 調 憲, 池上 徹, 播本 憲史, 伊藤 心二, 武石 一樹, 山下 洋市, 池田 哲夫, 内山 秀昭, 川中 博文, 前原 喜彦, Current status and controversy in liver transplantation 生体肝移植後の良好な治療成績を目指した治療戦略(Current status and controversy in liver transplantation Optimizing Outcomes in Living Donor Liver Transplantation), 日本肝胆膵外科学会・学術集会プログラム・抄録集, 27回, 390-390, 2015.06.
274. C型肝炎に対する肝移植 本邦の経験と今後の潮流.
275. Patricia Lopez, Gary Levy, Long-Bin Jeng, Kyung Suk Suh, Dong Jin Joo, Sung Gyu Lee, Wei-Chen Lee, Chao-Long Chen, Arvinder Singh Soin, Jae Won Joh, Tomoharu Yoshizumi, David Grant, El-Djouher Martzloff, Carole Sips, Zailong Wang, EVEROLIMUS WITH REDUCED TACROLIMUS VERSUS STANDARD TACROLIMUS IN LIVING-DONOR LIVER TRANSPLANT RECIPIENTS: BASELINE DATA FROM THE H2307 STUDY, TRANSPLANT INTERNATIONAL, 28, 459-459, 2015.11.
276. Hiroyuki Furukawa, Hiroto Matsuno, Toshiharu Kawahara, Masahiko Taniguchi, Takashi Kawai, Shinji Uemoto, Norihiro Kokudo, Susumu Eguchi, Tsuyoshi Shimamura, Koichi Mizuta, Tomoharu Yoshizumi, Hiroyuki Morikawa, Establishment of Educational Program in Liver Procurement With Both E-Learning Containing Animation of the Procedure and Simulation Using Large Animals, TRANSPLANTATION, 99, 249-250, 2015.07.
277. Fast track surgeryの現状と今後 栄養・感染症・緩和 生体肝移植におけるfast track surgeryに基づいた周術期管理の意義.
278. HBV関連生体肝移植後のHBV再発因子の解析.
279. Hirofumi Kawanaka, Tomohiko Akahoshi, Nao Kinjo, Norifumi Harimoto, Shinji Itoh, Norifumi Tsutsumi, Yoshihiro Matsumoto, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Laparoscopic Splenectomy with Technical Standardization and Selection Criteria for Standard or Hand-Assisted Approach in 390 Patients with Liver Cirrhosis and Portal Hypertension., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2015.04.011, 221, 2, 354-66, 2015.08, BACKGROUND: Laparoscopic splenectomy (LS) is still challenging in patients with liver cirrhosis and portal hypertension. This study was designed to establish safe and less invasive LS in patients with liver cirrhosis and portal hypertension. STUDY DESIGN: We analyzed 390 patients with liver cirrhosis and portal hypertension, who underwent LS between 1993 and 2013. Patients were divided into 3 time periods; early (1993 to 2004, n = 106); middle (2005 to 2008, n = 159); and late (2008 to 2013, n = 125). During the middle time period, standardized technique for LS and selection criteria for hand-assisted LS were adopted. Patients with spleen volume ≥ 1,000 mL by CT volumetry, large perisplenic collateral vessels, and/or Child-Pugh score ≥ 9, underwent hand-assisted LS. During the late time period, the selection criteria were refined and patients with spleen volume ≥ 600 mL underwent hand-assisted LS. RESULTS: Conversion to open splenectomy decreased (10.4% in the early time period, 1.9% in the middle time period, and 3.2% in the late time period, p = 0.004), median blood loss decreased (300g, 87g, and 98g, respectively, p < 0.001), and the success rate of pure LS tended to improve (87.2%, 89.5%, and 98.0%, respectively, p = 0.110). Mortality was 0% in each time period, Clavien-Dindo grade IIIb or more complications tended to decrease (5.7%, 2.5%, and 0.8%, respectively, p = 0.081), and technique-related complications decreased significantly (10.4%, 3.8%, and 2.4%, respectively, p = 0.014). CONCLUSIONS: Laparoscopic splenectomy is now a safe and less invasive approach, even in patients with liver cirrhosis and portal hypertension, because of its technical standardization with the refined selection criteria for pure or hand-assisted LS..
280. Daisuke Taniguchi, Norifumi Harimoto, Kazuki Takeishi, Shinji Itoh, Yoichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Hirofumi Kawanaka, Ken Shirabe, Yosuke Morodomi, Tetsuzo Tagawa, Tatsuro Okamoto, Yoshihiko Maehara, Liver transplantation followed by pulmonary resection complicated with end-stage liver cirrhosis: a case report., Anticancer research, 35, 6, 3411-4, 2015.06, BACKGROUND: With the recent popularization of living-donor liver transplantation (LDLT), it has become important to provide treatment for comorbidities in recipients. We report the case of a patient who was successfully treated with LDLT, followed by left upper lobectomy for lung cancer concomitant with decompensated liver cirrhosis. CASE REPORT: A 67-year-old female was admitted for treatment for severe liver cirrhosis. The lung cancer was identified preoperatively using computed tomography. We initially performed LDLT to improve liver function and coagulopathy; the patient was discharged postoperatively on day 39 without complication. Three months after LDLT, we performed a left upper lobectomy. RESULTS: The patient's postoperative course was uneventful and she was discharged after 11 days. CONCLUSION: We conclude that an aggressive and appropriate surgical strategy, including LDLT, is an effective curative treatment in patients with controllable malignancy, concomitant with severe liver dysfunction..
281. Masahiro Shimokawa, Shinji Itoh, Toru Ikegami, Kazuki Takeishi, Norifumi Harimoto, Yo-Ich Yamashita, Tomoharu Yoshizumi, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Local therapy improvement of outcome in a patient with recurrent hepatocellular carcinoma after living donor liver transplantation: a case report., Anticancer research, 35, 6, 3525-9, 2015.06, We describe a very rare case of recurrent hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT). A 47-year-old female underwent LDLT for HCC within Milan criteria, receiving a left liver lobe from her 38-year-old husband with an incompatible blood type. Thirty months after LDLT, however, enhanced computed tomography (CT) showed a tumor in her left adrenal gland; after another six months, enhanced CT and positron-emission tomography detected a frontal head bone tumor; enhanced CT performed 54 months after LDLT revealed a recurrent HCC in the liver graft. Each of these three tumors was surgically resected. Two months after hepatic partial resection, an enhanced CT showed another HCC in her liver graft, which was treated with local ablation therapy. One year after the last ablation treatment, the recipient is doing well without evidence of recurrence. At the time of detection of each of these tumors, the patient's serum concentration of hepatitis B virus surface antigen was elevated. Pathological examination showed that the resected tumors were moderately differentiated HCCs. Genotyping by microsatellite analysis confirmed their origin to be metastases of the primary HCC..
282. Shinji Itoh, Toru Ikegami, Tomoharu Yoshizumi, Huanlin Wang, Kazuki Takeishi, Norifumi Harimoto, Yo-Ichi Yamashita, Hirofumi Kawanaka, Shinichi Aishima, Ken Shirabe, Yoshihiko Maehara, Long-term outcome of living-donor liver transplantation for combined hepatocellular-cholangiocarcinoma., Anticancer research, 35, 4, 2475-6, 2015.04, BACKGROUND/AIM: Combined hepatocellular-cholangiocarcinoma (cHC-CC) is found unexpectedly in explanted or resected liver specimens. The current study evaluated the longterm outcomes of living-donor liver transplantation (LDLT) between patients with cHC-CC and hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We performed 178 LDLT including 8 patients of pathologically and immunohistochemically diagnosed cHC-CC who all underwent LDLT with a preoperative diagnosis of HCC by imaging study. RESULTS: Out of the 8 patients, 6 were within the Milan criteria and all were within the Kyushu University criteria. The 1-, 5- and 10-year overall survival (OS) and disease-free survival (DFS) rates after LDLT for patients with cHC-CC were 87.5, 72.9 and 48.6% and 85.7, 85.7 and 85.7%, respectively. The OS and DFS between patients with cHC-CC and HCC were not statistically different. CONCLUSION: LDLT for patients with cHC-CC using the Milan criteria or the Kyushu University criteria, as well as HCC, could have an acceptable long-term outcome..
283. NADPH oxidaseおよびToll like receptor4制御による脂肪肝温阻血再灌流傷害の改善.
284. NADPH oxidaseおよびToll like receptor 4制御による脂肪肝温阻血再灌流傷害の改善.
285. Shinji Shimoda, Satomi Hisamoto, Kenichi Harada, Sho Iwasaka, Yong Chong, Minoru Nakamura, Yuki Bekki, Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yoshihiko Maehara, Xiao-Song He, M Eric Gershwin, Koichi Akashi, Natural killer cells regulate T cell immune responses in primary biliary cirrhosis., Hepatology (Baltimore, Md.), 10.1002/hep.28122, 62, 6, 1817-27, 2015.12, UNLABELLED: The hallmark of primary biliary cirrhosis (PBC) is the presence of autoreactive T- and B-cell responses that target biliary epithelial cells (BECs). Biliary cell cytotoxicity is dependent upon initiation of innate immune responses followed by chronic adaptive, as well as bystander, mechanisms. Critical to these mechanisms are interactions between natural killer (NK) cells and BECs. We have taken advantage of the ability to isolate relatively pure viable preparations of liver-derived NK cells, BECs, and endothelial cells, and studied interactions between NK cells and BECs and focused on the mechanisms that activate autoreactive T cells, their dependence on interferon (IFN)-γ, and expression of BEC major histocompatibility complex (MHC) class I and II molecules. Here we show that at a high NK/BEC ratio, NK cells are cytotoxic for autologous BECs, but are not dependent on autoantigen, yet still activate autoreactive CD4(+) T cells in the presence of antigen presenting cells. In contrast, at a low NK/BEC ratio, BECs are not lysed, but IFN-γ production is induced, which facilitates expression of MHC class I and II molecules on BEC and protects them from lysis upon subsequent exposure to autoreactive NK cells. Furthermore, IFN-γ secreted from NK cells after exposure to autologous BECs is essential for this protective function and enables autoreactive CD4(+) T cells to become cytopathic. CONCLUSIONS: NK cell-mediated innate immune responses are likely critical at the initial stage of PBC, but also facilitate and maintain the chronic cytopathic effect of autoantigen-specific T cells, essential for progression of disease..
286. Tomohiro Iguchi, Ken Shirabe, Shinichi Aishima, Huanlin Wang, Nobuhiro Fujita, Mizuki Ninomiya, Yo-ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshinao Oda, Yoshihiko Maehara, New Pathologic Stratification of Microvascular Invasion in Hepatocellular Carcinoma: Predicting Prognosis After Living-donor Liver Transplantation., Transplantation, 10.1097/TP.0000000000000489, 99, 6, 1236-42, 2015.06, BACKGROUND: Vascular invasion of hepatocellular carcinoma (HCC) has a high incidence of recurrence after liver transplantation. Patients with microvascular invasion (MVI) show a high tumor grade; however, some show a good prognosis. This retrospective study aimed to investigate whether the degree of MVI affects prognosis after living-donor liver transplantation. METHODS: A total of 142 patients with HCC who had undergone living-donor liver transplantation were histologically evaluated about the number of invaded vessels and the maximum number of invading carcinoma cells. Patients with MVI were classified into two subgroups: high MVI group (n = 38), which showed more than 50 carcinoma cells in the vessels, with multiple invaded vessels; and low MVI group (n = 17), which showed MVI, but not high MVI. RESULTS: Analysis of recurrence-free survival showed that high MVI group had significantly poorer outcomes than the other groups (P < 0.001). High MVI group had significantly higher α-fetoprotein levels, des-γ-carboxy prothrombin levels, number of tumors, a larger tumor size, and a higher percentage of poorly differentiated HCC than non-MVI group. High MVI was an independent prognostic factor for recurrence-free survival (P = 0.030). Among patients exceeding the Milan criteria (n = 61), high MVI group had significantly poorer outcomes than the other groups for recurrence-free survival (P = 0.003). Patients in high MVI group had significantly higher des-γ-carboxy prothrombin levels and a larger tumor size than non-MVI group. High MVI was an independent prognostic factor for recurrence-free survival (P = 0.014). CONCLUSION: In living-donor liver transplantation for HCC, high MVI is a novel pathologic marker for predicting prognosis..
287. Huanlin Wang, Toru Ikegami, Noboru Harada, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Yo-Ichi Yamashita, Shinji Itoh, Norifumi Harimoto, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Optimal changes in portal hemodynamics induced by splenectomy during living donor liver transplantation., Surgery today, 10.1007/s00595-014-0999-9, 45, 8, 979-85, 2015.08, PURPOSES: The purpose of this study was to evaluate the impact of splenectomy in adult-to-adult living donor liver transplantation (LDLT). METHODS: Adult-to-adult LDLTs (n = 276) were divided into those with simultaneous splenectomy during LDLT (Splenectomy group, n = 154) and those without (Non-Splenectomy group, n = 122). RESULTS: In the Splenectomy group, splenectomy decreased the portal venous pressure from 24.0 to 19.1 mmHg (p < 0.001). At the end of surgery, the portal venous pressure was significantly lower and the graft compliance was significantly higher in the Splenectomy group compared with the Non-Splenectomy group. The graft portal venous flow was also better in the Splenectomy group (y = 625-5.1x; r (2) = 0.08, p < 0.01) than in the Non-Splenectomy group (y = 470-2.9x; r (2) = 0.04, p = 0.03). Fourteen days after LDLT, the total bilirubin and ascites output were lower in the Splenectomy group than in the Non-Splenectomy group. Among the patients with hepatitis C, splenectomy was associated with a significantly higher rate of a sustained viral response (59.4 vs. 35.9%, p = 0.020) than was noted in those without splenectomy (n = 39). There were no patients with post-splenectomy sepsis under vaccination. CONCLUSIONS: By decreasing the portal pressure and increasing the graft vascular compliance, splenectomy conferred better graft outcomes in adult-to-adult LDLT..
288. Daisuke Imai, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Norifumi Harimoto, PREEMPTIVE THORACIC DRAINAGE TO ERADICATE POSTOPERATIVE PULMONARY COMPLICATIONS AFTER LIVING DONOR LIVER TRANSPLANTATION, TRANSPLANT INTERNATIONAL, 28, 307-307, 2015.11.
289. S. Itoh, K. Shirabe, K. Kimura, H. Okabe, N. Harimoto, T. Ikegami, H. Uchiyama, T. Yoshizumi, T. Ikeda, Y. Maehara, Phase I study of sorafenib in combination with uracil-tegafur in patients with unresectable advanced hepatocellular carcinoma in Japan, ANNALS OF ONCOLOGY, 26, 65-65, 2015.12.
290. Norifumi Harimoto, Ken Shirabe, Toru Ikegami, Tomoharu Yoshizumi, Takashi Maeda, Kiyoshi Kajiyama, Takeharu Yamanaka, Yoshihiko Maehara, Postoperative complications are predictive of poor prognosis in hepatocellular carcinoma., The Journal of surgical research, 10.1016/j.jss.2015.06.012, 199, 2, 470-7, 2015.12, BACKGROUND: A retrospective study was performed at some high-volume institutions to clarify the prognostic significance of postoperative complications in patients who had undergone hepatectomy for hepatocellular carcinoma (HCC). No published studies have investigated the relationship between postoperative complications of Clavien-Dindo grade III or more and prognosis in patients who have undergone hepatic resection. METHODS: Patient data were retrospectively collected for 966 consecutive patients who had undergone hepatectomy for HCC with curative intent between January 2004 and December 2012. The patients were assigned to two groups according to the presence of postoperative complications. Clinicopathologic, surgical outcome, and long-term survival data were analyzed. RESULTS: Hospital deaths occurred in nine patients (0.9%). Postoperative complications were identified in 165 patients (17.1%). Compared with patients without complications, patients with complications had significantly larger tumors, more advanced-stage tumors, more poorly differentiated tumors, more intrahepatic metastasis, longer operation time, greater blood loss, more blood transfusion, and more anatomic resection and combined resection. The overall 5-y survival rates were 48.6% in patients with postoperative complications and 73.2% in patients without them. The 5-y recurrence-free survival rates were 23.7% in patients with postoperative complications and 36.7% in patients without them. Multivariate analysis revealed that longer operation time and lower serum albumin level of albumin were independent predictive factors for occurrence of postoperative complications. CONCLUSIONS: In patients with HCC, posthepatectomy complications are predictive of a worse overall survival, even when adjustments have been made for other known predictors..
291. Kazuki Takeishi, Takashi Maeda, Eiji Tsujita, Yo-Ichi Yamashita, Noboru Harada, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Predictors of intrahepatic multiple recurrences after curative hepatectomy for hepatocellular carcinoma., Anticancer research, 35, 5, 3061-6, 2015.05, BACKGROUND/AIM: Survival of patients with multiple recurrences (MR) of hepatocellular carcinoma (HCC) is very poor as recurrent tumors are usually aggressive and not amenable to curative resection. The present study aimed to investigate retrospectively predictors of intrahepatic MR of HCC after hepatectomy. PATIENTS AND METHODS: We reviewed 416 patients who underwent hepatectomy and developed intrahepatic recurrence during the follow-up period. According to the recurrence pattern, the patients were divided into two groups: 83 who had four or more recurrent lesions in the remnant liver were defined as the MR group and the others who constituted the control group. RESULTS: Multivariate analysis showed that micro-intrahepatic metastasis, α-fetoprotein and tumor size were independent risk factors for MR after hepatectomy. The combination of these three independent factors was significantly associated with MR. The recurrence rates within 1 year after hepatectomy of MR and control groups were 53.0% and 27.6%, respectively (p=0.0001). The 5-year overall survival rate of the MR group was 39%, which was significantly less than that of the control group (68%, p<0.0001). CONCLUSIONS: MR of HCC was associated with an earlier recurrence and poorer survival after hepatectomy. The combination of three independent factors for MR might help predict MR occurrence during the follow-up period..
292. Takeo Toshima, Ken Shirabe, Takeshi Kurihara, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Hirofumi Kawanaka, Tetsuo Ikeda, Yoshihiko Maehara, Profile of plasma amino acids values as a predictor of sepsis in patients following living donor liver transplantation: Special reference to sarcopenia and postoperative early nutrition., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12484, 45, 12, 1170-7, 2015.12, AIM: Sarcopenia is an independent predictor of mortality and sepsis after living donor liver transplantation (LDLT). However, the exact mechanisms by which sarcopenia affects poor prognosis or worse immunity against postoperative sepsis are unclear, particularly regarding muscular amino acid metabolism, and the authors aimed to identify the role of plasma amino acids in sarcopenia by retrospective study. METHODS: The area of the psoas muscle in 228 recipients of LDLT was retrospectively measured by dynamic computed tomography. Additionally, plasma amino acid levels were measured both pre- and postoperatively. The impact of plasma amino acids for postoperative sepsis and the relationship between sarcopenia and early nutrition after LDLT were analyzed. RESULTS: Among the plasma amino acids, only leucine, isoleucine and glutamine in patients with sarcopenia were significantly lower than those without sarcopenia (each, P < 0.05). Multivariate analysis identified the lower plasma glutamine levels as a risk factor of postoperative sepsis after LDLT (odds ratio 5.371, P = 0.002). In sarcopenia patients, plasma glutamine levels after LDLT were significantly decreased compared with before LDLT in patients both with and without postoperative early nutrition. However, in non-sarcopenia patients with early nutrition, plasma glutamine levels after LDLT were comparable with those before LDLT. CONCLUSION: This is the first report to study the profile of plasma amino acid change before and after LDLT. Low preoperative glutamine values were an independent risk factor for predicting postoperative sepsis. The efficacy of postoperative early nutrition may prevent postoperative sepsis by improving glutamine levels..
293. Tomoyuki Uchihara, Yo-Ichi Yamashita, Wang Hualin, Kazuki Takeishi, Shinji Itoh, Norihumi Harimoto, Tomoharu Yoshizumi, Shinichi Aishima, Ken Shirabe, Hideo Baba, Yoshihiko Maehara, Recurrence 11 years after complete response to gemcitabine, 5-Fluorouracil, and Cisplatin chemotherapy followed by radiotherapy in a patient with advanced pancreatic cancer: a case report., Anticancer research, 35, 5, 2867-71, 2015.05, A 63-year-old man diagnosed with locally advanced pancreatic ductal adenocarcinoma (PDAC; stage IIa) was treated with chemotherapy (gemcitabine, 5-fluorouracil and cisplatin) followed by radiotherapy. He had complete response by imaging and relapse-free survival for 11 years. However, he subsequently presented with local tumor recurrence and underwent pancreaticoduodenectomy followed by chemotherapy; a partial response was achieved. As in liver metastasis of colonic cancer, complete response by imaging in PDAC may not mean pathological complete response. We would propose the importance of adjuvant surgery for a patient with PDAC with complete response by imaging after chemoradiotherapy..
294. Sung Kwan Bae, Shinji Shimoda, Toru Ikegami, Tomoharu Yoshizumi, Norifumi Harimoto, Shinji Itoh, Yuji Soejima, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Risk factors for hepatitis B virus recurrence after living donor liver transplantation: A 17-year experience at a single center., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12489, 45, 12, 1203-10, 2015.12, AIM: The incidence of hepatitis B virus (HBV) recurrence after liver transplantation (LT) has been reduced by prophylaxis with hepatitis B immunoglobulin (HBIG) and nucleoside analogs, but the factors associated with HBV recurrence are unclear. The aim of this study was to determine the risk factors associated with HBV recurrence after living donor LT (LDLT). METHODS: A retrospective review was performed for 45 patients (28 male and 17 female; median age, 54 years) who underwent LDLT for HBV-related liver disease and were followed up for at least 6 months between October 1996 and June 2013. The virological data, tumor burden, antiviral therapy and immunosuppressive therapy were evaluated and compared between the HBV recurrence ad non-recurrence groups. RESULTS: Seven of the 45 patients (15.6%) developed post-LT HBV recurrence. The median interval between LDLT and HBV recurrence was 23.7 months (range, 0.8-35.9). Three of the seven patients (42.9%) developed recurrence after cessation of HBIG, and three (42.9%) were cases with hepatocellular carcinoma (HCC) recurrence after LDLT. The remaining case underwent transplantation from a donor with positive hepatitis B surface antigen. Based on the univariate and multivariate analyses, HBIG cessation (hazard ratio [HR], 20.17; 95% confidence interval [95% CI], 2.091-194.593; P = 0.009) and HCC recurrence (HR, 30.835; 95% CI, 3.132-303.593; P = 0.003) were independent risk factors for HBV recurrence after LDLT. CONCLUSION: In LDLT patients, cessation of HBIG and HCC recurrence were risk factors associated with HBV recurrence, so careful monitoring for serological HBV markers is needed in patients with these factors..
295. Rituximab投与ABO血液型不適合生体肝移植における安全性と有効性に関する後方視的調査研究
2013年に血液型不適合移植が実施された施設の外科医および肝臓専門医に対し、調査票を送付し、ABO血液型不適合生体肝移植(ABO-I LDLT)について後方視的に解析し、有効性および安全性を評価し、リツキシマブのABO-I LDLTにおける標準的な用法・用量について検討した。日本肝移植研究会レジストリーに登録され2013年に血液型不適合移植が実施された施設中15施設より移植前にリツキマシブを投与した成人33例、小児(18歳未満)4例の情報を回収した。レシピエントの移植時年齢は成人19~68歳(中央値53歳)、小児1歳3ヵ月~5歳3ヵ月(中央値3歳)、ドナーの年齢は成人21~59歳(中央値42歳)、小児30~46歳(中央値35.5歳)であった。成人の17例(52%)、小児の4例(100%)が親子間、成人の11例(33%)が夫婦間移植であった。原疾患は成人では肝細胞癌または肝癌が12例(36%)、B型肝硬変が4例(12%)、C型肝硬変が6例(18%)で、小児は胆道閉鎖症3例(75%)であった。移植術前のIgMピーク抗体中央値は成人中央値が96倍、小児中央値が80倍、移植術前のIgGピーク抗体中央値は成人中央値が128倍、小児が1.5倍であった。成人33例のリツキマシブ初回投与量は500mg/bodyが16例(48%)、375mg/m2が12例(36%)、300mg/bodyが4例(12%)。100mg/bodyが1例(3%)であった。.
296. Yo-Ichi Yamashita, Daisuke Imai, Yuki Bekki, Koichi Kimura, Yoshiriro Matsumoto, Hidekazu Nakagawara, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Shinichi Aishima, Yoshihiko Maehara, Surgical Outcomes of Hepatic Resection for Hepatitis B Virus Surface Antigen-Negative and Hepatitis C Virus Antibody-Negative Hepatocellular Carcinoma., Annals of surgical oncology, 10.1245/s10434-014-4261-x, 22, 7, 2279-85, 2015.07, BACKGROUND: The incidence of hepatitis B virus surface antigen-negative and hepatitis C virus antibody-negative hepatocellular carcinoma (NBNC-HCC) is gradually increasing. METHODS: A retrospective cohort study was performed in 694 patients who underwent curative hepatic resection for primary HCC from January 1990 to December 2011. RESULTS: In the NBNC-HCC group (n = 110), the complication rate of diabetic mellitus (38 %) was significantly higher than that of the B-HCC group (n = 110; 17 %), and their rate of alcohol abuse (38 %) was significantly higher than that of both the B-HCC (26 %) and C-HCC groups (n = 474; 22 %). In the NBNC-HCC group, the tumor diameter (4.5 ± 3.6 cm) was significantly larger than that of the C-HCC group (2.9 ± 1.8 cm), but the rate of histological cirrhosis (37 %) was significantly lower than those of both the B-HCC (67 %) and C-HCC (53 %) groups. There were no significant differences regarding overall and disease-free survival among the three groups. In the NBNC-HCC group, multiple intrahepatic or distant recurrences (25 %) were significantly higher than in the C-HCC group (17 %), and the rate of recurrence more than 2 years after hepatic resection (24 %) was significantly higher than that of the B-HCC group (12 %). CONCLUSIONS: The surgical outcomes of patients with NBNC-HCC were not significantly different compared with those of the patients with B-HCC or C-HCC. There was a substantial population with late recurrence among the patients with NBNC-HCC after curative hepatic resection, and thus not only long-term follow-up but also the early establishment of preventive methods for HCC recurrence from NBNC-hepatitis are necessary..
297. Yo-Ichi Yamashita, Yoshihiro Yoshida, Takeshi Kurihara, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Surgical results for recurrent hepatocellular carcinoma after curative hepatectomy: Repeat hepatectomy versus salvage living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.24111, 21, 7, 961-8, 2015.07, The aims of this study were to evaluate the efficacy of repeat hepatectomy (Hx) and salvage living donor liver transplantation (LDLT) for recurrent hepatocellular carcinoma (HCC). A retrospective cohort study was performed to analyze the surgical results of repeat Hx and salvage LDLT for patients with recurrent HCC within the Milan criteria from 1989 to 2012. A total of 159 patients were divided into 2 groups: a repeat Hx group (n = 146) and a salvage LDLT group (n = 13). Operative results and patient prognoses were compared between the 2 groups. The operative invasiveness, including the operation time (229.1 ± 97.7 versus 862.9 ± 194.4 minutes; P < 0.0001) and blood loss (596.3 ± 764.9 versus 24,690 ± 59,014.4 g; P < 0.0001), were significantly higher in the salvage LDLT group. The early surgical results, such as morbidity (31% versus 62%; P = 0.0111) and the duration of hospital stay (20 ± 22 versus 35 ± 21 days; P = 0.0180), were significantly worse in the salvage LDLT group. There was no significant difference in the overall survival (OS) rate, but the disease-free survival rate of the salvage LDLT group was significantly better (P = 0.0002). The OS rate of patients with grade B liver damage in the repeat Hx group was significantly worse (P < 0.0001), and the 5-year OS rate was quite low, that is, 20% (liver damage A, 77% for the repeat Hx group and 75% for the salvage LDLT group). The prognosis of patients with grade B liver damage after repeat Hx for recurrent HCC is poor, and salvage LDLT would be a potent option for such patients..
298. Y. I. Yamashita, K. Shirabe, T. Ikegami, T. Yoshizumi, E. Tsujita, M. Morita, Y. Maehara, Treatment strategy for recurrent hepatocellular carcinoma after curative heaptectomy: Repeat hepatectomy vs. salvage living donor liver transplantation, EUROPEAN JOURNAL OF CANCER, 51, S401-S401, 2015.09.
299. 【肝がん診療ガイドライン:どうする治療選択】 C-P C、ミラノ基準内かつ65歳以下 C-P Cの非代償性肝硬変・ミラノ基準内肝細胞癌患者に対する肝移植.
300. 【肝炎ウイルスA to E】 B型肝炎 肝移植後のHBV再感染予防.
301. 【肝疾患の病態と糖鎖科学の意義】 肝線維化マーカーWFA結合性M2 binding protein(M2BPGi)の臨床的意義 各種線維化マーカーとの比較.
302. 【臓器移植の術後管理再考-移植医が集中治療に望むこと】 成人生体肝移植周術期管理
生体肝移植(LDLT)後の成績向上には成人生体肝移植後特有の病態の理解、適切なグラフト選択、周術期管理や手術手技の工夫が寄与している。術前には非サルコペニア状態の維持、口腔内ケア、レシピエントの状態に応じたグラフト選択が肝要である。われわれが施行している術中の新たな工夫としては脾臓摘出の併施と胸腔ドレーンの挿入が有効である。術後は血行動態の安定、新鮮凍結血漿と血小板投与による凝固障害の補正、人工呼吸器からの早期脱離、適切な輸液・輸血による循環管理を行うことが予後に大きく影響する。中心静脈をはじめ、不要な点滴ルートの可及的早期抜去、術翌日からの経腸栄養などで敗血症の頻度を低下させることが成績向上に寄与していると考えられる。生体ドナーの安全性は今後も常に問題となりうる。われわれは、脳死下臓器提供の啓発活動、脳死肝移植の増加に向けた努力を常に忘れてはならない。(著者抄録).
303. 一本の経皮的な経路が経口内視鏡操作を安全で有効な治療に変える、胆道Rendezvous Techniqueの基本と応用.
304. 世界へ発信する肝臓外科医療 再発肝細胞癌に対する外科成績向上を目指した3回以上肝切除とSalvage Living Donor Liver Transplantation.
305. 世界へ発信する移植外科医療 生体肝移植成績向上に向けた術式の工夫と周術期管理.
306. 免疫抑制の進歩と展望 生体肝移植後腎障害の改善を目指した免疫抑制療法.
307. 再発肝細胞癌に対する外科治療の新展開 3回目以上再肝切除とSalvage Living Donor Liver Transplantationの臨床成績.
308. 再発肝細胞癌に対する肝移植の治療成績.
309. 印刷業勤務を背景に発症した肝内胆管癌の1例
47歳、男性。12年間印刷業に従事していた。心窩部痛の増悪のため前医を受診した際に肝内腫瘤を認め、当科紹介となった。精査にて脈管浸潤や複数のリンパ節転移を認める手術不適応な肝内胆管癌と診断された。CDDP+5-FU療法を施行したが発熱、嘔気の出現にて継続困難となった為、症状緩和目的に肝右三区域切除術が施行されたが癌の進行により死亡した。切除標本ではS6とS8/4の2ヶ所に胆管癌を認め、その2つの腫瘍間の胆管にBiliary intraepithelial neoplasiaが認められた。今回我々は、20年前に経験した肝内胆管癌症例に印刷業勤務の背景が存在していたため文献的考察を加えて報告する。(著者抄録).
310. 困難例に対する肝移植手術の工夫と限界 基礎研究・移植再生 生体肝移植手術の標準化と肝静脈吻合困難例に対する工夫.
311. 小児肝移植におけるウイルス感染の検討.
312. 当教室における血液型不適合生体肝移植の長期成績.
313. 当科における生体肝移植における胆管胆管吻合の成績.
314. 当科における肝移植後良性一過性高ALP血症5例の検討.
315. 成人生体肝移植後における長期予後因子の検討.
316. 本邦における肝移植の現状と展開 肝移植症例におけるサルコペニアの現状に関する研究.
317. 吉屋 匠平, 調 憲, 播本 憲史, 皆川 亮介, 山下 洋市, 池上 徹, 吉住 朋晴, 川中 博文, 梶山 潔, 前原 喜彦, 消化器外科における凝固線溶異常 肝切除後のPVTに対するエノキサパリンを用いた術後の抗凝固療法の有効性(Coagulation Abnormalities in Gastroenterological Surgery Efficacy of Postoperative Anticoagulation Therapy with Enoxaparin for PVT after Hepatectomy), 日本消化器外科学会総会, 70回, WS-12, 2015.07.
318. 消化器外科セミナー サルコペニアの概念とその対策.
319. 消化器外科領域における基礎研究 新規糖鎖蛋白WFA-M2BPの発現の分子機序と線維化マーカーとしての意義.
320. 生体 肝、腎移植ドナーの安全性について 現状と、向上に向けた工夫、取り組み 生体肝移植ドナー手術安全性の検討 576例の手術経験から.
321. 生体肝移植におけるグラフト選択に関する検討 とくに右・左葉両葉選択可能症例における右葉選択症例について.
322. 生体肝移植レシピエントの肝十二指腸靱帯剥離における結紮を用いない肝動脈処理による動脈解離予防効果と剥離手技の定型化.
323. 生体肝移植後E型肝炎持続感染が確認された1例.
324. 生体肝移植後SSIの発症危険因子と予後の検討.
325. 生体肝移植後合併症対策 短期から長期まで
小児例からはじまった生体肝移植が、成人例へと拡大され20年が経過した。特に成人間生体肝移植例でレシピエントの標準肝容積にくらべグラフト肝が小さいために発症する過小グラフト症候群あるいは術後敗血症は、病態の理解と対策さらにさまざまな手術手技と術後管理の工夫により克服されつつある。これにより、生体肝移植の成績は年々向上してきている。長期生存例が増加するなかで、移植後新たに発症する慢性疾患の予防および治療の重要性が明らかになってきた。長期経過中に発症する合併症はおのおのが密に関連しているので、各疾患の専門科も含めたtotal managementがさらなる長期予後に寄与すると考えられる。(著者抄録).
326. 生体肝移植後腎機能障害改善に向けたわれわれの治療戦略.
327. 移植医療におけるHCV治療up-to-date 生体肝移植後C型肝炎再発に対するDAAを用いた治療戦略.
328. 移植後C型肝炎再発に対する抗ウイルス治療と肝機能障害.
329. 移植成績から見た再肝移植と60歳以上レシピエントへの肝移植適応に関する検討.
330. 肝切除のためのデバイスの進歩 肝切除にマイクロサージェリーの技法を導入するAuto irrigation BipolarとEndo Quick Suture有用性の検討.
331. 肝癌に対する各種治療法の取り組み 肝細胞癌(HCC)に対する肝移植(LT)の位置づけと課題.
332. 肝硬変合併肝細胞癌に対する腹腔鏡下肝切除の意義.
333. 肝移植専門医増加を目指した生体肝移植手術手技の定型化と修練法の工夫.
334. 肝移植後C型肝炎再発に対する治療戦略 特殊病態への対応力が鍵である.
335. 肝細胞癌に対する腹腔鏡下肝切除術の治療成績.
336. 肝細胞癌に対する生体肝移植術における体内組成評価(骨格筋/内脂肪比)の意義に関する研究.
337. 肝細胞癌に対する生体肝移植術におけるBody compositionの意義に関する研究.
338. 肝胆膵 EOB-MRIおよび3D-CT volumetryを用いた新たな肝予備能評価の意義.
339. 池上 徹, 調 憲, 吉住 朋晴, 山下 洋市, 播本 憲文, 伊藤 心二, 武石 一樹, 川中 博文, 池田 哲夫, 前原 喜彦, 肝胆膵 成人間生体肝移植の移植物調達のための上正中切開術(Upper midline incision for graft procurement for adult-to-adult living donor liver transplantation), 日本外科学会定期学術集会抄録集, 115回, OP-069, 2015.04.
340. 肝胆膵 生体肝移植ドナー407例の3D画像を用いた解剖学的破格の検討 特に門脈・胆管走行の関連について.
341. 肝胆膵 生体肝移植におけるグラフト選択に関する検討 とくに右・左葉両葉選択可能症例における右葉選択症例について.
342. 肝胆膵 肝硬変症に対する腹腔鏡下脾摘術の合併症を克服するための手技の標準化と手術成績.
343. 肝胆膵 肝細胞癌における高度微小脈管侵襲を予測する血清中exosome内miRNAの同定.
344. 肝胆膵 肝臓の再生研究におけるオートファジーの意義.
345. 肝胆膵 脂肪肝マウスの肝切除後肝再生遅延におけるオートファジーの役割.
346. 肝胆膵 脂肪肝における温阻血再灌流傷害の増悪の分子機序解明と新しい治療の展開.
347. 肝胆膵 腹腔鏡によりもたらされる拡大視効果を利用した安全・確実な肝外グリソン鞘一括先行処理による系統的肝切除の定型化.
348. 肝胆膵 血清中糖鎖蛋白WFA-M2BPの発現の分子機序と線維化マーカーとしての意義.
349. 肝臓 肝細胞がん研究の最先端 肝細胞癌におけるSALL4、HDAC1、HDAC2の発現と臨床病理学的検討.
350. 肝臓外科領域における手術手技の工夫 上腹部正中切開による各種生体肝移植グラフト採取の工夫.
351. 肝臓疾患に対する内視鏡外科手術手技 肝腫瘍に対する完全腹腔鏡下肝切除術 特に難易度の高い前上および後区域に位置するの腫瘍の切除の工夫.
352. 肝静脈波形からみたB-RTOの適応について.
353. 脂肪肝温阻血再灌流傷害におけるNADPH oxidaseシグナルの関与とその制御.
354. 腹腔鏡下または小切開によるドナー肝切除の是非.
355. 腹腔鏡下肝切除術 肝硬変症例への適応拡大 肝硬変合併肝細胞癌に対する腹腔鏡下肝切除の意義.
356. 腹腔鏡下肝切除における止血法の工夫 最適な方法を求めて 3つの新開発-腹腔鏡下止血器具の腹腔鏡下肝切除における有用性の検討.
357. 腹腔鏡下肝切除術の適応拡大と標準化への工夫 腹腔鏡下肝切除術の安全性向上と適応拡大への工夫.
358. 池田 哲夫, 山下 洋市, 播本 憲史, 武石 一樹, 伊藤 心二, 池上 徹, 吉住 朋晴, 赤星 朋比古, 調 憲, 橋爪 誠, 前原 喜彦, 腹腔鏡下肝切除におけるトラブルシューティング(Troubleshooting in pure laparoscopic liver resection especially in patients with tumors in the anterosuperior and posterior segments), 日本肝胆膵外科学会・学術集会プログラム・抄録集, 27回, 328-328, 2015.06.
359. 腹腔鏡下肝切除の進歩と開腹手術へのフィードバック 肝胆膵 腹腔鏡下肝切除がもたらした再発見.
360. 腹腔鏡下脾臓摘出術のピットフォールとその対策 安全を担保した肝硬変症に対する腹腔鏡下脾摘術の手技の確立.
361. 今井 大祐, 調 憲, 山下 洋市, 吉住 朋晴, 内山 秀昭, 池上 徹, 播本 憲史, 伊藤 心二, 岡部 弘尚, 岡野 慎士, 相島 慎一, 前原 喜彦, 膵癌における間葉系形質の獲得とPD-L1の発現に関する臨床病理学的検討, 日本癌学会総会記事, 74回, J-1092, 2015.10.
362. 膵癌に対するFOLFIRINOXの治療成績と安全性に関する検討.
363. 自信を持って行おう! 肝移植後C型肝炎再発に対する治療.
364. 調 憲, 吉住 朋晴, 池上 徹, 播本 憲史, 伊藤 心二, 武石 一樹, 内山 秀昭, 前原 喜彦, 進化する生体肝移植(Evolution in living donor liver transplantation), 日本肝胆膵外科学会・学術集会プログラム・抄録集, 27回, 331-331, 2015.06.
365. 門脈圧亢進症時における外科治療の最前線 肝細胞癌肝切除に対する脾容積の意義と脾摘術の効果.
366. 高齢者消化器癌に対する治療戦略 高齢者肝細胞癌におけるサルコペニアの意義.
367. 3Dナビゲーションを用いた外科手術 生体医工学・医用画像解析に基づいた、曲げて、捻って内部構造の変化がはっきり見え、電気メスで切れる、肝臓手術ナビゲーションシステムの検討.
368. 65歳以上の高齢者における生体肝移植術の適応とその成績に関する検討.
369. Masanori Yoshimatsu, Ken Shirabe, Yoshihiro Nagao, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Tetsuo Ikeda, Katsunori Tatsugami, Yoshihiko Maehara, A safe combined nephrectomy and right lobectomy using the liver hanging maneuver for huge renal cell carcinoma directly invading the right lobe of the liver: report of a case., Surgery today, 10.1007/s00595-013-0693-3, 44, 9, 1778-82, 2014.09, We herein discuss a patient who underwent simultaneous combined right nephrectomy and right lobectomy of the liver. A 64-year-old male was diagnosed with a huge right renal cell carcinoma (RCC), 13 cm in diameter, which was invading directly into the right hepatic lobe. This type of RCC has been rarely reported, and an anterior approach using the liver hanging maneuver was extremely useful during hepatic parenchymal dissection. The liver parenchymal dissection was performed prior to mobilization of the liver, because the mobilization of the right lobe of the liver was impossible. During the hepatic parenchymal resection, the liver was suspended with the tape and transected, and thereafter, retroperitoneal dissection, nephrectomy and right lobectomy of the liver were completed. The patient was discharged from the hospital on the 12th postoperative day with an uneventful clinical course. The anterior approach using the liver hanging maneuver during hepatic parenchymal resection can be safe and feasible for huge RCC invading the right hepatic lobe..
370. Apelin/APJ系を介したKupffer細胞活性化による肝再生促進効果に関する基礎的研究.
371. Apelin/APJ系シグナル阻害による肝再生促進効果に関する基礎的研究.
372. B-RTO・手術療法の工夫 胃静脈瘤に対する腹腔鏡Hassab手術の手技の工夫.
373. Yoshihiro Nagao, Tomohiko Akahoshi, Hideo Uehara, Naotaka Hashimoto, Nao Kinjo, Hirofumi Kawanaka, Morimasa Tomikawa, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuuji Soejima, Ken Shirabe, Yoshihiko Maehara, Balloon-occluded retrograde transvenous obliteration is feasible for prolonged portosystemic shunts after living donor liver transplantation., Surgery today, 10.1007/s00595-013-0535-3, 44, 4, 633-9, 2014.04, PURPOSES: The purpose of our study was to evaluate the efficacy of balloon-occluded retrograde transvenous obliteration (B-RTO) in patients after living donor liver transplantation (LDLT). METHODS: Five patients with gastric varices (GVx) and/or liver dysfunction who were treated with B-RTO from January 2001 to December 2007 were enrolled in this study (GVx, n = 2; liver dysfunction, n = 1; both, n = 2). The eradication rate of the GVx, portal vein hemodynamics and improvement of liver function were evaluated. RESULTS: B-RTO was performed successfully, and the GVx disappeared or decreased markedly in all patients. Recurrence of GVx was not observed during the follow-up. Significantly increased portal vein inflow and improved liver function were observed in all patients. CONCLUSIONS: B-RTO may be an effective treatment for patients after LDLT to prevent bleeding from GVx or to modulate portal vein inflow that is reduced by prolonged large portosystemic shunts..
374. Yo-ichi Yamashita, Ken Shirabe, Kazuki Takeishi, Shinji Itoh, Norifumi Harimoto, Tom Ikegami, Tomoharu Yoshizumi, Hirofumi Kawanaka, Tetsuo Ikeda, Yoshihiko Maehara, CLINICAL RESULTS OF REPEAT HEPATECTOMY FOR RECURRENT HEPATOCELLULAR CARCINOMA: A SINGLE-CENTER EXPERIENCE, ANTICANCER RESEARCH, 34, 10, 6246-6247, 2014.10.
375. Koichi Kimura, Toru Ikegami, Yuki Bekki, Mizuki Ninomiya, Yo-Ichi Yamashita, Tomoharu Yoshizumi, Shohei Yoshiya, Yuji Soejima, Noboru Harada, Ken Shirabe, Yoshihiko Maehara, Clinical significance of gastrointestinal bleeding after living donor liver transplantation., Transplant international : official journal of the European Society for Organ Transplantation, 10.1111/tri.12325, 27, 7, 705-11, 2014.07, The clinical presentations of gastrointestinal bleeding (GIB) occurring after living donor liver transplantation (LDLT) have not been fully described. We performed a retrospective analysis of 297 LDLT cases. Nineteen patients (6.4%) experienced GIB after LDLT. The etiology of GIB included bleeding at the jejunojejunostomy following hepaticojejunostomy (n = 13), peptic ulcer disease (n = 2), portal hypertensive gastropathy (n = 2), and other causes (n = 2). Hemostasis was achieved in 13 patients (68.4%) by endoscopic (n = 3), surgical (n = 1), or supportive treatments (n = 15), but not in the other six patients. Graft dysfunction (P < 0.001), hepaticojejunostomy (P = 0.01), portal vein pressure at the end of surgery >20 mmHg (P = 0.002), and operative blood loss >10 L (P = 0.004) were risk factors. One-year graft survival rate was significantly lower in patients with GIB than in patients without GIB (P < 0.001). The inhospital mortality rate was 52.6% for patients with GIB, 75.0% for patients with graft dysfunction, and 14.3% for patients without graft dysfunction (P = 0.028). Despite its infrequency after LDLT, GIB has strong correlation with graft dysfunction and inhospital mortality..
376. C型肝炎・肝細胞癌に対する肝移植の現状と課題 肝移植後C型肝炎再発に対するDAAを用いた治療戦略.
377. Toru Ikegami, Daisuke Imai, Huanlin Wang, Tomoharu Yoshizumi, Yo-Ichi Yamashita, Mizuki Ninomiya, Tomohiro Iguchi, Yuki Bekki, Ken Shirabe, Yoshihiko Maehara, D-MELD as a predictor of early graft mortality in adult-to-adult living-donor liver transplantation., Transplantation, 10.1097/01.TP.0000435696.23525.d0, 97, 4, 457-62, 2014.02, BACKGROUND: Ensuring a good match between donor and recipient is critically important to achieve acceptable graft outcomes after living-donor liver transplantation (LDLT). Our objective was to evaluate the product of donor age and Model for End-stage Liver Disease score (D-MELD) as a predictor of graft survival after LDLT. METHODS: We retrospectively evaluated the records of 355 adults who underwent LDLT for chronic liver disease and explored the relationship between D-MELD and graft outcome. RESULTS: High MELD score and advanced donor age were significantly associated with graft survival; D-MELD had the strongest association with in-hospital mortality. Receiver operating characteristic curve analysis showed that a D-MELD score of 462 had the highest sensitivity for predicting in-hospital mortality. Patients were allocated to three groups based on D-MELD (Class A [≤449; n=142], Class B [450-899; n=163], and Class C [≥900; n=50]) and were found to have stratified cumulative 2-year graft survivals of 94.1%, 85.3%, and 63.1%, respectively (P<0.01). Although D-MELD Class C patients had larger graft volume-to-standard liver volume ratio (P<0.01) and received right lobe grafts more often (P<0.01), they still exhibited significantly higher rates of primary graft dysfunction (P<0.01) and in-hospital mortality (P<0.01). Outcomes in D-MELD Class C were significantly worse in hepatitis C-positive patients (P<0.05). CONCLUSIONS: The D-MELD score is a simple and reliable predictor of early graft survival that assists the matching of donors and recipients in LDLT in adults..
378. EOB-MRIを用いた生体肝移植ドナー、レシピエント術後の肝機能評価に関する研究.
379. Shohei Yoshiya, Toru Ikegami, Tomoharu Yoshizumi, Huanlin Wang, Noboru Harada, Yo-Ichi Yamashita, Akihiro Nishie, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Fairly rare de novo inflammatory pseudotumor in a graft after living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23828, 20, 5, 616-8, 2014.05.
380. Gemcitabine+low dose FP(GFP)療法と放射線治療でCRを得られた12年後に再発をきたした膵臓癌の1切除例.
381. HTLV-1が生体肝移植の成績に及ぼす影響に関する研究.
382. 池上 徹, 吉住 朋晴, 二宮 瑞樹, 副島 雄二, 井口 友宏, 山下 洋一, 内山 秀昭, 沖 栄次, 佐伯 浩司, 調 憲, 前原 喜彦, IS-2-5 Strategies and techniques in successful left lobe living donor liver transplantation in adults(IS-2 International Session (2) Liver transplantation), 日本外科学会雑誌, 115, 2, 78-78, 2014.03.
383. 山下 洋市, 調 憲, 井口 友宏, 二宮 瑞樹, 吉屋 匠平, 松本 佳大, 中川原 英和, 木村 光一, 今井 大祐, 別城 悠樹, 王 観林, 池上 徹, 吉住 朋晴, 川中 博文, 池田 哲夫, 内山 秀昭, 副島 雄二, 前原 喜彦, IS-9-3 Bile leakage after hepatic resection : Our attempts for prevention and management towards zero-morbidity(IS-9 International Session (9) Hepato-biliary surgery-2), 日本外科学会雑誌, 115, 2, 105-105, 2014.03.
384. Shohei Yoshiya, Yukiko Fujimoto, Yuki Bekki, Hideyuki Konishi, Yo-Ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Impact of epidermal growth factor single-nucleotide polymorphism on recurrence of hepatocellular carcinoma after hepatectomy in patients with chronic hepatitis C virus infection., Cancer science, 10.1111/cas.12415, 105, 6, 646-50, 2014.06, Epidermal growth factor (EGF) gene single-nucleotide polymorphism (SNP) is associated with an increased risk of hepatic tumors. The study aimed to elucidate the impact of EGF SNP and EGF receptor (EGFR) expression on the recurrence of hepatocellular carcinoma (HCC) after hepatectomy. To examine the impact of EGF SNP and EGFR on recurrent HCC, we retrospectively analyzed 141 HCC patients with chronic hepatitis C virus infection who underwent curative hepatectomy. The EGF *61 GG allele was present in 69 patients (48.9%), AG in 56 (39.7%) and AA in 16 (11.4%). The AA group had a significantly lower rate of intrahepatic metastasis (0% vs 16.5%, P = 0.02), lower serum EGF concentration (26.3 ± 15.9 pg/mL vs 43.4 ± 30.5 pg/mL, P = 0.02) and lower proportion of early recurrence (≤2 years; 28.6% vs 71.2%, P = 0.03) than the AG/GG group. The AA group had significantly higher recurrence-free survival than the AG/GG group (P = 0.04), but there was no significant difference in overall survival between these two groups (P = 0.97). High versus low EGFR expression analyzed by immunohistochemical staining in cancer cells was not significantly associated with overall survival (P = 0.37) or recurrence-free survival (P = 0.39). Therefore, EGF *61 AA was associated with a lower risk of recurrence after curative hepatectomy for HCC in patients with hepatitis C virus infection than other genotypes, but EGFR expression in cancer cells was not significantly associated with prognosis..
385. Tomoharu Yoshizumi, Ken Shirabe, Toni Ikegami, Norifumi Harimoto, Shinji Hoh, Kazuki Takeishi, Oichi Yamashita, Hirofumi Kawanaka, Tetsuo Ikeda, Yoshihiko Maehara, LIVING DONOR LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA WITHIN MILAN CRITERIA, ANTICANCER RESEARCH, 34, 10, 6250-6250, 2014.10.
386. Ken Shirabe, Takeo Toshima, Koichi Kimura, Yoichi Yamashita, Tetsuo Ikeda, Toru Ikegami, Tomoharu Yoshizumi, Koichiro Abe, Shinichi Aishima, Yoshihiko Maehara, New scoring system for prediction of microvascular invasion in patients with hepatocellular carcinoma., Liver international : official journal of the International Association for the Study of the Liver, 10.1111/liv.12459, 34, 6, 937-41, 2014.07, BACKGROUND & AIMS: The microvascular invasion of cancer cells (mvi) is a good prognostic factor after hepatic resection (HR) and liver transplantation for hepatocellular carcinoma (HCC). This study aimed to predict mvi in patients with HCC. METHODS: We studied 63 hepatectomized patients with HCC who had HCC without any extrahepatic metastases and vascular invasion, which were detected during preoperative evaluation. The preoperative clinicopathological data of these patients were analysed to predict presence of mvi. A scoring system was designed using significant risk factors. This system was applied to another series of 34 patients with HCC who underwent HR, and was evaluated for validation. RESULTS: Tumour size, serum des-gamma-carboxy prothrombin (DCP) levels and the maximum standardized uptake value (SUVmax) on 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography were independent clinical predictors for mvi after multivariate analyses. Tumour size, serum DCP levels, and values of SUVmax were used to plot a receiver operating characteristic curve for predicting mvi. Areas under the curve of tumour size, serum DCP levels and SUV max values, were 0.8652, 0.8027 and 0.7848 respectively. Maximal sensitivity and specificity were obtained when the tumour size was 3.6 cm, SUVmax was 4.2, and the serum DCP level was 101 mAU/ml. A scoring system was designed using these three variables. The sensitivity and specificity of our scoring system were 100% and 90.9%, respectively, in the validation test. CONCLUSION: Our scoring system for mvi, consisting of tumour size, serum DCP levels, and SUV max, provides a precise prediction of mvi..
387. Hirofumi Kawanaka, Tomohiko Akahoshi, Shinji Itoh, Tomohiro Iguchi, Norifumi Harimoto, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Kenji Takenaka, Yoshihiko Maehara, Optimizing risk stratification in portal vein thrombosis after splenectomy and its primary prophylaxis with antithrombin III concentrates and danaparoid sodium in liver cirrhosis with portal hypertension., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.07.939, 219, 5, 865-74, 2014.11, BACKGROUND: Decreased antithrombin III (ATIII) activity and large splenic vein diameter (SVD) are risk factors for portal vein thrombosis (PVT) after splenectomy in liver cirrhosis with portal hypertension. Antithrombin III concentrates can prevent PVT. This study was designed to stratify risks for PVT after splenectomy in cirrhotic patients and to develop prophylactic protocols for PVT. STUDY DESIGN: In 53 patients (testing cohort), the cutoff level of preoperative ATIII activity (≤60%) was evaluated for administration of ATIII concentrates. Antithrombin III activity and SVD were re-evaluated as criteria for prophylaxis of PVT. In 57 patients (validation cohort), the risk stratification of PVT and prophylactic protocols were validated. RESULTS: In the testing cohort, 10 (19%) of 53 patients had PVT. Risk level of PVT was stratified and prophylactic protocols were developed. Patients at low risk (ATIII activity ≥70% and SVD <10 mm) were not treated; those at high risk (ATIII activity <70% or SVD ≥10 mm) received ATIII concentrates (1,500 U/day) for 3 days; and those at highest risk (SVD ≥15 mm) received ATIII concentrates for 3 days, followed by danaparoid sodium (2,500 U/day) for 14 days and warfarin. In the validation cohort, 0 of 14 low-risk and 2 of 32 high-risk patients had PVT. Although 8 of 11 patients at highest risk had temporary PVT, it disappeared within 3 months postoperatively. Finally, only 2 (3.5%) of 57 patients had PVT. CONCLUSIONS: Risk stratification of PVT after splenectomy and prophylaxis with ATIII concentrates and danaparoid sodium dramatically reduced the incidence of PVT..
388. Satoshi Ida, Eiji Oki, Koji Ando, Yasue Kimura, Yo-ichi Yamashita, Hiroshi Saeki, Toru Ikegami, Tomoharu Yoshizumi, Masayuki Watanabe, Masaru Morita, Ken Shirabe, Tetsuya Kusumoto, Tetsuo Ikeda, Hideo Baba, Yoshihiko Maehara, Pure laparoscopic right-sided hepatectomy in the semi-prone position for synchronous colorectal cancer with liver metastases., Asian journal of endoscopic surgery, 10.1111/ases.12098, 7, 2, 133-7, 2014.05, INTRODUCTION: Simultaneous resection for colorectal cancer and synchronous colorectal liver metastases (SCRLM) has been found to be safe and effective. However, pure laparoscopic simultaneous resection (PULSAR) for primary colorectal cancer and SCRLM is usually difficult, especially in the right lobe of the liver. The purpose of this study was to assess the feasibility of PULSAR for patients with primary colorectal cancer and SCRLM. METHODS: From January 2008 to December 2012, a total of 10 patients (9 men and 1woman; mean age, 64 years) underwent PULSAR for a primary tumor and SCRLM. RESULTS: Seven patients (70%) with lesions in the right lobe (segments 6, 7, and 8) successfully underwent resection with a pure laparoscopic procedure while in the left semi-prone position. No patient was converted to conventional open surgery. The mean operative duration, volume of bleeding, and postoperative hospital stay were 606 ± 46 min, 585 ± 145 mL, and 18 ± 3.5 days, respectively. Although a liver abscess developed in one patient, no colonic complications or perioperative death occurred. CONCLUSION: PULSAR for primary colorectal cancer and SCRLM is a feasible multidisciplinary treatment. Moreover, PULSAR can be safely and effectively performed with the patient in the semi-prone position, even when SCRLM exists in the right lobe of the liver..
389. Tomoharu Yoshizumi, Toru Ikegami, Yuki Bekki, Mizuki Ninomiya, Hideaki Uchiyama, Tomohiro Iguchi, Yo-Ichi Yamashita, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Re-evaluation of the predictive score for 6-month graft survival in living donor liver transplantation in the modern era., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23804, 20, 3, 323-32, 2014.03, The limitations of donor age, graft size, and the Model for End-Stage Liver Disease (MELD) score have not been apparent in living donor liver transplantation (LDLT). Our team developed a formula for predicting graft survival after LDLT; the formula includes the graft weight, donor age, MELD score, and portosystemic shunt status. The aims of this study were to re-evaluate the reliability of our formula and to assess whether our modified treatment strategy has improved 6-month graft survival. Two hundred seventeen patients were allocated into 2 groups: patients with predictive scores ≥ 1.30 (n = 162) and patients with predictive scores < 1.30 (n = 55). The latter group was also divided into subgroups of patients with scores of 1.15 to 1.30 (n = 37) and patients with scores < 1.15 (n = 18). Survival rates for patients with scores < 1.30 were significantly worse than rates for patients with scores ≥ 1.30 (P = 0.006). Survival rates for patients with scores < 1.15 were significantly worse than rates for patients with scores of 1.15 to <1.30 (P < 0.001). A multivariate analysis showed that a predictive score < 1.15 (odds ratio = 7.87, P = 0.006) and a body mass index ≥ 30 kg/m(2) (odds ratio = 13.3, P < 0.001) were independent risk factors for 6-month graft mortality. In conclusion, predictive scores reliably predict 6-month graft survival and could allow a widening of the safe ranges for donor ages and graft sizes..
390. Toshiro Masuda, Ken Shirabe, Toru Ikegami, Norifumi Harimoto, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Tetsuo Ikeda, Hideo Baba, Yoshihiko Maehara, Sarcopenia is a prognostic factor in living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23811, 20, 4, 401-7, 2014.04, The aims of this study were to investigate sarcopenia as a novel predictor of mortality and sepsis after living donor liver transplantation (LDLT) and to evaluate the effects of early enteral nutrition on patients with sarcopenia. Two hundred four patients undergoing preoperative computed tomography within the month before LDLT were retrospectively evaluated. The lengths of the major and minor axes of the psoas muscle were simply measured at the caudal end of the third lumbar vertebra, and the area of the psoas muscle was calculated. A psoas muscle area lower than the 5th percentile for healthy donors of each sex was defined as sarcopenia. Ninety-six of the 204 patients (47.1%), including 58.3% (60/103) of the male patients and 35.6% (36/101) of the female patients, were diagnosed with sarcopenia. Sarcopenia was independently and significantly associated with overall survival: there was an approximately 2-fold higher risk of death for patients with sarcopenia versus patients without sarcopenia (hazard ratio = 2.06, P = 0.047). Sarcopenia was an independent predictor of postoperative sepsis (hazard ratio = 5.31, P = 0.009). Other independent predictors were a younger recipient age (P < 0.001) and a higher body mass index (P = 0.02). Early enteral nutrition within the first 48 hours after LDLT was performed for 24.2% in 2003-2007 and for 100% in 2008-2011, and the incidence of postoperative sepsis for patients with sarcopenia (n = 96) was 28.2% (11/39) in 2003-2007 and 10.5% (6/57) in 2008-2011 (P = 0.03). In conclusion, sarcopenia is an independent predictor of mortality and sepsis after LDLT. The incidence of postoperative sepsis was reduced even in patients with sarcopenia after the routine application of early enteral nutrition..
391. Yo-Ichi Yamashita, Daisuke Imai, Yuki Bekki, Kazuki Takeishi, Eiji Tsujita, Toru Ikegami, Tomoharu Yoshizumi, Tetsuo Ikeda, Ken Shirabe, Teruyoshi Ishida, Yoshihiko Maehara, Surgical outcomes of anatomical resection for solitary recurrent hepatocellular carcinoma., Anticancer research, 34, 8, 4421-6, 2014.08, BACKGROUND: For eradicating portal venous tumor extension and intrahepatic metastasis in hepatocellular carcinoma (HCC), anatomical resection is, in theory, preferable. PATIENTS AND METHODS: We carried-out a retrospective cohort study in 110 patients who underwent curative hepatic resection (anatomical resection; n=20, and limited resection; n=90) for solitary recurrent HCC from 1990-2010. RESULTS: No significant difference was found in short-term surgical results such as mortality, morbidity, and duration of hospital stay between the two groups. Anatomical resection did not influence overall and disease-free survival for all patients with a solitary recurrent HCC. In patients with cancer spread, such as pathological vascular invasion and intrahepatic metastasis (n=61), or with des-γ-carboxy prothrombin (DCP) ≥ 100 mAU/ml (n=73), the disease-free survival rate in the anatomical-resection group was significantly better than that in the limited-resection group (p=0.0452 and p=0.0345, respectively). CONCLUSION: Anatomical resection should be recommended only for HCC suspected of exhibiting cancer spread as reflected by DCP ≥ 100 mAU/ml in patients with solitary recurrent HCC..
392. 【C型肝炎治療困難例への対策】 生体肝移植後C型肝炎再発に対する治療戦略.
393. 【サルコペニアの定義と臨床的意義】 サルコペニアの定義 CT法を中心に
サルコペニアは加齢に伴う骨格筋量と筋力の低下とされてきたが、コンセンサスを得た定義はいまだに存在しない。われわれは健康な生体肝移植ドナーのCT画像を用いて、日本人における骨格筋面積の標準値算出式を作成し、サルコペニア診断における有用性を確認した。本稿では、CT画像による筋肉量の測定にもとづいたサルコペニアの定義に関する報告をレビューするとともに、最新の自験例から得られた知見について概説した。(著者抄録).
394. 【サルコペニア~医療職間連携による多角的アプローチ~】 肝移植におけるサルコペニアの意義
肝疾患におけるサルコペニアが今注目されている。肝疾患に伴うサルコペニアの進展は、肝細胞癌によるものや末期肝不全における肝機能低下によるものがある。いずれも肝細胞癌の肝切除後や肝移植後の予後因子として報告されている。肝細胞癌におけるサルコペニアは癌再発の危険因子として報告され、肝移植後のサルコペニアは肝移植早期の敗血症の危険因子として報告された。肝細胞癌におけるサルコペニアの機序は不明であるが、末期肝不全におけるサルコペニアは肝臓のエネルギー失調を代償するためのグリコーゲンやアミノ酸の供給を行うために、あるいは肝臓からの筋肥大を惹起する因子の低下により崩壊が進んでいる可能性がある。今後、運動療法や栄養療法によってサルコペニアの進行が食い止められ、肝疾患患者の生命予後が延長できるのかがこの分野の大きな関心となっている。(著者抄録).
395. 【小児肝胆膵疾患のトランジション】 小児肝疾患の外科的治療 肝移植.
396. 【消化器外科におけるチーム医療】 肝移植におけるチーム医療.
397. 【消化器外科手術ピットフォールとリカバリーショット】 術中出血対応法の基本.
398. 【肝癌に対する肝臓移植の適応拡大と制限】 ミラノ基準外症例における肝細胞癌に対する肝移植 適応拡大基準を中心に
ミラノ基準内の肝癌に対する肝移植成績は良好である。腫瘍径3cm以内3個以下あるいは5cm以下単発というミラノ基準は、わが国の肝癌に対する肝移植の保険適応基準であるが、ミラノ基準を超えた肝癌患者でも肝移植によって肝癌が治癒する症例の存在が知られている。肝癌以外の疾患に対する肝移植とミラノ基準内の肝癌に対する肝移植成績の比較では、ミラノ基準内肝癌に対する肝移植成績が有意に良好であった。肝癌以外の症例への肝移植が保険収載されていることから、肝癌に対する適応拡大は合理的である。各施設による複数の拡大基準が提唱されているが、適応拡大により利益を受ける患者数と再発の頻度を考慮した利益の最大化が重要である。(著者抄録).
399. 【高齢者外科:周術期栄養管理をめぐる諸問題】 高齢者膵頭十二指腸切除における周術期栄養管理の現状と問題点
膵頭十二指腸切除(Pancreaticoduodenectomy:PD)は、侵襲の大きな腹部手術の代表とされている。日本では人口の高齢化のためにますます多くの高齢者に治療法としてPDを提示しなければならない機会が増えると考えられる。75歳以上の高齢者に対するPDに関するメタアナリシスは、75歳以上の患者では在院死率と肺炎の合併率が上昇するとしている。われわれは、75歳以上の患者に対するPDでは創感染の合併率が高くなることを報告した。また高齢者では退院後1年以内の再入院率が高いとする報告もあり、高齢者ではPD後の回復遅延が活動性の不良を来している可能性が高い。われわれは75歳以上の高齢者におけるPDでは術後プレアルブミン値の回復が遅延している可能性を指摘しており、高齢者PDにおいては周術期経腸栄養などの積極的な栄養管理介入が必要ではないかと考えている。自見例を踏まえながら高齢者膵頭十二指腸切除における周術期栄養管理の現状と問題点に関して報告する。(著者抄録).
400. ここまできた、腹腔鏡下肝切除術 完全腹腔鏡下肝切除を安全に行うための解剖学的知識と外科的戦略.
401. エキスパートに学ぶ腹腔鏡下ヘルニア修復術 腹腔鏡下腹壁ヘルニア修復術における合併症を起こさないための手技の工夫について.
402. シンプルかつ安全な血液型不適合生体肝移植プロトコール.
403. 上皮性成長因子(EGF)遺伝子の一塩基多型がHCV患者の肝細胞癌の肝切除後再発に及ぼす影響.
404. 乳児生体肝移植における臓器立体モデルを用いた術前シミュレーションの有用性.
405. 内視鏡下手術における新たな工夫 内視鏡外科における切離、止血操作を安全、確実にするために開発されたElectrosurgical Device Auto-irrigation System(SJI)と体腔内Pre-tied Knot(EndoKnot)の有用性の検討.
406. 内視鏡外科の困難症例に対する安全な手技の工夫 胃静脈瘤に対する腹腔鏡下Hassab手術を安全に行うための手技の工夫.
407. 原発性胆汁性肝硬変に対する生体肝移植後の予後因子および晩期死因に関する検討.
408. 固形癌におけるProgrammed cell Death 1 Ligand 1(PDL1)発現の生物学的意義.
409. 地域医療における85歳以上高齢者に対する肝胆膵外科手術.
410. 大腸癌肝転移に対する腹腔鏡下肝切除術の有用性.
411. 家族性血球貪食症候群に伴う肝不全に対し緊急生体肝移植を行った1例.
412. 小児肝移植におけるサイトメガロウィルス感染.
413. 小児肝移植後に見られる良性一過性高ALP血症5例の臨床的検討.
414. 急性肝不全の治療戦略 当院における改正臓器移植法施行前後の急性肝不全に対する肝移植.
415. 池上 徹, 吉住 朋晴, 二宮 瑞樹, 副島 雄二, 井口 友宏, 山下 洋一, 内山 秀昭, 沖 栄次, 佐伯 浩司, 調 憲, 前原 喜彦, 成人の左葉生体肝移植成功における治療戦略と技術(Strategies and techniques in successful left lobe living donor liver transplantation in adults), 日本外科学会雑誌, 115, 臨増2, 78-78, 2014.03.
416. 成人間生体肝移植後の短期予後に影響を及ぼす因子に関する検討.
417. 成人間生体肝移植後の術後食道胃静脈瘤の危険因子と対策.
418. 手術成績向上に向けた周術期栄養療法 生体肝移植における周術期栄養療法の進歩.
419. 新しい組織学的悪性度規定因子からみた肝細胞癌に対する系統的切除の有用性の検討.
420. 新開発-Silicone Jacket IrrigatorによるAuto irrigation Modern Bipolar Systemを用いた肝切除術.
421. 普及を目指した腹腔鏡下肝切除術の手術手技 肝右葉前上区、後区域に存在する肝細胞癌に対する腹腔鏡下肝切除の治療成績.
422. 生体移植ドナーのより緻密な安全性を求めて 生体肝移植ドナー501例の軌跡 安全性の追求と低侵襲化.
423. 生体肝移植における呼吸器合併症予防への取り組み.
424. 生体肝移植における呼吸器合併症予防への取り組み.
425. 生体肝移植の術前シミュレーションにおける3Dプリンターの有用性.
426. 生体肝移植ドナー501例から学んだ安全な定型的肝切除.
427. 生体肝移植ドナー肝切除手術における工夫 上腹部正中切開による生体拡大肝左葉グラフト採取術.
428. 生体肝移植ドナーにおける肝切離中の気道内圧コントロールによる出血量の減少.
429. 生体肝移植レシピエント手術の定型化と若手への手術指導に関する検討.
430. 生体肝移植後B型肝炎再活性化予防法に関する検討.
431. 生体肝移植後C型肝炎再発に対する多角的治療戦略.
432. 生体肝移植後C型肝炎再発に対する多角的治療戦略.
433. 生体肝移植後に残存する門脈大循環シャントに対するB-RTOの意義について.
434. 生体肝移植後に静脈瘤破裂を来した症例に関する検討.
435. 生体肝移植後腎障害の危険因子とミコフェノールモフェチル単剤療法の有用性に関する検討.
436. 生体肝移植術後胆管吻合部狭窄の予防と対策.
437. 生体肝移植術後の消化管出血の病態と予後.
438. 生検後播種巣を含め繰り返す再発巣切除により長期生存を得た肝細胞癌の1例
症例は78歳,男性.肝S4の径7cmの腫瘍に対し経皮針生検を施行し,肝細胞癌(Hepatocellular carcinoma;HCC)と診断され,拡大内側区域切除術を施行した.生検より2年9ヵ月後に肝切除断端S8に径2cmの腫瘤と,横隔膜・胸壁・皮膚にそれぞれ1cmの腫瘤を指摘され,肝部分切除+横隔膜腫瘤摘出+胸壁合併切除+メッシュによる胸壁再建を施行した.摘出腫瘤は全て中分化型HCCで,肝内転移および生検ルート播種と診断した.その後も繰り返す肝内再発に対して肝切除1回(計4回),リピオドリゼーション5回(計6回),ネクサバール内服などで加療し,生検後9年1ヵ月の生存を得た.ガイドラインにもある通り,HCCを疑う肝腫瘍に対する針生検は慎重を期すべきであるものの,HCCは播種巣を含め繰り返す再発巣に対する切除などの積極的な治療が長期予後に繋がる場合がある.(著者抄録).
439. 用語解説 サルコペニア肥満
<Point>加齢に伴う骨格筋の減少として定義されているサルコペニアと、正常より体重が多い状態を示す肥満が併存した状態をサルコペニア肥満という。最近、筋肉量および筋肉機能を用いたサルコペニアの診断基準が欧州、アジアの各地域から報告されている。肥満の診断基準は体格指数(BMI)が一般的であるが、体内脂肪測定の有用性も報告されており、サルコペニア肥満における統一された診断基準はまだ確立されていない。(著者抄録).
440. 異常側副血行路に対するIVR治療の方法と成績 B-RTOにおけるHVPG変化率の意義.
441. 移植・再生医療の最前線 生体肝移植の成績向上を目指した我々の治療戦略.
442. 糖尿病性腎症をもつ生体肝移植症例に対してMycophenolate Mofetilを基本とした免疫抑制療法で導入した一例
症例は糖尿病性腎症を既往にもつ62歳女性で、今回、非代償性B型肝硬変に対する生体肝移植目的で当科紹介となった。長男をドナーとした生体肝移植を施行し、術前より糖尿病性腎症による腎機能を認め、また術中の下大静脈クランプによる腎うっ血が予想されたため、術後の免疫抑制療法の導入はMycophenolate Mofetil、steroidを中心に行った。術後6日目よりトランスアミラーゼの上昇を認め、急性拒絶を疑いCNIとしてTacrolimusを少量使用したが、腎機能の低下を認めたため中止した。その後は急性拒絶反応なく経過し、腎機能をはじめ、全身状態が安定した術後27日目よりCNIとして低用量のCyclosporinを追加した。その後の経過は良好で、現在も生存中であり、腎機能の悪化もみられない。.
443. 肝内胆管癌に対するR0切除を中心とした集学的治療の現状 補助化学療法や再発時切除の位置づけ.
444. 山下 洋市, 調 憲, 井口 友宏, 二宮 瑞樹, 吉屋 匠平, 松本 佳大, 中川原 英和, 木村 光一, 今井 大祐, 別城 悠樹, 王 観林, 池上 徹, 吉住 朋晴, 川中 博文, 池田 哲夫, 内山 秀昭, 副島 雄二, 前原 喜彦, 肝切除後の胆汁の遺漏 疾患ゼロ目標に向けての予防と管理の試み(Bile leakage after hepatic resection: Our attempts for prevention and management towards zero-morbidity), 日本外科学会雑誌, 115, 臨増2, 105-105, 2014.03.
445. 肝切除術におけるリスク評価と治療成績向上に向けた対策 EOB-MRIを用いた肝切除周術期の解剖に基づいた機能的肝容積評価に関する研究.
446. 肝切除術後門脈血栓症に対する低分子ヘパリンの予防効果の検討.
447. 肝疾患の病態と糖鎖抗原の意義 肝線維化マーカーWFA結合性M2 binding protein(WFA+-M2BP)の臨床的意義各種線維化マーカーとの比較について.
448. 肝癌に対する生体肝移植後の肝癌再発の新たな予後因子 侵襲の程度に基づく組織学的高度脈管侵襲分類の有用性.
449. 肝硬変に対する腹腔鏡下脾摘術を安全に行うためのHALSの適応を明確にした手技の標準化とその適正化.
450. 肝硬変症における脾摘術後門脈血栓に対する予防法の確立.
451. 肝硬変症における脾摘術後の門脈血行動態の変化からみた肝脾相関についての検討
肝硬変症における脾摘術後の門脈血行動態の変化からみた肝脾相関について検討した。腹腔鏡下脾摘術を施行した肝硬変症57例を対象とした。肝機能不良例が2/3を占め、摘出脾重量も平均554gと巨脾症例も多数含まれているため、手術の安全性を考慮し23例に用手補助下腹腔鏡下脾摘術を行い、開腹移行症例は認めなかった。牌摘前後の門脈血流速度に有意な変化を認めなかったが、門脈血流量、門脈断面積、うっ血係数は有意に低下した。肝静脈圧測定を行った18例においてHVPGは有意に低下し、平均低下率は25%であった。門脈血流量は有意に低下し、低下率は12%であった。肝内門脈血管抵抗は、平均21%低下した。末梢血ET-1、肝静脈血ET-1は有意に減少した。末梢血NOxは減少傾向、肝静脈血NOxは増加傾向を示した。.
452. 肝移植における周術期栄養管理による敗血症対策の標準化 敗血症におけるSarcopeniaとアミノ酸代謝の意義.
453. 肝移植におけるイノベーション 生体肝移植後成績向上を目指した治療戦略の構築.
454. 肝移植後の肝癌再発における脳死・生体肝移植の比較.
455. 肝移植術後敗血症ゼロを目指した我々の治療戦略.
456. 肝細胞癌に対する腹腔鏡下系統的肝切除における肝外グリソン鞘処理の実際.
457. 肝細胞癌手術症例におけるoccult B型肝炎ウイルス感染の現状と特徴.
458. 肝細胞癌治療における外科手術の位置づけ 再発肝細胞癌に対する外科治療 3回以上肝切除とSalvage Liver Transplantationの位置づけ.
459. 肝細胞癌治療のガイドライン・コンセンサス・アルゴリズムの検証 肝移植成績からみた肝癌治療アルゴリズムの検証.
460. 肝胆膵領域の腹腔鏡下手術において拡大視効果は何をもたらしたのか 腹腔鏡による拡大視効果を利した肝外グリソン鞘処理による系統的肝切除の実際.
461. 肝葉切除術に対する完全腹腔鏡下切除の功罪 肝葉切除術に対する完全腹腔鏡下切除の利点と課題.
462. 胆嚢・総胆管結石に対する処置とともに生体肝移植を施行した無症候性肝硬変の2例.
463. 胆道癌に対する肝移植
胆道癌に対する肝移植の良好な成績が欧米を中心に報告されつつある。歴史的に胆道癌に対する肝移植は、移植後早期に再発し予後不良で、胆道癌は肝移植の相対的禁忌とされてきた。しかし、最近の報告では症例の厳密な選択は必要であるが、術前補助化学放射線療法と肝移植により、移植後5年生存率は70%前後と他疾患のものと遜色ない。我が国では慢性的な脳死ドナー不足から、肝癌ではミラノ基準内のみが脳死肝移植の適応とされており、胆管癌に対しして肝移植を施行する場合、生体肝移植が必要である。原発性硬化性胆管炎に胆管癌を合併する事が多いが、生体肝移植後は脳死肝移植に比べ原発性硬化性胆管炎の再発が多く、胆管癌に対して生体肝移植を積極的に行うべきか、今後議論を重ねる必要がある。本稿では、胆道癌に対する肝移植に関する最近の欧米からの報告のレビューと自験例の検討から、胆道癌の治療としての肝移植の位置づけについて概説する。(著者抄録).
464. 胆道癌悪性度評価におけるFDG-PET/CTの役割.
465. 脂肪肝ラット温阻血再灌流傷害に関する基礎的研究.
466. 脂肪肝ラット温阻血再灌流傷害に関する基礎的研究.
467. 脂肪肝ラット温阻血再灌流傷害に対するNOX活性化に関する基礎的研究.
468. 腹腔鏡下肝切除 安全な系統的肝切除の実際と問題点 完全腹腔鏡下系統的肝切除のための流入血流遮断と術中ナビゲーション方法の検討.
469. 血液型不適合生体肝移植後に門脈血栓とVeno-occlusive Disease(VOD)を発症した1例.
470. 術中超音波ガイド下に広範囲門脈血栓を完全摘出した生体肝移植の一例.
471. 術前肝細胞癌の診断で、術後肝内胆管癌あるいは混合型肝癌と診断された症例に対する生体肝移植の成績.
472. 進行肝癌における炎症マーカーの意義.
473. 遅発性難治性胆汁漏により汎発性腹膜炎を呈した生体肝移植ドナーの1例 胆汁漏に対するランデブー法の有用性.
474. 門脈血栓合併食道胃静脈瘤の治療経験.
475. 門脈血栓症 肝切除後門脈血栓症症例の臨床経過とその予防法.
476. 高齢者に対する生体肝移植の適応と成績.
477. 二宮 瑞樹, 池田 哲夫, 調 憲, 萱島 寛人, 播本 憲史, 井口 友宏, 杉町 圭史, 山下 洋市, 池上 徹, 佐伯 浩司, 沖 英次, 内山 秀昭, 吉住 朋晴, 副島 雄二, 川中 博文, 森田 勝, 前原 喜彦, 3D-CT画像情報をもとにした肝静脈に対する血管内治療(Three-Dimensional Computed Tomography Image Based Endovascular Treatment for Hepatic Vein), 福岡医学雑誌, 10.15017/1430771, 104, 11, 469-72, 2013.11, 肝静脈吻合が必須の手技である生体肝移植術症例の増加に伴い、術後の肝静脈狭窄に対して経静脈的治療が必要となる症例が増えつつある。肝静脈はその解剖学的位置の特性により、経静脈的治療を行うにあたりいくつかのピットフォールが存在する。不十分な情報のもとに治療を行えば治療効果が得られないのみならず、合併症の発症にもつながる。三次元画像に基づいた治療前シミュレーションが安全で効果的な経静脈的肝静脈ステント治療に有効であったので報告する。(著者抄録).
478. 沖 英次, 坂口 善久, 大垣 吉平, 佐伯 浩司, 池上 徹, 南 一仁, 山下 洋市, 藤 也寸志, 副島 雄二, 安藤 幸滋, 三森 功士, 渡邊 雅之, 杉町 圭史, 内山 秀昭, 吉住 朋晴, 川中 博文, 森田 勝, 池田 哲夫, 前原 喜彦, 76歳以上高齢者に対する完全鏡視下幽門側胃切除術の検討(Totally Laparoscopic Distal Gastrectomy for Elderly Patients with Gastric Cancer), 福岡医学雑誌, 10.15017/1397857, 104, 9, 290-8, 2013.09, 【はじめに】高齢者に対する腹腔鏡下幽門側胃切除術(以下TLDG)の安全性とその有用性は確立されていない。本論文では、76歳以上の高齢者に対するTLDGの安全性と有効性を75歳以下の症例と比較検討した。【症例】2005年4月~2009年3月までの間に行われた完全鏡視下幽門側胃切除138例のうち、76歳以上20例と75歳以下の118例について、術中・術後合併症、術後経過などについて比較した。【結果】術前のASA statusは高齢者群で有意に悪く(P=0.013)、高血圧と呼吸疾患の合併は高齢者で多かった(P=0.032/P=0.005)。術中の出血量や手術時間、入院日数などに両者の違いはなかった。術後合併症は、重症なものは両者に違いはなかったが、創感染など軽微なものが高齢者に多かった。術後1年後の体重減少率や血液データなどに両者の違いは認められなかった。【結語】背景因子には違いはあるが、高齢者のTLDGは若年者と変わらず安全に施行可能であると考えられる。(著者抄録).
479. 戸島 剛男, 吉住 朋晴, 内山 秀昭, 池上 徹, 副島 雄二, 池田 哲夫, 川中 博文, 山下 洋市, 森田 勝, 沖 英次, 三森 功士, 杉町 圭史, 佐伯 浩司, 渡邊 雅之, 調 憲, 前原 喜彦, CD133発現陽性細胞が出現した肝移植後の肝細胞癌再発の1例(Effect of CD133-positive Stem Cells in Repeated Recurrence of Hepatocellular Carcinoma after Liver Transplantation: A Case Report), 福岡医学雑誌, 10.15017/1398608, 104, 10, 383-8, 2013.10, 肝移植は非代償性肝硬変を合併した肝細胞癌の症例に対する治療戦略として確立している。しかしながら、肝移植後に肝細胞癌の再発をみとめることも希ではなく、そのほとんどが移植後1~2年以内におこるとされている。また近年、CD133は現在肝の幹細胞のマーカーとして注目されている。われわれは肝移植後に7回の肺転移を繰り返し、胸腔鏡下に切除可能であった症例を経験した。原発巣、初回、2回目の再発まで癌部におけるCD133は陰性であったのにも関わらず、3回目以降の再発部にはCD133の発現は強陽性であった。患者は肝移植後9年の現在再発なく生存中である。本症例は肝移植後7回の再発を繰り返した。流血中のCD133陽性幹細胞の肝癌再発における臨床的な意義を示唆する貴重な症例と考え報告する。(著者抄録).
480. C型肝炎治療の新展開 生体肝移植後C型肝炎再発に対する治療戦略.
481. Toru Ikegami, Ken Shirabe, Takasuke Fukuhara, Norihiro Furusyo, Kazuhiro Kotoh, Masaki Kato, Shinji Shimoda, Shinichi Aishima, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Maehara, Early extensive viremia, but not rs8099917 genotype, is the only predictor for cholestatic hepatitis C after living-donor liver transplantation., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12003, 43, 6, 621-9, 2013.06, AIM: Cholestatic hepatitis C is one of the most serious but still unaddressed disorders after liver transplantation. METHODS: In this study, we analyzed 49 patients who underwent living-donor liver transplantation (LDLT) to treat hepatitis C virus (HCV) infection. RESULTS: Five patients developed cholestatic hepatitis C, with total bilirubin of 15.2 ± 3.1 mg/dL at diagnosis 6.2 ± 1.0 weeks after LDLT. Univariate analysis showed that larger graft to standard liver volume ratio, higher HCV RNA titer at 2 weeks, earlier peak HCV RNA titer and cytomegalovirus infection were the significant risk factors. The development of cholestatic hepatitis C was not significantly associated with interleukin-28B genotype (rs8099917); four out of five affected patients had the T/T genotype. Multivariate analysis showed that higher HCV RNA titer at 2 weeks was the only significant factor (P = 0.026) for the development of cholestatic hepatitis C. Receiver-operator curve analysis showed that that HCV RNA titer of more than 7.2 log10 IU/mL was the optimal cut-off for characterizing cholestatic hepatitis C. All of the patients were serum HCV RNA negative after treatment with pegylated interferon and ribavirin and all the patients are alive. CONCLUSION: Early extensive viremia, but not the rs8099917 genotype, was the only predictor for cholestatic hepatitis C after LDLT..
482. FDG-PETで高集積を呈した肉腫様変化を伴う肝内胆管癌の1例
症例は59歳,女性.近医にて肝腫瘍を指摘されて当院紹介となった.腹部造影CTにて肝外側区域を占める長径10cm大の分葉状腫瘤性病変を認め,肝内胆管癌と診断した.明らかなリンパ節転移は認めなかったものの,FDG-PETでは高集積(SUVmax=15.30)を呈する腫瘍であり,悪性度の高い腫瘍と考えられた.同症例に対し,肝拡大外側区域切除術を行った.病理組織所見で低分化の胆管細胞癌と診断され,一部に肉腫様変化を伴っていた.免疫組織化学染色ではCK7陽性,VimentinおよびCK19陰性であった.Ki-67 Labelling Indexは28%と高値であり,細胞増殖能の亢進を反映していると考えられた.術後経過は良好で,GEMにより術後補助化学療法を施行し,術後1年現在,無再発生存中である.肉腫様変化を伴う肝内胆管癌は予後不良な疾患であり,FDG-PETでの集積との関連は報告されていない.今回,FDG-PETで高集積を呈した1例を経験したので,若干の文献的考察を加えて報告する.(著者抄録).
483. Takeo Toshima, Mitsuo Shimada, Toru Ikegami, Toru Utsunomiya, Tetsuya Ikemoto, Yuji Morine, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Fairly rare spontaneous disappearance of a hepatic artery aneurysm following living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23676, 19, 8, 929-30, 2013.08.
484. 岡野 慎士, 近藤 晴彦, 戸島 剛男, 中川原 英和, 吉住 朋晴, 副島 雄二, 調 憲, 原田 守, 吉開 泰信, 前原 喜彦, Fas欠損アロ樹状細胞を用いた腫瘍内樹状細胞投与療法は有効な抗腫瘍効果を惹起する(Fas-Beflcient Fully Allogeneic Dendritic Cells Administered Via an Intratumoral Injection Route Show Efficient Antitumor Effects in Mmrine models), 福岡医学雑誌, 104, 1, 15-26, 2013.01, 樹状細胞はプロフェッショナル抗原提示細胞で強力な腫瘍関連抗原特異的CD8T細胞応答を惹起するため、それを利用した樹状細胞免疫療法は強力で特異的ながん免疫療法となることが期待できる。樹状細胞免疫療法において、アロの樹状細胞は、質的量的に樹状細胞が採取困難な患者における代価細胞として期待できるが、その有効性は議論の余地があり、実際、種々のプロトコールで良好な結果が得られていない。本研究において、我々は、Fasが正常なアロの樹状細胞の腫瘍内投与は全く抗腫瘍効果を発揮しないが、Fas欠損アロ樹状細胞を腫瘍内投与すると、同系マウスの樹状細胞に匹敵する抗腫瘍効果を発揮することを初めて報告する。この時、Fasが欠損している同系のマウスから得られた樹状細胞は同系の樹状細胞より強い効果を発揮することはなかったことから、Fasの欠損はアロ樹状細胞にのみにおこる不利な応答を克服するのに必要な分子であることが示唆された。更に、このFas欠損アロ樹状細胞を用いた腫瘍内樹状細胞療法は、宿主の主要組織適合抗原に拘束される腫瘍関連抗原特異的CD8T細胞応答を惹起した。よって、Fas分子の機能抑制を施したアロ樹状細胞は、自己樹状細胞が採取困難な患者の代価樹状細胞として有用である可能性が示唆された。(著者抄録).
485. Gemcitabine+5-Fluorouracil+Cisplatin療法が奏功し根治手術を施行し得た肝転移を伴う膵腺房細胞癌の1例
症例は60歳代男性で、心窩部痛を生じ腹部CT・超音波で膵頭部腫瘍、転移性肝腫瘍と診断された。腹部造影CTで径4cmの不整な造影効果を持つ境界不明瞭で内部不均一な腫瘤を認めた。前方浸潤を認め脾静脈・上腸間膜静脈・下腸間膜静脈の合流部への浸潤が疑われ、肝S7に同様の造影効果を認める径4.5cmの腫瘤を認めた。浸潤性膵管癌の典型例とは異なり明らかな造影効果を認め神経内分泌腫瘍との鑑別が必要と考え、肝生検を行った。比較的均一な腫瘍細胞が腺胞様構造や充実状構造で、免疫組織化学染色においてトリプシン陽性、クロモグラニン-A陰性で膵腺房細胞癌による肝転移と診断した。多剤併用療法であるゲムシタビン+5-フルオロウラシル+シスプラチン(GFP)療法を開始し、GFP療法2クール終了時点で腫瘤は径2cmと縮小を認めた。全身状態も良好で切除により肉眼的根治が可能と判断し膵頭十二指腸切除術、肝部分切除術を行った。腫瘍は上腸間膜静脈・中結腸静脈に強固に癒着していた。門脈を2cm合併切除し膵臓・十二指腸と周囲のリンパ節を一塊として摘出し門脈再建した。術後肝膿瘍・膵液瘻を発症したが経皮的ドレナーシで改善した。術後11ヵ月目に単発の肺転移をきたしゲムシタビン単独療法を行ったが術後23ヵ月目に生検に起因する右胸壁局所再発、単独肝転移を認め右胸壁腫瘍切除術、肝マイクロ波凝固術を行った。化学療法をS-1に変えたが多発肺転移、多発肝転移で術後30ヵ月目に死亡した。.
486. Mikihiro Kohno, Ken Shirabe, Yohei Mano, Jun Muto, Takashi Motomura, Kazuki Takeishi, Takeo Toshima, Masanori Yoshimatsu, Hideki Ijichi, Noboru Harada, Shinichi Aishima, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Granulocyte colony-stimulating-factor-producing hepatocellular carcinoma with extensive sarcomatous changes: report of a case., Surgery today, 10.1007/s00595-012-0202-0, 43, 4, 439-45, 2013.04, This report describes a rare case of hepatocellular carcinoma (HCC) producing granulocyte colony-stimulating factor (G-CSF). A 46-year-old male with chronic hepatitis B, who presented with fever, general malaise, loss of appetite, and weight loss, had a huge liver mass in the portal region. He had marked granulocytosis and his serum level of G-CSF was elevated. Complete tumor resection was performed, and the pathological assessment of the resected specimen revealed HCC with extensive sarcomatous changes and immunohistochemical staining for G-CSF and G-CSF receptor. Only a few cases of G-CSF-producing HCC have been reported, and this is the first case of G-CSF-producing HCC that also expressed G-CSF receptor..
487. HBcAb陽性ドナーから生体肝移植後に核酸アナログからB型肝炎ワクチンへ切り替えて安全に妊娠出産を行った2例
HBc抗体陽性ドナーからの生体肝移植術後、核酸アナログからB型肝炎ワクチンへ切り替え、安全に妊娠・出産を行った2例について報告した。2例は胆道閉鎖症のためHBc抗体陽性ドナーより右葉グラフトを用いた生体肝移植術を受けており、術後はゼフィックスもしくはバラクルードとB型肝炎免疫グロブリン(HBIG)の併用にてHBV再活性化を予防していたが、妊娠可能年齢であることから核酸アナログからB型肝炎ワクチン接種に切替え、HBIGを中止した。2例ともワクチン接種によって十分な能動免疫を獲得でき、B型肝炎再活性化の危険性を下げつつ、安全に健常児を出産することができた。B型肝炎ワクチン接種は、妊娠可能年齢の女性患者がHBc抗体陽性ドナーから肝移植術後に妊娠・出産を経験する際に、核酸アナログの投与を回避する有用な手段になると思われた。.
488. HCV肝炎に対する肝移植 C型肝硬変に対する生体肝移植の総合治療戦略.
489. Hideyuki Konishi, Ken Shirabe, Shohei Yoshiya, Tetsuo Ikeda, Toru Ikegami, Tomoharu Yoshizumi, Ayae Ikawa-Yoshida, Takashi Motomura, Takasuke Fukuhara, Yoshihiko Maehara, Hepatic interferon-gamma-induced protein-10 expression is more strongly associated with liver fibrosis than interleukin-28B single nucleotide polymorphisms in hepatocellular carcinoma resected patients with chronic hepatitis C., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12070, 43, 11, 1139-47, 2013.11, AIM: Single nucleotide polymorphisms (SNP) around IL-28B and interferon (IFN)-stimulated gene (ISG) expression are predictors of response to standard therapy involving IFN for chronic hepatitis C virus (HCV) infection. We analyzed the association between these predictors to improve the prediction of the response to IFN therapy after liver resection for hepatocellular carcinoma (HCC). METHODS: Data were collected from 74 patients with HCV-induced HCC. The IL-28B genotype and hepatic ISG mRNA levels were analyzed to clarify their association, focusing on the progression of liver fibrosis. RESULTS: Fifty patients were identified as having major alleles (rs8099917 TT) and the remaining 24 patients had minor alleles (rs8099917 TG or GG). Hepatic ISG15 expression was lower in the IL-28B major group than that in the IL-28B minor group (P < 0.005). IP-10 expression was similar between the IL-28B major and minor groups (P = 0.44). IP-10 expression was elevated with advancing stages of liver fibrosis in HCV infected patients (P = 0.005). In patients with mild or no fibrosis, the IL-28B major group had lower IP-10 expression than the IL-28B minor group (P = 0.02). However, in patients with advanced fibrosis, IP-10 expression was not different between the IL-28B major and minor groups (P = 0.66). CONCLUSION: Hepatic ISG15 expression is associated with IL-28B polymorphisms, while IP-10 is strongly affected by liver fibrosis..
490. IL28B遺伝子多型を生体移植適応の判断条件として活用したC型肝硬変の一例.
491. Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Takeo Toshima, Norifumi Harimoto, Yo-ichi Yamashita, Shohei Yoshiya, Yuji Soejima, Yoshihiko Maehara, Impact of Tumor Size, Number of Tumors, Neutrophil-to-Lymphocyte Ratio and Des-Gamma-Carboxy Prothrombin in Liver Transplantation for Hepatocellular Carcinoma, GASTROENTEROLOGY, 144, 5, S1044-S1044, 2013.05, 0.
492. Tomoharu Yoshizumi, Toru Ikegami, Shohei Yoshiya, Takashi Motomura, Yohei Mano, Jun Muto, Tetsuo Ikeda, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12016, 43, 7, 709-16, 2013.07, AIM: Hepatocellular carcinoma (HCC) is primarily treated with hepatic resection and/or locoregional therapy. When HCC recurs and further treatment is no longer possible owing to poor liver function, liver transplantation (LT) or living-donor LT (LDLT) is considered. The aim of this study was to clarify risk factors for tumor recurrence after LDLT in patients with recurrent HCC. METHODS: The study comprised 104 patients who had undergone LDLT because of end-stage liver disease with recurrent HCC. The recurrence-free survival rates after the LDLT were calculated. Risk factors for tumor recurrence were identified. RESULTS: The 1-, 3- and 5-year recurrence-free survival rates were 89.6%, 80.3% and 78.4%, respectively. By univariate analysis, the factors affecting recurrence-free survival were the sum of the largest tumor size and number of tumors of 8 or more (P < 0.0001), des-γ-carboxy prothrombin of more than 300 mAU/mL (P = 0.0001), and a neutrophil-to-lymphocyte ratio (NLR) of 4 or more (P = 0.0002), α-fetoprotein of more than 400 ng/mL (P = 0.0001) and bilobar tumor distribution (P = 0.046). A multivariate analysis identified independent risk factors for post-LDLT tumor recurrence including the sum of tumor size and number of tumors of 8 or more (P = 0.0004) and an NLR of 4 or more (P = 0.01). The 1- and 3- year recurrence-free survival rates in the recipients who had both risk factors were 30.0% and 15.0%, respectively. CONCLUSION: LDLT should not be performed for patients who have both independent risk factors after any treatments for HCC..
493. Noboru Harada, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Katsuhiro Asonuma, Yukihiro Inomata, Yoshihiko Maehara, Intrahepatic artery pseudoaneurysm associated with a metallic biliary stent after living donor liver transplantation: report of a case., Surgery today, 10.1007/s00595-012-0302-x, 43, 6, 678-81, 2013.06, An intrahepatic artery pseudoaneurysm (IHAA) is a very rare but potentially lethal complication occurring after liver transplantation. This report presents a case of an IHAA associated with a metallic biliary stent after liver transplantation. A 40-year-old male underwent living donor liver transplantation (LDLT) using a left lobe graft. The bile duct reconstruction was performed with Roux-en-Y hepaticojejunostomy. He developed obstructive jaundice 5 years after LDLT, and had biliary stricture of the anastomosis area, therefore, the two metallic biliary stents were finally positioned at the stricture of the biliary tract. He suddenly developed hematemesis 8 years after LDLT, and computerized tomography scan showed an IHAA. Although seven interlocking detachable coils were placed at the neck of the aneurysm, hematemesis recurred 3 days after the initial embolization. Therefore, retransplantation was successfully performed 25 days after the embolization of IHAA using a right lobe graft from his son. In conclusion, metal stent insertion can lead to the fatal complication of HAA. The placement of a metallic stent could have been avoided in this case. Percutaneous metallic stent insertion for biliary stenosis after liver transplantation should therefore only be performed in carefully selected patients..
494. Hiroto Kayashima, Ken Shirabe, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Liver regeneration and venous collateral formation in the right lobe living-donor remnant: segmental volumetric analysis and three-dimensional visualization., Transplantation, 10.1097/TP.0b013e31827147d8, 95, 2, 353-60, 2013.01, BACKGROUND: In left lobe (LL) living-donor liver transplantation (LDLT), hepatic venous congestion (HVC) caused by ligation of the middle hepatic vein tributaries is unavoidable in the right lobe (RL) donor remnant. METHODS: To clarify the impact of HVC on liver regeneration and venous collateral formation (VCF), we used three-dimensional computed tomography to examine the volumes of total/segmental liver and HVC and the degree of VCF; preoperative data were compared with data obtained on postoperative day (POD) 35 in 13 LL LDLT donors. RESULTS: On POD 35, the congestion rate decreased from 32.5% to 1.6% and the total liver regeneration rate was 81.7%. Preoperatively, the anterior sector-to-RL volume ratio was significantly lower, and the posterior sector-to-RL volume ratio was significantly higher than postoperatively (56.7% vs. 52.9%, P<0.01, and 36.9% vs. 41.5%, P<0.01, respectively). There was no correlation between degree of HVC and liver regeneration. Obvious VCF was found in five (38.5%) cases. The RL and posterior sector volume per square meter of body surface area in the VCF group were significantly lower than that in the non-VCF group (412 cm/m vs. 492 cm/m, P<0.01, and 140 cm/m vs. 190 cm/m, P<0.01, respectively). The preoperative congestion rate and liver regeneration rate were not significantly different between the groups. CONCLUSIONS: Reconstruction of the middle hepatic vein tributaries in the RL donor remnant might not be necessary in LL LDLT, because the HVC improved dramatically by POD 35 regardless of the development of VCF..
495. NBNC型肝癌(HCC)の切除例の臨床的病理学的特徴 Nicotinamide phosphoribosyltransferase(NMAPT1)の関与.
496. Takashi Motomura, Ken Shirabe, Yohei Mano, Jun Muto, Takeo Toshima, Yuichiro Umemoto, Takasuke Fukuhara, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment., Journal of hepatology, 10.1016/j.jhep.2012.08.017, 58, 1, 58-64, 2013.01, BACKGROUND & AIMS: Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Preoperative neutrophil-lymphocyte ratio (NLR) is a predictor of patient prognosis, but its mechanism has never been clarified. METHODS: We assessed outcomes in 158 patients who had undergone living-donor liver transplantation (LDLT) for HCC. Recurrence-free survival (RFS) was determined in patients with high (≥ 4) and low (<4) NLR. Levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68, and CD163 were measured. RESULTS: The 5-year RFS rate was significantly lower in patients with high (n=26) than with low (n=132) NLR (30.3% vs. 89.0%, p<0.0001), in patients with high (n=15) than with low (n=79) NLR who met the MC (73.6% vs. 100%, p=0.0008) and in patients with high (n=11) than with low (n=53) NLR who exceeded the MC (0% vs. 76.1%, p=0.0002). Tumor expression of VEGF, IL8, IL-17, CD68, and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 levels were significantly higher in the high-NLR group (p=0.01 each). The density of peritumoral CD163 correlated with the density of peritumoral IL-17-producing cells (p=0.04) and was significantly higher in the high-NLR group (p=0.005). CONCLUSIONS: NLR predicts outcomes after LDLT for HCC via the inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC..
497. Toshiro Masuda, Ken Shirabe, Shohei Yoshiya, Rumi Matono, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Hideo Baba, Yoshihiko Maehara, Nutrition support and infections associated with hepatic resection and liver transplantation in patients with chronic liver disease, Journal of Parenteral and Enteral Nutrition, 10.1177/0148607112456041, 37, 3, 318-326, 2013.05, Malnutrition is common in liver cirrhotic patients who will undergo liver resection or liver transplantation. A precise evaluation of their nutrition status is thus difficult because of the presence of ascites and the edema caused by their impaired protein synthesis. Both perioperative enteral and parenteral nutrition have benefits in reducing the morbidity and mortality of liver surgery, and in general, oral nutrition supplements are recommended. Branched-chain amino acids (BCAAs) promote protein and glycogen synthesis and regulate immune system function. Synbiotics, a combination of pro- and prebiotics, is reported to enhance immune responses. Oral nutrition support with BCAAs, synbiotics, and an immune-enhancing diet have a beneficial effect on preventing the perioperative infections associated with hepatic resection or liver transplantation. © 2012 American Society for Parenteral and Enteral Nutrition..
498. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Takeo Toshima, Takashi Motomura, Yoshihiko Maehara, One-step reconstruction of the right inferior hepatic veins using auto-venous grafts in living-donor liver transplantation., Surgery today, 10.1007/s00595-012-0449-5, 43, 7, 769-76, 2013.07, PURPOSES: Reconstruction of the right inferior hepatic vein (RIHV) presents a major technical challenge in living donor liver transplantation (LDLT) using right lobe grafts. METHODS: We studied 47 right lobe LDLT grafts with RIHV revascularization, comparing one-step reconstruction, performed post-May 2007 (n = 16), with direct anastomosis, performed pre-May 2007 (n = 31). RESULTS: In the one-step reconstruction technique, the internal jugular vein (n = 6), explanted portal vein (n = 5), inferior vena cava (n = 3), and shunt vessels (n = 2) were used as venous patch grafts for unifying the right hepatic vein, RIHVs, and middle hepatic vein tributaries. By 6 months after LDLT, there was no case of occlusion of the reconstructed RIHVs in the one-step reconstruction group, but a cumulative occlusion rate of 18.2 % in the direct anastomosis group. One-step reconstruction required a longer cold ischemic time (182 ± 40 vs. 115 ± 63, p < 0.001) and these patients had higher alanine transaminase values (142 ± 79 vs. 96 ± 46 IU/L, p = 0.024) on postoperative day POD 7. However, the 6-month short-term graft survival rates were 100 % with one-step reconstruction and 83.9 % with direct anastomosis, respectively. CONCLUSION: One-step reconstruction of the RIHVs using auto-venous grafts is an easy and feasible technique promoting successful right lobe LDLT..
499. Yohei Mano, Ken Shirabe, Yo-Ichi Yamashita, Norifumi Harimoto, Eiji Tsujita, Kazuki Takeishi, Shinichi Aishima, Toru Ikegami, Tomoharu Yoshizumi, Takeharu Yamanaka, Yoshihiko Maehara, Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis., Annals of surgery, 10.1097/SLA.0b013e318297ad6b, 258, 2, 301-5, 2013.08, OBJECTIVE: To clarify the prognostic value of the preoperative blood neutrophil-to-lymphocyte ratio (NLR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). BACKGROUND: Although a high NLR has been reported to be a predictor of poor survival in patients with various cancers, it has not been extensively examined in patients with HCC. METHODS: This retrospective study enrolled 958 patients who underwent hepatectomy without preoperative therapy for HCC from 1996 to 2009. Clinicopathological parameters, including NLR, were evaluated to identify predictors of overall and recurrence-free survival after hepatectomy. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. The best cutoff was determined with time-dependent receiver operating characteristic curve. To determine the mechanism of NLR elevation, immunohistological examination using CD163 staining was performed in 150 patients. RESULTS: Univariate and multivariate analyses showed that NLR was an independent prognostic factor in overall and recurrence-free survival. The best cutoff of NLR was 2.81, and 238 of 958 patients (24.8%) had NLR of more than 2.81. The 5-year survival rate after hepatectomy was 72.9% in patients with NLR less than 2.81 and 51.5% in those with NLR 2.81 or more (P < 0.0001). CD163-positive cell counts were significantly higher in tumors in the group with NLR 2.81 or more than in the group with NLR less than 2.81 (P = 0.0004). CONCLUSIONS: Our results show that NLR is an independent predictor of survival after hepatectomy in patients with HCC. Accumulation of tumor-associated macrophages in the tumor is associated with a high NLR..
500. Norifumi Harimoto, Ken Shirabe, Hidekazu Nakagawara, Takeo Toshima, Yo-Ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Yoshihiko Maehara, Prognostic factors affecting survival at recurrence of hepatocellular carcinoma after living-donor liver transplantation: with special reference to neutrophil/lymphocyte ratio., Transplantation, 10.1097/TP.0b013e3182a53f2b, 96, 11, 1008-12, 2013.12, BACKGROUND: In living-donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC), it is important to predict not only who may be susceptible to recurrence but also who may survive longer. The neutrophil/lymphocyte ratio (NLR) is useful to properly assess the patient without decreasing the long-term survival after LDLT. In this study, we investigated the relationship between NLR and prognosis of patients with recurrent HCC after LDLT. METHODS: In total, 167 LDLTs for HCC were enrolled in this study. Clinicopathologic factors for HCC recurrence after LDLT were investigated and prognostic factors were examined with respect to survival. RESULTS: The following factors were found to be significant in patients with HCC recurrence compared with the controls: α-fetoprotein ≧300 ng/mL, des-γ-carboxyprothrombin ≧300 mAU/mL, NLR ≧4, tumor number >3, tumor size ≧5 cm, duration of last treatment of HCC to LDLT <3 months, Milan criteria exceeded, histologic tumor number ≧10, histologic tumor size >5 cm, poor differentiation, presence of histologic vascular invasion, adjuvant chemotherapy, and interferon therapy against patients with hepatitis C virus. Male sex, interferon therapy against patients with hepatitis C virus, α-fetoprotein ≧300 ng/mL at recurrence, NLR ≧4 at recurrence, and nonsurgical resection for recurrent HCC were significantly related to poor prognosis. The 3-year survival rate after recurrence was 0% in patients with NLR ≧4 and 43.6% in patients with NLR <4. NLR was reelevated after LDLT in patients who later died; however, NLR gradually decreased in surviving patients. CONCLUSION: NLR at recurrence is a prognostic factor affecting survival after recurrence in LDLT for HCC..
501. Tetsuo Ikeda, Yohei Mano, Kazutoyo Morita, Naotaka Hashimoto, Hirohito Kayashima, Atsuro Masuda, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Pure laparoscopic hepatectomy in semiprone position for right hepatic major resection., Journal of hepato-biliary-pancreatic sciences, 10.1007/s00534-012-0558-y, 20, 2, 145-50, 2013.02, BACKGROUND: Pure laparoscopic liver resection is technically difficult for tumors located in the dorsal anterior and posterior sectors. We have developed a maneuver to perform pure laparoscopic hepatectomy in the semiprone position which was developed for resecting tumors located in these areas. METHODS: The medical records have been reviewed retrospectively in 30 patients who underwent laparoscopic liver resection in the semiprone position for carcinoma in the dorsal anterior or posterior sectors of the right liver between 2008 and 2011. RESULTS: Seventeen liver tumors were primary liver tumors and 13 were colorectal metastases. Of the 30 patients, 11 (36.6 %) underwent major hepatectomy [right hemihepatectomy in 7 (23.3 %) and posterior sectionectomy in 4 (13.3 %)]. Anatomical minor resection, such as S6 or S7 segmentectomy, was performed in five patients (16.6 %). Five patients with liver metastasis underwent a simultaneous laparoscopic resection. There was no mortality, reoperation, or conversion to open procedures. There were no hepatectomy-related complications such as postoperative bleeding, bile leakage, or liver failure. CONCLUSIONS: Pure laparoscopic hepatectomy in the semiprone position for tumors present in the dorsal anterior and posterior sectors is feasible and safe. This method expands the indications for laparoscopic liver resection for tumors..
502. Shohei Yoshiya, Ken Shirabe, Yoshihiro Matsumoto, Tetsuo Ikeda, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Yoshihiko Maehara, Rendezvous ductoplasty for biliary anastomotic stricture after living-donor liver transplantation., Transplantation, 10.1097/TP.0b013e31828a9450, 95, 10, 1278-83, 2013.05, BACKGROUND: Biliary anastomotic stricture (BAS) after living-donor liver transplantation (LDLT) is difficult to manage. We used rendezvous ductoplasty (RD) to treat BAS after LDLT. METHODS: We retrospectively analyzed 53 patients with BAS after adult-to-adult LDLT with duct-to-duct biliary reconstruction. RESULTS: BAS was classified according to endoscopic retrograde cholangiography findings after normal-pressure contrast injection: type I (n=32) in which the stricture was visualized; type II (n=13) in which the common hepatic duct and graft intrahepatic ducts were visualized, but the stricture was not visualized; or type III (n=8) in which the stricture and graft intrahepatic ducts were not visualized. In right lobe grafts, types II and III occurred more frequently than type I (P=0.0023). Type I had significantly shorter cold ischemic time (76±11 vs. 118±12 min; P=0.0155) and warm ischemic time (38±2 vs. 49±3 min; P=0.0069) than types II and III. The number of attempts to pass the guidewire through the stricture was significantly lower in type I (1.2±0.2 attempts) than type II (2.2±0.2 attempts; P=0.0018) or type III (2.8±0.3 attempts; P<0.0001). The treatment success rate was 78.1% for type I, 38.5% for type II, and 50.0% for type III (P=0.0282). RD was the first successful treatment in a higher proportion of types II and III patients than type I patients (66.7% vs. 6.3%; P<0.0001). Cumulative treatment success rates were not significantly different between the RD and the non-RD groups (P=0.0920). CONCLUSIONS: RD was a useful treatment for difficult cases of BAS after LDLT and achieved successful outcomes..
503. Yoshihiro Matsumoto, Toru Ikegami, Kazutoyo Morita, Tomoharu Yoshizumi, Hiroto Kayashima, Ken Shirabe, Yoshihiko Maehara, Renoportal anastomosis in right lobe living donor liver transplantation: report of a case., Surgery today, 10.1007/s00595-012-0351-1, 43, 11, 1316-20, 2013.11, End-stage liver disease is often accompanied by thrombosis of the portal vein and the formation of splanchnic collateral vessels. Successful liver transplantation in such situations is more likely if the surgeon uses a strategy to establish a graft inflow. A 59-year-old male with a decompensated liver secondary to idiopathic portal hypertension underwent living donor liver transplantation (LDLT) using a right lobe liver graft donated from his son. His portal venous trunk was atrophied and a splenorenal shunt drained the mesenteric venous flow into the systemic circulation. LDLT was performed with renoportal anastomosis (RPA) using his right internal jugular vein as an interposed venous graft, without dissecting the collateral vessels. Although he developed temporary functional hyperbilirubinemia, he was discharged from the hospital 23 days after LDLT. This case suggests that RPA is a useful technique to manage patients with an obstructed portal vein and a splenorenal shunt..
504. Yo-Ichi Yamashita, Ken Shirabe, Takeo Toshima, Eiji Tsuijita, Kazuki Takeishi, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara, Risk factors for recurrence after curative resection of hepatitis C-related hepatocellular carcinoma in patients without postoperative interferon therapy., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12091, 43, 12, 1313-20, 2013.12, AIM: Hepatitis C (HC)-related hepatocellular carcinoma (HCC; HC-HCC) is highly recurrent. METHODS: From 1995-2007, 183 curative hepatic resections for primary solitary HC-HCC without postoperative interferon therapy were included in this study. The patients were divided into three groups: (i) 2 cm or less (n = 56); (ii) more than 2 cm to less than 5 cm (n = 79); and (iii) 5 cm or more (n = 48). Independent risk factors for HC-HCC recurrence for each group were determined. RESULTS: Independent risk factors for recurrence were aspartate aminotransferase or alanine aminotransferase (AST/ALT) of 80 IU/L or more (hazard ratio [HR], 2.1; P = 0.02) in patients with HCC of 2 cm or less, des-γ-carboxy prothrombin of 100 mAU/mL or more (HR, 2.5; P = 0.02) and AST/ALT of 80 IU/L or more (HR, 2.1; P = 0.04) in patients with HCC of more than 2 cm to less than 5 cm, and the presence of macroscopic portal vein tumor thrombus (HR, 2.8; P = 0.02) and AST/ALT of 80 IU/L or more (HR, 2.1; P = 0.04) in patients with HCC of 5 cm or more. All 13 late recurrences of 1 year or more after hepatic resection (27.1%) in patients with HCC of 5 cm or more were accompanied by AST/ALT of 80 IU/L or more. CONCLUSION: AST/ALT of 80 IU/L or more is an independent risk factor for the recurrence of primary solitary HC-HCC after curative resection irrespective of the primary HC-HCC size..
505. Yuji Soejima, Jyun Muto, Rumi Matono, Mizuki Ninomiya, Tetsuo Ikeda, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Ken Shirabe, Yoshihiko Maehara, Strategic breakthrough in adult ABO-incompatible living donor liver transplantation: Preliminary results of consecutive seven cases, Clinical Transplantation, 10.1111/ctr.12060, 27, 2, 227-231, 2013.03, ABO-incompatibility is a major obstacle to expanding exiguous donor pools in adult liver transplantation, especially in countries where grafts from deceased donors are uncommon. We present our preliminary results of ABO-incompatible (ABO-I) adult living donor liver transplantation (LDLT) using a new, simple protocol. Seven consecutive cases of ABO-I LDLT were managed by the same protocol including pre-operative administration of a single dose of rituximab (375 mg/m2) followed by three to five sessions of plasma exchange before LDLT without portal infusion therapy. The triple immunosuppression protocol consisted of tacrolimus, mycophenolate mofetil and steroids, with mycophenolate mofetil starting seven d before LDLT. Splenectomy was performed for all cases. All patients are alive (100% survival) with a mean follow-up of 852 d (715-990 d). Neither antibody-mediated nor hyperacute rejection were encountered. There was only one episode of mild acute cellular rejection, for which steroid augmentation was effective. The median preformed isoagglutinin antibody titer before plasma exchange was 256, while the median antibody titer immediately before LDLT was 16. In conclusion, adult ABO-I LDLT results were excellent - comparable or even superior to those of ABO-compatible LDLT. ABO-I adult LDLT has now become a more applicable modality without the need for an appropriate donor. © 2013 John Wiley &
Sons A/S..
506. Toru Ikegami, Ken Shirabe, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Yo-ichi Yamashita, Norifumi Harimoto, Takeo Toshima, Shohei Yoshiya, Tetsuo Ikeda, Yoshihiko Maehara, Strategies for successful left-lobe living donor liver transplantation in 250 consecutive adult cases in a single center., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.11.011, 216, 3, 353-62, 2013.03, BACKGROUND: Living donor liver transplantation (LDLT) using left-lobe grafts was not generally recognized as feasible due to the problem of graft size. STUDY DESIGN: We retrospectively evaluated strategies for successful left-lobe LDLT in 250 consecutive cases stratified into 2 eras: Era 1 (n = 121), in which surgical procedures were continually refined, and Era 2 (n = 129), in which established procedures were used. RESULTS: Graft volume (GV) did not affect the incidence of graft function or survival. Era 2 patients had decreased portal vein (PV) pressure at closure (16.0 ± 3.5 mmHg vs 19.1 ± 4.6 mmHg, p < 0.01), increased PV flow/GV (301 ± 125 mL/min/100g vs 391 ± 142 mL/min/100g, p < 0.01), and improved graft survival rate (1-year: 90.6% vs 81.8%. p < 0.01) despite the smaller GV/standard volume (SLV) ratio (36.2% ± 5.2% vs 41.2% ± 8.8%, p < 0.01) compared with Era 1. Patients in Era 2 had lower PV pressure and greater PV flow (y = 598-5.7 x, p = 0.02) at any GV/SLV compared with cases in Era 1 (y = 480-4.3 x, p < 0.01), representing greater graft compliance. Univariate analysis for graft survival showed that Era 1, Model for End-Stage Liver Disease (MELD) score ≥ 20, inpatient status, closing portal venous pressure ≥ 20 mmHg, no splenectomy, and operative blood loss ≥ 10 L were the risk factors for graft loss, and multivariate analysis showed that Era 1 was the only significant factor (p < 0.01). During Era 2, development of primary graft dysfunction was associated with inpatient recipient status (p = 0.02) and donor age ≥ 45 years (p < 0.01). CONCLUSIONS: The outcomes of left-lobe LDLT were improved by accumulated experience and technical developments..
507. Yo-Ichi Yamashita, Ken Shirabe, Eiji Tsujita, Kazuki Takeishi, Tetsuo Ikeda, Tomoharu Yoshizumi, Yoshinari Furukawa, Teruyoshi Ishida, Yoshihiko Maehara, Surgical outcomes of pancreaticoduodenectomy for periampullary tumors in elderly patients., Langenbeck's archives of surgery, 10.1007/s00423-013-1061-x, 398, 4, 539-45, 2013.04, BACKGROUNDS: Pancreaticoduodenectomy (PD) is an aggressive surgery with considerable operative risks, but offers the only chance for cure in patients with periampullary tumors. A growing number of elderly patients are being offered PD because of the aging of populations in developed countries. We examined surgical outcomes of PD in patients aged 75 years and older (≥75 years). METHODS: A retrospective cohort study was performed in 65 consecutive patients who underwent PD for periampullary tumors at a single medical center during the 5 years from 2006 to 2010. We analyzed surgical outcomes such as mortality and morbidity after PD in patients aged ≥75 years (n = 21) compared to those in patients aged <75 years (n = 44). RESULTS: The positive rate of comorbidities such as hypertension was significantly higher in patients aged ≥75 years than in patients aged <75 years (76 vs. 48 %; p = 0.03). The incidence of wound infection was significantly higher in patients aged ≥75 years than in patients aged <75 years (19 vs. 0 %; p < 0.01). However, there was no significant difference in the mortality rate (0 vs. 2 %; p = 0.49) or the overall morbidity rate (33 vs. 32 %; p = 0.90). There was no significant difference in changes in body weight or serum albumin levels during the 3 months after PD between the two groups, but the recovery of serum prealbumin levels from 1 to 3 months after PD in patients aged ≥75 years was significantly delayed compared to that in patients aged <75 years (p = 0.04). There was no statistically significant difference in long-term survival between the two groups. CONCLUSIONS: Advanced age alone should not discourage surgeons from offering PD, although nutritional supports after PD for elderly patients aged ≥75 years are needed..
508. Makoto Hayashida, Yusuke Yanagi, Genshiro Esumi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Tomoaki Taguchi, THE OUTCOME OF LIVING DONOR LIVER TRANSPLANTATION FOR BILIARY ATRESIA : THE COMPARISON OF ADULTS AND CHILDREN, PEDIATRIC TRANSPLANTATION, 17, 100-100, 2013.08.
509. Shohei Yoshiya, Ken Shirabe, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo-ichi Yamashita, Norifumi Harimoto, Takeo Toshima, Yoshihiko Maehara, The Causes, Risk Factors, and Outcomes of Early Relaparotomy After Living Donor Liver Transplantation, GASTROENTEROLOGY, 144, 5, S1032-S1032, 2013.05, 0.
510. Y. Yamashita, K. Shirabe, T. Toshima, N. Harimoto, T. Ikegami, T. Yoshizumi, Y. Soejima, T. Ikeda, Y. Maehara, The predictors for micro-invasion of hepatocellular carcinoma <= 2 cm, EUROPEAN JOURNAL OF CANCER, 49, S206-S206, 2013.09.
511. 【最新 肝胆膵脾手術アトラス】 脾臓 肝移植における脾臓摘出術.
512. 【肝移植-現状と展望】 C型肝炎、肝硬変に対する肝移植
C型肝炎,肝硬変は肝移植適応疾患のなかで最多となっている.C型肝硬変は肝細胞不全であり,低ビリルビン値であっても急激に状態悪化すること,移植後グラフト再感染が必発であることから,他の適応疾患に比べ術後予後が不良である.術後予後向上のためには,適切な移植時期の選定,および術後再発に対するインターフェロン治療奏効率の向上が必須である.当科では,治療奏効率向上のため,副作用軽減のために低用量からの導入,術中同時脾臓摘出術,不反応症例へのインターフェロン交替療法,ウイルス因子・宿主因子の遺伝子解析による治療効果予測を行っている.今後は新規薬剤の導入による,さらなる術後成績向上が期待される.(著者抄録).
513. 【肝胆膵手術の適応決定-術式選択からみた術前・術中診断の要点-】 生体肝移植ドナーおよびレシピエント手術.
514. 【肝胆膵腹腔鏡下手術の秘策;合併症・偶発症回避のコツ】 腹腔鏡下膵切除術 腹腔鏡下膵体尾部切除時の郭清・膵切離のコツ 良性疾患もしくは良悪性境界病変に対する脾および脾動静脈を温存する腹腔鏡下膵体尾部切除術.
515. 【臓器移植の現況と今後の展望】 肝移植の現況と今後の展望
さまざまな創意と工夫により、わが国の成人間生体肝移植の成績は良好となってきた。本稿では、その過程で明らかになった知見の中から、グラフトの選択、門脈血流の制御あるいは経腸栄養など短期成績改善に向けた戦略、長期成績改善のためのC型肝炎再発例に対する治療と肝細胞癌に対する肝移植適応基準の作成、さらに薬剤性腎障害に対する工夫について概説する。また、生体ドナーの安全性の絶対的確保、quality of lifeに関する諸問題等を考慮すると、わが国においても脳死下臓器提供を増加させ、次の世代に引き継いでいくことが大変重要である。脳死下臓器提供啓発に向けた我々の活動についても紹介する。(著者抄録).
516. ジャイロセンサー付き3D内視鏡、内視鏡ホルダロボット、循環式気腹装置のトリオがもたらす次世代内視鏡下手術の展望 ジャイロセンサー付き高解像度3D内視鏡-内視鏡ホルダロボットViKY-循環式気腹装置エアシール・インテリジェント・フローシステムのトリオがもたらす次世代内視鏡下手術の展望 肝切除術における有用性の検討.
517. ハイリスク食道癌に対する手術適応の拡大.
518. 侵襲下における栄養療法の新展開 生体肝移植成績向上を目指した栄養療法の総合戦略.
519. 個別化治療を目指した肝細胞癌(HCC)の新たな総合治療戦略の構築.
520. 健常成人における体表面積を用いた標準骨格筋面積算出式の作成の試み CTによるSarcopeniaの診断にむけて.
521. 先天性ATIII欠乏症を伴う胆嚢癌疑いの症例に対して拡大胆嚢摘出術を施行した1例
76歳女。先天性アンチトロンビンIII(ATIII)欠乏症にてワーファリン内服中であり、血栓症の精査にて胆嚢腫瘍の可能性を指摘された。紹介入院時のATIII活性は39%であり、腹部CTでは胆嚢壁は全体的に肥厚して結石やdebrisと考える構造を認めた。胆汁細胞診はgroup 1で悪性所見は認めなかったが、悪性腫瘍の可能性も否定できなかったため、開腹拡大胆嚢摘出術を行い、胆嚢腺筋症に伴う慢性胆嚢炎と診断された。周術期管理は凝固機能亢進状態に伴う血栓症の予防に重点を置き、ATIII濃縮製剤による補充療法および術後早期からのワーファリン再開を含めた抗凝固療法と、理学療法を併用した結果、術直前のATIII活性は61%に留まったが、術後は明らかな血栓形成を認めることなく良好に経過し、術後7ヵ月現在まで血栓形成を認めていない。.
522. 内視鏡下肝切除術の手術手技 完全腹腔鏡下肝切除術:肝右葉後区域、上前区域の腫瘍に対する左半腹臥位、経胸-経横隔膜ポートを用いたDual approach、Bipolar Irrigation systemの有用性の検討.
523. 切除不能巨大肝腫瘍に対する体外肝切除術の手術手技と要点.
524. 切除肝細胞癌におけるProgrammed Death of Ligand 1(PDL1)発現の生物学的意義.
525. 切除肝細胞癌におけるProgrammed Death of Ligand 1(PDL1)発現の生物学的意義.
526. 単発再発肝細胞癌(≦5cm)に対する系統的切除の臨床成績.
527. 原発性胆汁性肝硬変に対する生体肝移植の予後因子および晩期死因に関する検討.
528. 外科代謝とアミノ酸 生体肝移植後における術後至適栄養管理の追求 敗血症の危険因子としてのSarcopeniaとグルタミン代謝の意義.
529. 外科系各科における鏡視下手術 転移性肝癌に対する腹腔鏡下肝切除術の工夫と成績.
530. 外科領域におけるゲノム研究の進歩 IL28B遺伝子多型解析による、肝移植後C型肝炎再発に対する革新的治療戦略.
531. 完全腹腔鏡下系統的肝切除術の工夫と成績.
532. 完全腹腔鏡下系統的肝切除術の安全性と要点.
533. 巨大肝細胞癌(>or=10cm)に対する肝切除成績 その適応と限界.
534. 当院における小児肝移植の術後合併症と予後.
535. 急性肝不全に対する総合的治療戦略.
536. 内山 秀昭, 調 憲, 吉住 朋晴, 池上 徹, 副島 雄二, 池田 哲夫, 川中 博文, 山下 洋市, 森田 勝, 沖 英次, 三森 功士, 杉町 圭史, 佐伯 浩司, 渡邊 雅之, 竹中 賢治, 前原 喜彦, 急性胆嚢炎に対する治療指針 全身麻酔可能と判断される場合には準緊急で腹腔鏡下胆嚢摘出術を施行するの検討(Verification of Our Therapeutic Criterion for Acute Cholecystitis: "Perform a Subemergency Laparoscopic Cholecystectomy when a Patient is Judged to be able to Tolerate General Anesthesia": The Experience, 福岡医学雑誌, 10.15017/1398602, 104, 10, 339-43, 2013.10, 【背景】急性胆嚢炎に対する現在の我々の治療方針は"全身麻酔可能と判断される場合には準緊急で腹腔鏡下胆嚢摘出術を行う"である。この治療方針の正当性を検証した。【方法】2011年4月から2013年9月までに行った急性胆嚢炎に対する腹腔鏡下胆嚢摘出術症例21例を対象とした。準緊急腹腔鏡下胆嚢摘出術は上記の治療指針に従って行った(準緊急群;n=16)。全身麻酔が安全に施行できないと判断された場合には経皮経肝胆嚢ドレナージを行い、全身状態が安定した後に腹腔鏡下胆嚢摘出術を行った(PTGBD群;n=5)。【結果】全症例に対して腹腔鏡で胆嚢摘出術を完遂した。平均総入院日数はPTGBD群と比較して準緊急群で有意に短かった(11.5±5.3対30.4±8.5日)。準緊急群では術前に既に酸素投与を必要としていた2例に術後の呼吸不全を認め、術後に人工呼吸管理を必要とした。一方PTGBD群では術後合併症を1例も認めなかった。【結語】急性胆嚢炎に対する準緊急腹腔鏡下胆嚢摘出術は、全身麻酔が可能と判断される場合には安全に施行することができ、早期の退院が可能であった。状態が不安定で全身麻酔が安全に施行することが難しいと判断される患者においてはPTGBDを施行した後、状態が安定してから腹腔鏡下胆嚢摘出術を行うことが絶対的に安全と考えられた。(著者抄録).
537. 慢性肝疾患における成人間生体肝移植後の術後食道胃静脈瘤の危険因子と対策.
538. 成人に到達した胆道閉鎖症症例に対する生体肝移植.
539. 副島 雄二, 調 憲, 吉住 朋晴, 内山 秀昭, 池上 徹, 山下 洋市, 池田 哲夫, 川中 博文, 杉町 圭史, 三森 功士, 渡邊 雅之, 森田 勝, 沖 英次, 佐伯 浩司, 前原 喜彦, 成人生体肝移植後門脈血栓症に対するRexシャント術(Rex Shunt for Portal Vein Thrombosis after Adult Living Donor Liver Transplantation), 福岡医学雑誌, 10.15017/1430770, 104, 11, 464-8, 2013.11, 肝移植後の門脈血栓症は比較的希な合併症であるが、門脈圧亢進症、グラフトロスにつながる重篤な合併症である。上腸間膜静脈と左門脈臍部間をバイパスするいわゆる「Rexシャント」は小児肝移植における門脈血栓に対する有用な治療オプションであるが、十分な長さのグラフトの確保が難しいため成人例における報告はいまだないのが現状である。本論文では、成人左葉生体肝移植後の門脈血栓症に対して、自身の内頸静脈と卵巣静脈をシャントグラフトとしてRexシャントを施行した一例を報告する。本シャントは術後2日目に閉塞したが、緊急血栓摘出および抗凝固療法を施行により術後8ヵ月の時点において開存中である。自家静脈を用いたRexシャント術は、成人症例においても生体肝移植後の門脈血栓症の治療法として有用な治療オプションである。(著者抄録).
540. 成人間生体肝移植術後のSurgical site infection(SSI)に関する検討.
541. 改正臓器移植法施行後の肝移植の現状と展望 脳死肝移植数増加に向けた対策に関する検討.
542. 最近のVTE(静脈血栓塞栓症)の予防と治療 肝切除におけるVTE予防のための低分子ヘパリン投与の安全性と門脈血栓症に対する予防効果.
543. 次世代の標準化に向けた肝癌の外科治療「開腹・鏡視下」 腹腔鏡下肝切除 肝全域での標準化への工夫 Semiprone、Bidirectional approach、Silicon Irrigatorの有用性.
544. 生体肝移植におけるドナーの安全性 生体肝移植ドナー手術安全性の再考 441例の手術経験から.
545. 生体肝移植における肝静脈再建の工夫 右下肝静脈を有する右葉グラフトにおける一括再建の有用性.
546. 生体肝移植の手術手技の工夫 生体肝移植における門脈圧コントロールを目指した胃食道静脈シャントと左胃動脈の一括切離法.
547. 生体肝移植グラフトに発症した感染性肝嚢胞の一例.
548. 永田 茂行, 調 憲, 杉町 圭史, 池上 徹, 吉住 朋晴, 内山 秀昭, 山下 洋市, 佐伯 浩司, 川中 博文, 三森 功士, 渡邊 雅之, 祇園 智信, 副島 雄二, 池田 哲夫, 辻谷 俊一, 前原 喜彦, 生体肝移植ドナーに対する抗酸化物質を用いた術前免疫栄養に関する予備試験(A Pilot Study of Preoperative Immunonutrition with Antioxidants in Living Donor Liver Transplantation Donors), 福岡医学雑誌, 104, 12, 530-8, 2013.12, 【目的】活性酸素が過剰に産生されることで外科手術後に組織破壊や臓器機能不全を招来することがこれまで報告されている。本研究では肝切除を受ける患者に抗酸化物質を含む術前免疫栄養を行い、術後経過に与える効果を検討した。【対象と方法】23名の生体肝移植ドナーを対象とした。通常の食事に加え、術前5日間抗酸化物質を豊富に含む栄養剤を摂取した実験群(AO群)と通常の食事のみのコントロール群(CT群)に無作為に分けた。フリーラジカル自動分析装置を用いて患者血清を吸光光度分析法にて抗酸化力を測定した。【結果】AO群の90.9%において免疫栄養後に抗酸化力が増加した。CT群に比較してAO群は術後により高い抗酸化力とトランスフェリン値を示した。またAO群は術後の白血球数、好中球数が低く、術後発熱期間が短かった。それ以外の栄養学的指標、肝機能、免疫学的指標、手術因子や術後経過に2群間に差を認めなかった。【結論】抗酸化物質を含む術前免疫栄養による明らかな臨床的アウトカムを示せなかったが、術後免疫応答を改善するのに有用である可能性が示唆された。(著者抄録).
549. 生体肝移植レシピエント手術による高度技能医育成に関する検討.
550. 生体肝移植・胆管空腸吻合後難治性胆管狭窄をランデブーテクニックで治療した2例.
551. 生体肝移植後における術後至適栄養管理の追求 敗血症の危険因子としてのSarcopeniaとグルタミンの意義.
552. 生体肝移植後グラフトロスにおける予後予測因子としてのSarcopenia(筋肉減少症)の有用性の検討.
553. 伊地知 秀樹, 吉住 朋晴, 池上 徹, 副島 雄二, 池田 哲夫, 川中 博文, 内山 秀昭, 山下 洋市, 森田 勝, 沖 英次, 三森 功士, 杉町 圭史, 佐伯 浩司, 渡邊 雅之, 調 憲, 前原 喜彦, 生体肝移植後肝細胞癌再発後の慢性B型肝炎の再発(Recurrent Hepatitis B Following Recurrence of Ilepatocellular Carcinoma after Living Donor Liver Transplantation), 福岡医学雑誌, 10.15017/1398607, 104, 10, 376-82, 2013.10, 肝移植後のB型肝炎の再発は移植成績を低下させる。生体肝移植後に肝細胞癌再発を認め、その後B型肝炎の再発を認めた2例を経験したので報告する。いずれもミラノ基準を超えた肝細胞癌とB型肝炎による非代償性肝硬変に対する生体肝移植後であった。B型肝炎に対する免疫グロブリンと核酸アナログが投与され、B型肝炎の再発予防が行われ、いずれも血中のB型肝炎は検出できないレベルでコントロールされていた。肝細胞癌はそれぞれ移植後5ヵ月、13ヵ月後に再発し、放射線療法と化学療法が施行された。抗ウイルス療法にもかかわらず、再発肝細胞癌に対する治療中にB型肝炎のDNAレベルは上昇した。HBs抗原陽性のレシピエントにおいては再発肝細胞癌の治療の間、B型肝炎再発予防を十分注意しながら行う必要がある。(著者抄録).
554. 生体肝移植術における非代償性肝硬変に対する新しい門脈血行動態コントロール法.
555. 生体肝移植術を含む3回の開腹術歴後に完全腹腔鏡下脾臓摘出術を施行し得た一例
50代女。47歳時に原発性胆汁性肝硬変にて生体肝移植術を施行された。49歳時に十二指腸乳頭部癌にて膵頭十二指腸切除術を施行された。その後、胆管炎を繰り返し、難治性胆管炎および腹壁瘢痕ヘルニアに対し52歳時にRoux-Y脚再々建術および腹壁瘢痕ヘルニア根治術を施行された。今回、ビリルビンの上昇を認め、肝生検で二次性胆汁性肝硬変と診断した。食道静脈瘤(F2RC2+)を認め、内視鏡的加療を行うもコントロール不良であり、脾腫による汎血球減少および食道静脈瘤の治療のため腹腔鏡下脾臓摘出術施行の方針となった。過去3回の開腹術歴と脾腫により、腹腔内癒着や脾臓周囲の視野不良が予想されたため、術式は敢えて完全腹腔鏡手術を選択した。ポートの位置を工夫することで良好な視野が確保でき、安全な手術が行えた。.
556. 生体肝移植術後胆管吻合部狭窄の予防と対策.
557. 生体肝移植術後早期の敗血症の危険因子としての血清IgG値の意義に関する研究.
558. 生体肝移植術後における胆汁うっ滞性C型肝炎発症の規定因子の検討.
559. 生体肝移植術後に生じた肝動脈仮性動脈瘤が自然消失した稀な一例.
560. 生体肝移植術術後肺炎の検討 病因、危険因子とその治療成績について.
561. 生体肝移植術術後肺炎の検討 病因、危険因子とその治療成績について.
562. 磁石圧迫吻合術により治癒し得た腹腔鏡下胆嚢摘出術中胆管損傷の1例
症例は84歳男性で、総胆管結石嵌頓による急性閉塞性化膿性胆管炎(AOSC)で救急搬送され、腹部CTで胆嚢結石・総胆管結石を認めた。緊急内視鏡的逆行性胆管造影(ERC)で総胆管内に透亮像を認め、チューブステントを留置した。入院19日後にERCを再検し、バルーンで少量のデブリス(血液成分屑)を排出した。26日目に退院し、胆嚢結石手術のため再入院したが、38℃台の熱発から腹部CTを施行した。総胆管結石再発で内視鏡的乳頭切開術を施行した。AOSCの発症から59日目に腹腔鏡下胆嚢摘出術を施行し、胆嚢壁は著明に肥厚し、周囲と癒着し、胆嚢摘出直後の右肝管損傷を認め、開腹術に移行した。右肝管を胆嚢管と誤認し、右肝管内に減圧チューブを留置し、5-0PDSで肝側右肝管損傷部を縫合閉鎖した。術後5日目に胆汁漏を認め、内視鏡的胆管ドレナージを試みたが胆汁漏の改善はみられなかった。胆嚢摘出術後31日目に再開腹し右肝管断端同士を外ステント留置下に縫合した。再手術後12日目に外ステント固定が不十分なため外ステントが吻合部より自然抜去した。再手術は困難を伴うため、磁石圧迫吻合術を行った。圧迫吻合術施行後6ヵ月目にチューブを抜去し、その後9ヵ月閉塞を認めず経過中である。.
563. 肝がん治療の最前線 再発肝癌に対する再肝切除の最前線 特に3回目以上再肝切除の妥当性.
564. 播本 憲史, 松山 博之, 梶山 潔, 長家 尚, 池上 徹, 吉住 朋晴, 副島 雄二, 調 憲, 池田 哲夫, 川中 博文, 内山 秀昭, 山下 洋市, 森田 勝, 沖 英次, 佐伯 浩司, 前原 喜彦, 肝下部下大静脈併用肝切除においてStroke Volume VariationはCVPと逆相関し出血量の指標となりうる(The Significance of Stroke Volume Variation During Hepatic Resection Under Infrahepatic Inferior Vena Cava and Portal Triad Clamping), 福岡医学雑誌, 10.15017/1398605, 104, 10, 362-9, 2013.10, 【はじめに】近年、stroke volume(一回拍出量)は呼吸性変動を受け、この変化量であるstroke volume variation(SVV)がfluid responsiveness(輸液反応性)の指標としてCVPよりも鋭敏であると言われている。動脈ラインにFloTrackを接続すればSVVは簡便に測定可能である。また肝切除における下大静脈クランプ(IVCC)は中心静脈圧(CVP)を下げ、出血コントロールに有用であるとの報告があるが、中心静脈路の確保が必要となる。【目的】IVCC併用肝切除時のSVがCVPの代用となり得るかを検討した。【対象】平成22年12月から2ヵ月間の肝切除14例(男10例、女4例、49~79歳)。全例ダブルルーメンの中心静脈カテーテルを挿入しCVPを測定、SVVはFloTrackを用いて測定した。肝切除はCUSAを用いてIVCC+Pringle法下に行った。【結果】IVCCにて有意にSVVが上昇したがCVPの有意な低下はみられなかった。Pringleのみでは両者とも変化を認めなかった。肝切除中、IVCC+Pringleにて有意にCVP低下、SVV上昇し、Pringle解除にて速やかに前値に戻った。SVVとCVPは有意に逆相関した。14例の出血量の中央値486g(120~2214)であり、出血量が486g以下の症例をA群(n=7)、以上の症例をB群(n=7)とし、A群ではIVCC時に有意にCVPが低下し、SVVが上昇していた。SVV18%以上の症例(n=4)では有意に出血量が少なかった。【結論】SVVはCVPと有意に相関しており、SVVの測定は、IVCC併用肝切除時にはCVPの代用となりうる。またSVV18%以上を目標にしたIHVCC併用肝切除は出血の軽減に寄与すると思われた。(著者抄録).
565. 肝内胆管気腫を伴う気腫性胆嚢炎に対して腹腔鏡下胆嚢摘出術を行った1例
症例は67歳女性で、脳腫瘍術後、認知症で加療中であった。腹痛、嘔吐が出現し、内服抗生剤を処方されたが改善しなかった。CTで気腫性胆嚢炎と診断された。腹部CTで胆嚢は著明に腫大し、壁内にガスがみられ、気腫性胆嚢炎の所見であった。胆嚢・胆嚢管内に小結石と思われる高吸収構造が多数存在した。左肝内胆管から総胆管にもガスが存在し、肝左葉表面にもガスを伴った液貯留がみられ膿瘍の所見であった。腹部MRIで総胆管結石の所見なく、胆道系に明らかな解剖学的所見はなかった。上部消化管内視鏡で十二指腸球後部~下行脚の粘膜はやや浮腫状で点状出血がみられた。セフォゾプラン塩酸塩を投与し、MRIによる胆道系の評価、上部消化管内視鏡検査を行い、心機能などの全身評価を行って手術した。胆嚢腫大により手術操作が困難なため胆嚢内容を吸引後、腹腔鏡下胆嚢挺出術を行った。術後、抗生剤をメロペネム水和物に変更した。術後、発作性心房細動を発症し、血圧低下によるノルアドレナリンの使用を必要としたが徐々に安定し、術後5日目に人工呼吸器を離脱し、術後7日目に集中治療室を退室しリハビリを行い、術後23日目に療養のため転院した。.
566. 肝内胆管癌に対するR0切除を中心とした集学的治療の現状.
567. 肝再生の機序解明と臨床への応用 肝再生におけるオートファジーの生物学的意義.
568. 肝切術後合併症としての門脈血栓症.
569. 肝切除後合併症としての門脈血栓.
570. 肝切除管理マニュアル 九州大学消化器・総合外科版.
571. 肝切除術中・術後合併症の予防策 生体肝移植右葉グラフト採取術における胆道合併症防止への取り組み.
572. 肝右葉グラフト採取術における胆道合併症予防.
573. 池上 徹, 吉住 朋晴, 副島 雄二, 池田 哲夫, 川中 博文, 内山 秀昭, 山下 洋市, 森田 勝, 沖 英次, 佐伯 浩司, 三森 功士, 杉町 圭史, 渡邊 雅之, 調 憲, 前原 喜彦, 肝左葉を用いた生体肝移植における門脈圧低下を目指した脾臓摘出術の適応に関する検討(The Application of Splenectomy to Decompress Portal Pressure in Left Lobe Living Donor Liver Transplantation), 福岡医学雑誌, 104, 9, 282-9, 2013.09, 【はじめに】生体肝移植に於いて、左葉グラフトを使用することはドナーの安全性をより高める意味で重要であるが、グラフトサイズが小さいことによりグラフト機能不全そしてグラフト不全に繋がる可能性も秘めている。我々は、摘脾を行うことで左葉グラフト移植をより安全に行う試みを行っている。【対象および方法】対象は左葉グラフトを用いた生体肝移植250例とした。摘脾群(n=98)および非摘脾群(n=152)の二群に分類し、背景因子、手術・術後因子、そしてグラフト生存に関する比較検討を行った。【結果】摘脾群は非摘脾に比し、有意にレシピエント年齢が高齢(54.5歳vs.46.3歳、p<0.01)、Child C症例が多く(64.8% vs.51.5%、p<0.01)、model for end-stage liverスコアが高値(17.8±8.1 vs.15.4±5.8、p<0.01)、そしてグラフト標準肝容積比が小さい(36.5±6.1% vs.40.2±8.2%、p<0.01)症例群であった。摘脾群では摘脾により門脈圧が有意に低下(23.5±5.2mmHg to 19.2±4.8mmHg、<0.01)した。また、摘脾群は非摘脾群に比し有意に開腹時門脈圧が高値(24.9±5.3mmHg vs.22.5±6.3mmHg、p<0.01)であったが、閉腹時門脈圧は低値(16.4±3.5mmHg vs.18.0±4.7mmHg、p<0.01)であった。そして術後14日目の総ビリルビン値および腹水排出量は摘脾群が非摘脾群に比し、それぞれ有意に低値(5.7±6.5mg/dl vs.8.7±8.9mg/dl、p<0.01)、少量(0.4±0.7L/day vs.0.7±0.4L/day、p=0.01)であった。そしてグラフトの5年生存率は摘脾群(86.8%)が非摘脾群(76.2%)に比し有意に良好であった(p=0.03)。【まとめ】左葉を用いた生体肝移植に於いて、摘脾を行うことはグラフト機能を改善するうえで有用な手段であると考えられた。(著者抄録).
574. 肝癌に対する各種治療の取り組み ChildB肝硬変合併肝癌に対する肝移植と肝切除(マイクロ波凝固術を含む)の比較.
575. 肝癌に対する肝移植の適応と限界 新たなバイオマーカーを用いた肝細胞癌に対する生体肝移植後再発予測の検討.
576. 肝硬変に伴う脾機能亢進症に対する腹腔鏡下脾臓摘出術における術前脾動脈塞栓術の有用性に関する検討.
577. 肝移植と門脈圧亢進症 生体肝移植後に増悪する食道胃静脈瘤に関する検討.
578. 肝移植のためのチーム作り 肝移植の成績向上に向けた我々のチーム作りへの取り組み.
579. 肝移植後の短期予後改善を目指した我々の治療戦略.
580. 肝移植後合併症の現状と対策 生体肝移植後外科的合併症の変遷とその対策.
581. 肝移植手術における技術的困難例に対する戦略 生体肝移植に於ける門脈血栓・門脈低形成症例に対する手術戦略.
582. 肝移植手術及び周術期管理を用いた外科医教育の取り組み.
583. 肝細胞癌における血管新生因子としてのapelin/APJ系の意義.
584. 肝細胞癌に対する腹腔鏡下肝切除の現状と展開.
585. 肝細胞癌に対する肝移植 肝癌に対する生体肝移植の新たな適応基準に関する検討.
586. 肝細胞癌外科手術症例におけるEGF遺伝子多型の臨床的意義.
587. 肝細胞癌外科的治療における術前末梢血好中球リンパ球比(Neutrophil/lymphocyte ratio:NLR)の意義 肝切除、生体肝移植後の新しい予後因子.
588. 肝静脈解剖に注目した肝切除 縮小肝右葉切除として右肝静脈領域切除と生体肝移植における内側区域のドレナージ形態に基づいた拡大肝右葉切除の有用性.
589. 木村 和恵, 松田 裕之, 佐伯 浩司, 沖 英次, 森田 勝, 杉町 圭史, 山下 洋市, 池上 徹, 内山 秀昭, 吉住 朋晴, 副島 雄二, 川中 博文, 池田 哲夫, 筒井 信一, 藤原 恵, 三森 功士, 渡邊 雅之, 石田 照佳, 前原 喜彦, 胃の早期腺扁平上皮癌の一例(A Case of Early Adenosquamous Carcinoma of the Stomach), 福岡医学雑誌, 10.15017/1397860, 104, 9, 315-20, 2013.09, 【はじめに】胃腺扁平上皮癌はまれな疾患であり、報告は様々だがおよそ胃癌の0.5%といわれている。早期癌に関する報告は非常に少なく、現在7例報告されているのみである。今回我々は本邦で8例目となる早期胃腺扁平上皮癌を経験したので報告する。【症例】77歳男性で上部消化管内視鏡検査で、胃角部に0-IIa+IIc病変を指摘され、生検では腺癌の診断であった。腹腔鏡補助下幽門側胃切除施行され、病理組織診断では胃腺扁平上皮癌、T1b(SM)N1 M0 StageIBと診断された。術後6ヵ月目のCTで肝臓に3ヶ所の転移を指摘され、再発に対してS-1/CDDP療法が施行された。現在1年7ヵ月生存中である。【考察】腺扁平上皮癌とは腺癌と扁平上皮癌が共存しており、うち扁平上皮癌が4分の1以上存在することが必要とされている。腺扁平上皮癌の報告は多数あるが、ほとんどの症例は肝転移や多発リンパ節転移を伴った進行した状態で発見されている。また症例が少なくまだ不明なことが多いが、基本的には予後不良といわれている。理由としては(1)多発肝転移や多発リンパ節転移を伴った進行癌で発見されている。(2)早期胃腺扁平上皮癌でも早期に再発する、ということが挙げられる。しかし、これまでの7例の早期癌症例において3例は言及されていないが、4例は無再発であり、4年以上生存している症例もあるため、胃腺扁平上皮癌が生物学的な特徴を有している可能性がある。本症例のように早期癌であってもわずか6ヵ月で再発をきたした症例もあることから、通常の腺癌よりは厳重な経過観察が必要であると考えられた。(著者抄録).
590. 藏重 淳二, 澤田 元太, 高橋 祐典, 江口 英利, 主藤 朝也, 池上 徹, 吉住 朋晴, 副島 雄二, 池田 哲夫, 川中 博文, 内山 秀昭, 山下 洋市, 森田 勝, 沖 英次, 佐伯 浩司, 杉町 圭史, 渡邊 雅之, 森 正樹, 馬場 秀夫, 三森 功士, 胃癌におけるMAL遺伝子抑制の意義(Suppression of MAL Gene Expression in Gastric Cancer Correlates with Metastasis and Mortality), 福岡医学雑誌, 10.15017/1398603, 104, 10, 344-9, 2013.10, われわれは癌組織において極めて高頻度に発現が減弱または消失しているMAL遺伝子を同定した。その発癌と癌進展にかかわる分子機序を明らかにするために、胃癌の株化細胞と臨床症例を用いた解析を行った。インフォームドコンセントを得た胃癌50症例を対象にReal time PCRにて半定量的にMAL発現量を求め、予後および臨床病理学的因子との関係を調べた。胃癌50例の37例(74%)は癌部においてMAL遺伝子の発現消失、減弱を認めた(低値群)。これを発現が比較的保たれている症例(高値群)と比較すると、高値群は低値群に比し予後良好であった。また低値群はリンパ節転移陽性例が多い傾向を示した。MALは胃癌において極めて高頻度に発現が減弱、消失していた。本来MALはゴルジ体またはERにおける蛋白輸送によって過集積を防ぐ機能を有する分子として報告されていたが、本研究でその発現喪失が胃癌進展に対しても深く関与することが示された。また、MAL遺伝子が胃癌における癌抑制遺伝子であることを示した。(著者抄録).
591. 吉永 敬士, 佐伯 浩司, 沖 英次, 森田 勝, 池田 哲夫, 杉町 圭史, 山下 洋市, 池上 徹, 内山 秀昭, 吉住 朋晴, 副島 雄二, 川中 博文, 三森 功士, 渡邊 雅之, 前原 喜彦, 胃癌・大腸癌症例に対するクレスチン(PSK)療法のレスポンダー探索(Prognostic Markers for Immunochemotherapy Using Tegafur-Uracil(UFT) and Protein-Bound Polysaccharide K(PSK)), 福岡医学雑誌, 10.15017/1440934, 104, 12, 549-58, 2013.12, 【背景】われわれはこれまでに健常人、胃・大腸癌患者リンパ球のPSK添加による幼若化反応(以下PSK-SI)の検討を行い、胃・大腸癌患者のPSK-SIは健常人に比し低値であること、胃・大腸癌患者のPSK-SI高値はPSKによる免疫療法のレスポンダー指標になる可能性があることを報告してきた。今回PSKによるリンパ球活性化が胃癌・大腸癌のPSK治療効果予測因子となるか否かを検討した。【対象と方法】解析対象は胃癌98症例、大腸癌術後135症例であった。患者の末梢血単核球を分離し、PSK添加、非添加下でのPSK-SIを3H-thymidine取り込みで評価した。胃癌ではPSK-SI 1.75倍以上を高値群、未満を低値群とし、大腸癌ではPSK-SI 2.1倍以上を高値群、未満を低値群とした。血中免疫抑制酸性蛋白(IAP)はTIA法で評価した。術後補助化学療法はUFT、PSKを術後15日より2年間連日投与した。各群の予後をPSK-SIとIAPの高値群、低値群間で解析した。【結果】胃癌・大腸癌症例のPSK-SI高値群、低値群で両群間患者背景に有意な差はなかった。また術前IAP(胃癌;≧400μg/ml、大腸癌;≧500μg/ml)とPSK-SI(胃癌;≧1.75、大腸癌;≧2.1)が高い患者群において、PSKを用いた術後補助免疫療法の有効性が高かった。【結語】今後のさらなる臨床試験がなされることが必要であるが、PSKによるリンパ球活性化が治療効果予測に有用な因子となる可能性が示唆された。(著者抄録).
592. 胃癌肝転移に対する切除例と化学療法例の検討
2005年4月~2012年3月迄の7年間に胃癌肝転移に対し、緩和治療を除く治療を行った31例(男性29例、女性2例、53~83歳、平均68.0±7.7歳)を対象に、治療の現状を確認し、治療成績について検討した。肝転移を診断された時期は初診時17例、術後再発14例であった。原発巣の病理所見は分化型腺癌14例、低分化型腺癌14例、壁深達度は粘膜下層までの早期癌4例で、他の27例は固有筋層以深の進行癌であった。リンパ節転移陰性例は4例で、他の27例はリンパ節転移陽性であった。肝切除を施行された6例中4例は胃切除後の術後再発に対して異時性に肝切除を施行し、2例は胃切除と同時に肝切除を施行した。原発巣の病理所見は1例がT1bN0の早期胃癌、他は全て進行胃癌であった。肝転移個数は最多で3個、腫瘍径は最大7.2cmであった。術式は肝部分切除術4例、前区域切除術・亜区域切除術各1例で、1例が顕微鏡的断端陽性であった。6例中5例で肝切除後に再発をきたし癌死した。1例は再発なく経過し、術後702日目に肺炎で死亡した。全31例の生存期間中央値は477日で、肝切除群では404日、化学療法群では511日で各群間に統計学的な有意差を認めなかった。.
593. 胆管内乳頭状腫瘍の2切除例.
594. 原田 昇, 調 憲, 吉住 朋晴, 池上 徹, 内山 秀昭, 副島 雄二, 山下 洋市, 佐伯 浩司, 沖 英次, 川中 博文, 森田 勝, 池田 哲夫, 松浦 弘, 岡留 健一郎, 前原 喜彦, 胆道癌の手術成績と術後補助化学療法の効果の検討(Surgical Treatment and Adjuvant Chemotherapy for Patients with Biliary Tract Cancer: Single Institution Experience of 100 Patients), 福岡医学雑誌, 104, 12, 539-48, 2013.12, 【はじめに】胆道癌は予後不良の疾患であり、治癒切除することが唯一の根治治療と考えられている。しかしながら、手術可能な胆管癌においても術後の再発率は高率である一方で、現在術後補助化学療法として大規模臨床試験で効果が証明されたものは存在しない。【目的】胆道癌の手術成績及び術後補助化学療法の効果について検討した。【対象・方法】1999年7月より2013年8月までにUICCステージでI、II、III、IVの切除可能胆道癌初回手術症例100例について手術成績、全生存率、無病率、予後規定因子を検討した。また術後補助化学療法の使用状況、副作用とその効果について検討した。【結果】100例中肝内胆管癌:肝門部胆管癌:肝外胆管癌:十二指腸乳頭部癌:胆嚢癌がそれぞれ17:12:26:16:29例であった。術後UICCのStage I:II:III:IVは20:41:30:9例であり、術後補助化学療法を16名(Stage I:II:III:IVで0:5:9:2例)に施行した。9名にジェムザール、7名にTS-1を使用し、半数が6ヵ月間の治療を完遂した。Grade2以上の副作用は10名に認められた。1、3、5年生存率はそれぞれ80.9%、48.6%、38.3%、1、3、5年無病率はそれぞれ59.8%、39.9%、24.9%であった。断端陽性は19名に認めた。術後化学療法施行群と施行なし群の5年生存率は40.4%と32.4%で両群間に有意差を認めなかった。術後の合併症は59%に認め、周術期死亡率は3%であった。多変量解析によってリンパ節転移陽性が唯一予後の独立規定因子であった(p=0.042)【まとめ】胆道癌手術後においてリンパ節陽性が独立予後不良因子であった。一方で術後補助化学療法の有効性は当検討では認められなかった。リンパ節陽性患者に対する術後補助化学療法の必要性が考慮され、今後大規模無作為試験による臨床試験が望まれた。(著者抄録).
595. 脳死ドナーの増加は肝移植成績を改善したか 改正臓器移植法前後での脳死肝移植症例に関する検討.
596. 脳死ドナーの増加は肝移植成績を改善したか 肝細胞癌患者に対する脳死・生体肝移植成績の比較検討.
597. 脳死肝臓移植増加に向けた九州臓器移植連携フォーラムの啓発活動 アンケート結果報告
大学病院内での講演、勉強会、講義、市民公開講座を聴講した医療従事者・医学部学生318名を対象にアンケート調査した。内訳は医学部医学科学生160名、看護師82名、歯科医師25名、医師24名、事務職10名、歯科衛生士5名、臨床検査技師3名、その他9名であった。回収は350名中192名で、31名は医療従事者で、学生318名と合わせて医療関係群349名、市民公開講座参加者中、医療従事者以外の161名を市民群として2群に分け、比較検討した。年齢については市民群が有意に高齢で、性別は両群間に有意差を認めなかった。医療関係群、市民群でそれぞれ脳死を人の死として許容するは各81%、82%、臓器提供意思表示をしているは各37%、40%、脳死家族が生前提供希望の場合提供に同意は各92%、95%と両群で差がなかった。脳死家族が生前提供意思不明の場合に提供に同意は医療関係群44%、市民群55%で市民群で高い傾向にあった。オプション提示を増やす対策として、両群共に講演会・公開講座・メディアの活動など啓発活動が必要とするは両群とも最多であった。医療関係者では説明が容易になるように法的及び院内体制整備によるオプション提示義務化が必要とする回答が次に多く、両群とも多かった意見は医療者教育の必要、院内コーディネーター制度整備であった。.
598. 腫瘍内の動脈および門脈の狭小化と閉塞を伴い広範囲壊死を来たしていた肝細胞癌の1切除例.
599. 腹壁瘢痕ヘルニアの腹腔鏡下ヘルニア修復術のエビデンスを問う 当科における腹腔鏡下腹壁ヘルニア修復術の手技の工夫と治療成績について.
600. 腹腔鏡がもたらした膵臓外科の新たな知見とは 腹腔鏡下膵切離における膵液漏の発生要因と新たな膵切離方法の検討 人工皮膚を応用した革新的切離手技.
601. [Optimum hepatic parenchymal dissection to prevent bile leak: a comparative study using electrosurgical and stapling devices in swine].
BACKGROUND: Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. PURPOSE: The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. METHODS: Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. RESULTS: Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. CONCLUSIONS: Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma..
602. 腹腔鏡下肝切除術の現状と今後のゆくえ 現状では腹腔鏡下肝切除が困難な肝右葉前上、後区域に対する左半腹臥位、肋間ポートを用いた手術手技の検討.
603. 腹腔鏡下肝切除の現状と適応拡大の試み 横隔膜ポートを用いた半腹臥位完全腹腔鏡下肝切除術の有用性の検討.
604. 腹腔鏡下脾臓摘出術の工夫とトレーニング 肝硬変症に対する腹腔鏡下脾摘術を安全に行うためのHALSの適応を明確にした手技の標準化とその適正化.
605. 腹腔鏡下腹壁ヘルニア修復術の手技の工夫と治療成績
2005年から2013年8月までに行った腹腔鏡下腹壁ヘルニア修復術65例を対象とし、再発や合併症を低減するための手技の工夫とその治療成績を報告した。当科では、腹壁ヘルニアの治療の基本はメッシュを用いた腹腔鏡下修復術と考え、ポート挿入位置、癒着剥離、メッシュのサイズの決定と固定部位のマーキング、メッシュの固定、seromaの予防、術後などの手技を工夫している。自験例では平均ヘルニア門長径8.3cm、平均手術時間177分、平均出血量23g、平均術後入院日数12.1日で開腹移行は4例(6.2%)であった。合併症は遅発性腸管損傷1例(1.5%)で、メッシュ感染やメッシュの癒着に伴う腸管瘻はなく、再発は傍ストーマヘルニアの1例(1.5%)のみで平均観察期間は2年であった。腹腔鏡下腹壁ヘルニア修復術は腹壁ヘルニア治療の第一選択になり得ると考えられた。.
606. 腹腔鏡下膵切除術における膵切断方法の検討.
607. 腹腔鏡下膵切除 注意すべき手術のポイント 完全腹腔鏡下膵切除術における膵切断方法の検討 切除症例と動物実験での検討.
608. 膵・胆道術後合併症に対するリカバリーショット 生体肝移植術後胆管吻合部狭窄に対する治療法 Simultaneous percutaneous and endoscopic approach(SPEA)の有用性.
609. 膵切除後の短期・長期合併症に対する予防策とその根拠 膵液漏ゼロを目指した我々の膵切離・再建法への取り組み.
610. 池田 哲夫, 赤星 朋比古, 川中 博文, 内山 秀昭, 山下 洋市, 森田 勝, 沖 英次, 佐伯 浩司, 杉町 圭史, 池上 徹, 吉住 朋晴, 副島 雄二, 調 憲, 三森 功士, 渡邊 雅之, 橋爪 誠, 前原 喜彦, 膵切離方法の検討 動物実験における高周波電気器機と吻合器の比較検討(Evaluation of a Transection Method for Distal Pancreatectomy: A Comparative Study on the Use of Electrosurgical and Stapling Devices in Swine), 福岡医学雑誌, 10.15017/1440930, 104, 12, 515-22, 2013.12, 【背景】膵臓に関する手術手技の進歩にも関わらず、膵切離後膵液瘻の発生頻度は減少しておらず、依然として最も重大な合併症である。【目的】この研究の目的は近年従来の膵管結紮、膵実質切離に変わって、鏡視下手術の普及と共に一般に行われるようになった。膵の高周波電気器機と吻合器での切離方法を動物実験によって評価し最適な切離方法を検討する事にある。【方法】4つの器機を用いて膵体部での切離を行った。使用した器具は(1)bi-polar thermofusion system(BiClamp)に自動irrigation装置を装着した器機(BI)(n=3)、(2)bi-polar tissue sealer(ENSEAL)(BS)(n=3)、(3)ultrasonic scissor(Harmonic ACE)(US)(n=3)、(4)endoscopic stapling device(ECHELON ENDOPATH)(ES)(n=3)である。ブタを用いて全麻下に、肝、膵、脾そして十二指腸を一回に摘出し膵体部の切断を4種の器具を用いて行った。十二指腸乳頭の膵管開口部より背側膵管にカニュレーションを行い膵切離断端の耐圧力を測定した。また高周波電気器機での切離断端のみではなく、吻合器での切離断端もpolyester resin樹脂化標本の研磨切片からStaplerの切離線の組織学的評価を行った。【結果】切離断端の膵管耐圧力はBIで約10mmの膵をthermofusion後に尾側で切断する方法のみで高い耐圧能を認め、他の方法と比較して有意な差を認めた(P<0.01)。組織学的にはBIでは15mm程度の熱変性を認めたのに対してBSやUSでは熱変性の深さは1mm程度であった。Staple切離線の組織所見では各々のstapleは正常に閉鎖した形となっていたが、stapleは膵実質に食い込んでおり切離面に開存した膵管を認めた。【結語】膵臓断端の十分な閉鎖は高周波電気器機や吻合器では得られなかった。適切な膵切離には膵の被膜の形態を考慮した閉鎖方法を検討する必要があると考えられた。(著者抄録).
611. 膵切離術の工夫 膵切離時膵液瘻の原因究明と新たな切離方法の開発.
612. 膵液漏ゼロを目指した我々の膵切離・再建の工夫.
613. 膵液漏ゼロを目指した膵切離・再建の工夫.
614. 膵粘液性嚢胞腺癌の破裂の1例
症例は41歳女性で、時々腹痛を自覚し、腹部造影CTで、左上腹部に13cm大の多房性腫瘍を認め、内部に隔壁構造を伴い、一部石灰化を認めた。腫瘍は大きく、由来は膵、十二指腸、後腹膜等が考えられた。翌日朝から突然強い下腹部痛が出現したため、救急搬送された。意識清明、下腹部に筋性防御を認め、腹部造影CTで左上腹部に多房性嚢胞性腫瘍を認めるが、前日のCTと比べ縮小し、腹水が出現し増加していた。腹部所見、CT検査所見から多房性嚢胞腫瘍破裂による腹膜炎と診断し緊急手術した。L字切開で開腹し、膿性腹水を認めたため腹水培養・細胞診を提出した。腫瘍は約10cmで腹腔内を占拠し、腫瘍発生部位同定は困難であった。腫瘍を後腹膜・周囲組織から剥離することで膵体尾部由来と判明したため尾側膵切除を行った。摘出した膵尾側に8cm大の多房性嚢胞を認め、病理検査結果は多房性嚢胞で嚢胞内腔面は粘液産生性の上皮で被覆され、卵巣様間質を伴い、上皮は腺腫から腺癌に相当する異型を呈し、癌細胞の巣状、管状の間質浸潤が認められたが浸潤は膵内に限局していた。以上より、膵粘液性嚢胞腺癌破裂および腹膜炎と診断した。術後経過は良好で11日目に退院し、術後2年経過したが再発所見を認めていない。.
615. 膵頭十二指腸切除後の胆管癌肝門部再発に対し前回吻合の全再吻合と拡大肝右葉切除を行った1例
64歳男。黄疸を主訴とした。中部胆管癌にて幽門輪温存膵頭十二指腸切除を受けるも肝側断端陽性、術後膵液瘻(ISGPF grade B)にて長期の洗浄ドレナージを要しており、術後約1年で主訴が出現した。入院時検査で肝胆道系酵素の著明な上昇、肝内胆管拡張と肝門部胆管の壁肥厚を認め、肝門部胆管癌再発による閉塞黄疸と診断された。経皮経肝胆道ドレナージチューブからの胆管造影にて左肝管から前後区域枝に至る狭窄を認め、切除可能の判断で開腹したところ、肝門部と膵空腸吻合部の強固な癒着を認め、これを剥離すると膿汁が排泄したため、膵空腸吻合の全再吻合と肝拡大右葉切除を行い、肉眼的治癒切除を達成できた。術後補助化学療法を1年行い、術後2年経過現在も再発なく経過している。.
616. 臓器・細胞移植医療の現状と展望 肝移植後の短期予後改善を目指した我々の治療戦略.
617. 臓器移植の現状と問題点 脳死下臓器提供増加に向けた九州臓器移植連携フォーラムの取り組み.
618. 池田 哲夫, 吉屋 匠平, 戸島 剛男, 播本 憲史, 山下 洋市, 池上 徹, 吉住 朋晴, 副島 雄二, 調 憲, 前原 喜彦, 良性疾患もしくは良悪性境界病変に対する腹腔鏡下脾および脾動静脈温存膵体尾部切除術(Laparoscopic Distal Pancreatectomy Preserving the Spleen and Splenic Vessels for Benign and Low-Grade Malignant Pancreatic Neoplasm), 福岡医学雑誌, 104, 3, 54-63, 2013.03, 膵体尾部切除術は術野が体腔深く、視野がとりづらい部位にあるが、再建が不要であることから、鏡視下手術の利点を十分に享受しうる術式と考えられる。腹腔鏡下膵体尾部切除術特に脾および脾動静脈を温存する術式は平成24年度から保険収載され膵体尾部の良性・低悪性度腫瘍に対する第一選択の術式として位置づけられてくると言っても過言ではないであろう。良性・低悪性度腫瘍に対しても従来は通常型膵癌と同様に脾切除を伴う膵体尾部切除を行うのが一般的であった。Warshawが最初に短胃動静脈を温存し脾動静脈を切離する方法を報告しさらにKimuraが脾動静脈を温存する方法を報告した。脾臓温存の意義は脾摘によってもたらされる敗血症、血小板上昇などの血液学的異常を防御できることである。また、癌に対する腫瘍免疫学的な側面からも脾温存は重要である。我々は良性および低悪性度膵腫瘍に対して最も低侵襲と考えられる、脾および脾動静脈を温存する膵体尾部切除術を腹腔鏡下手術の適応としている。脾および脾動静脈温存膵体尾部切除において問題となる点は、先ず特に重要な膵実質より合流する細かな静脈を処理して確実に脾静脈を温存する為の器具の選択と使用方法。そして、現在の所完全な解決方法は明らかとなっていないが、完全に剥離された脾動静脈が膵切断端に露出する手術方法であることから、重大な合併症となり得る膵液瘻を最大限予防し得る膵切断方法である。6症例(女性4名、男性2名)に対して脾および脾動静脈温存膵体尾部切除術を行った。全例で腹腔鏡下に完遂出来、手術時間は平均290.7分(211-377分)、平均出血量は43.5g(0-142g)、術後平均在院日数は11.8日(9-17日)。Grade B以上の明らかな膵液瘻は認められなかったが、術後7日目に行った腹部CT検査にて膵切離断端に仮性嚢胞を3症例に認めた。術後病理診断はserous cystadenomaが2症例、serous oligocystic adenoma、mucinous cystadenoma、neuroendocrine tumor、solid-pseudopapillary neoplasmが各々1症例であった。腹腔鏡下に脾および脾動静脈を温存する膵体尾部切除術は良性および低悪性度膵腫瘍に対して安全に施行可能な低侵襲で有るが、術後の膵液瘻を予防する膵切離方法に関しては、今後更なる改善策が必要と考えられた。(著者抄録).
619. 萎縮門脈に対して左腎静脈・間置内径静脈とグラフト門脈を吻合した生体肝移植の一例.
620. 術後合併症を回避するための膵切離・再建法 我々の膵液漏ゼロを目指した膵切離・再建法への取り組み.
621. 透析患者に対して生体肝移植術施行した一例.
622. 進行4型大腸癌に術後m-FOLFOX6療法が有効であった1例
症例は59歳男性で、便秘傾向となり大腸内視鏡で直腸~S状結腸に腸管内腔狭窄所見を認めた。通常の大腸癌と形態が異なり、原発不明の他臓器からの転移性大腸癌と診断された。腹部はやや膨隆し腸音は亢進し、下部消化管内視鏡で15~30cmの部位に瀰漫性管腔狭小化を認め、粘膜面は正常上皮に覆われた粘膜下腫瘍様小隆起により占められ、明らかな潰瘍や腫瘤の露出は指摘できなかった。病変部生検より低分化腺癌と診断した。注腸造影で直腸RSからS-D接合部近くに高度の毛羽立ち・浮腫像を認め病変は25cmであった。腹部CTでS状結腸に腸管壁肥厚を認め、管腔の軽度狭窄を認めた。骨盤内に腹水、下腸間膜根部レベルの傍大動脈リンパ節腫大を認めたが肝転移は認めなかった。4型大腸癌と診断しイレウス症状をきたしたため手術した。腹腔内に中等量腹水を認め、腫瘍はS-D接合部よりS状結腸~直腸に連続する全周性の硬い浸潤型で腹膜播種も認めた。明らかな肝転移は認めず傍大動脈リンパ節の肉眼的転移を認めた。開腹所見より根治手術は困難と考えHartmann術を行った。術後、麻痺性イレウスを認め、m-FOLFOX6療法による術後化学療法を行い傍大動脈リンパ節の著明な縮小を認めた。その後、FOLFIRIに変更したが癌性リンパ管症を発症し癌死した。.
623. 進行・再発肝細胞癌に対する治療戦略 肝細胞癌に対する生体肝移植後再発に対する治療戦略.
624. 佐伯 浩司, 沖 英次, 津田 康雄, 安藤 幸滋, 日吉 幸晴, 伊藤 修平, 森田 勝, 池田 哲夫, 杉町 圭史, 山下 洋市, 池上 徹, 内山 秀昭, 吉住 朋晴, 副島 雄二, 川中 博文, 三森 功士, 渡邊 雅之, 前原 喜彦, 進行胃癌に対する完全鏡視下胃切除術の妥当性(Relevance of Totally Laparoscopic Gastrectomy for Patients with Advanced Gastric Cancer), 福岡医学雑誌, 10.15017/1430773, 104, 11, 405-12, 2013.11, 【目的】胃癌に対する腹腔鏡下手術は広く普及したが、進行胃癌に対する適応の是非に関しては議論の余地がある。本研究の目的は、進行胃癌に対する完全腹腔鏡下胃切除術の有用性を明らかにすることである。【対象・方法】当科において完全腹腔鏡下胃切除術が施行されたIB期-III期進行胃癌症例38例の手術成績と予後を検討した。【結果】幽門側胃切除27例、胃全摘11例が施行された。郭清リンパ節個数は平均41個(16-87個)であった。平均出血量123ml、平均手術時間324分、術後合併症として出血を2例に認めたが、吻合部関連合併症および在院死は認めなかった。観察期間は8-72ヵ月で、再発は6例に認めた(腹膜播種3例、胸膜播種1例、卵巣転移1例、肝転移1例)。全生存率は1年94.7%、3年・5年76.3%であった。【結語】進行胃癌に対する腹腔鏡下胃切除術は安全に施行可能であり、予後も良好である。これらの結果を検証するための、前向き比較試験が必要である。(著者抄録).
625. 木村 光一, 池上 徹, 山下 洋市, 佐伯 浩司, 沖 英次, 吉住 朋晴, 内山 秀昭, 川中 博文, 副島 雄二, 森田 勝, 調 憲, 池田 哲夫, 前原 喜彦, 遅発性難治性胆汁漏により汎発性腹膜炎を呈した生体肝移植ドナーの1例 胆汁漏に対するランデブー法の有用性(Rendezvous Technique Treatment for Late-Onset Biliary Leakage after Major Hepatectomy of a Living Donor: Report of a Case), 福岡医学雑誌, 10.15017/1397859, 104, 9, 309-14, 2013.09, 【はじめに】肝切除後の胆汁漏は未だ完全には克服されておらず、難治例も散見される。今回我々は、生体肝移植ドナーの拡大左葉切除術後に、汎発性胆汁性腹膜炎を合併した前区域胆管側壁よりの遅発性胆汁漏の症例を経験した。胆汁漏原因を考察するとともに、治療として経肝的、経乳頭的な双方向性アプローチを駆使したランデブー法が有用であった症例を経験したので報告する。【症例】52歳男性、生体肝移植ドナーとして当科入院となり、拡大肝左葉切除術を施行。術後26日目に突然の腹痛が出現、血液検査にて肝胆道系酵素の上昇と腹部CTにて著明な腹水貯留を認めた。腹水穿刺の結果、胆汁漏による汎発性腹膜炎が疑われ緊急開腹術を施行した。手術所見としては、開腹時に多量の胆汁性腹水が見られ、瘻孔部は前・後区域胆管合流付近に認められた。各々にRTBDチューブを留置し経肝的ドレナージと瘻孔部の周囲のドレナージを行った。開腹ドレナージ術術後も難治化が予想されたため、術後24日目にERCでの経乳頭的ドレナージを追加して双方向ドレナージを開始した。術後70日目には完全内瘻化が可能となり良好な経過を得ている。本症例の胆汁漏の原因の1つとして、肝切離面にグリソンが近接していたこととエネルギーデバイスの使用からグリソンの熱損傷を考えた。エネルギーデバイスの選択によっては組織への過度な熱損傷が防ぎ得ると考えられる。【まとめ】難治化が予想される肝切除後の遅発性胆汁漏に対して、ランデブー法を用いることにより良好な経過を辿ることが出来た生体肝移植ドナーの1例を経験した。胆汁漏の原因についても併せて考察し、症例を報告する。(著者抄録).
626. 内山 秀昭, 調 憲, 吉住 朋晴, 池上 徹, 副島 雄二, 池田 哲夫, 川中 博文, 山下 洋市, 森田 勝, 沖 英次, 三森 功士, 杉町 圭史, 佐伯 浩司, 渡邊 雅之, 竹中 賢治, 前原 喜彦, 鏡面画像を利用した完全内臓逆位患者に対する肝切除の1例(Mirror Image Hepatectomy in a Patient with Situs Inversus Totalis), 福岡医学雑誌, 10.15017/1430776, 104, 11, 430-4, 2013.11, 【背景】完全内臓逆位患者に対する肝切除は、通常解剖とは完全に鏡面の解剖となるため、特に腫瘍が肝臓の深部に存在する場合には技術的に困難である。肝内脈管や胆道系の誤認は重篤な合併症に繋がる恐れがある。今回我々は完全内臓逆位患者に対する肝切除を、コンピュータで作成した鏡面像を利用しながら行った1例を経験したので報告する。【方法】症例は66歳女性で、C型肝炎の経過観察中、肝門部直上の深部に存在する、左右肝管を圧迫する5cmの肝細胞癌を指摘された。肝臓は中等量の腹水を伴う肝硬変で、肝移植を提示したが拒否され、切除を強く希望した。術前に複数の鏡面画像をコンピュータで作成し、通常解剖と仮定した上での手術計画を立てた。この鏡面画像を参照しながら腫瘍を核出した。【結果】手術時間は454分で、術中5単位の新鮮凍結血漿を輸血した。術後は難治性腹水を合併し、腹水穿刺を必要としたが、術後2ヵ月で自宅退院した。【結語】完全内臓逆位患者に対する肝切除を行う際、鏡面画像を作成することは、日ごろ親しんでいる通常解剖で手術計画を立てることができ、複雑な肝切除もより安全に手術を行うことが可能となる。(著者抄録).
627. 井口 友宏, 調 憲, 井上 健太郎, 伊藤 修平, 大賀 丈史, 野添 忠浩, 江崎 卓弘, 吉住 朋晴, 内山 秀昭, 副島 雄二, 池上 徹, 山下 洋市, 川中 博文, 池田 哲夫, 佐伯 浩司, 森田 勝, 前原 喜彦, 長期ステロイド内服患者の術後合併症におけるステロイド内服量の影響(Impact of High Preoperative Steroid Doses on Postoperative Complications among Patients on Prolonged Preoperative Steroid Therapy), 福岡医学雑誌, 104, 12, 499-506, 2013.12, コルチコステロイドは生体の恒常性を維持するのに必須なホルモンである。グルココルチコイドやその合成アナログであるステロイドは炎症性疾患や自己免疫性疾患に対して広く使用されている。長期間のステロイド治療により易感染、創傷治癒遷延、精神症状を引き起こすと報告されているが、術前のステロイド内服量と術後合併症との関連については言及されていない。種々の疾患に対し長期間ステロイド治療が行われ、全身麻酔下に外科手術を施行された25例を対象とした。ヒドロコルチゾンに換算したステロイド内服量(mg/day)の平均±標準偏差および中央値はそれぞれ39.2±31.0、20であった。25例中10例に術後合併症を認めた。ステロイド内服量とClavien-Dindo分類による術後合併症の重症度は有意に正の相関を示した(p=0.0171)。ヒドロコルチゾンに換算したステロイド内服量のcut-off値を80mg/day以上とした場合のClavien-Dindo分類III度の合併症の発生は感度100%、特異度87%であった。術前ステロイド内服量が80mg/day以上の患者では、術後重篤な合併症を引き起こしうる。より慎重な術式の選択などの工夫が肝要である。(著者抄録).
628. 食道癌克服にむけた術式の工夫.
629. 渡邊 雅之, 松浦 光貢, 馬場 秀夫, 吉住 朋晴, 池上 徹, 副島 雄二, 池田 哲夫, 川中 博文, 内山 秀昭, 山下 洋市, 森田 勝, 沖 英次, 三森 功士, 杉町 圭史, 佐伯 浩司, 前原 喜彦, 食道癌術後の胃管潰瘍心嚢穿破に対し胸腔鏡下心嚢切開ドレナージが有効であった一例(Thoracoscopic Pericardial Drainage for Gastric Tube Ulcer Penetrated into the Pericardium), 福岡医学雑誌, 10.15017/1398609, 104, 10, 389-93, 2013.10, 食道切除再建術後の胃管にできる消化性潰瘍は時として縦隔組織に穿通し、重篤な合併症を引き起こす。特に胸骨後経路に挙上された胃管の潰瘍は時として心嚢に穿派し、重篤な心外膜炎や心タンポナーデを引き起こす。今回われわれは、心嚢に穿通を来した胃管潰瘍に対して胸腔鏡下に心嚢切開ドレナージにより治癒しえた1例を経験したので報告する。症例は66歳男性。20ヵ月前に食道癌に対して食道切除術を施行し、胸骨後経路で胃管再建が施行されていた。急激な胸背部痛を主訴に救急外来を受診し、CTにて胃管潰瘍が心嚢に穿派し、心タンポナーデを来している所見を認めた。左胸腔経路で胸腔鏡下に心嚢切開ドレナージを行い、術後は合併症なく軽快した。胸腔鏡下心嚢ドレナージは低侵襲で胃管潰瘍の穿通に伴う感染性の心嚢液貯留の治療に有用と考えられた。(著者抄録).
630. 高齢者の手術適応を巡る諸問題 高齢者における膵頭十二指腸切除 栄養状態の回復が遅れ創感染が多い.
631. 鼠径部ヘルニアに対する腹膜の解剖を意識したtotally extra-peritoneal pre-peritoneal repair(TEPP)法の実際.
632. Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Authors' Reply to "Female-to-Male Match Predicted Poor Survival Following Living Donor Liver Transplantation-Some Issues Needed to be Clarified", TRANSPLANTATION, 10.1097/TP.0b013e3182654d56, 94, 6, E36-E36, 2012.09.
633. Child-Pugh Bの肝細胞癌症例に対する肝切除と生体肝移植の検討.
634. HMGB-1(high mobility group box 1)が肝線維化におよぼす影響の検討.
635. HTLV-1陽性症例に対する生体肝移植後ATL発症危険因子に関する検討.
636. IL12/DC併用術前免疫療法による肝移植後の肝細胞癌再発予防に関する研究.
637. Tomoharu Yoshizumi, Toru Ikegami, Shohei Yoshiya, Takashi Motomura, Yohei Mano, Jun Muto, Rumi Matono, Takeo Toshima, Tetsuo Ikeda, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Impact of up-to-seven criteria and neutrophil-to-lymphocyte ratio in liver transplantation for patients who received pretreatment for hepatocellular carcinoma, JOURNAL OF CLINICAL ONCOLOGY, 30, 15, 2012.05.
638. PSE無効例に対する腹腔鏡下脾臓摘出術の有用性の検討.
639. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Kazutoyo Morita, Takeo Toshima, Jun Muto, Shohei Yoshiya, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Surgical resection and its relationship to survival for recurrent hepatocellular carcinoma after living donor liver transplantation, JOURNAL OF CLINICAL ONCOLOGY, 30, 15, 2012.05.
640. 【B型肝炎:克服へのロードマップ】 B型肝炎再活性化と対策 HBV関連生体肝移植の現状と移植後HBV再活性化対策.
641. 【生体肝移植における凝固異常と血栓症】 生体肝移植レシピエント術後の静脈血栓症 凝固異常の観点から
肝移植後の静脈血栓症はグラフトに起因する静脈血栓症、深部静脈血栓症や肺動脈血栓塞栓症などの全身性血栓症に分類される。生体肝移植レシピエント術後では、とくに右葉グラフトにおける中肝静脈枝の再建に関連する静脈血栓症の頻度が高い。静脈血栓症は頻度こそ低いものの、グラフトロスにつながりうる重篤な合併症であり、その病態と治療法の理解が必須である。(著者抄録).
642. 【知っておくべき『肝疾患と皮膚病変』-ウイルス性肝炎治療を中心に】 (Part3)肝臓と皮膚疾患 症例編(case09) 生体肝移植とGVHD one-way donor recipient HLA matching.
643. 【肝細胞癌のすべて2012】 治療法の進歩 肝移植/外科の立場から.
644. 【術前・術後管理必携】 術式別術前・術後管理 膵、脾臓 脾臓摘出術.
645. ここまできた移植医療の進歩 生体肝移植後長期成績向上のための治療戦略の構築 原疾患治療を目指して.
646. この症例をどうするか「内視鏡外科」 肝右葉前区背側域および後区域の完全腹腔鏡下肝切除術 半腹臥位完全鏡視下肝切除術の有用性の検討.
647. バイオマーカー 肝細胞癌におけるFDG-PET検査のSUV max値亢進の生物学的意義の検討.
648. 侵襲に対する生体反応とその制御 肝再生におけるオートファジーの意義.
649. 内頸静脈を用いた生体肝移植右葉グラフトの中肝静脈分枝再建.
650. 内頸静脈を用いた生体肝移植右葉グラフトの中肝静脈分枝再建の有用性についての検討.
651. 半腹臥位経横隔膜ポート、Water-Dripping Modern Bipolarを用いた完全腹腔鏡下肝切除術の有用性の検討.
652. 多孔静脈の再建に内・外頸静脈を用いた右葉グラフト生体肝移植の一例
56歳男。30歳時に外傷性尿道断裂に対し開腹手術、輸血の既往があり、C型肝硬変による腹水貯留のため入退院を繰り返していた。今回、高度の腹水貯留、黄疸および肝性脳症を発症し生体肝移植目的に紹介となった。腹部は大量の腹水で膨満し下腿浮腫が著明で、肝機能障害を認めた。肝腎症候群状態でNH3 160μg/dlと高値で、HCV-Ab(+)、腫瘍マーカーはAFP 3.5ng/ml、PIVKA-II 0.2nAU/mlであった。また、Child-Pugh ScoreはGrade C(13点)、MELD scoreは21点であった。腹部CTでは、肝内門脈の狭小化、門脈血栓を認め腹水が大量に貯留していた。ドナーの肝術前評価は右葉グラフトの予想グラフト重量は713g、予想グラフト・標準肝容積比は49.6%となり、右肝静脈、右下肝静脈、V5、V8と4本の肝静脈が残ることが予想された。レシピエントは全肝摘出前に静脈再建のグラフトとして予め右内頸静脈・外頸静脈を採取した。摘出肝門脈は血栓血栓のため使用不可能であった。内頸静脈・外頸静脈を用いた多孔静脈一括再建で移植を施行した。術後は良好で、術後7日目のCTで右肝静脈、右下肝静脈、V5、V8のいずれも開存を認め、術後22日に退院した。.
653. 多施設共同による膵癌術後の膵液瘻に関する危険因子と予後規定因子の解析.
654. 安全確実な肝切除術の工夫 完全腹腔鏡下肝切除 安全性の向上と適応拡大のための工夫.
655. 完全腹腔鏡下膵切除術における膵切断方法の検討 切除症例と動物実験での検討.
656. 小児生体肝移植後の脱毛症.
657. 成人間生体肝移植術後の早期合併症により再開腹に至った症例の検討.
658. 最新の術後感染症対策 生体肝移植後細菌性敗血症の現状と対策.
659. 最近の消化器手術と栄養管理(肝胆膵) 肝移植における術前・術後栄養管理の術後感染症対策としての可能性.
660. 消化器臓器移植後の免疫抑制療法の新展開 生体肝移植後腎機能障害に対する対策 ミコフェノール酸モフェチル単剤療法の有用性.
661. 生体肝移植における脂肪肝ドナーダイエットの評価におけるMRIの有用性.
662. 生体肝移植における術後合併症対策 肝静脈・門脈・肝動脈・胆管 生体肝移植後の肝静脈、門脈、肝動脈、胆管合併症と対策.
663. 生体肝移植におけるSmall-for-size 病態の解明と対策 生体肝移植グラフトの短期予後を反映する新基準の提唱 Delayed functional hyperbilirubinemia(DFH).
664. 生体肝移植における胆管周囲の血流温存術式導入後の胆管狭窄に係わる危険因子.
665. 生体肝移植の肝拡大左葉グラフトドナーにおける残肝の再生の検討 とくに肝静脈側副血行路の形成について.
666. 生体肝移植を含む3回の開腹歴後に完全腹腔鏡下脾臓摘出術を施行し得た一例.
667. 生体肝移植ドナー肝切除に於ける片葉グリソンHangingによる肝門部処理 胆道合併症ゼロを目指して.
668. 生体肝移植ドナーに於ける胆道合併症減少への取り組み.
669. 生体肝移植後に合併した血栓性微小血管障害(TMA)の1例.
670. 生体肝移植後肝細胞癌再発に於ける外科的切除の有効性.
671. 生体肝移植術後胆管吻合部狭窄に対するsimultaneous percutaneous and endoscopic approach(SPEA)の有用性に関する検討.
672. 生体肝移植術後早期のVirtual Touch Tissue Quantification(VTTQ)によるグラフト肝硬度評価の有用性.
673. 生体肝移植術後菌血症に対する分枝鎖アミノ酸の効果に関する研究.
674. 生体肝移植術後の肝細胞癌再発における好中球リンパ球比の意義.
675. 移植医療における免疫抑制剤の使用法 生体肝移植後腎機能障害例に対する我々の免疫抑制法.
676. 移植医療のトピックス 脳死臓器移植など 生体肝移植の経験に基づいた脳死肝移植の適応に関する検討.
677. 肉腫様変化を伴ったStageI肝細胞癌の1切除例.
678. 肉腫様変化を伴う肝内胆管癌の一切除例.
679. 肝再生におけるオートファジーの生物学的意義.
680. 肝分化/再生/幹細胞 肝再生におけるオートファジーの生物学的意義.
681. 肝切除のためのModern Bipolar Electrocoagulatorの適切な使用方法.
682. 肝移植5年後に肝癌再発を認めた1例
一定基準内の肝細胞癌に対する肝移植は比較的良好な成績を収めるようになった.一方,肝移植後に肝癌再発をきたした症例の予後は極めて不良である1).それら移植後肝癌再発の特徴として,早期多臓器転移再発であり,ほとんどが術後2年以内,特に1年前後に多臓器転移で再発することが多い.今回われわれはミラノ基準外肝癌に対して生体肝移植を施行後,5年の期間を経て再発を認めた症例を経験したので,若干の文献的考察を加えて報告する.症例は60歳代の男性.C型肝硬変に合併したミラノ基準外肝細胞癌に対して生体肝移植術を施行した.術後再発なく経過観察されていたが,術後5年目に胃小彎のリンパ節転移性再発を発症し,腫瘍摘出術を施行した.さらにその5ヵ月後には移植肝の肝静脈根部にグラフト肝転移性再発を指摘され,放射線化学療法にて治療を行うも,生体肝移植より5年7ヵ月後に死亡した.(著者抄録).
683. 肝移植における門脈圧亢進症の取り扱い 生体肝移植に於ける治療成績向上を目指した門脈血行動態の適正化戦略.
684. 肝移植後5年目に肝癌再発を認めた1例.
685. 肝移植後ウイルス性肝炎の現状と対応 生体肝移植後C型肝炎に対するペグインターフェロン・リバビリン療法の展開.
686. 武藤 純, 調 憲, 吉屋 匠平, 的野 る美, 戸島 剛男, 播本 憲史, 山下 洋一, 池上 徹, 吉住 朋晴, 副島 雄二, 石神 康生, 前原 喜彦, 肝細胞癌におけるapelin/APJ系を介した新しい血管新生阻害療法に関する基礎的研究(Apelin/APJ system could be a new target of anti- angiogenic therapy against hepatocellular carcinoma), 日本癌学会総会記事, 71回, 64-64, 2012.08.
687. 肝細胞癌における新たな血管新生阻害療法の可能性Apelin/APJ系の意義.
688. 肝細胞癌に対する長期成績からみた系統的肝切除の意義.
689. 肝細胞癌に対する生体肝移植後の予後因子および分子標的としてのmicroRNAに関する検討.
690. 肝細胞癌の血管新生におけるapelin/APJ系の意義.
691. 肝臓・膵臓内視鏡外科の進歩と今後の課題(保険収載後の普及について) 完全腹腔鏡下肝切除 安全性の追求と適応拡大への工夫.
692. 肝静脈V4の解剖に基づく右葉グラフトを用いた生体肝移植の有効性に関する検討.
693. 胆汁鬱帯性肝硬変症の食道静脈瘤に対する予防的EVLの適応限界に関する検討.
694. 脳死肝移植の現状と我が国における今後の肝移植の展開 当科における脳死肝移植待機患者の現状と脳死肝移植の適応に関する検討.
695. 腎機能障害を合併する肝細胞癌患者における外科治療.
696. 副島 雄二, 池上 徹, 伊地知 秀樹, 池田 哲夫, 調 憲, 吉住 朋晴, 内山 秀昭, 山下 洋市, 播本 憲史, 戸島 剛男, 松浦 弘, 岡留 健一郎, 前原 喜彦, 腹腔鏡下肝切除における手術手技の工夫と変遷(Technical Evolution of Laparoscopic Hepatic Resection: A Single Institutional Experience), 福岡医学雑誌, 103, 11, 226-32, 2012.11, 【目的】腹腔鏡下肝切除は、未だ発展途上の術式である。今回、当施設における腹腔鏡下肝切除の術式工夫の変遷とその成績を検討した。【方法】2010年4月~2012年3月までに12例の腹腔鏡下肝切除:腹腔鏡補助下(Hybrid-LHR)5例、完全腹腔鏡下(Pure-LHR)7例を行った。手術適応はHCC9例、転移性肝癌3例であった。術式は外側区域切除(n=4:Hybrid-LHR n=2、Pure-LHR n=2)、部分切除(n=5:それぞれn=2、n=4)、左葉切除(n=1:Hybrid-LHR n=1)、右葉切除(n=1:Pure-LHR n=1)であった。Hybrid-LHR 5例は腹腔鏡補助下で肝脱転後、小開腹をおきCUSA、ソフト凝固で直視下に通常の肝切離を行った。Pure-LHR 7例では完全腹腔鏡にCUSA、腹腔鏡用ソフト凝固、バイクランプを基本デバイスとして用い通常の開腹肝切離と同様に肝切離を行った。【結果】前半5例と後半7例の平均手術時間3.8時間vs.6.1時間、出血量220ml vs.611ml、術後入院日数9.4日vs.7.4日であった。後半の1例に4単位の輸血を要した。肝切離面の癌浸潤は全例陰性であった。術後合併症は1例も認めなかった。【結論】腹腔鏡下肝切除はあらゆる腫瘍占拠部位に対して可能であり、有効な手術手技である。(著者抄録).
697. 腹腔鏡下肝切除術 腹腔鏡下肝切除術の安全性追求と適応拡大の工夫 半腹臥位、経横隔膜ポートの検討.
698. 腹腔鏡下肝切除の役割 手術方法の改善に伴う適応拡大と成績.
699. 腹腔鏡下肝切除を学ぶ 肝エネルギーデバイス(自動縫合器の使用法も含む).
700. 腹腔鏡下胆嚢摘出術における術中胆管損傷の予防法 ENBD術中胆管造影の有用性の検討.
701. 腹腔鏡下膵切除術における膵切断方法の検討.
702. 膵体尾部切除後膵液漏に対するRendezvous techniqueを用いた経皮的ドレナージが奏功した1例.
703. 膵尾側切除における膵切離法とその成績 最も安全な膵切断方法の検討 完全鏡視下膵体尾部切除症例と動物実験から.
704. 臓器移植法案改正後、急性肝不全に対する肝移植適応はどう変わったか? 改正臓器移植法施行前後の急性肝不全に対する生体肝移植.
705. 萎縮門脈を伴う肝硬変患者に対して左腎静脈門脈吻合を施行した生体肝移植の一例.
706. 術中の想定外の血管・胆管損傷にどう対処するか 動脈再建困難な生体肝移植における非解剖学的動脈再建の有用性.
707. 術前3D-CTに基づいた右肝静脈灌流域切除の安全性と有用性の検討.
708. 複数の静脈の再建に内・外頸静脈を用いた右葉グラフト生体肝移植の一例.
709. 超緊急生体肝移植により救命し得た亜急性型劇症肝炎の一例
60歳代女。発熱と食欲不振を認め、近医にて葛根湯を処方されていた。その後、全身倦怠感の増悪、両眼瞼結膜の黄染が出現した。黄疸および肝逸脱酵素高値が認められ、急性肝炎と診断され紹介された。画像上での肝萎縮はなかったが、肝酵素上昇と凝固系の消費を認め、脳症は認められなかったが、劇症化リスクが高い判断された。集中治療室にてステロイドパルス療法およびAT-III製剤投与を開始したが、2度の脳症が出現したため、亜急性型劇症肝炎と診断された。血漿交換を施行したが脳症は3度に進行し、治療抵抗性と判断され、発症11日目に緊急移植目的にヘリ搬送された。黄疸著明、少量腹水および意思疎通不可であったが脳幹反射は残存していた。腹部CTでは、著明な肝萎縮と少量の腹水を認めた。ドナーはレシピエントの長男(30歳代男)で、拡大左葉切除採取を行った。レシピエントの肝は表面顆粒状、辺縁はシャープで著明な萎縮を認め、グラフト肝とレシピエントの肝静脈および門脈の吻合で再還流を行った。胆道再建は胆管同士の吻合とした。やや高値の門脈圧は脾動脈結紮を行ったところ低下した。移植は搬送より6時間46分後と早期施行にも関わらず脳症が遷延したが、術後3日目に徐々に改善を認め、術後6日目にICU退室となった。ビリルビン高値が持続し腹水貯留も認めたが徐々に改善し、術後42日目に脳症による後遺症もなく退院となった。.
710. 転移性肝癌に対する腹腔鏡下肝切除術.
711. 転移性肝癌に対する腹腔鏡下肝切除.
712. 透析患者に対する生体肝移植の一例.
713. 骨格筋の標準値算出式に関する検討.
714. 80歳以上の超高齢者における肝細胞癌に対する肝切除術の安全性の検討.
715. 80歳以上肝細胞癌に対する肝切除術の検討.
716. ARFIを用いた生体肝移植ドナー術後肝再生過程の残肝、脾臓硬度の評価とその臨床的意義.
717. Acoustic Radiation Force Impulse(ARFI)を用いた肝硬度測定法による術後難治性腹水の予測について.
718. C型肝硬変に対するIFN導入目的の脾摘における、IL28B、ITPA遺伝子多型解析 脾摘の有用性.
719. Damege Control Surgeryにて救命し得た外傷性他臓器損傷の一例.
720. Tomoharu Yoshizumi, Ken Shirabe, Akinobu Taketomi, Hideaki Uchiyama, Torsi Ikegami, Noboru Harada, Hideki Ljichi, Yuji Soejima, Yoshihiko Maehara, Living Donor Liver Transplantation: Lessons Learned from 318 Consecutive Cases, LIVER TRANSPLANTATION, 17, 6, S267-S268, 2011.06.
721. A. Taketomi, J. Muto, T. Motomura, Y. Mano, K. Takeishi, T. Toshima, H. Ijichi, N. Harada, H. Uchiyama, T. Yoshizumi, K. Shirabe, Y. Maehara, Long-term outcomes of the patients with hepatocellular carcinoma after living donor liver transplantation using left lobe graft., JOURNAL OF CLINICAL ONCOLOGY, 29, 15, 2011.05.
722. Yuji Soejima, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegamiu, Yoshihiko Maehara, STRATEGIC BREAKTHROUGH AND PARADIGM SHIFT IN ADULT ABO-INCOMPATIBLE LIVER TRANSPLANTATION, TRANSPLANT INTERNATIONAL, 24, 12-12, 2011.09.
723. 【B型肝炎・肝移植後の再発予防法の現状】 HBc抗体陽性ドナーを用いた肝移植
肝移植においてHBs抗原陰性/HBc抗体陽性者をドナーとした場合、以前は特別な処置は必要ないと判断されていた。しかし、HBs抗体陰性レシピエントにHBc抗体陽性ドナーの肝臓を移植したあとのB型肝炎発症(いわゆる"de novo B型肝炎")が報告されて以来、さまざまな発症予防法が工夫されてきた。現在では、核酸アナログおよびHBIGの併用療法が普及し、ほぼ完全にde novo B型肝炎の発症を予防できるようになった。しかし、耐性株の出現や、医療経済的な面から新たな課題も浮き彫りになっている。最近では、新規核酸アナログであるエンテカビルを使用したde novo B型肝炎発症予防法が試みられている。今後は、これらの治療法の長期成績を検証し、HBc抗体陽性ドナーを用いた肝移植において、より効率的な発症予防法の確立が期待される。(著者抄録).
724. 【Changed!?臓器移植法改正施行後1年の現況】 さらに新しいチャレンジ DonorとRecipientの宿主遺伝子背景からみた再発HCVに対するIFN感受性予測.
725. 【C型肝炎のすべて2012】 インターフェロンの上手な使い方 肝移植後のHCV感染に対するPEG-IFN/Ribavirin療法.
726. 【肝癌の診療Up to date】 肝癌治療のアルゴリズム
肝細胞癌の治療は、肝切除、局所療法、TACE、肝移植、肝動注療法、ソラフェニブ内服など多岐にわたり、さらには肝機能や腫瘍因子などの制約を受ける。したがって、個々の症例においてどの治療を選択するかを考える上で治療アルゴリズムはきわめて重要である。日本での主な肝癌治療アルゴリズムとして、科学的根拠に基づく肝癌診療ガイドラインの「肝細胞癌治療アルゴリズム」と肝臓学会で提案された肝癌診療マニュアルの「コンセンサスに基づく肝細胞癌治療アルゴリズム」がある。また、海外ではBarcelona-Clinic-Liver-Cancer(BCLC)staging systemが普及している。本稿では、当科における肝細胞癌の外科治療成績も交えながら、これら3つの代表的な肝癌治療アルゴリズムを解説する。(著者抄録).
727. ゲノム解析による肝移植後再発C型肝炎に対する高精度IFN治療効果予測法の開発.
728. ヒトの癌組織におけるヒストンメチル基転移酵素WHSC1遺伝子の発現とその意義に関する検討.
729. 先天性胆道閉鎖症に対し生体肝移植術施行後、妊娠を契機としたラミブジン内服中止ののち、HBV感染を認めていない一症例.
730. 免疫抑制剤中止後の長期成績 生体肝移植術後ミコフェノール酸モフェチル単剤療法の有用性に関する検討.
731. 再発肝細胞癌に対する治療戦略 長期生存を目指した肝細胞癌術後再発への治療戦略 抗ウイルス療法、焼灼療法、肝移植による総合戦略.
732. 原疾患の背景の差異により生じているわが国の肝移植の特殊性(PSC、PBC) Primary Biliary Cirrhosis、Primary Sclerosing Cholangitisに対する生体肝移植の成績 特に移植後原疾患の再発に注目して.
733. 右葉グラフトを用いた生体肝移植 術前3D CTによる計画的ドナー肝右葉切除とグラフト中肝静脈枝再建.
734. 右葉グラフトを用いた生体肝移植 術前3D CTによる計画的ドナー肝右葉切除とグラフト中肝静脈枝再建.
735. 安全かつ確実な腹腔鏡下肝切除術を目指して 左半腹臥位から右側臥位までの体位変換、Glisson一括処理、Suspender Maneuverを用いた腹腔鏡下肝切除術の検討.
736. 宿主IL28B/ITPA遺伝子多型解析から見た移植後再発HCV治療戦略.
737. 宿主IL28B/ITPA遺伝子多型解析から見た移植後再発HCVに対する治療戦略.
738. 我が国の肝移植の現状と将来 肝移植の治療成績向上を目指した我々の新しい取り組みと展望.
739. 手術療法 肝細胞癌切除成績と新たな再発機序の解明.
740. 手術療法 肝細胞癌に対する新たな肝移植適応基準の検討.
741. 新しい手術器機の開発(肝臓・その他) 肝臓、膵臓切離のために新たに開発した水滴機能、可変機能、自己洗浄機能付きMonopolor、Bipolor鉗子の検討.
742. 新しい画像シミュレーションと基礎研究に基づく肝切除の安全性向上の追求.
743. 消化器外科における術前術後合併症とその対策(肝胆膵) 生体肝移植ドナー肝切除術における胆道合併症ゼロへの取り組み.
744. 消化器外科手術に活かす画像診断の新展開 肝臓外科領域における新しい非侵襲的臓器硬度測定法の確立と有用性.
745. 生体肝移植後の肝癌再発予防を目指したIL12/DC併用Neoadjuvant immunotherapyの展開.
746. 生体肝移植後腎機能障害に対するミコフェノール酸モフェチル単剤療法の有用性
わが国における生体肝移植の短期成績は向上してきたが、長期生存例におけるカルシニューリン阻害剤による腎機能障害が問題となっている。代謝拮抗剤であるMMFは、IMPからキサンチン酸への変換を触媒するIMP dehydrogenaseの活性を特異的に阻害することによりグアニル酸の合成を抑え、リンパ球の産生に必要な核酸の合成を抑制する。MMFは腎機能障害の副作用がないことから、肝移植後の免疫抑制剤として注目が集まっている。当科においても生体肝移植後腎機能障害をきたした症例に対して、MMF(セルセプト)の継続あるいは再開とカルシニューリン阻害剤の減量を行い、これまでに6例でセルセプト単剤療法を施行した。その結果、5例で血清クレアチニン値の改善を認めたが、急性拒絶反応を発症した症例はなく、消化器症状や汎血球減少などの副作用を認めた症例はなかった。いまだ観察期間が短いため、急性拒絶反応の発症に関しての言及はできないが、腎機能改善に対して本療法はきわめて有用であると考えられた。(著者抄録).
747. 岡野 慎士, 萱島 寛人, 戸島 剛男, 池上 徹, 吉住 朋晴, 副島 雄二, 武冨 紹信, 調 憲, 原田 守, 前原 喜彦, 移植後肝細胞癌再発制御におけるIL12と樹状細胞を用いた術前補助免疫療法の抗腫瘍効果の検討(Neoadjuvant immunotherapy using IL12/DC for control of recurrent hepatocellular carcinoma in immunosuppressed mice), 日本癌学会総会記事, 70回, 393-393, 2011.09.
748. 移植後胆道狭窄に対する治療の長期成績 成人間生体肝移植後の胆管狭窄がグラフトの長期予後に与える影響.
749. 肝・胆 肝細胞癌に対する生体肝移植後の予後因子としてのmicroRNA発現の意義.
750. 肝内胆管癌におけるRoundabout1(ROBO1)発現の臨床病理学的意義.
751. 肝再生におけるオートファジーの意義.
752. 肝再生におけるオートファジーの意義.
753. 肝再生医学研究の新展開 肝再生におけるオートファジーの意義.
754. 肝右葉に直接浸潤した巨大腎細胞癌に対して前方アプローチで肝腎同時切除した1例.
755. 肝嚢胞に対する腹腔鏡下手術の有用性と安全性.
756. 肝移植 現状と今後の課題 脳死肝移植の適応に関する検討 脳死ドナーの尊い意志を活用するために.
757. 肝移植後の門脈圧亢進症 生体肝移植後における脾機能亢進症持続症例の検討.
758. 肝細胞癌における肝移植の現状と課題 肝細胞癌に対する生体肝移植術後の新しい予後因子 好中球リンパ球比の解析.
759. 肝細胞癌におけるジアシルグリセロールキナーゼα発現の生物学的意義.
760. 肝細胞癌に対する左葉グラフトを用いた生体肝移植の長期成績.
761. 肝細胞癌に対する生体肝移植術後の、好中球リンパ球比による新しい予後因子.
762. 肝細胞癌を合併した生体肝移植症例におけるMRI造影剤EOB・プリモビストによる術前画像診断の有効性の検討.
763. 肝細胞癌進展におけるオートファジーの意義.
764. 肝胆膵領域癌における周術期因子の予後への影響(1) 肝細胞癌に対する肝切除後の肝外再発危険因子の検討.
765. 肝臓切除術における抗酸化物含有栄養剤の術前投与の有用性に関する検討.
766. 肥満レシピエントの生体肝移植成績に及ぼす影響に関する検討.
767. 胆道閉鎖症肝移植適応症例における移植前の栄養状態に関する検討.
768. 腎機能障害を合併する肝細胞癌患者における外科治療.
769. 腫瘍関連マクロファージによる肝細胞癌のSignal Transducer and Activated of Transcription 3(STAT3)活性化と臨床病理学的検討.
770. 腹腔鏡下肝・膵切除術の適応と工夫 完全腹腔鏡下肝切除術 部分切除から系統的肝切除へ向けた適応と工夫.
771. 腹腔鏡下胆嚢摘出術における術中胆管損傷の究極的な予防方法 ENBD術中胆管造影の有用性の検討.
772. 膵体尾部腫瘍に対する完全腹腔鏡下膵切除術 脾温存膵体尾部切除術2例を含む7例の工夫と成績.
773. 血管再建を伴う肝切除の手技上の工夫とその意義 右葉グラフトを用いた生体肝移植におけるState of the art 術前3D-CTによる計画的ドナー肝右葉切除とグラフト中肝静脈枝再建.
774. 術前FDG-PETの原発性肝癌の悪性度判定における有用性に関する検討.
775. 術前FDG-PETの原発性肝癌の悪性度判定における有用性に関する検討.
776. 術前FDG-PETの原発性肝癌の悪性度判定における有用性.
777. 超高齢者の肝細胞癌に対する肝切除術の安全性の検討 特に短期成績と肝再生について.
778. 門注療法を用いない血液型不適合移植に対する免疫抑制プロトコールの治療成績.
779. 門脈腫瘍栓を伴う進行肝癌の長期生存の因子 術後再発に対する治療戦略について.
780. 門脈腫瘍栓を伴う肝細胞癌切除後の長期生存に関する因子の検討.
781. Yuji Soejima, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yoshihiko Maehara, "All-in-One" Ex Vivo Self-Reconstruction Technique Using an Autologous Inferior Vena Cava for a Right Lobe Liver Graft with Multiple and Complex Venous Orifices, LIVER TRANSPLANTATION, 16, 6, S166-S166, 2010.06.
782. 40歳未満肝細胞癌の臨床学的特徴および肝切除術の臨床的意義.
783. 60歳以上の高齢者に対する成人間生体肝移植成績の検討.
784. B型肝炎に対する生体肝移植の成績と術後再発予防.
785. ChildB肝硬変肝癌に対する肝移植の適応と成績.
786. HBV陽性肝細胞癌患者における術後HBV治療の意義.
787. 【乳糜胸水・腹水を考える その原因と対策】 [術後合併症としての乳糜胸水・腹水 対応に困ったこの症例] 肝胆膵外科手術後の乳糜腹水 生体肝移植術後に発症した乳糜腹水の1例
わが国は有数の生体肝移植先進国となり,その成績も良好である.しかし,術後合併症は避けがたく,適切な術後管理が必須となる.乳糜腹水は生体肝移植術後には稀な合併症であるが,当科でも1例経験したので報告する.症例は40歳の女性,原発性胆汁性肝硬変に対して生体肝移植術を施行した.術後より多量の腹水を認めたが,術後21日目より乳糜腹水を発症した.低脂肪食への変更,完全静脈栄養への変更でも改善を認めず,完全静脈栄養およびソマトスタチンアナログの併用にて速やかに乳糜腹水の消退を認め,術後166日目に軽快退院となった.生体肝移植術後の乳糜腹水に対して,完全静脈栄養およびソマトスタチンアナログの併用は非常に効果的であった.(著者抄録).
788. 【先端的画像支援による肝胆道手術】 3D-CT 3D-CT支援による右肝静脈還流域切除.
789. ドナー・レシピエントの性別の相違による生体肝移植術後の長期成績.
790. ミコフェノール酸モフェチルを用いた新たな生体肝移植後免疫抑制導入法の確立.
791. 再発肝細胞がんに対する生体肝移植の治療成績.
792. 切除不能肝細胞癌に対するソラフェニブの使用経験.
793. 小さな肝がんに対する治療 手術vs RFA 小肝細胞癌に対する外科切除の成績の変遷 単施設22年の成績.
794. 拡大肝切除の術前評価と肝不全予防 新しい肝機能予測式による成人間生体肝移植術後の肝不全予知と脾臓摘出の効果に関する検討.
795. 最近5年間の成人生体肝移植施行例の短期成績とその評価 最近5年間の成人間生体肝移植の短期成績と成績向上への取り組み.
796. 生体肝移植310例におけるSSIの解析.
797. 生体肝移植におけるグラフトサイズを考える 肝左葉グラフトを第一選択とする生体肝移植ドナー選択基準の意義.
798. 発熱を契機に発見された肝未分化癌の1例
肝未分化癌は極めて稀であり,症例報告が散見される程度である.今回われわれは発熱を契機に発見された肝未分化癌の1切除例を経験したので報告する.症例は61歳,男性.1週間程度持続する微熱にて前医を受診した.胸部CTを施行されたところ,偶然肝腫瘤を指摘された.肝膿瘍を疑われ当院紹介となり,抗生剤投与にて治療開始された.入院中は解熱を認めず,腹部造影CTおよびMRI,肝生検等の精査にて原発性肝悪性腫瘍が疑われた.肝S7亜区域切除術が施行され,病理診断にて肝未分化癌の診断となった.術直前まで認めていた発熱は術後6日目に解熱,腫瘍壊死組織からの発熱であったと考えられた.肝未分化癌には明確な定義がなく,病理診断にて同診断に至ることは極めて稀である.また,早期に血行性・リンパ行性転移を起こし予後不良とされている.本症例では治癒切除が可能であった.術後8ヵ月の時点では再発を見ていないが,厳重な経過観察が必要と考えられる.(著者抄録).
799. 肝移植後早期合併症 生体肝移植術後に門脈血流確保が困難であった胆道閉鎖症の1例
11ヵ月男児。40生日時に胆道閉鎖症で肝門部空腸吻合術を施行されたが、減黄不良で肝機能障害が進行し、母親をドナーとする左葉グラフトを用いた生体肝移植を施行した。術中所見で門脈径は細く、ドナーのIMVを用いた門脈形成と、レシピエントの肝周囲に増生したcoronary veinの結紮を施行した。肝静脈はドナーの左肝静脈とレシピエントの中肝静脈を吻合し、肝動脈はドナーの左冠動脈と中肝動脈を一穴に形成してレシピエントの肝動脈と吻合した。再灌流直後の門脈血流は良好であったが、動脈吻合後に血流は消失し、門脈内に血栓を認め、血栓除去後に再吻合した。術後の減黄は良好で、肝障害も改善傾向にあったが、門脈血流の流量は低下傾向を示した。移植後8日目に肝逸脱酵素の急激な上昇を認め、血管造影で門脈血栓症と診断し、左腎静脈-大伏在静脈グラフト-門脈臍部吻合で門脈再建を施行した。その4日後に再度の門脈血栓症を来たし、脾動脈-グラフト吻合、脾臓摘出術を施行し、門脈血流は良好となった。しかし、その後腹腔内出血を繰り返し、多臓器不全に陥って移植後30日目に死亡した。剖検では移植肝の肝梗塞を認めた。.
800. 肝細胞癌におけるオートファジーの意義.
801. 武石 一樹, 武冨 紹信, 調 憲, 戸島 剛男, 本村 貴志, 間野 洋平, 伊地知 秀樹, 原田 昇, 内山 秀昭, 吉住 朋晴, 坂根 郁夫, 前原 喜彦, 肝細胞癌におけるDGKα発現の生物学的意義(The biological significance of diacylglycerol kinase alpha expression in hepatocellular carcinoma), 日本癌学会総会記事, 69回, 246-246, 2010.08.
802. 肝胆膵悪性腫瘍に対する内視鏡手術の導入 手術手技の工夫、評価と展望 肝悪性腫瘍に対する完全腹腔鏡下肝切除術 適応と手術手技の工夫.
803. 肝胆膵領域がんに対する鏡視下手術の適応・限界 肝癌に対する完全腹腔鏡下肝切除術(Pure laparoscopic hepatectomy:PLH)の適応と限界.
804. 脳死肝移植実施における現状と問題点 生体肝移植の経験から得た脳死肝移植の適応に関する検討.
805. 血液型不適合肝移植における新しい免疫抑制プロトコールの有用性.
806. 食道がん手術における補助療法の導入とその効果 食道癌に対する術前化学・放射線療法の意義.
807. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Hideaki Uchiyama, Tomoharu Yoshizumi, Keishi Sugimachi, Tomoharu Gion, Yoshihiko Maehara, A SINGLE CENTER EXPERIENCE OF 50 LIVING DONOR LIVER TRANSPLANTATIONS FOR ACUTE LIVER FAILURE, TRANSPLANT INTERNATIONAL, 22, 199-199, 2009.08.
808. ABO不適合生体肝移植術後にサイトメガロウイルス感染症を発症し,経過中に多形紅斑を認めた1例
21歳女性(血液型:O型)。患者は全身倦怠感、食欲不振、嘔吐で近医を受診、劇症肝炎と診断され、著者らの施設へ紹介となった。入院時、血漿交換や持続的血液濾過透析を行うも肝機能は改善せず、A型の継父をドナーとしたABO不適合生体肝移植が行われた。術後は免疫抑制剤投与で経過は良好であったが、術後19日目にサイトメガロウイルス(CMV)抗原陽性が認められ、ガンシクロビル(GCV)の投与を行うことで経過良好となった。だが、術後67日目に発熱、更に腹痛と下痢が生じ救急搬送された。所見ではCMV抗原の著増から内視鏡でCMV腸炎、CTでCMV肺炎が認められ、GCV投与で症状は徐々に改善し退院をみた。以後、手術から181日目にCMV抗原が上昇し、入院の上、GCV投与が行われたが、多形紅斑と両手足関節痛の出現から薬疹と考え、GCVを中止、4週間を経て紅斑と関節痛は改善した。目下、4ヵ月経過しているが再発は認められていない。.
809. ABO血液型不適合移植の現状と今後の展望 門脈・動脈注入療法を用いない新しい血液型不適合肝移植.
810. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Toshiharu Saibara, Takashi Nishizaki, Yoshihiko Maehara, Recurrent familial hypobetalipoproteinemia-induced nonalcoholic fatty liver disease after living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.21766, 15, 7, 806-9, 2009.07, Familial hypobetalipoproteinemia (FHBL) is one of the causes of nonalcoholic steatohepatitis (NASH) and a codominant disorder. Patients heterozygous for FHBL may be asymptomatic, although they demonstrate low plasma levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Here we report a nonobese 54-year-old man with decompensated liver cirrhosis who underwent living donor liver transplantation with his son as the donor. Low albuminemia and refractory ascites persisted after transplantation. A biopsy specimen obtained 11 months after liver transplantation revealed severe steatosis and fibrosis, and recurrent NASH was diagnosed on the basis of pathological findings. Both the patient's and donor's laboratory tests demonstrated low LDL cholesterol and apolipoprotein levels. Because mutations in messenger RNAs of microsomal triglyceride transfer protein and apolipoprotein B genes were excluded neither in the recipient nor in the donor, both were clinically diagnosed as being heterozygous for FHBL. We successfully treated the recipient with heterozygous FHBL-induced recurrent NASH after liver transplantation using our diet and exercise programs..
811. 【腫瘍占居部位からみた肝切除の手技と工夫】 巨大肝腫瘍に対する体外肝切除術.
812. Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Hideaki Uchiyama, Noboru Harada, Yo-ichi Yamashita, Hirofumi Kawanaka, Yoshihiko Maehara, THE BENEFICIAL ROLE OF SIMULTANEOUS SPLENECTOMY IN LIVING DONOR LIVER TRANSPLANTATION IN PATIENTS WITH SMALL-FOR-SIZE GRAFT., LIVER TRANSPLANTATION, 14, 7, S94-S94, 2008.07.
813. Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Yoichi Yamashita, Noboru Harada, Keishi Sugimachi, Yoshihiko Maehara, THE FACTORS ASSOCIATED WITH MAJOR COMPLICATIONS AFTER LIVING DONOR HFPATECTOMY, LIVER TRANSPLANTATION, 14, 7, S209-S209, 2008.07.
814. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, The use of explanted portal vein or shunt vessel for middle hepatic vein reconstruction in right lobe living donor liver transplantation., AMERICAN JOURNAL OF TRANSPLANTATION, 8, 613-613, 2008.05.
815. 【C型肝炎の肝移植 最近の進歩】 生体肝移植後ステロイドフリー免疫抑制法によるC型肝炎再発の制御
HCV陽性症例は、わが国における成人生体肝移植の適応疾患のなかで最多であり、今後も症例数が増加していくことが予想される。HCV陽性生体肝移植50例を免疫抑制導入法により3群にわけ、移植後HCV RNA量、急性拒絶反応の発生率、肝炎再発率、ペグインターフェロンの効果を検討した。ステロイドフリーによる免疫抑制導入法では、急性拒絶反応の発生率は低く、移植後2ヵ月間のHCV RNAが有意に低かった。組織学的再発率とペグインターフェロンの効果では差を認めず、今後の検討課題である。(著者抄録).
816. 【最新の肝胆膵の3Dイメージ】 生体肝移植術前評価における3D-CT画像の有用性
欧米とは異なり、本邦では脳死肝移植は普及せず、生体肝移植が主流である。症例数は年間400例を超え、世界でも有数の生体肝移植先進国となった。しかし、健常なドナーに手術を行う特殊な治療法であり、ドナーに対する安全性の評価が最も重要であることは言うまでもない。当科では、2種類の3D-CTソフト(zio M900およびREGION GROW)を用いて生体肝移植術前評価を施行している。3D-CT画像は肝容積測定や肝臓内の脈管の解剖把握に非常に有用であり、さらには、中肝静脈の分枝であるV5およびV8、右下肝静脈の還流領域の測定も可能である。生体肝移植の術前評価には必須の検査であり、今やなくてはならない存在である。当科での生体肝移植術前評価における2種類の3D-CTソフトの有用性とその使用方法を実際の画像を供覧しながら紹介し、当科での取り組みと、今後の展望について述べることとする。(著者抄録).
817. 【肝移植Crossfire】 PSCとPBCと肝移植 原発性硬化性胆管炎に対する胆管吻合の選択で差が生じるか.
818. 【術後良性胆管狭窄の治療戦略】 生体肝移植における胆管吻合部狭窄の現状
生体肝移植術術後の胆管吻合部狭窄は長期成績を左右する重要な因子である。生体肝移植症例244例を、胆道再建方法によって胆管胆管吻合群(DD群、n=157)と肝管空腸吻合群(HJ群、n=87)の2群に分け、比較検討を行った。移植後3年胆管狭窄率はDD群で25.9%、HJ群で27.8%であった。結節縫合のみを用いた症例、内外瘻ステントを使用した症例は有意に胆管狭窄の頻度が少なかった(p<0.05)。また胆管狭窄症例の内、内視鏡的逆行性胆道バルーン拡張(ERBD)あるいは経皮的胆道拡張(PTBD)にて治療可能であった症例は90.7%(49/54)であり、手術を要した症例5例はすべてHJ群の症例であった。ERBDあるいはPTBDは平均1.9回施行され、治療期間は平均358日であった。結節縫合・内部外瘻ステントを使用する胆管胆管吻合は、移植後胆管狭窄率の低下が期待され、また胆管狭窄時も内視鏡的治療を中心とした治療が可能であり、第一に選択されるべき方法であると考えられた。(著者抄録).
819. 肝細胞癌に対する肝移植医療の現状と九州大学における経験.
820. 脾臓摘出が生体防御に及ぼす効果に関する研究 制御性T細胞、NK細胞に着目して
基礎的検討としてマウスを用いて脾摘の制御性T細胞、NK細胞に対する影響、および癌免疫に対する影響を検討した。また、臨床的検討として肝硬変患者での脾臓摘出による末梢血リンパ球分画への影響を解析した。マウスを用いた基礎的検討では脾臓摘出により腸間膜リンパ節の制御性T細胞、NK細胞は共に減少した。制御性T細胞の減少に限れば腫瘍免疫は高まり、逆にNK細胞の減少に着目すれば腫瘍免疫は低下することが考えられた。脾臓摘出後に肝、肺のFoxp3 mRNA量を測定し、無処置のマウスと比較してFoxp3mRNA量は有意に増加した。臨床的検討では肝硬変に伴う脾機能亢進に対して脾臓摘出を行った症例の制御性T細胞およびNK細胞の末梢血中の変化を解析したが、脾臓摘出によるこれら細胞の明らかな変化は認めなかった。.
821. Yusuke Arakawa, Mitsuo Shimada, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Hirofumi Kanemura, Koutarou Miyake, Hisamitu Shinohara, Hiroki Mori Mami Kanamoto, Takuya Tokunaga, Kouji Sugimoto, Effects of splenectomy on liver function and liver regeneration after massive hepatectomy in rats, TRANSPLANT INTERNATIONAL, 20, 268-268, 2007.09.
822. Yuji Soejima, Akinobu Taketomi, Toru Ikegami, Yoichi Yamashita, Noboru Noboru, Shinji Ito, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoshihiko Maehara, Extra-small-for-size grafts in living donor liver transplantation, TRANSPLANT INTERNATIONAL, 20, 14-14, 2007.09.
823. Mami Kanamoto, Mitsuo Shimada, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Impact of a new refrigerator for the preservation of hepatic graft, TRANSPLANT INTERNATIONAL, 20, 289-289, 2007.09.
824. Yuji Morine, Jun Hanaoka, Mitsuo Shimada, Satoru Imura, Tetsuya Ikemoto, Yasuhumi Kanemura, Kotaro Miyake, Hiroki Mori, Yusuke Arakawa, Mami Kanamoto, Toru Ikegami, Tomoharu Yoshizumi, Kampo medicine "Juzen-taiho-to" reduces regulatory T cells, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 22, A215-A215, 2007.10.
825. Satoru Imura, Mitsuo Shimada, Tomoharu Yoshizumi, Mami Kanamoto, Jun Hanaoka, Hiroki Mori, Yusuke Arakawa, Kotaro Miyake, Tetsuya Ikemoto, Fumihiro Kanemura, Yuji Morine, Living-donor liver transplantation for a patient with extrahepatic malignancy, TRANSPLANT INTERNATIONAL, 20, 271-271, 2007.09.
826. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Noboru Harada, Hiroto Kayashima, Kenji Sanefuji, Shinji Itoh, Yo-Ichi Yamashita, Yoshihiko Maehara, Tomoharu Yoshizumi, Mitsuo Shimada, The extended indication and its results of living donor liver transplantation for hepatocellular carcinoma, TRANSPLANT INTERNATIONAL, 20, 272-272, 2007.09.
827. 【PIVKA-IIの新しい展開】 PIVKA-IIの臨床 肝細胞癌患者の術後再発予測におけるPIVKA-IIの有用性.
828. 【最新 肝胆膵手術アトラス】 肝外側区域切除.
829. 【生体臓器移植における看護】 肝移植レシピエントにおける病棟看護師の役割と看護.
830. 【肝不全の各種病態と新しい治療の視点】 術後肝不全に対する治療法の選択
肝不全は、肝細胞機能が低下した結果、代謝異常とそれによるさまざまな臨床症状を呈する病態で、肝切除およびそれに伴う生体への侵襲によって惹起される。肝切除後肝不全には、大量肝切除に起因するものや、黄疸肝や肝硬変など背景肝に起因するものがある。黄疸肝では、胆汁鬱滞により肝細胞ミトコンドリアの酸化的リン酸化が障害され、ATPの産生低下が起こる。さらに胆管炎を合併すると、減黄後も胆汁鬱滞が遷延するため、肝切除後肝障害の原因となる。また、肝切除術の対象として最も多い肝細胞癌は、背景に線維化を伴う慢性肝炎や肝硬変といった障害肝を有するため、肝切除限界は低く術後肝不全のリスクは高い。術後肝不全の治療の原則は、原因である肝機能障害・再生障害因子を除去し、機能不全に陥った肝臓の機能を代行・補助しながら、肝への血流、酸素供給を維持、改善させて肝再生を促すことである。呼吸・循環を適切に管理し、全身状態の改善・維持に努めることが基本であり、特殊な治療では、血液浄化療法、肝細胞保護・肝再生促進を目的とする治療および高圧酸素療法などがある。ただし、経過中に感染症などの合併症を併発することも少なくなく、多臓器不全へ進行した場合の予後は非常に厳しい。したがって、肝不全に対する治療法の検討も大切であるが、術後肝不全に陥らないために、術前の肝予備能や肝線維化・肝炎活動性の把握と適切な術式の選択が肝要である。(著者抄録).
831. 【肝胆膵がんと化学療法のすべて】 胆道疾患 薬剤からみた化学療法 肝内肝外胆管癌(胆道癌)に対するGFP化学療法.
832. ウイルス肝炎、特に肝細胞癌合併症例に対する生体肝移植適応評価の現況
2001年9月~2005年12月に著者等の施設でウイルス性肝炎を基礎疾患に有し、移植評価・治療を目的に入院となった78症例を対象に生体肝移植適応評価の現況について検討した。対象中B型肝炎ウイルス(HBV)感染は23例・C型肝炎ウイルス(HCV)感染は53名で、HBVとHCV両者の感染が2例であった。肝細胞癌(HCC)非合併群と合併群及びミラノ基準内群と逸脱群の比較検討する因子として年齢・性・入院時血液生化学検査値(血清アルブミン・総ビリルビン・ALT・プロトロンビン時間)を選択した。残存肝予備能の指標にはChild-Pughスコア・MELDスコアを、HCC合併例の進行度指標にはTMN分類・JISスコアを用い、現存するHCCサイズ(直径)と個数は断層CT画像にて検討した。その結果、著者等の施設の移植適応基準を満たした例は78例中51例(65.4%)、適応なし例が23例(29.5%)、適応評価中及び評価判定以前の死亡例が4例(5.1%)であった。2005年末の段階で適応ありと判定され既に生体肝移植を施行された例は43例で、適切なドナーが存在しなかったため脳死肝移植登録を行った例が6例であった。適応ありと判定された症例のうちHCC合併例は35例、保険適用基準の一つであるミラノ基準逸脱例は18例であり、基準内例に比べて残存肝機能が保たれていた。現在の保険適用は非代償性肝硬変であり、HCCが存在する場合にはミラノ基準を満たす必要がある。移植を希望する症例にはミラノ基準逸脱例が少なからず存在し、非代償性にまで至っていない例も存在する。以上より米国UNOSに示されるようにHCCステージを考慮した移植保険適用の配慮が必要と考えられた。.
833. 萱島 寛人, 武冨 紹信, 黒田 陽介, 原田 昇, 播本 憲史, 丸山 晴司, 杉町 圭史, 山下 洋市, 田口 健一, 吉住 朋晴, 副島 雄二, 足立 英輔, 前原 喜彦, 肝細胞癌における相同組み換えDNA二本鎖切断修復に関わるRad51蛋白発現の検討(Expression of Rad51 protein in hepatocellular carcinoma), 日本癌学会総会記事, 66回, 489-489, 2007.08.
834. 門亢症と生体肝移植 Small-for-sizeグラフトにおける門脈循環.
835. 5cm以上の肝細胞癌に対する術前TAE,リピオドリゼーションの有用性に関する検討.
836. B型肝炎に起因する重症肝疾患に対する生体肝移植術の成績と肝炎予防への取り組み.
837. C型肝炎陽性肝硬変に対する生体肝移植と術後低容量長期インターフェロン投与によるウィルスの制御.
838. HTLV-1陽性のドナーあるいはレシピエントにおける生体肝移植の問題点.
839. Impact of the portal segmentation procedure in 3D-CT graft simulation for living-donor liver transplantation.
840. 【ウイルス肝炎の肝移植】 生体肝移植後ステロイドフリー免疫抑制法によるC型肝炎再発の制御.
841. 【外科研修医マニュアル】 手術に必要な処置 ドレーン管理.
842. 【消化器疾患 state of arts II.肝・胆・膵】 治療法をめぐる最近の進歩 肝移植の現況と問題点 肝細胞癌に対する肝移植.
843. 【肝がん治療のすべて】 肝細胞癌 肝移植 ミラノ基準内と基準外手術の成績.
844. 【肝移植 その適応疾患と移植のタイミング】 B型肝炎肝硬変に対する肝移植
B型肝炎は肝移植の適応疾患として頻度が高い疾患である.B型肝炎に対する肝移植は,再発予防法が確立していなかった1980年代は成績不良であったが,抗B型肝炎ウイルス免疫グロブリン(HBIG)とラミブジンによる再発予防法が確立してからは肝移植の良い適応疾患となった.しかし,HBIGおよびラミブジン併用療法はQOLや経済的面から問題が多い.今後は高価なHBIGに代わりうるワクチンなどの予防法の開発や新たな抗ウイルス薬の臨床応用が課題である.また,ラミブジンの普及に伴い増加が予想されるラミブジン耐性YMDD変異株に対する対応策の確立も急務である(著者抄録).
845. 【肺高血圧症を診る】 診る 肺高血圧症の臨床分類各論 肝疾患に合併する肺高血圧症.
846. カラーグラフ 診療に役立つ肉眼像と組織像の理解 マクロからミクロ像を読む 肝悪性腫瘍.
847. ドレーン排液中T-bil濃度測定による肝切除後胆汁瘻モニタリングの意義.
848. フリーラジカルスカベンジャーの臨床応用基礎研究からの提案 虚血再灌流を中心に 肝臓.
849. 急性胆嚢炎に対する待機的腹腔鏡下胆嚢摘出術の位置づけ
急性胆嚢炎に対する待期的腹腔鏡下胆嚢摘出術(LC)の位置づけについて検討した.対象は過去12年間にLCを施行した急性胆嚢炎32例で,発症後2週間以内の早期LC群6例(男性3例,女性3例・平均年齢44歳)と2週間以降の待期LC群26例(男性15例,女性11例・平均年齢53歳)に分けて比較した.1)術前の患者背景因子の性別,年齢,入院時体温,WBC,CRP値は両群間で有意差はなかったが,待期LC群で肝機能障害が高度の傾向を認めた.2)平均手術時間は早期LC群250分,待機LC群182分で,開腹移行と術後合併症は両群ともに各1例といずれも両群間に有意差はなかった.3)平均総入院日数は早期LC群16日,待期LC群40日と待期LC群で有意に延長していたが,術後入院日数は早期LC群8日,待期LC群11日と有意差は認めなかった.以上,肝機能障害を有する症例や炎症が高度の症例では,保存的加療後に待期LCを行うことも重要な選択肢と考えられた.
850. 成人生体肝移植の短期・長期成績向上の工夫 成人間生体肝移植の治療成績:現状と今後の課題.
851. 消化器外科と栄養管理 生体肝移植における脂肪肝ドナーの栄養管理と超短期ダイエットの効果.
852. 生体肝移植における3D-CTを用いた術前グラフト評価の実際.
853. 生体肝移植におけるC型肝炎に対する戦略.
854. 吉住 朋晴, 武冨 紹信, 内山 秀昭, 原田 昇, 播本 憲史, 辻田 英司, 山下 洋市, 米村 祐輔, 副島 雄二, 前原 喜彦, 生体肝移植におけるグラフト肝鬱血域の臨床的意義とその対処 右葉グラフト生体肝移植に対する肝静脈再建の手術的戦略(Operative strategy of hepatic venous reconstruction for the living donor liver transplantation by using right lobe graft), 日本外科学会雑誌, 107, 臨増2, 97-97, 2006.03.
855. 生体肝移植におけるグラフト選択と手術手技 生体肝移植における右葉グラフト選択のアルゴリズムと手術手技の工夫.
856. 生体肝移植の血行再建手技の工夫.
857. 肝内胆管癌における術後予後規定因子の解析と治療戦略.
858. 肝切除後の高圧酸素療法によるVEGF発現誘導と肝障害抑制効果に関する研究.
859. 肝移植臨床の最前線 生体肝移植における脾臓摘出の有用性.
860. 肝細胞癌におけるGrb7シグナルの解明.
861. 肝細胞癌におけるマイクロサテライト不安定性の意義.
862. 山下 洋市, 武冨 紹信, 吉住 朋晴, 内山 秀昭, 辻田 英司, 播本 憲史, 原田 昇, 北川 大, 黒田 陽介, 萱島 寛人, 前原 喜彦, 肝細胞癌に対する系統的切除のエビデンス 肝部分切除術は肝細胞癌を伴う肝硬変患者(肝障害B)に有用である 5年間のフォローアップにより(Limited hepatic resection is effective for cirrhotic (Liver damage B) patients with Hepatocellular carcinoma over 5 years follow up), 日本外科学会雑誌, 107, 臨増2, 74-74, 2006.03.
863. 武冨 紹信, 吉住 朋晴, 内山 秀昭, 山下 洋市, 辻田 英司, 原田 昇, 播本 憲史, 伊地知 秀樹, 米村 祐輔, 北川 大, 黒田 陽介, 萱島 寛人, 前原 喜彦, 肝細胞癌に対する生体肝移植後再発の予測因子分析(Analysis of predictors of recurrence after living donor liver transplantation for hepatocellular carcinoma), 日本外科学会雑誌, 107, 臨増2, 273-273, 2006.03.
864. 肝細胞癌に対するケモリピオドリゼーションの治療効果とその予測因子に関する研究.
865. 肝細胞癌肝切除術後再発患者に対する動注用アイエコール(CDDP)+リピオドール併用治療の血漿中プラチナ濃度と副作用評価 phase I試験.
866. S Itoh, A Taketomi, S Tanaka, T Gion, T Yoshizumi, Y Soejima, K Shirabe, M Shimada, Y Maehara, Clinical and biological significance of growth factor receptor bound protein 7 on progression in hepatocellular carcinoma., JOURNAL OF CLINICAL ONCOLOGY, 23, 16, 843S-843S, 2005.06.
867. M Kohjima, M Nakamuta, M Fukushima, K Kotoh, M Enjoji, Y Soejima, T Yoshizumi, Y Maehara, Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells, AMERICAN JOURNAL OF TRANSPLANTATION, 5, 224-224, 2005.05.
868. Y Soejima, A Taketomi, T Yoshizumi, H Uchiyama, Y Maehara, Living-donor liver transplantation for patients with hepatocellular carcinoma exceeding milan cliteria: A single center experience of 56 cases., AMERICAN JOURNAL OF TRANSPLANTATION, 5, 429-429, 2005.05.
869. M Nakamuta, S Morizono, Y Soejima, T Yoshizumi, M Kohjima, K Kotoh, M Enjoji, A Taketomi, H Uchiyama, M Shimada, Y Maehara, Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation, AMERICAN JOURNAL OF TRANSPLANTATION, 5, 553-553, 2005.05.
870. 【ウイルス肝炎と肝移植】 施設における現状と対策 外科医より 九州大学病院において.
871. 【劇症肝不全】 劇症肝不全に対する肝移植.
872. 【生体肝移植をめぐる諸問題】 生体肝移植の現状をめぐる諸問題 肝硬変(B型肝炎)に対する肝移植
ウイルス肝炎(B型,C型肝炎)は,肝移植の適応疾患としてもっとも頻度が高い疾患である.B型肝炎に対する肝移植は,B型肝炎免疫グロブリン(HBIG)とラミブジンによる再発予防法が確立しているがコストがかかる.今後は高価なHBIGに代わりうるワクチンなどによる予防法の開発,新たな抗ウイルス薬の臨床応用が課題である.本稿では,B型肝炎に対する肝移植の現状と今後の方向性について私見を述べる(著者抄録).
873. 【肝移植の最新の進歩と問題点】 選択,適応基準とIC取得,実践時期の設定 HCV肝硬変(外科から).
874. 原発性肝細胞癌に対する生体肝移植の術前評価と治療成績.
875. 成人生体肝移植の現状と問題点 成人に対する生体肝移植時のグラフト選択に関する研究.
876. 拡大肝左葉および尾状葉切除 生体肝移植ドナー肝摘出.
877. 新規遺伝子導入法(Electro-sonoporation)を用いたInterleukin 12による同所性肝癌に対する遺伝子治療 マウスモデルでの検討.
878. 生体肝移植後長期合併症の胆管狭窄に対する内視鏡的治療と対策.
879. 生体肝移植術後急性拒絶反応に伴う急性肺障害に対し好中球エラスターゼ阻害剤(エラスポール)が著効した1例
64歳男.亜急性型劇症肝炎(原因不明)で長男をドナーとして生体肝移植術(肝左葉グラフト)を施行した.術後32日目より酸素化能が著明に低下し,肝生検で急性拒絶反応(ACR)と診断した.人工呼吸管理,ステロイドパルス療法,エラスポールの投与を開始した.徐々に呼吸機能は改善し,治療開始翌日には人工呼吸器を離脱した.また,治療開始3日目に高ビリルビン血症に対し血漿交換を施行した.治療開始7日目の胸部X線写真で異常陰影は著明に改善し,治療期間を通してエラスポール投与による副作用等は認めなかった.
880. 肝機能不良肝細胞癌に対するlimited resectionの妥当性に対する検討.
881. 肝細胞癌における血小板活性化因子受容体(platelet activating factor receptor,PAF-R)発現の意義.
882. Y Soejima, M Shimada, T Yoshizumi, Y Maehara, Biliary stricture after living donor liver transplantation., LIVER TRANSPLANTATION, 10, 6, C66-C66, 2004.06.
883. C型肝硬変に対する生体肝移植後に急速な経過をたどり死亡したfibrosing cholestatic hepatitisの1例
ウイルス性肝硬変に対する肝移植は近年増加傾向にある.C型肝硬変に対する移植の問題点は移植後のC型肝炎の再発であり,術後1年以内に50~60%が組織学的に慢性活動性肝炎を再発し,術後5年で約20%が肝硬変に進行するとされている.C型肝炎の場合,肝炎の再発はほとんどが軽度であり,緩徐な経過が特徴とされている.一方,fibrosing cholestatic hepatitis(FCH)は組織学的に胆汁うっ滞,門脈周囲の線維化,肝細胞腫大,軽度な炎症などの特徴を認め短期間で肝硬変に進行し,主にB型肝硬変における移植後の肝炎再発形式とされている.近年,C型肝硬変に対する移植後にもFCHが認められ,近年増加傾向にあるとされている.今回われわれはC型肝硬変に対する生体肝移植術後に高ビリルビン血症を認め組織学的に急速な線維化をきたし術後233日目にグラフト機能不全で死亡したFCH症例を経験したので報告する(著者抄録).
884. T Suehiro, M Shimada, Y Soejima, T Yoshizumi, Y Maehara, Is elderly recipient risk for living donor adult liver transplantation?, LIVER TRANSPLANTATION, 10, 6, C58-C58, 2004.06.
885. T Yoshizumi, M Shimada, Y Soejima, Y Yonemura, H Idichi, N Harada, S Shiotani, M Ninomiya, Y Maehara, The standard liver volume for Japanese adults: Comparison between the six formulas, LIVER TRANSPLANTATION, 10, 6, C25-C25, 2004.06.
886. 【急性肝不全の概念と分類の見直し】 急性肝不全生体肝移植症例の再検討.
887. 【生体肝移植とその短期および長期成績】 ドナー 脂肪肝グラフト
脳死肝移植では,脂肪肝グラフトの危険性はよく知られた事実であるが,生体肝移植における脂肪肝グラフトの危険性・安全性についてはあまり検討がなされていないのが現状である.そこで,生体肝移植における脂肪肝グラフト使用の現状と著者らの脂肪肝に対する対策について述べた.1)脂肪肝の頻度,2)脳死肝移植における脂肪肝グラフト,3)脂肪肝グラフトの機能不全のメカニズム,4)生体肝移植における脂肪肝グラフトの成績,5)脂肪肝ドナーに対する対策.
888. 【肝炎から肝がんまで】 肝がんの治療 肝移植.
889. 【肝細胞癌】 進行肝細胞癌に対する根治的治療法としての生体肝移植.
890. 【肝細胞癌の治療の進歩】 肝細胞癌に対する生体肝移植
わが国における生体肝移植数は3,000例を超え,最近では移植以外に治療法のない進行肝細胞癌に対する生体肝移植が増加している.脳死肝移植における提供肝の公平分配という原則にとらわれないため,ミラノ基準にこだわらずに他に有効な治療法がない症例を適応とする施設が多いのがわが国の特徴である.しかし,ミラノ基準外の症例は移植後の再発率も高い.今後の課題としては適応基準の適確化,さらに移植後免疫抑制下での肝細胞癌再発やC型肝炎再発の制御・予防法の確立が移植成績の向上に重要であると思われる(著者抄録).
891. 【肝臓,小腸移植の最前線】 私たちはこう考える 生体肝移植手術におけるドナー・レシピエントの安全性 ドミノ肝移植の現況と将来展望.
892. 【肝臓外科 課題とその対応】 肝移植 グラフトサイズと肝機能・移植成績.
893. 【進行肝癌の予後改善策】 進行肝癌に対するGFP療法を基本とした集学的治療
進行肝癌に対するGFP療法を基本とした集学的治療について検討した.対象は,従来基準で切除不能な進行・再発肝癌18例(男性16例,女性2例・平均年齢58歳)で,初回治療7例,再発11例,病期はStageIV Aが11例,IV Bが7例,治療はGEM,CDDP,5FUの3剤併用化学療法を施行した.その結果,治療効果はPR9例,SD5例,PD4例で,奏効率は50%,生存率は1年33%,2年19%であった.予後に影響する因子は肝機能(ChildA vs B,C),病期(StageIV A vs IV B),治療効果(PR vs SD,PD)であった.副作用はGrade3,4の頻度が39%で,うちGrade4の好中球減少を17%に認めたが,保存的治療で改善した.なお,初回治療7例中4例が切除可能となったが,うち2例は肝外転移,肝内多発性再発で1年以内に死亡,1例は術後2年9ヵ月無再発生存中,1例は術後1年目に肝内単発再発を認めたが,ラジオ波でのコントロールで術後2年再発なく生存中である.
894. 九州大学病院第三内科における急性肝不全の治療 生体肝移植への適応検討
生体肝移植の中でも術前の内科的治療および移植適応評価が困難な急性肝不全について,その背景,内科的治療,特に移植適応について検討した.入院した急性肝不全25例を対象とした.入院後の転帰は,内科的治療のみで軽快した症例は9例であり,残り16例が内科的治療に反応せず,移植が必要と判断した.1例に対して移植を施行し,残る5例は移植が施行できずに全例死亡の転帰となった.移植ができなった理由は,適切なドナーの不在(3例),腎不全(1例),経済的理由(1例)であった.移植施行11例中9例が生存し,2例(18%)が各々肝梗塞,脳浮腫で死亡した.9例は現在においても免疫抑制剤を服用しているほか特に問題なく生存し,通常の社会生活を送っている.今回肝容積に注目して,入院時の検査所見も含めて検討を行い独自の予後予測式を作成した.
895. 成人生体肝移植の適応拡大とその問題点(特に肝癌) 肝細胞癌に対する成人生体肝移植の適応基準と課題.
896. 生体肝移植における門脈血栓・閉塞に対する血行再建の工夫.
897. 移植医療の現状.
898. 肝切除標本からみた肝細胞癌の組織学的血管侵襲の危険因子の解析 肝癌に対する生体肝移植適応の確立.
899. 肝癌の診断と治療 硬変合併肝細胞癌に対する生体肝移植.
900. 肝細胞癌に対する鏡視下ラジオ波焼灼術(RFA)の有用性.
901. 血管再建を要する消化器外科手術(肝・胆・膵) 生体肝移植における術前・術後の門脈血栓・閉塞に対する血行再建.
902. 進行肝細胞癌に対する根治的治療法としての生体肝移植.
903. 【成人生体肝移植】 長期経過例における合併症
成人生体肝移植は,いまや末期肝疾患に対する根治療法として定着したといえる.成人生体肝移植のサイズの問題,外科的な問題,免疫抑制法が次第に解決され,70%以上の長期生存が期待されるようになった.しかし,今後,脳死肝移植と同様,C型肝炎の再発をはじめとする長期経過例における合併症が大きな問題となってくることが予想される.そこで,肝移植後の長期合併症の特徴,診断及び治療について述べた.
904. 【肝癌に対する生体肝移植】 術前術後化学療法.
905. 【肝細胞癌の治療方針 最近の進歩】 肝細胞癌に対する生体肝移植
肝癌に対する肝移植は当初成績が不良であったが,1990年代半ば頃より適応の厳格化により,成績が向上してきた.再発のリスクファクターとして腫瘍径,血管侵襲,低分化組織型が知られている.生体肝移植では,ドナーとレシピエントが1対1の親族関係であるため,肝癌に対する適応の拡大も可能である.九州大学での肝癌に対する生体肝移植は21例(ドミノ肝移植1例含む)であり17例が生存中,4例に再発を認め,Stage IV Aが3例,全例PIVKA-II>500mAU/mlであった.米国マウントサイナイの肝移植周術期化学療法の成績(5cm以上の肝癌患者の5年生存率55%)は注目に値する.
906. 生体肝移植における無輸血手術.
907. 肝切除術の合併症対策 生体肝移植ドナー肝切除における合併症対策.
908. 劇症肝不全に対する生体肝移植 九州大学における治療体制.
909. Epignathusの出生前MRI
母体は30歳で,2回目の妊娠であるが,1回目の妊娠分娩に異常はなかった.妊娠22週時のエコーで羊水過多症と胎児の顔面病変を認め,27週時に施行したMRIのT2強調矢状断像で前頭蓋底から顔面に突出する巨大な腫瘤を認めた.腫瘤の信号強度は脳よりやや高く,一部低信号の部分もみられた.水平断像では腫瘤が両側眼球の間に存在した.妊娠33週6日,エコー誘導下に胎児の腫瘤内嚢胞より385mlの溶液を穿刺排出し,その後帝王切開で出生した.身長は41.0cm,体重2260g,Apgarスコアは8/8点であった.口腔内は10×6×6cmの巨大な腫瘤で占められており,一部は口腔内より突出していた.腫瘤のため左眼と鼻は偏位し,左鼻孔と左眼裂は閉塞しており,出生後6時間半で呼吸不全のため死亡した.口腔内の腫瘤は組織学的に外・中胚葉成分からなり,成熟奇形腫と診断した.
910. Yoshikazu Yonemitsu, Eric W.F.W. Alton, Kimihiro Komori, Tomoharu Yoshizumi, Keizo Sugimachi, Yasufumi Kaneda, HVJ (Sendai virus) liposome-mediated gene transfer: Current status and future perspectives, International Journal of Oncology, 12, 6, 1277-1285, 1998.06, Haemagglutinating virus of Japan (HVJ
Sendai virus), a member of the mouse paramyxovirus family, has been combined with liposomes to produce a novel gene transfer system, namely HVJ liposomes. This vector system is defined as a 'hybrid vector', constructed with inactivated viral particles and non-viral (artificial) multi- or unilamellar liposomes containing gene expression cassettes and has several advantages in comparison with other viral or non-viral systems. Many studies have shown that this vector system can, not only produce efficient gene transfer using reporter genes, but also with resulting in vivo functional changes in several animal models of diseases. Despite these results, it is likely that the construct will need to be modified to improve gene transfer and expression efficiency and also to extend the potential disease targets. We review the present status of this hybrid vector system and also discuss possible modifications for future application to either in vivo analysis of specific gene expression or human gene therapy strategies for congenital or acquired diseases..
911. K YANAGA, Y SOEJIMA, T YOSHIZUMI, T NISHIZAKI, K TAKENAKA, K SUGIMACHI, SELECTIVE BALLOON OCCLUSION OF THE PORTAL TREE THROUGH THE UMBILICAL VEIN FOR HEPATIC RESECTION, BRITISH JOURNAL OF SURGERY, 82, 10, 1421-1421, 1995.10.
912. 長期透析療法中の閉塞性動脈硬化症に対する動脈血行再建例について
5年間に動脈血行再建を行った維持透析中のASO患者11例の平均は60歳であったが,50台,40台への拡がりをみせていた。糖尿病の合併率は45%であった。PAT 5例では遠隔期開存3,閉塞2例で,5例中3例は健在であったが,2例は死亡していた。バイパスあるいはTEA群,計7例7手術では全例生存,再建部は開存し,主訴は軽快,透析時の下肢痛は消失していた。透析のない日に待期的手術を施行,術後1日目より透析を開始している。術当日術前,術後1日目透析前の透析関連の臨床検査成績では,透析患者としては特に問題はなかった。通常ヘパリン透析患者の透析前と手術当日術前に相当する微量ヘパリン透析翌朝の凝固時間には有意差はなかったが,ともに健康人との間には有意差があり,凝固時間の延長がみられた.
913. Takeo Toshima, Nao Fujimori, Tomoharu Yoshizumi, Shinji Itoh, Yoshihiro Nagao, Noboru Harada, Takamasa Oono, Masaki Mori, A Novel Strategy of Endoscopic Ultrasonography-Guided Pancreatic Duct Drainage for Pancreatic Fistula After Pancreaticoduodenectomy., Pancreas, 10.1097/MPA.0000000000001729, 50, 2, e21-e22, 2021.02.
914. Shinji Itoh, Tomoharu Yoshizumi, Noboru Harada, Takeo Toshima, Yoshihiro Nagao, Takeshi Kurihara, Huanlin Wang, Tomonari Shimagaki, Toru Ikegami, Masaki Mori, A no-ligation technique to prevent intraoperative hepatic artery dissection in living-donor liver transplantation., Surgery today, 10.1007/s00595-021-02276-8, 51, 11, 1877-1880, 2021.04, Intrahepatic recipient hepatic artery dissection caused by hepatic artery thrombosis is a lethal complication of living-liver donor liver transplantation (LDLT). We herein report a new surgical technique that avoids the ligation of the recipient hepatic arteries in LDLT. Patients undergoing LDLT between 2009 and 2019 were evaluated. In the second half of this period, a technique involving no ligation of the recipient hepatic artery was initiated and its impact on the incidence of intrahepatic recipient hepatic artery dissection was determined. The middle and left hepatic arteries were ligated in 195 cases (53.4%), and the no-ligation technique was used in 170 (46.6%). The incidence of intraoperative hepatic artery dissection was significantly lower in the no-ligation group (n = 0, 0.0%) than in the ligation group (n = 10, 5.1%) (p = 0.0021). After propensity score matching to evaluate the patient characteristics, the incidence of intraoperative hepatic artery dissection was also significantly lower in the no-ligation group (n = 0, 0.0%) than in the ligation group (n = 6, 4.5%) (p = 0.0295). As a result, this new surgical technique is highly recommended to avoid recipient hepatic artery ligation in LDLT..
915. Norifumi Iseda, Shinji Itoh, Tomoharu Yoshizumi, Kyohei Yugawa, Akinari Morinaga, Takahiro Tomiyama, Takeo Toshima, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, ARID1A Deficiency Is Associated With High Programmed Death Ligand 1 Expression in Hepatocellular Carcinoma., Hepatology communications, 10.1002/hep4.1659, 5, 4, 675-688, 2021.04, The clinicopathological features of carcinomas expressing AT-rich interaction domain 1a (ARID1A) and programmed death ligand 1 (PD-L1) in HCC are poorly understood. Here, we examined ARID1A and PD-L1 expression in surgically resected primary hepatocellular carcinoma (HCC) and the association of ARID1A and PD-L1 expression with clinicopathological features and patient outcomes. Their association with ARID1A expression and tumor-associated CD68-positive macrophage was further explored. Using a database of 255 patients who underwent hepatic resection for HCC, immunohistochemical staining of ARID1A, PD-L1, and CD68 was performed. We also analyzed the expression PD-L1 after ARID1A knockdown in HCC cell lines. Samples from 81 patients (31.7%) were negative for ARID1A. Negative ARID1A expression was significantly associated with male sex, high alpha-fetoprotein, high des-gamma-carboxyprothrombin, large tumor size, high rate of poor differentiation, microscopic intrahepatic metastasis, and PD-L1 expression. In addition, negative ARID1A expression was an independent predictor for recurrence-free survival, overall survival, and positive PD-L1 expression. Stratification based on ARID1A and PD-L1 expression in cancer cells was also significantly associated with unfavorable outcomes. PD-L1 protein expression levels were increased through phosphoinositide 3-kinase/AKT signaling after ARID1A knockdown in HCC cells. HCC with ARID1A-low expression was significantly correlated with high levels of tumor-associated CD68-positive macrophage. Conclusion: Our large cohort study showed that ARID1A expression in cancer cells was associated with a poor clinical outcome in patients with HCC, PD-L1 expression in cancer cells, and tumor microenvironment. Therefore, ARID1A may be a potential molecular biomarker for the selection of patients with HCC for anti-programmed death 1/PD-L1 antibody therapy..
916. Takahiro Tomiyama, Takashi Motomura, Norifumi Iseda, Akinari Morinaga, Tomonari Shimagaki, Takeshi Kurihara, Huanlin Wang, Takeo Toshima, Yoshihiro Nagao, Shinji Itoh, Noboru Harada, Tomoharu Yoshizumi, Masaki Mori, Acute death caused by invasive aspergillosis after living-donor liver transplantation despite good graft function: a case report., Surgical case reports, 10.1186/s40792-021-01203-w, 7, 1, 118-118, 2021.05, BACKGROUND: Invasive aspergillosis (IA) is one of the most serious causes of death after liver transplantation (LT). IA is the second most common fungal infection, and its mortality rate exceeds 80%. CASE PRESENTATION: A 67-year-old man presented to our hospital because of fulminant hepatitis caused by hepatitis B virus. Candidiasis was detected in his sputum, and micafungin had already been administered. Living-donor LT was performed using a right lobe graft donated from his daughter with no intraoperative complications. Although he appeared to have good graft function, his oxygenation was inadequate, and a chest radiograph showed many invasive shadows on postoperative day 1. A computed tomography scan also showed many invasive shadows with the halo sign. A blood examination revealed positivity for Aspergillus antigen, and Aspergillus species were detected in his sputum. IA was diagnosed. The antifungal therapy was soon modified to amphotericin B combined with caspofungin. Despite good graft blood flow through the portal vein and hepatic artery and good graft function, the patient died of IA on postoperative day 3. The median time from LT to IA among reports published to date ranges from 18 to 25 days. CONCLUSIONS: The present report describes the first case of very early onset of IA after LT..
917. Keita Takahashi, Kazuya Imura, Keiko Nobukuni, Shoichi Sasaki, Taichi Nagano, Noboru Harada, Tomoharu Yoshizumi, Midoriko Higashi, Ken Yamaura, Anesthetic Management Using Low Fraction of Inspiratory Oxygen for Living Donor Liver Transplantation in a Patient With Hepatopulmonary Syndrome Complicated by Interstitial Pneumonia: A Case Report., Transplantation proceedings, 10.1016/j.transproceed.2021.08.007, 53, 8, 2556-2558, 2021.08, BACKGROUND: Hepatopulmonary syndrome frequently complicates end-stage liver disease. It causes hypoxemia and requires oxygen administration. Additionally, interstitial pneumonia causes hypoxemia; however, it is known to be aggravated by high-concentration oxygen administration. CASE PRESENTATION: A 71-year-old woman with hepatopulmonary syndrome and interstitial pneumonia underwent living donor liver transplantation, requiring conflicting management in terms of the inspiratory oxygen concentration. We achieved a low intraoperative fraction of inspiratory oxygen by increasing the cardiac output with intravenous catecholamines. As a result, the transplanted liver functioned well postoperatively, and the patient was discharged without exacerbation of the interstitial pneumonia. CONCLUSION: We suggest that patients with hepatopulmonary syndrome complicated with interstitial pneumonia can undergo successful living donor liver transplantation without the use of high inspiratory oxygen concentration by using catecholamines to maintain a high mixed venous oxygen saturation..
918. Kyohei Yugawa, Shinji Itoh, Tomoharu Yoshizumi, Norifumi Iseda, Takahiro Tomiyama, Akinari Morinaga, Takeo Toshima, Noboru Harada, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, CMTM6 Stabilizes PD-L1 Expression and Is a New Prognostic Impact Factor in Hepatocellular Carcinoma., Hepatology communications, 10.1002/hep4.1643, 5, 2, 334-348, 2021.02, CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) was identified as a regulator of programmed death ligand 1 (PD-L1), which induces antitumor immunity in several cancers. This study aimed to clarify the relationship between CMTM6 and PD-L1 expression and clinical outcomes in patients with hepatocellular carcinoma (HCC). In total, 259 patients with HCC who had undergone hepatic resection were enrolled. Immunohistochemical staining for CMTM6 and PD-L1 was performed. The relationships between CMTM6 expression and the clinicopathological characteristics and outcomes were analyzed. Additionally, the stabilization of PD-L1 expression and regulation of malignant activities by CMTM6 were examined in vitro. Our patients were divided into high (n = 65, 25.1%) and low (n = 194, 74.9%) CMTM6 expression groups. High CMTM6 expression was significantly associated with malignant aggregates, including poor differentiation (P < 0.0001), microscopic intrahepatic metastasis (P = 0.0369), and multiple intrahepatic recurrences (P = 0.0211). CMTM6 expression was significantly correlated with PD-L1 expression in HCC tissues (P < 0.0001). The patients were classified into three groups: high CMTM6/PD-L1 positive (n = 21), high CMTM6/ PD-L1 negative (n = 44), and low CMTM6 (n = 194) expression pattern groups. Overall survival was significantly different among the three groups (P < 0.0001). Additionally, immunohistochemical double staining revealed that CMTM6 and PD-L1 were co-expressed on HCC cells. In vitro, PD-L1 expression was enhanced at late time points in the presence of CMTM6 expression. CMTM6 also regulated epithelial-to-mesenchymal transition and stemness phenotypes in HCC cells. Conclusion: Our large cohort study found that CMTM6 co-expressed with PD-L1 was strongly associated with the clinical outcome in patients with HCC. The evaluation of CMTM6 combined with PD-L1 in HCC might be useful for patient selection in immune checkpoint therapy..
919. Chuan Lan, Yuki Kitano, Yo-Ichi Yamashita, Takanobu Yamao, Kiyoshi Kajiyama, Tomoharu Yoshizumi, Kengo Fukuzawa, Keishi Sugimachi, Yasuharu Ikeda, Hiroshi Takamori, Nobutomo Miyanari, Masahiko Hirota, Hideo Baba, Cancer-associated fibroblast senescence and its relation with tumour-infiltrating lymphocytes and PD-L1 expressions in intrahepatic cholangiocarcinoma., British journal of cancer, 10.1038/s41416-021-01569-6, 126, 2, 219-227, 2021.10, BACKGROUND: Caveolin-1 (CAV1) in cancer-associated fibroblasts (CAFs) has pro- or anti-tumourigenic effect depending on the cancer type. However, its effect in intrahepatic carcinoma (ICC) remains unknown. Therefore, this study aimed to investigate the relationship between CAV1 in CAFs and tumour-infiltrating lymphocyte (TIL) numbers or PD-L1 levels in ICC patients. METHODS: Consecutive ICC patients (n = 158) were enrolled in this study. The levels of CAV1 in CAFs, CD8 + TILs, Foxp3+ TILs and PD-L1 in cancer cells were analysed using immunohistochemistry. Their association with the clinicopathological factors and prognosis were evaluated. The correlation between these factors was evaluated. RESULTS: CAV1 upregulation in CAFs was associated with a poor overall survival (OS) (P < 0.001) and recurrence-free survival (P = 0.008). Clinicopathological factors were associated with high CA19-9 levels (P < 0.001), advanced tumour stage (P = 0.046) and lymph node metastasis (P = 0.004). CAV1 level was positively correlated with Foxp3+ TIL numbers (P = 0.01). There were no significant correlations between CAV1 levels and CD8 + TIL numbers (P = 0.80) and PD-L1 levels (P = 0.97). An increased CD8 + TIL number and decreased Foxp3+ TIL number were associated with an increased OS. In multivariate analysis, positive CAV1 expression in CAFs (P = 0.013) and decreased CD8 + TIL numbers (P = 0.021) were independent poor prognostic factors. CONCLUSION: Cellular senescence, represented by CAV1 levels, may be a marker of CAFs and a prognostic indicator of ICC through Foxp3+ TIL regulation. CAV1 expression in CAFs can be a therapeutic target for ICC..
920. Kyohei Yugawa, Tomoharu Yoshizumi, Yohei Mano, Shinji Itoh, Noboru Harada, Toru Ikegami, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Cancer-associated fibroblasts promote hepatocellular carcinoma progression through downregulation of exosomal miR-150-3p., European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 10.1016/j.ejso.2020.08.002, 47, 2, 384-393, 2021.02, PURPOSE: Hepatocellular carcinoma (HCC) is a common and deadly cancer. The prognosis of HCC is poor and is related to tumor progression. The malignant potential of HCC is regulated by the tumor microenvironment (TME). As cancer-associated fibroblasts (CAFs) help regulate tumor progression, understanding how they function in HCC could improve patient outcomes. The aim of this study was to determine whether specific microRNAs (miRNAs) in exosomes derived from CAFs might be involved in HCC progression. METHODS: MiRNA microarray assay was used to analyze miRNA profiles of exosomes derived from CAFs and normal fibroblasts (NFs) in HCC. Migration and invasion assays were performed to examine the effects of miR-150-3p on HCC in vitro. In addition, the relationships between prognosis of HCC patients and miR-150-3p expression in HCC tissues and plasma exosomes were retrospectively analyzed. RESULTS: MiR-150-3p was significantly reduced in CAFs-derived exosomes, and inhibited HCC migration and invasiveness. MiR-150-3p was transferred from CAFs transfected miR-150-3p to HCC cells through exosomes, and abrogated HCC migration and invasiveness. Furthermore, low miR-150-3p expression in HCC tissues was a significant risk factor for recurrence in HCC patients. More importantly, survival rate in patients with low miR-150-3p levels in plasma exosomes was significantly poor compared with that in patients with high miR-150-3p levels. CONCLUSIONS: Overall, our findings suggest that the loss of antitumoral miR-150-3p in CAFs-derived exosomes greatly promotes HCC progression. Exosomal miR-150-3p is a potential prognostic biomarker, and transferring miR-150-3p-loaded exosomes to HCC cells might become a novel therapeutic option..
921. Koichiro Morita, Akihiro Nishie, Yoshiki Asayama, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Nobuhiro Fujita, Toru Ikegami, Tomoharu Yoshizumi, Kousei Ishigami, Congestion Area of the Right Lobe Graft in Living Donor Liver Transplantation: Quantitative Evaluation of Hemodynamics Using Computed Tomography Perfusion., Transplantation proceedings, 10.1016/j.transproceed.2021.02.024, 53, 5, 1653-1658, 2021.06, BACKGROUND: The hemodynamics of congestion areas in the right lobe graft after living donor liver transplantation (LDLT) remains unclear. The aim of this study was to elucidate the hemodynamics of congestion areas in the right lobe graft after LDLT using computed tomography (CT) perfusion imaging and the dual-input maximum slope method. METHODS: Sixteen recipients underwent CT perfusion of the liver and portal phase abdominal to pelvic CT 1week after LDLT using a right lobe graft. The attenuation of segments V and VIII on the portal venous phase abdominal to the pelvic CT scan was classified into 3 categories: hyperattenuation, iso-attenuation, and hypoattenuation. Mean arterial blood flow (AF, mL/min/100 mL tissue), portal blood flow (PF, mL/min/100 mL tissue), and perfusion index (%) [PI = AF/(AF + PF) × 100] were compared between the hyperattenuation group and iso-attenuation group. The independent t test was used for these statistical analyses. RESULTS: On the portal phase abdominal scan, 15 segments, 16 segments, and 1 segment showed hyperattenuation, iso-attenuation, and hypoattenuation, respectively. The mean AF and PI of the hyperattenuation group (44.4 ± 24.4, 30.2 ± 13.5) were significantly higher than those of the iso-attenuation group (28.0 ± 7.8, 19.9 ± 6.2) (P < .05, P < .05). CONCLUSIONS: The congested liver segments showed high AF and high PI on CT perfusion imaging. This method enables the feasible quantification of the hemodynamics and the description of focal hemodynamic change in the graft after LDLT..
922. Noboru Harada, Tomoharu Yoshizumi, Masaki Mori, Current review of machine perfusion in liver transplantation from the Japanese perspective., Surgery today, 10.1007/s00595-021-02265-x, 52, 3, 359-368, 2021.03, In light of the present evidence, machine perfusion is opening up new horizons in the field of liver transplantation. Although many advances have been made in liver transplantation, organ preservation methods have so far changed very little. Static cold storage is universally used for graft preservation in liver transplantation; however, there is a need for better preservation methods, such as ex vivo machine perfusion, to improve the outcomes by decreasing warm ischemic damage. Based on the findings of basic and clinical trials, hypothermic and normothermic machine perfusion techniques are now commercially available and include the OrganOx metra, Liver Assist, Cleveland NMP device, Organ Care System, and LifePort Liver. Recent clinical trials have provided further evidence for the potential role of normothermic machine perfusion to resuscitate and subsequently improve utilization of marginal or currently discarded livers. Further studies are required to explore the longer-term outcomes, late biliary complications, outcomes in specific high-risk groups, viability biomarkers, optimum and maximum perfusion duration, perfusate composition, and liver-directed therapeutic interventions during normothermic machine perfusion. The use of organs from marginal donors after brain death, such as fatty livers and the livers from elderly donors with multiple comorbidities, may be accepted for machine perfusion in Japan in the near future..
923. Yukihisa Takayama, Akihiro Nishie, Daisuke Okamoto, Nobuhiro Fujita, Yoshiki Asayama, Yasuhiro Ushijima, Tomoharu Yoshizumi, Masami Yoneyama, Kousei Ishigami, Differentiating Liver Hemangioma from Metastatic Tumor Using T2-enhanced Spin-echo Imaging with a Time-reversed Gradient-echo Sequence in the Hepatobiliary Phase of Gadoxetic Acid-enhanced MR Imaging., Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine, 10.2463/mrms.mp.2020-0151, 21, 3, 445-457, 2021.04, PURPOSE: To evaluate the utility of T2-enhanced spin-echo imaging using the time-reversed gradient echo sequence (T2FFE imaging) in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI (Gd-EOB-MRI) for differentiating hemangiomas from metastatic tumors. METHODS: A total of 61 patients with 133 liver lesions, including 37 hemangiomas and 96 metastatic tumors, were scanned by Gd-EOB-MRI. Four data sets were independently analyzed by two readers: (1) 3D fat-suppressed T2-weighted imaging (FS-T2WI) alone; (2) the combination of 3D FS-T2WI and T2FFE imaging in the HBP of Gd-EOB-MRI; (3) the combination of 3D FS-T2WI, diffusion-weighted imaging (DWI) with the b-value of 1000 s/mm2 and the apparent diffusion coefficient (ADC); and (4) a dynamic study of Gd-EOB-MRI. After classifying the lesion sizes as ≤ 10 mm or > 10 mm, we conducted a receiver-operating characteristic analysis to compare diagnostic accuracies among the four data sets for differentiating hemangiomas from metastatic tumors. RESULTS: The areas under the curves (AUCs) of the four data sets of two readers were: (1) ≤ 10 mm (0.85 and 0.91) and > 10 mm (0.88 and 0.97), (2) ≤ 10 mm (0.94 and 0.94) and > 10 mm (0.96 and 0.95), (3) ≤ 10 mm (0.90 and 0.87) and > 10 mm (0.89 and 0.95), and (4) ≤ 10 mm (0.62 and 0.67) and > 10 mm (0.76 and 0.71), respectively. Data sets (2) and (3) showed no significant differences in AUCs, but both showed significantly higher AUCs compared to that of (4) regardless of the lesion size (P < 0.05). CONCLUSION: The combination of 3D FS-T2WI and T2FFE imaging in the HBP of Gd-EOB-MRI achieved an accuracy equivalent to that of the combination of 3D FS-T2WI, DWI, and ADC and might be helpful in differentiating hemangiomas from metastatic tumors..
924. Takuma Izumi, Yuhei Morioka, Syun-Ichi Urayama, Daisuke Motooka, Tomokazu Tamura, Takahiro Kawagishi, Yuta Kanai, Takeshi Kobayashi, Chikako Ono, Akinari Morinaga, Takahiro Tomiyama, Norifumi Iseda, Yukiko Kosai, Shoichi Inokuchi, Shota Nakamura, Tomohisa Tanaka, Kohji Moriishi, Hiroaki Kariwa, Tomoharu Yoshizumi, Masaki Mori, Yoshiharu Matsuura, Takasuke Fukuhara, DsRNA Sequencing for RNA Virus Surveillance Using Human Clinical Samples., Viruses, 10.3390/v13071310, 13, 7, 2021.07, Although viruses infect various organs and are associated with diseases, there may be many unidentified pathogenic viruses. The recent development of next-generation sequencing technologies has facilitated the establishment of an environmental viral metagenomic approach targeting the intracellular viral genome. However, an efficient method for the detection of a viral genome derived from an RNA virus in animal or human samples has not been established. Here, we established a method for the efficient detection of RNA viruses in human clinical samples. We then tested the efficiency of the method compared to other conventional methods by using tissue samples collected from 57 recipients of living donor liver transplantations performed between June 2017 and February 2019 at Kyushu University Hospital. The viral read ratio in human clinical samples was higher by the new method than by the other conventional methods. In addition, the new method correctly identified viral RNA from liver tissues infected with hepatitis C virus. This new technique will be an effective tool for intracellular RNA virus surveillance in human clinical samples and may be useful for the detection of new RNA viruses associated with diseases..
925. Katsuya Toshida, Shinji Itoh, Tomoharu Yoshizumi, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Takeo Toshima, Yoshihiro Nagao, Noboru Harada, Eiji Oki, Yoshiaki Nakamura, Takayuki Yoshino, Masaki Mori, Efficacy of pembrolizumab in microsatellite instability-high locally advanced cholangiocarcinoma: a case report., Clinical journal of gastroenterology, 10.1007/s12328-021-01458-8, 14, 5, 1459-1463, 2021.06, Cholangiocarcinoma is a biliary malignant tumor which can arise at any point of biliary tree. Surgical resection is the only curative treatment and chemotherapy is used for unresectable cases, but its prognosis is poor compared with other types of cancer. Recently, pembrolizumab (PEM), an anti-programmed cell death protein 1 (PD-1) antibody, has become available for microsatellite instability (MSI)-high advanced cancers. Here, we report the use of PEM for MSI-high locally advanced cholangiocarcinoma. A 57-year-old man presented to our department with jaundice. Contrast-enhanced computed tomography showed a solitary 28-mm-diameter tumor deep in the anterior segment of the liver. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography showed narrowing of the common bile duct and absence of contrast in the right hepatic duct, and tumor invaded from hilar region of liver into left hepatic duct. We diagnosed this as double primary cancers, locally advanced intrahepatic and distal cholangiocarcinomas. The patient began gemcitabine in combination with cisplatin therapy as first-line treatment and gemcitabine in combination with S-1 therapy as second-line treatment. However, the tumor gradually grew (maximum 69 mm), intrahepatic metastasis appeared, and tumor marker increased. Because MSI-high was confirmed not only by biopsy specimens but also by liquid biopsy, the patient began PEM (200 mg per every 3 weeks). After 15 cycles of PEM were administered over about 10 months, size of tumor was reduced and tumor marker dramatically decreased. We experienced the rare case which PEM has been successfully used for MSI-high double primary cancers..
926. Takeshi Kurihara, Shinji Itoh, Yasue Kimura, Eiji Oki, Tomoharu Yoshizumi, Mioko Matuo, Ryuji Yasumatsu, Keishi Sugimachi, Masaru Morita, Tetsuya Kusumoto, Kengo Fukuzawa, Naoya Yoshida, Hideo Baba, Masaki Mori, Feasibility of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma: a multi-center experience., Surgery today, 10.1007/s00595-021-02305-6, 51, 12, 1932-1937, 2021.05, PURPOSE: Patients with liver metastasis of head-and-neck carcinoma and esophageal carcinoma are generally not treated with hepatic resection, but there are no established standard treatment methods. We report 11 cases of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma performed at 5 Japanese institutions. METHODS: The subjects of this retrospective analysis were 11 patients who underwent hepatic resection for metastatic liver tumors, originating from head-and-neck carcinoma in 5 and from esophageal cancer in 6, between January, 2010 and March, 2020 RESULTS: There were nine men and two women (median age, 64 years; range 40-72 years). The primary disease was esophageal carcinoma in six patients and pharyngeal carcinoma in five patients. All cancers were squamous cell carcinoma. The time from the initial treatment to the diagnosis of liver metastasis was 15.3 months and the 1-year and 3-year overall survival rates after hepatic resection were 72% and 32%, respectively. The overall and disease-free survival rates after hepatic resection were significantly higher for patients who underwent hepatic resection more than 12 months after the initial treatment than for those who underwent hepatic resection within 12 months after the initial treatment (p = 0.0172 and p = 0.0120, respectively). CONCLUSIONS: Liver resection may prolong the survival of patients with liver metastases controlled for more than 12 months after the initial treatment of head and neck or esophageal carcinoma..
927. Shinji Itoh, Kyohei Yugawa, Tomoharu Yoshizumi, Yoshinao Oda, Masaki Mori, Immune microenvironment in primary and metastatic liver cancers., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13607, 51, 1, 3-4, 2021.01.
928. Katsuya Toshida, Takeo Toshima, Tomoharu Yoshizumi, Noboru Harada, Shinji Itoh, Yoshihiro Nagao, Huanlin Wang, Tomonari Shimagaki, Takeshi Kurihara, Masaki Mori, Immunosuppression Free Protocol for Liver Transplant from an Identical Twin Mimicking Positive Donor-Specific Antibodies: A Case Report., Transplantation proceedings, 10.1016/j.transproceed.2021.04.008, 53, 8, 2576-2579, 2021.05, There are some reported cases of liver transplant between identical twins with no immunosuppressants because of their matched HLA. However, there is no mention of donor-specific antibodies (DSA). Here, we report a rare case of living donor liver transplant (LDLT) between identical twins, mimicking DSA positivity, on a low-dose immunosuppression protocol. A 57-year-old man with acute liver failure underwent LDLT using the right lobe from his identical twin. Their blood types were identical on HLA matching. However, the preoperative DSA test results were positive for class II antibodies. This was supposed to be due to the relatively large amount of blood transfusion before testing: a total of 580 units of fresh frozen plasma for plasma exchange. The presence of class II antibodies for DSA positivity was the result of the passive immunity from transfusion, and this result could not be ignored, given the risk of rejection. Therefore, we arranged low-dose postoperative immunosuppressants using tacrolimus at a quarter dose and no mycophenolate mofetil. The postoperative course was uneventful. A few months after LDLT, the patient's DSA level was negative for class II antibodies, thus confirming our preoperative hypothesis of DSA as the result of transfusion. Currently, 6 months after LDLT, he is free from immunosuppressive medication with good liver function. When administering relatively large doses of fresh frozen plasma by repeated plasma exchange before LDLT, even between identical twins, it is important to consider that the DSA test could be positive and that immunosuppressive treatment should be performed carefully..
929. Shinji Itoh, Tomoharu Yoshizumi, Takahiro Tomiyama, Norifumi Iseda, Akinari Morinaga, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Yoshihiro Nagao, Takeo Toshima, Noboru Harada, Akihiro Nishie, Kousei Ishigami, Masaki Mori, Impact and risk factors for skeletal muscle mass loss after hepatic resection in patients with hepatocellular carcinoma., JGH open : an open access journal of gastroenterology and hepatology, 10.1002/jgh3.12588, 5, 7, 785-792, 2021.07, Background and Aim: The aims of this study were to determine whether a postoperative decrease in skeletal muscle mass (SMM) after hepatic resection can predict long-term outcomes in patients with hepatocellular carcinoma (HCC) and identify risk factors for SMM loss in patients who undergo hepatic resection. Methods: This was a large retrospective study of 400 patients who underwent hepatic resection for HCC and pre- and postoperative computed tomography (CT) scans. SMM was measured at the third lumbar vertebrae, and the postoperative change in SMM compared with preoperative values was calculated as Δ SMM. The cutoff value for the post-/preoperative ratio was set at 0.9. Results: Sixty patients (15.0%) developed SMM loss. These patients had a significantly prolonged prothrombin time (P = 0.0092), longer duration of surgery (P = 0.0021), more blood loss (P = 0.0040), and higher rate of postoperative complications (P = 0.0037) than those without SMM loss. Multivariate analysis revealed that prolonged prothrombin time and postoperative complications were independent risk factors for SMM loss after hepatic resection. Patients with SMM loss had significantly shorter overall survival (P = 0.0018) than the other patients had. SMM loss was an independent prognostic factor for overall survival (hazard ratio 1.551, 95% confidential interval 1.028-2.340, P = 0.0363). Conclusions: We demonstrated an association of SMM loss with postoperative complications and long-term prognosis in patients with HCC. Patients with prolonged prothrombin time, or postoperative complications, may need to maintain their SMM. Further prospective studies are needed to investigate whether nutritional support can improve SMM loss..
930. Shohei Yoshiya, Shinji Itoh, Tomoharu Yoshizumi, Kyohei Yugawa, Takeshi Kurihara, Takeo Toshima, Noboru Harada, Mikiko Hashisako, Hirotoshi Yonemasu, Kengo Fukuzawa, Yoshinao Oda, Masaki Mori, Impact of Capicua on Pancreatic Cancer Progression., Annals of surgical oncology, 10.1245/s10434-020-09339-z, 28, 6, 3198-3207, 2021.06, BACKGROUND: The transcription factor capicua (CIC) regulates mammalian development and homeostasis. Growing evidence shows that CIC suppresses various human cancers by directly repressing the downstream cancer-related target genes. This study investigated the clinical and biologic significance of CIC expression in pancreatic cancer (PC). METHODS: The study reviewed 132 patients with PC who underwent curative resection. The patients were divided into two groups according to CIC immunoreactivity score by immunohistochemistry, and the associations between CIC expression, clinicopathologic characteristics, and postoperative prognosis were investigated. Moreover, the influence of CIC expression on the malignant potential of PC cells was assessed with cell proliferation, motility assays, and use of quantitative real time-polymerase chain reaction and Western blot on the downstream target genes of CIC in knockdown experiments. RESULTS: The low-CIC expression group showed a higher proportion of lymphatic invasion (72.9% vs. 53.1%; p = 0.024), intrapancreatic neural invasion (94.1% vs. 81.3%; p = 0.021), and extrapancreatic plexus invasion (30.9% vs. 7.8%; p = 0.0006) than the high-CIC expression group as well as significantly worse overall survival (p = 0.0002) and recurrence-free survival (p = 0.0041) rates. Low CIC expression was an independent risk factor for poor prognosis (p = 0.038). Pancreatic cancer cells with knockdown CIC significantly enhanced cell motilities and cell cycle progression, promoted expression levels of ETV4 and MMP-9, and induced EMT. CONCLUSIONS: The study elucidated the association of low CIC expression with a poor prognosis for patients with PC and suggested that the CIC-ETV4-MMP-9 axis might control PC progression..
931. Shinji Itoh, Tomoharu Yoshizumi, Yoshiyuki Kitamura, Kyohei Yugawa, Norifumi Iseda, Tomonari Shimagaki, Yoshihiro Nagao, Takeo Toshima, Noboru Harada, Kenichi Kohashi, Shingo Baba, Kousei Ishigami, Yoshinao Oda, Masaki Mori, Impact of Metabolic Activity in Hepatocellular Carcinoma: Association With Immune Status and Vascular Formation., Hepatology communications, 10.1002/hep4.1715, 5, 7, 1278-1289, 2021.07, We evaluated the prognostic value of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC). Their association with programmed death ligand 1 (PD-L1) expression and vascular formation was further investigated. In this retrospective study, using a database of 418 patients who had undergone 18F-FDG PET/CT before hepatic resection for HCC, immunohistochemical staining of PD-L1, clusters of differentiation (CD) 8, CD68, and CD34 was performed. Patients with a high maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT showed a significantly worse recurrence-free survival (RFS) (hazard ratio [HR]: 1.500; 95% confidence interval [CI]: 1.088-2.069; P = 0.0133) and overall survival (OS) (HR: 2.259; 95% CI: 1.276-4.000; P = 0.0052) than patients with a low SUVmax. Logistic regression analysis showed that a high SUVmax in HCC was significantly associated with PD-L1-positive expression (odds ratio: 4.407; 95% CI: 2.265-8.575; P < 0.0001). SUVmax values of HCC were associated with intratumoral CD8-positive T-cell counts (P = 0.0044) and CD68-positive macrophage counts (P = 0.0061). Stratification based on SUVmax, PD-L1 expression, and the vessels that encapsulate tumor clusters (VETC) status was also significantly associated with RFS and OS. SUVmax, VETC, and PDL1 expression were independently predictive of survival on multivariable analysis. Conclusion: Our large cohort study showed that a high SUVmax on 18F-FDG PET/CT is associated with a poor clinical outcome and PD-L1 expression in patients with HCC. Additionally, stratification of patients based on the combination of SUVmax, PD-L1 expression, and the VETC status predicts poor clinical outcome..
932. Takanobu Hara, Susumu Eguchi, Tomoharu Yoshizumi, Nobuhisa Akamatsu, Toshimi Kaido, Takashi Hamada, Hiroyuki Takamura, Tsuyoshi Shimamura, Yuzo Umeda, Masahiro Shinoda, Yasuhiro Ogura, Takumi Fukumoto, Mureo Kasahara, Taizo Hibi, Koji Umeshita, Hiroyuki Furukawa, Hideki Ohdan, Incidental intrahepatic cholangiocarcinoma in patients undergoing liver transplantation: A multi-center study in Japan., Journal of hepato-biliary-pancreatic sciences, 10.1002/jhbp.896, 28, 4, 346-352, 2021.04, BACKGROUND: Intrahepatic cholangiocarcinoma had been considered a contraindication for liver transplantation because of poorer outcomes. However, incidental intrahepatic cholangiocarcinoma in the explanted liver has been reported because of the difficulty of obtaining an accurate diagnosis in cirrhotic livers on preoperative imaging. METHODS: We conducted a nationwide survey to analyze the incidence of incidental intrahepatic cholangiocarcinoma and outcomes after liver transplantation, in Japan. RESULTS: Forty-five of 64 institutions (70%) responded to our initial investigation. Between January 2001 and December 2015, 6627 liver transplantations were performed in these 45 institutions, with 19 cases (0.3%) of incidental intrahepatic cholangiocarcinoma reported from 12 transplant centers. Six cases were diagnosed as hepatocellular carcinoma preoperatively. The 1-, 3-, and 5-year recurrence-free survival rates were 79%, 45%, and 45%, respectively. Tumor recurrence after liver transplantation was found in 10 patients (53%). The 1-, 3-, and 5-year overall survival rates were 79%, 63%, and 46%, respectively. CONCLUSIONS: Intrahepatic cholangiocarcinoma at liver transplantation is associated with a high risk of recurrence and poor prognosis, even these tumors are detected incidentally in the explanted liver..
933. Koichi Kimura, Tomoharu Yoshizumi, Kensuke Kudo, Kanrin Oh, Takeshi Kurihara, Takeo Toshima, Shinji Itoh, Noboru Harada, Tetsuo Ikeda, Yoshihiko Maehara, Intractable Biliary Strictures After Living Donor Liver Transplantation: A Case Series., Transplantation proceedings, 10.1016/j.transproceed.2021.04.015, 53, 5, 1726-1730, 2021.06, BACKGROUND: Biliary stricture (BS) is a severe complication after liver transplantation. It is difficult to treat, especially after living donor liver transplantation (LDLT). We successfully treated 4 patients for intractable BS after LDLT. All patients had developed cholangitis with stenosis of bile ducts anastomosis. CASE 1: . A 65-year-old woman underwent LDLT with right lobe graft and duct-to-duct biliary reconstruction. Internal plastic stents inserted by endoscopic retrograde cholangiography (ERC) were changed quarterly for the next 2 years. CASE 2: A 55-year-old man underwent LDLT with right lobe graft and duct-to-duct biliary reconstruction. Insertion of internal plastic stents by ERC was attempted; however, the posterior bile duct branch showed complete obstruction. After percutaneous transhepatic biliary drainage (PTCD), the stents were inserted using the rendezvous technique of ERC and were changed by ERC quarterly for the next 3 years. CASE 3: A 22-year-old man underwent LDLT with left lobe graft and hepaticojejunostomy. An external drainage tube was inserted by PTCD, and stents were changed quarterly for the next 2 years. CASE 4: A 60-year-old man underwent LDLT with right lobe graft and hepaticojejunostomy. An external drainage tube was inserted by PTCD, and changed to a metallic stent after 1 year. Three months later the stent was extracted using the rendezvous technique of double balloon enteroscopy. CONCLUSION: BS of complete obstruction type after LDLT is difficult to treat. Appropriate procedures should be chosen based on the types of strictures and biliary reconstruction methods..
934. Taiga Wakabayashi, Andrea Benedetti Cacciaguerra, Ruben Ciria, Shunichi Ariizumi, Manuel Durán, Nicolas Golse, Satoshi Ogiso, Yuta Abe, Takeshi Aoki, Etsuro Hatano, Osamu Itano, Yoshihiro Sakamoto, Tomoharu Yoshizumi, Masakazu Yamamoto, Go Wakabayashi, Landmarks to identify segmental borders of the liver: A review prepared for PAM-HBP expert consensus meeting 2021., Journal of hepato-biliary-pancreatic sciences, 10.1002/jhbp.899, 29, 1, 82-98, 2021.01, BACKGROUND: In preparation for the upcoming consensus meeting in Tokyo in 2021, this systematic review aimed to analyze the current available evidence regarding surgical anatomy of the liver, focusing on useful landmarks, strategies and technical tools to perform precise anatomic liver resection (ALR). METHODS: A systematic review was conducted on MEDLINE/PubMed for English articles and on Ichushi database for Japanese articles until September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: A total of 3169 manuscripts were obtained, 1993 in English and 1176 in Japanese literature. Subsequently, 63 English and 20 Japanese articles were selected and reviewed. The quality assessment of comparative series and case series was revealed to be usually low; only six articles were qualified as high quality. Forty-two articles focused on analyzing intersegmental/sectional planes and their relationship with specific hepatic landmark veins. In 12 articles, the authors aimed to investigate liver surface anatomic structures, while 36 articles aimed to study technological tools and contrast agents for surgical segmentation during ALR. Although Couinaud's classification has remained the cornerstone in daily diagnostic/surgical practices, it does not always portray the realistic liver segmentation and there has been no standardization on which a single strategy should be followed to perform precise ALR. CONCLUSIONS: A global consensus should be pursued in order to establish clear guidelines and proper recommendations to perform ALR in the era of minimally invasive surgery..
935. Taichi Nagano, Shinji Itoh, Yu Miyashita, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Yoshihiro Nagao, Takeo Toshima, Noboru Harada, Kenichi Kohashi, Yutaka Ogata, Eiji Oki, Yoshinao Oda, Tomoharu Yoshizumi, Masaki Mori, Late recurrence of cancer stem cell-positive colorectal cancer liver metastases after 15 years., Clinical journal of gastroenterology, 10.1007/s12328-020-01330-1, 14, 2, 613-616, 2021.04, No cases of late recurrence of colorectal cancer liver metastasis (CRLM) over 10 years have been reported in the literature. A 72-year-old woman had a surgical history of sigmoid colectomy and partial hepatic resections for sigmoid colon cancer and multiple liver metastases 15 years previously. The patient had been postoperatively treated with chemotherapy for 6 months and was observed regularly with no recurrence. Computed tomography (CT) performed due to high carcinoembryonic antigen (CEA) revealed a tumor of 70 mm in diameter at the anterior segment of the liver and a 6-mm nodule at the left lateral segment. There was no other malignant finding. We performed central bisegmentectomy and partial resection of the liver. Pathological findings showed the tumors to be well to moderately differentiated adenocarcinoma, and positive cytokeratin 20 (CK20) and caudal-type homeobox transcription factor 2 (CDX2) expression with negative expression of cytokeratin 7 (CK7). In addition, the tumors showed cluster of differentiation 44 (CD44) and 133 (CD133) positive signified cancer stem cell immunohistochemically. The postoperative diagnosis was recurrence of hepatic metastasis of sigmoid colon cancer. We report a rare case of late recurrence of CRLM more than 15 years after the primary diagnosis..
936. Yukio Oshiro, Hiroshi Harada, Kiyoshi Hasegawa, Naotake Akutsu, Tomoharu Yoshizumi, Naoki Kawagishi, Koji Nanmoku, Naotsugu Ichimaru, Kenichi Okamura, Masahiro Ohira, Yoshihiro Itabashi, Nobuhiro Fujiyama, Kentaro Ide, Hideaki Okajima, Kohei Ogawa, Kosei Takagi, Hidetoshi Eguchi, Masahiro Shinoda, Kiyotaka Nishida, Jiro Shimazaki, Mitsugi Shimoda, Masaharu Takahashi, Hiroaki Okamoto, Shuji Suzuki, Loss of antibodies to hepatitis E virus in organ transplant patients with hepatitis E., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13637, 51, 5, 538-547, 2021.05, AIM: Studies regarding changes in antibodies to hepatitis E virus (HEV) after HEV infection in organ transplant patients are limited. This study aimed to clarify HEV infection trends in organ transplant patients who contracted HEV using data from a previous Japanese nationwide survey. METHODS: This study was undertaken from 2012 to 2019. Among 4518 liver, heart, and kidney transplant patients, anti-HEV immunoglobulin G (IgG) antibodies were positive in 164; data were collected from 106 of these patients, who consented to participate in the study. In total, 32 liver transplant patients, seven heart transplant patients, and 67 kidney transplant patients from 16 institutions in Japan were examined for IgG, IgM, and IgM antibodies to HEV and the presence of HEV RNA in the serum. The χ2 -test was used to determine the relationship between the early and late postinfection groups in patients with anti-HEV IgG positive-to-negative conversion rates. The Mann-Whitney U-test was used to compare clinical factors. RESULTS: Anti-HEV IgG positive-to-negative conversion occurred in 25 (23.6%) of 106 organ transplant patients. Of eight patients with hepatitis E who tested positive for HEV RNA, one (14.0%) had anti-HEV IgG positive-to-negative conversion. Twenty-four (24.5%) of 98 patients negative for HEV RNA had anti-HEV IgG positive-to-negative conversion. CONCLUSIONS: This study revealed, for the first time, the changes in HEV antibodies in organ transplant patients. Loss of anti-HEV IgG could often occur unexpectedly in organ transplant patients with previous HEV infection..
937. Kyohei Yugawa, Shinji Itoh, Tomoharu Yoshizumi, Akinari Morinaga, Norifumi Iseda, Takeo Toshima, Noboru Harada, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Lymphocyte-C-reactive protein ratio as a prognostic marker associated with the tumor immune microenvironment in intrahepatic cholangiocarcinoma., International journal of clinical oncology, 10.1007/s10147-021-01962-4, 26, 10, 1901-1910, 2021.06, BACKGROUND: Changes in immune cell and inflammation-associated protein levels, either independently or in combination, are commonly used as prognostic factors for various cancers. The ratio of lymphocyte count to C-reactive protein concentration (lymphocyte-CRP ratio; LCR) is a recently identified prognostic marker for several cancers. Here, we examined the prognostic value of LCR and its relationship to various aspects of the tumor immune microenvironment in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: This was a single-center, retrospective study of patients who underwent surgical resection for ICC between 1998 and 2018. Patients were dichotomized into high- and low-LCR status groups, and the relationships between LCR status, prognosis, and other clinicopathological characteristics were analyzed. Tumor-infiltrating CD8+ and FOXP3s+ lymphocytes and tumor expression of CD34 and programmed death-ligand 1 were evaluated by immunohistochemical staining of resected tumors. RESULTS: A total of 78 ICC patients were enrolled and assigned to the high (n = 44)- and low (n = 34)-LCR groups. Compared with the high-LCR group, patients in the low-LCR group had a significantly higher serum CA19-9 level (median 20.6 vs. 77.3 U/mL, P = 0.0017) and larger tumor size (median 3.5 vs. 5.5 cm, P = 0.0018). LCR correlated significantly with tumor microvessel density (r = 0.369, P = 0.0009) and CD8+ T lymphocyte infiltration (r = 0.377, P = 0.0007) but not with FOXP3+ T lymphocyte infiltration or tumor PD-L1 expression. Low-LCR status was significantly associated with worse overall survival by multivariate analysis (P = 0.0348). CONCLUSIONS: Low-LCR status may reflect a poor anti-tumor immune response and predict worse outcomes in ICC patients..
938. Norifumi Iseda, Shinji Itoh, Tomoharu Yoshizumi, Takahiro Tomiyama, Akinari Morinaga, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Takeo Toshima, Yoshihiro Nagao, Noboru Harada, Yoshinao Oda, Masaki Mori, Lymphocyte-to-C-reactive protein ratio as a prognostic factor for hepatocellular carcinoma., International journal of clinical oncology, 10.1007/s10147-021-01985-x, 26, 10, 1890-1900, 2021.07, BACKGROUND: Systemic inflammation has been correlated with worse survival for some cancers. We evaluated prognostic values of various inflammatory factor combinations in patients who underwent resections for hepatocellular carcinoma (HCC). METHODS: We retrospectively analysed 306 consecutive patients with HCC who underwent curative liver resections. After assessing eight combinations of inflammatory markers for predictive value for recurrence, we focused on lymphocyte-to-C-reactive protein ratio (LCR) to elucidate its associations with recurrence-free survival (RFS) and overall survival (OS) in univariate and multivariate analyses (Cox proportional hazards model). We also used immunohistochemical CD34 and CD8 staining to investigate the mechanism of LCR elevation. RESULTS: LCR showed the highest association with RFS in HCC patients among the compared indices. High preoperative LCR correlated with a high serum albumin concentration, small tumour size, early Barcelona Clinic Liver Cancer stage and low rates of microscopic vascular invasion and microscopic intrahepatic metastasis. Higher preoperative LCR was an independent predictor of longer RFS and OS in this cohort. High LCR patients had fewer vessels encapsulating tumour clusters, and higher intratumoural CD8+ T-cell counts than low LCR patients. CONCLUSIONS: Preoperative LCR is a novel and convenient prognostic marker for patients with HCC, and is associated with the tumour microenvironment immune status..
939. Sachiyo Yoshio, Tomonari Shimagaki, Ryuki Hashida, Takumi Kawaguchi, Yuriko Tsutsui, Yuzuru Sakamoto, Yuichi Yoshida, Hironari Kawai, Shiori Yoshikawa, Taiji Yamazoe, Taizo Mori, Yosuke Osawa, Shinji Itoh, Moto Fukai, Tomoharu Yoshizumi, Akinobu Taketomi, Masaki Mori, Tatsuya Kanto, Myostatin as a fibroblast-activating factor impacts on postoperative outcome in patients with hepatocellular carcinoma., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13667, 51, 7, 803-812, 2021.05, AIM: In patients with liver cirrhosis, high levels of serum myostatin are associated with poor prognosis. We aimed to clarify the influence of myostatin on the prognosis of patients with non-alcoholic fatty liver disease-hepatocellular carcinoma (NAFLD-HCC) without cirrhosis and on the progression of liver fibrosis. METHODS: Serum myostatin levels were evaluated in 234 patients who underwent primary surgical resection for single HCC. To clarify the impact of myostatin on liver fibrosis, we established human primary liver fibroblasts from resected livers, and cultured them in the presence of myostatin. RESULTS: The median age was 67.4 years, the median L3 skeletal muscle mass index was 44.4 cm2 /m2 , and the median body mass index was 23.4 kg/m2 . Eighty-two (35.0%) patients had sarcopenia (L3 skeletal muscle mass index: men <42, women <38 cm2 /m2 ). The etiologies of liver disease were hepatitis B virus (n = 61), hepatitis C virus (n = 86), and non-B non-C hepatitis (n = 87) including NAFLD (n = 74). High preoperative serum myostatin and vascular invasion were independent predictors of poor overall survival (OS). High serum myostatin was associated with poor OS in patients with no sarcopenia (n = 152). In patients without advanced liver fibrosis (Fibrosis stage, 0-2; n = 58), high levels of serum myostatin were also associated with poor OS, regardless of sarcopenia. Serum myostatin levels were increased with the progression of liver fibrosis. Liver fibroblasts were activated and produced collagen following stimulation with myostatin. CONCLUSIONS: In patients with NAFLD-HCC without advanced liver fibrosis, high levels of serum myostatin were associated with poor OS. Myostatin activated primary fibroblasts and stimulated collagen production..
940. Koichiro Morita, Akihiro Nishie, Yasuhiro Ushijima, Yukihisa Takayama, Nobuhiro Fujita, Yuichiro Kubo, Keisuke Ishimatsu, Tomoharu Yoshizumi, Junki Maehara, Kousei Ishigami, Noninvasive assessment of liver fibrosis by dual-layer spectral detector CT., European journal of radiology, 10.1016/j.ejrad.2021.109575, 136, 109575-109575, 2021.03, PURPOSE: To elucidate the diagnostic ability of liver fibrosis using (1) liver parenchymal iodine density on equilibrium computed tomographic imaging and (2) extracellular volume (ECV) measured by dual-layer spectral detector CT. METHODS: From April 2018 to June 2019, 68 patients [mean age, 62 years; 39 males, 29 females] underwent dynamic contrast-enhanced CT by a dual-layer spectral detector CT system before liver transplantation or liver resection. The iodine densities of liver parenchyma (I liver) and aorta (I aorta) were independently measured by two radiologists at the equilibrium phase. The iodine-density ratio (I-ratio) (I liver/ I aorta) and the CT-ECV were calculated. Spearman's rank correlation coefficient was used to analyze the relationship between the I-ratio or the CT-ECV and the fibrosis stage. A receiver operating characteristic (ROC) curve analysis was performed to determine the accuracy of the I-ratio and the CT-ECV for discriminating fibrosis stages. RESULTS: For both readers, the I-ratio and the CT-ECV increased significantly as the fibrosis stage advanced (I-ratio: rho = 0.380 and 0.443, p < 0.01; CT-ECV: rho = 0.423 and 0.469, p < 0.01). The CT-ECV showed better diagnostic accuracy for staging fibrosis, and the area under the ROC curve values for discriminating F4 stage were 0.884 and 0.925. The two readers' cutoff values of the CT-ECV for diagnosing fibrosis as F4 were 26.2 % and 29.3 %, with 95.0 % and 90.0 % sensitivity and 72.9 % and 85.4 % specificity, respectively. CONCLUSION: The liver parenchymal iodine density on the equilibrium phase and the CT-ECV can be useful for predicting a high stage of liver fibrosis..
941. Kyohei Yugawa, Shinji Itoh, Norifumi Iseda, Takeshi Kurihara, Yoshiyuki Kitamura, Takeo Toshima, Noboru Harada, Kenichi Kohashi, Shingo Baba, Kousei Ishigami, Yoshinao Oda, Tomoharu Yoshizumi, Masaki Mori, Obesity is a risk factor for intrahepatic cholangiocarcinoma progression associated with alterations of metabolic activity and immune status., Scientific reports, 10.1038/s41598-021-85186-6, 11, 1, 5845-5845, 2021.03, Body mass index (BMI) is well known to be associated with poor prognosis in several cancers. The relationship between BMI and the long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC) is incompletely understood. This study investigated the relationships of BMI with clinicopathological characteristics and patient outcomes, focusing on metabolic activity and immune status. The relationship between BMI and the maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was analyzed. In addition, immunohistochemistry was performed for programmed cell death-ligand 1 (PD-L1), cluster of differentiation 8 (CD8), and forkhead box protein P3 (Foxp3). Seventy-four patients with ICC were classified into normal weight (BMI < 25.0 kg/m2, n = 48) and obesity groups (BMI ≥ 25.0 kg/m2, n = 26), respectively. Serum carbohydrate antigen 19-9 levels were higher in the obesity group than in the normal weight group. Tumor size and the intrahepatic metastasis rate were significantly larger in the obesity group. Patients in the obesity group had significantly worse prognoses than those in the normal weight group. Moreover, BMI displayed a positive correlation with SUVmax on 18F-FDG PET/CT (n = 46, r = 0.5152). Patients with high 18F-FDG uptake had a significantly higher rate of PD-L1 expression, lower CD8 + tumor-infiltrating lymphocyte (TIL) counts, and higher Foxp3 + TIL counts. The elevated BMI might predict the outcomes of patients with ICC. Obesity might be associated with ICC progression, possibly through alterations in metabolic activity and the immune status..
942. Junji Kawasaki, Takeo Toshima, Tomoharu Yoshizumi, Shinji Itoh, Yohei Mano, Huanlin Wang, Norifumi Iseda, Noboru Harada, Yoshinao Oda, Masaki Mori, Prognostic Impact of Vessels that Encapsulate Tumor Cluster (VETC) in Patients who Underwent Liver Transplantation for Hepatocellular Carcinoma., Annals of surgical oncology, 10.1245/s10434-021-10209-5, 2021.06, BACKGROUND: There is limited published information about prognostic value of vessels that encapsulate tumor cluster (VETC) based on their involvement with immune cells in hepatocellular carcinoma (HCC). Our goal was to evaluate prognostic impact of VETC in patients who underwent living-donor liver transplantation (LDLT) for HCC, focusing on the involvement of VETC with immune status in tumor microenvironment (TME). METHODS: Using a database of 150 patients who underwent LDLT for HCC, immunohistochemical staining of CD34 for VETC, angiopoietin-2 (Ang-2), CD3, and CD68, was reviewed with patients' clinicopathological factors. RESULTS: A strong correlation between VETC pattern and malignant potential in HCC was observed; larger tumor size (P < 0.001), more numbers of tumors (P = 0.003), higher α-fetoprotein levels (P = 0.001), higher des-γ-carboxy prothrombin levels (P = 0.022), microvascular invasion (P < 0.001), and poor differentiation (P = 0.010). Overall survival (OS) of patients with VETC(+) was significantly lower than those with VETC(-) (P = 0.021; 5-year OS rates, 72.0% vs. 87.1%). Furthermore, the ratio of CD3(+) cells was significantly lower in VETC(+) group (P = 0.001), indicating that VETC activity may be strongly correlated with lymphocyte activity. Moreover, combination status of VETC(+)/CD3low was an independent risk factor for mortality (hazard ratio 2.760, 95% confidence interval 1.183-6.439, P = 0.019). Additionally, the combination of VETC expression with immune status (low CD3 levels) enabled further classification of patients based on their clinical outcome. CONCLUSIONS: Our results show the prognostic impact of VETC expression, tumor-infiltrating lymphocytes (TILs), and their combination in the setting of LDLT for HCC, which can be a novel prognostic biomarker for mortality after LDLT..
943. Kyohei Yugawa, Shinji Itoh, Tomoharu Yoshizumi, Norifumi Iseda, Takahiro Tomiyama, Takeo Toshima, Noboru Harada, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Prognostic impact of tumor microvessels in intrahepatic cholangiocarcinoma: association with tumor-infiltrating lymphocytes., Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 10.1038/s41379-020-00702-9, 34, 4, 798-807, 2021.04, Tumor microvessel density (MVD) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (ICC). Tumor-infiltrating lymphocytes (TILs) are also key components of the tumor microenvironment that play important roles in ICC progression. This study aimed to clarify the relationships between the MVD and immune status and prognosis in patients with ICC. Immunohistochemical staining for cluster of differentiation 34 (CD34), cluster of differentiation 8 (CD8), forkhead box protein P3 (Foxp3), and programmed death-ligand 1 (PD-L1) was performed. The relationships between the MVD and clinicopathological characteristics and outcomes were analyzed. Additionally, the correlations between the MVD, CD8+ and Foxp3+ TIL counts, and PD-L1 expression were evaluated. One hundred ICC patients were classified into high (n = 50) and low (n = 50) MVD groups. The serum platelet and carbohydrate antigen 19-9 levels were higher in the low MVD group than in the high MVD group (P = 0.017 and P = 0.008, respectively). The low MVD group showed a significantly larger tumor size (P = 0.016), more frequent microvascular invasion (P = 0.001), and a higher rate of intrahepatic (P = 0.023) and lymph node (P < 0.001) metastasis than the high MVD group. Moreover, the MVD showed a high positive correlation with CD8+ TILs (r = 0.754, P < 0.001) and a negative correlation with Foxp3+ TILs (r = -0.302, P = 0.003). In contrast, no significant correlation was observed between the MVD and PD-L1 expression in cancer cells (P = 0.817). Patients with low MVDs had a significantly worse prognosis than those with high MVDs. Furthermore, multivariable analyses revealed that a low MVD influenced recurrence-free survival. A decreased intratumoral MVD might predict ICC patient outcomes. Tumor microvessels might be associated with ICC progression, possibly by altering TIL recruitment..
944. Shinji Itoh, Eiji Tsujita, Kengo Fukuzawa, Keishi Sugimachi, Tomohiri Iguchi, Mizuki Ninomiya, Takashi Maeda, Kiyashi Kajiyama, Eisuke Adachi, Hideaki Uchiyama, Tohru Utsunomiya, Yasuharu Ikeda, Soichirou Maekawa, Takeo Toshima, Noboru Harada, Tomoharu Yoshizumi, Masaki Mori, Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: A multi-institutional retrospective study., Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 10.1016/j.pan.2021.08.003, 2021.08, BACKGROUND: The aim of this study was to investigate the clinical value of nutritional and immunological prognostic scores as predictors of outcomes and to identify the most promising scoring system for patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-institutional study. METHODS: Data were retrospectively collected for 589 patients who underwent surgical resection for PDAC. Prognostic analyses were performed for overall (OS) and recurrence-free survival (RFS) using tumor and patient-related factors, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), modified GPS, C-reactive protein-to-albumin ratio, Controlling Nutritional Status score, and the Geriatric Nutritional Risk Index. RESULTS: Compared with PDAC patients with high PNI values (≥46), low PNI (<46) patients showed significantly worse overall survival (OS) (multivariate hazard ratio (HR), 1.432; 95% CI, 1.069-1.918; p = 0.0161) and RFS (multivariate HR, 1.339; 95% CI, 1.032-1.736; p = 0.0277). High carbohydrate antigen 19-9 (CA19-9) values (≥450) were significantly correlated with shorter OS (multivariate HR, 1.520; 95% CI, 1.261-2.080; p = 0.0002) and RFS (multivariate HR, 1.533; 95% CI, 1.199-1.961; p = 0.0007). Stratification according to PNI and CA19-9 was also significantly associated with OS and RFS (log rank, P < 0.0001). CONCLUSIONS: Our large cohort study showed that PNI and CA19-9 were associated with poor clinical outcomes in PDAC patients following surgical resection. Additionally, combining PNI with CA19-9 enabled further classification of patients according to their clinical outcomes..
945. Shoichi Inokuchi, Shinji Itoh, Tomoharu Yoshizumi, Akinari Morinaga, Takeo Toshima, Kazuki Takeishi, Yoshihiro Nagao, Noboru Harada, Toru Ikegami, Mototsugu Shimokawa, Masaki Mori, Prognostic significance of systemic inflammation score in patients who undergo hepatic resection for hepatocellular carcinoma., Langenbeck's archives of surgery, 10.1007/s00423-021-02103-1, 406, 3, 773-779, 2021.05, PURPOSE: Systemic inflammation score (SIS) is a novel prognostic score (0, 1, or 2) for various cancers, based on preoperative serum albumin level and lymphocyte-to-monocyte ratio (LMR); modified SIS (mSIS) uses a different LMR cutoff value and was thought to be a more accurate predictor for cancer prognosis. Here, we assessed the prognostic value of SIS and mSIS in patients who receive hepatic resection for hepatocellular carcinoma (HCC). METHODS: We retrospectively evaluated SIS and mSIS of 314 patients after hepatic resection for HCC, against their clinicopathological factors and outcomes, using receiver operating characteristics (ROC) analysis over time. RESULTS: Among patients with preoperative SIS 2, significantly more HCC specimens were poorly differentiated (P = 0.0281), larger (P = 0.0006), and had more microscopic vascular invasion (P = 0.0136) than the SIS 0-1 group; the mSIS 2 group also had significantly larger tumors (P = 0.0039) than the mSIS 0-1 group. In ROC analysis, SIS was a better predictor of overall survival (OS) and recurrence-free survival (RFS) than mSIS. The SIS 2 group had shorter OS (P = 0.0015) and RFS (P = 0.0065) than other patients. In multivariate analysis, SIS 2 was an independent risk factor for shorter OS (hazard ratio (HR) 1.53, P = 0.0497) and RFS (HR 1.58, P = 0.0053). CONCLUSION: SIS is superior to mSIS in predicting prognosis of patients with HCC. mSIS is not a great predictor of prognosis in resected HCC..
946. Ryota Nakanishi, Eiji Oki, Hirofumi Hasuda, Eiki Sano, Yu Miyashita, Akihiro Sakai, Naomichi Koga, Naotaka Kuriyama, Kentaro Nonaka, Yoshiaki Fujimoto, Tomoko Jogo, Kentaro Hokonohara, Qingjiang Hu, Yuichi Hisamatsu, Koji Ando, Yasue Kimura, Tomoharu Yoshizumi, Masaki Mori, Radiomics Texture Analysis for the Identification of Colorectal Liver Metastases Sensitive to First-Line Oxaliplatin-Based Chemotherapy., Annals of surgical oncology, 10.1245/s10434-020-09581-5, 28, 6, 2975-2985, 2021.06, OBJECTIVE: The aim of this study was to develop a radiomics-based prediction model for the response of colorectal liver metastases to oxaliplatin-based chemotherapy. METHODS: Forty-two consecutive patients treated with oxaliplatin-based first-line chemotherapy for colorectal liver metastasis at our institution from August 2013 to October 2019 were enrolled in this retrospective study. Overall, 126 liver metastases were chronologically divided into the training (n = 94) and validation (n = 32) cohorts. Regions of interest were manually segmented, and the best response to chemotherapy was decided based on Response Evaluation Criteria in Solid Tumors (RECIST). Patients who achieved clinical complete and partial response according to RECIST were defined as good responders. Radiomics features were extracted from the pretreatment enhanced computed tomography scans, and a radiomics score was calculated using the least absolute shrinkage and selection operator regression model in a trial cohort. RESULTS: The radiomics score significantly discriminated good responders in both the trial (area under the curve [AUC] 0.8512, 95% confidence interval [CI] 0.7719-0.9305; p < 0.0001) and validation (AUC 0.7792, 95% CI 0.6176-0.9407; p < 0.0001) cohorts. Multivariate analysis revealed that high radiomics scores greater than - 0.06 (odds ratio [OR] 23.803, 95% CI 8.432-80.432; p < 0.0001), clinical non-T4 (OR 6.054, 95% CI 2.164-18.394; p = 0.0005), and metachronous disease (OR 11.787, 95% CI 2.333-70.833; p = 0.0025) were independently associated with good response. CONCLUSIONS: Radiomics signatures may be a potential biomarker for the early prediction of chemosensitivity in colorectal liver metastases. This approach may support the treatment strategy for colorectal liver metastasis..
947. Katsuya Toshida, Shinji Itoh, Tomoharu Yoshizumi, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Takeo Toshima, Yoshihiro Nagao, Noboru Harada, Kojiro Hata, Yoko Makihara, Hiroyuki Watanabe, Masaki Mori, Retrospective evaluation of the effect of Ninjin'yoeito in hepatocellular carcinoma patients treated with lenvatinib., Surgery today, 10.1007/s00595-021-02358-7, 2021.08, PURPOSES: Lenvatinib (LEN) is a molecular-target drug, used for unresectable hepatocellular carcinoma (HCC). It is associated with adverse events (AEs), including hypertension, proteinuria, fatigue, and anorexia, which may force dose reduction or discontinuation. Ninjin'yoeito (NYT) is a Chinese-Japanese herbal compound that can effectively treat fatigue and anorexia, and which has been used for chronic liver diseases. NYT reduces AEs and improves the liver function in patients treated with sorafenib but its effect on LEN is unclear. METHODS: The present study included 46 patients (male, n = 32; female, n = 14) who received LEN for HCC at our hospital. Their median age was 70 years (range 36-88 years), and their median body weight was 61.5 kg (range 38.4-97.0 kg). Patients were divided into two groups, depending on whether they received NYT medication. Their AEs and liver function were examined one month after starting LEN. RESULTS: The NYT group suffered less fatigue (63.6% vs. 11.4%, P = 0.0014) and showed elevated aspartate aminotransferase levels (45.5% vs. 14.3%, P = 0.0433) in comparison to the non-NYT group. The non-NYT group also showed a significantly exacerbated albumin-bilirubin (ALBI) grade (P = 0.0342) and ALBI score (average change: + 0.232, P = 0.0001) at 1 month in comparison to baseline. CONCLUSION: NYT apparently suppressed LEN-induced fatigue and helped maintain liver function in patients with HCC..
948. Daisuke Imai, Takashi Maeda, Huanlin Wang, Tomonari Shimagaki, Kensaku Sanefuji, Hiroto Kayashima, Shinichi Tsutsui, Hiroyuki Matsuda, Tomoharu Yoshizumi, Masaki Mori, Risk Factors for and Outcomes of Intraoperative Blood Loss in Liver Resection for Hepatocellular Tumors., The American surgeon, 10.1177/0003134820949995, 87, 3, 376-383, 2021.03, Intraoperative blood loss (IBL) during liver resection is a predictor of morbidity, mortality, and tumor recurrence after hepatectomy; however, there have been few reports on patient factors associated with increased IBL. We enrolled consecutive patients who underwent liver resection for primary liver malignancies, and evaluated the predictors of IBL using a data set in which factors that might influence IBL, such as surgical devices, methods and anesthetic technique, were all standardized. We studied 244 patients. A multivariate analysis revealed that higher IBL was an independent risk factor for post-hepatectomy liver failure grade ≥B and overall survival. Multiple linear regression analyses showed serum creatinine, clinically significant portal hypertension (CSPH), tumor size, and major hepatectomy were all significant predictors of IBL. In conclusion, higher IBL was significantly associated with increased morbidity and mortality in patients with primary HCC who underwent liver resection. The risk of IBL was related to several factors including tumor size, serum creatinine, CSPH, and major hepatectomy..
949. Tomoharu Yoshizumi, Shinji Itoh, Mototsugu Shimokawa, Shoichi Inokuchi, Noboru Harada, Kazuki Takeishi, Yohei Mano, Shohei Yoshiya, Takeshi Kurihara, Yoshihiro Nagao, Toru Ikegami, Yuji Soejima, Masaki Mori, Simultaneous splenectomy improves outcomes after adult living donor liver transplantation., Journal of hepatology, 10.1016/j.jhep.2020.08.017, 74, 2, 372-379, 2021.02, BACKGROUND & AIMS: Small-for-size graft (SFSG) syndrome is a major cause of graft loss after living donor liver transplantation (LDLT). Splenectomy (Spx) is an option to prevent this catastrophic complication, but its effect remains controversial. Herein, we aimed to elucidate the effect of simultaneous Spx on graft function and long-term outcomes after LDLT. METHODS: Three hundred and twenty patients were divided into 2 groups: those undergoing (n = 258) and those not undergoing (n = 62) simultaneous Spx. To overcome selection bias, propensity score matching (PSM) was performed (n = 50 in each group). RESULTS: Before PSM, recipients undergoing simultaneous Spx showed better graft function on post-operative day (POD) 7 and 14, as well as lower sepsis frequency within 6 months after LDLT and better graft survival rates compared to those not undergoing Spx. After PSM, compared to patients not undergoing Spx, those undergoing Spx had a lower frequency of early graft dysfunction on POD 7 (p = 0.04); a lower frequency of SFSG syndrome (p = 0.01), lower serum total bilirubin levels (p = 0.001), and lower international normalized ratio (p = 0.004) on POD 14; lower sepsis frequency within 6 months after LDLT (p = 0.02), and better graft survival rates (p = 0.04). Univariate analysis revealed that not undergoing Spx (hazard ratio 3.06; 95% CI 1.07-11.0; p = 0.037) was the only risk factor for graft loss after LDLT. CONCLUSIONS: Simultaneous Spx may prevent SFSG syndrome and is a predictive factor for graft survival after LDLT. Simultaneous Spx is recommended when a small graft (≤35% of standard liver weight) is predicted preoperatively, or for patients with portal hypertension or high portal pressure (above 20 mmHg) after reperfusion in LDLT. LAY SUMMARY: Living donor liver transplantation (LDLT) for patients with acute or chronic liver failure is an alternative to overcome the deceased donor shortage. The potential mismatch between graft and body size is a problem that needs to be solved for LDLT recipients. Herein, we evaluated the impact of simultaneous splenectomy and showed that it was associated with favorable outcomes in patients undergoing LDLT..
950. Shoichi Inokuchi, Tomoharu Yoshizumi, Takeo Toshima, Shinji Itoh, Kyohei Yugawa, Noboru Harada, Hiroyuki Mori, Takasuke Fukuhara, Yoshiharu Matsuura, Masaki Mori, Suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy., Cancer medicine, 10.1002/cam4.3519, 10, 5, 1501-1514, 2021.03, Autophagy removes damaged organelles to inhibit malignant transformation during tumor initiation. Once a cancer matures, it uses the autophagic pathway as an energy source. Optineurin (OPTN) is an autophagy adaptor protein that recruits microtubule-associated protein 1 light chain 3, an autophagosome marker, to the autophagosome. Despite studies of the relation between cancer progression and autophagy adaptor proteins, there are no reports to our knowledge of a correlation between hepatocellular carcinoma (HCC) and OPTN. We aimed here to investigate the effects of OPTN expression on HCC progression through autophagy. Immunohistochemistry was used to measure the OPTN expression in the tissues of 141 Japanese patients with HCC. The effects of OPTN expression on HCC progression and mitophagy were assessed using an OPTN knockout (KO) cell line in vitro. We used this KO cell line to establish and exploit a mouse model of HCC to determine the effects of OPTN expression on tumor progression. Immunohistochemical analysis showed that patients with elevated expression of OPTN experienced shorter overall survival (OS) and recurrence-free survival (RFS). OPTN KO cells proliferated relatively slower versus wild-type (WT) cells in vitro. Western blot analysis showed that mitophagy was suppressed in OPTN KO cells, and ATP synthesis and beta-oxidation were reduced. The mouse model of HCC showed that OPTN KO cells formed smaller tumors versus WT cells less 10 weeks after implantation. Overall, the present findings suggest that OPTN is a key mediator of mitophagy that contributes to HCC progression through mitochondrial energy production..
951. Huanlin Wang, Shinji Itoh, Yuji Matsumoto, Akihiro Nishie, Takeshi Kurihara, Tomonari Shimagaki, Yoshihiro Nagao, Takeo Toshima, Noboru Harada, Kenichi Kohashi, Yoshinao Oda, Kousei Ishigami, Haruhiko Maruyama, Tomoharu Yoshizumi, Masaki Mori, Surgically resected hepatic mass caused by fascioliasis., Clinical journal of gastroenterology, 10.1007/s12328-021-01339-0, 14, 2, 662-667, 2021.04, Fascioliasis is a parasitic infestation caused by the digenetic trematodes Fasciola hepatica and F. gigantica. It is not commonly seen in developed countries, so diagnosis there is always difficult as a result of confusion with other hepatic or biliary disorders. A 56-year-old man presented at our hospital with a hepatic mass that had been inadvertently discovered by ultrasonography. Abdominal computed tomography revealed a multi-cystic lesion distributed along the branch of the right bile duct. Endoscopic retrograde cholangiopancreatography showed serrated changes ranging from the upper level of the common bile duct to the right hepatic bile duct. Eosinophilia was not observed and tumor marker levels were within normal ranges. Following right lobectomy combined with bile duct reconstruction, a histological examination revealed cholangitis with inflammatory cell infiltration accompanied by parasite egg-like structures and Charcot-Leyden crystals. An additional serologic test was positive for F. hepatica antibodies. A diagnosis of fascioliasis was thus confirmed by histopathology and serology. Fascioliasis should be suspected if imaging findings such as multiple small hypodense lesions in the liver are observed, and serologic tests can be useful for differential diagnosis..
952. Shohei Yoshiya, Noboru Harada, Takahiro Tomiyama, Kazuki Takeishi, Takeo Toshima, Tomohiro Iguchi, Shinji Itoh, Mizuki Ninomiya, Tomoharu Yoshizumi, Masaki Mori, The Significant Prognostic Factors in Prolonged Intensive/High Care Unit Stay After Living Donor Liver Transplantation., Transplantation proceedings, 10.1016/j.transproceed.2021.02.020, 53, 5, 1630-1638, 2021.06, BACKGROUND: Prolonged stay in an intensive/high care unit (ICU/HCU) after living donor liver transplantation (LDLT) is a significant event with possible mortality. METHODS: Adult-to-adult LDLTs (n = 283) were included in this study. Univariate and multivariate analyses were performed for the factors attributed to the prolonged ICU/HCU stay after LDLT. RESULTS: Recipients who stayed in the ICU/HCU 9 days or longer were defined as the prolonged group. The prolonged group was older (P = .0010), had a higher model for end-stage liver disease scores (P < .0001), and had higher proportions of patients with preoperative hospitalization (P < .0001). Delirium (P < .0001), pulmonary complications (P < .0001), sepsis (P < .0001), reintubation or tracheostomy (P < .0001), relaparotomy due to bleeding (P = .0015) or other causes (P < .0001), and graft dysfunction (P < .0001) were associated with prolonged ICU/HCU stay. Only sepsis (P = .015) and graft dysfunction (P = .019) were associated with in-hospital mortality among patients with prolonged ICU/HCU stay or graft loss within 9 days of surgery. Among these patients, grafts from donors aged <42 years and with a graft-to-recipient weight ratio of >0.76% had significantly higher graft survival than grafts from others (P = .0013 and P < .0001, respectively). CONCLUSION: Prolonged ICU/HCU stay after LDLT was associated with worse short-term outcomes. The use of grafts of sufficient volume from younger donors might improve graft survival..
953. Takeo Toshima, Tomoharu Yoshizumi, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Yoshihiro Nagao, Shinji Itoh, Noboru Harada, Masaki Mori, Which is better to use "body weight" or "standard liver weight", for predicting small-for-size graft syndrome after living donor liver transplantation?, Annals of gastroenterological surgery, 10.1002/ags3.12412, 5, 3, 363-372, 2021.05, Aim: Little evidence about whether to apply graft-to-recipient body weight ratio (GRWR) or graft weight to standard liver weight (GW/SLW) for graft selection has been published. The aim of the present study was to clarify the importance of the correct use of GRWR and GW/SLW for selecting graft according to the recipients' physique in living donor liver transplantation (LDLT). Methods: Data were collected for 694 recipients who underwent LDLT between 1997 and 2020. Results: One of the marginal grafts meeting GW/SLW ≥ 35% but GRWR < 0.7% has been used in more recipients with men and higher body mass index (BMI), and the other meeting GRWR ≥ 0.7% but GW/SLW < 35% has been used in more recipients with women with lower BMI. In the cohort of BMI > 30 kg/m2, the recipients with GRWR < 0.7% had a significantly higher incidence of small-for-size graft syndrome (SFSS) compared to those with GRWR ≥ 0.7% (P = 0.008, 46.2% vs 5.9%), and using the cutoff of GW/SLW < 35% could not differentiate. In contrast, in the cohort of BMI ≤ 30 kg/m2, the recipients with GW/SLW < 35% also had a significantly higher incidence of SFSS (P = 0.013, 16.9% vs 9.4%). Multivariate analysis showed that GRWR < 0.7% [odds ratio (OR) 14.145, P = 0.048] was the independent risk factor for SFSS in obese recipients, and GW/SLW < 35% [OR 2.685, P = 0.002] was the independent risk factor in non-obese recipients. Conclusion: Proper use of the formulas for calculating GRWR and GW/SLW in choosing graft according to recipient BMI is important, not only to meet metabolic demand for avoiding SFSS but also to ameliorate donor shortages..
954. Yoshizumi T, Itoh S, Shimokawa M, Inokuchi S, Harada N, Takeishi K, Mano Y, Yoshiya S, Kurihara T, Nagao Y, Ikegami T, Soejima Y, Mori M., Simultaneous splenectomy improves outcomes after adult living donor liver transplantation., Journal of Hepatology, 10.1016/j.jhep.2020.08.017. , 74, 2, 372-379, 2021.02.
955. Masaru Harada, Yuichi Honma, Tomoharu Yoshizumi, Keiichiro Kumamoto, Shinji Oe, Noboru Harada, Aya Tanimoto, Kei Yabuki, Tsukasa Karasuyama, Akitoshi Yoneda, Michihiko Shibata, Idiopathic copper toxicosis: is abnormal copper metabolism a primary cause of this disease?, Medical molecular morphology, 10.1007/s00795-019-00227-4, 53, 1, 50-55, 2020.03, Idiopathic copper toxicosis (ICT) is characterized by marked copper deposition, Mallory-Denk body (MDB) formation and severe hepatic injury. Although the characteristics are apparently different from Wilson disease, large amounts of copper accumulate in the liver of the patients. We extensively treated a patient with ICT to reduce the body copper, however, the patient needed liver transplantation. Previous liver biopsy revealed high copper content. But extirpated liver contained an extremely small amount of copper, although MDBs and severe inflammation remained. These phenomena suggest abnormal copper metabolism is not the principle cause of ICT but some other abnormality must exist..
956. Akira Watanabe, Norihumi Harimoto, Kenichiro Araki, Norio Kubo, Takamichi Igarashi, Mariko Tsukagoshi, Norihiro Ishii, Takahiro Yamanaka, Tomoharu Yoshizumi, Ken Shirabe, Absolute Neutrophil Count Predicts Postoperative Prognosis in Mass-forming Intrahepatic Cholangiocarcinoma., Anticancer research, 10.21873/anticanres.13197, 39, 2, 941-947, 2019.02, BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (IHCC) is characterized by poor prognosis, and postoperative recurrence remains a problem. Thus, prognostic markers for IHCC are greatly needed. Recently, inflammatory factors were reported to be related to tumor progression and recurrence in various cancers. Therefore, the present study aimed to evaluate the prognostic ability of inflammatory factors. MATERIALS AND METHODS: Forty-four patients with mass-forming IHCC (m-IHCC) were retrospectively evaluated and the correlations between inflammatory markers, including neutrophil-to-lymphocyte ratio and, modified Glasgow prognostic score, and patient survival were assessed. RESULTS: The absolute neutrophil count (ANC) was significantly higher in the recurrence group than in the non-recurrence group (p=0.00568) and the most significant prognostic factor by multivariate analysis. Poor recurrence-free survival (RFS; p=0.00452) and cancer-specific survival (CSS; p=0.0323) were associated with high neutrophil levels. Moreover, neutrophil infiltration in the tumor site was positively correlated with ANC. CONCLUSION: ANC is associated with poor RFS, and could be used to predict recurrence in patients with m-IHCC..
957. Tomoharu Yoshizumi, Noboru Harada, Masaki Mori, Biliary Stricture: The Achilles Heel of Pediatric Living Donor Liver Transplantation., Transplantation, 10.1097/TP.0000000000002573, 103, 9, 1758-1759, 2019.09, Since a 1989 report demonstrating successful living donor liver transplantation (LDLT), living donors have been increasingly used to overcome the disparity between organ supply and demand, especially in the cases of pediatric patients. Although short-term graft outcomes after LDLT have improved significantly because of progress in surgical techniques and immunosuppression, biliary stricture (BS) remains the Achilles heel of pediatric LDLT and is the major cause of significant long-term morbidity. BS results in poor quality of life or even in graft loss after LDLT, with a reported incidence of BS after pediatric LDLT of 10% to 35%. The suggested risk factors for BS after LDLT are hepatic arterial thrombosis, bile duct ischemia, acute cellular rejection, older donor age, and ABO incompatibility. Duct-to-duct biliary reconstruction, which enables an endoscopic approach to be attempted after BS, is the preferred technique for LDLT. Endoscopic approaches are less invasive and more convenient for recipients than surgical and percutaneous interventions. However, the major cause of end-stage liver disease in pediatric recipients is biliary atresia, and hepaticojejunostomy is needed to reconstruct the bile duct because of the lack of recipient bile duct. Endoscopic approaches for BS are usually less favorable in patients with hepaticojejunostomy than in those with duct-to-duct biliary reconstruction. Treatment options for BS after hepaticojejunostomy at many centers thus involve interventional radiology or surgical reintervention. Although endoscopic approaches remain controversial in pediatric recipients, several reports have shown them to be safe and less invasive..
958. Yohei Mano, Sachiyo Yoshio, Hirotaka Shoji, Shimagaki Tomonari, Yoshihiko Aoki, Nobuyoshi Aoyanagi, Toru Okamoto, Yoshiharu Matsuura, Yosuke Osawa, Kiminori Kimura, Kyohei Yugawa, Huanlin Wang, Yoshinao Oda, Tomoharu Yoshizumi, Yoshihiko Maehara, Tatsuya Kanto, Bone morphogenetic protein 4 provides cancer-supportive phenotypes to liver fibroblasts in patients with hepatocellular carcinoma., Journal of gastroenterology, 10.1007/s00535-019-01579-5, 54, 11, 1007-1018, 2019.11, BACKGROUND: Cancer-associated fibroblasts (CAFs) are essential constituents of cancer-supportive microenvironments. The high incidence of hepatocellular carcinoma (HCC) in advanced fibrosis patients implies that fibroblasts have a promoting effect on HCC development. We aimed to explore the regulators of phenotypes and function of CAFs in the liver. METHODS: We established primary cancer-associated fibroblasts (CAFs) and non-cancerous liver fibroblasts (NFs) from 15 patients who underwent HCC resection. We compared phenotypes, capacity of cytokine/chemokine production and gene expression profiles between pairs of CAFs and NFs from the same donors. We examined resected tissue from additional 50 patients with HCC for immunohistochemical analyses. RESULTS: The CAFs expressed more ACTA2 and COL1A1 than the NFs, suggesting that CAFs are more activated phenotype. The CAFs produced larger amounts of IL-6, IL-8 and CCL2 than the NFs, which led to invasiveness of HuH7 in vitro. We found that Bone Morphogenetic Protein-4 (BMP4) is up-regulated in CAFs compared to NFs. The CAF phenotype and function were gained by BMP4 over-expression or recombinant BMP4 given to fibroblasts, all of which decreased with BMP4 knockdown. In tissues obtained from the patients, BMP4-positive cells are mainly observed in encapsulated fibrous lesions and HCC. Positive expression of BMP4 in HCC in resected tissues, not in fibroblasts, was associated with poorer postoperative overall survival in patients with HCC. CONCLUSION: Endogenous and exogenous BMP4 activate liver fibroblasts to gain capacity of secreting cytokines and enhancing invasiveness of cancer cells in the liver. BMP4 is one of the regulatory factors of CAFs functioning in the microenvironment of HCC..
959. Tatsunori Miyata, Yo-Ichi Yamashita, Tomoharu Yoshizumi, Masayuki Shiraishi, Masayuki Ohta, Susumu Eguchi, Shinichi Aishima, Hikaru Fujioka, Hideo Baba, CXCL12 expression in intrahepatic cholangiocarcinoma is associated with metastasis and poor prognosis., Cancer science, 10.1111/cas.14151, 110, 10, 3197-3203, 2019.10, Intrahepatic cholangiocarcinoma is a rare malignant biliary neoplasm that causes a poor prognosis even after curative hepatectomy. Liver metastasis is the major recurrence pattern of intrahepatic cholangiocarcinoma; therefore, the prevention of liver metastasis is a desirable objective. The aim of this study is to identify gene(s) related to liver metastasis of intrahepatic cholangiocarcinoma and to examine the inhibitory effects on metastasis of intrahepatic cholangiocarcinoma by controlling such gene(s). We collected 3 pairs of intrahepatic cholangiocarcinoma frozen samples, and 36 pairs (primary and metastatic lesions) of intrahepatic cholangiocarcinoma formalin-fixed paraffin-embedded samples, from patients who underwent surgical resection at hospitals related to the Kyushu Study Group of Liver Surgery between 2002 and 2016. We carried out cDNA microarray analyses and immunohistochemistry to identify candidate genes, and evaluated one of them as a therapeutic target using human cholangiocarcinoma cell lines. We identified 4 genes related to liver metastasis using cDNA microarray, and found that CXCL12 was the only gene whose expression was significantly higher in liver metastasis than in primary intrahepatic cholangiocarcinoma by immunohistochemistry (P = .003). In prognosis, patients in the high CXCL12 group showed a significantly poor prognosis in disease-free (P < .0001) and overall survival (P = .0004). By knockdown of CXCL12, we could significantly suppress the invasive and migratory capabilities of 2 human cholangiocarcinoma cell lines. Therefore, CXCL12 might be associated with metastasis and poor prognosis in intrahepatic cholangiocarcinoma..
960. Takuma Izumi, Kazuhito Sakata, Daisuke Okuzaki, Shoichi Inokuchi, Tomokazu Tamura, Daisuke Motooka, Shota Nakamura, Chikako Ono, Masahiro Shimokawa, Yoshiharu Matsuura, Masaki Mori, Takasuke Fukuhara, Tomoharu Yoshizumi, Characterization of human pegivirus infection in liver transplantation recipients, Journal of Medical Virology, 10.1002/jmv.25555, 91, 12, 2093-2100, 2019.12, © 2019 Wiley Periodicals, Inc. Approximately 2% of healthy persons are infected with human pegivirus (HPgV). HPgV is transmitted via vertical, sexual, and blood-borne routes. Recently, the association of HPgV infection with the risk of lymphoma was reported. Here, we examined the prevalence of chronic HPgV infection in liver transplantation (LT) recipients and patients with hepatectomy and the influence of HPgV infection after LT on clinical and perioperative factors. We enrolled 313 LT recipients and 187 patients with hepatectomy who received care at the Kyusyu University Hospital between May 1997 and September 2017. Of the 313 recipients and 187 patients enrolled in this study, 44 recipients (14.1%) and 2 patients (1.1%) had HPgV viremia, respectively. There was no significant association between HPgV infection and LT outcomes. Interestingly, one recipient was infected with HPgV during the peritransplant period, which was likely transmitted via blood transfusion because HPgV RNA was detected from the blood bag transfused to the recipient during LT. We reviewed the available literature on the prevalence HPgV infections in other organ-transplanted patients and whether they impacted clinical outcomes. They also had the higher prevalence of HPgV infection, while it appears to be of low or no consequences. In addition, HPgV infection induced the upregulation of interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells. LT recipients had higher HPgV viremia compared to patients with hepatectomy. Although HPgV infection was not associated with LT-related outcomes, it induced ISG expression in recipients..
961. Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Masaki Mori, Effective and Safe Living Donor Hepatectomy Under Intermittent Inflow Occlusion and Outflow Pressure Control., Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 10.1007/s11605-019-04196-y, 23, 7, 1529-1530, 2019.07.
962. Shohei Yoshiya, Kengo Fukuzawa, Shoichi Inokuchi, Yukiko Kosai-Fujimoto, Kensaku Sanefuji, Kentaro Iwaki, Akira Motohiro, Shinji Itoh, Noboru Harada, Toru Ikegami, Tomoharu Yoshizumi, Masaki Mori, Efficacy of Neoadjuvant Chemotherapy in Distal Pancreatectomy with En Bloc Celiac Axis Resection (DP-CAR) for Locally Advanced Pancreatic Cancer., Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 10.1007/s11605-019-04324-8, 24, 7, 1605-1611, 2019.07, BACKGROUNDS: Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is an extended surgical procedure for patients with locally advanced cancer of the pancreatic body and tail. Recently, the usability of neoadjuvant chemotherapy (NAC) in pancreatic cancer was reported. The purpose of this study was to clarify the impact of NAC on surgical outcomes and prognosis in DP-CAR patients. METHODS: This study retrospectively reviewed 20 consecutive patients who underwent DP-CAR at a single institution. RESULTS: Eleven of 20 patients (55.0%) received NAC. Their first regimens were gemcitabine (GEM) plus nab-PTX (n = 7, 63.6%), GEM plus S-1 (n = 3, 27.3%), and GEM (n = 1, 9.1%). Although two patients converted to a second regimen, none abandoned NAC due to adverse effects or could not undergo a planned procedure for disease progression. There were no significant differences in intraoperative variables, morbidity, including pancreatic fistula and delayed gastric emptying, and mortality between patients with and without NAC; however, patients with NAC had a significantly lower proportion of arterial invasion (p = 0.025), lymphatic invasion (p < 0.0001), and vascular invasion (p = 0.035). There were no significant differences in the induction rate of adjuvant chemotherapy (p = 0.201). The recurrence-free survival and overall survival rates in patients with NAC were significantly higher than in patients without NAC (p = 0.041 and p = 0.018, respectively). CONCLUSION: DP-CAR following NAC was associated with a preferable prognosis and had no negative effect on surgical outcomes. Therefore, NAC in DP-CAR patients might be a beneficial and safe therapeutic strategy..
963. Koichi Kimura, Kensuke Kudo, Tomoharu Yoshizumi, Takeshi Kurihara, Shohei Yoshiya, Yohei Mano, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Tetsuo Ikeda, Electrohydraulic lithotripsy and rendezvous nasal endoscopic cholangiography for common bile duct stone: A case report., World journal of clinical cases, 10.12998/wjcc.v7.i10.1149, 7, 10, 1149-1154, 2019.05, BACKGROUND: In patients with large stones in the common bile duct (CBD), advanced treatment modalities are generally needed. Here, we present an interesting case of a huge CBD stone treated with electrohydraulic lithotripsy (EHL) by the percutaneous approach and rendezvous endoscopic retrograde cholangiography (ERC) using a nasal endoscope. CASE SUMMARY: A 91-year-old woman underwent ERC for a symptomatic large CBD stone with a diameter of 50 mm. She was referred to our institution after the failure of lithotomy by ERC, and after undergoing percutaneous transhepatic biliary drainage. We attempted to fragment the stone by transhepatic cholangioscopy using EHL. However, the stones were too large and partly soft clay-like for lithotripsy. Next, we attempted lithotomy with ERC and cholangioscopy by the rendezvous technique using a nasal endoscope and achieved complete lithotomy. No complication was observed at the end of this procedure. CONCLUSION: Cholangioscopy by rendezvous technique using a nasal endoscope is a feasible and safe endoscopic method for removing huge CBD stones..
964. Toru Ikegami, Tomoharu Yoshizumi, Yuriko Tsutsui, Noboru Harada, Shinji Itoh, Shohei Yoshiya, Daisuke Imai, Hideaki Uchiyama, Masaki Mori, Extensive Thrombectomy as a Legitimate Strategy in Living Donor Liver Transplantation With Advanced Portal Vein Thrombosis., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.25623, 25, 12, 1768-1777, 2019.12, Management of portal vein thrombosis (PVT), especially advanced PVT involving the superior mesenteric vein (SMV), in living donor liver transplantation (LDLT) is challenging. There were 514 adults who underwent LDLT between 2005 and 2018 included in this retrospective study, and PVT was observed in 67 (13.0%) patients. The LDLT recipients with PVT were characterized by increased portal pressure at laparotomy (26.1 ± 6.0 versus 24.3 ± 5.9 mm Hg; P = 0.03) and at closure (16.8 ± 3.9 versus 15.6 ± 3.6 mm Hg; P = 0.02), increased operative blood loss (14.6 ± 29.7 versus 5.7 ± 6.3 L; P < 0.01), and decreased 1-year graft survival (83.5% versus 92.8%; P = 0.04). Among the 18 patients with atrophic or vanished portal vein on pre-LDLT computed tomography, significant portal atrophy was actually observed only in 1 (5.6%) patient during LDLT surgery. For advanced PVT (n = 7) involving SMV in era 1, we performed nonanatomical inflow reconstruction using interposition grafts, resulting in significant inflow problems in 4 (57.1%) patients. Thus, for the patients with advanced PVT (n = 4) in era 2, we abandoned nonanatomical reconstruction and applied extensive thrombectomy under ultrasound guidance with secure shunt ligation, resulting in no inflow problems and no graft loss. In conclusion, even for advanced PVT involving SMV, extensive thrombectomy under sonogram guidance followed by anatomical inflow reconstruction and shunt ligation is a legitimate strategy in adult LDLT with PVT..
965. Takeo Toshima, Tomoharu Yoshizumi, Masahiro Shimokawa, Toru Ikegami, Noboru Harada, Shinji Itoh, Yohei Mano, Takashi Motomura, Yuji Soejima, Yoshihiko Maehara, Feasibility of All-in-One Venoplasty With a Venous Cuff Using an Opened Round Ligament for the Right Lobe Graft in Living Donor Liver Transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.25339, 25, 1, 171-175, 2019.01.
966. Imai D, Yoshizumi T, Okano S, Itoh S, Ikegami T, Harada N, Aishima S, Oda Y, Maehara Y, IFN-γ Promotes Epithelial-Mesenchymal Transition and the Expression of PD-L1 in Pancreatic Cancer., The Journal of surgical research, 10.1016/j.jss.2019.02.038, 240, 115-123, 2019.08.
967. Noboru Harada, Tomoharu Yoshizumi, Hideaki Uchiyama, Yuji Soejima, Toru Ikegami, Shinji Itoh, Impact of hepatic artery size mismatch between donor and recipient on outcomes after living-donor liver transplantation using the right lobe., Clinical transplantation, 10.1111/ctr.13444, 33, 1, e13444, 2019.01, INTRODUCTION: The aim of this study was to evaluate the effect of hepatic artery (HA) size mismatch anastomosis on outcomes after living-donor liver transplantation (LDLT). MATERIALS AND METHODS: After excluding 128 patients with the exclusion criteria among 233 LDLTs using the right lobe, 104 LDLT patients were divided into two groups: donor HA diameter that was greater than or equal to the recipient HA diameter (D ≥ R group; n = 79), and donor HA diameter that was smaller than the recipient HA diameter (D < R group; n = 25). RESULTS: Hepatic artery-related complications occurred in only one patient (HA thrombosis; 1.0%) who was in the D < R group. The reconstructed HA flow in the D ≥ R group was significantly greater than that in the D < R group (P = 0.015). There was a higher incidence of anastomotic biliary stricture in the D < R group (32.0%) compared with the D ≥ R group (13.9%, P = 0.022) after LDLT. A multivariate analysis with Cox regression revealed that the HA anastomosis of the D < R group and hepaticojejunostomy were significant independent risk factors for postoperative anastomotic biliary stenosis. CONCLUSIONS: Hepatic artery anastomosis with a donor HA diameter smaller than that of the recipient HA might be an independent risk factor for postoperative biliary stenosis after LDLT using the right lobe..
968. Tomoharu Yoshizumi, Ken Shirabe, Masaki Mori, It is time to abandon the Milan criteria., Hepatobiliary surgery and nutrition, 10.21037/hbsn.2018.10.08, 8, 1, 56-58, 2019.02.
969. Yuki Morooka, Koji Umeshita, Akinobu Taketomi, Ken Shirabe, Tomoharu Yoshizumi, Mayumi Yamamoto, Tsuyoshi Shimamura, Akihiko Oshita, Hideki Ohdan, Naoki Kawagishi, Kuniko Hagiwara, Hidetoshi Eguchi, Hiroaki Nagano, Long-term donor quality of life after living donor liver transplantation in Japan., Clinical transplantation, 10.1111/ctr.13584, 33, 6, e13584, 2019.06, AIMS: This study examined the long-term quality of life (QOL) of living liver donors (LLDs) in Japan using both generic and LLD-specific instruments. METHODS: The sample comprised 374 LLDs from five university hospitals in Japan who underwent surgery more than a year previously. QOL was evaluated using the Short Form-36 health survey (SF-36) and LLD-QOL scale. RESULTS: SF-36 results indicated that the overall long-term QOL of LLDs was significantly better than the Japanese standard. When comparing by donor factors, LLDs whose recipients were children scored higher for "satisfaction" than those whose recipients were adults on the LLD-QOL scale. LLDs with complications had lower QOL for "scars" and "burden" on the LLD-QOL scale but no differences in SF-36 scores. LLDs with longer hospital stay had lower physical QOL on SF-36 and lower QOL for "scars" and "after-effects" on the LLD-QOL scale. LLDs whose recipients have died showed lower mental QOL on SF-36 and lower "satisfaction" and greater "lack of understanding of donor health" on the LLD-QOL scale. CONCLUSIONS: Our multicenter study clarified the long-term QOL of LLDs and suggested that donors' QOL was related to the donors' and recipients' ages, donor's complications and hospital stay length, and recipient's prognosis..
970. Yo-Ichi Yamashita, Katsunori Imai, Takayoshi Kaida, Takanobu Yamao, Masayo Tsukamoto, Shigeki Nakagawa, Hirohisa Okabe, Akira Chikamoto, Takatoshi Ishiko, Tomoharu Yoshizumi, Tetsuo Ikeda, Yoshihiko Maehara, Hideo Baba, Multimodal radiofrequency ablation versus laparoscopic hepatic resection for the treatment of primary hepatocellular carcinoma within Milan criteria in severely cirrhotic patients: long-term favorable outcomes over 10 years., Surgical endoscopy, 10.1007/s00464-018-6264-3, 33, 1, 46-51, 2019.01, BACKGROUND: Less invasiveness is an important consideration for the treatment of hepatocellular carcinoma (HCC) especially in patients with severe cirrhosis. METHODS: Between April 2000 and September 2016, 100 patients with liver damage B underwent multimodal radiofrequency ablation (RFA; n = 62) or laparoscopic hepatic resection (Lap-HR; n = 38) for primary HCC as defined by the Milan criteria. We compared the operative outcomes and patients' survival between the two groups. RESULTS: The RFA group showed worse liver functions as indicated by indocyanine green retention rate (32.9 vs. 22.4%; p < 0.0001) and serum albumin value (3.3 vs. 3.6 g/dl; p = 0.0029). As expected, RFA was less invasive, as indicated by the differences in operation time (166 vs. 288 min.; p < 0.0001) and blood loss (8 vs. 377 g; p < 0.0001). There was no significant difference in the morbidity rate between the two groups; however, the duration of hospital stay of the RFA group was significantly shorter (7 vs. 11 days; p = 0.0002). There were no significant between-group differences regarding overall or disease-free survival. CONCLUSION: Multimodal RFA for HCC in patients with severe cirrhosis is associated with less invasiveness and shorter hospital stays, with no compromise in the patients' survival. In patients with severe cirrhosis, it may be time to consider changing the standard treatment for primary HCC within the Milan criteria to multimodal RFA..
971. Mio Fukuda, Kimitaka Suetsugu, Soichiro Tajima, Yurie Katsube, Hiroyuki Watanabe, Noboru Harada, Tomoharu Yoshizumi, Nobuaki Egashira, Masaki Mori, Satohiro Masuda, Neutrophil Gelatinase-Associated Lipocalin Is Not Associated with Tacrolimus-Induced Acute Kidney Injury in Liver Transplant Patients Who Received Mycophenolate Mofetil with Delayed Introduction of Tacrolimus., International journal of molecular sciences, 10.3390/ijms20123103, 20, 12, 2019.06, Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication. The urinary neutrophil gelatinase-associated lipocalin (NGAL) level has been linked to tacrolimus-induced AKI in patients starting tacrolimus treatment the morning after liver transplantation. Here we tested this association using a different immunosuppression protocol: Mycophenolate mofetil administration beginning on Postoperative Day 1 and tacrolimus administration beginning on Postoperative Day 2 or 3. Urine samples were collected from 26 living donor liver transplant recipients before (Postoperative Day 1) and after (Postoperative Day 7 or 14) tacrolimus administration. NGAL levels were measured via enzyme-linked immunosorbent assays, as were those of three additional urinary biomarkers for kidney diseases: Monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), and human epididymis secretory protein 4 (HE4). HE4 levels after tacrolimus administration were significantly higher in patients who developed AKI (n = 6) than in those who did not (n = 20), whereas NGAL, MCP-1, and L-FABP levels did not differ significantly before or after tacrolimus administration. These findings indicate that NGAL may not be a universal biomarker of AKI in tacrolimus-treated liver transplant recipients. To reduce the likelihood of tacrolimus-induced AKI, our immunosuppression protocol is recommended..
972. Akihiro Nishie, Sadato Akahori, Yoshiki Asayama, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Kakihara, Tomohiro Nakayama, Yukihisa Takayama, Nobuhiro Fujita, Koichiro Morita, Keisuke Ishimatsu, Seiichiro Takao, Tomoharu Yoshizumi, Kenichi Kohashi, Yuanzhong Li, Hiroshi Honda, Prediction of Liver Fibrosis Using CT Under Respiratory Control: New Attempt Using Deformation Vectors Obtained by Non-rigid Registration Technique., Anticancer research, 10.21873/anticanres.13257, 39, 3, 1417-1424, 2019.03, AIM: To investigate whether liver fibrosis can be predicted by quantifying the deformity of the liver obtained based on computed tomographic (CT) images scanned under respiratory control. MATERIALS AND METHODS: For dynamic CT of 47 patients, portal venous and equilibrium phases were scanned during inspiration and expiration, respectively. After rigid registration of the two images, non-rigid registration of the liver was performed, and the amount and direction of each voxel's shift during non-rigid registration was defined as the deformation vector. The correlation of each CT parameter for the obtained deformation vectors with the pathologically-proven degree of liver fibrosis was assessed using Spearman's rank correlation test. Receiver operating characteristic curve analysis was conducted for prediction of liver fibrosis. RESULTS: The standard deviation, coefficient of variance (CV) and skewness were significantly negatively correlated with the degree of liver fibrosis (p=0.030, 0.009 and 0.037, respectively). Of these measures, CV was best correlated and significantly decreased as liver fibrosis progressed (rho=-0.376). CV showed accuracies of 66.0-70.2%, and the areas under curves were 0.654-0.727 for prediction of fibrosis of grade F1 or greater, F2 or greater, F3 or greater and F4 fibrosis. CONCLUSION: The deformation vector is a potential CT parameter for evaluating liver fibrosis..
973. Kyohei Yugawa, Shinji Itoh, Takeshi Kurihara, Shohei Yoshiya, Yohei Mano, Kazuki Takeishi, Noboru Harada, Toru Ikegami, Yuji Soejima, Masaki Mori, Tomoharu Yoshizumi, Skeletal muscle mass predicts the prognosis of patients with intrahepatic cholangiocarcinoma., American journal of surgery, 10.1016/j.amjsurg.2019.03.010, 218, 5, 952-958, 2019.11, BACKGROUND: We studied the prognostic impact of sarcopenia after hepatic resection for intrahepatic cholangiocarcinoma (ICC). METHODS: Sixty-one patients who underwent surgery for ICC during 2000-2017 were analyzed retrospectively. Psoas muscle areas were measured on CT scans at the third lumbar vertebra. Areas less than the sex-specific median were deemed low skeletal muscle masses (SMMs). RESULTS: Low-SMM patients were significantly more often older (p = 0.002) than high-SMM patients, had lower serum albumin (p = 0.004), higher serum C-reactive protein (CRP) (p = 0.002), and higher carbohydrate antigen 19-9 (p < 0.001). Five-year overall survival rates were 72.5% and 17.6% and 5-year recurrence-free survival rates were 58.6% and 21.1%, respectively, in high- and low-SMM patients. Multivariable analysis revealed that low SMM predicted unfavorable prognoses. SMM was associated with immune nutritional status (e.g., prognostic nutritional index, Glasgow prognostic score, CRP/albumin ratio). CONCLUSION: Low SMM was related to worse surgical outcomes in patients with ICC following hepatic resection..
974. Shinji Itoh, Tomoharu Yoshizumi, Kazuhisa Sakata, Takashi Motomura, Yohei Mano, Takeo Toshima, Norifumi Harimoto, Noboru Harada, Toru Ikegami, Yuji Soejima, Ryuichi Kusaba, Takahide Kamishima, Akihiro Nishie, Yoshihiko Maehara, Slow Gait Speed Is a Risk Factor for Complications After Hepatic Resection., Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 10.1007/s11605-018-3993-5, 23, 9, 1810-1816, 2019.09, PURPOSE: The aims of this study were to clarify the relationship of gait speed, hand grip strength, and skeletal muscle mass with complications after hepatic resection and to identify risk factors for complications in patients who underwent hepatic resection. METHODS: We evaluated the risk factors for complications after hepatic resection in 154 consecutive patients. Preoperative factors included gait speed, hand grip strength, and skeletal muscle mass. The gait speed and hand grip strength of patients were measured by physical therapists, and skeletal muscle mass was measured by computed tomography. Multivariate logistic regression analyses using preoperative factors were performed to assess predictors of the development of complications after hepatic resection. RESULTS: Thirty-three patients (21.4%) developed complications after hepatic resection. These patients had a significantly lower serum albumin level (p = 0.015), slower gait speed (p = 0.007), higher rate of hepatic resection ≥ 2 Couinaud segments (p = 0.014), and lower rate of laparoscopic hepatic resection (p = 0.017) than patients without complications. Multivariate analysis revealed that a gait speed ≤ 1.10 m/s and a serum albumin level of ≤ 4.0 g/dl were independent risk factors for complications after hepatic resection. CONCLUSIONS: Slow gait speed and low serum albumin level are significant risk factors for complications after hepatic resection. These data will be helpful for perioperative patient management..
975. Kyohei Yugawa, Tomoharu Yoshizumi, Yohei Mano, Takeshi Kurihara, Shohei Yoshiya, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Solitary fibrous tumor in the liver: case report and literature review., Surgical case reports, 10.1186/s40792-019-0625-6, 5, 1, 68-68, 2019.04, BACKGROUND: Solitary fibrous tumors (SFTs) are uncommon mesenchymal neoplasms that present most commonly at intrathoracic sites. SFTs of the liver are rare, with only a few having been reported in the English-language literature. We report a rare case of a hepatic SFT and literature review. CASE PRESENTATION: A 49-year-old woman underwent surgery for a cranial hemangiopericytoma two decades previously. She currently presented with malaise. Abdominal computed tomography (CT) showed a huge, sharply demarcated mass in the anterior segment of the liver. Tumor marker levels were within the normal range. Following central bisegmentectomy of the liver, histological examination of the specimen revealed that the tumor was composed of spindle and fibroblast-like cells with collagenous stroma. Immunohistochemically, the spindle cells were negative for CD34 but positive for STAT6. The NAB2-STAT6 fusion gene was detected by the reverse transcription polymerase chain reaction. A diagnosis of SFT was thus confirmed histopathologically and genetically. CONCLUSIONS: The SFT of the liver is an uncommon finding. Because there are no specific imaging features, it is difficult to diagnose the hepatic SFT preoperatively. We consider that careful surgical resection and postoperative follow-up are necessary for hepatic SFTs..
976. Toru Ikegami, Tomoharu Yoshizumi, Norifumi Harimoto, Masaki Mori, Splenectomy as Flow Modulation Strategy and Risk Factors of De Novo Portal Vein Thrombosis in Adult-to-Adult Living Donor Liver Transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.25494, 25, 8, 1281-1283, 2019.08.
977. Kazuhito Sakata, Tomoharu Yoshizumi, Takuma Izumi, Masahiro Shimokawa, Shinji Itoh, Toru Ikegami, Noboru Harada, Takeo Toshima, Yohei Mano, Masaki Mori, The Role of DNA Repair Glycosylase OGG1 in Intrahepatic Cholangiocarcinoma., Anticancer research, 10.21873/anticanres.13465, 39, 6, 3241-3248, 2019.06, BACKGROUND/AIM: The effects of oxidative stress on various carcinomas were reported in previous studies, but those in intrahepatic cholangiocarcinoma (ICC) have not been fully elucidated. The purpose of this study was, thus, to reveal the effects of oxidative DNA damage and repair enzymes on ICC. MATERIALS AND METHODS: The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-OHdG DNA glycosylase (OGG1) were immunohistochemically evaluated in specimens resected from 63 patients with ICC. RESULTS: Low OGG1 expression was related to tumour depth T4 (p=0.04), venous invasion (p=0.0005), lymphatic vessel invasion (p=0.03), and perineural invasion (p=0.03). Compared to the high-OGG1-expression group, patients with low OGG1 expression had a significantly poorer prognosis (overall survival: p=0.04, recurrence-free survival: p=0.02). Unlike for OGG1, the expression levels of 8-OHdG showed no association with prognosis. CONCLUSION: Oxidative DNA damage and DNA repair enzymes may be closely related to ICC progression..
978. Shohei Yoshiya, Ryosuke Minagawa, Keisuke Kamo, Meidai Kasai, Kenji Taketani, Takafumi Yukaya, Yasue Kimura, Tadashi Koga, Masanori Kai, Kiyoshi Kajiyama, Tomoharu Yoshizumi, Usability of Intraoperative Fluorescence Imaging with Indocyanine Green During Laparoscopic Cholecystectomy After Percutaneous Transhepatic Gallbladder Drainage., World journal of surgery, 10.1007/s00268-018-4760-1, 43, 1, 127-133, 2019.01, BACKGROUND: Patients with persistent symptoms of acute cholecystitis for >72 h who cannot undergo urgent laparoscopic cholecystectomy (LC) often undergo percutaneous transhepatic gallbladder drainage (PTGBD) and delayed LC. However, intraoperative near-infrared fluorescence with indocyanine green (ICG) has recently become available in various surgical settings. Therefore, we evaluated the usability of intraoperative fluorescence imaging with ICG for LC after PTGBD in patients with acute cholecystitis. METHODS: The preoperative and postoperative clinical characteristics of patients who underwent LC after PTGBD were retrospectively analyzed. RESULTS: In total, 130 patients were reviewed. Intraoperative ICG fluorescence imaging was used in 39 (30.0%) patients, and none developed adverse reactions. Patients with ICG fluorescence imaging had a significantly shorter operative time (129 ± 46 vs. 150 ± 56 min, p = 0.0455), markedly lower conversion rate (2.6% vs. 22.0%, p = 0.0017), and lower proportion of subtotal cholecystectomy (0.0% vs. 6.6%, p = 0.0359) than patients without ICG fluorescence imaging. Independent risk factors for conversion to laparotomy during LC after PTGBD were the performance of PTGBD after 48 h from onset (OR 3.52; 95% CI 1.11-12.21; p = 0.0322), an unremoved PTGBD tube on LC (4.48, 1.46-15.00, p = 0.0084), and surgery without ICG (8.00, 1.28-159.47, p = 0.0231). CONCLUSION: Intraoperative ICG fluorescence imaging produced better surgical outcomes without any adverse reactions. Early performance of PTGBD and intraoperative ICG fluorescence imaging can reduce the surgical difficulties in LC after PTGBD for acute cholecystitis..
979. 山下 奈真, 久松 雄一, 茂地 智子, 徳永 えり子, 佐伯 浩司, 沖 英次, 吉住 朋晴, 乳癌における腫瘍浸潤リンパ球の評価とその意義 In situ乳管癌の免疫微小環境の臨床的重要性(Clinical significance of the immune microenvironment of ductal carcinoma In Situ of the breast), 日本外科学会定期学術集会抄録集, 119回, PD-6, 2019.04.
980. Hirofumi Watanabe, Yoshiki Asayama, Akihiro Nishie, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Okamoto, Nobuhiro Fujita, Tomoharu Yoshizumi, Yoshinao Oda, Hiroshi Honda, A case of pseudoglandular hepatocellular carcinoma: The usefulness of a multimodal approach., Radiology case reports, 10.1016/j.radcr.2018.03.022, 13, 3, 689-692, 2018.06, Hepatocellular carcinoma (HCC) mainly composed of the pseudoglandular pattern is very rare. We present a case of pseudoglandular HCC that was hyperechoic on ultrasound, with strongly high signal intensity on T2-weighted imaging and weak arterial contrast enhancement. Computed tomography hepatic arteriography showed corona enhancement. Radiologists should keep in mind this combination of multimodal radiological findings for pseudoglandular HCC..
981. Akira Watanabe, Norifumi Harimoto, Kenichiro Araki, Tomoharu Yoshizumi, Kota Arima, Yoichi Yamashita, Hideo Baba, Higuchi Tetsuya, Hiroyuki Kuwano, Ken Shirabe, A new strategy based on fluorodeoxyglucose-positron emission tomography for managing liver metastasis from colorectal cancer., Journal of surgical oncology, 10.1002/jso.25250, 118, 7, 1088-1095, 2018.12, BACKGROUND: Prognostic models are needed to manage liver metastasis from colorectal cancer (CRLM). Thus, we developed an algorithm to guide treatment based on the standardized uptake value (SUV) from fluorodeoxyglucose-positron emission tomography (FDG-PET). METHODS: We retrospectively evaluated 148 patients who underwent surgery for CRLM, including 107 cases of primary surgery and 41 cases with preoperative chemotherapy before conversion surgery. We evaluated the prognostic value of perioperative SUV among primary surgery cases, as well as the prognostic value of the SUV change ratio after conversion surgery (postchemotherapy/prechemotherapy SUV). RESULTS: In the primary surgery group, recurrence-free survival (RFS) was independently predicted by an SUV of ≥6.04 (P = 0.042) and ≥4 liver metastases ( P = 0.003). The combination of an SUV of ≥6.04 and ≥4 liver metastases was strongly associated with poor RFS ( P < 0.001). In the conversion surgery group, the SUV change ratio was associated with tumor size change and pathological response. An SUV change ratio of ≥0.293 was associated with shorter RFS ( P = 0.006) and independently predicted RFS ( P = 0.026). We established a therapeutic algorithm for managing CRLM based on these results. CONCLUSION: FDG-PET may be useful for predicting recurrence and prognosis in cases of CRLM, and our algorithm may be useful for managing multiple CRLMs..
982. Shinji Itoh, Tomoharu Yoshizumi, Takahiro Tomino, Akihisa Nagatsu, Takashi Motomura, Noboru Harada, Norifumi Harimoto, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Associations between antibody to hepatitis B core antigen positivity and outcomes in hepatocellular carcinoma patients undergoing hepatic resection., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12939, 48, 3, E155-E161-E161, 2018.02, AIM: We aimed to evaluate the effect of antibody to hepatitis B core antigen (HBcAb) positivity on clinical outcomes after hepatic resection in hepatocellular carcinoma (HCC) patients with negative hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb), termed non-B, non-C HCC (NBNC-HCC), or with HCV-related HCC. METHODS: Two hundred and sixty-three patients who underwent hepatic resection for HCC and measurements of HBsAg, HCVAb, and HBcAb were enrolled in this study. RESULTS: The percentages of HBcAb positivity were 52.3% (n = 57) and 56.9% (n = 66) in patients with NBNC- and HCV-related HCC, respectively. The proportion of multiple NBNC-HCCs was significantly greater in patients with HBcAb positivity compared to HBcAb negativity (P = 0.028). There were no significant differences in the recurrence-free and overall survival rates between NBNC-HCC patients with HBcAb positivity versus negativity (P = 0.461 and P = 0.190, respectively). Furthermore, for HCV-related HCC patients, there were no significant differences in the baseline factors between patients with positive versus negative HBcAb. The proportion of patients with HBcAb-positive HCV-related HCC who underwent anatomical resection of the liver was significantly greater than that of HBcAb-negative patients, whereas the recurrence-free and overall survival rates were not significantly different (P = 0.158 and P = 0.191, respectively). CONCLUSION: In our study, the presence of HBcAb had no impact on surgical outcomes after hepatic resection in patients with NBNB- and HCV-related HCC. Occult HBV infection might be associated with hepatocarcinogenesis in patients with NBNC-related HCC..
983. 宮田 辰徳, 山下 洋市, 吉住 朋晴, 白石 祐之, 太田 正之, 江口 晋, 相島 慎一, 馬場 秀夫, 藤岡 ひかる, CXCL12は肝内胆管癌において肝内転移を促進する(CXCL12 is involved in liver metastasis of intrahepatic cholangiocarcinoma), 日本癌学会総会記事, 77回, 1350-1350, 2018.09.
984. Hirofumi Kawanaka, Tomohiko Akahoshi, Yoshihiro Nagao, Nao Kinjo, Daisuke Yoshida, Yoshihiro Matsumoto, Norifumi Harimoto, Shinji Itoh, Tomoharu Yoshizumi, Yoshihiko Maehara, Customization of laparoscopic gastric devascularization and splenectomy for gastric varices based on CT vascular anatomy., Surgical endoscopy, 10.1007/s00464-017-5646-2, 32, 1, 114-126, 2018.01, BACKGROUND: Laparoscopic gastric devascularization(Lap GDS) and splenectomy (SPL) for gastric varices is technically challenging because of highly developed collateral vessels and bleeding tendency. We investigated the feasibility of customization of Lap GDS and SPL based on CT vascular anatomy. METHODS: We analyzed 61 cirrhotic patients with gastric varices who underwent Lap GDS and SPL between 2006 and 2014. Lap GDS was customized according to the afferent feeding veins (left gastric vein (LGV) and/or posterior gastric vein (PGV)/short gastric vein (SGV)) and efferent drainage veins (gastrorenal shunt and/or gastrophrenic shunt, or numerous retroperitoneal veins) based on CT imaging. RESULTS: Thirty-four patients with efferent drainage veins suitable for balloon-occluded retrograde transvenous obliteration (B-RTO) underwent B-RTO instead of surgical GDS, with subsequent Lap SPL. Among 27 patients with gastric varices unsuitable for B-RTO, 15 patients with PGV/SGV underwent Lap GDS of the greater curvature and SPL, and 12 patients with LGV or LGV/PGV/SGV underwent Lap GDS of the greater and lesser curvature and SPL. The mean operation time was 294 min and mean blood loss was 198 g. There was no mortality or severe morbidity. Gastric varices were eradicated in all 61 patients, with no bleeding or recurrence during a mean follow-up of 55.9 months. The cumulative 3-, 5-, and 7-year survival rates were 92, 82, and 64%, respectively. CONCLUSIONS: Lap GDS and SPL customized based on CT vascular anatomy is a safe and effective procedure for treating gastric varices..
985. Takahiro Tomino, Hirotada Tajiri, Takaaki Tatsuguchi, Takahiro Shirai, Kounosuke Oisaki, Shigeki Matsunaga, Fumiyuki Sanematsu, Daiji Sakata, Tomoharu Yoshizumi, Yoshihiko Maehara, Motomu Kanai, Jean-François Cote, Yoshinori Fukui, Takehito Uruno, DOCK1 inhibition suppresses cancer cell invasion and macropinocytosis induced by self-activating Rac1P29S mutation., Biochemical and biophysical research communications, 10.1016/j.bbrc.2018.02.073, 497, 1, 298-304, 2018.02, Rac1 is a member of the Rho family of small GTPases that regulates cytoskeletal reorganization, membrane polarization, cell migration and proliferation. Recently, a self-activating mutation of Rac1, Rac1P29S, has been identified as a recurrent somatic mutation frequently found in sun-exposed melanomas, which possesses increased inherent GDP/GTP exchange activity and cell transforming ability. However, the role of cellular Rac1-interacting proteins in the transforming potential of Rac1P29S remains unclear. We found that the catalytic domain of DOCK1, a Rac-specific guanine nucleotide exchange factor (GEF) implicated in malignancy of a variety of cancers, can greatly accelerate the GDP/GTP exchange of Rac1P29S. Enforced expression of Rac1P29S induced matrix invasion and macropinocytosis in wild-type (WT) mouse embryonic fibroblasts (MEFs), but not in DOCK1-deficient MEFs. Consistently, a selective inhibitor of DOCK1 that blocks its GEF function suppressed the invasion and macropinocytosis in WT MEFs expressing Rac1P29S. Human melanoma IGR-1 and breast cancer MDA-MB-157 cells harbor Rac1P29S mutation and express DOCK1 endogenously. Genetic inactivation and pharmacological inhibition of DOCK1 suppressed their invasion and macropinocytosis. Taken together, these results indicate that DOCK1 is a critical regulator of the malignant phenotypes induced by Rac1P29S, and suggest that targeting DOCK1 might be an effective approach to treat cancers associated with Rac1P29S mutation..
986. Shinkichi Takamori, Kazuki Takada, Tetsuzo Tagawa, Gouji Toyokawa, Fumihiko Hirai, Nami Yamashita, Tatsuro Okamoto, Eiji Oki, Tomoharu Yoshizumi, Yoshinao Oda, Yoshihiko Maehara, Differences in PD-L1 expression on tumor and immune cells between lung metastases and corresponding primary tumors., Surgical oncology, 10.1016/j.suronc.2018.08.001, 27, 4, 637-641, 2018.12, BACKGROUND: It has been reported that the tumor microenvironment, including tumor-associated immune cells (ICs) and programmed cell death-ligand 1 (PD-L1) expression, differs between primary and metastatic tumors. This study aimed to elucidate the differences in PD-L1 expression on tumor cells (TCs) and ICs between lung metastases and corresponding primary tumors. METHODS: We analyzed paired lesions from 44 patients diagnosed with lung metastases between 2005 and 2017 at Kyushu University. The percentages of PD-L1-positive TCs and ICs in lung metastases and the primary tumor were classified into five categories (0: <1%; 1: 1%-4%; 2: 5%-9%; 3: 10%-49%; and 4: ≥50%). Lesions in which ≥1% of the TCs and ICs were PD-L1-positive were considered positive. RESULTS: The primary cancers included rectal (n = 19), colon (n = 10), liver (n = 10), bile duct (n = 2), stomach (n = 1), gall bladder (n = 1) and breast (n = 1). Discrepancies in PD-L1 expression on TCs and ICs between lung metastases and primary lesions were observed in 5 (11.4%, κ = 0.23) and 9 (20.5%, κ = 0.11) of the 44 cases, respectively. PD-L1 expression on ICs was higher in lung metastases than paired primary tumors (p = 0.026), although the percentage of PD-L1-positive TCs was not significantly different between lung metastases and primary tumors (p = 0.767). CONCLUSIONS: There were significant differences in PD-L1 expression on TCs and ICs between lung metastases and primary tumors. Clinicians should be aware of these differences in the tumor microenvironment when treating patients with immunotherapy..
987. Toshimi Kaido, Masahiro Shinoda, Yukihiro Inomata, Takahito Yagi, Nobuhisa Akamatsu, Yasutsugu Takada, Hideki Ohdan, Tsuyoshi Shimamura, Yasuhiro Ogura, Susumu Eguchi, Hidetoshi Eguchi, Satoshi Ogata, Tomoharu Yoshizumi, Toshihiko Ikegami, Michio Yamamoto, Satoshi Morita, Shinji Uemoto, Effect of herbal medicine daikenchuto on oral and enteral caloric intake after liver transplantation: A multicenter, randomized controlled trial., Nutrition (Burbank, Los Angeles County, Calif.), 10.1016/j.nut.2018.02.022, 54, 68-75, 2018.10, OBJECTIVE: Postoperative early oral or enteral intake is a crucial element of the Enhanced Recovery After Surgery (ERAS) protocol. However, normal food intake or enteral feeding cannot be started early in the presence of coexisting bowel dysfunction in patients undergoing liver transplantation (LT). The aim of this multicenter, randomized, double-blinded, placebo-controlled trial was to determine the enhancement effects of the Japanese herbal medicine Daikenchuto (DKT) on oral/enteral caloric intake in patients undergoing LT. METHODS: A total of 112 adult patients undergoing LT at 14 Japanese centers were enrolled. The patients were randomly assigned to receive either DKT or placebo from postoperative day (POD) 1 to 14. The primary endpoints were total oral/enteral caloric intake, abdominal distension, and pain on POD 7. The secondary endpoints included sequential changes in total oral/enteral caloric intake after LT, and portal venous flow volume and velocity in the graft. RESULTS: A total of 104 patients (DKT, n = 55; placebo, n = 49) were included in the analyses. There were no significant differences between the two groups in terms of primary endpoints. However, postoperative total oral/enteral caloric intake was significantly accelerated in the DKT group compared with the placebo group (P = 0.023). Moreover, portal venous flow volume (POD 10, 14) and velocity (POD 14) were significantly higher in the DKT group than in the placebo group (P = 0.047, P = 0.025, P = 0.014, respectively). CONCLUSIONS: Postoperative administration of DKT may enhance total oral/enteral caloric intake and portal venous flow volume and velocity after LT and favorably contribute to the performance of the ERAS protocol..
988. Long-Bin Jeng, Sung Gyu Lee, Arvinder Singh Soin, Wei-Chen Lee, Kyung-Suk Suh, Dong Jin Joo, Shinji Uemoto, Jaewon Joh, Tomoharu Yoshizumi, Horng-Ren Yang, Gi-Won Song, Patricia Lopez, Jossy Kochuparampil, Carole Sips, Shuhei Kaneko, Gary Levy, Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study., American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 10.1111/ajt.14623, 18, 6, 1435-1446, 2018.06, In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference -0.7% (90% CI -5.2%, 3.7%); P < .001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P < .001 for non-inferiority), but not superiority and was similar between groups overall (mean -8.0 vs. -12.1 mL/min/1.73 m2 , P = .108), and in patients continuing randomized treatment (-8.0 vs. -13.3 mL/min/1.73 m2 , P = .046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432..
989. Frequency and Characteristics of Occult Hepatitis B Infection Among Hepatocellular Carcinoma Patients in Japan..
990. Frequency and Characteristics of Occult Hepatitis B Infection Among Hepatocellular Carcinoma Patients in Japan..
991. Norifumi Iseda, Tomoharu Yoshizumi, Takeo Toshima, Akinari Morinaga, Takahiro Tomiyama, Junichi Takahashi, Takashi Motomura, Yohei Mano, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Hemophagocytic syndrome after living donor liver transplantation: a case report with a review of the literature., Surgical case reports, 10.1186/s40792-018-0505-5, 4, 1, 101-101, 2018.08, BACKGROUND: Hemophagocytic syndrome (HPS) is a rare and potentially fatal complication following liver transplantation. CASE PRESENTATION: A 63-year-old woman with decompensated liver cirrhosis secondary to hepatitis B virus infection underwent living donor liver transplantation using the right posterior section of her husband's liver (graft volume, 581 g; 56.8% of the recipient's standard liver volume). She developed small-for-size syndrome on postoperative day (POD) 7, and HPS was diagnosed on POD 12 by bone marrow aspiration (white blood cells, 300/μL; neutrophils, 30/μL). Given that she tested negative for viral (hepatitis B virus and cytomegalovirus) and bacterial infections, it was considered likely to be secondary HPS. Steroid pulse therapy was initiated, and her white blood cell count increased to 4290/μL on POD 15, indicating that her peripheral blood leukocytes had improved. There were no surgical complications, but the patient died of prolonged graft dysfunction with bacterial sepsis on POD 14. CONCLUSIONS: We report a rare case of HPS occurring 2 weeks after living donor liver transplantation with a right posterior section graft, diagnosed early via bone marrow aspiration. This clinical course implies an association between HPS and graft dysfunction such as small-for-size syndrome. Further studies of the mechanism of hypercytokinemia-induced HPS are required to confirm the optimal treatment for HPS..
992. Takeo Toshima, Tomoharu Yoshizumi, Toru Ikegami, Noboru Harada, Shinji Itoh, Yohei Mano, Takashi Motomura, Yuji Soejima, Yoshihiko Maehara, Impact of Osteopenia in Liver Cirrhosis: Special Reference to Standard Bone Mineral Density with Age., Anticancer research, 10.21873/anticanres.13009, 38, 11, 6465-6471, 2018.11, BACKGROUND/AIM: Computed tomography (CT) has recently been applied to measure bone mineral density (BMD). However, the definition of osteopenia, which means depletion of BMD, using CT remains controversial. The aim of this study was to establish formulae to calculate standard BMD. PATIENTS AND METHODS: Fifty healthy donors for liver transplantation underwent CT. BMD was measured as cross-sectional average pixel density (Hounsfield units) only in trabecular-bone at Th11 bottom. Validation was performed on another 50 healthy donors to check the accuracy of formulae for standard BMD. RESULTS: Measured BMD was significantly correlated with age in both males and females (p<0.0001). The formulae to calculate standard BMD were 308.82-2.49 × Age in males and 311.84-2.41 × Age in females. Estimated BMD was significantly correlated with measured BMD in males and females (p<0.0001). CONCLUSION: Osteopenia can be defined by the difference between measured data and calculated data using our new formula based on each age..
993. Jorge Guzman-Lepe, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Yang Wang, Wendy M Mars, Yoshinao Oda, Yuki Bekki, Masahiro Shimokawa, Huanlin Wang, Tomoharu Yoshizumi, Yoshihiko Maehara, Aaron Bell, Ira J Fox, Kazuki Takeishi, Alejandro Soto-Gutierrez, Liver-enriched transcription factor expression relates to chronic hepatic failure in humans., Hepatology communications, 10.1002/hep4.1172, 2, 5, 582-594, 2018.05, The mechanisms by which the liver fails in end-stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects. To study the relevance of transcription factor expression in terminal stages of chronic liver failure in humans, we analyzed the expression of liver-enriched transcription factors (LETFs) hepatocyte nuclear factor (HNF)4α, HNF1α, forkhead box protein A2 (FOXA2), CCAAT/enhancer-binding protein (CEBP)α, and CEBPβ. We then selected downstream genes responsible for some hepatic functions (ornithine transcarbamylase [OTC], cytochrome P450 3A4 [CYP3A4], coagulation factor VII [F7], cadherin 1 [CDH1], phospho-ezrin (Thr567)/radixin (Thr564)/moesin (Thr558) [p-ERM], phospho-myosin light chain [p-MLC], low-density lipoprotein receptor-related protein 1 [LRP1]) in liver tissue from patients at different stages of decompensated liver function based upon Child-Pugh classification, Model for End-Stage Liver Disease score, and degree of inflammatory activity/fibrosis. We first examined differential expression of LETF and determined whether a relationship exists between transcript and protein expression, and liver function. We found HNF4α expression was down-regulated and correlated well with the extent of liver dysfunction (P = 0.001), stage of fibrosis (P = 0.0005), and serum levels of total bilirubin (P = 0.009; r = 0.35), albumin (P < 0.001; r = 0.52), and prothrombin time activity (P = 0.002; r = 0.41). HNF4α expression also correlated with CYP3A4, OTC, and F7 as well as CDH1 RNA levels. The Rho/Rho-associated protein kinase pathways, which have been implicated in the regulation of HNF4α, were also differentially expressed, in concert with LRP1, a reported upstream regulator of RhoA function. Conclusion: HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. (Hepatology Communications 2018;2:582-594)..
994. Daisuke Imai, Tomoharu Yoshizumi, Kazuhito Sakata, Toru Ikegami, Shinji Itoh, Noboru Harada, Takashi Motomura, Takeo Toshima, Yohei Mano, Yuji Soejima, Yoshihiko Maehara, Long-term Outcomes and Risk Factors After Adult Living Donor Liver Transplantation., Transplantation, 10.1097/TP.0000000000002324, 102, 9, e382-e391-e391, 2018.09, BACKGROUND: Although risk factors for the long-term mortality of liver transplantation are well described, there is a lack of detailed study regarding these factors for adult living donor liver transplantation (LDLT). METHODS: We retrospectively analyzed 528 adult LDLT recipients in our hospital. The risk factors were analyzed for overall deaths more than 5 years post-LDLT. RESULTS: Over the 20-year follow-up, 137 patients died. Patient survival at 1, 3, 5, and 10 years post-LDLT was 87.8%, 81.8%, 79.4%, and 72.8%, respectively. The independent risk factors for more than 5 years post-LDLT overall death were hepatocellular carcinoma recurrence (hazard ratio [HR], 38.9; P < 0.001), lymphoid de novo malignancy (HR, 47.2; P = 0.001), primary sclerosing cholangitis as primary diagnosis (HR, 11.5; P < 0.001), chronic rejection (HR, 6.93; P = 0.006), acute rejection (HR, 2.96; P = 0.017), and bile duct stenosis (HR, 2.30; P = 0.045). CONCLUSIONS: Not only malignancies and rejection but also bile duct stenosis and primary sclerosing cholangitis had significant impacts on late period post-LDLT mortality..
995. Yohei Mano, Tomoharu Yoshizumi, Kyohei Yugawa, Masafumi Ohira, Takashi Motomura, Takeo Toshima, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Lymphocyte-to-Monocyte Ratio Is a Predictor of Survival After Liver Transplantation for Hepatocellular Carcinoma., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.25204, 24, 11, 1603-1611, 2018.11, Recent studies revealed that systemic inflammation was correlated with poorer prognosis in various cancers. We investigated the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients who underwent living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). We retrospectively analyzed the records of 216 patients who underwent LDLT for HCC. Patients were divided into high (n = 126) and low (n = 90) LMR groups. Their clinicopathological parameters and survival times were compared. To determine the mechanisms of the change in the LMR, we performed immunohistochemical analyses of CD3 and CD68 expression. A low LMR was significantly associated with a high Model for End-Stage Liver Disease score; a high Child-Pugh score; elevation of alpha-fetoprotein, des-gamma-carboxyprothrombin, and neutrophil-to-lymphocyte ratio; larger tumor size; more tumors; and poorer prognosis. A low LMR was associated with poor prognosis and represented an independent prognostic factor, particularly among patients beyond the Milan criteria. The ratio of CD3-positive to CD68-positive cells was significantly lower in the low-LMR group. In conclusion, our results show that the LMR was an independent predictor of survival of patients with HCC beyond the Milan criteria who underwent LDLT. The LMR reflected the immune status of the tumor microenvironment..
996. Tomonari Shimagaki, Tomoharu Yoshizumi, Norifumi Harimoto, Sachiyo Yoshio, Yutaka Naito, Yusuke Yamamoto, Takahiro Ochiya, Yoshihiro Yoshida, Tatsuya Kanto, Yoshihiko Maehara, MicroRNA-125b expression and intrahepatic metastasis are predictors for early recurrence after hepatocellular carcinoma resection., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12990, 48, 4, 313-321, 2018.03, AIM: Early hepatocellular carcinoma (HCC) recurrence after curative resection is a known poor prognostic factor. We aimed to identify microRNAs associated with recurrence after curative HCC resection. METHODS: To identify risk factors for early recurrence and metastasis, 694 patients who underwent primary curative HCC resection were analyzed. We evaluated microRNA expression in cancerous and non-cancerous tissues by microarray and quantitative PCR analyses using 16 HCC samples. We defined patients who had a recurrence within 1 year of resection as the early recurrence (ER) group, patients who had a recurrence within 1-5 years as the late recurrence (LR) group, and patients who did not recur during the 5-year observation period as the no recurrence (NR) group. We examined the relationship between microRNA expression and clinical features. RESULTS: Multivariate analysis revealed that α-fetoprotein >31 ng/mL, tumor size >4 cm, and intrahepatic metastasis (IM) were significant factors. Afterwards, microarray analyses revealed that microRNA (miR)-125b-5p and miR-148a-3p were significantly downregulated in recurrent cases. The ratio of miR-125b-5p expression in cancerous versus non-cancerous tissue (miR-125b ratio), but not miR-148a-3p, was significantly lower in the ER group. Early recurrence was associated with reduced overall survival compared with the LR and NR group. The miR-125b ratio was significantly lower in the ER group than in the LR and NR groups. Multivariate analysis showed that a low miR-125b ratio and IM were independently associated with ER and disease-free survival. CONCLUSIONS: Assessing tissue miR-125b-5p expression and IM is useful for stratifying patients at risk of early HCC recurrence after curative resection..
997. Yo-Ichi Yamashita, Katsunori Imai, Toshihiko Yusa, Yosuke Nakao, Yuki Kitano, Shigeki Nakagawa, Hirohisa Okabe, Akira Chikamoto, Takatoshi Ishiko, Tomoharu Yoshizumi, Shinichi Aishima, Yoshihiko Maehara, Hideo Baba, Microvascular invasion of single small hepatocellular carcinoma ≤3 cm: Predictors and optimal treatments., Annals of gastroenterological surgery, 10.1002/ags3.12057, 2, 3, 197-203, 2018.05, Background: Small hepatocellular carcinomas (HCC ≤3 cm) are generally considered to have low malignant potential; however, some of them display pathological microvascular invasion (MVI). Methods: Between 1991 and 2013, 414 patients with a single HCC ≤3 cm underwent curative hepatic resection (HR). Predictors for MVI were identified. Using another cohort (149 patients during 2000-2014), our predictors for MVI in HCC ≤3 cm were validated. In 428 patients with a single HCC ≤3 cm who had predictors for MVI, survival was compared among anatomical HR (n = 149), partial HR (n = 227), and radiofrequency ablation (RFA) (n = 52). Results: The positive rate of MVI reached 40.6% (168/414 patients). Independent predictors for MVI were as follows: tumor diameter ≥2 cm (odds ratio 1.84, P = .0052), alpha-fetoprotein (AFP) ≥200 ng/mL (odds ratio 1.82, P = .0466), and des-gamma-carboxy prothrombin (DCP) ≥40 mAU/mL (odds ratio 1.79, P = .0126). Matching at least one predictor among these three could predict MVI in HCC ≤3 cm well (sensitivity 82.8%, positive predictive value [PPV] 48.7%). This criterion could also predict MVI in HCC ≤3 cm well in another cohort (sensitivity 82.8%, PPV 30.3%). In patients with single HCC ≤3 cm matching our criterion for predicting MVI, anatomical HR led to significantly better survival in both disease-free (hazard ratio 0.689, P = .0231) and overall (hazard ratio 0.589, P = .0316) survivals. Conclusion: Matching at least one factor among three (tumor diameter ≥2 cm, AFP ≥200 ng/mL, or DCP ≥40 mAU/mL) can predict MVI in HCC ≤3 cm. In such patients, anatomical HR would be recommended to improve survival..
998. Kyohei Yugawa, Tomoharu Yoshizumi, Noboru Harada, Takashi Motomura, Norifumi Harimoto, Shinji Itoh, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Multiple hepatic sclerosing hemangiomas: a case report and review of the literature., Surgical case reports, 10.1186/s40792-018-0468-6, 4, 1, 60-60, 2018.06, BACKGROUND: Hepatic sclerosing hemangioma, a very rare benign tumor, is characterized by fibrosis and hyalinization occurring in association with degeneration of a hepatic cavernous hemangioma. Such atypical hemangiomas can be diagnosed incorrectly as primary or metastatic malignancies based on imaging characteristics. We present herein a rare case of giant and multiple hepatic sclerosing hemangiomas that are difficult to differentiate from hepatic malignancies and review the relevant literature. CASE PRESENTATION: The patient was a 48-year-old male who was found to have multiple hepatic tumors and a giant tumor (67 × 53 mm) superior to the inferior vena cave by an abdominal ultrasonography during a routine medical examination. The patient was referred to our hospital for further evaluations and diagnosis of the multiple hepatic tumors. Dynamic CT showed low-density tumors in the delayed phase suggestive of membrane-covered lesions. EOB-MRI demonstrated a mass with low-signal intensity mass on T1-weighted images and areas of high-signal intensity on T2-weighted images and a hypointense mass in the hepatobiliary phase, which showed high intensity on DWI-based ADC map. FDG-PET showed no accumulation of [18F]-FDG. A provisional diagnosis of multiple scirrhous hepatocellular carcinomas was made on the basis of these imaging studies, and caudate lobectomy of the liver and partial hepatectomy of S2 and S6 were performed. Histopathological examination showed that the tumors were composed of various sized irregularly dilated vessels with some blood thrombi, inflammatory cell infiltration, fibrous and hyalinized sclerotic or myxomatous stroma, resulting in a diagnosis of multiple hepatic sclerosing hemangiomas. CONCLUSIONS: Differentiation of multiple sclerosing hemangiomas from other hepatic malignant tumors, such as intrahepatic cholangiocarcinoma, metastatic liver cancer, and scirrhous hepatocellular carcinoma characterized by abundant fibrous stroma, is difficult because the radiological findings are very similar. Inclusion of hepatic sclerosing hemangioma in the differential diagnosis of multiple liver tumors could enable optimal management; this possibility is important to consider before planning invasive therapies..
999. Nao Nishida, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Kaname Kojima, Yosuke Kawai, Kazuko Ueno, Hitomi Nakamura, Noriyo Yamashiki, Tomohiro Tanaka, Sumito Tamura, Akira Mori, Shintaro Yagi, Yuji Soejima, Tomoharu Yoshizumi, Mitsuhisa Takatsuki, Atsushi Tanaka, Kenichi Harada, Shinji Shimoda, Atsumasa Komori, Susumu Eguchi, Yoshihiko Maehara, Shinji Uemoto, Norihiro Kokudo, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura, NELFCD and CTSZ loci are associated with jaundice-stage progression in primary biliary cholangitis in the Japanese population., Scientific reports, 10.1038/s41598-018-26369-6, 8, 1, 8071-8071, 2018.05, Approximately 10-20% of patients with primary biliary cholangitis (PBC) progress to jaundice stage regardless of treatment with ursodeoxycholic acid and bezafibrate. In this study, we performed a GWAS and a replication study to identify genetic variants associated with jaundice-stage progression in PBC using a total of 1,375 patients (1,202 early-stage and 173 jaundice-stage) in a Japanese population. SNP rs13720, which is located in the 3'UTR of cathepsin Z (CTSZ), showed the strongest association (odds ratio [OR] = 2.15, P = 7.62 × 10-7) with progression to jaundice stage in GWAS. High-density association mapping at the CTSZ and negative elongation factor complex member C/D (NELFCD) loci, which are located within a strong linkage disequilibrium (LD) block, revealed that an intronic SNP of CTSZ, rs163800, was significantly associated with jaundice-stage progression (OR = 2.16, P = 8.57 × 10-8). In addition, eQTL analysis and in silico functional analysis indicated that genotypes of rs163800 or variants in strong LD with rs163800 influence expression levels of both NELFCD and CTSZ mRNA. The present novel findings will contribute to dissect the mechanism of PBC progression and also to facilitate the development of therapies for PBC patients who are resistant to current therapies..
1000. Koichi Kimura, Tomoharu Yoshizumi, Shoichi Inokuchi, Shinji Itoh, Takashi Motomura, Yohei Mano, Takeo Toshima, Noboru Harada, Norifumi Harimoto, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Potential effect of recombinant thrombomodulin on ischemia-reperfusion liver injury in rats., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.13005, 48, 5, 391-396, 2018.04, AIM: Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High-mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage-associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury. METHODS: Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1. RESULTS: In rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(-) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(-) group after surgery (P < 0.001). The levels of tumor necrosis factor-α and interleukin-6 in the liver tissue 24 h after surgery were significantly lower in the rTM(+) group than the rTM(-) group (P < 0.001). The plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(-) group (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(-) group (P < 0.001). CONCLUSIONS: Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1..
1001. Kyohei Yugawa, Tomoharu Yoshizumi, Yohei Mano, Noboru Harada, Shinji Itoh, Toru Ikegami, Yuji Soejima, Nobuhiro Fujita, Kenichi Kohashi, Shinichi Aishima, Yoshinao Oda, Masaki Mori, Primary intrahepatic cholangiocarcinoma with sarcomatous stroma: case report and review of the literature., Surgical case reports, 10.1186/s40792-018-0543-z, 4, 1, 138-138, 2018.11, BACKGROUND: Hepatic carcinosarcomas, which include both carcinomatous and sarcomatous elements, are uncommon in adults. Although carcinosarcoma in hepatocellular carcinoma is occasionally reported, carcinosarcoma in intrahepatic cholangiocarcinoma (ICC) is an extremely rare ICC variant. Few such cases have been reported in English and no large study of its clinicopathological features exists. CASE PRESENTATION: Here, we report a 60-year-old man with an asymptomatic hepatic B infection who developed hepatic carcinosarcoma from an otherwise normal liver. The 6.0-cm tumor was accidentally discovered by PET-CT in a cancer examination. Serum examinations showed no elevation of tumor markers. He underwent left and caudate lobectomy of the liver. The diagnosis of intrahepatic cholangiocarcinoma with sarcomatous stroma was based on thorough pathologic examination and immunohistochemical staining. The tumor exhibited adenocarcinomatous and sarcomatous components; the adenocarcinomatous element was positive for epithelial markers, the sarcomatous element was positive for mesenchymal markers, but negative for epithelial markers. The patient made an uneventful recovery after surgery. At present, 14 months after surgery, he remains well with no evidence of tumor recurrence. CONCLUSIONS: We report an unusual case of hepatic carcinosarcoma (intrahepatic cholangiocarcinoma with sarcomatous stroma) and discuss the etiology and prognosis of this rare disease..
1002. Norifumi Harimoto, Tomoharu Yoshizumi, Shoichi Inokuchi, Shinji Itoh, Eisuke Adachi, Yasuharu Ikeda, Hideaki Uchiyama, Tohru Utsunomiya, Kiyoshi Kajiyama, Koichi Kimura, Fumiaki Kishihara, Keishi Sugimachi, Eiji Tsujita, Mizuki Ninomiya, Kengo Fukuzawa, Takashi Maeda, Ken Shirabe, Yoshihiko Maehara, Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma: A Multi-institutional Study., Annals of surgical oncology, 10.1245/s10434-018-6672-6, 25, 11, 3316-3323, 2018.10, BACKGROUND: The Controlling Nutritional Status (CONUT) score is an objective tool that is widely used to assess the nutritional status in patients, including those with cancer. The relationship between the CONUT score and prognosis in patients who have undergone hepatic resection has not been evaluated in a multi-institutional study. METHODS: Data were retrospectively collected for 2461 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent at 13 institutions between January 2004 and December 2015. Patients were assigned to two groups: preoperative CONUT scores ≤ 3 (low CONUT score) and ≥ 4 (high CONUT score). Clinicopathological characteristics, surgical outcomes, and long-term survival were compared using propensity score matching analysis. RESULTS: Of the 2461 patients, 540 (21.9%) had high (≥ 4) and 1921 (78.1%) had low (≤ 3) preoperative CONUT scores. Overall, a high CONUT score was significantly associated with older age, female sex, low body mass index, low serum albumin, high serum total bilirubin, low lymphocyte count, low serum cholesterol, shorter prothrombin time, higher indocyanine green retention test at 15 min, Child-Pugh B (vs. A), liver cirrhosis, minor resection, shorter operation time, massive blood loss, blood transfusion, and postoperative complications. After propensity score matching, a higher CONUT score was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS) using multivariate analysis. CONCLUSIONS: This retrospective, multi-institutional analysis showed that, in patients who undergo curative hepatectomy for HCC, the preoperative CONUT score is predictive of worse OS and RFS, even after propensity score matching analysis..
1003. Yohei Yamada, Ken Hoshino, Yasushi Fuchimoto, Kentaro Matsubara, Taizo Hibi, Hiroshi Yagi, Yuta Abe, Masahiro Shinoda, Minoru Kitago, Hideaki Obara, Takahito Yagi, Hideaki Okajima, Toshimi Kaido, Shinji Uemoto, Tatsuya Suzuki, Keiichi Kubota, Tomoharu Yoshizumi, Yoshihiko Maehara, Yukihiro Inomata, Yuko Kitagawa, Hiroto Egawa, Tatsuo Kuroda, Rituximab Induction to Prevent the Recurrence of PSC After Liver Transplantation-The Lessons Learned From ABO-Incompatible Living Donor Liver Transplantation., Transplantation direct, 10.1097/TXD.0000000000000760, 4, 2, e342, 2018.02, Background: Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx. Methods: We conducted a national survey and analyzed the outcome of recipients who underwent ABO-I LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove existing antibodies, and the use of immunosuppression to control humoral immunity. Rituximab was added to the immunosuppression regimen from 2006 onward; 5 patients received rituximab perioperatively. Results: All 7 recipients who underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we found that all 5 recipients from 2006 (who were treated with rituximab) retained an excellent graft function for more than 7 years without any recurrence of PSC. Conclusions: The findings of this study shed light on the efficacy of a novel strategy to prevent the recurrence of PSC and the possible mechanisms provided by rituximab treatment are discussed..
1004. Noboru Harada, Tomoharu Yoshizumi, Toru Ikegami, Shinji Itoh, Norihiro Furusho, Masaki Kato, Shinji Shimoda, Takasuke Fukuhara, Yuji Soejima, Yoshihiko Maehara, Serum Asunaprevir and Daclatasvir Concentrations and Outcomes in Patients with Recurrent Hepatitis C Who Have Undergone Living Donor Liver Transplantation., Anticancer research, 10.21873/anticanres.12885, 38, 9, 5513-5520, 2018.09, BACKGROUND/AIM: This study's aim was to investigate the safety and effectiveness of asunaprevir and daclatasvir treatment for recurrent hepatitis C virus (HCV) infection in transplant recipients. The study cohort comprised 14 transplant recipients with recurrent hepatitis C who were receiving asunaprevir and daclatasvir. PATIENTS AND METHODS: Serum concentrations of asunaprevir and daclatasvir, their therapeutic effects, trough concentrations/dose ratios of tacrolimus, and adverse effects were evaluated. RESULTS: Hepatitis C virus was still undetectable in 12 (85.7%) out of 14 patients 12 weeks after completing treatment. One week after starting treatment, asunaprevir concentrations were significantly higher in patients with baseline albumin concentrations ≤3.6 g/dl than in those with baseline albumin concentrations >3.6 g/dl. No marked fluctuations were identified in tacrolimus trough concentrations/dose ratios during the 24 weeks of therapy. CONCLUSION: Full doses of asunaprevir and daclatasvir-based treatment can be safely and effectively administered to liver transplant recipients for recurrent HCV genotype 1b after living donor liver transplantation (LDLT) with little effect on blood concentrations of tacrolimus..
1005. Norifumi Harimoto, Tomoharu Yoshizumi, Yukiko Fujimoto, Takashi Motomura, Youhei Mano, Takeo Toshima, Shinji Itoh, Noboru Harada, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Surgery for Hepatocellular Carcinoma in Patients with Child-Pugh B Cirrhosis: Hepatic Resection Versus Living Donor Liver Transplantation., World journal of surgery, 10.1007/s00268-018-4493-1, 42, 8, 2606-2616, 2018.08, BACKGROUND: Liver transplantation has been established as the optimal treatment for hepatocellular carcinoma in cirrhotic patients, but hepatic resection is also effective in patients with well-preserved liver function. Determining the suitable surgical treatment for patients with Child-Pugh class B cirrhosis is a more difficult challenge. METHODS: We retrospectively compared the results of hepatic resection and living donor liver transplantation for hepatocellular carcinoma in 137 patients with Child-Pugh class B cirrhosis. The procedures were performed at Kyushu University Hospital from April 2014 through October 2016. RESULTS: Patients who underwent hepatic resection were significantly older and had better liver function, larger tumor size, smaller number of tumors, and less surgical stress compared with patients who underwent living donor liver transplantation. The overall survival rate and the recurrence-free survival rate in patients with transplantation were significantly better than that in patients with resection. The multivariate analysis showed that recurrent hepatocellular carcinoma and microvascular invasion were significant prognostic factors for both overall and recurrence-free survival in the hepatic resection group. In the group with protein induced by vitamin K absence or antagonist-II ≥300 mAU/mL, both the overall survival curve and the recurrence-free survival curve in patients with living donor liver transplantation were not significantly different from those in patients with hepatic resection. CONCLUSIONS: Living donor liver transplantation for hepatocellular carcinoma in patients with Child-Pugh class B cirrhosis was favorable under the condition of protein induced by vitamin K absence or antagonist-II <300 mAU/mL in selected recipients and donors. Hepatic resection for recurrent hepatocellular carcinoma and excessive blood loss should be avoided in patients with Child-Pugh class B cirrhosis..
1006. Kousei Ishigami, Akihiro Nishie, Yoshiki Asayama, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Nobuhiro Fujita, Tomoharu Yoshizumi, Norifumi Harimoto, Takao Ohtsuka, Kohei Nakata, Hiroshi Honda, The prevalence of transpancreatic common hepatic artery and coexisting variant anatomy., Clinical anatomy (New York, N.Y.), 10.1002/ca.22957, 31, 4, 598-604, 2018.05, We studied the prevalence of the transpancreatic common hepatic artery (tp-CHA) and coexisting variant anatomy. The study group comprised 788 consecutive liver transplant donor candidates who had undergone thin-section multidetector-row computed tomography (MDCT) studies to investigate vascular anatomy. Multiplanar reformatted (MPR) images obtained from the arterial phase were retrospectively reviewed to assess the presence/absence of the tp-CHA. Five cases of tp-CHA with pancreaticobiliary tumors were also included in an investigation of the presence/absence of variant hepatic arteries, celiac stenosis, and circumportal pancreas. Three of the 788 (0.38%) donor candidates had a tp-CHA. Overall, eight tp-CHA cases were assessed for coexisting variant anatomy. Seven of these eight cases had a hepatomesenteric trunk, six had celiac stenosis, and two had a circumportal pancreas. The prevalence of the tp-CHA was 0.38% (approx. one in 260 in normal populations). A tp-CHA can commonly be associated with a hepatomesenteric trunk and celiac stenosis. A circumportal pancreas can also coexist with a tp-CHA. Clin. Anat. 31:598-604, 2018. © 2017 Wiley Periodicals, Inc..
1007. Daisuke Hashimoto, Akira Chikamoto, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Hideo Baba, Yoshihiko Maehara, A comparative study on the complications of conventional and end-to-side inserting pancreatojejunostomy after pancreaticoduodenectomy., Surgery today, 10.1007/s00595-016-1364-y, 47, 2, 238-244, 2017.02, PURPOSE: Pancreatico-digestive anastomosis is important in ensuring the safety of pancreaticoduodenectomy. This study compared the postoperative complications of a newly developed method of inserting end-to-side pancreaticojejunostomy with the conventional pancreaticojejunostomy after pancreaticoduodenectomy. METHODS: From April 2012 to December 2015, 108 consecutive patients underwent pancreaticoduodenectomy at Kumamoto University Hospital. A modified child's reconstruction was performed with the inserting or conventional pancreaticojejunostomy. The clinical course and the incidence of postoperative complications were retrospectively evaluated. RESULTS: Five patients were excluded, four who underwent hepato-pancreatoduodenectomy and one who did not require pancreaticojejunostomy because of an atrophic pancreatic remnant. Of the 103 patients that were included in the analysis, 41 and 62 underwent surgery with the inserting and conventional methods, respectively. The incidence of postoperative Clavien-Dindo grade > II complications was similar in the two groups [36.6 % (15/41) vs 27.4 % (17/62)]. However, the rates of grade C postoperative pancreatic fistula [7.3 % (3/41) vs 0 % (0/62) P = 0.030] and re-operation for postoperative complications [14.6 % (6/41) vs 3.2 % (2/62), P = 0.034] were significantly higher in the inserting group than in the conventional group. There were no in-hospital deaths in either group. CONCLUSIONS: The conventional pancreaticojejunostomy is safer than the end-to-side inserting pancreaticojejunostomy, as the latter is associated with a risk of severe complications. Improvements in pancreatico-digestive anastomosis techniques are required..
1008. Toru Ikegami, Yoshihide Ueda, Nobuhisa Akamatsu, Kohei Ishiyama, Ryoichi Goto, Akihiko Soyama, Kaori Kuramitsu, Masaki Honda, Masahiro Shinoda, Tomoharu Yoshizumi, Hideaki Okajima, Yuko Kitagawa, Yukihiro Inomata, Yonson Ku, Susumu Eguchi, Akinobu Taketomi, Hideki Ohdan, Norihiro Kokudo, Mitsuo Shimada, Katsuhiko Yanaga, Hiroyuki Furukawa, Shinji Uemoto, Yoshihiko Maehara, Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience., Clinical transplantation, 10.1111/ctr.13109, 31, 11, 2017.11, The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n = 1) in the NS3, and at L31 (n = 4), Y93 (n = 4), and L31/Y93 (n = 1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n = 12). Univariate analysis showed that a history of SMV (P < .01) and the presence of mutations in NS5A (P = .02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate..
1009. N. Harimoto, T. Yoshizumi, T. Izumi, T. Motomura, N. Harada, S. Itoh, T. Ikegami, H. Uchiyama, Y. Soejima, A. Nishie, T. Kamishima, R. Kusaba, K. Shirabe, Y. Maehara, Clinical Outcomes of Living Liver Transplantation According to the Presence of Sarcopenia as Defined by Skeletal Muscle Mass, Hand Grip, and Gait Speed, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2017.09.017, 49, 9, 2144-2152, 2017.11, Background. Sarcopenia is an independent predictor of death after living-donor liver transplantation (LDLT). However, the ability of the Asian Working Group for Sarcopenia criteria for sarcopenia (defined as reduced skeletal muscle mass plus low muscle strength) to predict surgical outcomes in patients who have undergone LDLT has not been determined.
Methods. This study prospectively enrolled 366 patients who underwent LDLT at Kyushu University Hospital. Skeletal muscle area (determined by computed tomography), hand-grip strength, and gait speed were measured in 102 patients before LDLT. We investigated the relationship between sarcopenia and surgical outcomes after LDLT performed in three time periods.
Results. The number of patients with lower skeletal muscle area has increased to 52.9% in recent years. The incidence of sarcopenia according to the Asian Working Group for Sarcopenia criteria was 23.5% (24/102). Patients with sarcopenia (defined by skeletal muscle area and functional parameters) had significantly lower skeletal muscle area and weaker hand-grip strength than did those without sarcopenia. Compared with non-sarcopenic patients, patients with sarcopenia also had significantly worse liver function, greater estimated blood loss, greater incidence of postoperative complications of Clavien-Dindo grade IV or greater (including amount of ascites on postoperative day 14, total bilirubin on postoperative day 14, and postoperative sepsis), and longer postoperative hospital stay. Multiple logistic regression analysis revealed sarcopenia as a significant predictor of 6-month mortality.
Conclusions. The combination of skeletal muscle mass and function can predict surgical outcomes in LDLT patients..
1010. Huanlin Wang, Kenichi Kohashi, Tomoharu Yoshizumi, Yukihiko Okumura, Yuki Tanaka, Masahiro Shimokawa, Takeshi Iwasaki, Shinichi Aishima, Yoshihiko Maehara, Yoshinao Oda, Coexpression of SALL4 with HDAC1 and/or HDAC2 is associated with underexpression of PTEN and poor prognosis in patients with hepatocellular carcinoma., Human pathology, 10.1016/j.humpath.2017.03.007, 64, 69-75, 2017.06, Spalt-like transcriptional factor 4 (SALL4), a stem marker, is reactivated in several cancers. A previous study has demonstrated that SALL4 interacts with the nucleosome remodeling deacetylase complex, which contains histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2). In this study, we investigated the expression status of SALL4, HDAC1, and HDAC2 and their relationship with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by immunohistochemical analysis of the posthepatectomy specimens of 135 patients with hepatocellular carcinoma who were treated at our hospital. Ninety-two frozen samples were subjected to quantitative reverse-transcription polymerase chain reaction analysis to detect the messenger RNA levels of PTEN. Seventy-six (56%) of 135 patients were positive for SALL4, and this group had a higher prevalence of hepatitis B antigen, a higher value of α-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKAII) and poor histologic differentiation. The 5-year survival rate was significantly lower in the SALL4-positive group. High HDAC1 expression (51%) was correlated with a poor histologic differentiation and a poor prognosis. High HDAC2 expression (46%) was associated with a higher prevalence of hepatitis B antigen positivity, a poor histologic differentiation and higher prevalence of vascular invasion, and a lower 5-year survival rate. Coexpression of SALL4 with HDAC1 and/or HDAC2 was correlated with underexpression of PTEN. Moreover, multivariable analysis revealed that coexpression of SALL4 with HDAC1 and/or HDAC2 was predictive of an unfavorable prognosis. Our data thus suggested that the combination of SALL4, HDAC1, and HDAC2 may provide a potential target for molecular therapy..
1011. Koichiro Morita, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Nobuhiro Fujita, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Hiroshi Honda, Does apparent diffusion coefficient predict the degree of liver regeneration of donor and recipient after living donor liver transplantation?, European journal of radiology, 10.1016/j.ejrad.2017.02.041, 90, 146-151, 2017.05, OBJECTIVE: To elucidate the relationship between the ADCs of the liver graft and the remnant liver and the degree of liver regeneration in LDLT. MATERIALS AND METHODS: 15 recipients and 15 corresponding donors underwent magnetic resonance imaging and computed tomography 1-2 weeks after living donor liver transplantation (LDLT). For diffusion-weighted imaging (DWI), a single-shot echo-planar sequence with b-factors of 0, 500, and 1000s/mm2 was scanned. ADCs of the liver parenchyma were calculated at b factors of 0 and 500 and 1000 (ADC 0-500-1000) or 0 and 500 (ADC 0-500) or 500 and 1000 (ADC 500-1000). The liver volume ratio at LDLT, the mean ADCs and the regeneration rate were compared between the graft and the remnant liver using paired-t tests. RESULTS: The mean liver volume ratio of the recipients (41.3±9.8%) tended to be smaller than that of the donors (51.8±13.8%). The mean ADC 0-500 of the remnant liver (1.72±0.33) was significantly higher than that of the graft (1.43±0.32). The regeneration rate of the graft (2.07±0.41) was significantly higher than that of the remnant liver (1.53±0.49). CONCLUSION: ADC 0-500 can describe differences in blood perfusion between liver grafts and the remnant liver according to the degree of liver regeneration..
1012. T. Motomura, T. Yoshizumi, H. Wang, A. Nagatsu, S. Itoh, N. Harada, N. Harimoto, T. Ikegami, H. Uchiyama, Y. Soejima, Y. Maehara, Duct-to-duct Biliary Reconstruction in Living-donor Liver Transplantation for Primary Sclerosing Cholangitis: Report of a Case, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2017.03.069, 49, 5, 1196-1198, 2017.06, Although Roux-en Y hepaticojejunostomy was previously recommended for the binary reconstruction in liver transplantation for primary sclerosing cholangitis (PSC), some recent reports showed no difference in the graft survival between Roux-en Y and duct-to duct anastomosis in deceased-donor liver transplantation. On the other hand, considering the risk of recurrence and the short length of the bile duct of the graft, duct-to-duct biliary anastomosis has never been reported in a patient undergoing living-donor liver transplantation (LDLT) for PSC. A 45 year-old male underwent LDLT using a left-lobe graft donated from his brother. Cholangiography showed no lesion in his common bile duct and duct-to-duct anastomosis was chosen for him. Fifteen months later, he suffered cholangitis due to PSC recurrence and endoscopic retrograde cholangiography was performed. The stents were inserted into his B2 and B3, and he remains well. Because of the ability to easily manage binary complication, duct-to-duct biliary reconstruction may become the first choice in LDLT for PSC without common bile duct lesions..
1013. Toru Ikegami, Tomonari Shimagaki, Junji Kawasaki, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Norifumi Harimoto, Shinji Itoh, Yuji Soejima, Yoshihiko Maehara, Eversion Technique to Prevent Biliary Stricture After Living Donor Liver Transplantation in the Universal Minimal Hilar Dissection Era., Transplantation, 10.1097/TP.0000000000001533, 101, 1, e20-e25-E25, 2017.01, BACKGROUND: Biliary anastomosis stricture (BAS) is still among the major concerns after living donor liver transplantation (LDLT), even after the technical refinements including the universal use of the blood flow-preserving hilar dissection technique. The aim of this study is to investigate what are still the factors for BAS after LDLT. METHODS: An analysis of 279 adult-to-adult LDLT grafts (left lobe, n = 161; right lobe, n = 118) with duct-to-duct biliary reconstruction, since the universal application of minimal hilar dissection technique and gradual introduction of eversion technique, was performed. RESULTS: There were 39 patients with BAS. Univariate analysis showed that a right lobe graft (P = 0.008), multiple bile ducts (P < 0.001), ductoplasty (P < 0.001), not using the eversion technique (P = 0.004) and fewer biliary stents than bile duct orifices (P = 0.002) were among the factors associated with BAS. The 1-year and 5-year BAS survival rates were 17.7% and 21.2% in the noneversion group (n = 134), and 6.2% and 7.9% in the eversion group (n = 145), respectively (P = 0.002). The perioperative factors including graft biliary anatomy were not different between everted (n = 134) and noneverted (n = 145) patients. CONCLUSIONS: The application of eversion technique under minimal hilar dissection technique could be a key for preventing BAS in duct-to-duct biliary reconstruction in LDLT..
1014. T. Shimauchi, K. Yamaura, M. Higashi, K. Abe, T. Yoshizumi, S. Hoka, Fibrinolysis in Living Donor Liver Transplantation Recipients Evaluated Using Thromboelastometry: Impact on Mortality, Transplantation Proceedings, 10.1016/j.transproceed.2017.09.025, 49, 9, 2117-2121, 2017.11, Background Inadequate hemostasis during living donor liver transplantation (LDLT) is mainly due to coagulopathy but may also include fibrinolysis. The purpose of this study was to determine the incidence of fibrinolysis and assess its relevance to mortality in LDLT. Methods The incidence and prognosis of fibrinolysis were retrospectively studied in 76 patients who underwent LDLT between April 2010 and February 2013. Fibrinolysis was evaluated and defined by maximum lysis (ML) >
15% within a 60-minute run time using thromboelastometry (ROTEM). Results Fibrinolysis was observed in 19 of the 76 (25%) patients before the anhepatic (pre-anhepatic) phase and was developed in 24 (32%) patients during and after the anhepatic (post-anhepatic) phase. In these 43 patients who had fibrinolysis, spontaneous recovery occurred in 29 patients (73%) within 3 hours after reperfusion of the liver graft. Recovery with tranexamic acid was noted in 2 patients with fibrinolysis in the post-anhepatic phase. Thrombosis in the portal vein and liver artery was noted in 14 patients, and the incidence was significantly greater in patients with post-anhepatic fibrinolysis than in those with pre-anhepatic fibrinolysis (P =.0017). Fibrinolysis that developed in the pre-anhepatic phase was associated with increased 30-day and 6-month mortalities (P =.0003 and.0026, respectively). Conclusions Fibrinolysis existed and developed in a large percentage of patients during LDLT. Thrombosis in the portal vein and hepatic artery was more common in patients with fibrinolysis in the post-anhepatic phase. Fibrinolysis that developed in the pre-anhepatic phase was associated with increased 30-day and 6-month mortalities..
1015. Shinji Itoh, Tomoharu Yoshizumi, Ken Shirabe, Koichi Kimura, Hirohisa Okabe, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Akihiro Nishie, Yoshihiko Maehara, Functional remnant liver assessment predicts liver-related morbidity after hepatic resection in patients with hepatocellular carcinoma., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12761, 47, 5, 398-404, 2017.04, AIM: We aimed to evaluate whether functional assessment of the future remnant liver is a predictor of postoperative morbidity after hepatic resection in patients with hepatocellular carcinoma (HCC). METHODS: One hundred forty-six patients who underwent hepatic resection for HCC were enrolled in this study. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI (EOB-MRI) analysis for functional liver assessment was carried out before hepatic resection. The signal intensity in the remnant liver was measured and divided by the signal intensity of the major psoas muscle (the liver to major psoas muscle ratio, LMR) for standardization. The remnant liver function was calculated using the formula (LMR on the hepatobiliary phase/LMR on the precontrast image). Computed tomography liver volumetry was also carried out. The remnant functional liver was calculated as the remnant liver volume or volumetric rate × remnant liver function by EOB-MRI. RESULTS: Morbidities developed in 19 (13.0%) patients. Morbidities associated with the liver occurred in 7 patients (4.7%). There was no mortality during surgery. Median remnant liver function scores using EOB-MRI and remnant functional liver using volumetric rate or volumetry were 1.82 (range, 1.25-2.96), 155.9 (range, 64.7-285.3), and 1027 (range, 369-2148), respectively. Logistic regression analysis identified the remnant functional liver volume as the only independent predictor for liver-related morbidity. CONCLUSION: Remnant functional liver volume using computed tomography liver volumetry and EOB-MRI was a significantly useful predictor for liver-related morbidity after hepatic resection in patients with HCC..
1016. Koichiro Yoshimaru, Toshiharu Matsuura, Yoshiaki Kinoshita, Makoto Hayashida, Yoshiaki Takahashi, Yusuke Yanagi, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara, Tomoaki Taguchi, Graft reduction using a powered stapler in pediatric living donor liver transplantation., Pediatric transplantation, 10.1111/petr.12985, 21, 6, 2017.09, Large-for-size syndrome is defined by inadequate tissue oxygenation, which results in vascular complications and graft compression after abdominal closure in living donor liver transplantation recipients. An accurate graft reduction that matches the optimal liver volume for the recipient is essential. We herein initially present the feasibility and safety of graft reduction using a powered stapler to obtain an optimal graft size. From October 1996 to October 2015, a total of eight graft reductions were performed using a powered stapler (group A; n=4) or by the conventional method using a cavitron ultrasonic surgical aspirator and portal triad suturing (group B; n=4). The background, intraoperative findings and the post-operative outcomes of these eight patients were retrospectively investigated. There were no statistically significant differences in the background of the patients in the two groups. Graft reduction was successfully achieved without any intraoperative complications in group A, whereas intraoperative complications, such as bleeding and bile leakage, occurred in two patients of group B. No post-operative surgical complications were detected on computed tomography; moreover, the serum aspartate aminotransferase level normalized significantly earlier in group A (P<.05). In summary, graft reduction using a powered stapler was feasible and safe in comparison with the conventional method..
1017. Toru Ikegami, Tomoharu Yoshizumi, Hideaki Uchiyama, Yuji Soejima, Noboru Harada, Yoshihiko Maehara, Hepatic artery reconstruction in living donor liver transplantation using surgical loupes: Achieving low rate of hepatic arterial thrombosis in 741 consecutive recipients-tips and tricks to overcome the poor hepatic arterial flow., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.24798, 23, 8, 1081-1082, 2017.08.
1018. Yuki Bekki, Tomoharu Yoshizumi, Shinji Shimoda, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Atsushi Kuno, Hisashi Narimatsu, Ken Shirabe, Yoshihiko Maehara, Hepatic stellate cells secreting WFA+ -M2BP: Its role in biological interactions with Kupffer cells., Journal of gastroenterology and hepatology, 10.1111/jgh.13708, 32, 7, 1387-1393, 2017.07, BACKGROUND AND AIM: Hepatic stellate cells (HSCs) play a central role in hepatic fibrosis and are regulated by Kupffer cells (KCs). Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) was recently identified as a serum marker for hepatic fibrosis. Although WFA+ -M2BP was identified as a ligand of Mac-2, the function of WFA+ -M2BP in hepatic fibrosis remains unclear. METHODS: Liver specimens were obtained from five patients with cirrhosis, five with chronic hepatitis, and five without hepatic fibrosis. WFA+ -M2BP kinetics were evaluated histologically and in subpopulations of liver cells such as HSCs, KCs, endothelial cells, biliary epithelial cells, and hepatocytes in in vitro culture. The function of WFA+ -M2BP in activated HSCs was evaluated using immunoblot analysis. RESULTS: Numbers of WFA+ -M2BP-positive cells in liver tissues increased with fibrosis stage. There were significant differences in WFA+ -M2BP levels between fibrosis stages F0 and F1-2 (P = 0.012) and between fibrosis stages F1-2 and F3-4 (P < 0.001). HSCs were the source of WFA+ -M2BP secretion in in vitro cultures of liver cells, as determined by sandwich immunoassay. Cells of the human HSC line LX-2 also secreted WFA+ -M2BP. Histologically, tissue sections showed that WFA+ -M2BP was located in Mac-2-expressing KCs. In vitro assays showed that exogenous WFA+ -M2BP stimulation enhanced Mac-2 expression in KCs and that HSCs co-cultured with KCs increased α-smooth muscle actin expression. Finally, Mac-2-depleted KCs with short interfering RNA had reduced α-smooth muscle actin expression following co-culturing with HSCs. CONCLUSIONS: WFA+ -M2BP from HSCs induces Mac-2 expression in KCs, which in turn activates HSCs to be fibrogenic..
1019. Toru Ikegami, Tomoharu Yoshizumi, Junji Kawasaki, Tomonari Shimagaki, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Hepatocellular carcinoma developed in a living donor after left lobe donation: a case for caution., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12786, 47, 7, 715-718, 2017.06, Although it has been recognized that those who are positive for anti-hepatitis B core antibody (anti-HBcAb) and negative for hepatitis B surface antigen (HBsAg) with normal liver function could be donors for living donor liver transplantation under appropriate prophylaxis, the negative impact of positive HBcAb on such donors themselves has not been reported. We present a case of a living donor with positive HBcAb, who donated his left lobe for his sister with unresectable giant hepatic hemangioma, and the donor himself developed a de novo hepatocellular carcinoma (HCC) 10 years after donation. He had been lost from the follow-up program since 1 year after donation. Imaging studies showed a heterogeneously enhanced mass compatible with HCC, which was 9 cm in size with portal invasion into the anterior portal vein of the remnant liver. Re-laparotomy for hepatectomy with the removal of the tumor thrombus in the anterior portal vein of the remnant liver was carried out, and he is free from recurrence 6 months after surgery on prophylactic sorafenib. At our institute, 58 (9.6%) donors among the 603 living donors were anti-HBcAb positive and anti-HBsAg negative, and we started regular HCC surveillance using sonogram every 6 months for these patients..
1020. Noboru Harada, Tomoharu Yoshizumi, Yo-Ichi Yamashita, Yuji Soejima, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Yoshihiko Maehara, Impact and Prediction of Lymph Node Involvement in Patients with Intrahepatic Cholangiocarcinoma After Curative Resection., Anticancer research, 10.21873/anticanres.11751, 37, 7, 3763-3769, 2017.07, BACKGROUND: The aim of this study was to identify the preoperative predictors of prognosis in patients with intrahepatic cholangiocarcinoma (ICC) undergoing resection. PATIENTS AND METHODS: We enrolled 90 patients with ICC who underwent surgical resection, including 59 in whom surgery was considered curative, and measured the overall survival (OS), recurrence-free survival (RFS), and other outcomes and potential prognostic factors. RESULTS: Multivariate Cox proportional hazards analysis showed that tumor in the resection margins (R>0) independently predicted long-term OS in the whole cohort. In the curatively-resected group (R0), lymph node involvement was the only independent predictor of long-term OS. Multiple tumors, perihilar tumor location and serum carcinoembryonic antigen (CEA) concentration >2.2 ng/ml were independent predictors of lymph node involvement before curative resection. CONCLUSION: Patients with ICC with multiple tumors, perihilar tumors and serum CEA concentration >2.2 ng/ml in association with lymph node involvement may need additional preoperative chemotherapy..
1021. Y. Soejima, T. Yoshizumi, T. Ikegami, N. Harimoto, N. Harada, S. Ito, T. Motomura, H. Uchiyama, Y. Maehara, In Situ Procurement of a Recipient's Portal Vein for a Right Lobe Liver Graft With Multiple Venous Orifices: A Case Report, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2016.10.028, 49, 1, 172-174, 2017.01, Reconstruction of multiple venous orifices of a right lobe graft is a time-consuming and troublesome procedure in right lobe living-donor liver transplantation. In the current study, we present a new venous reconstruction technique for a right lobe graft with multiple and complex hepatic vein (HV) orifices, in which procurement of the recipient's left portal vein was performed in situ to keep the anhepatic period to a minimum. All of the HV orifices were reconstructed together at the back table, while maintaining patency of the recipient's systemic and splanchnic circulation. A homologous vein graft and veno-venous bypass were not necessary. All HVs were patent during the follow-up and the patient was free from complications. In conclusion, the present technique is readily available for reconstruction of complex and multiple HV tributaries, while avoiding a long anhepatic time and the use of veno-venous bypass..
1022. A. Nagatsu, T. Yoshizumi, T. I. Kegami, N. Harimoto, N. Harada, Y. Soejima, A. Taketomi, Y. Maehara, In, Situ Posterior Graft Segmentectomy for Large-for-Size Syndrome in Deceased Donor Liver Transplantation in Adults: A Case Report, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2017.03.036, 49, 5, 1199-1201, 2017.06, Large-for-size syndrome (LFSS) is controversial in pediatric living donor liver transplantation patients and is associated with a poor graft outcome. Similar situations in deceased donor liver transplantation (DDLT) in adults have not been reported frequently, and there are no official guidelines worldwide. Deceased donation is extremely limited in Japan, and when a larger liver is allocated for a very sick small recipient in Japan, transplantation with a plan to address LFSS might be necessary. The patient is a 58-year-old female patient who had acute liver failure with coma. The graft-recipient weight ratio (GRWR) was 2.74%. Although the graft was enlarged by reperfusion, the intraoperative Doppler ultrasound, performed after reperfusion, showed sufficient graft in-flow and outflow. However, when the liver graft was situated appropriately into the right phrenic space supported by the rib cage and diaphragm, the blood flow in the hepatic vein and portal vein was significantly reduced. Graft blood flow did not improve without removing it from the right subphrenic space. Therefore, we decided to perform an in situ graft posterior segmentectomy, so that the graft right lobe was properly accommodated in the patient's right subphrenic space. After the segmentectomy of the graft, an intraoperative Doppler sonogram showed significantly improved blood flow. LFSS could be a significant operative challenge in adult DDLT, especially in areas with limited chances of DDLT. In situ posterior segmentectomy in the demarcated area could be a solution for treating patients with LFSS..
1023. Yoshihiro Yoshida, Tomoharu Yoshizumi, Huanlin Wang, Kazuhito Sakata, Masahiro Shimokawa, Takeshi Kurihara, Takashi Motomura, Shinji Itoh, Noboru Harada, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Liver transplantation for cryptogenic liver failure caused by diffuse hepatic angiosarcoma: case report., Surgical case reports, 10.1186/s40792-017-0296-0, 3, 1, 21-21, 2017.12, BACKGROUND: Primary hepatic angiosarcoma is a non-epithelial malignancy derived from sinusoidal endothelial cells, accounting for approximately 1.8% of primary hepatic malignancies. Diagnosis of primary hepatic angiosarcoma is complicated by difficulties in the qualitative radiological assessment of these tumors. Prognosis is very poor due to local recurrence and distant metastasis after liver resection or liver transplantation (LT). CASE PRESENTATION: This case report describes two patients with primary hepatic angiosarcoma who were diagnosed by histopathological examination of the explanted liver after LT. One patient had undergone living donor LT, and the other had undergone deceased donor LT. Neither showed evidence of malignancy on the pre-operative imaging tests. CONCLUSIONS: Hepatic angiosarcoma has a very high relapse rate after LT. Pre-transplant liver biopsy may be necessary to distinguish diffuse hepatic angiosarcoma from tumors of other origin in patients with cryptogenic liver failure..
1024. Hideaki Uchiyama, Shinji Itoh, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Yuji Soejima, Noboru Harada, Kazutoyo Morita, Takeo Toshima, Takashi Motomura, Yoshihiko Maehara, Living donor liver transplantation for hepatocellular carcinoma: results of prospective patient selection by Kyushu University Criteria in 7 years., HPB : the official journal of the International Hepato Pancreato Biliary Association, 10.1016/j.hpb.2017.08.004, 19, 12, 1082-1090, 2017.12, BACKGROUND: Expanding patient selection beyond the Milan criteria in living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) has long been a matter for debate. We have used the Kyushu University Criteria - maximum tumor diameter <5 cm or des-γ-carboxy prothrombin <300 mAU/ml - in LDLT for HCC since June 2007. The aim of the present study was to present the results of our prospective patient selection by Kyushu University Criteria and to confirm whether or not our criteria were justified. METHODS: The entire study period was divided into the pre-Kyushu era (July 1999-May 2007) and the Kyushu era (June 2007-November 2014). Eighty-nine and 90 patients underwent LDLT for HCC in the pre-Kyushu era and the Kyushu era, respectively. RESULTS: In the pre-Kyushu era, there were significant differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients. In the Kyushu era, however, the differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients disappeared. The 5-year overall patient survival in the Kyushu era was 89.4%. CONCLUSION: Our selection criteria enabled a considerable number of beyond-Milan patients to undergo LDLT without jeopardizing the recurrence-free, and disease-specific, and overall patient survival..
1025. Kousei Ishigami, Akihiro Nishie, Naoki Mochidome, Yoshiki Asayama, Yasuhiro Ushijima, Daisuke Kakihara, Daisuke Okamoto, Nobuhiro Fujita, Takao Ohtsuka, Yoshihiro Miyasaka, Tomoyuki Hida, Tomoharu Yoshizumi, Hiroshi Honda, Mucinous nonneoplastic cyst of the pancreas: CT and MRI appearances., Abdominal radiology (New York), 10.1007/s00261-017-1204-6, 42, 12, 2827-2834, 2017.12, PURPOSE: The purpose of this retrospective study was to evaluate imaging features of mucinous nonneoplastic cyst (MNNC) of the pancreas. MATERIALS AND METHODS: Three (0.9%) patients with MNNC of the pancreas were found in 335 surgically resected pancreatic cystic lesions. Three MDCT and two MRI/MRCP studies were retrospectively reviewed. RESULTS: Three cases of MNNC were found in the pancreatic neck, body, and tail, respectively. All the three cases were multilocular without communication with the main pancreatic duct (MPD), although upstream MPD dilatation was seen in two of the three cases. The signal intensity of the cyst fluid was low on T1-weighted, high on T2-weighted, and low on diffusion-weighted images. Cyst wall was thin in two cases, and the remaining case with obstructive pancreatitis showed visible cyst wall enhancement. CONCLUSION: Imaging findings of MNNC of the pancreas were nonspecific without communication with the MPD. Cyst wall is typically thin without visible enhancement..
1026. Hideaki Uchiyama, Norifumi Harimoto, Shinji Itoh, Tomoharu Yoshizumi, Toru Ikegami, Yoshihiko Maehara, Pleural Effusion After Hepatectomy for Hepatocellular Carcinoma: Risk Factor Analyses and Its Impact on Oncological Outcomes., World journal of surgery, 10.1007/s00268-016-3826-1, 41, 4, 1089-1099, 2017.04, BACKGROUND: Although posthepatectomy pleural effusion (PHPE) is a commonly observed phenomenon, its precise etiology and the impact of its emergence on oncological outcomes have still unknown. The aim of the current study was to retrospectively investigate risk factors for PHPE and its impact on oncological outcomes of hepatocellular carcinoma (HCC). METHODS: Medical records of 330 patients who underwent primary curative hepatectomy for HCC were reviewed. All 330 patients had CT around day 7 after hepatectomy, and the emergence of PHPE on CT was examined. Presumed 38 risk factors for the emergence of PHPE and already-known 9 risk factors together with PHPE for HCC recurrence and patient death after hepatectomy were analyzed. RESULTS: The overall incidence of PHPE was 54.5% (180/330). One hundred seventy-nine and 38 out of the 180 patients had right-sided PHPE and left-sided PHPE, respectively. The independent risk factors for right-sided PHPE were hepatitis B or C back ground, lower preoperative white blood cell count, larger intraoperative blood loss, longer operation time, subcostal incision, and longer total inflow occlusion time, while the only independent risk factor for left-sided PHPE was longer operation time. Left-sided PHPE was testified to be one of the independent risk factors not only for HCC recurrence but also for patient death. CONCLUSIONS: Although the cause of PHPE after hepatectomy might be multifactorial, the emergence of left-sided PHPE is a portent of worse oncological outcomes after curative hepatectomy for HCC and patients with left-sided PHPE need close follow-ups..
1027. Shinji Itoh, Hideaki Uchiyama, Yasuharu Ikeda, Kazutoyo Morita, Noboru Harada, Keishi Sugimachi, Hirofumi Kawanaka, Daisuke Korenaga, Tomoharu Yoshizumi, Kenji Takenaka, Yoshihiko Maehara, Post-hepatectomy Refractory Ascites in Cirrhotic Patients with Hepatocellular Carcinoma: Risk Factor Analysis to Overcome this Problematic Complication., Anticancer research, 37, 3, 1381-1385, 2017.03, BACKGROUND: Refractory ascites is a serious post-hepatectomy complication in cirrhotic patients with hepatocellular carcinoma (HCC). In order to avoid this complication, surgeons should preserve as much liver parenchyma as possible in performing hepatectomy in such patients. However, we still occasionally encounter refractory ascites even after limited or small hepatectomy. The aim of this study was to identify risk factors for post-hepatectomy refractory ascites in cirrhotic patients, focusing on limited or small hepatectomy. PATIENTS AND METHODS: The data of 73 cirrhotic patients with HCC who underwent limited or small hepatectomy were analyzed. Limited or small hepatectomy was defined as hepatectomy equal to or of less than subsegmentectomy. We compared the clinicopathological factors between patients with and without postoperative refractory ascites. RESULTS: Fourteen cirrhotic patients suffered postoperative refractory ascites. Total cholesterol, duration of operation, duration of Pringle maneuver, resection of segment VII, intraoperative blood loss, and intraoperative blood transfusion were found to be significant risk factors for postoperative refractory ascites in univariate analyses. Multivariate analysis revealed that resection of segment VII was an independent risk factor. CONCLUSION: Resection of segment VII necessitates extensive dissection of the right triangular or coronary ligaments, which could explain that it was an independent risk factor for post-hepatectomy refractory ascites. Surgeons should avoid extensive dissection of these ligaments in order to avoid this detrimental complication..
1028. Masayo Tsukamoto, Yo-Ichi Yamashita, Katsunori Imai, Naoki Umezaki, Takanobu Yamao, Hirohisa Okabe, Shigeki Nakagawa, Daisuke Hashimoto, Akira Chikamoto, Takatoshi Ishiko, Tomoharu Yoshizumi, Yoshihiko Maehara, Hideo Baba, Predictors of Cure of Intrahepatic Cholangiocarcinoma After Hepatic Resection., Anticancer research, 10.21873/anticanres.12164, 37, 12, 6971-6975, 2017.12, BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma, and has a poor prognosis. Surgical resection is the only option for a cure of ICC. Here we attempted to define the cure rate after hepatic resection for ICC and to identify the predictors for a cure. PATIENTS AND METHODS: Among the 96 patients who underwent R0 resections for primary ICC between 1990 and 2011 at the Kumamoto University Hospital and Kyushu University Hospital, those who were followed for ≥5 years after surgery were enrolled. "Cure" was defined as recurrence-free survival (RFS) of ≥5 years after surgery. RESULTS: A total of 81 patients were eligible. A cure was achieved in 37 patients (45.7%). The 5-year overall survival and RFS rates were 55.0% and 41.7%, respectively. A multivariate logistic regression analysis identified the absence of lymph node metastasis (relative risk (RR) 7.5, p=0.011) and the absence of microvascular invasion (RR 5.5, p=0.0137) as the independent predictors of achieving a cure. CONCLUSION: R0 resections achieved a cure in 45.7% of this series of ICC patients. The predictors of a cure identified here, i.e., absence of lymph node metastasis and absence of microvascular invasion, could contribute to the selection of patients who are not candidates for adjuvant chemotherapy..
1029. Noboru Harada, Tomoharu Yoshizumi, Takashi Maeda, Hiroto Kayashima, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Yoshihiko Maehara, Preoperative Pancreatic Stiffness by Real-time Tissue Elastography to Predict Pancreatic Fistula After Pancreaticoduodenectomy., Anticancer research, 10.21873/anticanres.11529, 37, 4, 1909-1915, 2017.04, AIM: To assess the correlations among pancreatic fibrosis, pancreatic stiffness, and postoperative pancreatic fistula (PF). PATIENTS AND METHODS: The study population consisted of 17 consecutively enrolled patients who underwent subtotal stomach-preserving pancreaticoduodenectomy (SSPPD). The liver fibrosis (LF) index as pancreatic stiffness was measured by real-time tissue elastography (RTE) before SSPPD. We also obtained the pathological fibrosis assessment of the pancreatic stump after SSPPD. RESULTS: The LF index was significantly correlated with pathological pancreatic stump fibrosis. The LF index of patients without PF was significantly higher than that of patients with PF. The optimal cut-off value of the LF index to predict postoperative PF was defined as an LF index ≤1.91. Multivariate analysis revealed that a preoperative LF index ≤1.91 was an independent predictive factor of postoperative PF. CONCLUSION: Evaluation of pancreatic stiffness using RTE might be an objective index to estimate pancreatic fibrosis and predict postoperative PF..
1030. Norifumi Harimoto, Tomoharu Yoshizumi, Kazuhito Sakata, Akihisa Nagatsu, Takashi Motomura, Shinji Itoh, Noboru Harada, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma., World journal of surgery, 10.1007/s00268-017-4097-1, 41, 11, 2805-2812, 2017.11, BACKGROUND: The Controlling Nutritional Status (CONUT) score is an objective tool widely used to assess nutritional status in patients with inflammatory disease, chronic heart failure, and chronic liver disease. The relationship between CONUT score and prognosis in patients who have undergone hepatic resection, however, has not been evaluated. METHODS: Data were retrospectively collected for 357 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent between January 2004 and December 2015. The patients were assigned to two groups, those with preoperative CONUT scores ≤3 (low CONUT score) and >3 (high CONUT score), and their clinicopathological characteristics, surgical outcomes, and long-term survival were compared. RESULTS: Of the 357 patients, 69 (19.3%) had high (>3) and 288 (80.7%) had low (≤3) preoperative CONUT scores. High CONUT score was significantly associated with HCV infection, low serum albumin and cholesterol concentrations, low lymphocyte count, shorter prothrombin time, Child-Pugh B and liver damage B scores, and blood transfusion. Multivariate analysis identified six factors prognostic of poor overall survival (older age, liver damage B score, high CONUT score, poor tumor differentiation, the presence of intrahepatic metastases, and blood transfusion) and five factors prognostic of reduced recurrence-free survival (older age, higher ICGR15, larger tumor size, presence of intrahepatic metastasis, and blood transfusion). CONCLUSIONS: In patients with HCC, preoperative CONUT scores are predictive of poorer overall survival, even after adjustments for other known predictors..
1031. Norifumi Harimoto, Tomoharu Yoshizumi, Kazuhito Sakata, Akihisa Nagatsu, Takashi Motomura, Shinji Itoh, Noboru Harada, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Prognostic significance of combined albumin-bilirubin and tumor-node-metastasis staging system in patients who underwent hepatic resection for hepatocellular carcinoma., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12868, 47, 12, 1289-1298, 2017.11, BACKGROUND: In recent years, the establishment of new staging systems for hepatocellular carcinoma (HCC) has been reported worldwide. The system combining albumin-bilirubin (ALBI) with tumor-node-metastasis stage, developed by the Liver Cancer Study Group of Japan, was called the ALBI-T score. METHODS: Patient data were retrospectively collected for 357 consecutive patients who had undergone hepatic resection for HCC with curative intent between January 2004 and December 2015. The overall survival and recurrence-free survival were compared by the Kaplan-Meier method, using different staging systems: the Japan integrated staging (JIS), modified JIS, and ALBI-T. RESULTS: Multivariate analysis identified five poor prognostic factors (higher age, poor differentiation, the presence of microvascular invasion, the presence of intrahepatic metastasis, and blood transfusion) that influenced overall survival, and four poor prognostic factors (the presence of intrahepatic metastasis, serum α-fetoprotein level, blood transfusion, and each staging system (JIS, modified JIS, and ALBI-T score)) that influenced recurrence-free survival. Patients for each these three staging system had a significantly worse prognosis regarding recurrence-free survival, but not with overall survival. The modified JIS score showed the lowest Akaike information criteria statistic value, indicating it had the best ability to predict overall survival compared with the other staging systems. CONCLUSIONS: This retrospective analysis showed that, in post-hepatectomy patients with HCC, the ALBI-T score is predictive of worse recurrence-free survival, even when adjustments are made for other known predictors. However, modified JIS is better than ALBI-T in predicting overall survival..
1032. Yoshiki Asayama, Akihiro Nishie, Kousei Ishigami, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Nobuhiro Fujita, Takao Ohtsuka, Tomoharu Yoshizumi, Shinichi Aishima, Yoshinao Oda, Hiroshi Honda, Prognostic significance of contrast-enhanced CT attenuation value in extrahepatic cholangiocarcinoma., European radiology, 10.1007/s00330-016-4621-y, 27, 6, 2563-2569, 2017.06, OBJECTIVES: To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). METHODS: This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT - attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT - attenuation value at unenhanced CT)] × 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. RESULTS: The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). CONCLUSIONS: The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. KEY POINTS: • Dynamic contrast study can evaluate the aggressiveness of extrahepatic cholangiocarcinoma. • A lower washout ratio was an independent prognostic factor for overall survival. • CT can predict survival and inform decisions on surgical options or chemotherapy..
1033. Takasuke Fukuhara, Satomi Yamamoto, Chikako Ono, Shota Nakamura, Daisuke Motooka, Hiroyuki Mori, Takeshi Kurihara, Asuka Sato, Tomokazu Tamura, Takashi Motomura, Toru Okamoto, Michio Imamura, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Kazuaki Chayama, Yoshiharu Matsuura, Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity., Scientific reports, 10.1038/srep45228, 7, 45228-45228, 2017.03, It is well documented that a variety of viral quasispecies are found in the patients with chronic infection of hepatitis C virus (HCV). However, the significance of quasispecies in the specific infectivity to individual cell types remains unknown. In the present study, we analyzed the role of quasispecies of the genotype 2a clone, JFH1 (HCVcc), in specific infectivity to the hepatic cell lines, Huh7.5.1 and Hep3B. HCV RNA was electroporated into Huh7.5.1 cells and Hep3B/miR-122 cells expressing miR-122 at a high level. Then, we adapted the viruses to Huh7 and Hep3B/miR-122 cells by serial passages and termed the resulting viruses HCVcc/Huh7 and HCVcc/Hep3B, respectively. Interestingly, a higher viral load was obtained in the homologous combination of HCVcc/Huh7 in Huh7.5.1 cells or HCVcc/Hep3B in Hep3B/miR-122 cells compared with the heterologous combination. By using a reverse genetics system and deep sequence analysis, we identified several adaptive mutations involved in the high affinity for each cell line, suggesting that quasispecies of HCV participate in cell-specific infectivity..
1034. Hirohisa Okabe, Daisuke Hashimoto, Akira Chikamoto, Morikatsu Yoshida, Katsunobu Taki, Kota Arima, Katsunori Imai, Yoshitaka Tamura, Osamu Ikeda, Takatoshi Ishiko, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Yo-Ichi Yamashita, Tomoharu Yoshizumi, Toru Beppu, Yasuyuki Yamashita, Hideo Baba, Yoshihiko Maehara, Shape and Enhancement Characteristics of Pancreatic Neuroendocrine Tumor on Preoperative Contrast-enhanced Computed Tomography May be Prognostic Indicators., Annals of surgical oncology, 10.1245/s10434-016-5630-4, 24, 5, 1399-1405, 2017.05, BACKGROUND: Prognostic indicators of the malignant potential of pancreatic neuroendocrine tumors (PNET) are limited. We assessed tumor shape and enhancement pattern on contrast-enhanced computed tomography as predictors of malignant potential. METHODS: Sixty cases of PNET patients undergoing curative surgery from 2001 to 2014 were enrolled onto our retrospective study. Preoperative enhanced CTs were assessed, and criteria defined for regularly shaped and enhancing tumors (group 1), and irregularly shaped and/or enhancing tumors (group 2). The relation of tumor shape and enhancement pattern to outcome was assessed. RESULTS: Interobserver agreement was substantial (kappa = 0.74). Group 2 (n = 24) was significantly correlated with synchronous liver metastasis (23 vs. 0 %), lymph node metastasis (36 vs. 3 %), pathologic capsular invasion (68 vs. 8 %), larger tumor size (30 vs. 12 mm), tumor, node, metastasis classification system (TNM) stage III/IV disease (46 vs. 3 %), and histologic grade 2/3 (41 vs. 0 %). Multivariate analysis revealed that tumor grade 2/3 and group 2 criteria correlated with tumor relapse (hazard ratio 6.5 and 13.6, P = 0.0071 and 0.039, respectively), and that only group 2 criteria were independently correlated with poor overall survival (hazard ratio 5.56e + 9, P = 0.0041). CONCLUSIONS: Irregular tumor shape/enhancement on preoperative computed tomography is a negative prognostic factor after curative surgery for PNET..
1035. T. Motomura, T. Yoshizumi, M. Ohira, Y. Mano, T. Toshima, S. Ltoh, N. Harada, N. Harimoto, T. Ikegami, Y. Soejima, Y. Maehara, Successful Recombinant Thrombomodulin Treatment for Thrombotic Microangiopathy After Liver Transplantation: A Case Report, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2017.09.014, 49, 10, 2409-2410, 2017.12, Transplant-associated thrombotic micro angiopathy (TA-TMA) is a rare but severe complication after liver transplantation. In contrast to other thrombotic microangiopathies, treatment for TA-TMA has yet to be clarified. A 52-year-old male patient with liver cirrhosis due to hepatitis C underwent split liver transplantation from a deceased donor. His clinical course was without complication until 4 days after transplantation, when he experienced impaired consciousness, hemolytic anemia with fragmented erythrocytes, and marked thrombocytopenia. TA-TMA was diagnosed, and recombinant thrombomodulin was administered for 4 days. The patient's clinical symptoms and laboratory data rapidly improved. He has been followed up for 6 months and has not shown any complications. The pathogenesis of TA-TMA is endothelial damage in the vasculature. Recombinant thrombomodulin, an endothelial cell-protecting agent, is a promising new therapeutic choice for TA-TMA after liver transplantation..
1036. Toru Ikegami, Tomoharu Yoshizumi, Jyunji Kawasaki, Akihisa Nagatsu, Hideaki Uchiyama, Noboru Harada, Norifumi Harimoto, Shinji Itoh, Takashi Motomura, Yuji Soejima, Yoshihiko Maehara, Surgical Resection for Lymph Node Metastasis After Liver Transplantation for Hepatocellular Carcinoma., Anticancer research, 10.21873/anticanres.11395, 37, 2, 891-895, 2017.02, BACKGROUND: Treatment strategies for lymph node (LN) metastasis after liver transplantation (LT) for hepatocellular carcinoma (HCC) have not been studied. PATIENTS AND METHODS: The treatment modes and outcomes in patients with LN metastasis after LT (n=6) for HCC were reviewed. RESULTS: The mean time from LT to LN recurrence was 2.0±1.3 years, and the locations of the LNs recurrences included the phrenic (n=2), common hepatic artery (n=2), inferior vena cava (n=1) and gastric (n=1) regions. Treatments included surgery alone (n=3), surgery followed by chemoradiation (n=1), radiation followed by chemotherapy (n=1), and chemotherapy, radiation and sorafenib (n=1). Although the patients receiving non-surgical treatments (n=3) died within 1.2 years, those who underwent surgical removal of the metastatic LNs survived 11.2 years, 4.5 years and 0.8 years, respectively, without any signs of re-recurrence. CONCLUSION: Surgical resection is the only feasible and potentially curative treatment for LN metastasis after LT for HCC..
1037. Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Shinji Ito, Noboru Harada, Takashi Motomura, Akihisa Nagatsu, Tetsuo Ikeda, Yoshihiko Maehara, Surgical Resection of Giant Pheochromocytomas Arising Behind the Retrohepatic Inferior Vena Cava., Anticancer research, 10.21873/anticanres.11318, 37, 1, 277-280, 2017.01, BACKGROUND: Surgical resection of retrocaval giant pheochromocytomas (PCs) and of extra-adrenal paragangliomas (EAPs) is a technically challenging procedure but data on these procedures are scarce. The purpose of this study was to present and evaluate our surgical results for such tumors. PATIENTS AND METHODS: We retrospectively analyzed four consecutive patients who had surgery for giant retro-caval PCs and EAPs in terms of surgical technique, resectability of the tumor, requirement for bypass, and postoperative complications. A laparoscopic approach was not feasible in all cases because of the undesirable location of the tumors. RESULTS: In all cases, the liver was completely mobilized from the right side to expose and control the supra- and infra-hepatic inferior vena cava. Resection of the tumors was feasible for all patients with a minimum titration of blood pressure during surgery. None of the cases required venous bypass. In the patient who had the largest tumor, the infra-hepatic inferior vena cava was transected temporally to obtain direct and maximum exposure of the tumor. None of the patients have had any postoperative complications and all are currently alive without recurrence and use of antihypertensive drugs. CONCLUSION: Resection of retrocaval giant PCs and EAPs is a safe procedure. Temporal transection of the infra-hepatic inferior vena cava can offer excellent exposure, especially for an extremely large tumor, without compromising hepatic and systemic hemodynamics..
1038. Fumihiro Shoji, Gouji Toyokawa, Noboru Harada, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tatsuro Okamoto, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Maehara, Surgical Treatment and Outcome of Patients with De Novo Lung Cancer After Liver Transplantation., Anticancer research, 10.21873/anticanres.11608, 37, 5, 2619-2623, 2017.05, BACKGROUND: De novo malignancy, including primary lung cancer, is one of the limitations to long-term survival after liver transplantation. The purpose of this study was to describe patients who developed de novo lung cancer after living-donor liver transplantation (LDLT) and investigate their clinicopathological features as well as the feasibility of surgical resection. PATIENTS AND METHODS: We investigated 554 patients who underwent LDLT. RESULTS: De novo lung cancer after LDLT was observed in five (0.9%) out of 554 studied patients: four men and one woman, aged 61-78 years (mean=67 years). All four men had a smoking history. Clinical stages of de novo lung cancer were stage IA in three patients, and stage IB and IV in one patient each. Three out of five patients underwent pulmonary lobectomy and pathological stage was IA in two patients and IIA in one. All patients who underwent surgery stopped immunosuppressive therapy 1 day preoperatively and restarted on postoperative day 1. There were no serious postoperative complications. All three patients are still alive without any recurrence, with survival ranging from 8 to 29 months, with an average of 16.3 months after diagnosis of lung cancer. CONCLUSION: Although the study population was small, these results suggest that pulmonary lobectomy of de novo lung cancer after LDLT, even under immunosuppressive conditions, is a feasible procedure and may yield a survival benefit..
1039. Daisuke Imai, Tomoharu Yoshizumi, Shinji Okano, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Yuji Soejima, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara, The prognostic impact of programmed cell death ligand 1 and human leukocyte antigen class I in pancreatic cancer., Cancer medicine, 10.1002/cam4.1087, 6, 7, 1614-1626, 2017.07, Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive tumor-microenvironment (TME) that supports the growth of tumors and mediates tumors enabling evasion of the immune system. Expression of programmed cell death ligand 1 (PD-L1) and loss of human leukocyte antigen (HLA) class I on tumor cells are methods by which tumors escape immunosurveillance. We examined immune cell infiltration, the expression of PD-L1 and HLA class I by PDA cells, and the correlation between these immunological factors and clinical prognosis. PDA samples from 36 patients were analyzed for HLA class I, HLA-DR, PD-L1, PD-1, CD4, CD8, CD56, CD68, and FoxP3 expression by immunohistochemistry. The correlations between the expression of HLA class I, HLA-DR, PD-L1 or PD-1 and the pattern of tumor infiltrating immune cells or the patients' prognosis were assessed. PD-L1 expression correlated with tumor infiltration by CD68+ and FoxP3+ cells. Low HLA class I expression was an only risk factor for poor survival. PD-L1 negative and HLA class I high-expressing PDA was significantly associated with higher numbers of infiltrating CD8+ T cells in the TME, and a better prognosis. Evaluation of both PD-L1 and HLA class I expression by PDA may be a good predictor of prognosis for patients. HLA class I expression by tumor cells should be evaluated when selecting PDA patients who may be eligible for treatment with PD-1/PD-L1 immune checkpoint blockade therapies..
1040. Ueda Y, Ikegami T, Akamatsu N, Soyama A, Shinoda M, Goto R, Okajima H, Yoshizumi T, Taketomi A, Kitagawa Y, Eguchi S, Kokudo N, Uemoto S, Maehara Y, Treatment with sofosbuvir and ledipasvir without ribavirin for 12 weeks is highly effective for recurrent hepatitis C virus genotype 1b infection after living donor liver transplantation: a Japanese multicenter experience., Journal of gastroenterology, 10.1007/s00535-017-1310-9, 52, 8, 986-991, 2017.08, Ueda Y, Ikegami T, Akamatsu N, Soyama A, Shinoda M, Goto R, Okajima H, Yoshizumi T, Taketomi A, Kitagawa Y, Eguchi S, Kokudo N, Uemoto S, Maehara Y, Journal of gastroenterology, 2017, 2017.
1041. Masahiro Satake, Keiji Matsubayashi, Yuji Hoshi, Rikizo Taira, Yasumi Furui, Norihiro Kokudo, Nobuhisa Akamatsu, Tomoharu Yoshizumi, Nobuhiro Ohkohchi, Hiroaki Okamoto, Masato Miyoshi, Akinori Tamura, Kyoko Fuse, Kenji Tadokoro, Unique clinical courses of transfusion-transmitted hepatitis E in patients with immunosuppression., Transfusion, 10.1111/trf.13994, 57, 2, 280-288, 2017.02, BACKGROUND: The high prevalence of specific immunoglobulin G for hepatitis E virus (HEV) in Japanese people raises the possibility of a high incidence of HEV-viremic blood donors and therefore frequent transfusion-transmitted HEV (TT-HEV). STUDY DESIGN AND METHODS: TT-HEV cases established in Japan through hemovigilance and those published in the literature were collected. Infectivity of HEV-contaminated blood components and disease severity in relation to immunosuppression were investigated. RESULTS: Twenty established TT-HEV cases were recorded over the past 17 years. A lookback study verified that five of 10 patients transfused with known HEV-contaminated blood components acquired HEV infection. The minimal infectious dose of HEV through transfusion was 3.6 × 104 IU. Nine of the 19 TT-HEV cases analyzed had hematologic diseases. Only two cases showed the maximal alanine aminotransferase level of more than 1000 U/L. Two patients with hematologic malignancy and two liver transplant recipients had chronic liver injury of moderate severity. CONCLUSION: The infectivity of HEV-contaminated components was 50%. Immunosuppression likely causes the moderate illness of TT-HEV, but it may lead to the establishment of chronic sequelae. Transfusion recipients, a population that is variably immunosuppressed, are more vulnerable to chronic liver injury as a result of TT-HEV than the general population is as a result of food-borne infection..
1042. Hideaki Uchiyama, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Hirohisa Okabe, Yuji Soejima, Yoshihiko Maehara, Use of internal jugular vein grafts in reconstructing multiple venous orifices of right hepatic grafts without the middle hepatic vein trunk., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.24644, 23, 1, 110-116, 2017.01.
1043. Masakazu Sugiyama, Tomoharu Yoshizumi, Yoshihiro Yoshida, Yuki Bekki, Yoshihiro Matsumoto, Shohei Yoshiya, Takeo Toshima, Toru Ikegami, Shinji Itoh, Norifumi Harimoto, Shinji Okano, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, p62 Promotes Amino Acid Sensitivity of mTOR Pathway and Hepatic Differentiation in Adult Liver Stem/Progenitor Cells., Journal of cellular physiology, 10.1002/jcp.25653, 232, 8, 2112-2124, 2017.08, Autophagy is a homeostatic process regulating turnover of impaired proteins and organelles, and p62 (sequestosome-1, SQSTM1) functions as the autophagic receptor in this process. p62 also functions as a hub for intracellular signaling such as that in the mammalian target of rapamycin (mTOR) pathway. Liver stem/progenitor cells have the potential to differentiate to form hepatocytes or cholangiocytes. In this study, we examined effects of autophagy, p62, and associated signaling on hepatic differentiation. Adult stem/progenitor cells were isolated from the liver of mice with chemically induced liver injury. Effects of autophagy, p62, and related signaling pathways on hepatic differentiation were investigated by silencing the genes for autophagy protein 5 (ATG5) and/or SQSTM1/p62 using small interfering RNAs. Hepatic differentiation was assessed based on increased albumin and hepatocyte nuclear factor 4α, as hepatocyte markers, and decreased cytokeratin 19 and SOX9, as stem/progenitor cell markers. These markers were measured using quantitative RT-PCR, immunofluorescence, and Western blotting. ATG5 silencing decreased active LC3 and increased p62, indicating inhibition of autophagy. Inhibition of autophagy promoted hepatic differentiation in the stem/progenitor cells. Conversely, SQSTM1/p62 silencing impaired hepatic differentiation. A suggested mechanism for p62-dependent hepatic differentiation in our study was activation of the mTOR pathway by amino acids. Amino acid activation of mTOR signaling was enhanced by ATG5 silencing and suppressed by SQSTM1/p62 silencing. Our findings indicated that promoting amino acid sensitivity of the mTOR pathway is dependent on p62 accumulated by inhibition of autophagy and that this process plays an important role in the hepatic differentiation of stem/progenitor cells. J. Cell. Physiol. 232: 2112-2124, 2017. © 2016 Wiley Periodicals, Inc..
1044. 伊藤 心二, 吉住 朋晴, 池田 哲夫, 川崎 淳司, 島垣 智成, 坂田 一仁, 下川 雅弘, 吉田 佳弘, 長津 明久, 間野 洋平, 本村 貴志, 原田 昇, 播本 憲史, 池上 徹, 副島 雄二, 前原 喜彦, 安全性に配慮した肝胆膵領域における腹腔鏡下手術 腹腔鏡下肝切除における我々独自の技術革新とその成績に関する検討, 日本外科学会定期学術集会抄録集, 117回, WS-7, 2017.04.
1045. 副島 雄二, 吉住 朋晴, 池上 徹, 播本 憲史, 原田 昇, 伊藤 心二, 本村 貴志, 長津 明久, 吉田 佳宏, 坂田 一仁, 下川 雅弘, 島垣 智成, 川崎 淳司, 池田 哲夫, 前原 喜彦, 日本と諸外国における生体肝移植の現状 成人生体肝移植における成績向上への取り組みとその成果, 日本外科学会定期学術集会抄録集, 117回, SY-5, 2017.04.
1046. 池上 徹, 吉住 朋晴, 二宮 瑞樹, 播本 憲史, 原田 昇, 伊藤 心二, 長津 明久, 本村 貴志, 副島 雄二, 前原 喜彦, 生体肝移植における肝再生についてのEOB-MRIを用いた機能的容積による評価(Liver regeneration in living donor liver transplantation evaluated by functional volumetry using EOB-MRI), 日本外科学会定期学術集会抄録集, 117回, PS-2, 2017.04.
1047. Kazuki Takeishi, Takashi Maeda, Yo-Ichi Yamashita, Eiji Tsujita, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, A Cohort Study for Derivation and Validation of Early Detection of Pancreatic Fistula After Pancreaticoduodenectomy., Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 10.1007/s11605-015-3030-x, 20, 2, 385-91, 2016.02, BACKGROUND: Pancreatic fistula (PF) remains the most important morbidity after pancreaticoduodenectomy (PD). Early drain removal was recently recommended. However, this is not applicable to all cases because the development of severe PF may not be obvious until a later postoperative day (POD). This study aimed to discover ways to detect clinically relevant PF early during the postoperative stage after PD. METHODS: We studied 120 patients who underwent PD. Grades B/C PF classified according to the International Study Group of Pancreatic Surgery guidelines were defined as clinically relevant PF. Logistic regression was used to identify detection factors for clinically relevant PF. Receiver operating characteristic curves were used to identify the optimal cutoff value for clinically relevant PF, and the k-fold cross-validation model to validate the cutoff value. RESULTS: Drain amylase on POD 1 and C-reactive protein (CPR) on POD 2 were independent factors for clinically relevant PF. Drain amylase >1300 IU/l on POD 1 and CRP >12.8 g/dl on POD 2 were the best cutoff values for clinically relevant PF detection and were confirmed by k-fold cross-validation. The sensitivity and specificity values were 79 and 81 %, respectively. CONCLUSIONS: Values of drain amylase and CRP combined were useful to distinguish clinically relevant PF..
1048. Kosuke Hirose, Hirohisa Okabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Koichi Kimura, Hideo Baba, Yoshihiko Maehara, A case report of bacteremia manifesting as an overwhelming postsplenectomy infection due to Streptococcus pneumoniae post vaccination., Surgical case reports, 10.1186/s40792-016-0173-2, 2, 1, 48-48, 2016.12, A 62-year-old woman was admitted for acute epigastralgia and high-grade fever of over 39 °C. The patient had undergone splenectomy for idiopathic portal hypertension 1 year ago and vaccination against Streptococcus pneumoniae immediately post operation. She developed localized peritoneal irritation and abdominal distension. Her serum creatinine had increased to 1.5 mg/dL and procalcitonin was 12.5 ng/ml. Computed tomography of the abdomen revealed edematous large intestine and increased ascites. From these results, the patient was considered to have spontaneous bacterial peritonitis (SBP). Vancomycin (VCM) and doripenem (DRPM) were administered to control the infection. Unexpectedly, S. pneumoniae was detected in the blood culture. Hence, ampicillin/sulbactam was administered after discontinuing VCM. The patient recovered without any life-threatening complications and was discharged after 10 days. In conclusion, overwhelming postsplenectomy infection (OPSI) due to S. pneumoniae could develop in patient with splenectomy even after vaccination. Although the bacteremia probably due to SBP and acute renal dysfunction was accompanied by OPSI, our patient recovered rapidly..
1049. Hirohisa Okabe, Akira Chikamoto, Masataka Maruno, Daisuke Hashimoto, Katsunori Imai, Katsunobu Taki, Kota Arima, Takatoshi Ishiko, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Tomoharu Yoshizumi, Toru Beppu, Hideo Baba, Yoshihiko Maehara, A long survivor with local relapse of hilar cholangiocarcinoma after R1 surgery treated with chemoradiotherapy: a case report and literature review., Surgical case reports, 10.1186/s40792-016-0195-9, 2, 1, 69-69, 2016.12, The treatment outcome of extrahepatic cholangiocarcinoma remains insufficient because it is difficult to obtain accurate diagnosis of tumor spreading and effective treatment agent is quite limited in spite of substantial current efforts, all of which have been unsuccessful except for gemcitabine plus cisplatin. The patient was a 60-year-old female who had developed hilar cholangiocarcinoma and underwent extrahepatic bile duct resection. Although it was conceivable that it would be the R1 resection, the patient wanted to receive limited resection to avoid postoperative complication mainly because she was depressed. In histology, interstitial spreading of tumor was appreciated at the surgical margin of bile duct. The patient did not accept to receive the additional treatment after the surgery and hardly visited the hospital to take the periodical test for monitoring the residual cancer cells. As expected, the local relapse of tumor was appreciated 1 year after the R1 surgery. She chose radiotherapy and agreed with subsequent S-1 treatment for 26 months. Consequently, elevated CA19-9 was decreased, and local relapse has been successfully controlled for more than 7 years after the relapse of tumor. Here, we report quite a rare case in terms of long survivor after chemoradiotherapy on locally relapsed unresectable hilar cholangiocarcinoma..
1050. Takeshi Kurihara, Tomoharu Yoshizumi, Shinji Itoh, Norifumi Harimoto, Noboru Harada, Toru Ikegami, Yuki Inagaki, Yukio Oshiro, Nobuhiro Ohkohchi, Hiroaki Okamoto, Yoshihiko Maehara, Chronic hepatitis E virus infection after living donor liver transplantation via blood transfusion: a case report., Surgical case reports, 10.1186/s40792-016-0159-0, 2, 1, 32-32, 2016.12, Although it occurs worldwide, hepatitis E virus (HEV) infection in developed countries is generally foodborne. HEV infection is subclinical in most individuals. Although fulminant liver failure may occur, progression to chronic hepatitis is rare. This study describes a 41-year-old man with liver cirrhosis caused by non-alcoholic steatohepatitis and hepatocellular carcinoma within the Milan criteria. His liver function was classified as Child-Pugh grade C. Living donor liver transplantation (LDLT) was performed, and he was discharged from the hospital on postoperative day (POD) 22. However, his alanine aminotransferase concentration began to increase on POD 60 and HEV infection was detected on POD 81. Retrospective assessments of stored blood samples showed that this patient became positive for HEV RNA on POD 3. The liver donor was negative for anti-HEV antibodies and HEV RNA. However, the platelet concentrate transfused into the liver recipient the day after LDLT was positive for HEV RNA. The patient remained positive for HEV infection for 10 months. Treatment with 800 mg/day ribavirin for 20 weeks reduced HEV RNA to an undetectable level. In conclusion, this report describes a patient infected with HEV through a blood transfusion after LDLT, who progressed to chronic hepatitis probably due to his immunosuppressed state and was treated well with ribavirin therapy..
1051. Koichi Kimura, Tomoharu Yoshizumi, Shinji Itoh, Norifumi Harimoto, Takashi Motomura, Noboru Harada, Akihisa Nagatsu, Toru Ikegami, Mizuki Ninomiya, Yuji Soejima, Yoshihiko Maehara, Efficacy of recombinant thrombomodulin for DIC after deceased donor liver transplantation: a case report., Surgical case reports, 10.1186/s40792-016-0208-8, 2, 1, 81-81, 2016.12, BACKGROUND: Disseminated intravascular coagulation (DIC) after liver transplantation (LT) is a difficult complication. We report a case of disseminated intravascular coagulation after deceased donor liver transplantation (DDLT) treated with recombinant thrombomodulin (rTM). CASE PRESENTATION: A 30-year-old woman underwent right tri-segment split graft DDLT for acute liver failure. She developed disseminated intravascular coagulation on post-operative day 5 with fever. Computed tomography revealed necrosis of hepatic segment IV, and her acute-phase disseminated intravascular coagulation score was seven points. She was given rTM, and the inflammation, liver function, and coagulation disorders immediately improved. However, pleural effusion drainage from the chest tube became bloody on post-operative day 11, and rTM was discontinued. She progressed well and was discharged from the hospital on post-operative day 28. rTM is an effective treatment for disseminated intravascular coagulation; however, rTM for cases with coagulation disorders, which can occur after liver transplantation, has both risks and benefits. CONCLUSIONS: We report a case of DIC after LT, in which rTM was potentially effective. Further studies are needed to determine the appropriate dosages, duration, and additional considerations for rTM therapy in liver transplantation patients..
1052. Y. Asayama, A. Nishie, K. Ishigami, Y. Ushijima, Y. Takayama, D. Okamoto, N. Fujita, Y. Kubo, S. Aishima, T. Yoshizumi, H. Honda, Fatty change in moderately and poorly differentiated hepatocellular carcinoma on MRI: a possible mechanism related to decreased arterial flow, CLINICAL RADIOLOGY, 10.1016/j.crad.2016.04.020, 71, 12, 1277-1283, 2016.12, AIM: To clarify the frequency of fatty change in moderately and poorly differentiated hepatocellular carcinomas (mHCCs and pHCCs) and its relationship to arterial blood flow.
MATERIALS AND METHODS: One hundred and thirty-six surgically resected HCC lesions were studied. All patients had undergone dynamic magnetic resonance imaging (MRI) with chemical-shift-encoded water-fat imaging (CSI). The presence of fat was identified by a signal drop-off on CSI and confirmed at pathology. Lesions were classified into four groups in the arterial phase; G1, hypointense; G2, isointense; G3, slightly and heterogeneously hyperintense; G4, markedly and homogeneously hyperintense. The number of cumulative arteries (CAs) in the tumours in the pathology examination were counted.
RESULTS: A fat component was observed significantly more frequently in the pHCCs (13/21; 61.9%) compared to the mHCCs (32/101; 31.7%; p=0.013). The numbers of lesions in each group were as follows: (G1, G2, G3, G4) = (18, 9, 23, 4) in the HCCs with fat; (1, 6, 24, 51) in the HCCs without fat (p<0.001); (5, 5, 18, 4) in the mHCCs with fat; (0, 3, 19, 47) in the mHCCs without fat (p<0.001); (11, 0, 2, 0) in the pHCCs with fat; (0, 2, 3, 3) in the pHCCs without fat (p=0.001). The number of CAs in the fat-containing HCCs (5.5 +/- 2.9) was significantly lower than that in the HCCs without fat (10.8 +/- 5.3; p<0.001).
CONCLUSION: A fat component was more commonly observed in the pHCCs than in the mHCCs. The present results showed a possible mechanism of fatty change in mHCCs and pHCCs in relation to decreased arterial blood supply. (C) 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved..
1053. Nobuhiro Fujita, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Ken Shirabe, Tomoharu Yoshizumi, Kazuhiro Kotoh, Norihiro Furusyo, Tomoyuki Hida, Yoshinao Oda, Taisuke Fujioka, Hiroshi Honda, Fibrosis in nonalcoholic fatty liver disease: Noninvasive assessment using computed tomography volumetry., World journal of gastroenterology, 10.3748/wjg.v22.i40.8949, 22, 40, 8949-8955, 2016.10, AIM: To evaluate the diagnostic performance of computed tomography (CT) volumetry for discriminating the fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 38 NAFLD patients were enrolled. On the basis of CT imaging, the volumes of total, left lateral segment (LLS), left medial segment, caudate lobe, and right lobe (RL) of the liver were calculated with a dedicated liver application. The relationship between the volume percentage of each area and fibrosis stage was analyzed using Spearman's rank correlation coefficient. A receiver operating characteristic (ROC) curve analysis was performed to determine the accuracy of CT volumetry for discriminating fibrosis stage. RESULTS: The volume percentages of the caudate lobe and the LLS significantly increased with the fibrosis stage (r = 0.815, P < 0.001; and r = 0.465, P = 0.003, respectively). Contrarily, the volume percentage of the RL significantly decreased with fibrosis stage (r = -0.563, P < 0.001). The volume percentage of the caudate lobe had the best diagnostic accuracy for staging fibrosis, and the area under the ROC curve values for discriminating fibrosis stage were as follows: ≥ F1, 0.896; ≥ F2, 0.929; ≥ F3, 0.955; and ≥ F4, 0.923. The best cut-off for advanced fibrosis (F3-F4) was 4.789%, 85.7% sensitivity and 94.1% specificity. CONCLUSION: The volume percentage of the caudate lobe calculated by CT volumetry is a useful diagnostic parameter for staging fibrosis in NAFLD patients..
1054. Takeshi Kurihara, Tomoharu Yoshizumi, Yoshihiro Yoshida, Toru Ikegami, Shinji Itoh, Norifumi Harimoto, Mizuki Ninomiya, Hideaki Uchiyama, Hirohisa Okabe, Koichi Kimura, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Graft selection strategy in adult-to-adult living donor liver transplantation: When both hemiliver grafts meet volumetric criteria., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.24431, 22, 7, 914-22, 2016.07, To ensure donor safety in living donor liver transplantation (LDLT), the left and caudate lobe (LL) is the preferred graft choice. However, patient prognosis may still be poor even if graft volume (GV) selection criteria are met. Our aim was to evaluate the effects of right lobe (RL) donation when the LL graft selection criteria are met. Consecutive donors (n = 135) with preoperative LL graft volumetric GV/standard liver volume (SLV) of ≥35% and RL remnant of ≥35% were retrospectively studied. Patients were divided into 2 groups: LL graft and RL graft. Recipient's body surface area (BSA), Model for End-Stage Liver Disease (MELD) score, and the donor's age were higher in the RL group. The donor's BSA and preoperative volumetric GV/SLV of the LL graft were smaller in the RL group. The predicted score (calculated using data for graft size, donor age, MELD score, and the presence of portosystemic shunt, which correlated well with graft function and with 6-month graft survival) of the RL group, was significantly lower if the LL graft were used, but using the actual RL graft improved the score equal to that of the LL group. Six-month and 12-month graft survival rates did not differ between the 2 groups. In patients with a poor prognosis, a larger RL graft improved the predicted score and survival was equal to that of patients who received LL grafts. In conclusion, graft selection by GV, donor age, and recipient MELD score improves outcomes in LDLT. Liver Transplantation 22 914-922 2016 AASLD..
1055. Yoshiki Asayama, Akihiro Nishie, Kousei Ishigami, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Nobuhiro Fujita, Tomoharu Yoshizumi, Tomoyuki Hida, Hiroshi Honda, Histogram analysis of noncancerous liver parenchyma on gadoxetic acid-enhanced MRI: predictive value for liver function and pathology., Abdominal radiology (New York), 10.1007/s00261-016-0753-4, 41, 9, 1751-7, 2016.09, PURPOSE: To clarify whether the heterogeneity of hepatic parenchyma in the hepatobiliary phase on gadoxetic acid-magnetic resonance (MR) imaging is correlated with liver damage. MATERIALS AND METHODS: We retrospectively examined the cases of 98 patients with or without chronic liver disease who underwent gadoxetic acid-enhanced 3T MR imaging before a hepatectomy between December 2010 and October 2014. For the evaluation of the heterogeneity of the signal intensity in the hepatobiliary phase, we placed the region of interest on the hepatic parenchyma, and the skewness and kurtosis were calculated using ImageJ software. A discriminant analysis was performed to examine the routine preoperative laboratory test results including indocyanine green retention at 15 min (ICG-R15), necro-inflammation grade, and liver fibrosis stage according to the METAVIR system: A0/1 (n = 69) and A2 (n = 29); F0/1 (n = 47), F2/3 (n = 31), and F4 (n = 20). RESULTS: The combination of skewness and kurtosis could discriminate the high ICG-R15 (>20) and low (<20) groups (lambda; 0.925, p = 0.025), necro-inflammatory grade (lambda; 0.926, p = 0.026), and fibrosis stage (lambda; 0.752, p < 0.0001) with statistical significance. The difference between the patients with normal values and those with an abnormal platelet count or aspartate transaminase level was also detectable (lambda; 0.901, p < 0.007, and lambda; 0.864, p = 0.001, respectively). CONCLUSION: Histogram analyses of the hepatobiliary phase of gadoxetic acid-enhanced MR imaging have potential as a biomarker for the assessment of liver function, liver fibrosis, and necro-inflammation..
1056. Satomi Hisamoto, Shinji Shimoda, Kenichi Harada, Sho Iwasaka, Shinya Onohara, Yong Chong, Minoru Nakamura, Yuki Bekki, Tomoharu Yoshizumi, Toru Ikegami, Yoshihiko Maehara, Xiao-Song He, M Eric Gershwin, Koichi Akashi, Hydrophobic bile acids suppress expression of AE2 in biliary epithelial cells and induce bile duct inflammation in primary biliary cholangitis., Journal of autoimmunity, 10.1016/j.jaut.2016.08.006, 75, 150-160, 2016.12, Understanding the mechanisms of chronic inflammation in primary biliary cholangitis (PBC) is essential for successful treatment. Earlier work has demonstrated that patients with PBC have reduced expression of the anion exchanger 2 (AE2) on biliary epithelial cells (BEC) and deletion of AE2 gene has led to a PBC-like disorder in mice. To directly address the role of AE2 in preventing PBC pathogenesis, we took advantage of our ability to isolate human BEC and autologous splenic mononuclear cells (SMC). We studied the influence of hydrophobic bile acids, in particular, glycochenodeoxycholic acid (GCDC), on AE2 expression in BEC and the subsequent impact on the phenotypes of BEC and local inflammatory responses. We demonstrate herein that GCDC reduces AE2 expression in BEC through induction of reactive oxygen species (ROS), which enhances senescence of BEC. In addition, a reduction of AE2 levels by either GCDC or another AE2 inhibitor upregulates expression of CD40 and HLA-DR as well as production of IL-6, IL-8 and CXCL10 from BEC in response to toll like receptor ligands, an effect suppressed by inhibition of ROS. Importantly, reduced AE2 expression enhances the migration of autologous splenic mononuclear cells (SMC) towards BEC. In conclusion, our data highlight a key functional role of AE2 in the maintenance of the normal physiology of BEC and the pathogenic consequences of reduced AE2 expression, including abnormal intrinsic characteristics of BEC and their production of signal molecules that lead to the chronic inflammatory responses in small bile ducts..
1057. Shinji Itoh, Ken Shirabe, Shunji Kohnoe, Noriaki Sadanaga, Kiyoshi Kajiyama, Motoyuki Yamagata, Hideaki Anai, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Impact of Recombinant Human Soluble Thrombomodulin for Disseminated Intravascular Coagulation., Anticancer research, 36, 5, 2493-6, 2016.05, BACKGROUND: Early treatment of disseminated intravascular coagulation (DIC) can be associated with improved early outcomes. We aimed to evaluate the effectiveness of recombinant human soluble thrombomodulin (rTM) administration in patients with peritonitis-induced DIC. PATIENTS AND METHODS: We treated 39 patients with DIC or pre-DIC caused by peritonitis at the Department of Surgery and Science, Kyushu University, and related facilities between January and December 2013. RESULTS: Patients surviving to 28 days after DIC treatment had significantly better platelet counts, DIC scores, and sequential organ failure assessment scores at 7 days than did those who died earlier than 28 days. Patients receiving rTM had significantly better overall survival rates at 28 days and the results of multivariate analysis showed that rTM administration for DIC treatment was a prognostic indicator of 28-day survival in patients with peritonitis. CONCLUSION: rTM administration for the treatment of DIC or pre-DIC complicated by peritonitis had acceptable early outcomes..
1058. Tomoharu Yoshizumi, Yasutsugu Takada, Ken Shirabe, Toshimi Kaido, Masaaki Hidaka, Masaki Honda, Takashi Ito, Masahiro Shinoda, Hideki Ohdan, Naoki Kawagishi, Yasuhiko Sugawara, Yasuhiro Ogura, Mureo Kasahara, Shoji Kubo, Akinobu Taketomi, Natsumi Yamashita, Shinji Uemoto, Hiroki Yamaue, Masaru Miyazaki, Tadahiro Takada, Yoshihiko Maehara, Impact of human T-cell leukemia virus type 1 on living donor liver transplantation: a multi-center study in Japan., Journal of hepato-biliary-pancreatic sciences, 10.1002/jhbp.345, 23, 6, 333-41, 2016.06, BACKGROUND: The natural history of human T-cell leukemia virus type 1 (HTLV-1), which causes adult T-cell leukemia (ATL) or HTLV-1 associated myelopathy, after liver transplantation is unclear. METHODS: We conducted a nationwide survey to investigate the impact of HTLV-1 status on living donor liver transplantation (LDLT) in Japan. We analyzed the cases of 82 HTLV-1-positive recipients and six HTLV-1-negative-before-LDLT recipients who received a hepatic graft from HTLV-1-positive donors. RESULTS: Adult T-cell leukemia developed in five recipients who ultimately died. Of these five, two received grafts from HTLV-1-positive donors and three from HTLV-1-negative donors. The 1-, 3-, and 5-year ATL development rates were 4.5%, 6.5%, and 9.2%, respectively. Fulminant hepatic failure as a pre-transplant diagnosis was identified as an independent risk factor for ATL development (P = 0.001). The 1-, 3-, and 5-year survival rates for HTLV-1-positive recipients who received grafts from HTLV-1-negative donors were 79.9%, 66.1%, and 66.1%, and from HTLV-1-positive donors were 83.3%, 83.3%, and 60.8%, respectively. The 1-year survival rate for HTLV-1-negative recipients who received grafts from HTLV-1-positive donors was 33.3%. CONCLUSIONS: Fulminant hepatic failure is an independent risk factor for ATL development in HTLV-1-positive recipients. Grafts from HTLV-1-positive living donors can be transplanted into selected patients..
1059. Norifumi Harimoto, Tomoharu Yoshizumi, Tomonari Shimagaki, Akihisa Nagatsu, Takashi Motomura, Noboru Harada, Hirohisa Okabe, Shinji Itoh, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Inflammation-based Prognostic Score in Patients with Living Donor Liver Transplantation for Hepatocellular Carcinoma., Anticancer research, 10.21873/anticanres.11137, 36, 10, 5537-5542, 2016.10, BACKGROUND: Inflammation-besed prognostic score including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), modified Glasgow prognostic score (mGPS) and prognostic nutritional index (PNI) have prognostic value in various malignancies. PATIENTS AND METHODS: We retrospectively investigated their prognostic value in 213 patients with living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). Disease-free survival (DFS) following LDLT was calculated; NLR, PLR, PNI and mGPS values in patients with and without recurrence were compared. Risk factors for HCC recurrence were identified by univariate and multivariate analyses. RESULTS: Both NLR and PLR were significantly increased in patients with recurrence. Multivariate analysis showed that des-gamma-carboxy prothrombin (DCP) ≥300 mAU/ml, NLR ≥2.66, <3 months between last HCC treatment to LDLT were independent predictors of DFS. CONCLUSION: Preoperative NLR was an independent, inflammation-based prognostic marker of DFS and was predictive of recurrence following LDLT..
1060. Koichi Kimura, Ken Shirabe, Tomoharu Yoshizumi, Kazuki Takeishi, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Shinji Okano, Yoshihiko Maehara, Ischemia-Reperfusion Injury in Fatty Liver Is Mediated by Activated NADPH Oxidase 2 in Rats., Transplantation, 10.1097/TP.0000000000001130, 100, 4, 791-800, 2016.04, BACKGROUND: Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery, and steatosis is a risk factor for liver damage. Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) contribute to liver dysfunction. Here we examined the role of NOX in I/R injury of fatty livers. METHODS: Rats were fed a methionine and choline-deficient diet to induce a fatty liver. Rats then underwent surgically induced partial hepatic ischemia followed by reperfusion. RESULTS: The overall survival rate after I/R was lower in rats with fatty livers than with normal livers (P < 0.01). Necrotic area and the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), TNFα, and IL-6 were higher in fatty liver tissue than in normal liver tissue (P < 0.01). The number of p47phox-positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 24 hours after reperfusion. The number of TLR-4 positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 4 and 24 hours after reperfusion coupled with a decreased number of high-mobility group box 1-positive hepatocytes. Apocynin significantly improved the survival rate, necrotic area, and concentrations of 8-hydroxy-2'-deoxyguanosine, TNFα, and IL-6 (P < 0.01). The protective effect of apocynin on fatty livers was greater than on normal livers. CONCLUSIONS: Ischemia-reperfusion injury was associated with increased high-mobility group box 1, TLR4, and NOX2. Inhibition of NOX activity improved oxidative stress and may prevent I/R injury in fatty liver..
1061. Noboru Harada, Takashi Maeda, Tomoharu Yoshizumi, Tetsuo Ikeda, Hiroto Kayashima, Toru Ikegami, Norifumi Harimoto, Shintaro Takaki, Yoshihiko Maehara, Laparoscopic Liver Resection Is a Feasible Treatment for Patients with Hepatocellular Carcinoma and Portal Hypertension., Anticancer research, 36, 7, 3489-97, 2016.07, AIM: To compare outcomes of patients with primary hepatocellular carcinoma (HCC) and portal hypertension (PHT) who underwent laparoscopic liver resection (LLR), open liver resection (OLR) or radiofrequency ablation (RFA). PATIENTS AND METHODS: We retrospectively reviewed 88 patients with primary HCC and PHT who underwent LLR (n=20), OLR (n=48) or RFA (n=20) and analyzed their outcomes by treatment group. To reduce selection bias, covariate distributions in groups were adjusted using inverse probability treatment weighting (IPTW). RESULTS: Five-year recurrence-free survival (RFS) was significantly better in the LLR and OLR than in the RFA group both before and after IPTW adjustment. The OLR group had significantly more postoperative complications than the RFA group; however, there was no significant difference in the postoperative complication rate between LLR and RFA groups. CONCLUSION: LLR may be a feasible treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or advanced hepatocellular carcinoma (A HCC) and PHT..
1062. Toru Ikegami, Tomoharu Yoshizumi, Kazuhito Sakata, Hideaki Uchiyama, Norifumi Harimoto, Noboru Harada, Shinji Itoh, Akihisa Nagatsu, Yuji Soejima, Yoshihiko Maehara, Left lobe living donor liver transplantation in adults: What is the safety limit?, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.24611, 22, 12, 1666-1675, 2016.12, Small-for-size syndrome (SFSS) is the most significant cause of graft loss after living donor liver transplantation (LDLT), especially after left lobe (LL) LDLT in adults. The safety limit of applying LL-LDLT in adults without severe SFSS with a high rate of lethality needs to be determined. A total of 207 LL-LDLTs in adults since September 2005 were evaluated to analyze the risk factors for severe SFSS, defined as a serum total bilirubin concentration of ≥20.0 mg/dL after LDLT. Although there were no significant differences in cumulative graft survival after LDLT between medium grafts (graft volume [GV] to standard liver volume [SLV] ratio ≥ 40.0%), small grafts (35.0% ≤ GV/SLV < 40.0%), and extra small grafts (GV/SLV < 35.0%), patients with severe SFSS showed a significantly lower 5-year graft survival rate than those without (42.9% versus 94.3%, respectively; P < 0.001). Multivariate analysis for severe SFSS after LL-LDLT showed that donor age of ≥48 years (P = 0.01), Model for End-Stage Liver Disease (MELD) score of ≥ 19 (P < 0.01), and end portal venous pressure of ≥19 mm Hg (P = 0.04) were the significant and independent factors for severe SFSS after LL-LDLT. Within such high-risk subgroups of patients with a donor age of ≥48 years or MELD score of ≥ 19 before LDLT, operative blood loss volume of ≥8.0 L was a risk factor for severe SFSS. LL-LDLT in adults could be indicated and provide acceptable outcomes for the combinations of donors aged < 48 years and recipients with a MELD score of <19. Smaller grafts might yield acceptable outcomes in appropriately selected donor-recipient combinations. Liver Transplantation 22 1666-1675 2016 AASLD..
1063. Tomonari Shimagaki, Tomoharu Yoshizumi, Shinji Itoh, Takashi Motomura, Akihisa Nagatsu, Noboru Harada, Norifumi Harimoto, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Liver resection with right hepatic vein reconstruction using the internal jugular vein: a case report., Surgical case reports, 10.1186/s40792-016-0258-y, 2, 1, 132-132, 2016.12, BACKGROUND: The role of hepatectomy for malignant liver tumors has expanded during the past decades, and vascular reconstruction during liver resection is sometimes necessary to achieve curative surgery. CASE PRESENTATION: We report a case of liver resection in a 54-year-old male who had liver metastasis that invaded the right hepatic vein. He had undergone laparoscopic low anterior resection for rectal cancer. Six months later, liver metastasis was detected. After the reduction of the tumor by preoperative chemotherapy, liver resection with right hepatic vein reconstruction using his own internal jugular vein graft was performed. The postoperative course was uneventful, and the patient was discharged 8 days after the surgery. CONCLUSIONS: Internal jugular vein grafts are superior to other types of vascular grafts for vascular reconstruction in liver surgery..
1064. Tomoharu Yoshizumi, Norifumi Harimoto, Shinji Itoh, Hirohisa Okabe, Koichi Kimura, Hideaki Uchiyama, Toru Ikegami, Tetsuo Ikeda, Yoshihiko Maehara, Living Donor Liver Transplantation for Hepatocellular Carcinoma within Milan Criteria in the Present Era., Anticancer research, 36, 1, 439-45, 2016.01, BACKGROUND: The aim of the present study was to clarify the outcome of living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria. PATIENTS AND METHODS: The study comprised of 197 adult patients. One hundred twenty-nine patients were within Milan criteria. The overall and recurrence-free survival rates after the LDLT were calculated. RESULTS: The 1-, 5- and 10-year overall survival rates were 94.5%, 89.9% and 88.6%, respectively. The 1-, 5- and 10-year recurrence-free survival rates were 100%, 97.0% and 94.0%, respectively. Four patients had HCC recurrence. The mean neutrophil to lymphocyte ratio (NLR) (6.75 vs. 2.75, p=0.002) or alpha-fetoprotein (AFP) (3,239 vs. 197, p<0.001) of these four recipients was significantly higher compared to that of 125 recipients without HCC recurrence. CONCLUSION: The outcome of LDLT for patients with HCC within Milan criteria was outstanding. Careful follow-up after LDLT is necessary for patients with high NLR or AFP..
1065. Yuki Bekki, Toru Ikegami, Yoshihiro Yoshida, Takashi Motomura, Shinji Itoh, Noboru Harada, Norifumi Harimoto, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara, Living donor liver transplantation indicated for compensated liver cirrhosis with symptomatic gallstone diseases: report of two cases., Surgical case reports, 10.1186/s40792-016-0172-3, 2, 1, 45-45, 2016.12, BACKGROUND: Surgical interventions for symptomatic gallstone disease could be dangerous in patients with severe comorbid conditions including liver cirrhosis. Here, we report our experience of living donor liver transplantation (LDLT) indicated for two patients with liver cirrhosis complicated with gallstone diseases. CASE 1: A 70-year-old woman with a history of hepatitis C virus infection was diagnosed as symptomatic choledocholithiasis. She had open cholecystectomy and choledochotomy with choledocholithotomy, which complicated with postoperative liver failure. Her Child-Pugh score increased from 7 to 12 points and Model for End-Stage Liver Disease (MELD) score from 11 to 36. She underwent LDLT, using the right lobe graft donated by her 47-year-old daughter. The post-transplant graft function was excellent, and the patient was discharged from the hospital on postoperative day 27. CASE 2: A 46-year-old man with a history of hepatitis B virus infection was diagnosed as cholecystitis. He had cholecystostomy without any complications and his Child-Pugh score remained to be 9 and MELD score 17, followed by LDLT using the right lobe graft donated by his 45-year-old wife. The post-transplant graft function was excellent, and the patient was discharged from the hospital on postoperative day 44. CONCLUSION: LDLT is one of treatment options when patients with Child-Pugh B cirrhosis accompanied with gallstone diseases, likely to be deteriorating their liver functions in the near future..
1066. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Koichi Kimura, Hirohisa Okabe, Yoshihiko Maehara, Living donor liver transplantation for intrahepatic arteriovenous fistula with hepatic artery reconstruction using the right gastroepiploic artery., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.24377, 22, 4, 552-6, 2016.04.
1067. Takeshi Kurihara, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Reply., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.24648, 22, 12, 1743-1743, 2016.12.
1068. H. Okabe, T. Yoshizumi, T. Ikegami, H. Uchiyama, N. Harimoto, S. Itoh, K. Kimura, H. Baba, Y. Maehara, Salvage Splenic Artery Embolization for Saving Falling Living Donor Graft due to Portal Overflow: A Case Report, Transplantation Proceedings, 10.1016/j.transproceed.2016.07.023, 48, 9, 3171-3173, 2016.11, Portal decompression is an approach for reducing portal overflow caused by small-for-size syndrome. We report the case of a patient who recovered from rapidly progressing hyperbilirubinemia caused by a small graft by decompressing portal overflow with splenic artery embolization following a living donor liver transplantation (LDLT). The patient was a 54-year-old man with end-stage liver disease secondary to alcoholic liver cirrhosis
the donor was his 54-year-old wife. The graft volume of the left lobe was 444 mL, which was 34.8% of the standard liver volume (SLV) and insufficient for the recipient
thus, the plan was to use the right lobe for the graft. The patient underwent LDLT with a right lobe graft
the volume to SLV ratio was 39.1%, and the graft-to-recipient-weight ratio was 0.72%. Although portal pressure was low during the operation, the patient eventually developed small-for-size syndrome after LDLT. It was conceivable that because the patient had splenomegaly, portal decompression would be effective. Splenic arterial embolization was performed successfully on postoperative day (POD) 7. The patient's total bilirubin level was increased to 40 mg/dL on POD16. Decreased portal flow, which was shown by ultrasound screening to be “to-and-flo,” increased again on POD23 to one-third of that on POD1. He was discharged without any infectious complications. Additional splenic artery embolization after LDLT may be a convenient option for reducing portal overflow for patients with splenomegaly if the portal decompression was not performed for some reason at the surgery..
1069. Tomohiko Akahoshi, Mitsuhiro Yasuda, Kenta Momii, Kensuke Kubota, Yuji Shono, Noriyuki Kaku, Kentaro Tokuda, Takashi Nagata, Tomoharu Yoshizumi, Ken Shirabe, Makoto Hashizume, Yoshihiko Maehara, Sarcopenia is a predictive factor for prolonged intensive care unit stays in high-energy blunt trauma patients., Acute medicine & surgery, 10.1002/ams2.195, 3, 4, 326-331, 2016.10, Aim: Sarcopenia has been increasingly reported as a prognostic factor for outcome in settings such as cirrhosis, liver transplantation, and emergent surgery. We aimed to elucidate the significance of sarcopenia in severe blunt trauma patients. Methods: We retrospectively analyzed 84 patients emergently admitted to the intensive care unit at Kyushu University Hospital (Fukuoka, Japan) from May 2012 to April 2015. We assessed the amount of skeletal muscle present according to computed tomography and its relevance to ventilation-free days, patients' length of stay in the intensive care unit, and 28-day mortality. Results: Twenty-five (29.7%) patients were defined as sarcopenic. Sixteen (19.7%) patients required 15 days or more in the intensive care unit. The major reason was a prolonged ventilation requirement due to flail chest (n = 7) or pneumonia (n = 3). Sarcopenic patients' stays in intensive care were significantly longer than those of non-sarcopenic patients (18.7 versus 6.4 days, respectively; P < 0.001). Univariate and multivariate analyses showed sarcopenia to be a significant risk factor for prolonged intensive care unit stay. Conclusion: Sarcopenia is a risk factor that predicts prolonged intensive care unit stay in high-energy blunt trauma patients..
1070. Yoshihide Ueda, Toru Ikegami, Akihiko Soyama, Nobuhisa Akamatsu, Masahiro Shinoda, Kohei Ishiyama, Masaki Honda, Shigeru Marubashi, Hideaki Okajima, Tomoharu Yoshizumi, Susumu Eguchi, Norihiro Kokudo, Yuko Kitagawa, Hideki Ohdan, Yukihiro Inomata, Hiroaki Nagano, Ken Shirabe, Shinji Uemoto, Yoshihiko Maehara, Simeprevir or telaprevir with peginterferon and ribavirin for recurrent hepatitis C after living-donor liver transplantation: A Japanese multicenter experience., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12684, 46, 13, 1285-1293, 2016.12, AIM: This study aimed to clarify the efficacy and safety of simeprevir, a second-generation NS3/4A inhibitor, with peginterferon and ribavirin for recurrent hepatitis C after liver transplantation. METHODS: A retrospective cohort study of living-donor liver transplant recipients with recurrent hepatitis C with the hepatitis C virus genotype 1 treated with either simeprevir- or telaprevir-based triple therapy was carried out at eight Japanese liver transplant centers. RESULTS: Simeprevir- and telaprevir-based triple therapies were given to 79 and 36 patients, respectively. Of the 79 patients treated with simeprevir-based triple therapy, 44 (56%) achieved sustained virological response 12 weeks (SVR12) after treatment ended, and there was no significant difference in the SVR12 between the simeprevir- and telaprevir-based triple therapy groups (69%). The rates of adverse events were not significantly different between the simeprevir- and telaprevir-based triple therapy groups, although the rate of patients who received blood cell transfusion and erythropoietin due to anemia and had renal insufficiency were significantly higher in the telaprevir group than in the simeprevir group. Three baseline factors, the presence of prior dual therapy with peginterferon and ribavirin (P = 0.001), a non-responder to the prior dual therapy (P < 0.001), and male sex (P = 0.040), were identified as significant predictive factors for non-SVR with simeprevir-based triple therapy. CONCLUSION: Simeprevir-based triple therapy for recurrent hepatitis C after living-donor liver transplantation resulted in a high SVR rate and good tolerability, especially in treatment-naïve patients..
1071. Shinji Itoh, Ken Shirabe, Tomoharu Yoshizumi, Kazuki Takeishi, Norifumi Harimoto, Toru Ikegami, Hirofumi Kawanaka, Akihiro Nishie, Takahide Kamishima, Yoshihiko Maehara, Skeletal muscle mass assessed by computed tomography correlates to muscle strength and physical performance at a liver-related hospital experience., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12537, 46, 4, 292-7, 2016.04, AIM: We aimed to evaluate whether skeletal muscle mass measured by computed tomography (CT) or bioelectrical impedance analysis (BIA) correlated to muscle strength and physical performance in liver-related hospital cases. METHODS: We prospectively conducted this study in 120 liver-related hospital cases. Skeletal muscle mass was measured by CT scan and BIA. Muscle strength was determined by hand grip strength and physical performance by usual gait speed. RESULTS: Skeletal muscle mass measured using CT significantly correlated to usual gait speed (r(2)  = 0.17, P < 0.0001) and hand grip strength (r(2)  = 0.66, P < 0.0001), but the correlations were lower using BIA (r(2)  = 0.1, P = 0.0005; r(2)  = 0.54, P < 0.0001). With regard to liver function, the relationship between skeletal muscle mass measured by CT and BIA and two muscle function parameters in the Child-Pugh A group were significant. In contrast, skeletal muscle mass measured by BIA in the Child-Pugh B or C group was not significantly related to usual gait speed. CONCLUSION: Skeletal muscle mass measured by CT was significantly correlated to hand grip strength and usual gait speed, with higher correlations compared with BIA. Moreover, skeletal muscle mass measured by CT significantly correlated with two muscle functions, even in patients with Child-Pugh B or C..
1072. Yo-Ichi Yamashita, Tomoharu Yoshizumi, Kengo Fukuzawa, Takashi Nishizaki, Eiji Tsujita, Kiyoshi Kajiyama, Yuji Soejima, Motoyuki Yamagata, Kazuharu Yamamoto, Eisuke Adachi, Keishi Sugimachi, Yasuharu Ikeda, Hideaki Uchiyama, Takashi Maeda, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Yoshihiko Maehara, Surgical Results of Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: a Multi-institutional Retrospective Study of 174 patients., Anticancer research, 36, 5, 2407-12, 2016.05, BACKGROUND: Postoperative pancreatic fistula (POPF) remains a major complication after pancreaticoduodenectomy (PD), and the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) after PD is poor. PATIENTS AND METHODS: A multi-institutional retrospective study was performed in 174 patients who underwent PD for PDAC from 2007 to 2012. The details of clinical data were examined, and risk factors for POPF and poor prognostic factors after PD were identified. RESULTS: POPF occured in 26 patients (15%), and 18 patients (10%) were diagnosed as Grade B/C POPF. The independent risk factors for Grade B/C POPF were body mass index (BMI) ≥25 (Odds Ratio [OR]=21.1, p=0.006) and absence of post-operative enteral nutrition (EN) (OR=10.2, p=0.04). The 1-, 3-, and 5-year overall survivals of patients with PDAC after PD were 76%, 35%, and 18%, respectively. R1/2 operation was identified as the only independent poor prognostic factor (Hazard Ratio=3.66; p=0.0002). CONCLUSION: Patients with BMI ≥25 should be closely monitored for POPF after PD. Post-operative EN might help prevent POPF. Performing R0 resection is an important goal for ensuring patient survival after PD for PDAC..
1073. Toru Ikegami, Tomoharu Yoshizumi, Yoshihro Yoshida, Takeshi Kurihara, Norifumi Harimoto, Shinji Itoh, Masahiro Shimokawa, Takasuke Fukuhara, Ken Shirabe, Yoshihiko Maehara, Telaprevir versus simeprevir for the treatment of recurrent hepatitis C after living donor liver transplantation., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12546, 46, 3, E136-45-45, 2016.03, AIM: Our aim was to evaluate the clinical outcomes of telaprevir (TVR)- or simeprevir (SMV)-based triple therapy for recurrent hepatitis C after living donor liver transplantation. METHODS: Twenty-six patients received antiviral therapy, consisting of either TVR (n = 12) or SMV (n = 14) in combination with pegylated interferon and ribavirin, plus cyclosporin. RESULTS: More patients had a dose reduction of the direct-acting agent (36.3% vs 0.0%, P = 0.02) or required blood transfusion for anemia (58.3% vs 7.1%, P < 0.01) in the TVR group. The cyclosporin trough/dose ratio increased significantly from week 0 to week 4 in the TVR group (1.6 ± 0.4 to 5.1 ± 2.0, P < 0.01), but not in the SMV group (1.2 ± 0.3 to 1.3 ± 0.2, P = 0.68). The 24-week cumulative viral clearance rate was 91.7% and 85.7% in the TVR and in SMV groups, respectively. The early viral response and sustained viral response rates were 91.7% and 83.3%, respectively, in the TVR group, compared with 85.7% and 64.3%, respectively, in the SMV group. Interferon-mediated graft dysfunction occurred in four and five patients in the TVR and SMV groups, respectively; two patients were treated by oral steroids, five by steroid pulse and two by thymoglobulin, resulting in viral breakthrough in one case. CONCLUSION: SMV-based triple therapy was associated with fewer adverse events and drug interactions with cyclosporin, and possibly less antiviral properties to TVR. Interferon-mediated graft dysfunction is a significant clinical problem that warrants particular caution following living donor liver transplantation..
1074. Toru Ikegami, Norifumi Harimoto, Masahiro Shimokawa, Tomoharu Yoshizumi, Hideaki Uchiyama, Shinji Itoh, Norihisa Okabe, Kazuhito Sakata, Akihisa Nagatsu, Yuji Soejima, Yoshihiko Maehara, The learning curves in living donor hemiliver graft procurement using small upper midline incision., Clinical transplantation, 10.1111/ctr.12850, 30, 12, 1532-1537, 2016.12, The learning curve for performing living donor hemiliver procurement (LDHP) via small upper midline incision (UMI) has not been determined. Living donors (n=101) who underwent LDHP via UMI were included to investigate the learning curve using cumulative sum analysis. The cumulative sum analysis showed that nine cases for right lobe (case #23) and 19 cases for left lobe (case #32 in the whole series) are needed for stable and acceptable surgical outcomes in LDHP via UMI. The established phase (n=69, since case #33) had a significantly shorter operative time, a smaller incision size, and less blood loss than the previous learning phase (n=32, serial case number up to the last 19th left lobe case). Multivariate analysis showed that the learning phase, high body mass index ≥25 kg/m2 , and left lobe graft procurement are the factors associated with surgical events including operative blood loss ≥400 mL, operative time ≥300 minutes, or surgical complications ≥Clavien-Dindo grade II. There is an obvious learning curve in performing LDHP via UMI, and 32 cases including both 19 cases for left lobe and nine cases for right lobe are needed for having stable and acceptable surgical outcomes..
1075. Hideaki Uchiyama, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Hirohisa Okabe, Koichi Kimura, Yoshihiko Maehara, The use of left grafts with a replaced or accessory left hepatic artery in adult-to-adult living donor liver transplantation: analyses of donor and recipient outcomes., Clinical transplantation, 10.1111/ctr.12783, 30, 9, 1021-7, 2016.09, In living donor liver transplantation (LDLT), a left hepatic graft occasionally includes a replaced or accessory left hepatic artery (LHA). The procuring of such grafts requires extensive dissection along the lesser curvature of the stomach to elongate the replaced or accessory LHA on the donor side. On the recipient side, complicated arterial reconstruction is often necessary to use such grafts. We retrospectively reviewed the medical records of 206 adult recipients who underwent LDLT and their respective donors. The recipients and donors were divided into two groups according to the presence of the replaced or accessory LHA. Twenty-five grafts included a replaced or accessory LHA. Only one hepatic artery-related complication was observed in the current series, in which a pseudoaneurysm arose at the site of anastomosis between the donor accessory LHA and the recipient LHA. There was no increase in the incidence of postoperative complications in the donors with a replaced or accessory LHA in comparison with the donors without these arteries. The use of left hepatic grafts that included a replaced LHA or accessory LHA did not have any negative impact on the outcomes on either the donor or the recipient side..
1076. Shinji Itoh, Shunji Kohnoe, Ken Shirabe, Daisuke Yoshida, Hirofumi Kawanaka, Tomoharu Yoshizumi, Toru Ikegami, Yo-Ichi Yamashita, Takeshi Kurihara, Yoshihiko Maehara, Validity of Hepatic or Pancreatic Resection for Elderly Patients Aged 85 Years or Older at a Single Community Hospital in Japan., Anticancer research, 36, 8, 4289-92, 2016.08, AIM: To evaluate the efficacy of age on the surgical outcomes in hepatic or pancreatic resection. PATIENTS AND METHODS: We performed 50 hepatic or pancreatic resections in our community hospital and divided them into 2 groups based on age: patients aged ≥85 years old and patients aged <85 years old. We calculated the Estimation of Physiologic Ability and Surgical Stress (E-PASS) score and the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) system and compared the surgical outcome between the two groups. RESULTS: There was no significant difference between the two groups with regard to E-PASS and POSSUM scores. Patients aged ≥85 years had a significantly higher frequency of anti-platelet agents. The incidence of postoperative complications and mortality in patients ≥85 years old were comparable to those in patients aged <85 years old. CONCLUSION: Hepatic or pancreatic resection for elderly patients aged 85 years or older can be safely performed under a given careful patient selection..
1077. [CURRENT STATUS OF HEPATOBILIARY PANCREATIC SURGERY FOR ELDERLY PATIENTS]..
1078. Daisuke Imai, Yo-ichi Yamashita, Toru Ikegami, Takeo Toshima, Norifumi Harimoto, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Tetsuo Ikeda, Yoshihiko Maehara, A "rendezvous technique" for treating a pancreatic fistula after distal pancreatectomy., Surgery today, 10.1007/s00595-013-0740-0, 45, 1, 96-100, 2015.01, BACKGROUND: Pancreatic fistulae are a major complication of distal pancreatectomy (DP). Some cases of severe pancreatic fistula require invasive procedures. There have been some reports concerning the effectiveness of pancreatic duct drainage through an endoscopic transpapillary approach for pancreatic fistulae. CASE PRESENTATION: We herein present a case of a pancreatic fistula after DP that was successfully treated with percutaneous pancreatic duct drainage, which was performed using a combined percutaneous and endoscopic approach, named the "rendezvous technique". In our case, we performed distal pancreatectomy with celiac artery resection for a locally advanced pancreatic body cancer. On postoperative day (POD) 7, the drain amylase level increased up to 37,460 IU/l. Computed tomography (CT) revealed peripancreatic fluid collections. On POD 10, we placed a catheter in the main pancreatic duct using the rendezvous technique. CT on POD 14 revealed a decrease in the size of the peripancreatic fluid collection, and contrast imaging from the drains on POD 22 revealed almost complete disappearance of the fluid collection. We withdrew the pigtail catheter on POD 27 and the percutaneous pancreatic duct drain on POD 36. This patient was discharged from our hospital on POD 40. CONCLUSION: We herein report a new approach called the "rendezvous technique" for the management of pancreatic fistulae after DP that can be used instead of a stressful nasopancreatic tube..
1079. Yuki Inagaki, Yukio Oshiro, Tomohiro Tanaka, Tomoharu Yoshizumi, Hideaki Okajima, Kohei Ishiyama, Chikashi Nakanishi, Masaaki Hidaka, Hiroshi Wada, Taizo Hibi, Kosei Takagi, Masaki Honda, Kaori Kuramitsu, Hideaki Tanaka, Taiji Tohyama, Toshihiko Ikegami, Satoru Imura, Tsuyoshi Shimamura, Yoshimi Nakayama, Taizen Urahashi, Kazumasa Yamagishi, Hiroshi Ohnishi, Shigeo Nagashima, Masaharu Takahashi, Ken Shirabe, Norihiro Kokudo, Hiroaki Okamoto, Nobuhiro Ohkohchi, A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis E in Liver Transplant Recipients in Japan, EBIOMEDICINE, 10.1016/j.ebiom.2015.09.030, 2, 11, 1607-1612, 2015.11, Background: Recently, chronic hepatitis E has been increasingly reported in organ transplant recipients in European countries. In Japan, the prevalence of hepatitis E virus (HEV) infection after transplantation remains unclear, so we conducted a nationwide cross-sectional study to clarify the prevalence of chronic HEV infection in Japanese liver transplant recipients.Methods: A total of 1893 liver transplant recipients in 17 university hospitals in Japan were examined for the presence of immunoglobulin G (IgG), IgM and IgA classes of anti-HEV antibodies, and HEV RNA in serum.Findings: The prevalence of anti-HEV IgG, IgM and IgA class antibodies was 2.9% (54/1893), 0.05% (1/1893) and 0% (0/1893), respectively. Of 1651 patients tested for HEV RNA, two patients (0.12%) were found to be positive and developed chronic infection after liver transplantation. In both cases, HEV RNA was also detected in one of the blood products transfused at the perioperative period. Analysis of the HEV genomes revealed that the HEV isolates obtained from the recipients and the transfused blood products were identical in both cases, indicating transfusion-transmitted HEV infection.Interpretation: The prevalence of HEV antibodies in liver transplant recipients was 2.9%, which is low compared with the healthy population in Japan and with organ transplant recipients in European countries; however, the present study found, for the first time, two Japanese patients with chronic HEV infection that was acquired via blood transfusion during or after liver transplantation. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)..
1080. Takeo Toshima, Ken Shirabe, Toru Ikegami, Tomoharu Yoshizumi, Atsushi Kuno, Akira Togayachi, Masanori Gotoh, Hisashi Narimatsu, Masaaki Korenaga, Masashi Mizokami, Akihito Nishie, Shinichi Aishima, Yoshihiko Maehara, A novel serum marker, glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP), for assessing liver fibrosis., Journal of gastroenterology, 10.1007/s00535-014-0946-y, 50, 1, 76-84, 2015.01, BACKGROUND: Recently, a novel marker, hyperglycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP), was developed for liver fibrosis using the glycan "sugar chain"-based immunoassay; however, the feasibility of WFA(+)-M2BP for assessing liver fibrosis has not been proven with clinical samples of hepatitis. METHODS: Serum WFA(+)-M2BP values were evaluated in 200 patients with chronic liver disease who underwent histological examination of liver fibrosis. The diagnostic accuracy of WFA(+)-M2BP values was compared with various fibrosis markers, such as ultrasound based-virtual touch tissue quantification (VTTQ), magnetic resonance imaging based-liver-to-major psoas muscle intensity ratio (LMR), and serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index (APRI). RESULTS: Serum WFA(+)-M2BP levels in patients with fibrosis grades F0, F1, F2, F3, and F4 had cutoff indices 1.62, 1.82, 3.02, 3.32, and 3.67, respectively, and there were significant differences between fibrosis stages F1 and F2, and between F2 and F3 (P < 0.01). The area under the receiver operating characteristic curves for the diagnosis of fibrosis (F ≥ 3) using serum WFA(+)-M2BP values (0.812) was almost comparable to that using VTTQ examination (0.814), but was superior to the other surrogate markers, including LMR index (0.766), APRI (0.694), hyaluronic acid (0.683), and type 4 collagen (0.625) (P < 0.01 each). CONCLUSIONS: Serum WFA(+)-M2BP values based on a glycan-based immunoassay is an accurate, reliable, and reproducible method for the assessment of liver fibrosis. This approach could be clinically feasible for evaluation of beneficial therapy through the quantification of liver fibrosis in hepatitis patients if this measurement application is commercially realized..
1081. Shohei Yoshiya, Ken Shirabe, Daisuke Imai, Takeo Toshima, Yo-ichi Yamashita, Toru Ikegami, Shinji Okano, Tomoharu Yoshizumi, Hirofumi Kawanaka, Yoshihiko Maehara, Blockade of the apelin-APJ system promotes mouse liver regeneration by activating Kupffer cells after partial hepatectomy., Journal of gastroenterology, 10.1007/s00535-014-0992-5, 50, 5, 573-82, 2015.05, BACKGROUND: Liver regeneration after massive hepatectomy or living donor liver transplantation is critical. The apelin-APJ system is involved in the regulation of cardiovascular function, inflammation, fluid homeostasis, the adipo-insular axis, and angiogenesis, but its function in liver regeneration remains unclear. METHODS: We investigated the impact of pharmacologic blockade of the apelin-APJ system, using the specific APJ antagonist F13A on liver regeneration after hepatectomy in mice. RESULTS: F13A-treated mice had significantly higher serum concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 than control mice, due to F13A-promoted activation of Kupffer cells. Compared with untreated mice, F13A enhanced the signal transducer and activator of transcription 3 and mitogen-activated protein kinase pathways, stimulated cell-cycle progression, and promoted hepatocyte proliferation and liver regeneration without inducing apoptosis or inflammation in regenerating livers. In vitro, Kupffer cells expressed APJ and were activated directly by F13A treatment, releasing TNF-α and IL-6. Moreover, F13A-treated mice had a higher survival rate than untreated mice in the extended hepatectomy model. CONCLUSIONS: F13A treatment promotes early phase liver regeneration after hepatectomy by promoting the activation of Kupffer cells and increasing serum levels of TNF-α and IL-6. F13A treatment may become a therapeutic option to facilitate efficient liver regeneration after liver surgery..
1082. K. Takeishi, K. Shirabe, Y. Yoshida, Y. Tsutsui, T. Kurihara, K. Kimura, S. Itoh, N. Harimoto, Y. I. Yamashita, T. Ikegami, T. Yoshizumi, A. Nishie, Y. Maehara, Correlation between portal vein anatomy and bile duct variation in 407 living liver donors, American Journal of Transplantation, 10.1111/ajt.12965, 15, 1, 155-160, 2015.01, Our aim was to determine whether variant bile duct (BD) anatomy is associated with portal vein (PV) and/or hepatic artery (HA) anatomy. We examined the associations between BD anatomy and PV and/or HA anatomy in 407 living donor transplantation donors. We also examined whether the right posterior BD (RPBD) course was associated with the PV and/or HA anatomy. Variant PV, HA and BD anatomies were found in 11%, 25% and 25%, respectively, of 407 donors enrolled in this study. The presence of a variant BD was more frequently associated with a variant PV than with a normal PV (61% vs. 20%, p<
0.0001). By contrast, the presence of a variant HA was not associated with a variant BD. A supraportal RPBD was found in 357 donors (88%) and an infraportal RPBD was found in 50 donors (12%). An infraportal RPBD was significantly more common in donors with a variant PV than in donors with a normal PV (30% vs. 10%, p=0.0004). Variant PV, but not variant HA, anatomies were frequently associated with variant BD anatomy. Additionally, an infraportal RPBD was more common in donors with a variant PV than in donors with a normal PV. This study investigating the anatomy of 407 living liver donors indicates that variant portal vein, but not variant hepatic artery, anatomies are frequently associated with variant bile duct anatomy..
1083. M. Ninomiya, K. Shirabe, H. Kayashima, T. Ikegami, A. Nishie, N. Harimoto, Y. Yamashita, T. Yoshizumi, H. Uchiyama, Y. Maehara, Functional assessment of the liver with gadolinium-ethoxybenzyl-diethylenetriamine penta-acetate-enhanced MRI in living-donor liver transplantation, British Journal of Surgery, 10.1002/bjs.9820, 102, 8, 944-951, 2015.07, Background A precise estimation of the capacity of the remnant liver following partial liver resection is important. In this study, the regional function of the liver in patients undergoing living-donor liver transplantation was evaluated by gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (EOB)-enhanced MRI, with special reference to the congested region. Methods EOB-MRI analysis was performed before hepatectomy in donors, and 7days after surgery in the donor and recipient. In the hepatocyte phase, from images obtained 15min after Primovist® injection, the signal intensity in each liver segment was measured and divided by the signal intensity of the erector spinae muscle (liver to muscle ratio, LMR) for standardization. Inter-regional differences in LMRs were analysed in donors and recipients. Results Thirty-two living donors and 31 recipients undergoing living-donor liver transplantation were enrolled. In donors, the LMRs of the remnant left lobe were almost equivalent among the liver segments. In the remnant right lobe without the middle hepatic vein, the mean(s.d.) LMR for congested segments (S5 and S8) was significantly lower than that for non-congested segments (S6 and S7): 2·60(0·52) versus 3·64(0·56) respectively (P<
0·001). After surgery, values in the non-congested region were almost identical to those in the preoperative donor liver. LMR values in the left and right lobe graft were significantly lower than those in the corresponding segment before donor surgery (P<
0·001). Conclusion The function of the congested region secondary to outflow obstruction in the remnant donor liver was approximately 70 per cent of that in the non-congested region. EOB-MRI is a promising tool to assess regional liver function, with good spatial resolution. Estimation of hepatic functional reserve in liver surgery.
1084. N. Harimoto, H. Wang, T. Ikegami, K. Takeishi, S. Itoh, Y. I. Yamashita, T. Yoshizumi, S. Aishima, K. Shirabe, Y. Oda, Y. Maehara, Hepatology: Rare Stevens-Johnson syndrome and vanishing bile duct syndrome induced by acetaminophen, requiring liver transplantation, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.12849, 30, 4, 656-656, 2015.04.
1085. T. Yoshizumi, S. Itoh, D. Imai, T. Ikegami, M. Ninomiya, T. Iguchi, N. Harimoto, K. Takeishi, Y. Kimura, H. Uchiyama, Y. Soejima, T. Ikeda, H. Kawanaka, K. Shirabe, Y. Maehara, Impact of Platelets and Serotonin on Liver Regeneration After Living Donor Hepatectomy, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2014.11.050, 47, 3, 683-685, 2015.04, Background. Several animal models have revealed that platelet-derived serotonin initiates liver regeneration after hepatectomy. However, there are few reports regarding the effects of serotonin in the clinical setting. The aim of this study was to explore the impact of serotonin and platelets in the early phase after healthy living donor hepatectomy.
Study Design. Stored samples from 34 living donors who received left lobectomy with caudate lobectomy (LL+C) or right lobectomy (RL) were available in the study. Serum serotonin levels and platelet counts associated with liver regeneration such as whole liver volume and hepatic graft weight (GW) were retrospectively collected from the database and analyzed.
Results. The remnant liver volume rate of RL grafts was smaller than that of LL+C grafts (45.4% vs 64.7%; P < .001). The regeneration rate at 7 days after surgery did not differ between the 2 groups (123% vs 122%). The serotonin levels and platelet counts decreased after surgery until postoperative day 3, then increased thereafter. The platelet counts and serotonin levels of LL+C donors were significantly higher than those of RL donors.
Conclusions. Our findings suggest that platelets and serotonin play a pivotal role in initiating liver regeneration in the remnant liver..
1086. Takeshi Kurihara, Yo-Ichi Yamashita, Yoshihiro Yoshida, Kazuki Takeishi, Shinji Itoh, Norifumi Harimoto, Tomoharu Yoshizumi, Ken Shirabe, Tetsuo Ikeda, Yoshihiko Maehara, Indocyanine Green Fluorescent Imaging for Hepatic Resection of the Right Hepatic Vein Drainage Area., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2015.05.009, 221, 3, e49-53-53, 2015.09.
1087. Takeo Toshima, Toru Ikegami, Yoshihiro Matsumoto, Shohei Yoshiya, Norifumi Harimoto, Yo-ichi Yamashita, Tomoharu Yoshizumi, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, One-step venous reconstruction using the donor's round ligament in right-lobe living-donor liver transplantation., Surgery today, 10.1007/s00595-014-1004-3, 45, 4, 522-5, 2015.04, We herein report the use of an opened round ligament as a venous patch graft for inferior right hepatic vein (IRHV) reconstruction and anastomosis to the inferior vena cava (IVC) in living-donor liver transplantation (LDLT) using a right-lobe (RL) graft. After laparotomy, the donor's round ligament was harvested and opened, and the semi-transparent umbilical vein, which was 7.0 cm in length and 3.0 cm in width, was carefully trimmed on the back table for use as a patch graft. The right hepatic vein of the graft was anastomosed to the harvested patch, and the IRHV was anastomosed to an independent hole made in the wall on the other side of the patch, to form a bridged vascular patch for anastomosis to the IVC. The interposition graft filled promptly and provided a good outflow from the posterior segment. This is the first report of venous reconstruction using a donor's round ligament graft in RL-LDLT..
1088. Norifumi Harimoto, Tetsuo Ikeda, Kazuki Takeishi, Shinji Itoh, Yo-Ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Outcomes After Laparoscopic Hepatectomy in the Semi-prone Position for Hepatocellular Carcinoma Located in Segment 6, 7, or 8., Anticancer research, 35, 7, 4167-70, 2015.07, BACKGROUND: This retrospective study investigated outcomes after laparoscopic hepatectomy in the semi-prone position compared to open hepatectomy in the conventional supine position, for HCC (hepatocellular carcinoma) located in segment 6, 7, or 8. PATIENTS AND METHODS: Patients were divided into two groups according to the surgical approach. The clinicopathological and surgical outcomes were analyzed. RESULTS: There were no significant differences in patient-related or tumor-related factors between the two groups. The laparoscopic-hepatectomy group had significantly less blood loss, fewer postoperative complications, and a shorter hospital stay than the open-hepatectomy group. There were no in-hospital deaths. The postoperative change in the serum C-reactive protein was a significantly larger decrease in the group treated with laparoscopic hepatectomy than that in the open-hepatectomy group. CONCLUSION: Laparoscopic hepatectomy in the semi-prone position for HCC is safe and minimally invasive, and can reduce intraoperative bleeding, postoperative complications, and hospital stay compared to open hepatectomy..
1089. Hideaki Uchiyama, Kazutoyo Morita, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Kenji Takenaka, Yoshihiko Maehara, Pancreatic Transection Using Tape Sling and Ultrasonic Aspirator Dissection Technique in Pancreaticoduodenectomy and Distal Pancreatectomy., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2015.08.005, 221, 5, e91-5-5, 2015.11.
1090. Yuichiroh Umemoto, Shinji Okano, Yoshihiro Matsumoto, Hidekazu Nakagawara, Rumi Matono, Shohei Yoshiya, Yo-Ichi Yamashita, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Mamoru Harada, Shinichi Aishima, Yoshinao Oda, Ken Shirabe, Yoshihiko Maehara, Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy., Journal of gastroenterology, 10.1007/s00535-014-0933-3, 50, 1, 65-75, 2015.01, BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Surgery is potentially curative, but high recurrence rates worsen patient prognosis. The interaction between the proteins programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) is an important immune checkpoint. The significance of PD-L1 expression and human leukocyte antigen class I (HLA class I), recognized by CD8 T cells, in the prognosis of patients with HCC remains to be determined. METHODS: We assessed the levels of PD-L1 and HLA class I expression on HCC samples from 80 patients who had undergone hepatectomy at our institution, and evaluated the correlations between PD-L1 and HLA class I expression and patient prognosis. RESULTS: High HLA class I expression was correlated with significantly better recurrence-free survival (RFS), but not overall survival (OS). Multivariate analysis showed that high HLA class I expression was an independent predictor of improved RFS. Low expression of PD-L1 on HCC tended to predict better OS, but the difference was not statistically significant. PD-L1 expression on HCC correlated with the number of CD163-positive macrophages and HLA class I expression with CD3-positive cell infiltration. Univariable and multivariable analyses showed that combined PD-L1 low/HLA class I high expression on HCCs was prognostic for improved OS and RFS. CONCLUSIONS: PD-L1 status may be a good predictor of prognosis in HCC patients with high HLA class I expression. Novel therapies targeting the PD-L1/PD-1 pathway may improve the prognosis of patients with HCC..
1091. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Akinobu Taketomi, Yoshihiko Maehara, Small-for-Size Syndrome, Transplantation of the Liver: Third Edition, 10.1016/B978-1-4557-0268-8.00055-5, 719-728, 2015.01.
1092. Qingjiang Hu, Kazuki Takeishi, Yo-Ichi Yamashita, Tetsuo Ikeda, Huanlin Wang, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Splenectomy Followed by Hepatectomy for Hepatocellular Carcinoma with Hypersplenism and Portal Hypertension Caused by Macroglobulinemia., Anticancer research, 35, 7, 4077-81, 2015.07, AIM: To describe a patient with hepatocellular carcinoma (HCC), accompanied by hypersplenism and portal hypertension caused by macroglobulinemia, who underwent splenectomy followed by hepatectomy. CASE REPORT: A 74-year-old man was admitted to our Hospital. He had previously developed primary macroglobulinemia, which had been completely cured by chemotherapy. At admission, he had a low platelet count (52 × 10(3)/μl), and his liver function was impaired. Imaging showed a 5-cm-sized tumor, an esophageal varix, and splenomegaly, but not liver cirrhosis. The patient underwent splenectomy for hypersplenism and portal hypertension; the weight of his spleen was 2,400 g. After splenectomy, his platelet count increased to 259 × 10(3)/μl and his liver function was improved. He safely underwent hepatectomy for HCC. The patient was discharged 14 days later without morbidity. CONCLUSION: These findings suggest that hepatectomy following splenectomy for hypersplenism and portal hypertension caused by macroglobulinemia, may effectively cure HCC in patients with liver dysfunction and thrombocytopenia..
1093. Hideyuki Konishi, Ken Shirabe, Hidekazu Nakagawara, Norifumi Harimoto, Yo-Ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshinao Oda, Yoshihiko Maehara, Suppression of silent information regulator 1 activity in noncancerous tissues of hepatocellular carcinoma: Possible association with non-B non-C hepatitis pathogenesis., Cancer science, 10.1111/cas.12653, 106, 5, 542-9, 2015.05, Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+) )-dependent protein deacetylase. In mice, mSirt1 deficiency causes the onset of fatty liver via regulation of the hepatic nutrient metabolism pathway. In this study, we demonstrate SIRT1 expression, activity and NAD(+) regulation using noncancerous liver tissue specimens from hepatocellular carcinoma patients with non-B non-C (NBNC) hepatitis. SIRT1 expression levels were higher in NBNC patients than in healthy donors, while SIRT1 histone H3K9 deacetylation activity was suppressed in NBNC patients. In the liver of hepatitis patients, decreased NAD(+) amounts and its regulatory enzyme nicotinamide phosphoribosyltransferase expression levels were observed, and this led to inhibition of SIRT1 activity. SIRT1 expression was associated with HIF1 protein accumulation in both the NBNC liver and liver cancer cell lines. These results may indicate that the NBNC hepatitis liver is exposed to hypoxic conditions. In HepG2 cells, hypoxia induced inflammatory chemokines, such as CXCL10 and MCP-1. These inductions were suppressed in rich NAD(+) condition, and by SIRT1 activator treatment. In conclusion, hepatic SIRT1 activity was repressed in NBNC patients, and normalization of NAD(+) amounts and activation of SIRT1 could improve the inflammatory condition in the liver of NBNC hepatitis patients..
1094. K. Takeishi, T. Ikegami, T. Yoshizumi, S. Itoh, N. Harimoto, N. Harada, E. Tsujita, Y. Kimura, Y. Yamashita, K. Saeki, E. Oki, K. Shirabe, Y. Maehara, Thymoglobulin for Steroid-Resistant Immune-Mediated Graft Dysfunction During Simeprevir-Based Antiviral Treatment for Post-Transplantation Hepatitis C: Case Report, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2014.11.056, 47, 3, 794-795, 2015.04, Introduction. Immune-mediated graft dysfunction (IGD), a recently established disease entity with unfavourable outcome, is an antigraft immune reaction during interferon-based antiviral treatment for hepatitis C virus (HCV) infection after liver transplantation (LT). We report a case having steroid-resistant acute cellular rejection (ACR) type IGD, which was successfully treated using thymoglobulin.
Case Report. A 56-year-old woman with recurrent HCV after LT was commenced on antiviral treatment including simeprevir, pegylated-interferon (IFN) 2a, and ribavirin. A negative serum HCV-RNA was confirmed after 4 weeks. After 12 weeks of therapy, severe liver dysfunction developed, despite a constantly negative HCV-RNA. Liver biopsy revealed portal and periportal inflammatory infiltrates including numerous eosinophils, lymphocytes, and bile duct damages, indicating ACR. IFN therapy was ceased, and she was treated with steroid pulse treatment, followed by high-level immunosuppression maintenance. However, ACR was irremediable. Thereafter she was treated with thymoglobulin (75 mg/d for 5 days). Her serum alanine aminotransaminase and total bilirubin levels decreased immediately, and her liver biopsy specimen showed no activity. During these periods of the treatment, the HCV-RNA became positive and the liver enzyme elevated, but other liver function tests still remained within normal range.
Conclusion. Thymoglobulin could be the best choice in steroid-resistant IGD during antiviral treatment for post-transplantation recurrent hepatitis C..
1095. T. Ikegami, T. Yoshizumi, Y. Soejima, N. Harimoto, S. Itoh, K. Takeishi, H. Uchiyama, H. Kawanaka, Y. I. Yamashita, E. Tsujita, N. Harada, E. Oki, H. Saeki, Y. Kimura, K. Shirabe, Y. Maehara, Triple therapy using direct-acting agents for recurrent hepatitis C after liver transplantation: A single-center experience, Transplantation Proceedings, 10.1016/j.transproceed.2014.10.058, 47, 3, 730-732, 2015.04, Background Hepatitis C viral graft reinfection is almost a universal event after liver transplantation with consequent disease progression. Methods We applied triple therapy (n = 21) with the use of telaprevir (TVR
n = 12) or simeprevir (SVR
n = 9). Results TVR was given at the dose 1,500 mg daily (n = 11) with reduced dose of cyclosporine at 25% to 50%, and SVR was given at the dose 100 mg daily with unadjusted cyclosporine, followed by 12 weeks of dual therapy. The early viral response was achieved in 91.7% (n = 11), end of treatment response rate was 91.7% (n = 11), and sustained viral response rate was 83.3% (n = 10) in the TVR group, and respective rates were 88.9% (n = 8), 77.8% (n = 7), and 77.8% (n = 7) in the SVR group. Although granulocyte colony-stimulating factor was not given in the patients with triple therapy, blood transfusion was performed in 7 cases (58.3%) in the TVR group and 1 case (11.1%) in the SVR group. Interferon-mediated graft dysfunction was observed in 4 cases (33.3%) in the TVR group and 3 cases (33.3%) in the SVR group, respectively. The cumulative viral clearance rates in triple (n = 21) and dual (n = 105) therapy were 95.0% and 18.1% at 12 weeks, and 95.0% and 40.0%, respectively, at 24 weeks (P <
.01). Conclusions Although careful monitoring for possible adverse events is required during treatment, triple therapy with the use of direct-acting agents are very effective in treating hepatitis C after liver transplantation..
1096. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Tomoharu Yoshizumi, Yo-Ichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, A high MELD score, combined with the presence of hepatitis C, is associated with a poor prognosis in living donor liver transplantation., Surgery today, 10.1007/s00595-013-0523-7, 44, 2, 233-40, 2014.02, PURPOSE: The feasibility of performing living donor liver transplantation (LDLT) for patients with high end-stage liver disease (MELD) scores needs to be assessed. METHODS: A total of 357 patients who underwent LDLT were included in this analysis. RESULTS: Overall, 46 patients had high MELD scores (≥ 25) and their graft survival was similar to that in patients with low MELD scores (<25; n = 311; p = 0.395). However, among patients with high MELD scores, a multivariate analysis showed that the presence of hepatitis C (p = 0.013) and LDLT in Era-I (p = 0.036) was significantly associated with a poorer prognosis. Among patients with hepatitis C (n = 155), the 5-year graft survival rate was significantly lower in patients with high MELD scores (33.7 %, p < 0.001) than in patients with low MELD scores. The 5-year graft survival rate was significantly lower in patients in Era-I (n = 119) compared with those in Era-II/III when stratified by low (73.0 vs. 82.5 %, p = 0.040) and high (55.0 vs. 86.1 %, p = 0.023) MELD scores. Among the patients with high MELD scores, those with hepatitis C and LDLT in Era-I had the worst 5-year graft survival rate (14.3, p < 0.001). CONCLUSION: The graft outcomes in patients with high MELD scores and the presence of hepatitis C were found to be particularly poor..
1097. T. Toshima, T. Ikegami, K. Kimura, N. Harimoto, Y. Yamashita, T. Yoshizumi, Y. Soejima, T. Ikeda, K. Shirabe, Y. Maehara, Application of Postoperative Model for End-Stage Liver Disease Scoring System for Evaluating Liver Graft Function After Living Donor Liver Transplantation, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2013.09.034, 46, 1, 81-86, 2014.01, Background. The Model for End-Stage Liver Disease (MELD) score has been validated to predict the mortality rate of patients with various chronic liver diseases on the waiting list for liver transplantation (LT). The aim of this study was to assess the value of the postoperative MELD scoring system as an early postoperative predictor of outcome in patients undergoing living donor LT (LDLT).
Methods. A retrospective analysis of 217 adult-to-adult LDLT patients was performed. The values of the MELD score on various postoperative days (PODs) as predictors of graft loss within 6 months after LDLT were examined by calculating the areas under the receiver operating characteristic (AUROC) curves. The 6-months graft survival rates were compared between patients with (n = 22) and without (n = 195) graft loss. Univariate and multivariate analyses were performed to identify the factors associated with mortality.
Results. The MELD score on POD2 was a predictor of graft loss, with an AUROC c-statistic of 0.779, a specificity of 79.5%, and a sensitivity of 68.2% at optimal cutoff, whereas the preoperative MELD score c-statistic was 0.605 with 44.6% sensitivity. Multivariate analyses for postoperative mortality revealed MELD-POD2 >= 19 (odds ratio, 5.601; 95% confidence interval [CI], 1.395-4.508; P = .0009) as an independent predictor of short-term graft loss following LDLT, in addition to preoperative hospitalization status. Later MELD POD scores were also predictive of graft loss.
Conclusions. The early postoperative MELD scoring system is feasible as an index for prediction of postoperative mortality following LDLT..
1098. Takeo Toshima, Ken Shirabe, Yoshihiro Matsumoto, Shohei Yoshiya, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Yoshihiko Maehara, Autophagy enhances hepatocellular carcinoma progression by activation of mitochondrial β-oxidation., Journal of gastroenterology, 10.1007/s00535-013-0835-9, 49, 5, 907-16, 2014.05, BACKGROUND: Several types of cancers, including hepatocellular carcinoma (HCC), show resistance to hypoxia and nutrient starvation. Autophagy is a means of providing macromolecules for energy generation under such stressed-conditions. The aim of this study was to clarify the role of autophagy in HCC development under hypoxic conditions. METHODS: The expression of microtubule-associated protein 1 light chain 3 (LC3), which is a key gene involved in autophagosome formation, was evaluated in human HCC using immunohistochemistry and western blot. The relationship between LC3 and hypoxia-induced factor 1α (HIF1α) expression was examined using real-time PCR. In addition, human HCC cell line Huh7 was treated with pharmacological autophagy-inhibitor and inactive mutant of Atg4B (Atg4B(C74A)) under hypoxic condition to evaluate the effects of hypoxia-induced autophagy on cell survival, intracellular ATP, and mitochondrial β-oxidation. RESULTS: LC3 was significantly highly expressed in HCC as compared with noncancerous tissues. LC3 expression, correlated with HIF1α expression, was also significantly correlated with tumor size, and only in the context of large tumors, was an independent predictor of HCC recurrence after surgery. In addition, Huh7 treated with autophagy-inhibitor under hypoxia had lower viability, with low levels of intracellular ATP due to impaired mitochondrial β-oxidation. CONCLUSIONS: Autophagy in HCC works to promote HIF1α-mediated proliferation through the maintenance of intracellular ATP, depending on the activation of mitochondrial β-oxidation. These findings demonstrated the feasibility of anti-autophagic treatment as a potential curative therapy for HCC, and improved understanding of the factors determining adaptive metabolic responses to hypoxic conditions..
1099. Toru Ikegami, Yuki Bekki, Daisuke Imai, Tomoharu Yoshizumi, Mizuki Ninomiya, Hiromitsu Hayashi, Yo-Ichi Yamashita, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Clinical outcomes of living donor liver transplantation for patients 65 years old or older with preserved performance status., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23825, 20, 4, 408-15, 2014.04, The purpose of this study was to determine the outcomes of living donor liver transplantation (LDLT) for elderly recipients. We reviewed 411 adult-to-adult LDLT cases, including 46 recipients who were 65 years old or older and 365 recipients who were less than 65 years old. The elderly group had a higher proportion of females (P = 0.04) and a smaller body surface area (P < 0.001) and more frequently underwent transplantation because of hepatitis C (P < 0.001) or hepatocellular carcinoma (P < 0.001). Elderly patients had less advanced liver disease with lower Model for End-Stage Liver Disease (MELD) scores (P = 0.02) and preserved health without the need for prolonged hospitalization (P < 0.01). The transplanted graft volume/standard liver volume ratios were similar for the 2 groups (P = 0.22). The elderly group had fewer episodes of acute rejection (P = 0.03) but had more neuropsychiatric complications (P = 0.01). The 5- and 10-year graft survival rates were comparable for the elderly group (89.8% and 77.8%, respectively) and the younger group (79.4% and 72.9%, respectively; P = 0.21). Seven recipients were 70 years old or older, and they had a mean MELD score of 15.6 ± 5.2; 6 of these patients were treated as outpatients before LDLT. All were alive after LDLT and showed good compliance with medical management with a mean follow-up of 5.7 ± 3.0 years. In conclusion, LDLT can be safely performed and has acceptable long-term outcomes for low-risk elderly recipients with preserved performance status..
1100. Kensuke Kudou, Mizuki Ninomiya, Tomohiro Iguchi, Norifumi Harimoto, Shinji Itoh, Noboru Harada, Kazuki Takeishi, Yo-Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Cystic liver infection after living donor liver transplantation: a case report., Case reports in gastroenterology, 10.1159/000363375, 8, 2, 169-74, 2014.05, There are no reports of cystic liver infection after liver transplantation. Herein, we report a rare case of cystic liver graft infection after living donor liver transplantation (LDLT). The patient was a 24-year-old man with primary sclerosing cholangitis who underwent right lobe graft LDLT. Preoperative abdominal computed tomography (CT) revealed a liver cyst at segment 8 of the donor liver. Biliary reconstruction was performed with hepaticojejunostomy. The postoperative course was uneventful until the patient developed a high fever and abdominal pain 15 months after LDLT. Abdominal contrast CT revealed abscess formation. Percutaneous drainage of the cyst was performed and purulent liquid was drained. The fever gradually subsided after treatment. On follow-up CT, the size of the infected liver cyst was decreased. Clinicians should be aware of the potential for cystic liver infection when using grafts with liver cysts, particularly when biliary reconstruction is performed with hepaticojejunostomy..
1101. T. Yoshizumi, K. Shirabe, T. Ikegami, N. Yamashita, Y. Mano, S. Yoshiya, R. Matono, N. Harimoto, H. Uchiyama, T. Toshima, Y. Maehara, Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis, TRANSPLANT INFECTIOUS DISEASE, 10.1111/tid.12188, 16, 2, 225-231, 2014.04, BackgroundSeveral studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT).
MethodsBlood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650mg/dL within 7days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3months after LDLT were analyzed.
ResultsFifty (28.2%) recipients experienced bacterial infection within 3months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15mmHg were independent risk factors for developing bacterial infection within 3months of LDLT (P < 0.0001 P=0.0008, and P=0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3months. Hypogammaglobulinemia, operative time >14h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P=0.009, P=0.001, P=0.003, and P=0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively.
ConclusionsHypogammaglobulinemia within 7days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis..
1102. Mizuki Ninomiya, Shinichi Aishima, Tomoharu Yoshizumi, Toru Ikegami, Huanlin Wang, Norifumi Harimoto, Shinji Ito, Hideaki Uchiyama, Yuji Soejima, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Different histological sequelae of immune-mediated graft dysfunction after interferon treatment in transplanted dual grafts from living donors., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23996, 20, 12, 1520-2, 2014.12.
1103. Shinji Itoh, Ken Shirabe, Yoshihiro Matsumoto, Shohei Yoshiya, Jun Muto, Norifumi Harimoto, Yo-Ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Akihiro Nishie, Yoshihiko Maehara, Effect of body composition on outcomes after hepatic resection for hepatocellular carcinoma., Annals of surgical oncology, 10.1245/s10434-014-3686-6, 21, 9, 3063-8, 2014.09, PURPOSE: To evaluate the effect of body composition on outcomes after hepatic resection for patients with hepatocellular carcinoma (HCC). METHODS: We performed 190 hepatic resections for HCC and divided the patients into 2 groups on the basis of visceral fat area (VFA), assessed by computed tomographic measurement at the level of the umbilicus, into high VFA (H-VFA) (n = 106) and low VFA (L-VFA) (n = 84) groups. We compared the surgical outcomes between the two groups. RESULTS: L-VFA was significantly correlated with a lower body mass index, sarcopenia, lower serum albumin, and liver cirrhosis. There was no difference in the incidence of postoperative complications and mortality between the 2 groups. Patients in the L-VFA group had a significantly poorer prognosis than those in the H-VFA group in terms of both overall (P = 0.043) and recurrence-free (P = 0.001) survival. The results of multivariate analysis showed that sarcopenia rather than L-VFA was an independent and prognostic indicator after hepatic resection with HCC. CONCLUSIONS: Body composition is an important factor affecting cancer outcomes after hepatic resection for HCC in Japan..
1104. H. Kawanaka, T. Akahoshi, N. Kinjo, T. Iguchi, M. Ninomiya, Y-I Yamashita, T. Ikegami, T. Yoshizumi, K. Shirabe, Y. Maehara, Effect of laparoscopic splenectomy on portal haemodynamics in patients with liver cirrhosis and portal hypertension, BRITISH JOURNAL OF SURGERY, 10.1002/bjs.9622, 101, 12, 1585-1593, 2014.11, Background: The effect of splenomegaly in patients with liver cirrhosis and portal hypertension is not fully understood. This study was designed to determine the effect of laparoscopic splenectomy on portal haemodynamics in these patients.
Methods: Patients with liver cirrhosis and portal hypertension who underwent laparoscopic splenectomy in Kyushu University Hospital from January 2006 to March 2009 were evaluated retrospectively. Correlations between splenic size and portal haemodynamics, and changes in portal haemodynamics and in levels of the vasoactive agents endothelin (ET) 1 and nitric oxide metabolites (NOx) before and 7-10 days after laparoscopic splenectomy were analysed.
Results: Portal venous (PV) blood flow, PV cross-sectional area and PV congestion index correlated significantly with splenic size (P < 0.050). All three were significantly reduced following splenectomy in 59 patients. The hepatic venous pressure gradient, measured in 18 patients, decreased by 25 per cent after splenectomy (P < 0.001). Portal vascular resistance was also reduced, by 21 per cent (P = 0.009). The peripheral blood concentration of ET-1 decreased from 2.95 to 2.11 pg/ml (P < 0.001), and that of NOx tended to decrease (from 29.2 to 25.0 pg/ml; P = 0.068). In hepatic venous blood, the level of ET-1 decreased from 2.37 to 1.83 pg/ml (P = 0.006), whereas NOx concentration tended to increase (from 24.5 to 30.9 pg/ml; P = 0.067).
Conclusion: In patients with liver cirrhosis and portal hypertension, splenectomy reduced portal venous pressure. A decrease in splanchnic blood flow, by eliminating splenic blood flow, and reduction in intrahepatic vascular resistance, by normalizing hepatic concentrations of ET-1 and NOx, may both have contributed..
1105. Yo-Ichi Yamashita, Yuki Bekki, Daisuke Imai, Toru Ikegami, Tomoharu Yoshizumi, Tetsuo Ikeda, Hirofumi Kawanaka, Akihiro Nishie, Ken Shirabe, Yoshihiko Maehara, Efficacy of postoperative anticoagulation therapy with enoxaparin for portal vein thrombosis after hepatic resection in patients with liver cancer., Thrombosis research, 10.1016/j.thromres.2014.07.038, 134, 4, 826-31, 2014.10, BACKGROUNDS: Enoxaparin, low-molecular-weight heparin, has become a routine thromboprophylaxis in general surgery. STUDY DESIGN: A retrospective cohort study was performed in 281 patients who underwent hepatic resections for liver cancers from 2011 to 2013. These patients were divided into two groups; an enoxaparin (-) group (n=228) and an enoxaparin (+) group (n=53). Short-term surgical results including venous thromboembolism (VTE) and portal vein thrombosis (PVT) were compared. RESULTS: In the enoxaparin (+) group, the patients' age (65 vs. 69 years; p=0.01) and BMI (22.9 vs. 24.4; p<0.01) were significantly higher. According to the symptomatic VTE, symptomatic pulmonary embolism occurred in one patient (0.4%) in the enoxaparin (-) group, but the complication rate was not significantly different (p=0.63). The complication rate of PVT was significantly lower in the enoxaparin (+) group (10 vs. 2%; p=0.04). The independent risk factors for PVT were an operation time ≥ 300 minutes (Odds ratio 6.66) and non-treatment with enoxaparin (Odds ratio 2.49). CONCLUSIONS: Postoperative anticoagulant therapy with enoxaparin could prevent PVT in patients who underwent hepatic resection for liver cancers..
1106. Hideki Ijichi, Ken Shirabe, Yoshihiro Matsumoto, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Kazutoyo Morita, Takeo Toshima, Yohei Mano, Yoshihiko Maehara, Evaluation of graft stiffness using acoustic radiation force impulse imaging after living donor liver transplantation., Clinical transplantation, 10.1111/ctr.12457, 28, 11, 1256-62, 2014.11, Acoustic radiation force impulse (ARFI) imaging is an ultrasound-based modality to evaluate tissue stiffness using short-duration acoustic pulses in the region of interest. Virtual touch tissue quantification (VTTQ), which is an implementation of ARFI, allows quantitative assessment of tissue stiffness. Twenty recipients who underwent living donor liver transplantation (LDLT) for chronic liver diseases were enrolled. Graft types included left lobes with the middle hepatic vein and caudate lobes (n = 11), right lobes (n = 7), and right posterior segments (n = 2). They underwent measurement of graft VTTQ during the early post-LDLT period. The VTTQ value level rose after LDLT, reaching a maximum level on postoperative day 4. There were no significant differences in the VTTQ values between the left and right lobe graft types. Significant correlations were observed between the postoperative maximum value of VTTQ and graft volume-to-recipient standard liver volume ratio, portal venous flow to graft volume ratio, and post-LDLT portal venous pressure. The postoperative maximum serum alanine aminotransferase level and ascites fluid production were also significantly correlated with VTTQ. ARFI may be a useful diagnostic tool for the noninvasive and quantitative evaluation of the severity of graft dysfunction after LDLT..
1107. Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Frequent plasma cell hepatitis during telaprevir-based triple therapy for hepatitis C after liver transplantation., Journal of hepatology, 10.1016/j.jhep.2013.10.037, 60, 4, 894-6, 2014.04.
1108. H. Konishi, T. Motomura, Y. Matsumoto, N. Harimoto, T. Ikegami, T. Yoshizumi, Y. Soejima, K. Shirabe, T. Fukuhara, Y. Maehara, Interferon-lambda4 genetic polymorphism is associated with the therapy response for hepatitis C virus recurrence after a living donor liver transplant, JOURNAL OF VIRAL HEPATITIS, 10.1111/jvh.12154, 21, 6, 397-404, 2014.06, The standard therapy against hepatitis C virus (HCV) recurrence postliver transplantation includes interferon (IFN) and ribavirin. IFNL4 ss469415590 polymorphism has been reported as a novel predictor of the response to IFN therapy for chronic HCV infection. We examined the impact of IFNL4 polymorphism on the responsiveness to IFN therapy after liver transplantation. Tissue specimens were collected from 80 HCV-infected recipients and 78 liver donors, and their IFNL4 ss469415590 genotype, hepatic IFNL4 and interferon-stimulated genes' mRNA expression levels were examined. The association of the polymorphism and expression levels in terms of the IFN therapy response to HCV recurrence was analysed. Most individuals who had rs8099917 risk alleles also had ss469415590 risk alleles (R-2=0.9). Sustained virological response (SVR) rates were higher in both liver graft recipients and transplants with ss469415590 TT/TT alleles than in those with the risk G allele (P=0.003 and P=0.005, respectively). In recipients with ss469415590 TT/TT, IFNL4 TT mRNA levels showed no significant differences between livers of patients who responded to therapy and those who did not (P=0.4). In recipients with the risk G allele, IFNL4 G mRNA expression levels were significantly lower in SVR patients than in non-SVR patients (P=0.02). Hepatic interferon stimulable genes and IFNL4 mRNA expression were correlated. Our findings suggest that analysing the ss469415590 genotype and IFNL4 G expression provides a novel prediction strategy for the possible response to IFN therapy after liver transplantation..
1109. Tetsuo Ikeda, Takao Toshima, Norifumi Harimoto, Youichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Laparoscopic liver resection in the semiprone position for tumors in the anterosuperior and posterior segments, using a novel dual-handling technique and bipolar irrigation system., Surgical endoscopy, 10.1007/s00464-014-3469-y, 28, 8, 2484-92, 2014.08, BACKGROUND: Hepatic tumors in the lower edge and lateral segments are commonly treated by laparoscopic liver resection. Tumors in the anterosuperior and posterior segments are often large and locally invasive, and resection is associated with a higher risk of insufficient surgical margins, massive intraoperative bleeding, and breaching of the tumor. Laparoscopic surgery for such tumors often involves major hepatectomy, including resection of a large volume of normal liver tissue. We developed a novel method of laparoscopic resection of tumors in these segments with the patient in the semiprone position, using a dual-handling technique with an intercostal transthoracic port. The aim of this study was to evaluate the safety and usefulness of our technique. METHODS: Of 160 patients who underwent laparoscopic liver resection at our center from June 2008 to May 2013, we retrospectively reviewed those with tumors in the anterosuperior and posterior segments. Patients were placed supine or semilateral during surgery until January 2010 and semiprone from February 2010. RESULTS: Before the introduction of the semiprone position in February 2010, a total of 7 of 40 patients (17.5%) with tumors in the anterosuperior and posterior segments underwent laparoscopic liver resection, and after introduction of the semiprone position, 69 of 120 patients (57.5%) with tumors in the anterosuperior and posterior segments underwent laparoscopic liver resection (P < 0.001). There were no conversions to open surgery, reoperations, or deaths. The semiprone group had a significantly higher proportion of patients who underwent partial resection or segmentectomy of S7 or S8, lower intraoperative blood loss, and shorter hospital stay than the supine group (all P < 0.05). Postoperative complication rates were similar between groups. CONCLUSIONS: Laparoscopic liver resection in the semiprone position is safe and increases the number of patients who can be treated by laparoscopic surgery without increasing the frequency of major hepatectomy..
1110. Sho Nishimura, Hiroshi Saeki, Toru Ikegami, Koji Ando, Yo-Ichi Yamashita, Eiji Oki, Tomoharu Yoshizumi, Masaru Morita, Ken Shirabe, Yoshihiko Maehara, Living donor liver transplantation followed by total gastrectomy--a two-stage planed operative strategy for early gastric cancer concomitant with decompensated liver cirrhosis., Anticancer research, 34, 8, 4307-10, 2014.08, AIM: With the recent popularization of living donor liver transplantation (LDLT), providing treatment for comorbidities in LDLT recipients has become important. We report the first case of a patient who was successfully treated with LDLT followed by total gastrectomy for early gastric cancer concomitant with decompensated liver cirrhosis. CASE REPORT: A 64-year-old female was admitted for the treatment of severe liver cirrhosis. The patient's preoperative liver function was evaluated as Child-Pugh classification grade C. Upper gastrointestinal endoscopy revealed early gastric cancer. We first performed LDLT to improve her liver function and coagulopathy. Nineteen days after the LDLT, we performed total gastrectomy. RESULTS: The patient's postoperative course was uneventful and she left our hospital on the 18th day after gastrectomy. The final pathological diagnosis of gastric cancer was Stage IA. CONCLUSION: Aggressive and adequate surgical strategy including LDLT is effective as curative treatment in patients with controllable malignancy concomitant with severe liver dysfunction..
1111. Toru Ikegami, Tomoharu Yoshizumi, Yo-ichi Yamashita, Noboru Harada, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Obstructing Spontaneous Major Shunt Vessels Is or Might Not Be Mandatory in Living Donor Liver Transplantation: The Authors' Reply, TRANSPLANTATION, 10.1097/TP.0000000000000096, 97, 9, E53-E53, 2014.05.
1112. Toru Ikegami, Tomoharu Yoshizumi, Yo-Ichi Yamashita, Noboru Harada, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Obstructing spontaneous major shunt vessels is or might not be mandatory in living donor liver transplantation: the authors' reply., Transplantation, 10.1097/TP.0000000000000096, 97, 9, e53, 2014.05.
1113. Shohei Yoshiya, Ken Shirabe, Hidekazu Nakagawara, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Yo-Ichi Yamashita, Norifumi Harimoto, Akihiro Nishie, Takeharu Yamanaka, Yoshihiko Maehara, Portal vein thrombosis after hepatectomy., World journal of surgery, 10.1007/s00268-013-2440-8, 38, 6, 1491-7, 2014.06, BACKGROUND: Although various complications after hepatectomy have been reported, there have been no large studies on postoperative portal vein thrombosis (PVT) as a complication. This study evaluated the incidence, risk factors, and clinical outcomes of PVT after hepatectomy. METHODS: The preoperative and postoperative clinical characteristics of patients who underwent hepatectomy were retrospectively analyzed. RESULTS: A total of 208 patients were reviewed. The incidence of PVT after hepatectomy was 9.1 % (n = 19), including main portal vein (MPV) thrombosis (n = 7) and peripheral portal vein (PPV) thrombosis (n = 12). Patients with MPV thrombosis had a significantly higher incidence of right hepatectomy (p < 0.001), larger resection volume (p = 0.003), and longer operation time (p = 0.021) than patients without PVT (n = 189). Multivariate analysis identified right hepatectomy as a significant independent risk factor for MPV thrombosis (odds ratio 108.9; p < 0.001). Patients with PPV thrombosis had a significantly longer duration of Pringle maneuver than patients without PVT (p = 0.002). Among patients who underwent right hepatectomy, those with PVT (n = 6) had a significantly lower early liver regeneration rate than those without PVT (n = 13; p = 0.040), and those with PVT had deterioration of liver function on postoperative day 7. In all patients with MPV thrombosis who received anticoagulation therapy, PVT subsequently resolved. CONCLUSIONS: Postoperative PVT after hepatectomy is not rare. It is closely related to delayed recovery of liver function and delayed liver regeneration..
1114. Daisuke Imai, Toru Ikegami, Takeo Toshima, Tomoharu Yoshizumi, Yo-ichi Yamashita, Mizuki Ninomiya, Norifumi Harimoto, Shinji Itoh, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Preemptive thoracic drainage to eradicate postoperative pulmonary complications after living donor liver transplantation., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.09.006, 219, 6, 1134-42, 2014.12, BACKGROUND: Thoracic fluid retention after living donor liver transplantation (LDLT) has various negative consequences, including atelectasis, pneumonia, and respiratory distress or failure. STUDY DESIGN: We analyzed the clinical impact of preemptive thoracic drainage in 177 patients undergoing adult-to-adult LDLT for chronic liver diseases at a single center. Recipients were divided into 2 time periods. The earlier cohort (n = 120) was analyzed for risk factors for postoperative atelectasis retrospectively; the later cohort (n = 57), with a risk factor for postoperative atelectasis, underwent preemptive thoracic drainage prospectively. The incidence of postoperative pulmonary complications was compared between these 2 cohorts. RESULTS: Independent risk factors for atelectasis in earlier cohort were body mass index ≥27 kg/m(2) (p < 0.001), performance status ≥3 (p = 0.003) and model for end-stage liver disease score ≥23 (p = 0.005). The rates of atelectasis (21.1% vs 42.5%, p = 0.005) and pneumonia (1.8% vs 10.0%, p = 0.049) were significantly lower in later than in earlier cohort. Moreover, the mean durations of ICU stay (3.6 ± 0.2 days vs 5.7 ± 0.6 days, p = 0.038) and postoperative oxygen support (5.1 ± 0.8 days vs 7.1 ± 0.5 days, p = 0.037) were significantly shorter in the later than in the earlier cohort. There were no significant differences in the incidence of adverse events associated with thoracic drainages between these 2 cohorts. CONCLUSIONS: Preemptive thoracic drainage for transplant recipients at high risk of postoperative atelectasis could decrease morbidities after LDLT..
1115. Toru Ikegami, Tomoharu Yoshizumi, Masaki Kato, Satomi Yamamoto, Takasuke Fukuhara, Yoshiharu Matsuura, Shota Nakamura, Shinji Itoh, Ken Shirabe, Yoshihiko Maehara, Reduced-dose telaprevir-based triple antiviral therapy for recurrent hepatitis C after living donor liver transplantation., Transplantation, 10.1097/TP.0000000000000166, 98, 9, 994-9, 2014.11, INTRODUCTION: The feasibility of telaprevir-based triple therapy for recurrent hepatitis C after liver transplantation (LT) has not been evaluated in Asian patients. METHODS: Eleven Japanese patients received reduced-dose telaprevir (1500 mg) and adjusted-dose cyclosporine after LT. Six patients were nonresponders and three were transient responders to dual therapy. RESULTS: Rapid viral response, early viral response, end of treatment response, and sustained viral response were achieved in 27.3%, 90.9%, 90.9%, and 81.8% of patients, respectively. One patient had viral breakthrough at week 8 with a T54A mutation in NS3. Deep sequence analysis showed that the T54A mutation reverted to wild-type after stopping telaprevir administration. Seven patients developed severe anemia, and six received blood transfusions (4-20 U). Their hemoglobin and estimated glomerular filtration rate remained significantly lower than pretreatment values at 36 weeks after treatment. Four patients developed plasma cell hepatitis after completing telaprevir treatment, and it was treated by increasing the immunosuppressants. Although the cyclosporine level/dose ratio was 2.7 times higher at week 4 than before treatment, it was 0.7 times lower at week 36. CONCLUSIONS: Reduced-dosed telaprevir-based triple antiviral therapy achieved a high viral clearance rate in Japanese patients after LT. Major adverse events included severe anemia, renal dysfunction, and plasma cell hepatitis..
1116. H. Uchiyama, K. Shirabe, H. Nakagawara, T. Ikegami, T. Toshima, Y. Soejima, T. Yoshizumi, Y.‐I. Yamashita, N. Harimoto, T. Ikeda, Y. Maehara, Revisiting the Safety of Living Liver Donors by Reassessing 441 Donor Hepatectomies: Is a Larger Hepatectomy Complication‐Prone?, American Journal of Transplantation, 10.1111/ajt.12559, 14, 2, 367-374, 2014.02.
1117. Tomoharu Yoshizumi, Toru Ikegami, Koichi Kimura, Hideaki Uchiyama, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Selection of a right posterior sector graft for living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23924, 20, 9, 1089-96, 2014.09, Right posterior sector (RPS) grafts have been used to overcome graft size discrepancies, the major concern of living donor liver transplantation. Previous studies have reported the volumetry-based selection of RPS grafts without anatomical exclusion. We reviewed our data and established selection criteria for RPS grafts. The procurement of RPS grafts [conventional (n = 3) and extended (n = 5)] was performed for 8 of 429 recipients at our center. Extended RPS grafts contained the drainage area of the right hepatic vein. The mean graft weight (GW) according to 3-dimensional computed tomography volumetry was 488 g, and the GW/standard liver weight (SLW) ratio was 42.6%. The mean actual GW was 437 g, and the GW/SLW ratio was 38.4%. One donor exhibited standard bifurcation of the right portal vein (PV) and the left PV, and 2 donors exhibited trifurcation of the left PV, the right anterior portal vein (APV), and the posterior PV. The remaining 5 donors exhibited APV branching from the left PV, which is the most suitable anatomy for RPS grafts. Two recipients died of sepsis or small-for-size graft syndrome. One underwent retransplantation because of an intractable bile leak and fibrosing cholestatic hepatitis. Intractable bile duct (BD) stenosis developed in 4 of the 6 survivors. In conclusion, with the significant complications and potential concerns associated with RPS grafts, these grafts should be used very rarely and with extreme caution. Donors with the standard bifurcation of the PV and the posterior BD running through the dorsal side of the posterior PV are not suitable candidates for RPS grafts. Extended RPS graft procurement is recommended for easier parenchymal transection..
1118. Tomoharu Yoshizumi, Ken Shirabe, Hidekazu Nakagawara, Toru Ikegami, Norifumi Harimoto, Takeo Toshima, Yo-Ichi Yamashita, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara, Skeletal muscle area correlates with body surface area in healthy adults., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12119, 44, 3, 313-8, 2014.03, AIM: Depletion of skeletal muscle mass (sarcopenia) predicts survival in patients with cancer or liver cirrhosis. Recently, many reports have used computed tomography (CT) to measure muscle area to define sarcopenia. However, the definition of sarcopenia using CT has not been fully determined. The aim of this study was to establish formulae to calculate the standard area of skeletal muscle. METHODS: Forty-five healthy adults (24 men and 21 women, aged 21-66 years) who wished to donate part of their liver for transplantation underwent CT. Cross-sectional areas (cm(2) ) of skeletal muscle were measured at the caudal end of the third lumbar vertebra. Regression analysis was performed to establish formulae to calculate the standard area of skeletal muscle. A validation conducted on 30 other healthy adults was performed to check the accuracy of formulae. RESULTS: Men had a median skeletal muscle area of 155.0 cm(2) (range, 114.0-203.0), compared with 111.7 cm(2) (range, 89.8-139.3) in women (P < 0.001). Furthermore, skeletal muscle area significantly correlated with body surface area (BSA) in men (P < 0.0001, r(2)  = 0.60) and women (P < 0.0001, r(2)  = 0.78). The formulae to calculate skeletal muscle area were 126.9 × BSA - 66.2 in men and 125.6 × BSA - 81.1 in women. The estimated muscle area significantly correlated with actual muscle area in men (P = 0.003, r(2)  = 0.64) and women (P = 0.0001, r(2)  = 0.70). CONCLUSION: Sarcopenia can be defined by the difference between measured data and calculated data using our new formulae..
1119. Toru Ikegami, Ken Shirabe, Yo-ichi Yamashita, Tomoharu Yoshizumi, Norifumi Harimoto, Kazuki Takeishi, Eiji Tsujita, Shinji Itoh, Yoshihiko Maehara, Small upper midline incision for living donor hemi-liver graft procurement in adults., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.04.021, 219, 3, e39-43-E43, 2014.09.
1120. Takahiro Tomino, Yo-Ichi Yamashita, Tomohiro Iguchi, Shinji Itoh, Mizuki Ninomiya, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Tetsuo Ikeda, Shinichi Aishima, Ken Shirabe, Yoshihiko Maehara, Spontaneous massive necrosis of hepatocellular carcinoma with narrowing and occlusion of the arteries and portal veins., Case reports in gastroenterology, 10.1159/000362440, 8, 1, 148-55, 2014.01, We herein present the case of a 77-year-old man who had fever and right hypochondriac pain. He visited his doctor and underwent contrast computed tomography (CT), and he was suspected to have a liver abscess. He received an antibiotic treatment and his symptoms soon disappeared, but the tumor did not get smaller and its density on contrast CT image got stronger. He underwent biopsy and moderately differentiated hepatocellular carcinoma (HCC) was found. Extended left hepatic and caudate lobectomy was performed. Histological examination showed moderately differentiated HCC with narrowing and occlusion both in the arteries and portal veins associated with mild chronic inflammation. The mechanisms of spontaneous regression of HCC, such as immunological reactions and tumor hypoxia, have been proposed. In our case, histological examination showed the same findings. However, the mechanism is complex, and therefore further investigations are essential to elucidate it..
1121. Toru Ikegami, Huanlin Wang, Tomoharu Yoshizumi, Takeo Toshima, Shinichi Aishima, Takasuke Fukuhara, Norihiro Furusyo, Kazuhiro Kotoh, Shinji Shimoda, Ken Shirabe, Yoshihiko Maehara, Strategies to treat interferon-induced graft dysfunction after living donor liver transplantation for hepatitis C., Hepatology international, 10.1007/s12072-013-9496-2, 8, 2, 285-92, 2014.04, PURPOSE: Interferon-induced graft dysfunction (IGD) is a poorly defined, unrecognized, but potentially serious condition for patients receiving antiviral drugs after liver transplantation for hepatitis C. METHODS: We evaluated the characteristics of 80 patients who received pegylated interferon-based antiviral treatment for hepatitis C after living donor liver transplantation (LDLT). RESULTS: Eight patients experienced IGD either during (n = 6) or after completing (n = 2) antiviral treatment. Pathological diagnosis included acute cellular rejection (ACR, n = 1), plasma cell hepatitis (PCH, n = 2), PCH plus ACR (n = 3), and chronic rejection (CR, n = 2). One patient with CR initially presented with PCH plus ACR and the other presented with ACR; both had apparent cholestasis. The six patients with ACR or PCH without cholestasis were successfully treated by discontinuing antiviral treatment and increasing immunosuppression, including steroids. By contrast, both of the patients with CR and cholestasis experienced graft loss, despite aggressive treatment. Univariate analysis showed that pegylated interferon-α2a-based treatment (75 vs. 26.4 %, p < 0.01) was the only significant factor for IGD, and was associated with decreased 5-year graft survival (93.4 vs. 71.4 %, p = 0.04). CONCLUSIONS: IGD is a serious condition during or even after antiviral treatment for hepatitis C after LDLT. Early recognition, diagnosis, discontinuation of interferon, and introduction of steroid-based treatment may help to save the graft..
1122. Takeo Toshima, Ken Shirabe, Takasuke Fukuhara, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Shinji Okano, Yoshihiko Maehara, Suppression of autophagy during liver regeneration impairs energy charge and hepatocyte senescence in mice., Hepatology (Baltimore, Md.), 10.1002/hep.27140, 60, 1, 290-300, 2014.07, UNLABELLED: Autophagy is a homeostatic mechanism that regulates protein and organelle turnover and uses the amino acids from degraded proteins to produce adenosine 5'-triphosphate (ATP). We investigated the activity of autophagy-associated pathways in liver regeneration after partial hepatectomy (PHx) in liver-specific autophagy-related gene 5 (Atg5) knockout (KO) mice. Liver regeneration was severely impaired by 70% PHx, with a reduction in postoperative mitosis, but a compensating increase in hepatocyte size. PHx induced intracellular adenosine triphosphate and β-oxidation reduction as well as injured cellular mitochondria. Furthermore, PHx in Atg5 KO mice enhanced hepatic accumulation of p62 and ubiquitinated proteins. These results indicated that reorganization of intracellular proteins and organelles during autophagy was impaired in the regenerating liver of these mice. Up-regulation of p21 was associated with hepatocyte senescence, senescence-associated β-galactosidase expression, irreversible growth arrest, and secretion of senescence-associated molecules, including interleukin (IL)-6 and IL-8. CONCLUSION: These findings indicate that autophagy plays a critical role in liver regeneration and in the preservation of cellular quality, preventing hepatocytes from becoming fully senescent and hypertrophic..
1123. Jun Muto, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Shinichi Aishima, Kousei Ishigami, Yoshikazu Yonemitsu, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara, The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma., Anticancer research, 34, 10, 5313-20, 2014.10, AIM: The apelin-APJ system regulates angiogenesis, and is overexpressed in several types of cancer. The aim of this study was to clarify the role of the apelin-APJ system in the angiogenesis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Expressions of angiogenic factors and vascular markers were investigated in specimens from 90 HCC patients. A subcutaneous HCC tumor mouse model was treated with the APJ antagonist, F13A, and tumor growth and vascular development were assessed. RESULTS: APJ expression was observed in arteriole-smooth muscle. Higher amounts of APJ(+)-arteriole and apelin were detected in tumors (p<0.001 for both). APJ(+)-arteriole and apelin expression were more commonly observed in moderately- and poorly-differentiated than in well-differentiated HCC (p ≤ 0.003). HCC with irregular dilated arteries expressed higher levels of apelin (p=0.012). Tumor growth was inhibited by treatment with F13A (p<0.001), and arterioles were decreased in the treated group (p=0.047), in vivo. CONCLUSION: Apelin-APJ is overexpressed, and works as a signal for arteriogenesis in HCC..
1124. Hiroto Kayashima, Ken Shirabe, Rumi Matono, Shohei Yoshiya, Kazutoyo Morita, Kenji Umeda, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Three-dimensional computed tomography analysis of variations in the middle hepatic vein tributaries: proposed new classification., Surgery today, 10.1007/s00595-014-0836-1, 44, 11, 2077-85, 2014.11, PURPOSE: To evaluate the anatomical variations in the middle hepatic vein tributaries (V5/V8) for determining the reconstruction strategy in right lobe living donor liver transplantation (LDLT). METHODS: The V5/V8 variations were examined in 268 patients and were classified into three and two types, respectively. The reconstruction rate (RR), patency rate (PR) and clinical outcomes were retrospectively evaluated in 46 right lobe LDLT cases. RESULTS: In terms of V5 variations, the RR and PR were significantly higher for type 2 than type 3 (82.6 vs. 44.4 % and 73.7 vs. 25.0 %, respectively). The alanine aminotransferase level on postoperative day (POD) 5 in the V5 patent group was significantly lower than in the occluded group (123 vs. 191 IU/dL). Regarding V8 variations, the RR and PR were significantly higher for type 1 than type 2 (44.4 vs. 17.6 % and 75.0 vs. 33.3 %, respectively). The aspartate aminotransferase level on POD 3 was significantly lower in the V8 patent group than in the occluded group (50 vs. 121 IU/dL). CONCLUSION: For right lobe grafts with single large V5 (type 2) or V8 (type 1) variations, reconstruction is necessary. Our new classification of the MHV tributaries is useful for determining the reconstruction strategy to use in right lobe LDLT..
1125. Daisuke Matsuda, Takeo Toshima, Toru Ikegami, Norifumi Harimoto, Yo-Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Thrombotic microangiopathy caused by severe graft dysfunction after living donor liver transplantation: report of a case., Clinical journal of gastroenterology, 10.1007/s12328-013-0446-2, 7, 2, 159-63, 2014.04, Thrombotic microangiopathy (TMA) is a life-threatening complication after transplantation including liver transplantation, and its typical clinical picture is characterized by hemolytic anemia, thrombocytopenia, renal dysfunction, neurological abnormalities, and fever. We report the case of a 56-year-old female with end-stage liver disease who underwent living donor liver transplantation (LDLT), and whose postoperative course was characterized by renal failure and progressive hyperbilirubinemia. Two weeks after LDLT, she started to show progressive thrombocytopenia, anemia, oliguria, and encephalopathy. From these clinical manifestations, she was diagnosed as having TMA and underwent plasma exchanges with continuous hemodialysis under temporary holding calcineurin inhibitors. The patient promptly responded to the treatment, with improved hematological, hepatic, and renal conditions, and was discharged from hospital a month later in a stable condition. We describe this case of TMA after LDLT with poor graft function and extensively review the disease in liver transplant recipients..
1126. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Yoichi Yamashita, Hirofumi Kawanaka, Tetsuo Ikeda, Masaru Morita, Eiji Oki, Yoshihiko Maehara, Use of living donor liver grafts with double or triple arteries., Transplantation, 10.1097/01.TP.0000442687.33536.c4, 97, 11, 1172-7, 2014.06, BACKGROUND: Hepatic grafts used in living donor liver transplantation (LDLT) sometimes have two or more arteries, in which surgeons are required to perform complex arterial reconstruction. The aim of the current study was to demonstrate whether selecting living donor liver grafts with double or triple arteries yielded the same outcomes as grafts with a single artery. METHODS: We retrospectively investigated the outcomes of LDLT focusing on the numbers of arteries on grafts. Four hundred forty-six cases of LDLT performed between October 1996 and October 2012 were retrospectively analyzed. The cases were divided into the following three groups according to the number of arteries on a graft: the single (n=331), the double (n=108), and the triple (n=7) groups. RESULTS: Artery-related complications occurred in five cases in the single group, two cases in the double group, and no case in the triple group. Although the overall graft survival was comparable among the three groups, there was a tendency of worsened graft survival and increased incidence of anastomotic biliary stricture after liver transplantation in right hepatic grafts with double arteries. CONCLUSIONS: The use of grafts with double or triple arteries yielded favorable outcomes with minimum artery-related complications compared with grafts with a single artery. However, the use of right hepatic grafts with double arteries is discouraging in the current study..
1127. [Case report of introducing MMF and steroids as an immunosuppressive therapy after living-donor liver transplantation for a patient with the diabetic nephropathy]..
1128. Y. Yoshida, T. Ikegami, T. Yoshizumi, T. Toshima, Y. -I. Yamashita, S. Yoshiya, K. Shirabe, Y. Maehara, rs8099917 and Viral Genotyping as Indications for Living Donor Liver Transplantation for Hepatitis C: A Case Report, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2013.09.059, 46, 7, 2426-2429, 2014.09, Introduction. Appropriate antiviral treatment is essential for living donor liver transplantation (LDLT) to be effective for treating hepatitis C. However, it has never been reported that pre-LDLT genetic analyses of both host and virus, with prediction of the outcome of post-LDLT antiviral treatment, indicated LDLT for a borderline case.
Case Report. We have reported the case of a 68-year-old woman with liver cirrhosis caused by genotype 1b hepatitis C, a history of ruptured esophageal varices, and adequately controlled minor ascites. Her liver function was classified as Child-Pugh grade B. The donor was a 42-year-old woman with an estimated left lobe graft volume (GV) of 33.8% based on the standard liver volume of the recipient. Molecular analyses used to confirm the indication of LDLT for this combination revealed the following: The rs8099917 genotype was TIT in the donor and recipient, the HCV core protein was double wild type, there were no mutations in the interferon sensitivity-determining region, and 8 mutations were found in the interferon/ribavirin resistance-determining region. LDLT was performed because very high sensitivity to interferon treatment was predicted.
Discussion. Six months after LDLT and uneventful post-LDLT courses, pegylated interferon-alpha 2a and ribavirin were administered under immunosuppression with cyclosporine and mycophenolate mofetil. This regimen was continued for 48 weeks, resulting in a viral response at 10 weeks and a sustained viral response, as predicted. Conclusions. We have reported the usefulness of molecular analyses of host and viral factors for indicating LDLT to treat hepatitis C in a borderline case..
1129. Akinobu Taketomi, Ken Shirabe, Jun Muto, Shohei Yoshiya, Takashi Motomura, Yohei Mano, Tohru Ikegami, Tomoharu Yoshizumi, Kenji Sugio, Yoshihiko Maehara, A rare point mutation in the Ras oncogene in hepatocellular carcinoma., Surgery today, 10.1007/s00595-012-0462-8, 43, 3, 289-92, 2013.03, PURPOSE: The Ras gene is one of the oncogenes most frequently detected in human cancers, and codes for three proteins (K-, N-, and H-Ras). The aim of this study was to examine the mutations in codons 12, 13 and 61 of the three Ras genes in cases of human hepatocellular carcinoma (HCC). METHODS: Paired samples of HCC and corresponding non-malignant liver tissue were collected from 61 patients who underwent hepatectomy. A dot-blot analysis was used to analyze the products of the polymerase chain reaction (PCR) amplification of codons 12, 13, and 61 of K-, N- and H-Ras for mutations. RESULTS: Only one mutation (K-Ras codon 13; Gly to Asp) was detected among the 61 patients. Interestingly, this patient had a medical history of surgery for both gastric cancer and right lung cancer. No mutations were found in codons 12 and 61 of K-Ras or codons 12, 13 and 61 of the N-Ras and H-Ras genes in any of the HCCs or corresponding non-malignant tissues. CONCLUSIONS: These findings indicated that the activation of Ras proto-oncogenes by mutations in codons 12, 13, and 61 does not play a major role in hepatocellular carcinogenesis..
1130. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Tetsuo Ikeda, Yoshihiko Maehara, A simple and secure ligation of the main pancreatic duct in distal pancreatectomy., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.10.021, 216, 3, e23-5-5, 2013.03.
1131. Hideki Ijichi, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Youhei Mano, Shinichi Aishima, Koichiro Abe, Hiroshi Honda, Yoshihiko Maehara, Clinical usefulness of (18) F-fluorodeoxyglucose positron emission tomography/computed tomography for patients with primary liver cancer with special reference to rare histological types, hepatocellular carcinoma with sarcomatous change and combined hepatocellular and cholangiocarcinoma., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/j.1872-034X.2012.01107.x, 43, 5, 481-7, 2013.05, AIM: The role of (18) F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis and staging of primary liver cancer has been demonstrated in several reports. However, no preoperative evaluations of sarcomatous hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (cHCC-CC) with FDG-PET have been reported so far. METHODS: Fifty-three HCC patients and three cHCC-CC patients who received liver resection or living-donor liver transplantation were enrolled in this study. All 56 patients had undergone preoperative FDG-PET, and a total of 67 HCC and three cHCC-CC were analyzed histologically. The relationship between clinicopathological features and the maximum standardized uptake value (SUVmax) of tumors were evaluated. RESULTS: The detection rate of HCC by FDG-PET was 43.3 %, and the sensitivity of FDG-PET for the detection of HCC was significantly associated with tumor differentiation, tumor size and microvascular invasion. All three cHCC-CC were detected by FDG-PET. The SUVmax values of the three sarcomatous HCC (SUVmax 14.1, 18.6 and 25.0) and the three cHCC-CC (SUVmax 9.9, 12.0 and 13.0) were higher than that of the poorly differentiated HCC (mean SUVmax 5.7 ± 2.3). CONCLUSION: SUVmax may be a useful diagnostic tool for the preoperative evaluation of the aggressiveness of primary liver cancers such as sarcomatous HCC and cHCC-CC..
1132. Kazutoyo Morita, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Naotaka Hashimoto, Yohei Mano, Tatsunori Miyata, Yuji Soejima, Yoshihiko Maehara, Feasible isolated liver transplantation for a cirrhotic patient on chronic hemodialysis., Case reports in gastroenterology, 10.1159/000354140, 7, 2, 299-303, 2013.05, End-stage liver and kidney disease (ELKD) is an indication for deceased donor simultaneous liver-kidney transplantation. Although a few cases of living donor liver-kidney transplantation have been reported, the invasiveness remains to be discussed. Living donor liver transplantation (LDLT) is an alternative choice for ELKD, but has never been reported. Here, we report a case of successful LDLT for a patient with ELKD on hemodialysis. The patient was a 63-year-old male and had decompensated hepatitis C cirrhosis with seronegativity for hepatitis C virus. He had non-diabetic end-stage renal failure and had been on hemodialysis for 3 years. He was in good general condition except for hepatic and renal failure. The living donor was his 58-year-old healthy wife. A right lobe graft was transplanted to the recipient under continuous hemodiafiltration (CHDF) and extracorporeal veno-venous bypass. CHDF was continued until postoperative day 4, at which point CHDF was converted to hemodialysis. His posttransplant course was good and he was discharged on postoperative day 36. To the best of our knowledge, this is the first report of LDLT for a patient on chronic hemodialysis. Therefore, being on hemodialysis is not a contraindication for LDLT. LDLT is feasible for a patient with ELKD on hemodialysis..
1133. K. Shirabe, T. Motomura, K. Takeishi, K. Morita, H. Kayashima, A. Taketomi, T. Ikegami, Y. Soejima, T. Yoshizumi, Y. Maehara, HUMAN EARLY LIVER REGENERATION AFTER HEPATECTOMY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA: SPECIAL REFERENCE TO AGE, SCANDINAVIAN JOURNAL OF SURGERY, 102, 2, 101-105, 2013.06, Background and Aims: This study was conducted to clarify the effects of age on human liver regeneration.
Patients and Methods: Thirty major hepatectomies, equal to or more than two segmentectomies for hepatocellular carcinoma, were performed. Ages ranged from 37 to 85 years and five octogenarians were included. The early regenerative index was defined: (liver volume after 7 days after hepatectomy -estimated remnant liver volume before hepatectomy)/estimated remnant liver volume, using three-dimensional computed tomographic volumetry. Farnesoid X receptor and forkhead box ml expression in the liver, which has been reported to age-related decrease of liver regeneration in animal model, were examined using real-time polymerase chain reaction. The patients were divided into two groups: low early regenerative index (n = 15), early regenerative index less than 55% and high early regenerative index (n = 15), early regenerative index equal to or more than 55%.
Results: The mean early regenerative index was 57%. Age (R-2 = 0.274, P = 0.003) and estimated blood loss (R-2 = 0.134, P = 0.0466) were inversely correlated with the early regenerative index, and the expression of farnesoid X receptor and forkhead box ml was not. The incidence of posthepatectomy liver failure in the low early regenerative index group was higher than that in the high early regenerative index group (P = 0.0421).
Conclusions: Age and intraoperative blood loss are inversely correlated with early liver regeneration in humans. In elderly patients, massive blood loss should be avoided in view of liver regeneration..
1134. Yu Saito, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Koji Yamasaki, Noriaki Sadanaga, Hiroshi Matsuura, Kenichiro Okadome, Hepatic artery aneurysm in a patient with hepatitis C liver cirrhosis: report of a case., Clinical journal of gastroenterology, 10.1007/s12328-013-0372-3, 6, 2, 169-72, 2013.04, Visceral artery aneurysms are rare, with an incidence rate of only 0.01-0.2 % in routine autopsies, and hepatic artery aneurysms account for approximately 20 % of these aneurysms. Despite recent advances in therapeutic techniques and diagnostic tools, the management of visceral artery aneurysms remains clinically challenging. We report a case of hepatic artery aneurysm with liver cirrhosis due to hepatitis C in an 81-year-old woman. A computed tomography scan demonstrated a hepatic artery aneurysm 4.4 cm in diameter. She underwent successful aneurysmectomy with vascular anastomosis. A computed tomography scan on postoperative day 7 demonstrated patent hepatic artery. The patient was followed-up for 1 year after surgery and died owing to progressive liver failure. However, she did not show any hepatic artery problem such as hepatic arterial thrombosis or occlusion. We discuss the risk factors of atherosclerosis in patients with liver cirrhosis, and present an overview of the treatment of hepatic artery aneurysms..
1135. Ikegami T, Shirabe K, Yoshizumi T, Furusyo N, Kotoh K, Kato M, Shimoda S, Soejima Y, Motomura T, Fukuhara T, Maehara Y, Impact of conversion from pegylated interferon-α2b to interferon-α2a for treating recurrent hepatitis C after liver transplantation., Transplantation, 10.1097/TP.0b013e318283a82e, 95, 6, e38-e42, 2013.05.
1136. Toru Ikegami, Ken Shirabe, Hidekazu Nakagawara, Tomoharu Yoshizumi, Takeo Toshima, Yuji Soejima, Hideaki Uchiyama, Yo-Ichi Yamashita, Norifumi Harimoto, Yoshihiko Maehara, Obstructing spontaneous major shunt vessels is mandatory to keep adequate portal inflow in living-donor liver transplantation., Transplantation, 10.1097/TP.0b013e318288cadc, 95, 10, 1270-7, 2013.05, BACKGROUND: It has not been addressed whether the major spontaneous portosystemic shunt vessels should be ligated in living-donor liver transplantation (LDLT). METHODS: We performed a retrospective analysis of 324 cases of adult-to-adult LDLT. RESULTS: Factors associated with the presence of major (>10 mm) shunt vessels (n=130) included portal vein (PV) thrombosis (27.7%), lower PV pressure at laparotomy, Child-Pugh class C, and transplantation of right-side grafts. The types of major portosystemic shunt vessels included splenorenal shunts (46.2%), gastroesophageal shunts (26.9%), mesocaval shunts (13.8%), and others (13.1%). Ligation of the major shunt vessels increased PV pressure (mean [SD], from 16.8 [3.9] mm Hg to 18.6 [4.3] mm Hg; P<0.001) and PV flow (mean [SD], from 1.35 [0.67] L/min to 1.67 [0.67] L/min; P<0.001) into the grafts. Post-LDLT computed tomography showed patent major shunts in 14 patients. Nine of such patients (64.3%) with unligated major shunt vessels (undetected shunt vessels, n=5; incomplete ligation, n=2; and the shunt was newly created or left open to maintain high PV pressure after reperfusion, n=3) required secondary interventions. Two of these patients died because of graft dysfunction. PV flow was significantly lower in the nine patients who underwent secondary ligation of the major shunt vessels compared with patients with successful primary ligation (mean [SD], 0.96 [0.34] L/min vs. 1.65 [0.63] L/min; P=0.001). CONCLUSIONS: It is an appropriate option to obstruct the major portosystemic shunt vessels to ensure adequate graft inflow in LDLT..
1137. Toru Ikegami, Huanlin Wang, Daisuke Imai, Yuki Bekki, Tomoharu Yoshizumi, Yo-Ichi Yamashita, Takeo Toshima, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Pathological analysis of opened round ligaments as venous patch grafts in living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23716, 19, 11, 1245-51, 2013.11, Although the round ligament, including the umbilical vein, could be used as a venous graft in living donor liver transplantation (LDLT), no studies have determined its appropriate use on the basis of pathological findings. We prospectively examined 19 LDLT cases in which the donor's round ligament was procured and used as a venous graft. The round ligaments were categorized into 3 types based on the CD31 immunohistochemistry of tissue cross-sections: (I) canalized umbilical veins (n = 7 or 36.8%), (II) capillary umbilical vessels (n = 4 or 21.1%), and (III) occluded umbilical veins (n = 8 or 42.1%). After dilatation and incision, the round ligaments provided patch grafts that were 5.8 ± 0.4 cm long and 1.8 ± 1.2 cm wide. However, histological studies showed the absence of fine intimal layers on the dilated round ligaments after mechanical maneuvers. The ligaments were used to cuff the venous orifices in 15 patients (left lobe, n = 8; right lobe, n = 7) and were used as venous bridges in 4 patients (left lobe, n = 2; right lobe, n = 2). We detected no thrombosis at the implant sites after LDLT. Our pathological findings indicate that opened round ligaments can be used safely as venous patch grafts in LDLT..
1138. N. Harimoto, K. Shirabe, Y. I. Yamashita, T. Ikegami, T. Yoshizumi, Y. Soejima, T. Ikeda, Y. Maehara, A. Nishie, T. Yamanaka, Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma, British Journal of Surgery, 10.1002/bjs.9258, 100, 11, 1523-1530, 2013.10, Background Sarcopenia was identified recently as a poor prognostic factor in patients with cancer. The present study investigated the effect of sarcopenia on short- and long-term outcomes following partial hepatectomy for hepatocellular carcinoma (HCC), and aimed to identify prognostic factors. Methods Data were collected retrospectively for all consecutive patients who underwent hepatectomy for HCC with curative intent between January 2004 and December 2009. Patients were assigned to one of two groups according to the presence or absence of sarcopenia, assessed by computed tomographic measurement of muscle mass at the level of the third lumbar vertebra. Clinicopathological, surgical outcome and long-term survival data were analysed. Results Sarcopenia was present in 75 (40·3 per cent) of 186 patients, and was significantly correlated with female sex, lower body mass index and liver dysfunction, as indicated by abnormal serum albumin levels and indocyanine green retention test at 15 min values. In patients with, and without sarcopenia, the 5-year overall survival rate was 71 and 83·7 per cent respectively, and the 5-year recurrence-free survival rate was 13 and 33·2 per cent respectively. Multivariable analysis revealed that reduced skeletal muscle mass was predictive of an unfavourable prognosis. Conclusion Sarcopenia was predictive of worse overall survival even when adjusted for other known predictors in patients with HCC after partial hepatectomy. © 2013 British Journal of Surgery Society Ltd. Published by John Wiley &
Sons Ltd..
1139. Yo-ichi Yamashita, Ken Shirabe, Eiji Tsuijita, Kazuki Takeishi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Tohru Utsunomiya, Yoshihiko Maehara, Third or more repeat hepatectomy for recurrent hepatocellular carcinoma., Surgery, 10.1016/j.surg.2013.04.046, 154, 5, 1038-45, 2013.11, BACKGROUND: We sought to evaluate the surgical results of third or more repeat hepatectomy for recurrent hepatocellular carcinoma (HCC). The role of repeat hepatectomy for recurrent HCC, especially in cases with third or more repeat hepatectomy, is controversial. METHODS: We performed A retrospective, cohort study to analyze the surgical results of repeat hepatectomy performed at a single medical center from 1989 to 2011. A total of 1,000 hepatectomies for HCC were divided into 3 groups: A first hepatectomy group (n = 791), second hepatectomy group (n = 163), and third or more hepatectomy group (n = 46). Operative results and patient prognoses were compared among the 3 groups. RESULTS: There were no differences in early surgical results such as mortality and morbidity among the 3 groups. The 5-year survival rates after the first, second, and third or more hepatectomy were 67%, 60%, and 43%, respectively (P = .1913). There was a significant difference in disease-free survival among the 3 groups, and the 5-year disease-free survival rates after first, second, and third or more hepatectomy were 37%, 29%, and 18%, respectively (P = .0169). CONCLUSION: Third or more repeat hepatectomy for recurrent HCC was performed safely and associated with relatively long-term survival. Third or more repeat hepatectomy for recurrent HCC seems justified, but high rate of HCC recurrence remains a problem..
1140. Naotaka Hashimoto, Tomohiko Akahoshi, Masahiro Kamori, Morimasa Tomikawa, Daisuke Yoshida, Yoshihiro Nagao, Kazutoyo Morita, Hiroto Kayashima, Toru Ikegami, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Treatment of bleeding rectal varices with transumbilical venous obliteration of the inferior mesenteric vein., Surgical laparoscopy, endoscopy & percutaneous techniques, 10.1097/SLE.0b013e31828031ec, 23, 3, e134-7, 2013.06, A 56-year-old male with alcohol-induced liver cirrhosis developed rectal varices. He had a prior history of treatment for esophageal varices with endoscopic variceal ligation. Despite the repeated treatment for rectal varices with endoscopic variceal ligation, endoscopic injection sclerotherapy, and surgery, the bleeding from the rectal varices could not be controlled. Multidetector-row computed tomography and 3D-angiography revealed the hemodynamic profile of the rectal varices. We next approached the rectal varices through the umbilical vein on the abdominal wall, and successfully embolized the varices continuing from the inferior mesenteric vein using coils and a 5% solution of ethanolamine oleate with iopamidol..
1141. T. Yoshizumi, T. Ikegami, T. Toshima, N. Harimoto, H. Uchiyama, Y. Soejima, Y. Yamashita, K. Shirabe, Y. Maehara, Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma, Transplantation Proceedings, 10.1016/j.transproceed.2013.05.001, 45, 9, 3310-3313, 2013.11, We have proposed risk factors for tumor recurrence, such as tumor nodule ≥5 cm and des-gamma-carboxy prothrombin ≥300 mAU/mL after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors for HCC recurrence and mortality within our criteria. We enrolled 152 adult recipients who had undergone LDLT for end-stage liver disease with HCC who met our criteria. The recurrence-free survival rates after LDLT were calculated. Risk factors for tumor recurrence were identified. On univariate analysis, factors affecting recurrence-free survival were pretransplant treatment for HCC, neutrophil-to-lumphocyte ratio (NLR) >
4, alpha-fetoprotein ≥400 ng/mL, ≥5 nodules, and bilobar tumor distribution. Multivariate analysis identified that NLR >
4 and ≥5 nodules were independent risk factors for tumor recurrence after LDLT (P =.003 and P =.002, respectively). Two-step selection criteria enable selection of patients who have high-risk of tumor recurrence. © 2013 by Elsevier Inc. All rights reserved..
1142. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Hiroto Kayashima, Yoshihiko Maehara, Use of the SAND balloon catheter in single-incision laparoscopic cholecystectomy for acute cholecystitis., Asian journal of endoscopic surgery, 10.1111/ases.12005, 6, 2, 134-6, 2013.05, INTRODUCTION: SILS for acute cholecystitis is technically challenging because of the difficulties in obtaining optical surgical field. MATERIALS AND SURGICAL TECHNIQUE: A 2-cm incision was made through the umbilicus, a single port and trocars were introduced, and the abdomen was then insufflated. A 5-mm SAND balloon punctured the abdominal wall and then the gallbladder wall. The distal and proximal balloons were inflated to prevent bile leakage, and the bile was aspirated. The collapsed gallbladder was then retracted cephalad, the critical structures were exposed, and the cystic artery and duct were divided. The gallbladder was dissected and removed through the umbilicus, and the abdomen was closed. We performed this procedure in three cases with acute cholecystitis. Operative times were 95, 133 and 244 min, blood loss was 5, 10 and 43 mL, and postoperative hospital stay was 2, 2 and 3 days, respectively. DISCUSSION: The single-incision laparoscopic approach with the SAND balloon is a feasible technique for acute cholecystitis..
1143. Noboru Harada, Ken Shirabe, Hideki Ijichi, Rumi Matono, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Yoshihiko Maehara, Acoustic radiation force impulse imaging predicts postoperative ascites resulting from curative hepatic resection for hepatocellular carcinoma., Surgery, 10.1016/j.surg.2011.12.035, 151, 6, 837-43, 2012.06, BACKGROUND: Measurement of liver stiffness using Virtual Touch Tissue Quantification (VTTQ) based on acoustic radiation force impulse imaging reflects the degree of hepatic fibrosis and reserve. This prospective study investigated how well the VTTQ value predicts the development of postoperative complications before curative hepatic resection for hepatocellular carcinoma (HCC). METHODS: The study enrolled 50 consecutive patients between February 2009 and October 2010 whose preoperative VTTQ values were determined before they underwent curative hepatic resection for HCC. We assessed the relationship between postoperative complications and VTTQ values. RESULTS: The study included 41 (82%) patients with chronic hepatitis and 9 (18%) with nonviral cirrhosis. The mean VTTQ value was 1.60 (m/sec), which correlated with the fibrosis stage (P = .0058). The VTTQ value was the only variable correlated with postoperative ascites that did not respond to pharmacologic treatment and required invasive management. Univariate and subsequent multivariate analyses revealed that the preoperative VTTQ value was the only independent risk factor for predicting the development of postoperative ascites (cutoff, 1.68 cm/sec; P = .007; odds ratio, 76.481). The area under the receiver operating characteristic curve for the diagnosis of postoperative ascites using VTTQ values was 0.90, whereas those using the aspartate transaminase-to-platelet ratio index and indocyanine green retention rate at 15 minutes values were 0.68 and 0.55, respectively. CONCLUSION: These data suggest that the VTTQ value is a reliable surrogate marker for predicting postoperative ascites before curative hepatic resection for HCC..
1144. Jun Muto, Yohei Mano, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Additional resection of the pancreas body prevents postoperative pancreas fistula in patients with portal annular pancreas who undergo pancreaticoduodenectomy., Case reports in gastroenterology, 10.1159/000335210, 6, 1, 131-4, 2012.01, Portal annular pancreas (PAP) is a rare variant in which the uncinate process of the pancreas extends to the dorsal surface of the pancreas body and surrounds the portal vein or superior mesenteric vein. Upon pancreaticoduodenectomy (PD), when the pancreas is cut at the neck, two cut surfaces are created. Thus, the cut surface of the pancreas becomes larger than usual and the dorsal cut surface is behind the portal vein, therefore pancreatic fistula after PD has been reported frequently. We planned subtotal stomach-preserving PD in a 45-year-old woman with underlying insulinoma of the pancreas head. When the pancreas head was dissected, the uncinate process was extended and fused to the dorsal surface of the pancreas body. Additional resection of the pancreas body 1 cm distal to the pancreas tail to the left side of the original resection line was performed. The new cut surface became one and pancreaticojejunostomy was performed as usual. No postoperative complications such as pancreatic fistula occurred. Additional resection of the pancreas body may be a standardized procedure in patients with PAP in cases of pancreas cut surface reconstruction..
1145. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Tomoharu Yoshizumi, Mizuki Ninomiya, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Bacterial sepsis after living donor liver transplantation: the impact of early enteral nutrition., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2011.12.001, 214, 3, 288-95, 2012.03, BACKGROUND: Bacterial sepsis is a significant problem that must be addressed after living donor liver transplantation (LDLT). STUDY DESIGN: A retrospective analysis of 346 adult-to-adult LDLT patients was performed. RESULTS: Forty-six patients (13.3%) experienced bacterial sepsis, with primary and secondary origins in 23.9% and 76.1%, respectively. Gram-negative bacteria accounted for 71.7% of the bacteria isolated. The 2-year cumulative graft survival rate in patients with bacterial sepsis was 45.7%. Patients with bacterial sepsis secondary to pneumonia (n = 12) had poorer 2-year graft survival rates (16.7%) than did those with primary or other types of secondary sepsis (p = 0.004). Multivariate analysis showed that intraoperative massive blood loss >10L (p < 0.001) and no enteral feeding started within 48 hours after transplantation (p = 0.005) were significant risk factors for bacterial sepsis. Among patients who received enteral nutrition, the incidences of bacterial sepsis in patients who received enteral nutrition within 48 hours (n = 135) or later than 48 hours (n = 57) were 5.9% and 21.0%, respectively (p = 0.002). The incidence of early graft loss was 8-fold higher in recipients with massive intraoperative blood loss without early enteral nutrition (p < 0.001). CONCLUSIONS: Early enteral nutrition was associated with significantly reduced risk of developing bacterial sepsis after LDLT..
1146. Kazuki Takeishi, Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Takashi Motomura, Toru Ikegami, Tomoharu Yoshizumi, Fumio Sakane, Yoshihiko Maehara, Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras-Raf-MEK-ERK pathway., Journal of hepatology, 10.1016/j.jhep.2012.02.026, 57, 1, 77-83, 2012.07, BACKGROUND & AIMS: Diacylglycerol kinases (DGKs) were recently recognized as key regulators in cell signaling pathways. We investigated whether DGKα is involved in human hepatocellular carcinoma (HCC) progression. METHODS: We silenced or overexpressed DGKα in HCC cells and assessed its effect on tumor progression. DGKα expression in 95 surgical samples was analyzed by immunohistochemistry, and the expression status of each sample was correlated with clinicopathological features. RESULTS: DGKα was detected in various HCC cell lines but at very low levels in the normal liver. Knockdown of DGKα significantly suppressed cell proliferation and invasion. Overexpression of wild type (WT) DGKα, but not its kinase-dead (KD) mutant, significantly enhanced cell proliferation. DGKα knockdown impaired MEK and ERK phosphorylation, but did not inhibit Ras activation in HCC cells. In a xenograft model, WT DGKα overexpression significantly enhanced tumor growth compared to the control, but KD DGKα mutant had no effect. Immunohistochemical studies showed that DGKα was expressed in cancerous tissue, but not in adjacent non-cancerous hepatocytes. High DGKα expression (≥20%) was associated with high Ki67 expression (p<0.05) and a high rate of HCC recurrence (p=0.033) following surgery. In multivariate analyses, high DGKα expression was an independent factor for determining HCC recurrence after surgery. CONCLUSIONS: DGKα is involved in HCC progression by activation of the MAPK pathway. DGKα could be a novel target for HCC therapeutics as well as a prognostic marker..
1147. Takashi Motomura, Ken Shirabe, Norihiro Furusyo, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tomohiko Akahoshi, Morimasa Tomikawa, Takasuke Fukuhara, Jun Hayashi, Yoshihiko Maehara, Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype., BMC gastroenterology, 10.1186/1471-230X-12-158, 12, 158-158, 2012.11, BACKGROUND: IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined. METHODS: Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen. RESULTS: Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy. CONCLUSIONS: IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype..
1148. Takashi Motomura, Erina Koga, Akinobu Taketomi, Takasuke Fukuhara, Yohei Mano, Jun Muto, Hideyuki Konishi, Takeo Toshima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/j.1872-034X.2011.00927.x, 42, 3, 288-95, 2012.03, AIM:   A genetic polymorphism of inosine triphosphate pyrophosphatase (ITPA) has been associated with pegylated-interferon/ribavirin (PEG-IFN/RBV)-induced anemia in chronic hepatitis C patients. However, correlation of the genetic variant with anemia following liver transplantation has not been determined. METHODS:   Sixty-three hepatitis C virus (HCV)-positive patients who underwent liver transplantation and PEG-IFN/RBV therapy were enrolled. The rs1127354 was determined for each individual. RESULTS:   There was no relationship with anemia or RBV dosage in patients carrying the CC allele (CC group, n = 43) and those carrying the CA allele (CA group, n = 20). The incidence of hemoglobin (Hb) decline >3 g/dL (CC: 4.7%, CA: 0%) was relatively low, whereas the incidence of Hb levels <10 g/dL (CC: 18.6%, CA: 30.0%) was high. Univariate analysis revealed that splenectomy inversely correlated with Hb levels <10 g/dL at 4 weeks (P = 0.04). Among the 22 patients who did not undergo splenectomy, the incidence of Hb levels <10 g/dL tended to be lower in the seven patients carrying the CA allele (28.6%) than in the 15 patients with the CC allele (60.0%). CONCLUSION:   The ITPA genetic polymorphism does not correlate with post-transplant PEG-IFN/RBV-induced anemia. Splenectomy is useful in preventing anemia regardless of the ITPA genotype..
1149. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Shohei Yoshiya, Takeo Toshima, Takashi Motomura, Yuji Soejima, Hideaki Uchiyama, Yoshihiko Maehara, En bloc stapling division of the gastroesophageal vessels controlling portal hemodynamic status in living donor liver transplantation., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.02.016, 214, 6, e53-6-6, 2012.06.
1150. Toru Ikegami, Ken Shirabe, Rumi Matono, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Etiologies, risk factors, and outcomes of bacterial pneumonia after living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23483, 18, 9, 1060-8, 2012.09, The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short-term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram-negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P = 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post-LDLT pneumonia was associated with the following post-LDLT events: the prolonged use of mechanical ventilation (≥3 days), a prolonged stay in the intensive care unit (≥7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed-onset pneumonia, which occurred at least 10 days after transplantation (n = 15), and it was significantly associated with graft dysfunction. A combination of broad-spectrum antibiotics and aminoglycosides provided cover for most gram-negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad-spectrum antibiotics. Delayed-onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed..
1151. Hideaki Uchiyama, Ken Shirabe, Masaru Morita, Yoshihiro Kakeji, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Noboru Harada, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Expanding the applications of microvascular surgical techniques to digestive surgeries: a technical review., Surgery today, 10.1007/s00595-011-0032-5, 42, 2, 111-20, 2012.01, In living donor liver transplantation (LDLT), it is considered safer to reconstruct hepatic arteries (HAs) under a microscope than under conventional loupe magnification, because graft HA stumps are generally thin and short with an average diameter of approximately 2 mm. We first applied microvascular surgical techniques to HA reconstruction for LDLT in 1996. In most cases, we use a disposable double-clip to secure the graft and recipient arteries, and interrupted 8-0 nonabsorbable monofilament sutures. We next started performing resection and reconstruction of the right HA in a surgery for hilar cholangioma using the same technique as in LDLT. Lately, we have started applying microvascular surgical techniques to various digestive surgeries; namely, supercharge and superdrainage in esophageal surgery, vascular reconstruction in free jejunal interposition grafts for cervical esophageal cancer, resection and reconstruction of spontaneous HA aneurysms, jejunal artery reconstruction for spontaneous superior mesenteric artery dissections, and so forth. Mastering this technique is time consuming. However, once a surgeon masters the technique it has almost unlimited applications, and most vital vessels can be safely reconstructed using this method. We herein provide a technical review of the application of microvascular surgical techniques for various digestive surgeries..
1152. Rumi Matono, Shohei Yoshiya, Takashi Motomura, Takeo Toshima, Hiroto Kayashima, Toshiro Masuda, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Factors linked to longterm survival of patients with hepatocellular carcinoma accompanied by tumour thrombus in the major portal vein after surgical resection., HPB : the official journal of the International Hepato Pancreato Biliary Association, 10.1111/j.1477-2574.2011.00436.x, 14, 4, 247-53, 2012.04, OBJECTIVES: The prognosis in patients with hepatocellular carcinoma (HCC) accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this study was to clarify the factors linked to survival of >5 years after hepatectomy in HCC patients with MPVTT. METHODS: Twenty-nine HCC patients with MPVTT were divided into two groups comprising, respectively, patients who survived >5 years after hepatectomy (survivors, n= 5) and those who did not (non-survivors, n= 24). The two groups were compared. RESULTS: Overall survival rates at 1, 3 and 5 years were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had recurrences of HCC in which the number of recurrent nodules was under four. Three (21.4%) of the 14 non-survivors who underwent curative resection experienced recurrences of HCC and all of them demonstrated fewer than four recurrent nodules (P= 0.0114). Local therapy, such as radiofrequency ablation and resection of recurrence, had more often been used in survivors than in non-survivors (P= 0.0364). CONCLUSIONS: Although surgical outcomes in patients with HCC accompanied by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the number of recurrent nodules is less than four, local therapy should be selected with the aim of achieving 5-year survival..
1153. T. Yoshizumi, K. Shirabe, T. Ikegami, H. Kayashima, N. Yamashita, K. Morita, T. Masuda, N. Hashimoto, A. Taketomi, Y. Soejima, Y. Maehara, Impact of Human T Cell Leukemia Virus Type 1 in Living Donor Liver Transplantation, AMERICAN JOURNAL OF TRANSPLANTATION, 10.1111/j.1600-6143.2012.04037.x, 12, 6, 1479-1485, 2012.06, Human T cell leukemia virus type 1 (HTLV-1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV-1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV-1 status in living donor liver transplantation (LDLT). Twenty-six of 329 (7.9%) HTLV-1 carriers underwent primary LDLT. One recipient negative for HTLV-1 before LDLT received a graft from an HTLV-1 positive donor. Eight donors were HTLV-1 positive. Twenty-seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV-1 positive donors and two from negative donors. The 1-, 3- and 5-year HTLV-1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score = 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV-1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development..
1154. Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara, Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma: report of a case., Surgery today, 10.1007/s00595-012-0332-4, 42, 12, 1210-4, 2012.12, The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection..
1155. Y. Soejima, K. Shirabe, A. Taketomi, T. Yoshizumi, H. Uchiyama, T. Ikegami, M. Ninomiya, N. Harada, H. Ijichi, Y. Maehara, Left Lobe Living Donor Liver Transplantation in Adults, AMERICAN JOURNAL OF TRANSPLANTATION, 10.1111/j.1600-6143.2012.04022.x, 12, 7, 1877-1885, 2012.07, Adult left lobe (LL) living donor liver transplantation (LDLT) has not generally been recognized as a feasible procedure because of the problem of graft size. The objectives of this study were to assess the feasibility and short- and long-term results of adult LL LDLT in comparison with right lobe (RL) LDLT. Data on 200 consecutive LL LDLTs, including five retransplants, were retrospectively compared with those of 112 RL LDLTs, in terms of survival, complications and donor morbidity. The mean graft weight to standard volume ratio of LL grafts was 38.7% whereas that of RL grafts was 47.6% (p < 0.0001). The 1-, 5- and 10-year patient survival rates of LL LDLT were 85.6%, 77.9% and 69.5%, respectively, which were comparable to those of RL LDLT (89.8%, 71.3% and 70.7%, respectively). The incidence of small-for-size syndrome was higher in LL LDLT (19.5%) than in RL LDLT (7.1%) (p < 0.01). The overall donor morbidity rates were comparable between LL (36.0%) and RL (34.8%), whereas postoperative liver function tests and hospital stay were significantly better (p < 0.0001) in LL donors. In conclusion, adult LL LDLT has comparable outcomes to that of RL LDLT. LL LDLT is viable and is the first choice in adult LDLT..
1156. Takeo Toshima, Ken Shirabe, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Outcome of hepatectomy for hepatocellular carcinoma in patients with renal dysfunction., HPB : the official journal of the International Hepato Pancreato Biliary Association, 10.1111/j.1477-2574.2012.00452.x, 14, 5, 317-24, 2012.05, OBJECTIVES: There are few reports on the efficacy of hepatectomy for hepatocellular carcinoma (HCC) in patients with renal dysfunction (RD). This study aimed to clarify the validity of hepatectomy for treating HCC in RD patients, and to compare postoperative courses in RD and non-RD patients. METHODS: The clinical features of 722 HCC patients who underwent curative hepatectomy between 1986 and 2009 were retrospectively reviewed. Seventeen patients (2.4%) with preoperative serum creatinine levels of >2.0 mg/dl were defined as the RD group, and, of these, seven who did not receive preoperative haemodialysis were defined as borderline patients. Clinicopathological characteristics and postoperative outcomes were compared between the RD group (n= 17) and the non-RD group (n= 705). The postoperative courses of borderline patients were reviewed in detail. RESULTS: Overall survival (P= 0.177) and disease-free survival (P= 0.942) after hepatectomy did not differ significantly between the groups. Incidences of massive ascites (35.3% vs. 14.3%; P= 0.034) and pleural effusion (52.9% vs. 17.6%; P= 0.001), defined as massive effusion (ME), were significantly higher in the RD group than in the non-RD group. Hypoalbuminaemia (≤2.8 g/dl; P= 0.031), heavy blood loss (≥1000 ml; P= 0.012) and intraoperative blood transfusion (P= 0.007) were risk factors for ME. Among the borderline patients, serum creatinine values were not increased immediately after surgery and four patients underwent haemodialysis. CONCLUSIONS: Preoperative hypoalbuminaemia, heavy blood loss and blood transfusion are independent risk factors for ME in RD patients. Preoperative improvement of anaemia and reduction of blood loss by meticulous surgical techniques may prevent ME in RD patients who require hepatectomy for HCC..
1157. T. Ikegami, K. Shirabe, T. Yoshizumi, S. Aishima, Y. A. Taketomi, Y. Soejima, H. Uchiyama, H. Kayashima, T. Toshima, Y. Maehara, Primary Graft Dysfunction After Living Donor Liver Transplantation Is Characterized by Delayed Functional Hyperbilirubinemia, AMERICAN JOURNAL OF TRANSPLANTATION, 10.1111/j.1600-6143.2012.04052.x, 12, 7, 1886-1897, 2012.07, The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult-to-adult LDLT grafts without anatomical, immunological or hepatitis-related issues were included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH-20) was used to characterize PGD. DFH-20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH-20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PT-INR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH-20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH-20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality..
1158. Hideaki Uchiyama, Hiroto Kayashima, Rumi Matono, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Toshiharu Matsuura, Tomoaki Taguchi, Yoshihiko Maehara, Relevance of HLA compatibility in living donor liver transplantation: The double-edged sword associated with the patient outcome, Clinical Transplantation, 10.1111/ctr.12019, 26, 5, E522-E529, 2012.09, HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA-A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host-versus-graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft-versus-host disease (GVHD) was also analyzed. No recipients with recipient-against-donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with "R→D MM 0" together with "donor-against-recipient MM 3" died of fatal GVHD. HLA compatibility in LDLT not only affected the long-term acceptance of graft livers but also the risk of fatal GVHD. © 2012 John Wiley &
Sons A/S..
1159. Tomoharu Yoshizumi, Ken Shirabe, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Masanori Yoshimatsu, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Risk factors that increase mortality after living donor liver transplantation., Transplantation, 10.1097/TP.0b013e318238dacd, 93, 1, 93-8, 2012.01, BACKGROUND: Female liver to male recipient is a well-accepted risk factor for graft loss in cadaveric liver transplantation. However, gender matching is infeasible because of an insufficient number of available donors. No studies have been performed on the role of gender in the field of living donor liver transplantation. This report investigates the effect of gender mismatch on the outcome of living donor liver transplantation. METHODS: A total of 335 patients and donors were classified into four groups according to the following gender combinations: male donor to male recipient group (n=104), male donor to female recipient group (n=120), female donor to male recipient (FM) group (n=59), and female donor to female recipient group (n=52). Patient and graft survival were compared among the groups. We performed a multivariable analysis to identify the factors associated with patient mortality. RESULTS: The 1-, 3-, 5-, and 10-year patient survival rates in the FM group were 80.6%, 66.8%, 61.8%, and 47.7%, respectively. The FM group showed significantly shorter patient survival compared with the other three groups. Independent risk factors for patient mortality were: FM group (P=0.006), pretransplant diabetes mellitus (P=0.001), and a model for end-stage liver disease score more than or equal to 20 (P=0.004). CONCLUSIONS: Male recipients of transplants from female donors, pretransplant diabetes mellitus, and a model for end-stage liver disease score more than or equal to 20 have poor survival rates..
1160. Ken Shirabe, Yohei Mano, Jun Muto, Rumi Matono, Takashi Motomura, Takeo Toshima, Kazuki Takeishi, Hidekaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Masaru Morita, Shunichi Tsujitani, Yoshihisa Sakaguchi, Yoshihiko Maehara, Role of tumor-associated macrophages in the progression of hepatocellular carcinoma., Surgery today, 10.1007/s00595-011-0058-8, 42, 1, 1-7, 2012.01, Recent studies have shown that the tumor microenvironment plays an important role in cancer progression. Tumor-associated macrophages (TAMs), in particular, have been found to be associated with tumor progression. Macrophages have multiple biological roles, including antigen presentation, target cell cytotoxicity, removal of foreign bodies, tissue remodeling, regulation of inflammation, induction of immunity, thrombosis, and endocytosis. Recent immunological studies have identified two distinct states of polarized macrophage activation: the classically activated (M1) and the alternatively activated (M2) macrophage phenotypes. Bacterial moieties such as lipopolysaccharides and the Th1 cytokine interferon-γ polarize macrophages toward the M1 phenotype. The M2 polarization was discovered as a response to the Th2 cytokine interleukin-4. In general, M2 macrophages exert immunoregulatory activity, participate in polarized Th2 responses, and aid tumor progression. TAMs have recently been found to play an important role in hepatocellular carcinoma (HCC) progression. Based on the properties of TAMs, obtained from pathological examination of resected specimens, we have identified new therapeutic approaches, involving the targeting of TAMs with adjuvant therapy after hepatic resection for HCC. This review discusses the roles of TAM in HCC progression and the possibility of new therapies targeting TAMs..
1161. Shohei Yoshiya, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation., Transplantation, 10.1097/TP.0b013e31826969e6, 94, 9, 947-52, 2012.11, BACKGROUND: Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. METHODS: A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. RESULTS: The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). CONCLUSIONS: Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group..
1162. Toru Ikegami, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yoshihiko Maehara, The impact of renal replacement therapy before or after living donor liver transplantation, Clinical Transplantation, 10.1111/j.1399-0012.2011.01450.x, 26, 1, 143-148, 2012.01, Introduction: The impact of renal replacement therapy (RRT) in living donor liver transplantation (LDLT) has not yet been investigated. Methods: Among 253 LDLT patients, RRT was started before (RRT-Pre, n=9), or after (RRT-Post, n=27) LDLT. The clinical outcomes were reviewed. Results: The one-yr graft survival rate was 94.1% without RRT, and 63.9% and in those with RRT (p<
0.0001). Among the RRT patients, the RRT-Pre patients exhibited acute liver failure, hepatorenal syndrome and high model for end-stage liver disease score (35±12), whereas the RRT-Post patients had sepsis as a comorbidity. The one-yr graft survival rate was 100.0% in the RRT-Pre patients vs. 51.9% in the RRT-Post patients (p<
0.01). The duration of RRT was significantly shorter in the RRT-Pre patients than that in the RRT-Post patients (5.3±2.1 vs. 17.8±14.1d, p=0.02). The mean duration between starting RRT and LDLT was 2.1±0.7d in the Pre-RRT patients. Conclusion: The RRT-Pre patients had excellent outcomes because the severe condition was primarily treated by LDLT after short-term pre-transplant RRT. Post-transplant uncontrollable sepsis was the major cause of graft loss in patients who receive RRT after LDLT. © 2011 John Wiley &
Sons A/S..
1163. Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Kazutoyo Morita, Naotaka Hashimoto, Hiroto Kayashima, Tohru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihko Maehara, The long-term outcomes of patients with hepatocellular carcinoma after living donor liver transplantation: a comparison of right and left lobe grafts., Surgery today, 10.1007/s00595-011-0086-4, 42, 6, 559-64, 2012.06, PURPOSE: The feasibility of living donor liver transplantation (LDLT) using left lobe (LL) grafts has been demonstrated. However, the long-term outcome of the hepatocellular carcinoma (HCC) patients with LL grafts has not been elucidated. The aim of this study was to analyze the long-term outcomes after LDLT for HCC according to the graft type. METHODS: A retrospective analysis was performed evaluating the outcomes of LL graft recipients (n = 82) versus recipients of RL grafts (n = 46). The analysis endpoints were the overall and recurrence-free survival after LDLT. The demographics of both recipients and donors, and the tumor characteristics associated with the graft type were also analyzed. RESULTS: The graft volume (436 ± 74 g), as well as the graft volume-standard liver volume rate (38.3 ± 6.2%) of the LL graft group were significantly decreased as compared to those of the RL graft group (569 ± 82 g, 46.3 ± 6.7%; p < 0.01). The 1-, 3-, 5- and 7-year overall survival rates of the LL graft group were 88.2, 80.2, 75.7 and 72.4%, respectively, which were not significantly different compared to those of the RL graft group (95.4, 87.3, 87.3 and 87.3%). The recurrence-free survival rates of the LL graft group (89.1% at 1 year, 78.8% at 3 years, 75.8% at 5 years and 70.3% at 7 years) were similar to those of the RL graft group (88.6, 88.6, 88.6 and 88.6%). The mean peak postoperative total bilirubin levels and duration of hospital stay after surgery for the LL grafting donors were significantly decreased as compared to those of the RL grafting donors (p < 0.01). The rate of severe complications (over Clavien's IIIa) associated with LL graft procurement was 6.2%, which was lower than that in the RL graft group (15.6%). CONCLUSIONS: The long-term outcomes in the HCC patients with LL grafts were similar to those of patients receiving RL grafts, and the outcomes of the donors of LL grafts were more favorable. Therefore, LL grafts should be considered when selecting LDLT for HCC to ensure donor safety..
1164. Akinobu Taketomi, Kazuki Takeishi, Yohei Mano, Takeo Toshima, Takashi Motomura, Shinichi Aishima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Total resection of the right hepatic vein drainage area with the aid of three-dimensional computed tomography., Surgery today, 10.1007/s00595-011-0021-8, 42, 1, 46-51, 2012.01, PURPOSE: We analyzed the feasibility and safety of our preliminary surgical approach for total hepatic resection of the right hepatic vein drainage area (THR-RHV) with the aid of three-dimensional computed tomography (3D-CT) guidance. METHODS: Clinical findings and 3D-CT volumetry results were investigated in five patients who underwent THR-RHV for a hepatic malignant tumor close to the right hepatic vein (RHV). RESULTS: The mean estimated remnant liver volume after a conventional right lobectomy was 474 ml, whereas that after THR-RHV was 614 ml, indicating that 140 ml (13.8%) of additional liver volume had been preserved by performing THR-RHV. The median operative time, mean ischemic time, and mean blood loss during surgery were 406 min, 51 min, and 587 ml, respectively. Histological examinations confirmed a negative surgical margin in all five patients. The mean liver volume estimated by 3D-CT was 458 ml, whereas the mean actual resected liver volume was 468 g, resulting in a mean error ratio of 3.1%. CONCLUSIONS: THR-RHV allowed for a higher remnant liver volume than that after conventional right lobectomy of the liver, and proved feasible with acceptable perioperative results. This technique thus promotes both safety and curability for patients with a tumor close to the RHV..
1165. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Use of an internal jugular vein graft for middle hepatic vein tributary reconstruction in right-lobe living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31825b75b6, 94, 2, e17-e18, 2012.07.
1166. Takeo Toshima, Akinobu Taketomi, Toru Ikegami, Takasuke Fukuhara, Hiroto Kayashima, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, V5-drainage-preserved right lobe grafts improve graft congestion for living donor liver transplantation., Transplantation, 10.1097/TP.0b013e3182488bd8, 93, 9, 929-35, 2012.05, BACKGROUND: Right lobe (RL) grafts without middle hepatic vein for living donor liver transplantation (LDLT) result in congestion of recipients' livers and sometimes in unfavorable postoperative course. This study aimed to evaluate the feasibility of our new V5-drainage-preserved RL (VP-RL) graft. METHODS: Based on a review of 49 donors' livers in a retrospective study using three-dimensional reconstruction-computed tomography volumetry, hepatic vein draining segment 4 (V4) anatomy was classified into three types: inferior V4 dominant (A); superior V4 dominant (B); and umbilical vein to left hepatic vein dominant (C). Differences in functional graft volume (GV) and remnant liver volume (RV) between VP-RL and modified RL (M-RL) grafts with all three types were evaluated. In a prospective study of actual 15 LDLT, the outcome of venous reconstruction and postoperative parameters with VP-RL grafts compared with M-RL grafts was analyzed. RESULTS: In the retrospective study using three-dimensional reconstruction-computed tomography volumetry, in types B and C, functional GV of VP-RL was larger than that of M-RL (P<0.05) without impaired donors' functional RV, whereas functional RV in VP-RL was significantly decreased in type A (P<0.05). In the prospective study of actual 15 LDLT, using VP-RL with types B and C, size and number of venous reconstructions, and functional GV and postoperative parameters, such as postoperative serum total bilirubin levels and ascites volume, were significantly improved compared with those using M-RL (P<0.05). CONCLUSIONS: Using preoperative V4 anatomical classification, VP-RL graft procurement is a valuable strategy in RL-LDLT to improve postoperative course of both recipients and donors..
1167. Mami Kanamoto, Mitsuo Shimada, Yuji Morine, Tomoharu Yoshizumi, Satoru Imura, Toru Ikegami, Hiroki Mori, Yusuke Arakawa, Beneficial Effects of Follistatin in Hepatic Ischemia-Reperfusion Injuries in Rats, DIGESTIVE DISEASES AND SCIENCES, 10.1007/s10620-010-1401-4, 56, 4, 1075-1081, 2011.04, Ischemia-reperfusion injury has been demonstrated in a variety of clinical settings. The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. Follistatin, an activin-binding protein, binds to activins and subsequently blocks their action. It was reported that blockade of the action of activin with administration of follistatin accelerates recovery from ischemia renal injury. This study was conducted to investigate the involvement of the activin-follistatin system in hepatic ischemia-reperfusion injury.
Total hepatic ischemia for 30 min was performed followed by reperfusion in a rat model. Rats were divided into two groups: a follistatin group and a control group. Follistatin (1 mu g/body), which is an activin-binding protein, was administered at the time of reperfusion.
Though 80% of animals survived in the follistatin group, four of five animals died in the control group within 3 days after reperfusion (p < 0.05). AST was significantly lower at 3 h after reperfusion in the follistatin group (p < 0.05). LDH was also lower at 6 h after reperfusion in the follistatin group (p < 0.05). Follistatin inhibited the mRNA expression of the beta A subunit of activin. Moreover, the expression of IL-6, which is an inflammatory cytokine, was suppressed at 6 h after reperfusion in the follistatin group (p < 0.05).
The present study demonstrated that treatment with follistatin reduced the expression of IL-6 and activin resulting in beneficial support for hepatic ischemia-reperfusion injuries..
1168. Ken Shirabe, Takeo Toshima, Akinobu Taketomi, Kennichi Taguchi, Tomoharu Yoshizumi, Hideaki Uchiyama, Norifumi Harimoto, Kiyoshi Kajiyama, Akinori Egashira, Yoshihiko Maehara, Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan., Liver international : official journal of the International Association for the Study of the Liver, 10.1111/j.1478-3231.2011.02572.x, 31, 9, 1366-72, 2011.10, BACKGROUND & AIMS: Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC. METHODS: Hepatocyte AFB1-DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non-B non-C hepatocellular carcinoma (NBNC HCC). RESULTS: AFB1-DNA adducts were detected in hepatocyte nuclei in 18/279 patients (6%), including 13/83 patients (16%) with NBNC HCC and 5/51 patients (10%) expressing hepatitis B surface antigen. None of the patients with HCV Ab (n=136) were positive for AFB1-DNA. The incidence of the G-T transversion and mutations in exon 7 of TP53 in patients with AFB1-DNA adducts were significantly higher in patients with than in patients without AFB1-DNA adducts. All three patients with the codon 249 AGG-AGT mutation had AFB1-DNA adducts. CONCLUSION: Although exposure to AFB1 is thought to be low in Japan, it is still associated with hepatocarcinogenesis, particularly in NBNC HCC and hepatitis B individuals..
1169. Hideaki Uchiyama, Yohei Mano, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Ken Shirabe, Yoshihiko Maehara, Kinetics of anti-blood type isoagglutinin titers and B lymphocytes in ABO-incompatible living donor liver transplantation with rituximab and plasma exchange., Transplantation, 10.1097/TP.0b013e318231e9f8, 92, 10, 1134-9, 2011.11, BACKGROUND: A novel immunosuppression protocol using rituximab and plasma exchange treatment was developed for ABO-incompatible living donor liver transplantation (ABO-I LDLT). The aim of this study was to investigate the kinetics of anti-blood type isoagglutinin titers and the number of blood B lymphocytes in ABO-I LDLT with the new protocol and their impact on the outcomes after ABO-I LDLT. METHODS: Fifteen patients underwent ABO-I LDLT plus splenectomy with the new protocol between November 2005 and December 2010, and their data were retrospectively analyzed. RESULTS: CD19-positive lymphocytes in the blood rapidly disappeared after rituximab treatment and began to recover approximately 6 months later. Anti-blood type isoagglutinin titers were lowered by pretransplant plasma exchange (2(3)∼2(12)→2(1)∼2(8)). Although the anti-donor blood type isoagglutinin titers remained consistently low after transplantation in comparison to the pretreatment levels, they persisted long after LDLT, whereas posttransplant biopsy specimens showed sustained A/B antigens on the graft livers. ABO-I hepatitis C virus-positive patients were prone to acceleration of hepatitis C viremia and cytomegalovirus antigenemia in comparison to the control patients. CONCLUSIONS: Although the new protocol for ABO-I LDLT yielded great success with 100% graft survival, the acceptable anti-blood type isoagglutinin titers just before LDLT, and its application to hepatitis C-positive patients must be determined..
1170. Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Toru Ikegami, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yoshihiko Maehara, Living donor liver transplantation in patients who have received pretransplant treatment for hepatocellular carcinoma, Transplantation, 10.1097/TP.0b013e318210de92, 91, 8, e61-e62, 2011.04.
1171. Toru Ikegami, Ken Shirabe, Kazutoyo Morita, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Hiroto Kayashima, Naotaka Hashimoto, Yoshihiko Maehara, Minimal hilar dissection prevents biliary anastomotic stricture after living donor liver transplantation., Transplantation, 10.1097/TP.0b013e3182336073, 92, 10, 1147-51, 2011.11, BACKGROUND: We introduced a new technique called minimal hilar dissection (Min-HD) technique in living donor liver transplantation (LDLT) to keep vascular networks around the recipient's bile duct. The aim of this study is to investigate whether the Min-HD technique could prevent biliary anastomotic stricture (BAS) after LDLT with duct-to-duct biliary reconstruction. METHODS: An analysis of 214 adult-to-adult LDLT grafts (left lobe, n=135; right lobe, n=76; posterior segment, n=3) with duct-to-duct biliary reconstruction was performed. RESULTS: There were 46 cases with BAS. The incidence of BAS was 32.1% in the conventional technique group (n=84) and 14.6% in the Min-HD technique group (n=130, P=0.003). Multivariate regression analysis regarding BAS was carried out and detected hepatic artery flow less than 50 mL/min (P=0.002), not using the Min-HD technique (P=0.011), biliary anastomotic leakage (BAL, P=0.027) and ductoplasty (P=0.039) for the significant risk factors for BAS. The incidence BAL was 11.9% in the conventional technique group and 0.7% in the Min-HD technique group (P=0.002). No other factors showed an impact on the occurrence of BAL. The treatments for BAS were performed by endoscopic or percutaneous procedures. The cumulative completion rate of the treatment after developing BAS was 45.1% and 78.6% at 1- and 3-year, respectively. The median period for treating BAS was 10.8 months. CONCLUSION: The Min-HD technique is a rational surgical method, and it has the potential for preventing BAS and BAL after duct-to duct biliary reconstruction in LDLT..
1172. Takeo Toshima, Ken Shirabe, Kazuki Takeishi, Takashi Motomura, Youhei Mano, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, New method for assessing liver fibrosis based on acoustic radiation force impulse: a special reference to the difference between right and left liver., Journal of gastroenterology, 10.1007/s00535-010-0365-7, 46, 5, 705-11, 2011.05, BACKGROUND: Virtual touch tissue quantification (VTTQ) based on acoustic radiation force impulse (ARFI) imaging has been developed as a noninvasive bedside method for the assessment of liver stiffness. In this study, we examined the diagnostic performance of ARFI imaging in 103 patients, focusing on the difference in VTTQ values between the right and left liver lobes. METHODS: We evaluated VTTQ values of the right and left lobes in 79 patients with chronic liver disease who underwent histological examination of liver fibrosis and in 24 healthy volunteers. The diagnostic accuracy of VTTQ was compared with several serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index. RESULTS: The VTTQ values (meters per second) in the right and left lobes were 1.61 ± 0.51 and 1.90 ± 0.68, respectively, and the difference was statistically significant (P < 0.0001). The VTTQ values in both liver lobes were correlated significantly with histological fibrosis grades (P < 0.001). The standard deviations of the VTTQ values in the right lobe were significantly lower than those in the left lobe (P < 0.001). The area under the receiver-operating characteristic curve for the diagnosis of fibrosis (F ≥ 3) using VTTQ values in both liver lobes was superior to serum markers, especially in the right lobe. CONCLUSIONS: VTTQ is an accurate and reliable tool for the assessment of liver fibrosis. VTTQ of the right lobe was more accurate for diagnosing liver fibrosis than in the left lobe..
1173. Tetsuo Ikeda, Yusuke Yonemura, Naoyuki Ueda, Akira Kabashima, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yosihiro Kakeji, Masaru Morita, Shunichi Tsujitani, Yoshihiko Maehara, Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver to minimize intraoperative bleeding., Surgery today, 10.1007/s00595-010-4479-6, 41, 12, 1592-8, 2011.12, PURPOSE: Although laparoscopic liver resection has been widely adopted, performing a pure laparoscopic right hepatectomy remains a challenging procedure. The aim of this report is to evaluate the efficiency of a pure laparoscopic right hepatectomy (PLRH) in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver. METHODS: Pure laparoscopic right hepatectomy was performed in the semi-prone position with the use of an intrahepatic Glissonian approach and modified hanging maneuver for patients with primary liver cancer (n = 3) and metastatic liver cancer (n = 1). RESULTS: The intraoperative total blood loss was only 95-140 g (mean: 126.2 g). None of the patients required a blood transfusion, and no serious complications were encountered. The durations of the surgeries ranged from were 308 to 445 min (mean: 394.8 min). The postoperative hospital stay was 8-11 days (mean 9.5 days). CONCLUSION: Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver is thus considered to be a safe modality, which minimizes intraoperative bleeding..
1174. Toru Ikegami, Takashi Maeda, Hiroto Kayashima, Eiji Oki, Tomoharu Yoshizumi, Yoshihisa Sakaguchi, Yasushi Toh, Ken Shirabe, Yoshihiko Maehara, Soft coagulation, polyglycolic acid felt, and fibrin glue for prevention of pancreatic fistula after distal pancreatectomy., Surgery today, 10.1007/s00595-010-4433-7, 41, 9, 1224-7, 2011.09, PURPOSE: To evaluate the effectiveness of using soft coagulation followed by the application of polyglycolic acid (PGA) felt and fibrin glue to prevent pancreatic fistula (PF) after distal pancreatectomy (DP). METHODS: A soft coagulation system was applied on the cut surface of the pancreas after ligating the main pancreatic duct, followed by the application of layers of PGA felt and fibrin glue on the layers, to prevent the development of a PF after DP. RESULTS: This technique was applied in nine patients, with mean drain amylase levels of 372 ± 296, 185 ± 209, 54 ± 40, and 47 ± 34 IU/l on days 1, 3, 5, and 7, respectively, after DP. Only one patient (11.1%) showed a Grade A PF on day 3 after surgery; none of the other patients developed a fistula. CONCLUSIONS: This technique is an effective prophylactic measure to prevent the development of a PF after DP..
1175. Mizuki Ninomiya, Ken Shirabe, Hideki Ijichi, Takeo Toshima, Noboru Harada, Hideaki Uchiyama, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Temporal changes in the stiffness of the remnant liver and spleen after donor hepatectomy as assessed by acoustic radiation force impulse: A preliminary study., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/j.1872-034X.2011.00809.x, 41, 6, 579-86, 2011.06, AIM:   Virtual touch tissue quantification (VTTQ) is an implementation of ultrasound acoustic radiation force impulse imaging that provides numerical measurements of tissue stiffness. We have evaluated the temporal changes of the remnant liver and spleen after living donor hepatectomy with special reference to the differences between right and left liver donation. METHODS:   Nineteen living donors who received right lobectomy (small remnant liver [SRL] group; n = 7) or extended left and caudate lobectomy (large remnant liver [LRL] group; n = 12) were enrolled. They underwent measurement of liver and spleen VTTQ before and after donor surgery. RESULTS:   Virtual touch tissue quantification of the remnant liver increased postoperatively until postoperative day (POD) 3-5, and the values in the SRL group were significantly higher than those in the LRL group at POD 3-9. The values of the spleen also increased after donor surgery and the values in the SRL group were significantly higher than those in the LRL group at POD 3-14. A significant positive correlation between postoperative maximum value of VTTQ and postoperative maximum total bilirubin levels was observed. In liver transplant recipients, there was a significant positive correlation between preoperative spleen VTTQ and the corresponding actual portal venous pressure that was measured at the time of transplant surgery. CONCLUSION:   Stiffness of the remaining liver and spleen in the smaller remnant liver group became harder than that in the larger remnant liver group. Perioperative measurement of liver and spleen VTTQ seems to be a useful means for assessing the physiology of liver regeneration..
1176. T. Motomura, A. Taketomi, T. Fukuhara, Y. Mano, K. Takeishi, T. Toshima, N. Harada, H. Uchiyama, T. Yoshizumi, Y. Soejima, K. Shirabe, Y. Matsuura, Y. Maehara, The Impact of IL28B Genetic Variants on Recurrent Hepatitis C in Liver Transplantation: Significant Lessons from a Dual Graft Case, AMERICAN JOURNAL OF TRANSPLANTATION, 10.1111/j.1600-6143.2011.03537.x, 11, 6, 1325-1329, 2011.06, IL28B genetic polymorphism is related to interferon-sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51-year-old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated-interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients..
1177. T. Ikegami, Y. Soejima, K. Shirabe, A. Taketomi, T. Yoshizumi, H. Uchiyama, T. Fukuhara, T. Ikeda, Y. Maehara, Evolving Strategies to Prevent Biliary Strictures After Living Donor Liver Transplantation, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2010.07.091, 42, 9, 3624-3629, 2010.11, Introduction. The optimal surgical technique has not been elucidated that reduces the occurrence of biliary strictures after living donor liver transplantation (LDLT).
Method. We performed retrospective analysis of 193 consecutive LDLTs, including 78 right and 115 left lobe grafts. An external biliary stent was used for all of the cases.
Results. The overall 1-, 3-, and 5-year biliary stricture free survival rates were 87.5%, 85.3%, and 85.3%, respectively. The 1- and 3-year biliary stricture free survival rates for duct-to-duct reconstruction were 86.9% and 84.9%, and those for hepaticojejunostomy were 90.1% and 80.8%, respectively. A multivariate analysis revealed that the original number of graft bile ducts greater than the number of external stents, right lobe grafts, bile leaks, and recipient age older than 60 years represented the significant risk factors (P < .05) to develop a biliary stricture after LDLT. All cases with biliary strictures (n = 61) were initially managed nonsurgically, but 4 patients ultimately required interventions.
Conclusions. Biliary reconstruction in LDLT using an appropriate number of external stents resulted in fairly acceptable outcomes. However, not only the proper use of stents or graft selection, but also nonsurgical factors, are important factors that determine the incidence of biliary strictures after LDLT..
1178. Takasuke Fukuhara, Toru Ikegami, Kazutoyo Morita, Kenji Umeda, Shigeru Ueda, Shigeyuki Nagata, Keishi Sugimachi, Tomonobu Gion, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Impact of preoperative serum sodium concentration in living donor liver transplantation., Journal of gastroenterology and hepatology, 10.1111/j.1440-1746.2009.06162.x, 25, 5, 978-84, 2010.05, BACKGROUND AND AIMS: The importance of hyponatremia in deceased donor liver transplantation (DDLT) has been recently discussed frequently. However, its impact on the outcomes in living donor liver transplantation (LDLT) has not yet been elucidated. The current study was designed to demonstrate the impact of pre-transplant sodium concentration on postoperative clinical outcomes. METHODS: One hundred and thirty-four patients who underwent LDLT for end-stage liver diseases were examined to evaluate the significance of pre-transplant hyponatremia (Na < or = 130 mEq/L) on the short-term clinical outcomes and the efficacy of the Model for End-Stage Liver Disease and serum sodium (MELD-Na) score using the sodium concentration and original MELD score. RESULTS: The preoperative sodium and MELD score for all patients were 133.9 mEq/L (range: 109-142) and 16.2 (range: 6-38), respectively. According to a multivariate analysis, not only the MELD score (P = 0.030) but also the sodium concentration (P = 0.005) were found to be significant predictive factors for short-term graft survival. Preoperative hyponatremia was a significant risk factor for the occurrence of sepsis (P < 0.001), renal dysfunction (P < 0.001) and encephalopathy (P = 0.026). The MELD-Na score was 19.6 (range: 6-51) and the area under the receiver-operator curve of that (c-statistics: 0.867) was higher than MELD score and sodium concentration (c-statistics: 0.820 and 0.842, respectively). CONCLUSION: Preoperative hyponatremia was a significant risk for postoperative complications and short-term graft loss. The addition of sodium concentration to MELD score might therefore be an effective predictor for post-transplant short-term mortality in LDLT..
1179. Akinobu Taketomi, Takasuke Fukuhara, Kazutoyo Morita, Hiroto Kayashima, Mizuki Ninomiya, Yoichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihko Maehara, Improved results of a surgical resection for the recurrence of hepatocellular carcinoma after living donor liver transplantation., Annals of surgical oncology, 10.1245/s10434-010-0999-y, 17, 9, 2283-9, 2010.09, PURPOSE: This study was designed to analyze the clinical outcomes of the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and to evaluate the efficacy of a surgical resection in treating such a recurrence. METHODS: A total of 101 adult LDLT recipients with HCC between 1996 and 2007, including 17 who had recurrent HCC, were reviewed. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics, laboratory valuables, and tumor characteristics were analyzed. Any medical or surgical treatments that had been administered for any recurrence also were considered. RESULTS: The mean duration until the initial recurrence after LDLT and the mean duration until death after the initial recurrence were 12.9 months and 12.0 months, respectively. A univariate analysis showed that gender, interferon therapy, early posttransplant tumor recurrence, and eligibility for a surgical resection all had a beneficial impact on survival from tumor recurrence. A surgical resection of tumor relapse was the most important variable in our study, and therefore the patients were divided into two groups: surgical therapy group (n = 9), and nonsurgical therapy group (n = 7). Interestingly, the overall survival rates of the surgical group were significantly better than those of the nonsurgical group and were similar to that of the patients without HCC recurrence. CONCLUSIONS: Surgical therapy might be useful for patients who experience a recurrence of HCC after LDLT to improve their outcome, when such treatment is available..
1180. Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Natsumi Yamashita, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Mizuki Ninomiya, Yoshihiko Maehara, Living donor liver transplantation in patients older than 60 years., Transplantation, 10.1097/TP.0b013e3181e81b2d, 90, 4, 433-7, 2010.08, BACKGROUND: Living donor liver transplantation (LDLT) has been performed in adult patients. However, there are a few reports on how recipient age affects the outcome of LDLT. This study assessed LDLT outcome in patients aged 60 years or older. METHODS: A total of 267 patients were enrolled and classified into two groups: those younger than 60 years (younger group, n=210) and those aged 60 years or older (older group, n=57). The 6-month and 1-, 3-, and 5-year patient survivals and the incidence of complications were compared. Multivariate analysis was performed to identify the risk factors. RESULTS: Fifty-five of 57 (96.5%) donors in the older group were younger than 50 years (range 25-47 years), whereas only 177 of 210 (84.3%) donors in the younger group were younger than 50 years (P<0.0001). The 6-month and 1-, 3-, and 5-year patient survival rates of the older group were 92.9%, 85.3%, 72.7%, and 70.3%, respectively, whereas those of the younger group were 87.4%, 85.8%, 80.2%, and 78.2%, respectively. Neither difference was significant. A multivariate analysis revealed that the presence of diabetes, lack of hepatocellular carcinoma, and Model for End-Stage Liver Disease (MELD) Score more than or equal to 20 were independent risk factors for survival less than 1 year after LDLT (P=0.0003, P=0.014, and P=0.041, respectively). Another multivariate analysis revealed that the lack of consanguinity, MELD Score more than or equal to 20, and male recipient were independent risk factors for death 1 year or more after LDLT (P=0.004, P=0.005, and P=0.015, respectively). CONCLUSION: Recipient age did not affect LDLT outcome when patients with MELD Score less than 20 received grafts from consanguineous donors..
1181. Keishi Sugimachi, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Yo-Ichi Yamashita, Kenji Umeda, Kazutoyo Morita, Yoshihiko Maehara, Successful curative extracorporeal hepatic resection for far-advanced hepatocellular carcinoma in an adolescent patient., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.22051, 16, 5, 685-7, 2010.05.
1182. Tomonobu Gion, Akinobu Taketomi, Ken Shirabe, Hirofumi Hasegawa, Takayuki Hamatsu, Yo-Ichi Yamashita, Keishi Sugimachi, Tomoharu Yoshizumi, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, The role of serum interleukin-8 in hepatic resections., Surgery today, 10.1007/s00595-008-4086-y, 40, 6, 543-8, 2010.06, PURPOSE: Interleukin-8 (IL-8) is a neutrophil chemotactic factor, which is associated with some inflammatory diseases and various types of surgical stress. The aim of this study was to investigate whether the early postoperative serum IL-8 level may potentially be a new indicator of a surgical stress in patients undergoing a hepatic resection. METHODS: The serum IL-8 levels were measured in 37 patients who underwent a hepatectomy. The serum IL-8 levels were serially measured using an enzyme-linked immunosorbent assay both before and after a hepatic resection. In addition, the correlation between the postoperative IL-8 value and several clinical variables were examined. RESULTS: The mean level of IL-8 significantly increased immediately after the operation (P < 0.01 vs before the operation) and decreased on the first postoperative day (POD 1, P < 0.05 vs after the operation). The early postoperative IL-8 levels positively correlated with the length of the procedure (r = 0.383; P < 0.05), the estimated blood loss (r = 0.483; P < 0.01) and the serum bilirubin level on POD 1 (r = 0.390; P < 0.05), and inversely correlated with the white blood cell counts (r = -0.388; P < 0.05) and lymphocyte counts on POD 1 (r = -0.424; P < 0.05). In a comparison of the postoperative IL-8 levels with the surgical factors, there was a significant difference in the extension of the resection (P < 0.05) and in blood transfusion. The patients with a fever of more than 38 degrees C showed higher levels of IL-8 immediately after the operation than those without fever (P < 0.01). CONCLUSIONS: The early postoperative serum IL-8 level was found to correlate with the degree of the severity of surgery in patients undergoing a hepatic resection, and it is also considered to be a new indicator of surgical stress and liver injury..
1183. Ken Shirabe, Takashi Motomura, Jun Muto, Takeo Toshima, Rumi Matono, Yohei Mano, Kazuki Takeishi, Hideki Ijichi, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Tumor-infiltrating lymphocytes and hepatocellular carcinoma: pathology and clinical management., International journal of clinical oncology, 10.1007/s10147-010-0131-0, 15, 6, 552-8, 2010.12, The presence of tumor-infiltrating lymphocytes (TILs) in hepatocellular carcinoma (HCC) is relatively rare. The prognosis of patients with HCC and marked TILs is better than that of patients with HCC without TILs. TILs in HCC tissues are mainly T cells, and previous reports suggested that TILs might be important antitumor effector cells. TILs have been extensively analyzed, and subpopulations of CD3(+), CD4(+), and CD8(+) T cells are often present in HCC. Some studies have reported that the percentage of CD8(+) T cells, which might have cytotoxic activity, is decreased in tumors with TILs, as compared with noncancerous tissues. Although the antitumor effects of TILs seem to be impaired in HCCs, the underlying mechanism has remained unclear until quite recently. Pathological and in vitro studies have now shown that regulatory T cells play important roles in the deterioration of the antitumor effects of TILs. The aim of this review is to introduce recent pathological findings for TILs in HCC and to evaluate new therapeutic strategies in this field..
1184. Yusuke Arakawa, Mitsuo Shimada, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Hirohumi Kanemura, Beneficial effects of splenectomy on massive hepatectomy model in rats, HEPATOLOGY RESEARCH, 10.1111/j.1872-034X.2008.00469.x, 39, 4, 391-397, 2009.04, Possible spleno-hepatic relationships during hepatectomy remain unclear. The purpose of this study was to investigate the impact of splenectomy during massive hepatectomy in rats.
Rats were divided into the following two groups: 90% hepatectomy (Hx group), hepatectomy with splenectomy (Hx+Sp group). The following parameters were evaluated; survival rate, biochemical parameters, quantitative RT-PCR for hemeoxygenase-1 (HO-1) and tumor necrosing factor alpha (TNF alpha), immunohistochemical staining for HO-1, proliferating cell nuclear antigen labeling index and liver weights.
The survival rate after massive hepatectomy significantly improved in Hx+Sp group as well as serum biochemical parameters, compared with Hx group (P < 0.05). HO-1 positive hepatocytes and its mRNA expression significantly increased and TNF alpha mRNA expression significantly decreased in Hx+Sp group compared with Hx group (P < 0.05). Moreover, liver regeneration was significantly accelerated at 48 and 72 h after hepatectomy in Hx+Sp group.
Splenectomy had beneficial effects on massive hepatectomy by ameliorating liver injuries and promoting preferable liver regeneration..
1185. Toru Ikegami, Takeo Toshima, Kazuki Takeishi, Yuji Soejima, Hirofumi Kawanaka, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Bloodless splenectomy during liver transplantation for terminal liver diseases with portal hypertension., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2008.10.034, 208, 2, e1-4-4, 2009.02.
1186. Kensaku Sanefuji, Hiroto Kayashima, Tomohiro Iguchi, Keishi Sugimachi, Yo-Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Takashi Nishizaki, Akinobu Taketomi, Yoshihiko Maehara, Characterization of hepatocellular carcinoma developed after achieving sustained virological response to interferon therapy for hepatitis C., Journal of surgical oncology, 10.1002/jso.21176, 99, 1, 32-7, 2009.01, BACKGROUND: Interferon (IFN) reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). However, HCC develops in the some patients who have achieved a sustained virological response (SVR). The aim of this study was to clarify the features and prognosis of SVR patients who developed HCC. MATERIALS AND METHODS: Twenty-six patients who underwent curative hepatectomy for initial HCC after IFN therapy were closely investigated. Twenty patients who were seropositive for HCV-RNA (non-SVR), and a further 6 patients who achieved SVRs (SVR) were included. We analyzed the clinicopathological features, immunological expression levels of p53 and whether HCV-RNA is present in the excised liver. RESULTS: The liver functions of the SVR group were almost better than those of the non-SVR group. However, there was no significant difference in pathological features, surgical factors and prognosis between the groups. In one case with SVR out of eight specimens tested was HCV-RNA detected in the non-cancerous tissue. Immunohistochemistry revealed overexpression of p53 in eight HCCs (100%) from SVR patients. CONCLUSION: Recurrent HCC still developed after the curative hepatectomy, even if viral elimination had been successful. And molecular alterations in hepatocarcinogenesis of SVR patients might be different from those of CHC patients..
1187. Yuuta Kasagi, Koji Yamazaki, Akihiko Nakashima, Takeshi Yamana, Nami Yamashita, Hiroto Kayashima, Yuji Hoshino, Mayumi Ishida, Tomoharu Yoshizumi, Noriaki Sadanaga, Atsushi Fukuda, Hiroshi Matsuura, Kenichiro Okadome, Chondroblastic osteosarcoma arising from the pleura: Report of a case, SURGERY TODAY, 10.1007/s00595-009-3995-8, 39, 12, 1064-1067, 2009.12, Extraskeletal osteosarcoma is an uncommon malignant neoplasm. The origin of osteosarcoma in the pleura is extremely rare, with only four such cases so far documented in the literature to the best of our knowledge. We herein report the case of a 64-year-old Japanese man in whom a left pneumonectomy and pleurectomy were carried out to remove a huge tumor. The pathological examination confi rmed a diagnosis of chondroblastic osteosarcoma that had originally arisen from the pleura..
1188. Akinobu Taketomi, Hiroto Kayashima, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, Donor risk in adult-to-adult living donor liver transplantation: impact of left lobe graft., Transplantation, 10.1097/TP.0b013e3181943d46, 87, 3, 445-50, 2009.02, BACKGROUND: To ensure donor safety in adult-to-adult living donor liver transplantation, we established a selection criterion for donors in which left lobe (LL) was the first choice of graft. METHODS: Two hundred six consecutive donors were retrospectively studied. Donors were divided into two groups according to graft type: LL graft (n=137) and right lobe (RL) graft (n=69). RESULTS: Although mean intraoperative blood loss of LL was significantly increased compared with RL, mean peak postoperative total bilirubin levels and duration of hospital stay after surgery were significantly less for LL than RL (P<0.05). No donor died or suffered a life-threatening complication during the study period. The overall complication rate was 34.0%, including biliary complications in 5.3%. The number of biliary complications was four (2.9%) in LL and seven (10.1%) in RL (P<0.05). Logistic regression analysis revealed that only graft type (LL vs. RL) is significantly related to the occurrence of biliary complications (odds ratio 0.11; P=0.0012). The cumulative overall graft survival rates in the recipients with LL were not significantly different from that in the recipients with RL. CONCLUSIONS: LL grafting should be considered favorably when selecting donors for adult-to-adult living donor liver transplantation..
1189. T. Yoshizumi, Y. Ikeda, Y. Kaneda, K. Sueishi, Ex Vivo Transfer of Nuclear Factor-κB Decoy Ameliorates Hepatic Cold Ischemia/Reperfusion Injury, Transplantation Proceedings, 10.1016/j.transproceed.2008.10.101, 41, 5, 1504-1507, 2009.06, Cold ischemia/reperfusion injury of the hepatic graft has been attributed to the release of various inflammatory cytokines. Specific inhibition of these cytokines may improve viability of the hepatic graft upon reperfusion. Herein we have assessed the efficacy of cis element decoy against nuclear factor-κB binding site delivery to the hepatic tissue in a rodent liver transplantation model. At 8 hours after reperfusion of the liver, significant reduction was noted in the livers treated with decoy in the release of cytosolic enzymes from the hepatocytes and in serum tumor necrosis factor α (P <
.05). The neutrophilic infiltration into the hepatic grafts was significantly suppressed in the livers treated with decoy oligodeoxynucleotides (ODNs). Decoy ODNs against nuclear factor-κB binding site delivery improved the viability of the hepatic graft against cold ischemia/reperfusion injury in the rodent liver transplantation model. © 2009 Elsevier Inc. All rights reserved..
1190. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hirofumi Kawanaka, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Hypersplenism after living donor liver transplantation, Hepato-Gastroenterology, 56, 91-92, 778-782, 2009.05, Background/Aims: It has not determined whether post-transplant persistent hypersplenism (PTPH) occurs after living donor liver transplantation (LDLT). Methodology: One hundred and ninety-four patients who survived more than 6 months after LDLTs were examined for the evaluation to determine the incidence of PTPH (leukocyte counts <
3,500/μL and/or platelet counts <
7.5×104/μL). In addition, 154 patients without a splenectomy were evaluated for the risk factors for PTPH. Results: The incidence of PTPH was 20.1% (n=31/154), and the occurrence ranged between 1.1 and 9.9 years after the LDLT, with the mean follow-up periods of 3.3±2.5 years. Multivariate analysis showed that portal pressure >
30mmHg at the time of the laparotomy (p<
0.01) and post-LDLT small for size syndrome (p<
0.01) are risk factors for PTPH. For those with severe portal hypertension (>
30 mmHg at laparotomy), the splenectomy tended to give better survival rate (p=0.09) without increasing the rate of septic complications. Conclusions: Hypersplenism did persist in a proportion of patients after LDLT. A high-risk for PTPH, especially severe portal hypertension, may be an indication for a splenectomy during LDLT in order to achieve uncomplicated post-transplant recovery. © H.G.E. Update Medical Publishing S.A..
1191. Akinobu Taketomi, Kensaku Sanefuji, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uhciyama, Toru Ikegami, Noboru Harada, Yoichi Yamashita, Keishi Sugimachi, Hiroto Kayashima, Tomohiro Iguchi, Yoshihko Maehara, Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation., Transplantation, 10.1097/TP.0b013e3181943bee, 87, 4, 531-7, 2009.02, BACKGROUND: Because many patients who did not meet the Milan criteria have survived long after undergoing living donor liver transplantation (LDLT), extended criteria for recipient with hepatocellular carcinoma (HCC) are therefore considered to be necessary. METHODS AND RESULTS: A total of 90 consecutive adult LDLT recipients with HCC between 1996 and 2007 were reviewed. The recurrence-free survival rates of all 90 patients were 86.0%, 81.3%, and 81.3% at 1, 3, and 5 years, respectively. Fourteen of 90 patients developed a recurrence of tumor after the LDLT. The tumor recurrences were diagnosed within 1 year after the LDLT in 11 (78.6%) patients. In a multivariate analysis, both the tumor size of less than 5 cm (P=0.0202) and the des-gamma-carboxy prothrombin (DCP) level of less than 300 mAU/mL (P=0.0001) were found to be favorable independent factors for the recurrence of HCC after LDLT. Therefore, the authors devised new selection criteria for HCC patients (a tumor size of <5 cm or a DCP of <300 mAU/mL). The 1-, 3-, and 5-year overall or recurrence-free survival rates of the 85 patients who met the new criteria were 92.3%, 85.9%, and 82.7%, or 90.5%, 87.0%, and 87.0%, respectively, which were significantly different from those of the five patients who did not meet the new criteria (P<0.0001). CONCLUSIONS: A combination of two factors, namely the tumor size and the DCP level, was found to be useful for expanding the selection of LDLT candidates for HCC..
1192. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Shigeyuki Nagata, Yoshihiko Maehara, Potential risk in using hepatic veins of a native liver for reconstructing accessory veins in right lobe living donor graft, Transplantation, 10.1097/TP.0b013e3181aae502, 88, 1, 143-144, 2009.07.
1193. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Tomohiro Iguchi, Naotaka Hashimoto, Yoshihiko Maehara, Rituximab, IVIG, and plasma exchange without graft local infusion treatment: a new protocol in ABO incompatible living donor liver transplantation., Transplantation, 10.1097/TP.0b013e3181adcae6, 88, 3, 303-7, 2009.08, BACKGROUND: Although graft local infusion (GLI) treatment via the portal vein or the hepatic artery has been the pivotal strategy in ABO incompatible (ABOi) living donor liver transplantation (LDLT) in Japan, the procedure is associated with a high rate of catheter-associated complications. METHODS: A new ABOi-LDLT protocol has been implemented using rituximab, intravenous immune globulin (IVIG), plasma exchange (PE), and splenectomy, without using GLI, on four patients, since 2007. Three other patients, treated before 2007, received GLI. RESULTS: Three of the four patients with liver cirrhosis received rituximab over 3 weeks before LDLT, followed by PEs and post-LDLT IVIG, resulting in no rebound elevation of the isoagglutinin titers. The remaining patient, with fulminant hepatitis, received rituximab 3 days before the LDLT, resulting in antibody-mediated rejection, successfully treated by IVIG and PE. All four patients that were treated with the new protocol are alive, 26, 8, 6, and 5 months after ABOi-LDLT with normal liver function. Two of the three other patients with GLI, before 2007, had catheter-associated complications, including one graft loss. CONCLUSION: The new ABOi-LDLT protocol using rituximab, IVIG, and PE, without the use of GLI, therefore seems to be a safe and an effective treatment modality..
1194. T. Ikegami, A. Taketomi, Y. Soejima, T. Yoshizumi, T. Fukuhara, K. Kotoh, S. Shimoda, M. Kato, Y. Maehara, The Benefits of Interferon Treatment in Patients Without Sustained Viral Response After Living Donor Liver Transplantation for Hepatitis C, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2009.08.070, 41, 10, 4246-4252, 2009.12, Although it has been recognized that interferon (IFN) treatment is crucial for recurrent hepatitis C after liver transplantation, its benefits have not been determined among patients without a sustained viral response (SVR).
Methods. Eighty patients who received IFN plus ribavirin treatment after living donor liver transplantation were grouped as follows: group I (n = 18) SVR; group II (n = 25) no-SVR but viral response [VR] positive; Group III (n = 13) no-VR but biochemical response [BR] positive; and group IV (n = 24) no-VR and no-BR.
Results. In groups II and III, not only the histological activity grade and fibrosis stage, but also the serum parameters including transaminases and type IV collagen were stable for 3 years after induction of IFN-based treatment. In group 1, the activity grade and fibrosis stage significantly improved (P < .01). In group IV, the fibrosis stage significantly deteriorated (P < .01); the serum transaminases and type IV collagen were significantly higher than the other groups (P < .01). The mean duration of IFN treatment was significantly longer among group II (96 weeks) compared with the other cohorts (P < .05). The 5-year graft survival rate in groups II (91%) and III (100%) were comparable to those of group I (100%); group IV (62%) was significantly lower than the other groups (P < .05).
Conclusion. IFN treatment was beneficial even among subjects with IFN-dependent VR or BR, although they did not achieve SVR..
1195. Toru Ikegami, Mitsuo Shimada, Satoru Imura, Yuji Soejima, Tomoharu Yoshizumi, Jun Hanaoka, Yuji Morine, Yoshihiko Maehara, The Changes of the Medial Right Lobe, Transplanted With Left Lobe Liver Graft From Living Donors, TRANSPLANTATION, 10.1097/TP.0b013e318195c2a3, 87, 5, 698-703, 2009.03, Background. Procurement of left lobe (LL) living donor graft with medial right lobe (mRL) might be an innovative technique.
Methods. The grafts were procured from a living donor, exposing the right anterior Glissonean pedicles, after confirmation of the demarcation line by test-clamping of the right Glissonean pedicle. Based on serial computed tomography, the increase in the graft volume (GV) after addition of mRL and changes in volumes were evaluated.
Results. The addition of mRL (n = 7) increased GV by 48 +/- 9 g, which corresponded to a 4% increase in GV-to-standard liver volume ratio. After transplantation, mRL volume has increased in all cases. The regeneration rate of the mRL and other LL segments 1 month after transplantation was 61% +/- 18% and 146% +/- 15%, respectively. Viable hepatic parenchyma with marginal bile duct dilatations in transplanted mRL was observed in all the cases. Marginal enhancement was observed in those cases with promoted regeneration of transplanted mRL. In the cranial part of the mRL, portal branching from the left portal vein, over the middle hepatic vein, was observed in all cases.
Conclusion. This technique affords all increase in GV in living donor LL procurement, and should increases the application of LL grafts in living donor liver transplantation..
1196. Satoru Imura, Mitsuo Shimada, Kotaro Miyahe, Tetsuya Ikemoto, Yuji Morine, Tomoharu Yoshizumi, A new technique to acquire additional liver volume for left lobe graft in living donor liver transplantation, HEPATO-GASTROENTEROLOGY, 55, 85, 1206-1210, 2008.07, Background/Aims: Left lobe graft is an ideal option to minimize potential risk for the donor in adult living-donor liver transplantation (LDLT). However, its use is restricted due to size limitations. The purpose of this study was to determine the impact of a new technique for the acquisition of additional liver volume for left lobe graft.
Methodology: Three donors underwent left hepatic lobectomy by exploiting a new technique as follows: a demarcation line was marked by clamping the right first Glisson's pedicle. A parenchymal transection plane was located 1cm right side from the demarcation line and just on the left side of the right anterior Glisson's pedicle. A part of the anterior segment added to the left lobe graft by this procedure belonged to right anterior segment by preoperative CT. The preoperative volumetry of the liver was performed using the 3D-CT software, which was able to calculate total liver volume and the volume of each vessel's territories. Additional liver volume was calculated by preoperative CT scan and defined as part of the perfusion area by the right anterior portal branch. Blood perfusion of the additional liver area was postoperatively assessed by dynamic CT, and graft outcome was also evaluated.
Results: An additional gain ranged from 40mL to 51mL (mean 41.8mL). GV/SLV was 35.7, 60.0, and 41.0%. The rate of additional volume in GV/SLV ranged from 7.2-8.4% (mean 7.6%). All grafts functioned well. The CT scan performed on early postoperative period confirmed excellent blood perfusion the additional segment. No complication attributable to small-for-size graft was noted.
Conclusions: This new technique for left lobe graft harvesting proved a promising approach to gain additional volume, thereby avoiding small-for-size graft in adult LDLT..
1197. Yuji Soejima, Takasuke Fukuhara, Kazutoyo Morita, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara, A simple hilar dissection technique preserving maximum blood supply to the bile duct in living donor liver transplantation., Transplantation, 10.1097/TP.0b013e318188d4dc, 86, 10, 1468-9, 2008.11, Duct-to-duct reconstruction is associated with a higher incidence in biliary strictures in living donor liver transplantation (LDLT). However, a standard dissection technique for the recipient's bile duct has not been established. Here, we describe a simple bile duct dissection technique preserving maximum vascular integrity during total hepatectomy of the recipient. The present technique might facilitate duct-to-duct bile duct reconstruction in both right and left lobe LDLT and, thus, contribute to reduce biliary complications such as biliary strictures. We believe that this technique can be a standard in the field of LDLT..
1198. Hiroto Kayashima, Akinobu Taketomi, Yusuke Yonemura, Hideki Ijichi, Noboru Harada, Tomoharu Yoshizumi, Yuji Soejima, Kengo Yoshimitsu, Yoshihiko Maehara, Accuracy of an age-adjusted formula in assessing the graft volume in living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.21547, 14, 9, 1366-71, 2008.09, In living donor liver transplantation, the estimated graft volume (GV) from young donors tends to be overestimated. One reason for this error may be a decrease in GV due to dehydration by University of Wisconsin (UW) solution. The aim of this study was to clarify (1) the usefulness of an age-adjusted formula and (2) the correlation between the decrease in GV and donor age. First, we created the age-adjusted formula using regression analysis retrospectively in 167 donors, and we evaluated the difference in the error ratio of GV from the age-adjusted formula and 3-dimensional computed tomography (3D-CT) prospectively in 49 donors. Second, we measured intraoperative GV both before and after flushing with UW solution and calculated the decrease ratio, and we then evaluated the difference in the decrease ratio between young donors and older donors prospectively in 41 donors. The age-adjusted formula was created as follows: age-adjusted GV = 70.767 + (0.703 x GV estimated with 3D-CT volumetry) + (1.298 x donor age). The mean error ratio for the age-adjusted formula (9.6%) was significantly lower than that from 3D-CT (14.0%). The mean decrease ratio in all 41 donors was 5.4%, and that in young donors (6.9%) was significantly higher than that in older donors (4.4%). In conclusion, although younger donor age is a major factor for estimation errors in hepatic volumetry, our age-adjusted formula is very useful in reducing the error in estimating GV..
1199. Shigeyuki Nagata, Mitsuo Shimada, Yuji Soejima, Takashi Nishizaki, Tomoharu Yoshizumi, Yoshihiho Maehara, Adult-to-adult living donor liver transplantation in severe portosystemic shunt cases, HEPATO-GASTROENTEROLOGY, 55, 82-83, 666-669, 2008.03, To date, the need for spontaneous portosystemic shunt division during adult-to-adult living donor liver transplantation (LDLT) remains unknown. This study reports 2 patients with large portosystemic shunts who required LDLT. The first patient was a 40-year-old male with liver cirrhosis due to hepatitis C. The angiogram showed splenosystemic shunts with hepatopetal flow. Shunt occlusion was not performed after implanting a small-size graft because sufficient portal blood flow was observed. On the first postoperative day, portal blood flow was not detected; therefore shunt. occlusion was per formed and the portal blood flow was restored. The second patient was a 51-year-old female with primary biliary cirrhosis. Marked collateral circulation with hepatofugal flow was observed. Shunt occlusion was performed after implanting a medium-size graft. Postsurgery, hepatopetal portal blood flow was observed and the postoperative course was satisfactory. These cases demonstrate that large portosystemic shunts should be ligated to maintain adequate portal blood flow that corresponds to the graft volume..
1200. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Yo-ichi Yamashita, Shinji Itoh, Yosuke Kuroda, Yoshihiko Maehara, Assessment of graft fibrosis by transient elastography in patients with recurrent hepatitis C after living donor liver transplantation., Transplantation, 10.1097/01.tp.0000297248.18483.16, 85, 1, 69-74, 2008.01, BACKGROUND: Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness and therefore can be a promising tool to evaluate liver fibrosis and avoid liver biopsy. We prospectively assessed the performance of transient elastography in patients with recurrent hepatitis C virus after living donor liver transplantation, in comparison with the surrogate serum markers. METHODS: Fifty-six patients with recurrent hepatitis C virus after living donor liver transplantation, who underwent both liver biopsy and transient elastography were included in this study. The grade of liver fibrosis (the Scheuer classification) obtained by biopsy was compared to liver stiffness measured by the transient elastography. RESULTS: The fibrosis grades were as follows: F0, n=22; F1, n=13; F2, n=9; F3, n=7; and F4, n=5. Liver stiffness values ranged from 2.9 to 72.0 kPa. The optimal cutoff values were 8.8 kPa for F>or=1, 9.9 kPa for F>or=2, 15.4 kPa for F>or=3, and 26.5 kPa for F>or=4. The area under the receiver operator characteristic curve for the diagnosis of fibrosis (F>or=2) by transient elastography was 0.92, while that by hyaluronic acid, type 4 collagen, alanine aminotransferase, and the aspartate transaminase to platelets ratio index were 0.52, 0.62, 0.64, and 0.70, respectively. CONCLUSIONS: These data suggest that transient elastography is a simple, noninvasive and reliable tool to assess liver fibrosis in patients with recurrent hepatitis C virus after living donor liver transplantation..
1201. Nao Kinjo, Hirofumi Kawanaka, Morimasa Tomikawa, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Shohei Yamaguchi, Daisuke Yoshida, Yoshihiko Maehara, B-RTO for ectopic variceal bleeding after living donor liver transplantation, HEPATO-GASTROENTEROLOGY, 55, 81, 241-243, 2008.01, Gastrointestinal bleeding (GIB) is a serious gas-troenterological complication after orthotropic liver transplantation, as well as living donor liver transplantation (LDLT). Although ectopic varices are rare causes of GIB, they may lead to life-threatening bleeding and it is difficult to diagnose them. We herein report a rare case of a jejunal variceal bleeding in a recipient five years after LDLT for primary sclerosing cholangitis with successful result by balloon-occluded retrograde transvenous obliteration (B-RTO)..
1202. Takuya Tokunaga, Toru Ikegami, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Hisamitsu Shinohara, Mitsuo Shimada, Beneficial Effects of Fluvastatin on Liver Microcirculation and Regeneration After Massive Hepatectomy in Rats, DIGESTIVE DISEASES AND SCIENCES, 10.1007/s10620-008-0241-y, 53, 11, 2989-2994, 2008.11, Fluvastatin, the first entirely synthetic statin, has a significant cholesterol-lowing effect comparable with other statins. In addition, it has been shown to inhibit oxidative stress and improve vascular endothelial function. The aim of this study was to clarify the pretreatment effects of fluvastatin on liver function after massive hepatectomy in rats. Six-week-old male Wister rats were divided into two groups: a fluvastatin group (group F), pretreated with oral administration of fluvastatin (20 mg/kg per day) for 2 days before 90% hepatectomy; and a control group (group C), pretreated with vehicle for 2 days before hepatectomy. Animals were sacrificed at 0, 12, 24, 48, and 72 h after hepatectomy. The liver regeneration rate, liver function tests, and hepatic stellate cell activation were examined. The liver regeneration rate in group F was significantly higher at 72 h after hepatectomy (P < 0.05). The serum level of total bilirubin in group F was significantly lower at 48 h after hepatectomy (P < 0.05). Sinusoidal area in group F was maintained histologically. Furthermore, the expression of alpha smooth-muscle actin (alpha-SMA) protein in the liver was inhibited in group F at 48 h after hepatectomy. This study demonstrated the beneficial effects of fluvastatin in a lethal massive hepatectomy model using rats, with improved hepatic regeneration and microcirculations, by inhibiting the activation of hepatic stellate cells..
1203. Shinji Shimoda, Kenichi Harada, Hiroaki Niiro, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Koichi Tsuneyama, Minoru Nakamura, Atsumasa Komori, Kiyoshi Migita, Yasuni Nakanuma, Hiromi Ishibashi, Carlo Selmi, M Eric Gershwin, Biliary epithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells., Hepatology (Baltimore, Md.), 10.1002/hep.22102, 47, 3, 958-65, 2008.03, UNLABELLED: Primary biliary cirrhosis (PBC) is characterized by the highly selective autoimmune injury of small intrahepatic bile ducts, despite widespread distribution of mitochondrial autoantigens. On this basis, it has been suggested that the targeted biliary epithelial cells (BECs) play an active role in the perpetuation of autoimmunity by attracting immune cells via chemokine secretion. To address this issue, we challenged BECs from patients with PBC and controls using multiple Toll-like receptor (TLR) ligands as well as autologous liver-infiltrating mononuclear cells (LMNCs) with subsequent measurement of BEC phenotype and chemokine production and LMNC chemotaxis by quantifying specific chemokines. Our data reflect that BECs from PBC patients and controls express similar levels of TLR subtypes, CD40, and human leukocyte antigen DRalpha (HLA-DRalpha) and produce equivalent amounts of chemokines in our experimental conditions. Interestingly, however, BEC-expressed chemokines elicit enhanced transmigration of PBC LMNCs compared with controls. Furthermore, the addition of autologous LMNCs to PBC BECs led to the production of higher levels of chemokines and enhanced the expression of CD40 and HLA-DRalpha. CONCLUSION: We submit that the proinflammatory activity of BECs in PBC is secondary to the intervention of LMNCs and is not determined per se. These data support the hypothesis that BECs are in fact "innocent victims" of autoimmune injury and that the adaptive immune response is critical in PBC..
1204. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Characteristics of biliary reconstruction using a T-tube as compared with other methods in left-lobe adult living-donor liver transplantation, Journal of Hepato-Biliary-Pancreatic Surgery, 10.1007/s00534-007-1259-9, 15, 3, 346-347, 2008.05.
1205. Mami Kanamoto, Tomoharu Yoshizumi, Toru Ikegami, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Nobuya Sano, Mitsuo Shimada, Cholangiolocellular carcinoma containing hepatocellular carcinoma and cholangiocellular carcinoma, extremely rare tumor of the liver: A case report, Journal of Medical Investigation, 10.2152/jmi.55.161, 55, 1-2, 161-165, 2008.02, Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor which was first defined by Steiner, et al. in 1957 (1). CLC is thought to be derived from Hering's canal because tumor glands of CLC are morphologically similar to cholangioles. Recently, Theise, et al. reported that Hering's canal might be composed of hepatic stem cells (3). In addition, CLC sometimes contains a hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC) component within the tumor. Those findings suggest that CLC might originate from hepatic stem cells. On the other hand, because of its low frequency, clinicopatholigical features of CLC have not been fully clarified yet. We herein report a case of a 71-year old man with CLC. Based on preoperative imagings, the hepatic tumor was diagnosed as HCC, and he underwent a partial hepatectomy. The tumor contained both a HCC and CCC-like area. In immunohistochemistry, cytokeratin (CK) 7, CK20, CAM5.2 was positive, and CK19 was negative, therefore the tumor was diagnosed as CLC. The diagnostic criteria have not been described clearly, so CLC is difficult to diagnose preoperatively. Further studies are needed to clarify the clinical and clinicopatholigical features of CLC..
1206. T. Ikegami, A. Taketomi, R. Ohta, Y. Soejima, T. Yoshizumi, M. Shimada, Y. Maehara, Donor age in living donor liver transplantation, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2008.02.084, 40, 5, 1471-1475, 2008.06, Background. We sought to elucidate the influence of donor age in living donor liver transplantation (LDLT) using either left lobe (LL) or right lobe (RL) grafts.
Methods. Recipients (n = 232) were categorized as: group O/LL (LL, donor age >50, n = 20); group Y/LL (LL, donor age <= 50, n = 140); Group O/RL (RL, donor age >50, n = 12); and group Y/RL (RL, donor age <= 50, n = 61). We compared post-LDLT graft functions.
Results. Among LL LDLT, the incidence of small-for-size syndrome was significantly greater for group O/LL compared with group Y/LL (60.0% vs 16.3%, P < .01). However, the cumulative 5-year graft survivals were 73.8% in group 0 and 76.7% in group Y without substantial difference. In RL LDLT, the post-LDLT morbidity and mortality were similar for group O/RL and group Y/RL.
Conclusion. Partial liver grafts, even though LL grafts, from older donors can be used safely with caution in LDLT..
1207. T. Yoshizumi, A. Taketomi, H. Kayashima, Y. Yonemura, N. Harada, H. Ijichi, Y. Soejima, T. Nishizaki, Y. Maehara, Estimation of standard liver volume for Japanese adults, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2008.02.082, 40, 5, 1456-1460, 2008.06, Introduction. Accurate pretransplant estimation of the recipient's standard liver volume (SLV) is important. The purpose of this study was to compare reported formulas for clinical estimation of liver volume among Japanese adults.
Methods. We reviewed data on 70 healthy adults (46 men, 24 women, ages 20 to 65 years old) evaluated for living donor liver transplantation. Liver volume (LV) was measured using two- or three-dimensional computed tomography volumetry (CTV). The formulas of DeLand (LV = 1020 X body surface area [BSA] - 220), Urata (LV = 706.2 X BSA + 2.4), Noda (LV = 50.12 X BW0.78), Heinemann (LV = 1072.8 X BSA - 345.7), Vauthey (LV = 18.51 X BW + 191.8) and Yoshizumi (LV = 772 X BSA) were applied to estimate LV. We calculated the differences for individual donors betwen CTV and LV estimated by each formula.
Results. Mean LVs as estimated by the formulae of DeLand and Heinemann et al were significantly greater (P <.01) than the mean CTV, while LV estimated by the formula of Urata was significantly less (P <.05) than the CTV. The formulas of DeLand and Heinemann overestimated LV, while the formula of Urata underestimated it. The formulae of Noda et al and Yoshizumi et al tended to underestimate the LV when the 3 CTV was greater than 1600 cm. When the Yoshizumi formula was applied, the number of donors with an acceptable difference (15%) between CTV and estimated LV was 55 (78.6%).
Conclusions. The Yoshizumi formula was applicable, especially for patients with a BSA < 2.0, whereas the well-known Urata formula made LV underestimates..
1208. Kotaro Miyake, Tomoharu Yoshizumi, Satoru Imura, Koji Sugimoto, Erdenebulgan Batmunkh, Hirofumi Kanemura, Yuji Morine, Mitsuo Shimada, Expression of hypoxia-inducible factor-1 alpha, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma, PANCREAS, 36, 3, E1-E9, 2008.04, Objectives: Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a transcription factor that plays an important role in tumor growth and metastasis. Inhibition of histone deacetylase shows a marked inhibition of HIF1 alpha expression; however, the association between HIF-1 alpha and histone deacetylase 1 (HDAC1), metastasis-associated protein 1 (MTA1) is not fully understood.
Methods: Hypoxia-inducible factor 1 alpha, HDAC1, and MTA1 expressions were detected by immunohistochemistry in 39 pancreatic carcinoma patients. The correlations between the expression of HIF-1 alpha, HDAC1, or MTA1 and clinical features and the prognosis were analyzed.
Results: Hypoxia-inducible factor 1 alpha, HDAC1, and MTA1 positive stainings were found in 41%, 56%, and 31%, respectively. There was no correlation between HIF-1 alpha, HDAC1, or MTA1 expression levels and any clinical parameters. The survival rate for patients with HIF-1 alpha and HDAC1-positive stainings were significantly lower than for patients with HIF-1 alpha and HDAC1-negative stainings. The MTA1 overexpression group did not have a significantly lower prognosis than the MTA1 underexpression group. The survival rate for the HDAC1(+)/MTA1(2-3) group was significantly lower than for the other groups.
Conclusions: These results suggest that HIF-1 alpha expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis for pancreatic carcinoma and indicates that HIF-1 alpha and HDAC1/MTA1 are a promising therapeutic target in pancreatic carcinoma treatment..
1209. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hiroto Kayashima, Kensaku Sanefuji, Tomoharu Yoshizumi, Noboru Harada, Yo-Ichi Yamashita, Yoshihiko Maehara, Extracorporeal hepatic resection for unresectable giant hepatic hemangiomas., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.21272, 14, 1, 115-7, 2008.01.
1210. Tomoharu Yoshizumi, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hiroto Kayashima, Yo-Ichi Yamashita, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, Graft size, donor age, and patient status are the indicators of early graft function after living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.21462, 14, 7, 1007-13, 2008.07, No reliable model for predicting early graft function and patient survival after living donor liver transplantation (LDLT) exists. The aim of this study was to establish a new formula for predicting early graft function and prognosis using technetium-99m galactosyl-human serum albumin (Tc-GSA) liver scintigraphy. The ratio of the hepatic uptake ratio of Tc-GSA to the clearance index of Tc-GSA (LHL/HH) was determined 7 days after LDLT. There were 22 patients with a ratio greater than 1.3 and 6 patients with a ratio less than 1.3. Graft function on the 14th postoperative day (POD) was compared between the 2 groups. A new formula to predict the LHL/HH score was established as follows: LHL/HH (predictive score) = 0.011 x graft weight (%) - 0.016 x donor age - 0.008 x Model for End-Stage Liver Disease score - 0.15 x shunt (if present) + 1.757 (r(2) = 0.497, P < 0.01). This predicted LHL/HH ratio was compared to the graft function on POD 14 for 110 LDLT patients. The total bilirubin (TB) and prothrombin time international normalized ratio (PT-INR) in the group with an LHL/HH score > or = 1.3 were lower than those in the group with an LHL/HH score < 1.3. The TB, PT-INR, and volume of ascites in the group with a predictive score > or = 1.3 (n = 86) were lower than those in the group with a score < 1.3 (n = 24). The 6-month survival probability was improved in the group with a predictive score > or = 1.3. In conclusion, this preoperative calculated LHL/HH score is correlated with graft function and short-term prognosis. Thus, this predictive model may allow transplant surgeons to use a living donor left lobe graft with greater confidence..
1211. Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Hideaki Uchiyama, Toru Ikegami, Noboru Harada, Hiroto Kayashima, Yo-Ichi Yamashita, Mitsuo Shimada, Yoshihiko Maehara, Impact of donor age and recipient status on left-lobe graft for living donor adult liver transplantation., Transplant international : official journal of the European Society for Organ Transplantation, 10.1111/j.1432-2277.2007.00561.x, 21, 1, 81-8, 2008.01, Donor safety is the priority when performing a living donor adult liver transplantation (LDALT). We herein present our findings using left-lobe graft in LDALT. Data on 119 recipients who underwent the LDALT, and on 119 donors who underwent extended left lobectomy were reviewed. The recipients were divided into groups above (n = 19) and below (n = 100) 50 years of donor age, into groups above (n = 63) and below (n = 56) 40% of graft size (graft volume/standard liver volume, GV/SLV), and above (n = 25) and below (n = 94) 20 of pre-operative model for end-stage liver disease (MELD). Total bilirubin (TB), volume of ascites, prothrombin time international normalized ratio on postoperative day 14 or survival rates were compared. TB (mg/dl) or volume of ascites (ml) of the group in donor age < 50 years was better than that of the group in donor age > or = 50 years (7.4 vs. 14.7 or 788 vs. 1379, P < 0.001 or P < 0.005, respectively). The graft and patient survival rates of the lower MELD group tended to be better than that of the higher MELD group. LDALT can be safely performed using a left-lobe graft. However, when using the graft from the donor > or = 50 years, especially for the recipients with the MELD > or = 20, the indications should be carefully discussed..
1212. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishihawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiho Maehara, Hiroyuhi Kuwano, Is an elderly recipient a risk for living donor adult liver transplantation?, HEPATO-GASTROENTEROLOGY, 55, 82-83, 653-656, 2008.03, Background/Aims: In cadaveric liver transplantation, it has been reported that elderly recipients over 60 years are at risk because of high incidence of complication and malignancy. However, in living-donor adult liver transplantation (LDALT), it is unclear whether the elderly recipient is risky or not risky. In this study, the outcome after LDALT of elderly patients has been evaluated.
Methodology: One hundred twenty two consecutive LDALT recipients were studied. The recipients were divided into an elderly group (older than 60 yrs, n=21), and a control group (younger than 60 yrs, n=101). Comparative examination of background factors, postoperative complications and de nouo malignancy was carried out.
Results: Elderly patients more frequently received transplantation for hepatocellular carcinoma. Pre-transplant liver damage such as Child-Pugh, MELD or bilirubin level was same among the groups. There was no significant difference in posttransplant complications except renal failure. Postoperative renal failure (postoperative creatinine level over 2mg/dL) occurred in 29% (n=5) of the elderly group us. 8% (n=6) of the control group. De nouo malignancy occurred in I case (lung) in the elderly group and 1 case (Vater) in the control group. In the control group, the 1, 3 and 5 year patient survival rates were 78.5%, 73.1% and 71.4%, respectively. And in the elderly group, the 1, 3 and 5 year patient survival rates were 85.7%, 81.0% and 70.8%, respectively.
Conclusions: It may be, we concluded that living donor adult liver transplantation is good treatment for end stage liver diseases in elderly recipients over 60 years. However caution should be taken in the administration of medicine, including immunosup-pressants or antibiotics, do to a propensity for postoperative renal failure in elderly recipients..
1213. Yuji Soejima, Makoto Meguro, Akinobu Taketomi, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Shinji Ito, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara, Left lobe living donor liver transplantation in an adult patient with situs inversus: technical considerations., Transplant international : official journal of the European Society for Organ Transplantation, 10.1111/j.1432-2277.2007.00607.x, 21, 4, 384-9, 2008.04, Situs inversus (SI) is a rare congenital disorder involving a complete mirror image of the thoracic and abdominal organs. Living donor liver transplantation (LDLT) in SI cases poses particular challenges on account of its technical complexity, and only a few cases have been reported. Here, we present an adult with SI who was managed successfully by LDLT using a left lobe graft. Some technical modifications, including triangulated anastomosis of the hepatic vein, were required but no vascular graft was necessary. Graft function and vascular integrity were excellent throughout the postoperative course, although sepsis secondary to wound infection with methicillin-resistant Staphylococcus aureus developed. In conclusion, LDLT using a left lobe graft is a feasible procedure for patients with SI, even for adults. Therefore, this condition, while rare, should not be a contraindication for LDLT. Meticulous preoperative simulation and planning of the vascular reconstruction are important steps in LDLT for this rare anomaly..
1214. Toru Ikegami, Yuji Soejima, Ryuji Ohta, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Yoshihiko Maehara, Living donor liver transplantation for hepatitis B associated liver diseases: A 10-year experience in a single center, Hepato-Gastroenterology, 55, 85, 1445-1449, 2008.07, Background/Aims: Hepatic failure associated with hepatitis B virus (HBV) is one of the main indications for living donor liver transplantation (LDLT). Methodology: Twenty-nine LDLTs, including liver cirrhosis due to HBV (LC-B) (n=17) and fulminant hepatitis B (FH-B) (n=12) were reviewed. Prophylaxis for reinfection was performed with a combination of lamivudine, or hepatitis B immune globulin (HBIG) or adefovir, depending on the viral status. The changes in serological markers, recurrence and survival rate were examined. Results: There were 3 patients with re-emergencies of HBV surface antigen (HBsAg): suspension of HBIG for giving vaccination for HBV (n=1), HBsAg positive donor (n=1) and non-compliance for HBIG (n=1). All patients with YMDD mutants (n=9), except the case with HBsAg positive donor (n=1), were successfully protected by the triple therapy of lamivudine, adefovir and HBIG. No graft loss was due to the recurrence of HBV. Conclusion: The basic strategy using a combination of HBIG and antiviral agents gave acceptable long-term outcomes for LDLT for HBV associated liver diseases. The close monitoring of HBV viral status after transplantation is still crucial in managing these patients. © H.G.E. Update Medical Publishing S.A..
1215. Y. Soejima, A. Taketomi, T. Ikegami, T. Yoshizumi, H. Uchiyama, Y. Yamashita, M. Meguro, N. Harada, M. Shimada, Y. Maehara, Living donor liver transplantation using dual grafts from two donors: A feasible option to overcome small-for-size graft problems?, AMERICAN JOURNAL OF TRANSPLANTATION, 10.1111/j.1600-6143.2008.02153.x, 8, 4, 887-892, 2008.04, Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small-for-size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large-size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small-for-size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small-for-size graft problems without increasing independent donor risks..
1216. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Kensaku Sanefuji, Hiroto Kayashima, Mitsuo Shimada, Yoshihiko Maehara, Living donor liver transplantation for acute liver failure: a 10-year experience in a single center., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2007.08.018, 206, 3, 412-8, 2008.03, BACKGROUND: Living donor liver transplantation has become an accepted treatment for various terminal liver diseases. STUDY DESIGN: Forty-two living donor liver transplantations performed for acute liver failure during a 10-year period at Kyushu University Hospital were reviewed. RESULTS: Causes of liver failure included hepatitis B (n=12), hepatitis C (n=1), autoimmune hepatitis (n=2), Wilson's disease (n=3), and unknown causes (n=24). The graft types were: left lobe (n=33), right lobe (n=8), and lateral segment (n=1). The mean graft volume to standard liver volume ratios were 42.2+/-9.2% in left lobe grafts and 50.5+/-3.9% in right lobe grafts (p < 0.05). Extubation was significantly delayed in grade IV encephalopathy patients (73.7 +/-18.2 hours) compared with patients with other grades (p < 0.01 to grades I and II, p < 0.05 to grade III). All other patients, except one with a subarachnoid hemorrhage, had complete neurologic recovery after transplantation. The 1- and 10-year survival rates were 77.6% and 65.5%, respectively, for grafts, and 80.0% and 68.2%, respectively, for patients. CONCLUSIONS: Outcomes of living donor liver transplantation for acute liver failure are fairly acceptable despite severe general conditions and emergent transplant settings. Living donor liver transplantation is now among the currently accepted life-saving treatments of choice for acute liver failure, although innovative medical treatments for this disease entity are still anticipated..
1217. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Living donor liver transplantation for fulminant hepatic failure from ABO-incompatible donors [1], Transplant International, 10.1111/j.1432-2277.2007.00588.x, 21, 3, 284-285, 2008.03.
1218. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Maehara, Living donor liver transplantation for acute liver failure using left lobe grafts [1], Transplantation, 10.1097/01.tp.0000296815.71784.3f, 85, 1, 160-161, 2008.01.
1219. Yuji Soejima, Naoyuki Ueda, Takasuke Fukuhara, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara, One-step venous reconstruction for a right lobe graft with multiple venous orifices in living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.21401, 14, 5, 706-8, 2008.05.
1220. Y. Soejima, S. Ueda, K. Sanefuji, H. Kayashima, T. Yoshizumi, T. Ikegami, Y. Yamashita, K. Sugimachi, T. Iguchi, A. Taketomi, Y. Maehara, Sequential pancreaticoduodenectomy after living donor liver transplantation for cholagiocacinoma, AMERICAN JOURNAL OF TRANSPLANTATION, 10.1111/j.1600-6143.2008.02346.x, 8, 10, 2158-2162, 2008.10, Liver transplantation (LT) for patients with primary sclerosing cholangitis (PSC) is often contraindicated due to concomitant occurrence of cholangiocarcinoma (CC). Cases of simultaneous pancreaticoduodenectomy (PD) with LT have been sporadically reported; however, the applicability of such an invasive procedure to patients with CC has not been validated. We report here a case of sequential PD performed 44 days after a successful living donor liver transplantation (LDLT) using a left lobe graft. Although a clear pancreatic juice leakage through the drain persisted for days after surgery, the patient recovered from the complication and was discharged 32 days after the procedure. Currently, 1 year after LDLT, the patient is doing well with no evidence of recurrence. In conclusion, a sequential PD following LDLT is a safe and feasible option to treat CC complicating PSC. Long-term follow-up and accumulation of cases are necessary to evaluate the effectiveness of this procedure for this complicated disease..
1221. Hideki Ijichi, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yusuke Yonemura, Yoshihiko Maehara, Successful management of chylous ascites after living donor liver transplantation with somatostatin., Liver international : official journal of the International Association for the Study of the Liver, 10.1111/j.1478-3231.2007.01556.x, 28, 1, 143-5, 2008.01, Chylous ascites is a rare complication following liver transplantation. A variety of treatment options have been proposed for the management of chylous ascites; however, their effectiveness following a liver transplant is unknown. A 40-year-old woman who underwent living donor liver transplantation for primary biliary cirrhosis developed chylous ascites 21 days after the transplant. A conventional treatment consisting of a low-fat diet with total parenteral nutrition failed to treat the complication for 104 days. However, the use of somatostatin in combination with total parenteral nutrition resulted in a rapid falloff in chyle output without any adverse effects. Somatostatin and total parenteral nutrition are an effective option for the treatment of chylous ascites after living donor liver transplantation..
1222. Tomoharu Yoshizumi, Akinobu Taketomi, Hiroto Kayashima, Noboru Harada, Hideaki Uchiyama, Yo-Ichi Yamashita, Toru Ikegami, Yuji Soejima, Takashi Nishizaki, Mitsuo Shimada, Yoshihiko Maehara, Successful treatment for a patient with hemophagocytic syndrome after a small-for-size graft liver transplantation, Hepato-Gastroenterology, 55, 82-83, 359-362, 2008.03, Hemophagocytic syndrome (HPS) is a hematological disorder caused by activated T lymphocytes, which leads to the proliferation of stimulated macrophages that phagocytose and destroy circulating blood elements and their precursors within bone marrow, and lead to the further production of inflammatory cytokines. Living donor liver transplantation (LDLT) between adults has been performed to compensate for the shortage of available organs. There have been some reports concerning HPS after LDLT
however, its prognosis is disappointingly poor. In particular, there is no report of treated HPS developed after LDLT using small-for-size left lobe grafts. We herein report a case of HPS in a 63-year old woman who underwent LDLT using left lobe graft weighing only 330g. The HPS was diagnosed on postoperative day 13, and was successfully treated using a combination of intravenous immunoglobulin, granulocyte colony stimulating factor, conversion of calcineurin inhibitor and steroid pulse. The trigger of HPS may not only be systemic infection, but also hypercytokinemia caused by various factors. HPS is a fatal complication in immunologically compromised patients
however, early and accurate diagnosis could lead to an adequate treatment and improve the outcome. © H.G.E. Update Medical Publishing S.A..
1223. Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Noboru Harada, Yo-ichi Yamashita, Hirofumi Kawanaka, Takashi Nishizak, Yoshihiko Maehara, The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft., Transplant international : official journal of the European Society for Organ Transplantation, 10.1111/j.1432-2277.2008.00678.x, 21, 9, 833-42, 2008.09, Small-for-size (SFS) graft syndrome is one of the major causes of graft loss in living donor liver transplantation (LDLT). We examined whether splenectomy is beneficial for overcoming SFS graft syndrome in LDLT. The patients were classified into two groups: the Sp (-) group (n=69), in which splenectomy was not performed, and the Sp (+) group (n=44), in which it was. The incidence of SFS graft syndrome was investigated. Risk factors of SFS graft syndrome were identified by univariate- and multivariate analysis. To clarify whether splenectomy is beneficial for patients with a SFS graft, subgroup analysis was performed for patients who had a graft weight-to-standard liver weight (GW-SLW) ratio of 40% or less (n=50). Thirty-one of 113 patients developed SFS graft syndrome. A multivariate analysis identified that having a male donor was an independent risk factor of SFS graft syndrome. SFS graft syndrome occurred in 11 of 50 patients with a GW-SLW ratio<40%, and Sp (-) was an independent risk factor for the occurrence of SFS graft syndrome in patients (P=0.014). Simultaneous splenectomy is favorable for overcoming SFS graft syndrome in LDLT patients with a GW-SLW of 40% or less..
1224. Toru Ikegami, Akinobu Taketomi, Ryuji Ohta, Yiji Soejima, Tomoharu Yoshizumi, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, The risks of HBV infection after liver transplantation from HBc antibody positive donor to HBs antibody positive recipient, Hepato-Gastroenterology, 55, 88, 2162-2165, 2008.11, The rate of de novo hepatitis B infection, after liver transplantation from a hepatitis B core antibody (HBcAb) (+) donor to a surface antibody (HBsAb) (+) recipient bas not yet elucidated. Four recipients with HBsAb (+) and HBcAb, (+), who received living donor grafts from HBcAb (+) donors were herein reviewed. They received lamivudine monotherapy: three patients with HBsAb titer >
10 IU/L did not demonstrate the onset of HBsAg, whereas one patient with HBsAb titer <
10 IU/L developed hepatitis B antigen (HBsAg) 4 years after transplantation. An HBsAb (+) patient with a titer of >
10 IU/L is therefore considered not to require combination therapy when receiving an HBcAb (+) liver graft. However, a great deal of caution is necessary in patients with a negative or low HBsAb titers <
10 IU/L. © H.G.E. Update Medical Publishing S.A., Athens-Stuttgart..
1225. Toru Ikegami, Mitsuo Shimada, Satoru Imura, Tomoharu Yoshizumi, Yusuke Arakawa, Takuya Tokunaga, Yuji Morine, Hirofumi Kanemura, The timing of liver transplantation after primary hepatectomy for hepatocellular carcinoma: A special reference to recurrence pattern and Milan criteria, TRANSPLANTATION, 10.1097/TP.0b013e3181814de2, 86, 5, 641-646, 2008.09, Introduction. Hepatic resection (HR) is commonly applied as first-line treatment of hepatocellular carcinoma (HCC) even in the era of liver transplantation (LT).
Methods. Outcomes and detailed recurrence pattern of 80 patients, who underwent curative HR for HCC were examined referring to Milan criteria.
Results. (1) After HR for HCCs exceeding Milan criteria (n=41), recurrence within the criteria was observed in 13 patients (group-A) and recurrence not-meeting the criteria was observed in 22 patients (group-B). group-A showed better 3-year recurrence-free survival rate than group-B (85.7% vs. 23.9%, P<0.05). Tumor size more than or equal to 6 cm was identified as the significant factor for having recurrence as in group-A pattern (P<0.05). Among the patients in group-A, re-recurrence after treating recurrent HCC was observed in eight patients (61.5%) with increased rate of extra-Milan criteria recurrence at 12 months from the initial recurrence. (11) After HR for HCCs meeting Milan criteria (n = 39), recurrences within the criteria was observed in 15 patients (group-C) and recurrence not-meeting the criteria was observed in five patients (group-D). The 3-year recurrence-free survival rate was 62.8% in group-C and 40.0% in group-D (P<0.05). Increased rate of extra-Milan re-recurrence was observed later than 12 months from the recurrence in group-C.
Conclusions. For HCCs not meeting Milan criteria, secondary LT after primary HR could be applied for a proportion of cases with less aggressiveness. For those meeting Milan criteria, primary LT should be the first therapeutic option. However, secondary LT could be offered for those with re-recurrence within criteria after primary HR..
1226. Hiroki Mori, Hisamitsu Shinohara, Yusuke Arakawa, Hirofumi Kanemura, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Toru Ikegami, Tomoharu Yoshizumi, Mitsuo Shimada, Beneficial effects of hyperbaric oxygen pretreatment on massive hepatectomy model in rats, TRANSPLANTATION, 10.1097/01.tp.0000291/78.86758.1d, 84, 12, 1656-1661, 2007.12, Background. The purpose of this study was to investigate the impact of hyperbaric oxygen (HBO) pretreatment in massive hepatectomy model, a surrogate model of small-for-size graft, using rats.
Methods. (Experiment I) Rats were divided into the following four groups: HBO (-), HBO-1D (day), HBO-3D, and HBO-5D. Samples were taken after the completion of HBO pretreatment, and the following parameters were evaluated: reverse transcription polymerase chain reaction and immunohistochemical staining for HSP 70 and HO-1; biochemical parameters; and liver weight to body weight ratio (Lw/Bw ratio). (Experiment II) Rats were divided into four groups as follows; 70% hepatectomy (Hx), 70% Hx-HBO, 90% Hx, and 90% Hx-HBO group. Samples were taken 12, 24, 48, and 72 hr after hepatectomy and the following parameters were investigated: biochemical analysis; Lw/Bw ratio; PCNA labeling index; and survival.
Results. (Experiment 1) The expression of HSP70 mRNA was significantly increased in the HBO-3D group compared with the HBO (-) group (P < 0.05). HSP70- and HO-1-positive hepatocytes were significantly increased in the HBO-3D group compared with the HBO (-) group (P < 0.05). (Experiment II) Transaminases were significantly decreased in both 70% and 90% Hx-HBO groups compared with Hx alone group (P < 0.05). The Lw/Bw ratio and PCNA labeling index of the 90% Hx-HBO group were significantly increased compared with the 90% Hx group, 24, 48 and 72 hr after hepatectomy (P < 0.05). The survival rate in the 90% Hx-HBO group was significantly higher than that in the 90% Hx group (P=0.01).
Conclusions. HBO pretreatment had beneficial effects in a massive hepatectomy model in rats via the induction of HSP70 and HO-1..
1227. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hideaki Uchiyama, Mitsuo Shimada, Yoshihiko Maehara, Explanted portal vein grafts for middle hepatic vein tributaries in living-donor liver transplantation., Transplantation, 10.1097/01.tp.0000296483.89112.4c, 84, 7, 836-41, 2007.10, BACKGROUND: The availability of a venous graft is limited in the setting of living donor liver transplantation (LDLT), and the management of the middle hepatic vein middle hepatic vein tributaries in right lobe LDLT still remains controversial. METHODS: Twenty-three right lobe LDLT grafts, with the reconstruction of middle hepatic vein tributaries using the explanted portal veins from the explanted livers, were evaluated for the patency, postLDLT liver function tests, and graft survival. RESULTS: The methods of outflow reconstruction were classified into three types: the interposition of the graft to the middle/left hepatic vein (n=12), to the vena cava (n=9), and to the vena cava as a co-orifice with the graft right hepatic vein (n=2). The 1- and 3-year patency rates were 76.7% and 76.7% respectively, with the graft occlusion in five cases. The occluded cases (n=5) had significantly higher aspartate aminotransferase and alanine transaminase levels as compared with those of patent cases (n=18) at 4 weeks after transplantation (P<0.01). However, there was no significant difference in the total bilirubin and prothrombin time in either group during the observation periods. The 1- and 3-year graft survival rates were 91.1% and 91.1%, respectively. In addition, there was no graft loss due to occlusion. CONCLUSION: The use of the recipient's explanted full-length hilar portal vein for the reconstruction of the middle hepatic vein tributaries is thus considered to be a feasible and valuable strategy in the setting of a right lobe LDLT, where appropriate vascular grafts are not always available..
1228. Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Shinich Aishima, Takahiro Terashi, Mitsuo Shimada, Yoshihiko Maehara, Extended indication for living donor liver transplantation in patients with hepatocellular carcinoma., Transplantation, 10.1097/01.tp.0000259015.46798.ec, 83, 7, 893-9, 2007.04, BACKGROUND: Liver transplantation is an accepted treatment option for patients with otherwise untreatable hepatocellular carcinoma (HCC). The present study assessed the outcome of living donor liver transplantation (LDLT) under extended selection criteria based on a single-center experience. METHODS: A total of 60 patients who underwent LDLT for HCC were included. Our indication for LDLT included HCC without extrahepatic spread or macroscopic vascular invasion. The size and number of HCC nodules were not limited. Recurrence-free survival rates according to various factors were compared to identify risk factors for recurrence. RESULTS: Forty patients (67%) preoperatively exceeded the Milan criteria. The median follow-up was 437 days (range: 23-1,385 days). The overall 1- and 3-year actuarial survival rates were 88.4 and 68.6%, respectively. HCC recurred in eight patients (14.3%) within a mean follow-up of 288 days; all were patients who exceeded the Milan criteria. The 1-, 2- and 3-year recurrence-free survival rates of patients who fulfilled the Milan criteria were 100%, 100%, and 100%, respectively, whereas those of patients who exceeded the criteria were 83.0%, 74.0%, and 74.0%, respectively. Tumor diameter >5 cm was significantly associated with worse prognosis, but the number of tumors was not. A preoperative des-gamma-carboxy prothrombin value >300 mAU/ml was strongly associated with the high recurrence rate. These two variables were significant in multivariate analysis. CONCLUSIONS: LDLT was shown to offer acceptable results in patients who exceeded the Milan criteria. The indication for LDLT can therefore be expanded beyond the Milan criteria, especially for patients with small multiple tumors <5 cm..
1229. Hideaki Uchiyama, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hideki Ijichi, Hepatic artery aneurysm arising from an interposition vein graft four years after auxiliary partial orthotopic liver transplantation, TRANSPLANT INTERNATIONAL, 10.1111/j.1432-2277.2006.00402.x, 20, 2, 197-200, 2007.02.
1230. Yuji Soejima, Toru Ikegami, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yoichi Yamashita, Yoshihiko Maehara, Hepatitis B vaccination after living donor liver transplantation., Liver international : official journal of the International Association for the Study of the Liver, 10.1111/j.1478-3231.2007.01521.x, 27, 7, 977-82, 2007.09, BACKGROUND: The efficacy of hepatitis B vaccination after living donor liver transplantation (LDLT) in patients transplanted anti-HBc-positive grafts or in patients who underwent LDLT for fulminant hepatitis B remains unknown. METHOD: A total of 11 recipients who underwent LDLT between October 1996 and October 2002 prospectively received hepatitis B vaccination three times within 6 months, starting a few weeks after the cessation of hepatitis B immunoglobulin (HBIG) prophylaxis. Serial quantification of the hepatitis B surface antibody (HBsAb) was performed. RESULTS: At the last follow-up, six out of 11 patients (54.5%) had seroconversion and were free from HBIG thereafter. Four out of those six responders had a peak HBsAb level of more than 1000 IU/L, while the other two patients had peak HbsAb levels below 1000 IU/L. Five patients never responded to the treatment and were back to HBIG prophylaxis. The average age of the six responders was 25.5 years, which was significantly younger than that of non-responders (44.4 years, P<0.05). None had side effects or hepatitis B infection during the study period. CONCLUSIONS: In conclusion, the use of this treatment modality could be used to reduce the cost of HBIG..
1231. Yo-Ichi Yamashita, Kengo Fukuzawa, Akinobu Taketomi, Shinichi Aishima, Tomoharu Yoshizumi, Hideaki Uchiyama, Eiji Tsujita, Norifumi Harimoto, Noboru Harada, Kenzo Wakasugi, Yoshihiko Maehara, Mucin-hypersecreting bile duct neoplasm characterized by clinicopathological resemblance to intraductal papillary mucinous neoplasm (IPMN) of the pancreas., World journal of surgical oncology, 10.1186/1477-7819-5-98, 5, 98-98, 2007.08, BACKGROUND: Although intraductal papillary mucinous neoplasm (IPMN) of the pancreas is acceptable as a distinct disease entity, the concept of mucin-secreting biliary tumors has not been fully established. CASE PRESENTATION: We describe herein a case of mucin secreting biliary neoplasm. Imaging revealed a cystic lesion 2 cm in diameter at the left lateral segment of the liver. Duodenal endoscopy revealed mucin secretion through an enlarged papilla of Vater. On the cholangiogram, the cystic lesion communicated with bile duct, and large filling defects caused by mucin were observed in the dilated common bile duct. This lesion was diagnosed as a mucin-secreting bile duct tumor. Left and caudate lobectomy of the liver with extrahepatic bile duct resection and reconstruction was performed according to the possibility of the tumor's malignant behavior. Histological examination of the specimen revealed biliary cystic wall was covered by micropapillary neoplastic epithelium with mucin secretion lacking stromal invasion nor ovarian-like stroma. The patient has remained well with no evidence of recurrence for 38 months since her operation. CONCLUSION: It is only recently that the term "intraductal papillary mucinous neoplasm (IPMN)," which is accepted as a distinct disease entity of the pancreas, has begun to be used for mucin-secreting bile duct tumor. This case also seemed to be intraductal papillary neoplasm with prominent cystic dilatation of the bile duct..
1232. S. Shiotani, M. Shimada, A. Taketomi, Y. Soejima, T. Yoshizumi, K. Hashimoto, H. Shimokawa, Y. Maehara, Rho-kinase as a novel gene therapeutic target in treatment of cold ischemia/reperfusion-induced acute lethal liver injury: effect on hepatocellular NADPH oxidase system, GENE THERAPY, 10.1038/sj.gt.3303000, 14, 19, 1425-1433, 2007.10, In the transplant surgery, reactive oxygen species (ROS) from the reperfused tissue cause ischemia-reperfusion injury, resulting in the primary graft failure. We have recently reported that Rho-kinase, an effecter of the small GTPase Rho, plays an important role in the ROS production in the hyperacute phase of reperfusion; however, the sources and mechanisms of the ROS production remain to be elucidated. The aim of this study was to investigate the source of ROS production with a special reference to Rho-kinase to develop a new strategy against ischemia-reperfusion injury. In an in vivo rat model of liver transplantation, Kupffer cells in the graft were depleted using liposome-encapsulated dichloromethylene diphosphonate to examine the source of ROS production. The effect of adenoviral-mediated overexpression of a dominant-negative Rho-kinase (AdDNRhoK) in hepatocytes in the graft was also examined. Kupffer cells were not involved in the ROS production, whereas the AdDNRhoK transfection to hepatocytes significantly suppressed the ROS production. Furthermore, the ROS production was dose-dependently inhibited by apocynin, an NADPH oxidase inhibitor. Expression of DNRhoK also suppressed the release of pro-inflammatory cytokines, and ameliorated the lethal liver injury with a significant prolongation of the survival. These results suggest that the Rho-kinase-mediated pathway plays a crucial role in the ROS production through NADPH oxidase in hepatocytes during the hyperacute phase of reperfusion in vivo. Thus, Rho-kinase in hepatocytes may be a new therapeutic target for the prevention of primary graft failure in liver transplantation..
1233. Kotaro Miyake, Satoru Imura, Tomoharu Yoshizumi, Tetsuya Ikemoto, Yuji Morine, Mitsuo Shimada, Role of thymidine phosphorylase and orotate phosphoribosyltransferase mRNA expression and its ratio to dihydropyrimidine dehydrogenase in the prognosis and clinicopathological features of patients with pancreatic cancer, INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 10.1007/s10147-006-0634-x, 12, 2, 111-119, 2007.04, Background. Thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD) are important enzymes related to the metabolism of 5-fluorouracil and its derivatives. In this study, we analyzed the expression of these enzymes and evaluated the association between the expression of these enzymes and clinicopathological features and prognosis in patients with pancreatic cancer.
Methods. TP, OPRT, and DPD mRNA expressions were detected using a real-time reverse transcriptional-polymerase chain reaction method or by immunohistochemistry, using surgical specimens obtained from 25 patients with pancreatic cancer.
Results. TP mRNA expression was lower in cases with an alpha infiltration growth pattern than in cases with other infiltration growth patterns (P < 0.05). OPRT mRNA expression was higher in poorly differentiated-type cases than in differentiated type cases (P < 0.05). TP-, OPRT-, and DPD-positive stainings were found in 15 of 24 cases (63%), 10 of 19 cases (53%), and 14 of 21 cases (67%), respectively. There were significant correlations or trends between the mRNA and protein expressions of TP, OPRT, and DPD. Patients with a low TP/DPD ratio survived significantly longer than those with a high ratio (P < 0.05). Multivariate analysis demonstrated a significantly poorer outcome in patients with a high TP/DPD ratio compared with in patients with a low ratio (P < 0.05).
Conclusion. The TP/DPD ratio might be useful as a prognostic factor in patients with pancreatic cancer..
1234. T. Ikegami, A. Taketomi, Y. Soejima, T. Iguchi, K. Sanefuji, H. Kayashima, T. Yoshizumi, N. Harada, Y. Maehara, Successful ABO incompatible living donor liver transplantation in a patient with high isoagglutinin titer using high-dose intravenous immunoglobulin, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2007.09.028, 39, 10, 3491-3494, 2007.12, The optimal management in living donor liver transplantation using an ABO incompatible donor with a high isoagglutinin titer is still uncertain. Our patient was a 20-year-old woman with fulminant hepatitis. The only available donor was her 54-year-old father-in-law of an incompatible blood type. The initial isoagglutinin titer was 2048X. She received 375 mg/m(2) of anti-CD20 antibody 3 days before the living donor liver transplantation with concomitant splenectomy. Despite daily plasma exchanges after transplantation, the isoagglutinin titer started to shoot up to its maximum value of 2048X, with a sudden decline in the bile output. High-dose intravenous immunoglobulin (0.6 g/kg) was given after the plasma exchanges; thereafter, her liver function tests stabilized without a further increase in the isoagglutinin titer. We showed the effectiveness of high-dose intravenous immunoglobulin for the management of the rebound elevation of isoagglutinin titer. The combination of anti-CD20 antibody and daily plasma exchanges seemed ineffective for such a situation. This strategy might be another management option for ABO incompatible liver transplantation..
1235. Yuji Soejima, Mitsuo Shimada, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Makoto Nakamuta, Yoshihiko Maehara, Successful living donor liver transplantation using a graft from a hepatitis B surface antigen-positive donor., Liver international : official journal of the International Association for the Study of the Liver, 10.1111/j.1478-3231.2007.01528.x, 27, 9, 1282-6, 2007.11, BACKGROUND/AIMS: Liver transplantation using a graft from a donor with a positive hepatitis B surface antigen (HBsAg) has been contraindicated owing to the extremely high risk for recurrent disease leading to graft loss. However, the severe shortage of donors often forces the transplant community to utilize suboptimal donors, especially in the setting of living donor liver transplantation (LDLT). METHOD: Here, we report a case of successful LDLT for a patient with hepatitis B-related cirrhosis utilizing a graft from an HBsAg-positive 'healthy carrier' donor using a combination prophylaxis of lamivudine and adefovir dipivoxil. RESULTS: To date, the patient has been doing well with normal liver function tests and liver histological findings at 4 years after the transplantation and the donor has also been doing well. CONCLUSIONS: Although virological recurrence appears to be universal despite prophylaxis, re-evaluation of the use of a graft from a healthy HBsAg-positive donor is warranted in this era of combination prophylaxis..
1236. Tomoharu Yoshizumi, Mitsuo Shimada, Yuji Soejima, Takahiro Terashi, Akinobu Taketomi, Yoshihiko Maehara, Successful pylorus-preserving pancreaticoduodenectomy for a patient with carcinoma of the papilla Vater two years after living donor liver transplantation, HEPATO-GASTROENTEROLOGY, 54, 75, 941-943, 2007.04, Liver transplantation has been recognized as the treatment for various kinds of end-stage liver diseases. Standardized surgical technique, potent immunosuppressive agents and diligent postoperative care have made it possible for patients to survive for a longer period. For this reason, recurrent primary disease and/or de novo malignancy regarded as chronic immunosuppressant have been paid a great deal of attention.
Even pancreas cancer after liver transplantation is extremely rare and has never been successfully treated. Furthermore, cancer of the papilla Vater, which is less frequent than pancreas cancer after liver transplantation has not been reported as yet.
In this paper we, discuss the first case of cancer of the papilla Vater, which was successfully treated by pylorus-preserving pancreaticoduodenectomy two years after a living related liver transplantation using a left lobe. In addition, we discuss the type of malignancy after liver transplantation..
1237. Ken Shirabe, Shinji Itoh, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Shin-Ichi Aishima, Yoshihiko Maehara, The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin., Journal of surgical oncology, 10.1002/jso.20655, 95, 3, 235-40, 2007.03, The microvascular invasion of cancer cells (mvi) is a good prognostic factor after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The aim of this study is to predict mvi in patients with HCC who were candidates for OLT. We studied 218 patients with HCC resections who had HCC without any extrahepatic metastases and vascular invasion detected during preoperative evaluation. We analyzed the clinico-pathological data of these patients to predict the mvi presence. The mvi prediction scoring system was made and the accuracy of this system was examined using independent clinico-pathologic factors. The size and histological grade of the tumor were significantly correlated with the mvi. The des-gamma-carboxy prothrombin (DCP) is a mvi predictor. The sensitivity of our mvi prediction system was 75% and the specificity was 85% in 32 patients who underwent living-donor liver transplantations for HCC. Our study shows that besides the tumor size and histological grade, a measurement of the serum DCP levels could be a good predictor for mvi. A tumor biopsy and a preoperative measurement of DCP could improve the selection of patients with HCC for OLT. Our scoring system for mvi provides us a precise prediction of the presence of mvi..
1238. Noriaki Kawano, Kazuya Shimoda, Fumihiko Ishikawa, Akinobu Taketomi, Tomoharu Yoshizumi, Shinji Shimoda, Shuro Yoshida, Koji Uozumi, Shinsuke Suzuki, Yoshihiko Maehara, Mine Harada, Adult T-cell leukemia development from a human T-cell leukemia virus type I carrier after a living-donor liver transplantation., Transplantation, 10.1097/01.tp.0000235186.30113.c7, 82, 6, 840-3, 2006.09, Adult T-cell leukemia (ATL) develops in a human T-cell leukemia virus type I (HTLV-I) carrier. The development of malignancy during immunosuppressive treatment following organ transplantation is one of the late fatal complications. We describe the development of three cases of ATL in eight HTLV-I carriers within 164 living-donor liver transplant recipients undergoing immunosuppressive treatment. All three cases were immunosuppressed with tacrolimus. Acute-type ATL was diagnosed at 6, 9, and 25 months after living-donor liver transplantation, based on increased numbers of CD4+25+ lymphocytes exhibiting "flower-like" nuclei, and the elevation of lactate dehydrogenase. Southern blot analysis demonstrated the clonal proliferation of ATL cells in peripheral blood. The ATL cells originated from the recipient, as demonstrated by fluorescence in situ hybridization analysis using sex chromosomal markers. Our observations suggest that immunosuppressive treatment for the prevention of graft rejection after living-donor liver transplantation may induce the development of ATL in an HTLV-I carrier..
1239. Yuji Soejima, Tomoaki Taguchi, Keiko Ogita, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Takuro Ohno, Mitsuo Shimada, Yoshihiko Maehara, Auxiliary partial orthotopic living donor liver transplantation for a child with congenital absence of the portal vein., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.20692, 12, 5, 845-9, 2006.05, Congenital absence of the portal vein (CAPV) is a rare malformation of the mesenteric vasculature in which visceral venous blood bypasses the liver, completely draining into the systemic circulation through a congenital porto-systemic shunt. Liver transplantation has rarely been indicated for patients with this disease. We present a child with CAPV who was managed successfully by living donor auxiliary partial orthotopic liver transplantation (APOLT), while preserving the right lobe of the native liver. In conclusion, APOLT for patients with CAPV is a feasible and ideal procedure because portal vein (PV) diversion is not necessary..
1240. Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yusuke Yonemura, Tetsuo Ikeda, Mitsuo Shimada, Yoshihiko Maehara, Biliary strictures in living donor liver transplantation: incidence, management, and technical evolution., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 12, 6, 979-86, 2006.06, Biliary complications, biliary strictures (BS) in particular, continue to be a significant cause of morbidity after LDLT despite technical refinement. In this study, we assessed the incidence of BS and their management in living donor liver transplantation (LDLT) with special reference to the type of biliary reconstruction. A total of 182 LDLTs performed at our institution for either adult (n = 157) or pediatric (n = 25) patients were included in the study. The duct-to-duct (DD) biliary reconstruction was performed for 106 cases, while the conventional Roux-en-Y hepaticojejunostomy (HJ) was utilized for the remaining 76 cases. Overall, BS developed in 46/182 (25.3%) of the cases (DD, 26.4%; HJ, 25.0%). The 1- and 3-year cumulative incidences of BS were 22.9% and 31.9%, respectively, in the DD group, and 15.2% and 29.1%, respectively, in the HJ group (P= not significant). The left-lobe LDLT was more prone to develop BS. Continuous anastomosis tended to be associated with the high incidence of BS in the DD group. The incidence of anastomotic leak was significantly lower in the DD group. Intervention via either pre-cutaneous or endoscopic approach was successful in the majority of cases, although recurrence could occur in some patients. In conclusion, BS was not associated with the type of reconstruction in LDLT. The primary radiological or endoscopic interventions were satisfactory treatments of choice. Technical refinement is an important factor to reduce the incidence of BS..
1241. Shinichi Aishima, Yousuke Kuroda, Yunosuke Nishihara, Kenichi Taguchi, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi, Characteristic differences according to the cirrhotic pattern of advanced primary biliary cirrhosis: Macronodular cirrhosis indicates slow progression., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1016/j.hepres.2006.07.008, 36, 3, 188-94, 2006.11, It is important to evaluate advanced primary biliary cirrhosis (PBC) clinicopathologically to clarify its progressive mechanism. According to the cirrhotic pattern, 26 cases of explanted PBC were classified into non-cirrhotic (n=4), macronodular (n=4), mixed nodular (n=6), and micronodular cirrhosis (n=12), to compare their clinical and morphological features. In addition, the degree of preserved intrahepatic bile ducts and other histologic features were analyzed. Patients at living donor liver transplantation (LDLT) in the macronodular cirrhosis were significantly older than those in the micronodular cirrhosis. The mean duration between clinical presentation and LDLT in the macronodular cirrhosis was significantly longer than in the micronodular cirrhosis. The non-cirrhotic group showed a short duration between clinical presentation and LDLT. The ratio of explanted liver volume to standard liver volume (ELV/SLV) indicates that macronodular cirrhosis revealed more atrophic change than that in the other three types. The density of remnant intrahepatic bile ducts of less than 50mum per group in cases of macronodular cirrhosis was significantly higher than that in cases of micronodular cirrhosis. Therefore, different cirrhotic patterns of advanced PBC were correlated with the disease progression and the degree of bile duct disappearance. The macronodular cirrhotic patients were older, had a longer disease course, yet had less bile duct loss. We suggest that macronodular cirrhosis and micronodular cirrhosis of PBC are different type of PBC..
1242. Hideki Ijichi, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Mitsuo Shimada, Yoshihiko Maehara, Effect of hyperbaric oxygen on cold storage of the liver in rats., Liver international : official journal of the International Association for the Study of the Liver, 26, 2, 248-53, 2006.03, BACKGROUND: The depletion of biochemical energy stores during prolonged cold storage is one of the most critical events of cold ischemia-reperfusion (CI/R) injury. The aim of this study was to evaluate the effect of hyperbaric oxygen (HBO) treatment on CI/R injury. METHODS: Livers were harvested from male Wistar rats and stored for 24 h at 4 degrees C in University of Wisconsin solution (Group 1). Others were additionally treated with HBO during the preservation period (Group 2). At the end of the 24 h cold preservation, the concentrations of hepatic enzymes and lipid peroxidation (LPO) in the effluent and the hepatic adenosine triphosphate (ATP) levels were measured. After preservation, the livers were reperfused for 90 min with an oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. RESULTS: In group 2, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and LPO into the effluent at the end of preservation were decreased and the depletion of ATP was prevented (P<0.05). After reperfusion, the portal flow was significantly improved in group 2 (P<0.05). The time-dependent increase of alanine aminotransferase levels (ALT) observed in group 1 was suppressed significantly in group 2, and total bile production during 90 min of reperfusion was significantly greater in group 2 (P<0.05). The structure of the livers in group 2 was significantly well maintained, and the liver weight change ratio was significantly greater in group 1 (P<0.05). CONCLUSIONS: HBO treatment during cold storage seems to prevent hepatic ischemic injury and have protective effects against CI/R injury by attenuating the depletion of energy stores..
1243. Y Soejima, A Taketomi, T Yoshizumi, H Uchiyama, N Harada, H Ijichi, Y Yonemura, M Shimada, Y Maehara, Feasibility of left lobe living donor liver transplantation between adults: An 8-year, single-center experience of 107 cases, AMERICAN JOURNAL OF TRANSPLANTATION, 10.1111/j.1600-6143.2006.01284.x, 6, 5, 1004-1011, 2006.05, Operative mortality for a right lobe (RL) donor in adult living donor liver transplantation (LDLT) is estimated to be as high as 0.5-1%. To minimize the risk to the donor, left lobe (LL)-LDLT might be an ideal option in adult LDLT. The aim of the study was to assess the feasibility of LL-LDLT between adults based on a single-center experience of 107 LL-LDLTs performed over 8 years. The mean graft weight of ILL grafts was 452 g, which amounted to 40.5% of the estimated standard liver volume of the recipients. The overall 1-, 3- and 5-year patient survival rates in LL-LDLT were 81.4, 76.9 and 74.7%, respectively, which were comparable to those of RL-LDLT. Twenty-six grafts (24.3%) were lost for various reasons with three losses directly attributable to small-for-size graft syndrome. Post-operative liver function and hospital stay in LL donors were significantly better and shorter than that in RL donors, while the incidence of donor morbidity was comparable between LL and RL donors. In conclusion, LL-LDLT was found to be a feasible option in adult-to-adult LDLT. Further utilization of LL grafts should be undertaken to keep the chance of donor morbidity and mortality minimal..
1244. Yo-Ichi Yamashita, Akinobu Taketomi, Kengo Fukuzawa, Tomoharu Yoshizumi, Hideaki Uchiyama, Mitsuo Simada, Ken Shirabe, Kenzo Wakasugi, Yoshihiko Maehara, Gemcitabine combined with 5-fluorouracil and cisplatin (GFP) in patients with advanced biliary tree cancers: A pilot study, Anticancer Research, 26, 1 B, 771-775, 2006.01, Background: Advanced biliary tree cancers have poor prognosis and chemotherapy has been shown to have little impact. To date, no standard chemotherapy regimens have been established. A pilot study to evaluate gemcitabine/5-Fluorouracil(5-FU)/cisplatin(CDDP) (GFP) chemotherapy in patients with advanced biliary tree cancers was performed. Patients and Methods: Eight patients with advanced intrahepatic cholangiocarcinoma and gallbladder carcinoma with no prior chemotherapy were treated with a 4-week cycle GFP chemotherapy consisting of gemcitabine at 1000 mg/m2 on days 1, 8, and 15, and of 5-FU at 250 mg/patient and CDDP at 5 mg/patient on days 1 to 5, 8 to 12 and 22 to 26. Results: Of these 8 patients, no complete responses (CR) were observed, but 3 patients (37.5%) demonstrated partial responses (PR) with an additional 3 patients (37.5%) having stable diseases (SD), as assessed by RECIST. Two patients with PR and 1 patient with SD were treated by curative operation after GFP chemotherapy and all of them survived with no recurrence. The median overall survival time was 23.5 months, and median time to progression was 14.5 months. Grade 3/4 side-effects, such as leukopenia, thrombocytepenia and anemia were found in 4 patients (50%), but no patients dropped out because of toxicity. Conclusion: This GFP chemotherapy has promising antitumor activity and is well tolerated in patients with advanced biliary tree cancers. This regimen warrants further evaluation in a phase II study including larger numbers of patients..
1245. Hideki Ijichi, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Yusuke Yonemura, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, Hyperbaric oxygen induces vascular endothelial growth factor and reduces liver injury in regenerating rat liver after partial hepatectomy., Journal of hepatology, 45, 1, 28-34, 2006.07, BACKGROUND/AIMS: The aim of this study was to investigate the effect and the mechanism of hyperbaric oxygen treatment on regenerating rat liver after partial hepatectomy (PH). METHODS: Wistar rats underwent a 70% PH, followed by treatment with hyperbaric oxygen starting 8 h after PH. The regenerated liver weight and serum parameters were compared. Proliferation of both hepatocytes and sinusoidal endothelial cell (SEC) was also monitored by evaluating the proliferating cell nuclear antigen (PCNA) labeling index. Furthermore, the hepatic adenosine triphosphate levels and vascular endothelial growth factor (VEGF) protein expression were analyzed at different times. RESULTS: Hyperbaric oxygen treatment significantly reduced the serum alanine aminotransferase levels at 24 h, total bilirubin and total bile acid levels at 48 and 72 h, respectively. No significant differences in the hepatic adenosine triphosphate levels, the restitution of liver weight, or PCNA positive hepatocytes were observed between the two groups. The PCNA positive SEC, in contrast, was significantly increased in the hyperbaric oxygen group at 48h, furthermore, the hyperbaric oxygen treatment significantly increased the expression of VEGF protein in the regenerating liver at 24 and 48 h. CONCLUSIONS: Hyperbaric oxygen treatment can be considered as a therapeutic modality after massive PH..
1246. Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Tomoharu Yoshizumi, Keiji Kishikawa, Yoshihiko Maehara, Reconstruction of the middle hepatic vein tributaries using the recipient's recanalized umbilical vein in right-lobe living-donor liver transplantation., Surgery, 139, 3, 442-5, 2006.03, BACKGROUND: Right-lobe grafts without the middle hepatic vein (MHV) can cause severe congestion of the anterior segment in living-donor liver transplantation (LDLT). However, the indications and methods for reconstructing the MHV or its tributaries remain controversial. METHODS: We herein describe two cases of the successful use of the recipient's recanalized umbilical vein as an interposition graft to drain the major MHV tributaries in right-lobe LDLTs. RESULTS: After surgery, both right-lobe grafts are currently functioning well and all of the reconstructed venous tributaries have been confirmed to be patent by doppler ultrasonography. The histopathological features of the recanalized umbilical vein showed an intact intima with thickened media. CONCLUSIONS: The use of the recipient's recanalized umbilical vein is a good option for reconstructing MHV tributaries in right-lobe LDLTs..
1247. Hideaki Uchiyama, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hideki Ijichi, Yusuke Yonemura, Yoshihiko Maehara, Successful adult-to-adult living donor liver transplantation in a patient with moderate to severe portopulmonary hypertension., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.20691, 12, 3, 481-4, 2006.03, Portopulmonary hypertension (PPHTN) is one of the most devastating consequences of end-stage liver cirrhosis. When a patient has moderate to severe PPHTN, his or her candidature for liver transplantation is denied. Here we report a successful adult-to-adult living donor liver transplantation (LDLT) in a patient with moderate to severe PPHTN. The patient was a 58-yr-old female who was diagnosed with end-stage liver cirrhosis due to chronic hepatitis C. Preoperative evaluation revealed that the patient had moderate to severe PPHTN. Her mean pulmonary artery pressure (mPAP) was 35-47 mmHg without treatment. Continuous epoprostenol therapy was introduced to lower the mPAP. She underwent LDLT using an extended right hepatic lobe graft which was donated by her daughter. Prolonged artificial ventilation was necessary until postoperative day (POD) 25, after which her general condition gradually improved. By POD 72, she was in good condition and was allowed to leave the hospital. Currently, 1 yr after the operation, she visits the outpatient clinic regularly and enjoys a normal life. It should be noted, however, that the PPHTN markedly improved but did not completely resolve, as assessed by right heart catheterization 1 yr after successful LDLT..
1248. Tomoharu Yoshizumi, Yoshikazu Yonemitsu, Yasuhiro Ikeda, Yasufumi Kaneda, Katsuhiko Yanaga, Keizo Sugimachi, Katsuo Sueishi, Tumor necrosis factor-a antisense transfer remarkably improves hepatic graft viability., Liver international : official journal of the International Association for the Study of the Liver, 26, 4, 451-6, 2006.05, BACKGROUND: Cold ischemia/reperfusion injury of the hepatic graft, an unsolved problem in liver transplantations, is attributed to the release of inflammatory cytokines, especially the tumor necrosis factor- (TNF) alpha, from activated Kupffer cells (KC). Therefore, the specific inhibition of TNF-alpha could improve the viability of the hepatic graft upon reperfusion. METHODS: We assessed the efficacy of TNF-alpha antisense (TNF-AS) oligodeoxynucleotides (ODNs) delivery to KC in a rodent liver transplantation model. RESULTS: Seventy-one percent of the animals that received 6 hours preserved grafts in baths of lactated Ringer's solution (4 degrees C) and were treated with TNF-AS survived for over 14 days. Eighty percent of the animals treated with vehicle, sense ODNs, or balanced salt saline (BSS) died. Four hours after reperfusion of the liver, a significant reduction was noted in livers treated with TNF-AS in the release of cytosolic enzymes from the hepatocytes and the serum TNF-alpha (P<0.05). The expressions of TNF-alpha on KC and of intercellular adhesion molecule-1 on sinusoidal endothelial cells were completely suppressed in TNF-AS-treated livers. CONCLUSIONS: TNF-AS delivery improves the viability of the hepatic graft, and this technique may solve hepatic graft nonfunction in a clinical setting..
1249. T Suehiro, M Shimada, K Kishikawa, T Shimura, Y Soejima, T Yoshizumi, K Hashimoto, Y Mochida, S Hashimoto, Y Maehara, H Kuwano, Effect of intraportal infusion to improve small for size graft injury in living donor adult liver transplantation, TRANSPLANT INTERNATIONAL, 10.1111/j.1432-2277.2005.00159.x, 18, 8, 923-928, 2005.08, The most important problem in the living donor adult liver transplantation (LDALT) is a small for size graft. Although a right lobe graft is used in many cases in order to avoid small for size graft, for a donor, the risk has few in left lobe graft. We evaluate the effect of an intraportal infusion treatment to the small for size graft. One hundred and twelve patients who underwent LDALT were studied. The graft weight recipient standard liver volume ratio (GV/SLV) of these patients were 50% or less. We divided the patients into following two groups; infusion group (n = 53) and control group (n = 59). For the infusion group, 16 G double lumen catheter was inserted into portal vein and nafamostat mesilate (protease inhibitor which stabilize coagulofibrinolytic state; 200 mg/day), prostaglandin E, (vasodilator and hepatoprotective effect; 500 mu g/day) and thromboxane A(2) synthetase inhibitor (vasodilator and anticoagulant effect; 160 mg/day) were administrated continuously for 7 days. Small-for-size graft syndrome was defined as bilirubin > 10 mg/dl and ascites > 1000 cc on postoperative day (POD) 14. Comparison examination of a background factors and postoperative bilirubin and amount of ascites was carried out. The mean GV/SLV did not have the difference at 39.1% of infusion group, and 38.3% of control group (P = 0.58). By the control group, 15 patients (25.4%) were small-for-size graft syndrome, however, there was only two (3.8%) small-for-size graft syndrome in infusion group (P = 0.04). The bilirubin levels of infusion and control group on 7 and 14 POD were 9.9 and 7.8 vs. 9.5 and 10.5 mg/dl, respectively. The amount of ascites of infusion group on 7 and 14 POD were 870 and 430 cc, respectively. On the contrary, in control group, the amount of ascites on 7 and 14 POD were 1290 and 1070 cc, respectively. Bilirubin levels and the amount of ascites on 7 and 14 POD were lower in the patients with infusion group then those with control group. There were no differences between infusion group and control group in age, sex and Child's classification. The intraportal infusion had an effect in prevention of hyperbilirubinemia and loss in quality of excessive ascites in the patients with small for size graft. This was suggested to be what is depended on the improvement of the microcirculation insufficiency considered one of the causes of small-for-size graft syndrome..
1250. Shunsaku Katsura, Keiko Ogita, Tomoaki Taguchi, Sachiyo Suita, Tomoharu Yoshizumi, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, Effect of liver transplantation on multiple bone fractures in an infant with end-stage biliary atresia: a case report., Pediatric surgery international, 21, 1, 47-9, 2005.01, Osteodystrophy is frequently found in children with chronic cholestatic liver disease. We herein report an end-stage case of biliary atresia that was associated with multiple bone fractures and severe growth retardation. The patient, an 8-month-old female, underwent a living-related liver transplantation and thereafter showed a dramatic improvement in growth and decrease in bone fractures. A correction of the liver function is therefore considered to be a key factor in treating osteodystrophy that is related to chronic cholestatic liver disease. It is also essential to perform liver transplantation at the most appropriate time to enhance and support the growth of these patients..
1251. Keiko Ogita, Tomoaki Taguchi, Yuji Soejima, Satoshi Ieiri, Shunsaku Katsura, Narito Takada, Toshiharu Matsuura, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Sachiyo Suita, Fatty liver caused by portal vein thrombosis after living donor liver transplantation: a case report., Journal of pediatric surgery, 40, 8, E7-9, 2005.08, Portal vein thrombosis (PVT) is a rare complication that occurs after liver transplantation: however, it cannot be ignored as a cause of graft loss and death. We herein report a pediatric case of PVT that caused a fatty change in the graft after living donor liver transplantation. The portal vein was successfully reconstructed using the left great saphenous vein of the same donor. Moreover, the fatty liver recovered after the operation. Our case suggests that the finding of fatty liver is an important marker of PVT and immediate portal reconstruction is performed..
1252. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiko Maehara, Hiroyukl Kuwano, Impact of graft hepatic vein inferior vena cava reconstruction with graft venoplasty and inferior vena cava cavoplasty in living donor adult liver transplantation using a left lobe graft, Transplantation, 10.1097/01.tp.0000173776.66867.f5, 80, 7, 964-968, 2005.10, Background. Hepatic venous reconstruction is critical in living donor adult liver transplantation (LDALT) because outflow obstruction in small for size graft may lead to graft dysfunction or loss. We describe the usefulness of venoplasties of the graft hepatic vein (HV) and graft HV-recipient inferior vena cava (IVC) reconstruction in LDALT using a left lobe graft. Methods. Sixty patients who underwent LDALT were studied. We divided the patients into following two groups: venoplasty group (n=30) and control group (n=30). For the patients with venoplasty group, venoplasty of the graft and recipient IVC cavoplasty was made to widen the orifice. Comparison examination of a background factors and postoperative bilirubin and the ascites was carried out. Results. The mean graft volume standard liver volume ratio (GV/SLV) did not have the difference at 41.7% of venoplasty group, and 42.1% of control group (p=NS). The diameter of the hepatic vein in control and venoplasty group before and after venoplasty is 26.9±5.5, 28.2±2.9, and 34.1±3.9 mm, respectively. The diameter of the hepatic vein after venoplasty is larger than that of before venoplasty and of control (P<
0.05). Mean total bilirubin level on postoperative day (POD) 7 is 13.8±9.3 mg/dl in control group and 7.0±3.3 mg/dl in venoplasty group (P<
0.05). Mean amount of ascites on POD 7 and 14 are 1576±1113 and 1397±1661 cc in control group, and 736±416 and 550±385 cc in venoplasty group, respectively (P<
0.05). Two-year survival rate is 75.2% in control group and 86.6% in venoplasty group (P<
0.05). Conclusions. We conclude that in LDALT using left lobe graft, HV-IVC reconstruction with graft venoplasty and IVC cavoplasty is useful not only to prevent outflow block but also to improve graft function. Copyright © 2005 by Lippincott Williams &
Wilkins..
1253. T Suehiro, M Shimada, K Kishikawa, T Shimura, Y Soejima, T Yoshizumi, K Hashimoto, Y Mochida, Y Maehara, H Kuwano, In situ dye injection bile leakage test of the graft in living donor liver transplantation, TRANSPLANTATION, 10.1097/01.tp.0000181166.63783.69, 80, 10, 1398-1401, 2005.11, Background. Bile leakage after living donor liver transplantation (LDLT) remains a serious problem, resulting in lower survival rates. The aim of this study is to clarify the benefits of in situ leakage testing of the cut surface of grafts in LDLT.
Methods. A total of 135 LDLTs were analyzed. The patients were divided into the following two groups according to the in situ dye injection leakage test of the cut surface: test group (n=40) and control group (n=40). The incidence of bile leakage and the risk factors were identified by analyzing the recipients, donors, and transplantation variables.
Results. Bile leakage occurred in 12.5% (10/80) of LDLTs. In the control group, there were nine cases of bile leakage (22.5%). On the other hand, there was only one case (2.5%) of bile leakage in the test group (P<0.05). The bile leakage case in the test group was resolved preservationally. However, 2 of the 9 (22.2%) bile leakage cases in the control group required surgery.
Conclusion. Although there is biliary complication, especially bile leakage from the cut surface, as an inevitable consequence of LDLT, this study suggests that there is advantage in conducting bile leakage testing to minimize the incidence of bile leakage from the cut surface, which is associated with a high risk of graft failure..
1254. T Suehiro, M Shimada, K Kishikawa, T Shimura, Y Soejima, T Yoshizumi, K Hashimoto, Y Mochida, Y Maehara, H Kuwano, Influence of HLA compatibility and lymphocyte cross-matching on acute cellular rejection following living donor adult liver transplantation, LIVER INTERNATIONAL, 10.1111/j.1478-3231.2005.01160.x, 25, 6, 1182-1188, 2005.12, Background: Reports on the relevance of immunogenetic factors in living donor adult liver transplantation (LDALT) are often conflicting or inconclusive. We therefore investigated the human leukocyte antigen (HLA) mismatches, lymphocyte crossmatch positivity, and the reactivity in mixed lymphocyte culture (MLC) in a series of LDALT. Methods: A total of 104 LDALT patients were studied. The minimum follow-up was 12 months, and the graft survival rates were assessed. The incidence of the most common complications was analyzed. And the influence of HLA, the flow cytometric analysis findings, enhanced cytotoxic cross-matching and MLC on graft survival, and acute rejection was also investigated. Results: As a result, 96 negative cross-matching and eight positive cross-matching cases were identified. Positive cytotoxic cross-matching had a significant effect on graft survival (P < 0.05), while flow cytometric cross-matching also had an additional effect on acute rejection (P < 0.05). The MLC of the patients with three HLA mismatches was significantly higher than the MLC of patients with zero HLA mismatches. The incidence of acute cellular rejection (ACR) was higher in the patients with three mismatches than in the other patients, and moderate rejection only occurred in the patients with three mismatches. Conclusion: HLA mismatching was not statistically associated with the overall graft survival after LDALT. The graft failure rates were higher in the positive cross-matching cases and therefore a strong immuosuppressant might be needed for positive cross-matching cases..
1255. M Shimada, Y Yonemura, H Ijichi, N Harada, S Shiotani, M Ninomiya, T Terashi, T Yoshizumi, Y Soejima, Y Maehara, Living donor liver transplantation for hepatocellular carcinoma: A special reference to a preoperative des-gamma-carboxy prothrombin value, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2005.12.030, 37, 2, 1177-1179, 2005.03, Background. Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence in living donor liver transplantation (LDLT) with special reference to preoperative DCP values.
Methods. Forty consecutive adult HCC patients who underwent LDLT were examined for a correlation between the DCP value and vascular invasion. Risk factors for recurrence were also investigated using clinicopathological variables including preoperative DCP levels.
Results. The incidence of positive histological vascular invasion in patients with DCP values above 300 mAU/mL was higher than that with those with DCP value below 300 mAU/mL. Other significant risk factors for recurrence were over 5 cm tumor diameter, not meeting the Milan criteria, AFP value > 400 ng/mL, histological vascular invasion, poorly differentiated histology, and male gender. Among the patients who did not meet the Milan criteria, those with both no more than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good prognosis.
Conclusions. A high DCP value, namely > 300 mAU/mL correlated with histological vascular invasion and was one of the strongest prognostic variables. Therefore, special attention should be paid to HCC patients with high DCP values. No correlation between the number of tumor nodules and recurrence was found; therefore, the Milan criteria may require revision regarding the number of tumor nodules..
1256. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiko Maehara, Hiroyuki Kuwano, Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation., Liver international : official journal of the International Association for the Study of the Liver, 25, 6, 1169-74, 2005.12, BACKGROUND: Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors. METHODS: We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA. RESULTS: All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months. CONCLUSIONS: Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors..
1257. Makoto Nakamuta, Shusuke Morizono, Yuji Soejima, Tomoharau Yoshizumi, Shinji Aishima, Shin-Ichiro Takasugi, Kengo Yoshimitsu, Munechika Enjoji, Kazuhiro Kotoh, Akinobu Taketomi, Hideaki Uchiyama, Mitsuo Shimada, Hajime Nawata, Yoshihiko Maehara, Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation, Transplantation, 10.1097/01.tp.0000166009.77444.f3, 80, 5, 608-612, 2005.09, Background. The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. Methods. Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. Results. The treatment significantly improved macrovesicular steatosis (30±4% vs. 12±2% [mean±SEM], P= 0.0028). Body weight and BMI were significantly reduced (73.7±3.2 kg vs. 66.9±2.9 kg, P=0.0033, 26.4±0.7 kg/m2 vs. 24.1±0.8 kg/m2, P=0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n=7) and donor liver without hepatic steotosis (n=37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. Conclusions. The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen. Copyright © 2005 by Lippincott Williams &
Wilkins..
1258. Yusuke Yonemura, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Tomonobu Gion, Noboru Harada, Hideki Ijichi, Kengo Yoshimitsu, Yoshihiko Maehara, Validity of preoperative volumetric analysis of congestion volume in living donor liver transplantation using three-dimensional computed tomography., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.20537, 11, 12, 1556-62, 2005.12, Reconstruction of middle hepatic vein (MHV) tributaries is controversial in right-lobe living donor liver transplantation (LDLT). This study aimed to evaluate the appropriateness of reconstructing MHV tributaries by volumetry using 3-dimensional computed tomography (3D-CT). Between November 2003 and January 2005, 42 donor livers (right-lobe graft, n = 25; left-lobe graft, n = 17) were evaluated using this software. The total congestion volume (CV) associated with the MHV tributaries and the inferior right hepatic vein (IRHV), and graft volume (GV) were calculated. In recipients with right-lobe grafts, CV/(right liver volume [RLV]) and (GV - CV)/(standard liver volume [SLV]) were compared between 2 groups: with reconstruction (n = 16) and without reconstruction (n = 9). To evaluate the influence of CV on the remnant right lobe in donors, total bilirubin was compared between 2 groups: high CV (CV > 20%, n = 13) or low CV (CV < or = 20%, n = 4). The mean CV/RLV ratio was 32.3 +/- 17.1% (V5, 15.2 +/- 9.9%; V8, 9.2 +/- 4.1%; and IRHV, 8.5 +/- 11.4%) and the maximum ratio was as high as 80.8%. The mean (GV - CV)/SLV ratio before reconstruction in patients with or without reconstruction resulted in 33.5 +/- 12.8% and 55.4 +/- 12.9%, respectively (P < 0.01). In donors, total bilirubin was significantly high in the high CV group on postoperative day 1 compared with the low CV group (P < 0.05). In conclusion, calculation of CV using 3D-CT software proved to be very useful. We concluded that this evaluation should be an integral part of procedure planning, especially for right-lobe LDLT..
1259. Noboru Harada, Mitsuo Shimada, Tomoharu Yoshizumi, Taketoshi Suehiro, Yuji Soejima, Yoshihiko Maehara, A simple and accurate formula to estimate left hepatic graft volume in living-donor adult liver transplantation., Transplantation, 77, 10, 1571-5, 2004.05, BACKGROUND: In the field of living-donor adult liver transplantation, a small-for-size graft often occurs, particularly when using left-lobe grafts. This is because of the limited volumes associated with left-lobe grafts. The accurate preoperative evaluation of graft volumes is crucial to avoid this complication. The aim of this study is to clarify the usefulness of a new formula to estimate the left-lobe graft volume. METHOD: In 61 left-lobe grafts, a new formula was created with stepwise regression analysis using the following variables: height, weight, the thoracic and abdominal distance from anterior to posterior side (A-P), and distance from left to right side (L-R) of the initial 20 donors. With another 41 donors, the difference between the actual and estimated graft volume using the formula and two- and three-dimensional computed tomography was prospectively evaluated. RESULTS: On the basis of the results of the stepwise regression analysis, a new formula was created as follows: graft volume (ml) = 313.4 + 7.7 x weight (kg)-12.6 x thoracic L-R (cm). The difference between the actual and estimated graft volumes using the formula was significantly better (10.8 +/- 9.5%) than that of the volumetry using two-dimensional computed tomography (16.3 +/- 10.1%) (P < 0.05). CONCLUSIONS: In conclusion, the new formula can estimate the actual graft volume more accurately than conventional volumetry with two-dimensional computed tomography. The formula is useful to estimate the volume of left-lobe graft in living-donor adult liver transplantation..
1260. M Shimada, H Ijichi, Y Yonemura, N Harada, S Shiotani, M Ninomiya, T Yoshizumi, Y Soejima, T Suehiro, Y Maehara, Is graft size a major risk factor in living-donor adult liver transplantation?, TRANSPLANT INTERNATIONAL, 10.1007/s00147-004-0720-9, 17, 6, 310-316, 2004.07, Graft size is known to be a major risk factor in living donor adult liver transplantation (LDALT). The aim of this study is to reassess whether graft size is a critical factor in LDALT or not. A series of 75 LDALTs excluding auxiliary transplantation and ABO blood-type incompatible transplantation were analyzed. The patients were divided into two groups, according to graft volume (GV) and standard liver volume (SLV): group 1 (small-size group) (GV/SLV: <40%), and group 2 (non-small-size group) (greater than or equal to40%). Perioperative clinical data were compared between the two groups, including graft survival and postoperative complications. These parameters were also compared under the conditions of cirrhotic recipients. No difference in graft survival was found between the two groups. No difference was found in incidence of postoperative complications, such as intractable ascites and persistent hyperbilirubinemia. Even in cirrhotic patients with Child-Pugh's class C, there was no difference in graft survival between the two groups. Risk factors related to graft loss were a preoperative urgent status due to chronic liver disease, pre-operative hyperbilirubinemia of over 10 mg/dl, and ABO blood type of not identical but compatible combination between donor and recipient. Graft size is not always considered to be a major risk factor in LDALT, although the number of patients was small in this study. Therefore, a left-lobe graft, even a "small-for-size" graft for adult recipients, remains a feasible option in LDALT..
1261. S Shiotani, M Shimada, Y Soejima, T Yoshizumi, S Uemoto, T Kiuchi, K Tanaka, Y Maehara, S100 ss protein: The preoperative new clinical indicator of brain damage in patients with fulminant hepatic failure, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2004.09.030, 36, 9, 2713-2716, 2004.11, The aim of this study was to clarify the role of serum S100beta on the accurate assessment of reversibility of brain damage after fulminant hepatic failure (FHF). Among the 13 patients with FHF enrolled in this study, 12 underwent living donor liver transplantation; one patient could not the procedure because of volvulus of the sigmoid colon.
Serum S100beta was serially measured using a chemiluminescent immunoassay. Preoperative serum S100beta in patients with diffuse brain edema was significantly higher than that in patients with localized brain edema (P < 0.05). Patients with preoperative brain death showed serum S100beta levels over 7.0 /mug/L.
Serum S100beta levels correlated with the degree of brain edema of FHF. It has the potential to be a new clinical, noninvasive indicator of brain damage due to FHF..
1262. M Shimada, H Ijichi, Y Yonemura, N Harada, S Shiotani, M Ninomiya, T Terashi, T Yoshizumi, Y Soejima, T Suehiro, Y Maehara, The impact of splenectomy or splenic artery ligation on the outcome of a living donor adult liver transplantation using a left lobe graft, HEPATO-GASTROENTEROLOGY, 51, 57, 625-629, 2004.05, Background/Aims: The aim of this study was to clarify the impact of splenectomy or splenic artery ligation on the outcome in living donor adult liver transplantation (LDALT) using a left lobe graft.
Methodology: Forty-eight LDALT cases using a left lobe graft were enrolled in this study. The patients were classified into two groups: Group A (n=40), in which neither a splenectomy nor a splenic artery ligation was performed, and Group B (n=8), in which a splenectomy (n=6) or a splenic artery ligation (n=2) was performed. Indications for splenectomy were as follows: 1) demonstrating a hypersplenism and/or 2) having splenic aneurysms.
Results: None of the patients receiving a splenectomy or a splenic artery ligation experienced any septic complication in this series. The graft-recipient weight ratio in group B tended to be smaller than in group A. In group B, all patients were classified into Child's class C or B. The incidence of esophageal varices in group B was significantly higher than in group A. Moreover, the platelet count and the white blood cell count in group B were significantly lower than in group A. No statistical difference was found in postoperative functional cholestasis and intractable ascites. None of the participants in group B experienced both postoperative hyperbilirubinemia and intractable ascites, which were characterized as a small-for-size graft after LDALT. The patient survival rate in group B seems to be better than in group A. In a majority of the cases the portal pressure as well as the portal vein flow after a splenectomy decreased in comparison to that before the splenectomy.
Conclusions: Splenectomy or splenic artery ligation is considered to be beneficial for improving the outcome in LDALT using a left lobe graft..
1263. Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Keiji Kishikawa, Tomoharu Yoshizumi, Koji Hashimoto, Ryosuke Minagawa, Shoji Hiroshige, Takahiro Terashi, Mizuki Ninomiya, Satoko Shiotani, Noboru Harada, Keizo Sugimachi, Use of steatotic graft in living-donor liver transplantation., Transplantation, 76, 2, 344-8, 2003.07, BACKGROUND: The degree of fatty infiltration in hepatic grafts is known to be an important risk factor for primary graft nonfunction in cadaveric liver transplantation. However, the effect of hepatic steatosis in living-donor liver transplantation (LDLT) has not yet been well defined. In this study, we evaluated the impact that the degree of hepatic graft steatosis has on the outcome of LDLT. METHODS: Sixty consecutive donors and recipients who underwent LDLT between October 1996 and August 2001 at Kyushu University Hospital were the subjects of this study. The pathologic findings of the prereperfusion biopsy of the graft were classified into the following three groups according to the degree of macrovesicular steatosis: None (n=23), 0% steatosis; Mild (n=23), 0% to 20% steatosis; and Moderate (n=6), 20% to 50% steatosis. Liver function tests including total bilirubin (at postoperative day [POD] 7), the peak alanine aminotransferase (ALT) and prothrombin time (at POD 3), and both patient and graft survival were compared among the groups. Furthermore, we also compared the donor parameters including the peak ALT and total bilirubin (at POD 3) and the operative time, blood loss, and length of hospital stay after surgery. RESULTS: The 1-year patient and graft survival were comparable among the groups. The peak ALT was significantly higher in the Moderate group (606+/-641 IU/L) than in the None (290+/-190 IU/L) and Mild (376+/-296 IU/L) groups. Total bilirubin (POD 7) and prothrombin time (POD 3) were comparable among the groups. The donor parameters were comparable among the groups except for the fact that the donor body weight of the Mild and Moderate groups were significantly heavier (P<0.0001) than that of the None group. CONCLUSIONS: In conclusion, the use of a fatty liver graft up to the moderate level can be justified in LDLT, even though ischemia-reperfusion injury tends to be severe in such grafts..
1264. Shinji Okano, Masatoshi Eto, Yukihiro Tomita, Tomoharu Yoshizumi, Hisakata Yamada, Ryosuke Minagawa, Kenichi Nomoto, Keizo Sugimachi, Kikuo Nomoto, Cyclophosphamide-induced tolerance in rat orthotopic liver transplantation, Transplantation, 10.1097/00007890-200102150-00019, 71, 3, 447-456, 2001.02, Background. We previously established a cyclophosphamide (CP)-induced tolerance system in rodent skin graft models. In this study, we applied this system to rat liver transplantation. Methods. Lewis recipients were inoculated on day -2 with spleen and bone marrow cells (SC+BMC) from Dark Agouti (DA) donors, followed by 100 mg/kg CP on day 0. On day 25, DA livers were orthotopically grafted. We assessed the alloresponses to the donors of the long-term surviving recipients, using the second skin grafting and in vitro assay. Results. The recipients that had been treated with SC+BMC and CP survived for more than 165 days. None of control group that received SC+BMC alone (mean survival times [MST]=13.8 days), CP alone (MST=40.0), SC+BMC from third-party PVG rats and CP (MST=45.0), or no treatment (MST=13.8) survived over 50 days. The donor-specific tolerance was confirmed by second skin grafts onto recipients with permanent DA liver grafts, which accepted DA skins (MST>
75) but not PVG (MST=8.3). However, the lymphocytes from the tolerant recipients showed alloresponse to DA in vitro. To investigate whether the T helper type 2 deviation contributed to this "split tolerance," we assessed the production of cytokines in mixed lymphocyte reaction. Interleukin 2 and interferon-γ were detected but interleukin 4 was not. Conclusions. These data showed that this protocol induced split tolerance in rat liver transplantation and, furthermore, the mechanism of split tolerance was not due to T helper 2 deviation..
1265. T Nishizaki, T Ikegami, S Hiroshige, K Hashimoto, H Uchiyama, T Yoshizumi, K Kishikawa, M Shimada, K Sugimachi, Small graft for living donor liver transplantation, ANNALS OF SURGERY, 233, 4, 575-580, 2001.04, Objective To evaluate the impact of graft size on recipients in living donor liver transplantation (LDLT) to establish a clinical guideline for the minimum requirement.
Summary Background Data Although the minimum graft size required for LDLT has been reported to be 30% to 40% of graft volume (GV)/standard liver volume (SLV), the safety limit of the graft size was unknown.
Methods A total of 33 cases of LDLT, excluding auxiliary transplantation, were reviewed with a minimum observation period of 4 months. The 33 patients were divided into three groups according to GV/SLV: medium-size graft group, small-size graft group, and extra-small graft group. The effect of GV/SLV on graft function, graft regeneration, and survival was evaluated.
Results The overall patient survival rate was 94% at a mean follow-up of 15 months with a minimum observation period of 4 months, There were no statistically significant differences in postoperative bilirubin clearance, alanine aminotransferase, prothrombin time, and frequency of postoperative complications among the three groups. One week after transplantation, the regeneration rate (GV at 1 week/harvested GV) in the extra-small and small groups was significantly higher than that of the medium group. The graft and patient survival rates were both 100% in the extra-small group, 75% and 88% in the small group, and 90% and 95% in the medium group.
Conclusions Small-for-size grafts less than 30% of SLV can be used with careful intraoperative and postoperative management until the grafts regenerate..
1266. K. Hashimoto, T. Nishizaki, T. Yoshizumi, H. Uchiyama, S. Okano, T. Ikegami, K. Yanaga, K. Sugimachi, Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation, Transplantation, 10.1097/00007890-200011150-00009, 70, 9, 1318-1322, 2000.11, Background. Proinflammatory cytokines such as interleukin 1-β (IL-1β) and tumor necrosis factor-α (TNF-α) play an important role in the development of hepatic ischemia/reperfusion injury. FR167653 has been characterized as a potent suppressant of IL-1β and TNF-α production. The aim of this study was to evaluate the effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation. Methods. Donor livers were preserved with cold University of Wisconsin solution for 48 hr and transplanted orthotopically. Immediately after reperfusion, FR167653 (1 mg/kg, FR-treated group) or normal saline solution (control group) was administered i.v.. The severity of liver injury was determined by hepatic enzyme levels as well as by histological findings. The accumulation of IL-1β and TNF-α mRNA in the liver was analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Tissue factor expression was subjected to immunohistochemical analysis. Results. In the FR-treated group, release of aspartate aminotransferase and alanine aminotransferase after reperfusion was significantly lower (P<
0.05 and P<
0.02, respectively), and histological liver injury was less prominent, than in the control group. Accumulation of IL-1β and TNF-α mRNA was suppressed in the FR-treated liver. Tissue factor expression on Kupffer cells and sinusoidal endothelial cells, marked in the control group, was almost absent in the FR-treated group. Seven-day survival in the FR-treated group (75%) was significantly better than that in the control group (12.5%) (P<
0.01). Conclusions. These results indicate that treatment with FR167653 ameliorates cold ischemia/reperfusion injury in liver transplantation..
1267. T Nishizaki, K Kishikawa, T Yoshizumi, H Uchiyama, S Okano, T Ikegami, K Hashimoto, K Nomoto, M Shimada, K Yanaga, K Takenaka, K Sugimachi, Y Ando, M Ando, Domino liver transplantation from a living related donor, TRANSPLANTATION, 70, 8, 1236-1239, 2000.10, Background. Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery Lie in the small size of the graft volume and the short length of the vascular cuffs in the graft.
Methods. The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient, At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A).
Results. The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence.
Conclusion, A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis..
1268. Y Soejima, K Yanaga, T Nishizaki, T Yoshizumi, H Uchiyama, K Sugimachi, Effect of specific neutrophil elastase inhibitor on ischemia/reperfusion injury in rat liver transplantation, JOURNAL OF SURGICAL RESEARCH, 86, 1, 150-154, 1999.09, Activated neutrophils have been implicated as playing an important role in ischemia/reperfusion injury of the liver by releasing toxic mediators such as oxygen free radicals and elastases. In the present study, we evaluated the effect of a novel, specific neutrophil elastase inhibitor (ONO-5046) on cold-ischemia/reperfusion injury of the liver allograft in rodents. Livers from male Lewis rats were procured and stored cold (4 degrees C) in lactated Ringer's solution and transplanted orthotopically. Recipients were divided into three groups: Vehicle group, 5-h preservation and vehicle (n = 8); ONO-5046 group, 5-h preservation and administration of ONO-5046 (n = 8); and Control group, minimum preservation only (n = 8). Bile output after reperfusion was significantly larger in the ONO5046 group compared to the Vehicle group (P < 0.05 or less). Sinusoidal endothelial cell function represented by the serum hyaluronic acid concentration at 120 min after reperfusion of the ONO-5046 group was significantly lower than that in the Vehicle group (17.0 +/- 7.9 vs 36.2 +/- 14.9 ng/ml, P < 0.05), whereas serum transaminase levels 120 min after reperfusion were comparable between the two groups. Liver tissue energy charge 120 min after reperfusion was significantly better in the ONO-5046 group compared to the Vehicle group (P < 0.05). Furthermore, the number of neutrophils infiltrating the allograft after reperfusion was significantly depressed in the ONO-5046 group compared to the Vehicle group (P < 0.02). These data suggest that the neutrophil elastase might cause liver damage early after reperfusion in cold stored liver, which can be ameliorated by the administration of a specific neutrophil elastase inhibitor, ONO5046. (C) 1999 Academic Press..
1269. H Uchiyama, K Yanaga, T Nishizaki, Y Soejima, T Yoshizumi, K Sugimachi, Effects of deletion variant of hepatocyte growth factor on reduced-size liver transplantation in rats, TRANSPLANTATION, 68, 1, 39-44, 1999.07, Background The deletion variant of hepatocyte growth factor (dHGF) exerts mitogenic and antifibrotic effects. The purpose of this study was to evaluate the effect of dHGF on rats that had undergone syngeneic or allogeneic reduced-size (60%) orthotopic liver transplantation (ROLT).
Methods. Starting immediately after the syngeneic (Lewis to Lewis) and allogeneic (Lewis to Brown Norway) BOLT, 500 mu g/kg dHGF was administered i.v. twice a day until the day the rats were killed. Its effect on hepatic graft weight, regeneration, and biochemical parameters was evaluated.
Results. dHGF promoted restoration of the liver volume and liver regeneration as well as protein synthesis in the rats that under-event syngeneic BOLT. In the rats that underwent allogeneic BOLT, dHGF reduced the level of serum cytosolic enzymes related to acute cellular rejection, but a significant improvement in liver regeneration and protein synthesis was not seen. When tacrolimus was administered to prevent rejection of the allogeneic grafts, the beneficial effect of dHGF was apparent, and was as beneficial as in syngeneic ROLT.
Conclusions. Administering dHGF after liver transplantation augments the regeneration and functional recovery of partial liver grafts and reduces hepatocyte injury in acute cellular rejection..
1270. T Yoshizumi, K Yanaga, Y Soejima, T Maeda, H Uchiyama, K Sugimachi, Amelioration of liver injury by ischaemic preconditioning, BRITISH JOURNAL OF SURGERY, 85, 12, 1636-1640, 1998.12, Background Ischaemic preconditioning, i.e. preparatory brief ischaemia before subsequent longs ischaemia, can effectively protect the heart from ischaemia-reperfusion injury in animals. The purpose of this study was to demonstrate the same phenomenon in the liver.
Methods Using warm ischaemia-reperfusion of 70 per cent of the liver followed by resection of the non-ischaemic portion in rats. livers with 10 min of ischaemic preconditioning, i.e. 10 min of warm ischaemia and reperfusion, were compared with those that had not been subjected to such a manoeuvre.
Results At 120 min after reperfusion following 40 min of warm ischaemia, the livers with 10 min of ischaemic preconditioning had a significantly lower mean(s.d.) serum alanine aminotransferase level (492(217) versus 1236(695) units/l; P<0.005) and lactic dehydrogenase level (7905(4002) versus 15 066(9201) units/l; P <0.05), as well as a higher bile output (0.12(0.03) versus 0.09(0.04) ml per g liver; P<0.05) and liver tissue adenosine 5'-triphosphate level (78(13) versus 61(11) per cent; P<0.05) than the control livers. The necrosis rate, histologically defined as the percentage of necrotic area in given liver sections, was reduced significantly by this manoeuvre (mean(s.d.) 1.3(1.3) versus 5.3(1.7) per cent; P<0.05).
Conclusion Ischaemic preconditioning exerts a protective effect on hepatic warm ischaemia-reperfusion injury. Such a manoeuvre may be useful for hepatic resection in the clinical setting..
1271. Y Soejima, K Yanaga, T Nisizaki, T Yoshizumi, H Uchiyama, K Sugimachi, Effect of thromboxane synthetase inhibitor on non-heart-beating donors in rat orthotopic liver transplantation, SURGERY, 123, 1, 67-72, 1998.01, Background. The use of non-heart-beating donors could relieve donor organ shortage provided that the outcome of the recipients is not jeopardized.
Methods. In this study we evaluated the effect of thromboxane synthetase inhibitor (OKY-046) on non-heart-beating donors in orthotopic liver transplantation in rodents. OKY-046 (OKY group, n = 8) or vehicle (control group, n = 8) was given to the donor animals for 60 minutes before the induction of 30 minutes of warm ischemia to the liver before transplantation and survival, and several parameters were compared between the two groups.
Results. All recipients in the control group died within 2 days, whereas 67% of those of the OKY group had a 2-day survival and 44% had a 2-week survival (p < 0.01). Bile output from the allograft for 2 hours after reperfusion was significantly larger in the OKY group at all time points (p < 0.05). Furthermore, serum transaminase levels 10 minutes after reperfusion were significantly lower in the OKY group (p < 0.05), although those 120 minutes after reperfusion were comparable between the two groups. The thromboxane B-2 level in liver tissue 10 and 120 minutes after reperfusion was significantly lower in the OKY group compared with the control group (p < 0.02 and p < 0.05, respectively).
Conclusions. These results indicate that OKY-046 given to the donor before the induction of warm ischemia could ameliorate ischemia/reperfusion injury of the hepatic allograft by reducing thromboxane A(2) production after reperfusion..
1272. Katsuhiko Yanaga, Tomoharu Yoshizumi, Hideaki Uchiyama, Shinji Okano, Kenji Takenaka, Keizo Sugimachi, Detection of hepatitis C virus RNA in bile, American Journal of Gastroenterology, 92, 10, 1927-1928, 1997.10, Objectives: The infectivity of bile in patients with hepatitis C virus (HCV) infection remains to be clarified. The purpose of this study was to document the detection of HCV-RNA in bile of patients with HCV infection. Methods: Bile and serum samples were tested for HCV RNA by a two-step polymerase chain reaction technique in 12: patients with HCV infection. Results: HCV-RNA was detected in the serum of all 12 patients, whereas 6 of 12 bile samples (50%) tested positive. Comparison of laboratory data between patients with and without HCV-RNA in bile demonstrated statistically higher serum total billrubin among those with positive bile HCV RNA than those without, but other clinical and biochemical variables as well as hepatitis activity scores were comparable between the two groups. Conclusions: Bile of HCV antibody-positive patients could be infectious..
1273. Y Soejima, K Yanaga, T Nishizaki, T Yoshizumi, H Uchiyama, K Sugimachi, The fate of non-absorbable suture in growing vascular anastomoses in liver transplantation, HEPATO-GASTROENTEROLOGY, 44, 13, 227-230, 1997.01, Background/Aims: Anastomotic structure of the portal vein is an uncommon complication, of orthotopic liver transplantation for which the etiology is unclear. In the present study, we evaluated the fate of continuous anastomosis by non-absorbable suture material in. growing vessels after orthotopic Liver transplantation in pigs.
Materials and Methods: A pig which had undergone orthotopic liver transplantation 54 months earlier was autopsied and inspected for vascular growth and their anastomotic patency.
Results: The pig weighed 270kg (1,080%) at 54 months after orthotopic liver transplantation. The liver was normal in appearance and weighed 4,100g (770%). All the vessels anastomosed were patent. However, luminal stenosis of the portal vein was identified at the anastomosis site, where intraluminal protrusion of the anastomosis was prominent. The inability of the suture material to grow longer than its full Length along with the growth of the portal vein was suggested to be the main cause of the stenosis.
Conclusion: We conclude that the use of nonabsorbable sutures could cause late vascular anastomotic structure in pediatric orthotopic liver transplantation..
1274. S Wakiyama, K Yanaga, Y Soejima, T Nishizaki, T Yoshizumi, K Sugimachi, Assessment of hepatic graft injury by graft effluent in rodents: N-acetyl-beta-glucosaminidase and type III procollagen peptide, TRANSPLANT INTERNATIONAL, 9, 4, 359-363, 1996.07, We studied the significance of N-acetyl-beta-glucosaminidase (beta-NAG) and type III procollagen peptide (P-III-P) in the effluent of rodent hepatic grafts. After total hepatectomy, the livers were preserved in chilled, lactated Ringer's solution and then divided into five groups (n = 10 each): group 1, 4 h preservation only; group 2, 4 h preservation and rewarming; group 3, 6 h preservation only; group 4, 6 h preservation and rewarming; and group 5, minimal preservation only. The beta-NAG of groups 2 and 4 was significantly higher than that of groups 1 and 3 (0.98 +/- 0.5 U/l vs 0.21 +/- 0.12 U/l; P < 0.01 and 1.76 +/- 0.67 U/l vs 0.38 +/- 0.25 U/l, respectively; P < 0.01), while that of group 4 was significantly higher than that of group 2 (1.76 +/- 0.67 U/l vs 0.98 +/- 0.50 U/l; P < 0.05). The P-III-P of group 4 was significantly higher than that of group 2 (0.133 +/- 0.008 U/ml vs 0.110 +/- 0.015 U/ml; P < 0.01). We conclude that beta-NAG is a novel parameter of parenchymal and nonparenchymal cells, while P-III-P reflects the integrity of the hepatic sinusoidal extracellular matrix..
1275. T Nishizaki, T Matsumata, K Yanaga, Y Soejima, T Yoshizumi, K Takenaka, K Sugimachi, Management of hepatic duct injury during hemihepatic vascular occlusion, BRITISH JOURNAL OF SURGERY, 83, 2, 185-185, 1996.02.
1276. Y Soejima, K Yanaga, S Wakiyama, T Nishizaki, T Yoshizumi, K Sugimachi, Serum hyaluronic acid as a reliable parameter of allograft viability in porcine liver transplantation, HEPATO-GASTROENTEROLOGY, 43, 9, 590-595, 1996.05, Background/Aims: Hyaluronic acid is an endogenous glycosaminoglycan which is selectively degraded by hepatic sinusoidal endothelial cells. We evaluated the significance of serum hyaluronic acid clearance aas an early indicator of allograft viability in porcine liver transplantation.
Materials and Methods: According to the survival period, animals were divided into two groups: Group I (n=8) for survival equal or over four days and Group II (n=5) for survival less than four days. Serial serum hyaluronic acid concentrations were measured before and after reperfusion in the recipient.
Results: In both groups, serum hyaluronic acid levels during the anhepatic period increased rapidly 9-fold from the preoperative value due to the absence of clearance by hepatic endothelial cells. In Group I, serum hyaluronic acid peaked at 15 min postreperfusion and decreased thereafter. In contrast, Group II failed to show clearance of hyaluronic acid after reperfusion. The serum hyaluronic acid value 120 min after reperfusion was 1,029+/-357 mu g/L in Group I, and 1,856+/-263 mu g/L in Group II (p<0.01). Conventional parameters of liver function such as aspartate transaminase, lactic dehydrogenase, ammonia, lactate, and local bile acids were comparable between the two groups.
Conclusions: The clearance of the serum hyaluronic acid reflects hepatic sinusoidal endothelial cell function and is a reliable and early marker of hepatic allograft viability..
1277. T NISHIZAKI, K TAKENAKA, T YOSHIZUMI, K YANAGA, Y SOEJIMA, K SHIRABE, K SUGIMACHI, ALTERATION IN LEVELS OF HUMAN HEPATOCYTE GROWTH-FACTOR FOLLOWING HEPATECTOMY, JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS, 181, 1, 6-10, 1995.07, BACKGROUND: The clinical significance of changes in serum human hepatocyte growth factor (hHGF) in patients having hepatectomy remains unclear, partly because of various perioperative factors, such as underlying diseases and surgical procedures.
STUDY DESIGN: Human hepatocyte growth factor was measured preoperatively and then on postoperative days 1, 3, 5, and 7. In 49 (79 percent) of 62 patients studied, serum hHGF increased postoperatively and peaked on postoperative day 1 or 3 (group 1), while in the other 13 patients (21 percent), it decreased on postoperative day 1 (group 2).
RESULTS: The preoperative clinical parameters were comparable between the two groups except for indocyanine green retention rate at 15 minutes (16.6 compared with 23.4 percent; p<0.05). Operative stress and histology of the nontumorous portion of the liver were also comparable between the two groups. Postoperatively, alanine aminotransferase was significantly higher in group 1 than in group 2 on postoperative days 1 and 3. Regeneration of the remnant liver one month after hepatectomy was significantly higher in group 1 than in group 2 (5+/-9 percent compared with -6+/-8 percent; p<0.01), The incidence of postoperative hepatic failure was significantly higher in group 2 than in group 1 (15 compared with zero percent; p<0.05).
CONCLUSIONS: These observations led to the thesis that changes in serum hHGF levels after hepatectomy are an indicator of hepatic regeneration and also will serve as one factor to predict postoperative hepatic failure..
1278. K YANAGA, S WAKIYAMA, Y SOEJIMA, T YOSHIZUMI, T NISHIZAKI, K SUGIMACHI, HEPATITIS-C VIRUS-INFECTION AMONG JAPANESE GENERAL SURGICAL PATIENTS, WORLD JOURNAL OF SURGERY, 19, 5, 694-697, 1995.09, The incidence of hepatitis C virus (HCV) antibody positivity is unknown. The purpose of this study was to clarify the prevalence of HCV infection among surgical patients and to identify high risk surgical patients. HCV antibody tests were performed in 789 surgical patients between April 1991 and March 1992. Of these patients, 129 (16.3%) tested positive, which was much higher than the positivity of the ordinary Japanese. Hepatobiliary diseases and portal hypertension were associated with a higher positivity than other disease categories (94 of 206, 45.6% versus 35 of 583, 6%; p < 0.0001). Patients above 50 years of age had a higher positivity than their younger counterparts (118 of 578, 20.4% versus 11 of 211, 5.3%; p < 0.0001). The HCV positivity was as high as 54.1% (119 of 220) among surgical patients with known risk factors for hepatitis, in contrast to only 1.9% (10 of 569) among those without such risk factors. We conclude that surgical patients have a high incidence of HCV infection, for whom medical professionals should pay special attention to avoid disease transmission..
1279. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hiroto Kayashima, Kensaku Sanefuji, Tomoharu Yoshizumi, Noboru Harada, Yo Ichi Yamashita, Yoshihiko Maehara, Extracorporeal hepatic resection for unresectable giant hepatic hemangiomas, Liver Transplantation, 10.1002/lt.21272, 14, 1, 115-117, 2008.01.
1280. Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Hideaki Uchiyama, Toru Ikegami, Noboru Harada, Hiroto Kayashima, Yo Ichi Yamashita, Mitsuo Shimada, Yoshihiko Maehara, Impact of donor age and recipient status on left-lobe graft for living donor adult liver transplantation, Transplant International, 10.1111/j.1432-2277.2007.00561.x, 21, 1, 81-88, 2008.01, Donor safety is the priority when performing a living donor adult liver transplantation (LDALT). We herein present our findings using left-lobe graft in LDALT. Data on 119 recipients who underwent the LDALT, and on 119 donors who underwent extended left lobectomy were reviewed. The recipients were divided into groups above (n = 19) and below (n = 100) 50 years of donor age, into groups above (n = 63) and below (n = 56) 40% of graft size (graft volume/standard liver volume, GV/SLV), and above (n = 25) and below (n = 94) 20 of pre-operative model for end-stage liver disease (MELD). Total bilirubin (TB), volume of ascites, prothrombin time international normalized ratio on postoperative day 14 or survival rates were compared. TB (mg/dl) or volume of ascites (ml) of the group in donor age < 50 years was better than that of the group in donor age ≥ 50 years (7.4 vs. 14.7 or 788 vs. 1379, P < 0.001 or P < 0.005, respectively). The graft and patient survival rates of the lower MELD group tended to be better than that of the higher MELD group. LDALT can be safely performed using a left-lobe graft. However, when using the graft from the donor ≥ 50 years, especially for the recipients with the MELD ≥ 20, the indications should be carefully discussed..
1281. Yuji Soejima, Akinobu Taketomi, Toru Ikegami, Tomoharu Yoshizumi, Hideaki Uchiyama, Tomonobu Gion, Keishi Sugimachi, Shigeyuki Nagata, Yoshihiko Maehara, Liver transplantation for hepatocellular carcinoma
status quo and experience in Kyushu University, Fukuoka igaku zasshi = Hukuoka acta medica, 99, 5, 95-101, 2008.01.
1282. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Maehara, Living donor liver transplantation for acute liver failure using left lobe grafts [1], Transplantation, 10.1097/01.tp.0000296815.71784.3f, 85, 1, 160-161, 2008.01.
1283. Hideki Ijichi, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yusuke Yonemura, Yoshihiko Maehara, Successful management of chylous ascites after living donor liver transplantation with somatostatin, Liver International, 10.1111/j.1478-3231.2007.01556.x, 28, 1, 143-145, 2008.01, Chylous ascites is a rare complication following liver transplantation. A variety of treatment options have been proposed for the management of chylous ascites; however, their effectiveness following a liver transplant is unknown. A 40-year-old woman who underwent living donor liver transplantation for primary biliary cirrhosis developed chylous ascites 21 days after the transplant. A conventional treatment consisting of a low-fat diet with total parenteral nutrition failed to treat the complication for 104 days. However, the use of somatostatin in combination with total parenteral nutrition resulted in a rapid falloff in chyle output without any adverse effects. Somatostatin and total parenteral nutrition are an effective option for the treatment of chylous ascites after living donor liver transplantation..
1284. Hiroki Mori, Hisamitsu Shinohara, Yusuke Arakawa, Hirofumi Kanemura, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Toru Ikegami, Tomoharu Yoshizumi, Mitsuo Shimada, Beneficial effects of hyperbaric oxygen pretreatment on massive hepatectomy model in rats, Transplantation, 10.1097/01.tp.0000291778.86758.1d, 84, 12, 1656-1661, 2007.12, BACKGROUND. The purpose of this study was to investigate the impact of hyperbaric oxygen (HBO) pretreatment in massive hepatectomy model, a surrogate model of small-for-size graft, using rats. METHODS. (Experiment I) Rats were divided into the following four groups: HBO (-), HBO-1D (day), HBO-3D, and HBO-5D. Samples were taken after the completion of HBO pretreatment, and the following parameters were evaluated: reverse transcription polymerase chain reaction and immunohistochemical staining for HSP 70 and HO-1; biochemical parameters; and liver weight to body weight ratio (Lw/Bw ratio). (Experiment II) Rats were divided into four groups as follows; 70% hepatectomy (Hx), 70% Hx-HBO, 90% Hx, and 90% Hx-HBO group. Samples were taken 12, 24, 48, and 72 hr after hepatectomy and the following parameters were investigated: biochemical analysis; Lw/Bw ratio; PCNA labeling index; and survival. RESULTS. (Experiment I) The expression of HSP70 mRNA was significantly increased in the HBO-3D group compared with the HBO (-) group (P<0.05). HSP70- and HO-1-positive hepatocytes were significantly increased in the HBO-3D group compared with the HBO (-) group (P<0.05). (Experiment II) Transaminases were significantly decreased in both 70% and 90% Hx-HBO groups compared with Hx alone group (P<0.05). The Lw/Bw ratio and PCNA labeling index of the 90% Hx-HBO group were significantly increased compared with the 90% Hx group, 24, 48 and 72 hr after hepatectomy (P<0.05). The survival rate in the 90% Hx-HBO group was significantly higher than that in the 90% Hx group (P=0.01). CONCLUSIONS. HBO pretreatment had beneficial effects in a massive hepatectomy model in rats via the induction of HSP70 and HO-1..
1285. T. Ikegami, A. Taketomi, Y. Soejima, T. Iguchi, K. Sanefuji, H. Kayashima, T. Yoshizumi, N. Harada, Y. Maehara, Successful ABO Incompatible Living Donor Liver Transplantation in a Patient With High Isoagglutinin Titer Using High-Dose Intravenous Immunoglobulin, Transplantation Proceedings, 10.1016/j.transproceed.2007.09.028, 39, 10, 3491-3494, 2007.12, The optimal management in living donor liver transplantation using an ABO incompatible donor with a high isoagglutinin titer is still uncertain. Our patient was a 20-year-old woman with fulminant hepatitis. The only available donor was her 54-year-old father-in-law of an incompatible blood type. The initial isoagglutinin titer was 2048×. She received 375 mg/m2 of anti-CD20 antibody 3 days before the living donor liver transplantation with concomitant splenectomy. Despite daily plasma exchanges after transplantation, the isoagglutinin titer started to shoot up to its maximum value of 2048×, with a sudden decline in the bile output. High-dose intravenous immunoglobulin (0.6 g/kg) was given after the plasma exchanges; thereafter, her liver function tests stabilized without a further increase in the isoagglutinin titer. We showed the effectiveness of high-dose intravenous immunoglobulin for the management of the rebound elevation of isoagglutinin titer. The combination of anti-CD20 antibody and daily plasma exchanges seemed ineffective for such a situation. This strategy might be another management option for ABO incompatible liver transplantation..
1286. Yuji Soejima, Mitsuo Shimada, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Makoto Nakamuta, Yoshihiko Maehara, Successful living donor liver transplantation using a graft from a hepatitis B surface antigen-positive donor, Liver International, 10.1111/j.1478-3231.2007.01528.x, 27, 9, 1282-1286, 2007.11, Background/Aims: Liver transplantation using a graft from a donor with a positive hepatitis B surface antigen (HBsAg) has been contraindicated owing to the extremely high risk for recurrent disease leading to graft loss. However, the severe shortage of donors often forces the transplant community to utilize suboptimal donors, especially in the setting of living donor liver transplantation (LDLT). Method: Here, we report a case of successful LDLT for a patient with hepatitis B-related cirrhosis utilizing a graft from an HBsAg-positive 'healthy carrier' donor using a combination prophylaxis of lamivudine and adefovir dipivoxil. Results: To date, the patient has been doing well with normal liver function tests and liver histological findings at 4 years after the transplantation and the donor has also been doing well. Conclusions: Although virological recurrence appears to be universal despite prophylaxis, re-evaluation of the use of a graft from a healthy HBsAg-positive donor is warranted in this era of combination prophylaxis..
1287. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hideaki Uchiyama, Mitsuo Shimada, Yoshihiko Maehara, Explanted portal vein grafts for middle hepatic vein tributaries in living-donor liver transplantation, Transplantation, 10.1097/01.tp.0000296483.89112.4c, 84, 7, 836-841, 2007.10, BACKGROUND. The availability of a venous graft is limited in the setting of living donor liver transplantation (LDLT), and the management of the middle hepatic vein middle hepatic vein tributaries in right lobe LDLT still remains controversial. METHODS. Twenty-three right lobe LDLT grafts, with the reconstruction of middle hepatic vein tributaries using the explanted portal veins from the explanted livers, were evaluated for the patency, postLDLT liver function tests, and graft survival. RESULTS. The methods of outflow reconstruction were classified into three types: the interposition of the graft to the middle/left hepatic vein (n=12), to the vena cava (n=9), and to the vena cava as a co-orifice with the graft right hepatic vein (n=2). The 1- and 3-year patency rates were 76.7% and 76.7% respectively, with the graft occlusion in five cases. The occluded cases (n=5) had significantly higher aspartate aminotransferase and alanine transaminase levels as compared with those of patent cases (n=18) at 4 weeks after transplantation (P<0.01). However, there was no significant difference in the total bilirubin and prothrombin time in either group during the observation periods. The 1- and 3-year graft survival rates were 91.1% and 91.1%, respectively. In addition, there was no graft loss due to occlusion. CONCLUSION. The use of the recipient's explanted full-length hilar portal vein for the reconstruction of the middle hepatic vein tributaries is thus considered to be a feasible and valuable strategy in the setting of a right lobe LDLT, where appropriate vascular grafts are not always available..
1288. S. Shiotani, M. Shimada, A. Taketomi, Y. Soejima, T. Yoshizumi, K. Hashimoto, H. Shimokawa, Y. Maehara, Rho-kinase as a novel gene therapeutic target in treatment of cold ischemia/reperfusion-induced acute lethal liver injury
Effect on hepatocellular NADPH oxidase system, Gene Therapy, 10.1038/sj.gt.3303000, 14, 19, 1425-1433, 2007.10, In the transplant surgery, reactive oxygen species (ROS) from the reperfused tissue cause ischemia-reperfusion injury, resulting in the primary graft failure. We have recently reported that Rho-kinase, an effecter of the small GTPase Rho, plays an important role in the ROS production in the hyperacute phase of reperfusion; however, the sources and mechanisms of the ROS production remain to be elucidated. The aim of this study was to investigate the source of ROS production with a special reference to Rho-kinase to develop a new strategy against ischemia-reperfusion injury. In an in vivo rat model of liver transplantation, Kupffer cells in the graft were depleted using liposome-encapsulated dichloromethylene diphosphonate to examine the source of ROS production. The effect of adenoviral-mediated overexpression of a dominant-negative Rho-kinase (AdDNRhoK) in hepatocytes in the graft was also examined. Kupffer cells were not involved in the ROS production, whereas the AdDNRhoK transfection to hepatocytes significantly suppressed the ROS production. Furthermore, the ROS production was dose-dependently inhibited by apocynin, an NADPH oxidase inhibitor. Expression of DNRhoK also suppressed the release of pro-inflammatory cytokines, and ameliorated the lethal liver injury with a significant prolongation of the survival. These results suggest that the Rho-kinase-mediated pathway plays a crucial role in the ROS production through NADPH oxidase in hepatocytes during the hyperacute phase of reperfusion in vivo. Thus, Rho-kinase in hepatocytes may be a new therapeutic target for the prevention of primary graft failure in liver transplantation..
1289. Yuji Soejima, Toru Ikegami, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yoichi Yamashita, Yoshihiko Maehara, Hepatitis B vaccination after living donor liver transplantation, Liver International, 10.1111/j.1478-3231.2007.01521.x, 27, 7, 977-982, 2007.09, Background: The efficacy of hepatitis B vaccination after living donor liver transplantation (LDLT) in patients transplanted anti-HBc-positive grafts or in patients who underwent LDLT for fulminant hepatitis B remains unknown. Method: A total of 11 recipients who underwent LDLT between October 1996 and October 2002 prospectively received hepatitis B vaccination three times within 6 months, starting a few weeks after the cessation of hepatitis B immunoglobulin (HBIG) prophylaxis. Serial quantification of the hepatitis B surface antibody (HBsAb) was performed. Results: At the last follow-up, six out of 11 patients (54.5%) had seroconversion and were free from HBIG thereafter. Four out of those six responders had a peak HBsAb level of more than 1000 IU/L, while the other two patients had peak HbsAb levels below 1000 IU/L. Five patients never responded to the treatment and were back to HBIG prophylaxis. The average age of the six responders was 25.5 years, which was significantly younger than that of non-responders (44.4 years, P < 0.05). None had side effects or hepatitis B infection during the study period. Conclusions: In conclusion, the use of this treatment modality could be used to reduce the cost of HBIG..
1290. Yo ichi Yamashita, Kengo Fukuzawa, Akinobu Taketomi, Shinichi Aishima, Tomoharu Yoshizumi, Hideaki Uchiyama, Eiji Tsujita, Norifumi Harimoto, Noboru Harada, Kenzo Wakasugi, Yoshihiko Maehara, Mucin-hypersecreting bile duct neoplasm characterized by clinicopathological resemblance to intraductal papillary mucinous neoplasm (IPMN) of the pancreas, World Journal of Surgical Oncology, 10.1186/1477-7819-5-98, 5, 2007.08, Background: Although intraductal papillary mucinous neoplasm (IPMN) of the pancreas is acceptable as a distinct disease entity, the concept of mucin-secreting biliary tumors has not been fully established. Case presentation: We describe herein a case of mucin secreting biliary neoplasm. Imaging revealed a cystic lesion 2 cm in diameter at the left lateral segment of the liver. Duodenal endoscopy revealed mucin secretion through an enlarged papilla of Vater. On the cholangiogram, the cystic lesion communicated with bile duct, and large filling defects caused by mucin were observed in the dilated common bile duct. This lesion was diagnosed as a mucin-secreting bile duct tumor. Left and caudate lobectomy of the liver with extrahepatic bile duct resection and reconstruction was performed according to the possibility of the tumor's malignant behavior. Histological examination of the specimen revealed biliary cystic wall was covered by micropapillary neoplastic epithelium with mucin secretion lacking stromal invasion nor ovarian-like stroma. The patient has remained well with no evidence of recurrence for 38 months since her operation. Conclusion: It is only recently that the term "intraductal papillary mucinous neoplasm (IPMN)," which is accepted as a distinct disease entity of the pancreas, has begun to be used for mucin-secreting bile duct tumor. This case also seemed to be intraductal papillary neoplasm with prominent cystic dilatation of the bile duct..
1291. Sawako Inoue, Shusuke Morizono, Shinsaku Yamashita, Yuki Horikawa, Motoyuki Kohjima, Yuzuru Miyagi, Tsuyosi Yoshimoto, Kazuhiro Kotoh, Munechika Enjoji, Ryoichi Takayanagi, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Makoto Nakamuta, Estimation of indication for living donor liver transplantation in patients with HCV and/or HBV infection, Fukuoka igaku zasshi = Hukuoka acta medica, 98, 7, 295-300, 2007.07, We evaluated 78 patients with chronic viral hepatitis for liver transplantation. 51 patients met our original criteria for liver transplantation, and 35 patients of them suffered from hepatocellular carcinoma (HCC). Patients with HCC were significantly older and showed higher prothrombin activity than those without HCC. Eighteen of 35 patients with HCC did not meet the Milan criteria, and they showed lower levels of total bilirubin, Child-Pugh score, and MELD score than those who met the criteria. Theses results indicate that acceptability for transplantation should be evaluated soon after the patients have become candidates for liver transplantation. In Japan, decompensated liver cirrhosis is a necessary condition for the application of public health insurance against liver transplantarion and, in cases with HCC, it is necessary to meet the Milan criteria. Application to liver transplantation should also be considered based on HCC stage such as the UNOS scoring system..
1292. Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Shinich Aishima, Takahiro Terashi, Mitsuo Shimada, Yoshihiko Maehara, Extended indication for living donor liver transplantation in patients with hepatocellular carcinoma, Transplantation, 10.1097/01.tp.0000259015.46798.ec, 83, 7, 893-899, 2007.04, BACKGROUND. Liver transplantation is an accepted treatment option for patients with otherwise untreatable hepatocellular carcinoma (HCC). The present study assessed the outcome of living donor liver transplantation (LDLT) under extended selection criteria based on a single-center experience. METHODS. A total of 60 patients who underwent LDLT for HCC were included. Our indication for LDLT included HCC without extrahepatic spread or macroscopic vascular invasion. The size and number of HCC nodules were not limited. Recurrence-free survival rates according to various factors were compared to identify risk factors for recurrence. RESULTS. Forty patients (67%) preoperatively exceeded the Milan criteria. The median follow-up was 437 days (range: 23-1,385 days). The overall 1- and 3-year actuarial survival rates were 88.4 and 68.6%, respectively. HCC recurred in eight patients (14.3%) within a mean follow-up of 288 days; all were patients who exceeded the Milan criteria. The 1-, 2- and 3-year recurrence-free survival rates of patients who fulfilled the Milan criteria were 100%, 100%, and 100%, respectively, whereas those of patients who exceeded the criteria were 83.0%, 74.0%, and 74.0%, respectively. Tumor diameter >5 cm was significantly associated with worse prognosis, but the number of tumors was not. A preoperative des-gamma-carboxy prothrombin value >300 mAU/ml was strongly associated with the high recurrence rate. These two variables were significant in multivariate analysis. CONCLUSIONS. LDLT was shown to offer acceptable results in patients who exceeded the Milan criteria. The indication for LDLT can therefore be expanded beyond the Milan criteria, especially for patients with small multiple tumors <5 cm..
1293. Kotaro Miyake, Satoru Imura, Tomoharu Yoshizumi, Tetsuya Ikemoto, Yuji Morine, Mitsuo Shimada, Role of thymidine phosphorylase and orotate phosphoribosyltransferase mRNA expression and its ratio to dihydropyrimidine dehydrogenase in the prognosis and clinicopathological features of patients with pancreatic cancer, International Journal of Clinical Oncology, 10.1007/s10147-006-0634-x, 12, 2, 111-119, 2007.04, Background. Thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD) are important enzymes related to the metabolism of 5-fluorouracil and its derivatives. In this study, we analyzed the expression of these enzymes and evaluated the association between the expression of these enzymes and clinicopathological features and prognosis in patients with pancreatic cancer. Methods. TP, OPRT, and DPD mRNA expressions were detected using a real-time reverse transcriptional-polymerase chain reaction method or by immunohistochemistry, using surgical specimens obtained from 25 patients with pancreatic cancer. Results. TP mRNA expression was lower in cases with an alpha infiltration growth pattern than in cases with other infiltration growth patterns (P < 0.05). OPRT mRNA expression was higher in poorly differentiated-type cases than in differentiated type cases (P < 0.05). TP-, OPRT-, and DPD-positive stainings were found in 15 of 24 cases (63%), 10 of 19 cases (53%), and 14 of 21 cases (67%), respectively. There were significant correlations or trends between the mRNA and protein expressions of TP, OPRT, and DPD. Patients with a low TP/DPD ratio survived significantly longer than those with a high ratio (P < 0.05). Multivariate analysis demonstrated a significantly poorer outcome in patients with a high TP/DPD ratio compared with in patients with a low ratio (P < 0.05). Conclusion. The TP/DPD ratio might be useful as a prognostic factor in patients with pancreatic cancer..
1294. Tomoharu Yoshizumi, Mitsuo Shimada, Yuji Soejima, Takahiro Terashi, Akinobu Taketomi, Yoshihiko Maehara, Successful pylorus-preserving pancreaticoduodenectomy for a patient with carcinoma of the papilla vater two years after living donor liver transplantation, Hepato-gastroenterology, 54, 75, 941-943, 2007.04, Liver transplantation has been recognized as the treatment for various kinds of end-stage liver diseases. Standardized surgical technique, potent immunosuppressive agents and diligent postoperative care have made it possible for patients to survive for a longer period. For this reason, recurrent primary disease and/or de novo malignancy regarded as chronic immunosuppressant have been paid a great deal of attention. Even pancreas cancer after liver transplantation is extremely rare and has never been successfully treated. Furthermore, cancer of the papilla Vater, which is less frequent than pancreas cancer after liver transplantation has not been reported as yet. In this paper we discuss the first case of cancer of the papilla Vater, which was successfully treated by pylorus-preserving pancreaticoduodenectomy two years after a living related liver transplantation using a left lobe. In addition, we discuss the type of malignancy after liver transplantation..
1295. Ken Shirabe, Shinji Itoh, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Shin Ichi Aishima, Yoshihiko Maehara, The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma - With special reference to the serum levels of des-gamma-carboxy prothrombin, Journal of Surgical Oncology, 10.1002/jso.20655, 95, 3, 235-240, 2007.03, The microvascular invasion of cancer cells (mvi) is a good prognostic factor after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The aim of this study is to predict mvi in patients with HCC who were candidates for OLT. We studied 218 patients with HCC resections who had HCC without any extrahepatic metastases and vascular invasion detected during preoperative evaluation. We analyzed the clinico-pathological data of these patients to predict the mvi presence. The mvi prediction scoring system was made and the accuracy of this system was examined using independent clinico-pathologic factors. The size and histological grade of the tumor were significantly correlated with the mvi. The des-gamma-carboxy prothrombin (DCP) is a mvi predictor. The sensitivity of our mvi prediction system was 75% and the specificity was 85% in 32 patients who underwent living-donor liver transplantations for HCC. Our study shows that besides the tumor size and histological grade, a measurement of the serum DCP levels could be a good predictor for mvi. A tumor biopsy and a preoperative measurement of DCP could improve the selection of patients with HCC for OLT. Our scoring system for mvi provides us a precise prediction of the presence of mvi..
1296. Hideaki Uchiyama, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hideki Ijichi, Yusuke Yonemura, Yoshihiko Maehara, Hepatic artery aneurysm arising from an interposition vein graft four years after auxiliary partial orthotopic liver transplantation [2], Transplant International, 10.1111/j.1432-2277.2006.00402.x, 20, 2, 197-200, 2007.02.
1297. Shinichi Aishima, Yousuke Kuroda, Yunosuke Nishihara, Kenichi Taguchi, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi, Characteristic differences according to the cirrhotic pattern of advanced primary biliary cirrhosis
Macronodular cirrhosis indicates slow progression, Hepatology Research, 10.1016/j.hepres.2006.07.008, 36, 3, 188-194, 2006.11, It is important to evaluate advanced primary biliary cirrhosis (PBC) clinicopathologically to clarify its progressive mechanism. According to the cirrhotic pattern, 26 cases of explanted PBC were classified into non-cirrhotic (n = 4), macronodular (n = 4), mixed nodular (n = 6), and micronodular cirrhosis (n = 12), to compare their clinical and morphological features. In addition, the degree of preserved intrahepatic bile ducts and other histologic features were analyzed. Patients at living donor liver transplantation (LDLT) in the macronodular cirrhosis were significantly older than those in the micronodular cirrhosis. The mean duration between clinical presentation and LDLT in the macronodular cirrhosis was significantly longer than in the micronodular cirrhosis. The non-cirrhotic group showed a short duration between clinical presentation and LDLT. The ratio of explanted liver volume to standard liver volume (ELV/SLV) indicates that macronodular cirrhosis revealed more atrophic change than that in the other three types. The density of remnant intrahepatic bile ducts of less than 50 μm per group in cases of macronodular cirrhosis was significantly higher than that in cases of micronodular cirrhosis. Therefore, different cirrhotic patterns of advanced PBC were correlated with the disease progression and the degree of bile duct disappearance. The macronodular cirrhotic patients were older, had a longer disease course, yet had less bile duct loss. We suggest that macronodular cirrhosis and micronodular cirrhosis of PBC are different type of PBC..
1298. Noriaki Kawano, Kazuya Shimoda, Fumihiko Ishikawa, Akinobu Taketomi, Tomoharu Yoshizumi, Shinji Shimoda, Shuro Yoshida, Koji Uozumi, Shinsuke Suzuki, Yoshihiko Maehara, Mine Harada, Adult T-cell leukemia development from a human T-cell leukemia virus type I carrier after a living-donor liver transplantation, Transplantation, 10.1097/01.tp.0000235186.30113.c7, 82, 6, 840-843, 2006.09, Adult T-cell leukemia (ATL) develops in a human T-cell leukemia virus type I (HTLV-I) carrier. The development of malignancy during immunosuppressive treatment following organ transplantation is one of the late fatal complications. We describe the development of three cases of ATL in eight HTLV-I carriers within 164 living-donor liver transplant recipients undergoing immunosuppressive treatment. All three cases were immunosuppressed with tacrolimus. Acute-type ATL was diagnosed at 6, 9, and 25 months after living-donor liver transplantation, based on increased numbers of CD4+25+ lymphocytes exhibiting "flower-like" nuclei, and the elevation of lactate dehydrogenase. Southern blot analysis demonstrated the clonal proliferation of ATL cells in peripheral blood. The ATL cells originated from the recipient, as demonstrated by fluorescence in situ hybridization analysis using sex chromosomal markers. Our observations suggest that immunosuppressive treatment for the prevention of graft rejection after living-donor liver transplantation may induce the development of ATL in an HTLV-I carrier..
1299. Hideki Ijichi, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Yusuke Yonemura, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, Hyperbaric oxygen induces vascular endothelial growth factor and reduces liver injury in regenerating rat liver after partial hepatectomy, Journal of Hepatology, 10.1016/j.jhep.2005.12.021, 45, 1, 28-34, 2006.07, Background/Aims: The aim of this study was to investigate the effect and the mechanism of hyperbaric oxygen treatment on regenerating rat liver after partial hepatectomy (PH). Methods: Wistar rats underwent a 70% PH, followed by treatment with hyperbaric oxygen starting 8 h after PH. The regenerated liver weight and serum parameters were compared. Proliferation of both hepatocytes and sinusoidal endothelial cell (SEC) was also monitored by evaluating the proliferating cell nuclear antigen (PCNA) labeling index. Furthermore, the hepatic adenosine triphosphate levels and vascular endothelial growth factor (VEGF) protein expression were analyzed at different times. Results: Hyperbaric oxygen treatment significantly reduced the serum alanine aminotransferase levels at 24 h, total bilirubin and total bile acid levels at 48 and 72 h, respectively. No significant differences in the hepatic adenosine triphosphate levels, the restitution of liver weight, or PCNA positive hepatocytes were observed between the two groups. The PCNA positive SEC, in contrast, was significantly increased in the hyperbaric oxygen group at 48 h, furthermore, the hyperbaric oxygen treatment significantly increased the expression of VEGF protein in the regenerating liver at 24 and 48 h. Conclusions: Hyperbaric oxygen treatment can be considered as a therapeutic modality after massive PH..
1300. Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yusuke Yonemura, Tetsuo Ikeda, Mitsuo Shimada, Yoshihiko Maehara, Biliary strictures in living donor liver transplantation
Incidence, management and technical evolution, Liver Transplantation, 10.1002/lt.20740, 12, 6, 979-986, 2006.06, Biliary complications, biliary strictures (BS) in particular, continue to be a significant cause of morbidity after LDLT despite technical refinement. In this study, we assessed the incidence of BS and their management in living donor liver transplantation (LDLT) with special reference to the type of biliary reconstruction. A total of 182 LDLTs performed at our institution for either adult (n = 157) or pediatric (n = 25) patients were included in the study. The duct-to-duct (DD) biliary reconstruction was performed for 106 cases, while the conventional Roux-en-Y hepaticojejunostomy (HJ) was utilized for the remaining 76 cases. Overall, BS developed in 46/182 (25.3%) of the cases (DD, 26.4%; HJ, 25.0%). The 1- and 3-year cumulative incidences of BS were 22.9% and 31.9%, respectively, in the DD group, and 15.2% and 29.1%, respectively, in the HJ group (P = not significant). The left-lobe LDLT was more prone to develop BS. Continuous anastomosis tended to be associated with the high incidence of BS in the DD group. The incidence of anastomotic leak was significantly lower in the DD group. Intervention via either precutaneous or endoscopic approach was successful in the majority of cases, although recurrence could occur in some patients. In conclusion, BS was not associated with the type of reconstruction in LDLT. The primary radiological or endoscopic interventions were satisfactory treatments of choice. Technical refinement is an important factor to reduce the incidence of BS..
1301. Yuji Soejima, Tomoaki Taguchi, Keiko Ogita, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Takuro Ohno, Mitsuo Shimada, Yoshihiko Maehara, Auxiliary partial orthotopic living donor liver transplantation for a child with congenital absence of the portal vein, Liver Transplantation, 10.1002/lt.20692, 12, 5, 845-849, 2006.05, Congenital absence of the portal vein (CAPV) is a rare malformation of the mesenteric vasculature in which visceral venous blood bypasses the liver, completely draining into the systemic circulation through a congenital porto-systemic shunt. Liver transplantation has rarely been indicated for patients with this disease. We present a child with CAPV who was managed successfully by living donor auxiliary partial orthotopic liver transplantation (APOLT), while preserving the right lobe of the native liver. In conclusion, APOLT for patients with CAPV is a feasible and ideal procedure because portal vein (PV) diversion is not necessary..
1302. Y. Soejima, A. Taketomi, T. Yoshizumi, H. Uchiyama, N. Harada, H. Ijichi, Y. Yonemura, M. Shimada, Y. Maehara, Feasibility of left lobe living donor liver transplantation between adults
An 8-year, single-center experience of 107 cases, American Journal of Transplantation, 10.1111/j.1600-6143.2006.01284.x, 6, 5 I, 1004-1011, 2006.05, Operative mortality for a right lobe (RL) donor in adult living donor liver transplantation (LDLT) is estimated to be as high as 0.5-1%. To minimize the risk to the donor, left lobe (LL)-LDLT might be an ideal option in adult LDLT. The aim of the study was to assess the feasibility of LL-LDLT between adults based on a single-center experience of 107 LL-LDLTs performed over 8 years. The mean graft weight of LL grafts was 452 g, which amounted to 40.5% of the estimated standard liver volume of the recipients. The overall 1-, 3- and 5-year patient survival rates in LL-LDLT were 81.4, 76.9 and 74.7%, respectively, which were comparable to those of RL-LDLT. Twenty-six grafts (24.3%) were lost for various reasons with three losses directly attributable to small-for-size graft syndrome. Post-operative liver function and hospital stay in LL donors were significantly better and shorter than that in RL donors, while the incidence of donor morbidity was comparable between LL and RL donors. In conclusion, LL-LDLT was found to be a feasible option in adult-to-adult LDLT. Further utilization of LL grafts should be undertaken to keep the chance of donor morbidity and mortality minimal..
1303. Tomoharu Yoshizumi, Yoshikazu Yonemitsu, Yasuhiro Ikeda, Yasufumi Kaneda, Katsuhiko Yanaga, Keizo Sugimachi, Katsuo Sueishi, Tumor necrosis factor-α antisense transfer remarkably improves hepatic graft viability, Liver International, 10.1111/j.1478-3231.2006.01252.x, 26, 4, 451-456, 2006.05, Background: Cold ischemia/reperfusion injury of the hepatic graft, an unsolved problem in liver transplantations, is attributed to the release of inflammatory cytokines, especially the tumor necrosis factor- (TNF) α, from activated Kupffer cells (KC). Therefore, the specific inhibition of TNF-α could improve the viability of the hepatic graft upon reperfusion.: We assessed the efficacy of TNF-α antisense (TNF-AS) oligodeoxynucleotides (ODNs) delivery to KC in a rodent liver transplantation model. Results: Seventy-one percent of the animals that received 6 hours preserved grafts in baths of lactated Ringer's solution (4°C) and were treated with TNF-AS survived for over 14 days. Eighty percent of the animals treated with vehicle, sense ODNs, or balanced salt saline (BSS) died. Four hours after reperfusion of the liver, a significant reduction was noted in livers treated with TNF-AS in the release of cytosolic enzymes from the hepatocytes and the serum TNF-α (P<0.05). The expressions of TNF-α on KC and of intercellular adhesion molecule-1 on sinusoidal endothelial cells were completely suppressed in TNF-AS-treated livers. Conclusions: TNF-AS delivery improves the viability of the hepatic graft, and this technique may solve hepatic graft nonfunction in a clinical setting..
1304. Hideki Ijichi, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Mitsuo Shimada, Yoshihiko Maehara, Effect of hyperbaric oxygen on cold storage of the liver in rats, Liver International, 10.1111/j.1478-3231.2005.01218.x, 26, 2, 248-253, 2006.03, Background: The depletion of biochemical energy stores during prolonged cold storage is one of the most critical events of cold ischemiareperfusion (CI/R) injury. The aim of this study was to evaluate the effect of hyperbaric oxygen (HBO) treatment on CI/R injury. Methods: Livers were harvested from male Wistar rats and stored for 24 h at 4 °C in University of Wisconsin solution (Group 1). Others were additionally treated with HBO during the preservation period (Group 2). At the end of the 24 h cold preservation, the concentrations of hepatic enzymes and lipid peroxidation (LPO) in the effluent and the hepatic adenosine triphosphate (ATP) levels were measured. After preservation, the livers were reperfused for 90 min with an oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. Results: In group 2, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and LPO into the effluent at the end of preservation were decreased and the depletion of ATP was prevented (P < 0.05). After reperfusion, the portal flow was significantly improved in group 2 (P < 0.05). The time-dependent increase of alanine aminotransferase levels (ALT) observed in group 1 was suppressed significantly in group 2, and total bile production during 90 min of reperfusion was significantly greater in group 2 (P < 0.05). The structure of the livers in group 2 was significantly well aintained, and the liver weight change ratio was significantly greater in group 1 (P < 0.05). Conclusions: HBO treatment during cold storage seems to prevent hepatic ischemic injury and have protective effects against CI/R injury by attenuating the depletion of energy stores..
1305. Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Tomoharu Yoshizumi, Keiji Kishikawa, Yoshihiko Maehara, Reconstruction of the middle hepatic vein tributaries using the recipient's recanalized umbilical vein in right-lobe living-donor liver transplantation, Surgery, 10.1016/j.surg.2005.08.005, 139, 3, 442-445, 2006.03, Background. Right-lobe grafts without the middle hepatic vein (MHV) can cause severe congestion of the anterior segment in living-donor liver transplantation (LDLT). However, the indications and methods for reconstructing the MHV or its tributaries remain controversial. Methods. We herein describe two cases of the successful use of the recipient's recanalized umbilical vein as an interposition graft to drain the major MHV tributaries in right-lobe LDLTs. Results. After surgery, both right-lobe grafts are currently functioning well and all of the reconstructed venous tributaries have been confirmed to be patent by doppler ultrasonography. The histopathological features of the recanalized umbilical vein showed an intact intima with thickened media. Conclusions. The use of the recipient's recanalized umbilical vein is a good option for reconstructing MHV tributaries in right-lobe LDLTs..
1306. Hideaki Uchiyama, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hideki Ijichi, Yusuke Yonemura, Yoshihiko Maehara, Succesful adult-to-adult living donor liver transplantation in a patient with moderate to severe portopulmonary hypertension, Liver Transplantation, 10.1002/lt.20691, 12, 3, 481-484, 2006.03, Portopulmonary hypertension (PPHTN) is one of the most devastating consequences of end-stage liver cirrhosis. When a patient has moderate to severe PPHTN, his or her candiclature for liver transplantation is denied. Here we report a successful adult-to-adult living donor liver transplantation (LDLT) in a patient with moderate to severe PPHTN. The patient was a 58-yr-old female who was diagnosed with end-stage liver cirrhosis due to chronic hepatitis C. Preoperative evaluation revealed that the patient had moderate to severe PPHTN. Her mean pulmonary artery pressure (mPAP) was 35-47 mmHg without treatment. Continuous epoprostenol therapy was introduced to lower the mPAP. She underwent LDLT using an extended right hepatic lobe graft which was donated by her daughter. Prolonged artificial ventilation was necessary until postoperative day (POD) 25, after which her general condition gradually improved. By POD 72, she was in good condition and was allowed to leave the hospital. Currently, 1 yr after the operation, she visits the outpatient clinic regularly and enjoys a normal life. It should be noted, however, that the PPHTN markedly improved but did not completely resolve, as assessed by right heart catheterization 1 yr after successful LDLT..
1307. Yo Ichi Yamashita, Akinobu Taketomi, Kengo Fukuzawa, Tomoharu Yoshizumi, Hideaki Uchiyama, Mitsuo Simada, Ken Shirabe, Kenzo Wakasugi, Yoshihiko Maehara, Gemcitabine combined with 5-fluorouracil and cisplatin (GFP) in patients with advanced biliary tree cancers
A pilot study, Anticancer research, 26, 1 B, 771-775, 2006.01, Background: Advanced biliary tree cancers have poor prognosis and chemotherapy has been shown to have little impact. To date, no standard chemotherapy regimens have been established. A pilot study to evaluate gemcitabine/5-Fluorouracil(5-FU)/cisplatin(CDDP) (GFP) chemotherapy in patients with advanced biliary tree cancers was performed. Patients and Methods: Eight patients with advanced intrahepatic cholangiocarcinoma and gallbladder carcinoma with no prior chemotherapy were treated with a 4-week cycle GFP chemotherapy consisting of gemcitabine at 1000 mg/m2 on days 1, 8, and 15, and of 5-FU at 250 mg/patient and CDDP at 5 mg/patient on days 1 to 5, 8 to 12 and 22 to 26. Results: Of these 8 patients, no complete responses (CR) were observed, but 3 patients (37.5%) demonstrated partial responses (PR) with an additional 3 patients (37.5%) having stable diseases (SD), as assessed by RECIST. Two patients with PR and 1 patient with SD were treated by curative operation after GFP chemotherapy and all of them survived with no recurrence. The median overall survival time was 23.5 months, and median time to progression was 14.5 months. Grade 3/4 side-effects, such as leukopenia, thrombocytepenia and anemia were found in 4 patients (50%), but no patients dropped out because of toxicity. Conclusion: This GFP chemotherapy has promising antitumor activity and is well tolerated in patients with advanced biliary tree cancers. This regimen warrants further evaluation in a phase II study including larger numbers of patients..
1308. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiko Maehara, Hiroyuki Kuwano, Influence of HLA compatibility and lymphocyte cross-matching on acute cellular rejection following living donor adult liver transplantation, Liver International, 10.1111/j.1478-3231.2005.01160.x, 25, 6, 1182-1188, 2005.12, Background: Reports on the relevance of immunogenetic factors in living donor adult liver transplantation (LDALT) are often conflicting or inconclusive. We therefore investigated the human leukocyte antigen (HLA) mismatches, lymphocyte crossmatch positivity, and the reactivity in mixed lymphocyte culture (MLC) in a series of LDALT. Methods: A total of 104 LDALT patients were studied. The minimum follow-up was 12 months, and the graft survival rates were assessed. The incidence of the most common complications was analyzed. And the influence of HLA, the flow cytometric analysis findings, enhanced cytotoxic cross-matching and MLC on graft survival, and acute rejection was also investigated. Results: As a result, 96 negative cross-matching and eight positive cross-matching cases were identified. Positive cytotoxic cross-matching had a significant effect on graft survival (P<0.05), while flow cytometric cross-matching also had an additional effect on acute rejection (P <0.05). The MLC of the patients with three HLA mismatches was significantly higher than the MLC of patients with zero HLA mismatches. The incidence of acute cellular rejection (ACR) was higher in the patients with three mismatches than in the other patients, and moderate rejection only occurred in the patients with three mismatches. Conclusion: HLA mismatching was not statistically associated with the overall graft survival after LDALT. The graft failure rates were higher in the positive cross-matching cases and therefore a strong immuosuppressant might be needed for positive cross-matching cases..
1309. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiko Maehara, Hiroyuki Kuwano, Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation, Liver International, 10.1111/j.1478-3231.2005.01165.x, 25, 6, 1169-1174, 2005.12, Background: Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors. Methods: We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA. Results: All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months. Conclusions: Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors..
1310. Yusuke Yonemura, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Tomonobu Gion, Noboru Harada, Hideki Ijichi, Kengo Yoshimitsu, Yoshihiko Maehara, Validity of Preoperative volumetric analysis of congestion volume in living donor liver transplantation using three-dimensional computed tomography, Liver Transplantation, 10.1002/lt.20537, 11, 12, 1556-1562, 2005.12, Reconstruction of middle hepatic vein (MHV) tributaries is controversial in right-lobe living donor liver transplantation (LDLT). This study aimed to evaluate the appropriateness of reconstructing MHV tributaries by volumetry using 3-dimensional computed tomography (3D-CT). Between November 2003 and January 2005, 42 donor livers (right-lobe graft, n = 25; left-lobe graft, n = 17) were evaluated using this software. The total congestion volume (CV) associated with the MHV tributaries and the inferior right hepatic vein (IRHV), and graft volume (GV) were calculated. In recipients with right-lobe grafts, CV/(right liver volume [RLV]) and (GV - CV)/(standard liver volume [SLV]) were compared between 2 groups: with reconstruction (n = 16) and without reconstruction (n = 9). To evaluate the influence of CV on the remnant right lobe in donors, total bilirubin was compared between 2 groups: high CV (CV > 20%, n = 13) or low CV (CV ≤ 20%, n = 4). The mean CV/RLV ratio was 32.3 ± 17.1% (V5, 15.2 ± 9.9%; V8, 9.2 ± 4.1%; and IRHV, 8.5 ± 11.4%) and the maximum ratio was as high as 80.8%. The mean (GV - CV)/SLV ratio before reconstruction in patients with or without reconstruction resulted in 33.5 ± 12.8% and 55.4 ± 12.9%, respectively (P < 0.01). In donors, total bilirubin was significantly high in the high CV group on postoperative day 1 compared with the low CV group (P < 0.05). In conclusion, calculation of CV using 3D-CT software proved to be very useful. We concluded that this evaluation should be an integral part of procedure planning, especially for right-lobe LDLT..
1311. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiko Maehara, Hiroyuki Kuwano, In situ dye injection bile leakage test of the graft in living donor liver transplantation, Transplantation, 10.1097/01.tp.0000181166.63783.69, 80, 10, 1398-1401, 2005.11, Background. Bile leakage after living donor liver transplantation (LDLT) remains a serious problem, resulting in lower survival rates. The aim of this study is to clarify the benefits of in situ leakage testing of the cut surface of grafts in LDLT. Methods. A total of 135 LDLTs were analyzed. The patients were divided into the following two groups according to the in situ dye injection leakage test of the cut surface: test group (n=40) and control group (n=40). The incidence of bile leakage and the risk factors were identified by analyzing the recipients, donors, and transplantation variables. Results. Bile leakage occurred in 12.5% (10/80) of LDLTs. In the control group, there were nine cases of bile leakage (22.5%). On the other hand, there was only one case (2.5%) of bile leakage in the test group (P<0.05). The bile leakage case in the test group was resolved preservationally. However, 2 of the 9 (22.2%) bile leakage cases in the control group required surgery. Conclusion. Although there is biliary complication, especially bile leakage from the cut surface, as an inevitable consequence of LDLT, this study suggests that there is advantage in conducting bile leakage testing to minimize the incidence of bile leakage from the cut surface, which is associated with a high risk of graft failure..
1312. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiko Maehara, Hiroyukl Kuwano, Impact of graft hepatic vein inferior vena cava reconstruction with graft venoplasty and inferior vena cava cavoplasty in living donor adult liver transplantation using a left lobe graft, Transplantation, 10.1097/01.tp.0000173776.66867.f5, 80, 7, 964-968, 2005.10, Background. Hepatic venous reconstruction is critical in living donor adult liver transplantation (LDALT) because outflow obstruction in small for size graft may lead to graft dysfunction or loss. We describe the usefulness of venoplasties of the graft hepatic vein (HV) and graft HV-recipient inferior vena cava (IVC) reconstruction in LDALT using a left lobe graft. Methods. Sixty patients who underwent LDALT were studied. We divided the patients into following two groups: venoplasty group (n=30) and control group (n=30). For the patients with venoplasty group, venoplasty of the graft and recipient IVC cavoplasty was made to widen the orifice. Comparison examination of a background factors and postoperative bilirubin and the ascites was carried out. Results. The mean graft volume standard liver volume ratio (GV/SLV) did not have the difference at 41.7% of venoplasty group, and 42.1% of control group (p=NS). The diameter of the hepatic vein in control and venoplasty group before and after venoplasty is 26.9±5.5, 28.2±2.9, and 34.1±3.9 mm, respectively. The diameter of the hepatic vein after venoplasty is larger than that of before venoplasty and of control (P<0.05). Mean total bilirubin level on postoperative day (POD) 7 is 13.8±9.3 mg/dl in control group and 7.0±3.3 mg/dl in venoplasty group (P<0.05). Mean amount of ascites on POD 7 and 14 are 1576±1113 and 1397±1661 cc in control group, and 736±416 and 550±385 cc in venoplasty group, respectively (P<0.05). Two-year survival rate is 75.2% in control group and 86.6% in venoplasty group (P<0.05). Conclusions. We conclude that in LDALT using left lobe graft, HV-IVC reconstruction with graft venoplasty and IVC cavoplasty is useful not only to prevent outflow block but also to improve graft function..
1313. Makoto Nakamuta, Shusuke Morizono, Yuji Soejima, Tomoharau Yoshizumi, Shinji Aishima, Shin Ichiro Takasugi, Kengo Yoshimitsu, Munechika Enjoji, Kazuhiro Kotoh, Akinobu Taketomi, Hideaki Uchiyama, Mitsuo Shimada, Hajime Nawata, Yoshihiko Maehara, Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation, Transplantation, 10.1097/01.tp.0000166009.77444.f3, 80, 5, 608-612, 2005.09, Background. The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. Methods. Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. Results. The treatment significantly improved macrovesicular steatosis (30±4% vs. 12±2% [mean±SEM], P= 0.0028). Body weight and BMI were significantly reduced (73.7±3.2 kg vs. 66.9±2.9 kg, P=0.0033, 26.4±0.7 kg/m2 vs. 24.1±0.8 kg/m2, P=0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n=7) and donor liver without hepatic steotosis (n=37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. Conclusions. The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen..
1314. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Shinji Hashimoto, Yoshihiko Maehara, Hiroyuki Kuwano, Effect of intraportal infusion to improve small for size graft injury in living donor adult liver transplantation, Transplant International, 10.1111/j.1432-2277.2005.00159.x, 18, 8, 923-928, 2005.08, The most important problem in the living donor adult liver transplantation (LDALT) is a small for size graft. Although a right lobe graft is used in many cases in order to avoid small for size graft, for a donor, the risk has few in left lobe graft. We evaluate the effect of an intraportal infusion treatment to the small for size graft. One hundred and twelve patients who underwent LDALT were studied. The graft weight recipient standard liver volume ratio (GV/SLV) of these patients were 50% or less. We divided the patients into following two groups; infusion group (n = 53) and control group (n = 59). For the infusion group, 16 G double lumen catheter was inserted into portal vein and nafamostat mesilate (protease inhibitor which stabilize coagulofibrinolytic state; 200 mg/day), prostaglandin E1 (vasodilator and hepatoprotective effect; 500 μg/ day) and thromboxane A2 synthetase inhibitor (vasodilator and anticoagulant effect; 160 mg/day) were administrated continuously for 7 days. Small-for-size graft syndrome was defined as bilirubin >10 mg/dl and ascites >1000 cc on postoperative day (POD) 14. Comparison examination of a background factors and postoperative bilirubin and amount of ascites was carried out. The mean GV/SLV did not have the difference at 39.1% of infusion group, and 38.3% of control group (P = 0.58). By the control group, 15 patients (25.4%) were small-for-size graft syndrome, however, there was only two (3.8%) small-for-size graft syndrome in infusion group (P = 0.04). The bilirubin levels of infusion and control group on 7 and 14 POD were 9.9 and 7.8 vs. 9.5 and 10.5 mg/dl, respectively. The amount of ascites of infusion group on 7 and 14 POD were 870 and 430 cc, respectively. On the contrary, in control group, the amount of ascites on 7 and 14 POD were 1290 and 1070 cc, respectively. Bilirubin levels and the amount of ascites on 7 and 14 POD were lower in the patients with infusion group then those with control group. There were no differences between infusion group and control group in age, sex and Child's classification. The intraportal infusion had an effect in prevention of hyperbilirubinemia and loss in quality of excessive ascites in the patients with small for size graft. This was suggested to be what is depended on the improvement of the microcirculation insufficiency considered one of the causes of small-for-size graft syndrome..
1315. Keiko Ogita, Tomoaki Taguchi, Yuji Soejima, Satoshi Ieiri, Shunsaku Katsura, Narito Takada, Toshiharu Matsuura, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Sachiyo Suita, Fatty liver caused by portal vein thrombosis after living donor liver transplantation
A case report, Journal of Pediatric Surgery, 10.1016/j.jpedsurg.2005.05.029, 40, 8, E7-E9, 2005.08, Portal vein thrombosis (PVT) is a rare complication that occurs after liver transplantation: however, it cannot be ignored as a cause of graft loss and death. We herein report a pediatric case of PVT that caused a fatty change in the graft after living donor liver transplantation. The portal vein was successfully reconstructed using the left great saphenous vein of the same donor. Moreover, the fatty liver recovered after the operation. Our case suggests that the finding of fatty liver is an important marker of PVT and immediate portal reconstruction is performed..
1316. M. Shimada, Y. Yonemura, H. Ijichi, N. Harada, S. Shiotani, M. Ninomiya, T. Terashi, T. Yoshizumi, Y. Soejima, Y. Maehara, Living donor liver transplantation for hepatocellular carcinoma
A special reference to a preoperative des-gamma-carboxy prothrombin value, Transplantation Proceedings, 10.1016/j.transproceed.2004.12.030, 37, 2, 1177-1179, 2005.03, Background. Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence in living donor liver transplantation (LDLT) with special reference to preoperative DCP values. Methods. Forty consecutive adult HCC patients who underwent LDLT were examined for a correlation between the DCP value and vascular invasion. Risk factors for recurrence were also investigated using clinicopathological variables including preoperative DCP levels. Results. The incidence of positive histological vascular invasion in patients with DCP values above 300 mAU/mL was higher than that with those with DCP value below 300 mAU/mL. Other significant risk factors for recurrence were over 5 cm tumor diameter, not meeting the Milan criteria, AFP value >400 ng/mL, histological vascular invasion, poorly differentiated histology, and male gender. Among the patients who did not meet the Milan criteria, those with both no more than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good prognosis. Conclusions. A high DCP value, namely >300 mAU/mL correlated with histological vascular invasion and was one of the strongest prognostic variables. Therefore, special attention should be paid to HCC patients with high DCP values. No correlation between the number of tumor nodules and recurrence was found; therefore, the Milan criteria may require revision regarding the number of tumor nodules..
1317. Shunsaku Katsura, Keiko Ogita, Tomoaki Taguchi, Sachiyo Suita, Tomoharu Yoshizumi, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, Effect of liver transplantation on multiple bone fractures in an infant with end-stage biliary atresia
A case report, Pediatric surgery international, 10.1007/s00383-004-1262-z, 21, 1, 47-49, 2005.01, Osteodystrophy is frequently found in children with chronic cholestatic liver disease. We herein report an end-stage case of biliary atresia that was associated with multiple bone fractures and severe growth retardation. The patient, an 8-month-old female, underwent a living-related liver transplantation and thereafter showed a dramatic improvement in growth and decrease in bone fractures. A correction of the liver function is therefore considered to be a key factor in treating osteodystrophy that is related to chronic cholestatic liver disease. It is also essential to perform liver transplantation at the most appropriate time to enhance and support the growth of these patients..
1318. Akinobu Taketomi, Yuuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoshihiko Maehara, Living donor liver transplantation for the patient with hepatocellular carcinoma, Gan to kagaku ryoho. Cancer & chemotherapy, 31, 13, 2118-2121, 2004.12, Since 1989, over 3,000 living donor liver transplantation (LDLTx) were performed in Japan. Among them, LDLTx for advanced hepatocellular carcinoma (HCC) with severe liver cirrhosis have recently increased. LDLTx for HCC has been offered only when liver function was severely impaired, or HCC became uncontrollable by other modalities such as hepatic resection or ablation therapies, which often exceeded the Milan criteria. One-and 3-year survivals were 84.6% and 73.3%, respectively. When exceeding the Milan criteria, tumor size over 5 cm, vascular invasion, grade of histologic differentiation of HCC, and high PIVKA-II over 300 mAU/ml were independent risk factors for HCC recurrence. Prevention of HCC or hepatitis C recurrence after transplantation should be resolved to improve graft and patient survival..
1319. S. Shiotani, M. Shimada, Y. Soejima, T. Yoshizumi, S. Uemoto, T. Kiuchi, K. Tanaka, Y. Maehara, S100β protein
The preoperative new clinical indicator of brain damage in patients with fulminant hepatic failure, Transplantation Proceedings, 10.1016/j.transproceed.2004.09.030, 36, 9, 2713-2716, 2004.11, The aim of this study was to clarify the role of serum S100β on the accurate assessment of reversibility of brain damage after fulminant hepatic failure (FHF). Among the 13 patients with FHF enrolled in this study, 12 underwent living donor liver transplantation; one patient could not the procedure because of volvulus of the sigmoid colon. Serum S100β was serially measured using a chemiluminescent immunoassay. Preoperative serum S100β in patients with diffuse brain edema was significantly higher than that in patients with localized brain edema (P < 0.05). Patients with preoperative brain death showed serum S100β levels over 7.0 μg/L. Serum S100β levels correlated with the degree of brain edema of FHF. It has the potential to be a new clinical, noninvasive indicator of brain damage due to FHF..
1320. M. Shimada, H. Ijichi, Y. Yonemura, N. Harada, S. Shiotani, M. Ninomiya, T. Yoshizumi, Y. Soejima, T. Suehiro, Y. Maehara, Is graft size a major risk factor in living-donor adult liver transplantation?, Transplant International, 10.1111/j.1432-2277.2004.tb00448.x, 17, 6, 310-316, 2004.07, Graft size is known to be a major risk factor in living donor adult liver transplantation (LDALT). The aim of this study is to reassess whether graft size is a critical factor in LDALT or not. A series of 75 LDALTs excluding auxiliary transplantation and ABO blood-type incompatible transplantation were analyzed. The patients were divided into two groups, according to graft volume (GV) and standard liver volume (SLV): group 1 (small-size group) (GV/ SLV: < 40%), and group 2 (non-small-size group) (≥40%). Perioperative clinical data were compared between the two groups, including graft survival and postoperative complications. These parameters were also compared under the conditions of cirrhotic recipients. No difference in graft survival was found between the two groups. No difference was found in incidence of postoperative complications, such as intractable ascites and persistent hyperbilirubinemia. Even in cirrhotic patients with Child-Pugh's class C, there was no difference in graft survival between the two groups. Risk factors related to graft loss were a preoperative urgent status due to chronic liver disease, pre-operative hyperbilirubinemia of over 10 mg/dl, and ABO blood type of not identical but compatible combination between donor and recipient. Graft size is not always considered to be a major risk factor in LDALT, although the number of patients was small in this study. Therefore, a left-lobe graft, even a "small-for-size" graft for adult, recipients, remains a feasible option in LDALT..
1321. G. E. Gondolesi, Tomoharu Yoshizumi, C. Bodian, L. Kim-Schluger, T. Schiano, T. Fishbein, M. Schwartz, C. Miller, S. Emre, Accurate method for clinical assessment of right lobe liver weight in adult living-related liver transplant, Transplantation Proceedings, 10.1016/j.transproceed.2004.04.094, 36, 5, 1429-1433, 2004.06, Introduction Prior to transplantation of segmental liver grafts to adult recipients, it is crucial to confirm that the graft size is safe for the donor, yet adequate for the recipient's metabolic needs. Computed tomography (CT) and magnetic resonance imaging (MRI) are the current best standards. We applied a new formula to estimate right liver lobe weight in living donors and compared our results with CT and MRI. Methods Between August 1998 and December 20, 91 adults received right lobes from living donors. Donor liver volumes were assessed by CT or MRI. Actual weights of right lobe grafts were determined after back table flushing. We estimated whole liver weights using the formula: 772 × body surface area (BSA). Right lobe liver weight was calculated as 57% of the estimated whole liver weight (R-57). Results Mean actual right lobe weight (n = 90) was 855.83 ± 183.4 g. Estimated right lobe weight was 858.08 ± 90.80 (R-57, P = NS); 1077.35 ± 263.07 mL for CT (P = .0001), and 1185.07 ± 350.10 mL for MRI (P = .0001). Mean graft-recipient weight ratio (GRWR) was 1.23%; there was no significant difference with R-57 GRWR but there was a difference from CT and MRI-GRWR (P = .001). The proportion of cases of estimated right lobe weight and GRWR within 20% of the corresponding actual value were 80% and 90%, respectively, for R-57 versus 36% and 43% for the imaging studies (P = .0001). Conclusion With readily available software to calculate BSA, physicians can predict right lobe weight knowing only the donor's height and weight. CT and MRI will only be necessary for anatomic liver mapping..
1322. Noboru Harada, Mitsuo Shimada, Tomoharu Yoshizumi, Taketoshi Suehiro, Yuji Soejima, Yoshihiko Maehara, A simple and accurate formula to estimate left hepatic graft volume in living-donor adult liver transplantation, Transplantation, 10.1097/01.TP.0000131991.10802.AA, 77, 10, 1571-1575, 2004.05, Background. In the field of living-donor adult liver transplantation, a small-for-size graft often occurs, particularly when using left-lobe grafts. This is because of the limited volumes associated with left-lobe grafts. The accurate preoperative evaluation of graft volumes is crucial to avoid this complication. The aim of this study is to clarify the usefulness of a new formula to estimate the left-lobe graft volume. Method. In 61 left-lobe grafts, a new formula was created with stepwise regression analysis using the following variables: height, weight, the thoracic and abdominal distance from anterior to posterior side (A-P), and distance from left to right side (L-R) of the initial 20 donors. With another 41 donors, the difference between the actual and estimated graft volume using the formula and two-and three-dimensional computed tomography was prospectively evaluated. Results. On the basis of the results of the stepwise regression analysis, a new formula was created as follows: graft volume (ml)=313.4+7.7xweight (kg)-12.6xthoracic L-R (cm). The difference between the actual and estimated graft volumes using the formula was significantly better (10.8±9.5%) than that of the volumetry using two-dimensional computed tomography (16.3±10.1%) (P<0.05). Conclusions. In conclusion, the new formula can estimate the actual graft volume more accurately than conventional volumetry with two-dimensional computed tomography. The formula is useful to estimate the volume of left-lobe graft in living-donor adult liver transplantation..
1323. Mitsuo Shimada, Hideki Ijichi, Yusuke Yonemura, Noboru Harada, Satoko Shiotani, Mizuki Ninomiya, Takahiro Terashi, Tomoharu Yoshizumi, Yuji Soejima, Taketoshi Suehiro, Yoshihiko Maehara, The impact of splenectomy or splenic artery ligation on the outcome of a living donor adult liver transplantation using a left lobe graft, Hepato-gastroenterology, 51, 57, 625-629, 2004.05, Background/Aims: The aim of this study was to clarify the impact of splenectomy or splenic artery ligation on the outcome in living donor adult liver transplantation (LDALT) using a left lobe graft. Methodology: Forty-eight LDALT cases using a left lobe graft were enrolled in this study. The patients were classified into two groups: Group A (n=40), in which neither a splenectomy nor a splenic artery ligation was performed, and Group B (n=8), in which a splenectomy (n=6) or a splenic artery ligation (n=2) was performed. Indications for splenectomy were as follows: 1) demonstrating a hypersplenism and/or 2) having splenic aneurysms. Results: None of the patients receiving a splenectomy or a splenic artery ligation experienced any septic complication in this series. The graft-recipient weight ratio in group B tended to be smaller than in group A. In group B, all patients were classified into Child's class C or B. The incidence of esophageal varices in group B was significantly higher than in group A. Moreover, the platelet count and the white blood cell count in group B were significantly lower than in group A. No statistical difference was found in postoperative functional cholestasis and intractable ascites. None of the participants in group B experienced both postoperative hyperbilirubinemia and intractable ascites, which were characterized as a small-for-size graft after LDALT. The patient survival rate in group B seems to be better than in group A. In a majority of the cases the portal pressure as well as the portal vein flow after a splenectomy decreased in comparison to that before the splenectomy. Conclusions: Splenectomy or splenic artery ligation is considered to be beneficial for improving the outcome in LDALT using a left lobe graft..
1324. Akinobu Taketomi, Yuji Soejima, Tomonobu Gion, Noboru Harada, Norifumi Harimoto, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara, Current status and future prospects for liver transplantation
Kyushu University Hospital experience, Fukuoka igaku zasshi = Hukuoka acta medica, 95, 10, 269-273, 2004.01.
1325. Shusuke Morizono, Makoto Nakamura, Motoyuki Kohjima, Izuru Miyagi, Tsuyoshi Yoshimoto, Eiichirou Arimaura, Kazuhiro Kotoh, Munechika Enjoji, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Mitsuo Shimada, Yoshihiko Maehara, Hajime Nawata, Evaluation of acute hepatic failure treated at the Department of Medicine III, Kyushu University Hospital
indications for living-donor liver transplantation, Fukuoka igaku zasshi = Hukuoka acta medica, 95, 12, 321-331, 2004.01, To evaluate indications for living-donor liver transplantation (LDLT), we examined 25 consecutive patients with acute hepatic failure admitted to the Department of Medicine III, Kyushu University Hospital between November 2001 and July 2004. These cases were diagnosed as fluminant hepatitis (n=13), severe-type acute hepatitis (n=11), or late-onset hepatic failure (n=1). Nine patients (36%) improved with conservative treatment (conservative treatment group), and the other 16 patients (64%) needed LDLT (LDLT indicated group). In the LDLT indicated group, 11 patients received LDLT, and 4 died because of lack of LDLT donors (n=3), or renal failure (n=1). The LDLT survival rate was 82% (9/11); two patients died due to hepatic infarction and brain edema, respectively. It is very important to predict whether a patient with acute hepatic failure belongs to the conservative treatment group or the LDLT indicated group on admission. Therefore, we analyzed variables that could influence prognosis, including, parameters of hepatic function and platelet counts on admission, and relative hepatic volume (%), which represents the ratio of hepatic volume measured by CT relative to standard hepatic volume calculated with body surface area. Univariate logistic analysis showed that relative hepatic volume, gammaglutamyl transpeptidase (gamma-GTP), alkaline phosphatase (ALP), and the ratio of direct bilirubin to total bilirubin (DB/TB) were significant predictors of survival (p < 0.05). Using these factors plus prothrombin time (PT) and total cholesterol, both of which were relatively significant predictors of survival (p < 0.2), we proposed a model for predicting the probability of survival by the stepwise method. Consequently, we proposed a model using four parameters: ALP, GGTP, PT, and relative hepatic volume (Volume) as shown below: p(%) = 1/(1+exp (-(-36.2375 + ALP x 0.0251 + gamma-GTP x 0.0102 + PT x 0.2558 + Volume 21.2158))) x 100. This model showed a significant correlation between prediction and consequence of survival (r2 = 0.7388, p = 0.0003). In conclusion, LDLT is an effective treatment for acute hepatic failure. The results of this study suggested that our model can adequately predict prognosis in the early phase of acute hepatic failure..
1326. Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Keiji Kishikawa, Tomoharu Yoshizumi, Koji Hashimoto, Ryosuke Minagawa, Shoji Hiroshige, Takahiro Terashi, Mizuki Ninomiya, Satoko Shiotani, Noboru Harada, Keizo Sugimachi, Use of steatotic graft in living-donor liver transplantation, Transplantation, 10.1097/01.TP.0000071205.52835.A4, 76, 2, 344-348, 2003.07, Background. The degree of fatty infiltration in hepatic grafts is known to be an important risk factor for primary graft nonfunction in cadaveric liver transplantation. However, the effect of hepatic steatosis in living-donor liver transplantation (LDLT) has not yet been well defined. In this study, we evaluated the impact that the degree of hepatic graft steatosis has on the outcome of LDLT. Methods. Sixty consecutive donors and recipients who underwent LDLT between October 1996 and August 2001 at Kyushu University Hospital were the subjects of this study. The pathologic findings of the prereperfusion biopsy of the graft were classified into the following three groups according to the degree of macrovesicular steatosis: None (n=23), 0% steatosis; Mild (n=23), 0% to 20% steatosis; and Moderate (n=6), 20% to 50% steatosis. Liver function tests including total bilirubin (at postoperative day [POD] 7), the peak alanine aminotransferase (ALT) and prothrombin time (at POD 3), and both patient and graft survival were compared among the groups. Furthermore, we also compared the donor parameters including the peak ALT and total bilirubin (at POD 3) and the operative time, blood loss, and length of hospital stay after surgery. Results. The 1-year patient and graft survival were comparable among the groups. The peak ALT was significantly higher in the Moderate group (606±641 IU/L) than in the None (290±190 IU/L) and Mild (376±296 IU/L) groups. Total bilirubin (POD 7) and prothrombin time (POD 3) were comparable among the groups. The donor parameters were comparable among the groups except for the fact that the donor body weight of the Mild and Moderate groups were significantly heavier (P<0.0001) than that of the None group. Conclusions. In conclusion, the use of a fatty liver graft up to the moderate level can be justified in LDLT, even though ischemia-reperfusion injury tends to be severe in such grafts..
1327. T. Yoshizumi, G. E. Gondolesi, C. A. Bodian, H. Jeon, M. E. Schwartz, T. M. Fishbein, C. M. Miller, Sukru Emre, A simple new formula to assess liver weight, Transplantation Proceedings, 10.1016/S0041-1345(03)00482-2, 35, 4, 1415-1420, 2003.06, Introduction. In cadaveric or segmental liver transplantation, accurate assessment of graft volume is desirable but not always easy to achieve based on donor morphometric data. We sought to establish a simple, reliable formula for accurate prediction of liver volume. Methods. Data from 1,413 cadaveric adult and pediatric liver donors were analyzed using simple and multiple regression analysis. Liver weight (LW) was plotted against age, height, body weight (BW), body surface area (BSA) or body mass index (BMI); a formula was developed using simple regression: LW (g) = 772 (g/m2) × BSA, r = 0.73, P < .01. For donors with BSA ≤1.0, a pediatric factor (PF) of 1.0 was included, resulting in the formula: LW (g) = 772 (g/m2) × BSA - 38PF, r = 0.73, P < .01. We then applied our formula on 5 published formulae to estimate LW of our donors. Results. Among donors with BSA >1.0, there was no significant difference between the actual and the estimated mean LW as calculated by the new formula. For pediatric donors, there was no significant difference between estimated and actual mean liver weight with any formula. When the new formula was applied, the difference between the actual and the estimated liver weight was acceptable (<20%) in 1040 (73.6%) cases. In all races, there was no significant difference between actual and estimated mean liver weight as calculated by this formula. Conclusion. A simple formula to calculate liver weight in donors with BSA >1.0 is: LW = 772 × BSA, and for donors with BSA ≤1.0: Liver Weight = 772 × BSA - 38..
1328. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Maehara, Rie Nakao, Kazuhiro Hayashida, Makoto Nakamuta, Hiroshi Honda, Kazuo Irita, Kenji Kodama, Shoichi Inaba, Takuro Taniyama, Living donor liver transplantation for fulminant hepatic failure--medical treatment organization in Kyushu University, Fukuoka igaku zasshi = Hukuoka acta medica, 93, 8, 141-152, 2002.01, Liver transplantation has been recognized as an effective therapeutic method for end-stage liver disease in Japan. Fulminant hepatic failure is also an indication for liver transplantation, and the number of patients undergoing liver transplantation has been increasing. Reversibility and urgency are characteristics of fulminant hepatitis. If given appropriate critical support, many patients recover spontaneously. However, many patients develop cerebral edema or multiorgan failure before the liver can regenerate. From October 1996 to July 2002, living donor liver transplantation (LDLT) was performed to 84 end stage liver disease patients in Kyushu University. Twenty-four (28.6%) of 84 LDLTs were for fulminant hepatic failure. In Kyushu University, LDLT candidates including urgent cases were discussed with indication in the liver transplantation committee (the medical professions division and an outside-the-university committee are included) and then the coordinator committee performs informed consent. LDLT can be performed only by cooperation of each section concerned such as Transfusion part, Medicine part, Radiation part, Operation part, Intensive Care Unit and so on. In this paper, we outline about fulminant hepatic failure and living donor liver transplantation, and describe the fulminant hepatitis medical treatment organization in Kyushu University..
1329. Charles M. Miller, Gabriel E. Gondolesi, Sander Florman, Cal Matsumoto, Luis Muñoz, Tomoharu Yoshizumi, Tarik Artis, Thomas M. Fishbein, Patricia A. Sheiner, Leona Kim-Schluger, Thomas Schiano, Benjamin L. Shneider, Sukru Emre, Myron E. Schwartz, One hundred nine living donor liver transplants in adults and children
A single-center experience, Annals of surgery, 10.1097/00000658-200109000-00004, 234, 3, 301-312, 2001.09, Objective: To summarize the evolution of a living donor liver transplant program and the authors' experience with 109 cases. Summary Background Data: The authors' institution began to offer living donor liver transplants to children in 1993 and to adults in 1998. Methods: Donors were healthy, ages 18 to 60 years, related or unrelated, and ABO-compatible (except in one case). Donor evaluation was thorough. Liver biopsy was performed for abnormal lipid profiles or a history of significant alcohol use, a body mass index more than 28, or suspected steatosis. Imaging studies included angiography, computed tomography, endoscopic retrograde cholangiopancreatography, and magnetic resonance imaging. Recipient evaluation and management were the same as for cadaveric transplant. Results: After ABO screening, 136 potential donors were evaluated for 113 recipients; 23 donors withdrew for medical or personal reasons. Four donor surgeries were aborted; 109 transplants were performed. Fifty children (18 years or younger) received 47 left lateral segments and 3 left lobes; 59 adults received 50 right lobes and 9 left lobes. The average donor hospital stay was 6 days. Two donors each required one unit of banked blood. Right lobe donors had three bile leaks from the cut surface of the liver; all resolved. Another right lobe donor had prolonged hyperbilirubinemia. Three donors had small bowel obstructions; two required operation. All donors are alive and well. The most common indications for transplant were biliary atresia in children (56%) and hepatitis C in adults (40%); 35.6% of adults had hepatocellular carcinoma. Biliary reconstructions in all children and 44 adults were with a Roux-en-Y hepaticojejunostomy; 15 adults had duct-to-duct anastomoses. The incidence of major vascular complications was 12% in children and 11.8% in adult recipients. Children had three bile leaks (6%) and six (12%) biliary strictures. Adult patients had 14 (23.7%) bile leaks and 4 (6.8%) biliary strictures. Patient and graft survival rates were 87.6% and 81%, respectively, at 1 year and 75.1% and 69.6% at 5 years. In children, patient and graft survival rates were 89.9% and 85.8%, respectively, at 1 year and 80.9% and 78% at 5 years. In adults, patient and graft survival rates were 85.6% and 77%, respectively, at 1 year. Conclusion: Living donor liver transplantation has become an important option for our patients and has dramatically changed our approach to patients with liver failure. The donor surgery is safe and can be done with minimal complications. We expect that living donor liver transplants will represent more than 50% of our transplants within 3 years..
1330. T. Yoshizumi, T. Ikeda, S. Ohta, S. Nagata, T. Sonoda, K. Sugimachi, Abdominal ultrasonography reveals the perforation site of duodenal ulcers., Surgical endoscopy, 10.1007/s004640042011, 15, 7, 2001.07, Regardless of whether or not the laparoscopic approach is used, the simple closure using an omental patch is considered to be preferable to other surgical therapies for a duodenal ulcer perforation. We used abdominal ultrasonography (US) to identify the perforation site of the duodenal ulcer. To our knowledge, this is the first report describing how the perforation site of duodenal ulcers can be identified using US. Three patients diagnosed with perforated duodenal ulcers based on abdominal computed tomography and abdominal radiographic findings were scheduled for surgery. Under general anesthesia, US demonstrated free air on the liver and a "fish-eye sign" when the anterior or lateral wall was perforated. We performed a simple closure using an omental patch through a skin incision measuring only 3 cm in diameter above the area showing the fish-eye sign. The postoperative recovery was no different from that seen when a laparoscopic approach is used at our hospital. Even though the laparoscopic procedure is still the surgical modality of choice, the US technique allows for a successful diagnosis without invasive examinations. We believe that most surgeons and/or radiologists should try to detect the fish-eye sign using US as the diagnostic modality of first choice if they suspect a duodenal ulcer perforation. This technique allows us to mark the perforation site accurately before surgery..
1331. T. Nishizaki, T. Ikegami, S. Hiroshige, K. Hashimoto, H. Uchiyama, T. Yoshizumi, K. Kishikawa, M. Shimada, K. Sugimachi, Small graft for living donor liver transplantation, Annals of surgery, 10.1097/00000658-200104000-00014, 233, 4, 575-580, 2001.04, Objective. To evaluate the impact of graft size on recipients in living donor liver transplantation (LDLT) to establish a clinical guideline for the minimum requirement. Summary Background Data. Although the minimum graft size required for LDLT has been reported to be 30% to 40% of graft volume (GV)/standard liver volume (SLV), the safety limit of the graft size was unknown. Methods. A total of 33 cases of LDLT, excluding auxiliary transplantation, were reviewed with a minimum observation period of 4 months. The 33 patients were divided into three groups according to GV/SLV: medium-size graft group, small-size graft group, and extra-small graft group. The effect of GV/SLV on graft function, graft regeneration, and survival was evaluated. Results. The overall patient survival rate was 94% at a mean follow-up of 15 months with a minimum observation period of 4 months. There were no statistically significant differences in postoperative bilirubin clearance, alanine aminotransferase, prothrombin time, and frequency of postoperative complications among the three groups. One week after transplantation, the regeneration rate (GV at 1 week/harvested GV) in the extra-small and small groups was significantly higher than that of the medium group. The graft and patient survival rates were both 100% in the extra-small group, 75% and 88% in the small group, and 90% and 95% in the medium group. Conclusions. Small-for-size grafts less than 30% of SLV can be used with careful intraoperative and postoperative management until the grafts regenerate..
1332. Shinji Okano, Masatoshi Eto, Yukihiro Tomita, Tomoharu Yoshizumi, Hisakata Yamada, Ryosuke Minagawa, Kenichi Nomoto, Keizo Sugimachi, Kikuo Nomoto, Cyclophosphamide-induced tolerance in rat orthotopic liver transplantation, Transplantation, 10.1097/00007890-200102150-00019, 71, 3, 447-456, 2001.02, Background. We previously established a cyclophosphamide (CP)-induced tolerance system in rodent skin graft models. In this study, we applied this system to rat liver transplantation. Methods. Lewis recipients were inoculated on day -2 with spleen and bone marrow cells (SC+BMC) from Dark Agouti (DA) donors, followed by 100 mg/kg CP on day 0. On day 25, DA livers were orthotopically grafted. We assessed the alloresponses to the donors of the long-term surviving recipients, using the second skin grafting and in vitro assay. Results. The recipients that had been treated with SC+BMC and CP survived for more than 165 days. None of control group that received SC+BMC alone (mean survival times [MST]=13.8 days), CP alone (MST=40.0), SC+BMC from third-party PVG rats and CP (MST=45.0), or no treatment (MST=13.8) survived over 50 days. The donor-specific tolerance was confirmed by second skin grafts onto recipients with permanent DA liver grafts, which accepted DA skins (MST> 75) but not PVG (MST=8.3). However, the lymphocytes from the tolerant recipients showed alloresponse to DA in vitro. To investigate whether the T helper type 2 deviation contributed to this "split tolerance," we assessed the production of cytokines in mixed lymphocyte reaction. Interleukin 2 and interferon-γ were detected but interleukin 4 was not. Conclusions. These data showed that this protocol induced split tolerance in rat liver transplantation and, furthermore, the mechanism of split tolerance was not due to T helper 2 deviation..
1333. K. Hashimoto, T. Nishizaki, T. Yoshizumi, H. Uchiyama, S. Okano, T. Ikegami, K. Yanaga, K. Sugimachi, Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation, Transplantation, 10.1097/00007890-200011150-00009, 70, 9, 1318-1322, 2000.11, Background. Proinflammatory cytokines such as interleukin 1-β (IL-1β) and tumor necrosis factor-α (TNF-α) play an important role in the development of hepatic ischemia/reperfusion injury. FR167653 has been characterized as a potent suppressant of IL-1β and TNF-α production. The aim of this study was to evaluate the effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation. Methods. Donor livers were preserved with cold University of Wisconsin solution for 48 hr and transplanted orthotopically. Immediately after reperfusion, FR167653 (1 mg/kg, FR-treated group) or normal saline solution (control group) was administered i.v.. The severity of liver injury was determined by hepatic enzyme levels as well as by histological findings. The accumulation of IL-1β and TNF-α mRNA in the liver was analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Tissue factor expression was subjected to immunohistochemical analysis. Results. In the FR-treated group, release of aspartate aminotransferase and alanine aminotransferase after reperfusion was significantly lower (P<0.05 and P<0.02, respectively), and histological liver injury was less prominent, than in the control group. Accumulation of IL-1β and TNF-α mRNA was suppressed in the FR-treated liver. Tissue factor expression on Kupffer cells and sinusoidal endothelial cells, marked in the control group, was almost absent in the FR-treated group. Seven-day survival in the FR-treated group (75%) was significantly better than that in the control group (12.5%) (P<0.01). Conclusions. These results indicate that treatment with FR167653 ameliorates cold ischemia/reperfusion injury in liver transplantation..
1334. Takashi Nishizaki, Keishi Kishikawa, Tomoharu Yoshizumi, Hideaki Uchiyama, Shinji Okano, Toru Ikegami, Koji Hashimoto, Kenichi Nomoto, Mitsuo Shimada, Katsuhiko Yanaga, Kenji Takenaka, Keizo Sugimachi, Yukio Ando, Masayuki Ando, Domino liver transplantation from a living related donor, Transplantation, 10.1097/00007890-200010270-00019, 70, 8, 1236-1239, 2000.10, Background. Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. Methods. The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). Results. The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. Conclusion. A domino OLT from the living related donor can therefore be done safely when tention is paid to the graft volume and the length of the vascular cuffs for anastomosis..
1335. T. Yoshizumi, Tetsuo Ikeda, T. Shimizu, S. Ohta, S. Nagata, T. Sonoda, K. Sugimachi, Clip migration causes choledocholithiasis after laparoscopic cholecystectomy., Surgical endoscopy, 14, 12, 2000.01, The migration of surgical clips after laparoscopic procedures was first reported in 1992, but such instances are extremely rare. We herein demonstrate a case of a migrated metal clip, which had been applied originally to the cystic duct, but thereafter had moved to the common bile duct. This clip caused choledocholithiasis in a patient 1 year after a laparoscopic cholecystectomy. A 63-year-old man underwent a laparoscopic cholecystectomy. During the operation, the inflamed cystic duct was divided accidentally, and three clips were applied immediately. The patient complained of upper abdominal pain from postoperative day 8. Endoscopic retrograde cholangiography demonstrated bile leakage from the cystic duct, but showed no clips or choledochal stones. The patient complained of severe upper abdominal and back pain 1 year after the operation. Endoscopic retrograde cholangiography showed a metal clip in the common bile duct and choledochal stones above the clip. The clip and the cholesterol stones were removed using a basket catheter. Three clips applied to the cystic duct should have been removed because of the necrosis in the remaining cystic duct. Thereafter, the clip may have migrated through the stump of the cystic duct into the lower part of the common bile duct. This clip seems to have later caused choledocholithiasis resulting from stagnation of the bile flow. Bile leakage after an operation seems to increase the risk of clip migration. Regardless of the primary lesion, a careful follow-up evaluation is necessary for patients demonstrating complications..
1336. Yuji Soejima, Katsuhiko Yanaga, Takashi Nishizaki, Tomoharu Yoshizumi, Hideaki Uchiyama, Keizo Sugimachi, Effect of specific neutrophil elastase inhibitor on ischemia/reperfusion injury in rat liver transplantation, Journal of Surgical Research, 10.1006/jsre.1999.5661, 86, 1, 150-154, 1999.09, Activated neutrophils have been implicated as playing an important role in ischemia/reperfusion injury of the liver by releasing toxic mediators such as oxygen free radicals and elastases. In the present study, we evaluated the effect of a novel, specific neutrophil elastase inhibitor (ONO-5046) on cold- ischemia/reperfusion injury of the liver allograft in rodents. Livers from male Lewis rats were procured and stored cold (4°C) in lactated Ringer's solution and transplanted orthotopically. Recipients were divided into three groups: Vehicle group, 5-h preservation and vehicle (n = 8); ONO-5046 group, 5-h preservation and administration of ONO-5046 (n = 8); and Control group, minimum preservation only (n = 8). Bile output after reperfusion was significantly larger in the ONO5046 group compared to the Vehicle group (P < 0.05 or less). Sinusoidal endothelial cell function represented by the serum hyaluronic acid concentration at 120 min after reperfusion of the ONO-5046 group was significantly lower than that in the Vehicle group (17.0 ± 7.9 vs 36.2 ± 14.9 ng/ml, P < 0.05), whereas serum transaminase levels 120 min after reperfusion were comparable between the two groups. Liver tissue energy charge 120 min after reperfusion was significantly better in the ONO-5046 group compared to the Vehicle group (P < 0.05). Furthermore, the number of neutrophils infiltrating the allograft after reperfusion was significantly depressed in the ONO-5046 group compared to the Vehicle group (P < 0.02). These data suggest that the neutrophil elastase might cause liver damage early after reperfusion in cold-stored liver, which can be ameliorated by the administration of a specific neutrophil elastase inhibitor, ONO-5046..
1337. Hideaki Uchiyama, Katsuhiko Yanaga, Takashi Nishizaki, Yuji Soejima, Tomoharu Yoshizumi, Keizo Sugimachi, Effects of deletion variant of hepatocyte growth factor on reduced-size liver transplantation in rats, Transplantation, 10.1097/00007890-199907150-00008, 68, 1, 39-44, 1999.07, Background. The deletion variant of hepatocyte growth factor (dHGF) exerts mitogenic and antifibrotic effects. The purpose of this study was to evaluate the effect of dHGF on rats that had undergone syngeneic or allogeneic reduced-size (60%) orthotopic liver transplantation (ROLT). Methods. Starting immediately after the syngeneic (Lewis to Lewis) and allogeneic (Lewis to Brown Norway) ROLT, 500 μg/kg dHGF was administered i.v. twice a day until the day the rats were killed. Its effect on hepatic graft weight, regeneration, and biochemical parameters was evaluated. Results. dHGF promoted restoration of the liver volume and liver regeneration as well as protein synthesis in the rats that underwent syngeneic ROLT. In the rats that underwent allogeneic ROLT, dHGF reduced the level of serum cytosolic enzymes related to acute cellular rejection, but a significant improvement in liver regeneration and protein synthesis was not seen. When tacrolimus was administered to prevent rejection of the allogeneic grafts, the beneficial effect of dHGF was apparent, and was as beneficial as in syngeneic ROLT. Conclusions. Administering dHGF after liver transplantation augments the regeneration and functional recovery of partial liver grafts and reduces hepatocyte injury in acute cellular rejection..
1338. T. Yoshizumi, K. Yanaga, Y. Soejima, T. Maeda, H. Uchiyama, K. Sugimachi, Amelioration of liver injury by ischaemic preconditioning, British Journal of Surgery, 10.1046/j.1365-2168.1998.00917.x, 85, 12, 1636-1640, 1998.12, Background. Ischaemic preconditioning, i.e. preparatory brief ischaemia before subsequent long ischaemia, can effectively protect the heart from ischaemia-reperfusion injury in animals. The purpose of this study was to demonstrate the same phenomenon in the liver. Methods. Using warm ischaemia-reperfusion of 70 per cent of the liver followed by resection of the non-ischaemic portion in rats, livers with 10 min of ischaemic preconditioning, i.e. 10 min of warm ischaemia and reperfusion, were compared with those that had not been subjected to such a manoeuvre. Results. At 120 min after reperfusion following 40 min of warm ischaemia, the livers with 10 min of ischaemic preconditioning had a significantly lower mean (s.d.) serum alanine aminotransferase level (492 (217) versus 1236 (695) units/l; P < 0.005) and lactic dehydrogenase level (7905 (4002) versus 15,066 (9201) units/l; P < 0.05), as well as a higher bile output (0.12 (0.03) versus 0.09 (0.04) ml per g liver; P < 0.05) and liver tissue adenosine 5'-triphosphate level (78 (13) versus 61 (11) per cent; P < 0.05) than the control livers. The necrosis rate, histologically defined as the percentage of necrotic area in given liver sections, was reduced significantly by this manoeuvre (mean (s.d.) 1.3 (1.3) versus 5.3 (1.7) per cent; P < 0.05). Conclusion. Ischaemic preconditioning exerts a protective effect on hepatic warm ischaemia-reperfusion injury. Such a manoeuvre may be useful for hepatic resection in the clinical setting..
1339. Yoshikazu Yonemitsu, Eric W.F.W. Alton, Kimihiro Komori, Tomoharu Yoshizumi, Keizo Sugimachi, Yasufumi Kaneda, HVJ (Sendai virus) liposome-mediated gene transfer
Current status and future perspectives, International journal of oncology, 12, 6, 1277-1285, 1998.06, Haemagglutinating virus of Japan (HVJ; Sendai virus), a member of the mouse paramyxovirus family, has been combined with liposomes to produce a novel gene transfer system, namely HVJ liposomes. This vector system is defined as a 'hybrid vector', constructed with inactivated viral particles and non-viral (artificial) multi- or unilamellar liposomes containing gene expression cassettes and has several advantages in comparison with other viral or non-viral systems. Many studies have shown that this vector system can, not only produce efficient gene transfer using reporter genes, but also with resulting in vivo functional changes in several animal models of diseases. Despite these results, it is likely that the construct will need to be modified to improve gene transfer and expression efficiency and also to extend the potential disease targets. We review the present status of this hybrid vector system and also discuss possible modifications for future application to either in vivo analysis of specific gene expression or human gene therapy strategies for congenital or acquired diseases..
1340. Y. Soejima, K. Yanaga, T. Nisizaki, T. Yoshizumi, H. Uchiyama, K. Sugimachi, Effect of thromboxane synthetase inhibitor on non-heart-beating donors in rat orthotopic liver transplantation, Surgery, 10.1016/S0039-6060(98)70230-2, 123, 1, 67-72, 1998.01, Background. The use of non-heart-beating donors could relieve donor organ shortage provided that the outcome of the recipients is not jeopardized. Methods. In this study we evaluated the effect of thromboxane synthetase inhibitor (OKY-046) on non-heart-beating donors in orthotopic liver transplantation in rodents. OKY-046 (OKY group, n = 8) or vehicle (control group, n = 8) was given to the donor animals for 60 minutes before the induction of 30 minutes of warm ischemia to the liver before transplantation and survival, and several parameters were compared between the two groups. Results. All recipients in the control group died within 2 days, whereas 67% of those of the OKY group had a 2-day survival and 44% had a 2-week survival (p < 0.01). Bile output from the allograft for 2 hours after reperfusion was significantly larger in the OKY group at all time points (p < 0.05). Furthermore, serum transaminase levels 10 minutes after reperfusion were significantly lower in the OKY group (p < 0.05), although those 120 minutes after reperfusion were comparable between the two groups. The thromboxane B2 level in liver tissue 10 and 120 minutes after reperfusion was significantly lower in the OKY group compared with the control group (p < 0.02 and p < 0.05, respectively). Conclusions. These results indicate that OKY-046 given to the donor before the induction of warm ischemia could ameliorate ischemia/reperfusion injury of the hepatic allograft by reducing thromboxane A2 production after reperfusion..
1341. Katsuhiko Yanaga, Tomoharu Yoshizumi, Hideaki Uchiyama, Shinji Okano, Kenji Takenaka, Keizo Sugimachi, Detection of hepatitis C virus RNA in bile, American Journal of Gastroenterology, 92, 10, 1927-1928, 1997.10, Objectives: The infectivity of bile in patients with hepatitis C virus (HCV) infection remains to be clarified. The purpose of this study was to document the detection of HCV-RNA in bile of patients with HCV infection. Methods: Bile and serum samples were tested for HCV RNA by a two-step polymerase chain reaction technique in 12: patients with HCV infection. Results: HCV-RNA was detected in the serum of all 12 patients, whereas 6 of 12 bile samples (50%) tested positive. Comparison of laboratory data between patients with and without HCV-RNA in bile demonstrated statistically higher serum total billrubin among those with positive bile HCV RNA than those without, but other clinical and biochemical variables as well as hepatitis activity scores were comparable between the two groups. Conclusions: Bile of HCV antibody-positive patients could be infectious..
1342. T. Yoshizumi, Y. Iso, C. Yasunaga, S. Kitano, K. Sugimachi, Laparoscopic splenectomy for splenic hamartoma, Surgical endoscopy, 10.1007/s004649900469, 11, 8, 848-849, 1997.08, Advances in imaging techniques have made preoperative diagnosis of splenic tumors possible. A case of successful laparoscopic splenectomy for splenic hamartoma is described here and the indications of this technique are discussed..
1343. Katsuhiko Yanaga, Tomoharu Yoshizumi, Kimihiro Komori, Takashi Nishizaki, Munetaka Masuda, Keizo Sugimachi, Balloon catheter-assisted inferior vena cava tumor thrombectomy without thoracotomy, Hepato-gastroenterology, 44, 15, 796-797, 1997.07, We report a technique for tumor thrombectomy of the inferior vena cava for renal cell carcinoma extending into the right atrium that abrogates the need for thoracotomy or sternotomy..
1344. Yuji Soejima, Katsuhiko Yanaga, Takashi Nishizaki, Tomoharu Yoshizumi, Hideaki Uchiyama, Keizo Sugimachi, The fate of non-absorbable suture in growing vascular anastomoses in liver transplantation, Hepato-gastroenterology, 44, 13, 227-230, 1997.03, Background/Aims: Anastomotic stricture of the portal vein is an uncommon complication of orthotopic liver transplantation for which the etiology is unclear. In the present study, we evaluated the fate of continuous anastomosis by non-absorbable suture material in growing vessels after orthotopic liver transplantation in pigs. Materials and Methods: A pig which had undergone orthotopic liver transplantation 54 months earlier was autopsied and inspected for vascular growth and their anastomotic patency. Results: The pig weighed 270 kg (1,080%) at 54 months after orthotopic liver transplantation. The liver was normal in, appearance and weighed 4,100 g (770%). All the vessels anastomosed were patent. However, luminal stenosis of the portal vein was identified at the anastomosis site, where intraluminal protrusion of the anastomosis was prominent. The inability of the suture material to grow longer than its full length along with the growth of the portal vein was suggested to be the main cause of the stenosis. Conclusion: We conclude that the use of non-absorbable sutures could cause late vascular anastomotic stricture in pediatric orthotopic liver transplantation..
1345. Y. Yonemitsu, Y. Kaneda, A. Muraishi, T. Yoshizumi, K. Sugimachi, K. Sueishi, HVJ (Sendai virus)-cationic liposomes
A novel and potentially effective liposome-mediated technique for gene transfer to the airway epithelium, Gene Therapy, 10.1038/sj.gt.3300463, 4, 7, 631-638, 1997.01, We designed a novel technique for targeted gene transfer into the airway epithelium. This was constructed using multilamellar cationic liposomes, containing N-(α-trimethylammonioacetyl)-didodecyl-D-glutamate chloride, phosphatidylcholine and cholesterol and fused with haemagglutinating virus of Japan (HVJ), namely HVJ cationic liposomes. Single aerosol delivery of this novel vector to the airway of rats led to a highly efficient and widespread transduction of fluorescein isothiocyanate-labeled oligonucleotides or lacZ gene into the bronchial epithelium and X alveolar macrophages, but not into the alveolar epithelium. The efficiency of gene transfer to the airway epithelium with a single administration of the lacZ gene was about 47.6% in the trachea, 39.0% in the bronchi and proximal bronchioli, and 2.9% in the terminal bronchioli, respectively (mean value, n = 6). Expression level of the luciferase gene delivered with this novel system was much higher than that without HVJ, in both the trachea and lung tissue. Two pretreatment HVJ-cationic liposome vehicles every other week resulted in minimal inflammatory infiltration in the subepithelial layer with no significant reduction in efficiency of the following gene transfer. We propose that this novel HVJ cationic liposome-mediated gene transfer system may be suitable for clinical gene therapy to treat subjects with lethal lung diseases such as cystic fibrosis..
1346. Yuji Soejima, Katsuhiko Yanaga, Shigeki Wakiyama, Takashi Nishizaki, Tomoharu Yoshizumi, Keizo Sugimachi, Serum hyaluronic acid as a reliable parameter of allograft viability in porcine liver transplantation, Hepato-gastroenterology, 43, 9, 590-595, 1996.07, Background/Aims: Hyaluronic acid is an endogenous glycosaminoglycan which is selectively degraded by hepatic sinusoidal endothelial cells. We evaluated the significance of serum hyaluronic acid clearance as an early indicator of allograft viability in porcine Liver transplantation. Materials and Methods: According to the survival period, animals were divided into two groups: Group I (n = 8) for survival equal or over four days and Group II (n = 5) for survival less than four days. Serial serum hyaluronic acid concentrations were measured before and after reperfusion in the recipient. Results: In both groups, serum hyaluronic acid levels during the anhepatic period increased rapidly 9-fold from the preoperative value due to the absence of clearance by hepatic endothelial cells. In Group I, serum hyaluronic acid peaked at 15 min postreperfusion and decreased thereafter. In contrast, Group II failed to show clearance of hyaluronic acid after reperfusion. The serum hyaluronic acid value 120 min after reperfusion was 1,029 ± 357 μg/L in Group I, and 1,856 ± 263 μg/L in Group II (p < 0.01). Conventional parameters of liver function such as aspartate transaminase, lactic dehydrogenase, ammonia, lactate, and total bile acids were comparable between the two groups. Conclusions: The clearance of the serum hyaluronic acid reflects hepatic sinusoidal endothelial cell function and is a reliable and early marker of hepatic allograft viability..
1347. T. Nishizaki, T. Matsumata, K. Yanaga, Y. Soejima, T. Yoshizumi, K. Takenaka, K. Sugimachi, Management of hepatic duct injury during hemihepatic vascular occlusion, British Journal of Surgery, 10.1002/bjs.1800830211, 83, 2, 1996.02.
1348. Shigeki Wakiyama, Katsuhiko Yanaga, Yuji Soejima, Takashi Nishizaki, Tomoharu Yoshizumi, Keizo Sugimachi, Assessment of hepatic graft injury by graft effluent in rodents
JV-acetyl-β-glucosaminidase and type III procollagen peptide, Transplant International, 10.1111/j.1432-2277.1996.tb00891.x, 9, 4, 359-363, 1996.01, We studied the significance of N-acetyl-β-glucosaminidase (β-NAG) and type III procollagen peptide (P-III-P) in the effluent of rodent hepatic grafts. After total hepatectomy, the livers were preserved in chilled, lactated Ringer's solution and then divided into five groups (n = 10 each): group 1, 4 h preservation only; group 2, 4 h preservation and rewarming; group 3, 6 h preservation only; group 4, 6 h preservation and rewarming; and group 5, minimal preservation only. The β-NAG of groups 2 and 4 was significantly higher than that of groups 1 and 3 (0.98 ±0.5 U/l vs 0.21 ±0.12 U/l; P < 0.01 and 1.76 ±0.67 U/l vs 0.38 ±0.25 U/l, respectively; P < 0.01), while that of group 4 was significantly higher than that of group 2 (1.76 ±0.67 U/l vs 0.98 ±0.50 U/l; P < 0.05). The P-IIIP of group 4 was significantly higher than that of group 2 (0.133 ± 0.008 U/ml vs 0.110 ±0.015 U/ml; P < 0.01). We conclude that β-NAG is a novel parameter of parenchymal and nonparenchymal cells, while P-III-P reflects the integrity of the hepatic sinusoidal extracellular matrix..
1349. Katsuhiko Yanaga, Takashi Nishizaki, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Keizo Sugimachi, Nobumitsu Morimoto, Seizaburo Kashiwagi, Requirements for the establishment of cadaveric liver transplantation in Japan, Japanese Journal of Gastroenterological Surgery, 10.5833/jjgs.29.903, 29, 4, 903-906, 1996.01, We report our experience with patient registration and care, and describe requirements for establishing a cadaveric liver transplantation protram in Japan. Since June 1991, 26 candidates have been evaluated for liver transplants (LTx) in our program. Of these, five patients had one or two concomitant hepatocellular carcinomas (HCCs) 1-2.5 cm in diameter, for which four were treated by ethanol injection. Five patients died waiting, and three underwent LTx abroad, while another received an ABO incompatible LTx from a non-heart beating donor in our program and died of multi-organ failure. Another patient lost candidacy for resuming drinking, leaving three waiting. Donor referral remains rare in Japan, where we encourage early patient registration in anticipation of long waiting, and now exclude malignancies other than a solitary HCC less than 2 cm, complicating non-B and Child C cirrhosis. Other requirements for a cadaveric liver transplant program were detailed..
1350. Katsuhiko Yanaga, Shigeki Wakiyama, Yuji Soejima, Tomoharu Yoshizumi, Takashi Nishizaki, Keizo Sugimachi, Hepatitis C virus infection among Japanese general surgical patients, World journal of surgery, 10.1007/BF00295906, 19, 5, 694-696, 1995.09, The incidence of hepatitis C virus (HCV) antibody positivity is unknown. The purpose of this study was to clarify the prevalence of HCV infection among surgical patients and to identify high risk surgical patients. HCV antibody tests were performed in 789 surgical patients between April 1991 and March 1992. Of these patients, 129 (16.3%) tested positive, which was much higher than the positivity of the ordinary Japanese. Hepatobiliary diseases and portal hypertension were associated with a higher positivity than other disease categories (94 of 206, 45.6% versus 35 of 583, 6%; p<0.0001). Patients above 50 years of age had a higher positivity than their younger counterparts (118 of 578, 20.4% versus 11 of 211, 5.3%; p<0.0001). The HCV positivity was as high as 54.1% (119 of 220) among surgical patients with known risk factors for hepatitis, in contrast to only 1.9% (10 of 569) among those without such risk factors. We conclude that surgical patients have a high incidence of HCV infection, for whom medical professionals should pay special attention to avoid disease transmission..
1351. T. Nishizaki, K. Takenaka, T. Yoshizumi, K. Yanaga, Y. Soejima, K. Shirabe, K. Sugimachi, Alteration in levels of human hepatocyte growth factor following hepatectomy, Journal of the American College of Surgeons, 181, 1, 6-10, 1995.01, BACKGROUND: The clinical significance of changes hi serum human hepatocyte growth factor (hHGF) in patients having hepatectomy remains unclear, partly because of various perioperative factors, such as underlying diseases and surgical procedures. STUDY DESIGN: Human hepatocyte growth factor was measured preoperatively and then on postoperative days 1, 3, 5, and 7. In 49 (79 percent) of 62 patients studied, serum hHGF increased postoperatively and peaked on postoperative day 1 or 3 (group 1), while in the other 13 patients (21 percent), it decreased on postoperative day 1 (group 2). RESULTS: The preoperative clinical parameters were comparable between the two groups except for indocyanine green retention rate at 15 minutes (16.6 compared with 23.4 percent; p<0.05). Operative stress and histology of the nontumorous portion of the liver were also comparable between the two groups. Postoperatively, alanine aminotransferase was significantly higher in group 1 than in group 2 on postoperative days 1 and 3. Regeneration of the remnant liver one month after hepatectomy was significantly higher hi group 1 than in group 2 (5±9 percent compared with -6±8 percent; p<0.01). The incidence of postoperative hepatic failure was significantly higher in group 2 than in group 1 (15 compared with zero percent; p<0.05). CONCLUSIONS: These observations led to the thesis that changes in serum hHGF levels after hepatectomy are an indicator of hepatic regeneration and also will serve as one factor to predict postoperative hepatic failure..
1352. K. Yanaga, Yuji Soejima, Tomoharu Yoshizumi, T. Nishizaki, K. Takenaka, K. Sugimachi, Selective balloon occlusion of the portal tree through the umbilical vein for hepatic resection, British Journal of Surgery, 10.1002/bjs.1800821041, 82, 10, 1421, 1995.01.
1353. Kazutoyo Morita, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Naotaka Hashimoto, Yohei Mano, Tatsunori Miyata, Yuji Soejima, Yoshihiko Maehara, Feasible isolated liver transplantation for a cirrhotic patient on chronic hemodialysis, Case Reports in Gastroenterology, 10.1159/000354140, 7, 2, 299-303, 2013.01, End-stage liver and kidney disease (ELKD) is an indication for deceased donor simultaneous liver-kidney transplantation. Although a few cases of living donor liver-kidney transplantation have been reported, the invasiveness remains to be discussed. Living donor liver transplantation (LDLT) is an alternative choice for ELKD, but has never been reported. Here, we report a case of successful LDLT for a patient with ELKD on hemodialysis. The patient was a 63-year-old male and had decompensated hepatitis C cirrhosis with seronegativity for hepatitis C virus. He had non-diabetic end-stage renal failure and had been on hemodialysis for 3 years. He was in good general condition except for hepatic and renal failure. The living donor was his 58-year-old healthy wife. A right lobe graft was transplanted to the recipient under continuous hemodiafiltration (CHDF) and extracorporeal veno-venous bypass. CHDF was continued until postoperative day 4, at which point CHDF was converted to hemodialysis. His posttransplant course was good and he was discharged on postoperative day 36. To the best of our knowledge, this is the first report of LDLT for a patient on chronic hemodialysis. Therefore, being on hemodialysis is not a contraindication for LDLT. LDLT is feasible for a patient with ELKD on hemodialysis..
1354. Hiroto Kayashima, Ken Shirabe, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Liver regeneration and venous collateral formation in the right lobe living-donor remnant
Segmental volumetric analysis and three-dimensional visualization, Transplantation, 10.1097/TP.0b013e31827147d8, 95, 2, 353-360, 2013.01, BACKGROUND: In left lobe (LL) living-donor liver transplantation (LDLT), hepatic venous congestion (HVC) caused by ligation of the middle hepatic vein tributaries is unavoidable in the right lobe (RL) donor remnant. METHODS: To clarify the impact of HVC on liver regeneration and venous collateral formation (VCF), we used three-dimensional computed tomography to examine the volumes of total/segmental liver and HVC and the degree of VCF; preoperative data were compared with data obtained on postoperative day (POD) 35 in 13 LL LDLT donors. RESULTS: On POD 35, the congestion rate decreased from 32.5% to 1.6% and the total liver regeneration rate was 81.7%. Preoperatively, the anterior sector-to-RL volume ratio was significantly lower, and the posterior sector-to-RL volume ratio was significantly higher than postoperatively (56.7% vs. 52.9%, P<0.01, and 36.9% vs. 41.5%, P<0.01, respectively). There was no correlation between degree of HVC and liver regeneration. Obvious VCF was found in five (38.5%) cases. The RL and posterior sector volume per square meter of body surface area in the VCF group were significantly lower than that in the non-VCF group (412 cm/m vs. 492 cm/m, P<0.01, and 140 cm/m vs. 190 cm/m, P<0.01, respectively). The preoperative congestion rate and liver regeneration rate were not significantly different between the groups. CONCLUSIONS: Reconstruction of the middle hepatic vein tributaries in the RL donor remnant might not be necessary in LL LDLT, because the HVC improved dramatically by POD 35 regardless of the development of VCF..
1355. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Mirror image hepatectomy in a patient with situs inversus totalis., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 430-434, 2013.01, Hepatectomy in a patient with situs inversus patient is technically challenging because of its complete mirror image anatomy, especially for a tumor located deep in the liver. Incorrectly identifying intrahepatic vessels and biliary system would lead to serious complications. We experienced a hepatectomy for a tumor in a patient with situs inversus totalis with referring to computer-generated mirror images. A 66-year-old female patient with situs inversus totalis was diagnosed with hepatocellular carcinoma, 5 cm in diameter, centrally located just above the hepatic hilum compressing the right and left hepatic duct. The liver infected with hepatitis C was cirrhotic with a moderate amount of ascites. We preoperatively created several diagrams of the mirror image anatomy and made plans for how to resect this tumor, presupposing the patient had an ordinary anatomy. The tumor was successfully enucleated with referring to these diagrams. The operation time was 454 minutes. Five units of fresh frozen plasma was transfused intraoperatively. Although she suffered refractory ascites which needed repeated paracentesis, she managed to leave the hospital two months after the operation. Creating a mirror image anatomy enables surgeons to safely perform a complex hepatectomy in a patient with situs inversus totalis..
1356. Takashi Motomura, Ken Shirabe, Yohei Mano, Jun Muto, Takeo Toshima, Yuichiro Umemoto, Takasuke Fukuhara, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment, Journal of Hepatology, 10.1016/j.jhep.2012.08.017, 58, 1, 58-64, 2013.01, Background & Aims: Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Preoperative neutrophil-lymphocyte ratio (NLR) is a predictor of patient prognosis, but its mechanism has never been clarified. Methods: We assessed outcomes in 158 patients who had undergone living-donor liver transplantation (LDLT) for HCC. Recurrence-free survival (RFS) was determined in patients with high (≥4) and low (<4) NLR. Levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68, and CD163 were measured. Results: The 5-year RFS rate was significantly lower in patients with high (n = 26) than with low (n = 132) NLR (30.3% vs. 89.0%, p <0.0001), in patients with high (n = 15) than with low (n = 79) NLR who met the MC (73.6% vs. 100%, p = 0.0008) and in patients with high (n = 11) than with low (n = 53) NLR who exceeded the MC (0% vs. 76.1%, p = 0.0002). Tumor expression of VEGF, IL8, IL-17, CD68, and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 levels were significantly higher in the high-NLR group (p = 0.01 each). The density of peritumoral CD163 correlated with the density of peritumoral IL-17-producing cells (p = 0.04) and was significantly higher in the high-NLR group (p = 0.005). Conclusions: NLR predicts outcomes after LDLT for HCC via the inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC..
1357. Keiji Yoshinaga, Hiroshi Saeki, Eiji Oki, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Prognostic markers for immunochemotherapy using tegafur -uracil (UFT) and protein-bound polysaccharide K (PSK)., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 549-558, 2013.01, We previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels. 98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years. There were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant. Serum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary..
1358. Hiroshi Saeki, Eiji Oki, Yasuo Tsuda, Koji Ando, Yukiharu Hiyoshi, Shuhei Ito, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Relevance of totally laparoscopic gastrectomy for patients with advanced gastric cancer., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 405-412, 2013.01, Although the use of laparoscopic gastrectomy for gastric cancer has been widespread, it has remained controversial whether it can be applied for the patients with advanced gastric cancer. The aim of this study was to clarify the safety and usefulness of totally laparoscopic gastrectomy for patients with advanced gastric cancer. Totally laparoscopic gastrectomy was applied for a total of 38 patients with pStage IB-III advanced gastric cancer at our institute. The surgical and long-term results were analyzed in those patients. Twenty-seven patents underwent distal gastrectomy and 11 patients underwent total gastrectomy. The mean number of dissected lymph nodes was 41 (range, 16-87). The mean length of the operation and amount of blood loss was 324 min and 123 ml, respectively. Two cases of postoperative bleeding were noted, while neither anastomosis-related complications nor in-hospital death was observed. The follow-up period after surgery was 8-72 months. Postoperative recurrence was observed in 6 patients (peritoneal dissemination: 3 patients, pleural dissemination: 1 patient, liver metastasis: 1 patient, ovarian metastasis: 1 patient). The overall survival rates at 1, 3 and 5 years were 94.7%, 76.3% and 76.3%, respectively. Totally laparoscopic gastrectomy is safe and can lead to satisfactory long-term outcomes in cases of advanced gastric cancer. Prospective controlled studies are warranted to confirm our findings..
1359. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo Ichi Yamashita, Tetsuo Ikeda, Hirofumi Kawanaka, Keishi Sugimachi, Koshi Mimori, Masayuki Watanabe, Masaru Morita, Eiji Oki, Hiroshi Saeki, Yoshihiko Maehara, Rex shunt for portal vein thrombosis after adult living donor liver transplantation., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 464-468, 2013.01, Portal vein thrombosis (PVT) after liver transplantation is a relatively common but serious complication which could lead to portal hypertension or a direct graft loss. A "Rex" shunt created between the superior mesenteric vein (SMV) and the umbilical portion of the left portal vein can be a useful option to treat PVT after pediatric liver transplantation, however, its application to adult patients has not been reported so far because appropriate vein grafts are hardly available. Herein we present a case of PVT after left lobe living donor liver transplantation (LDLT) who underwent the procedure using the own inferior jugular vein and the gonadal vein as a shunt graft. The shunt was patent immediately after the procedure but was thrombosed 2 days after probably due to the insufficient inflow from the SMV and the absence of anticoagulation therapy, for which emergent thrombectomy and ligation of the significant hepatofugal collateral veins followed by full anti-coagulation therapy were performed. The shunt remains open at 8 month after the procedure with a normal anmonia level and liver function. In conclusion, the Rex shunt using recipient's autologous vein grafts is a feasible and valuable option for adult patients to treat PVT after LDLT..
1360. Masayuki Watanabe, Koki Matsuura, Hideo Baba, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Yoshihiko Maehara, Thoracoscopic pericardial drainage for gastric tube ulcer penetrated into the pericardium., Unknown Journal, 104, 10, 389-393, 2013.01, Peptic ulcer occurring in the gastric conduit for esophageal reconstruction sometimes penetrates into the mediastinal structures. We herein reported a case of pericardial penetration of gastric tube ulcer successfully treated with thoracoscopic pericardial drainage. A 66-year-old Japanese man, who had undergone esophagectomy for esophageal cancer 20 months before, visited our emergency room complaining severe back pain. Computed tomography revealed gastric tube ulcer penetrated into the pericardial space. Thoracoscopic pericardiotomy and drainage was performed and the patient made an uneventful recovery. Thoracoscopic pericardial drainage is useful to manage acute pyogenic pericarditis due to penetration of peptic ulcer which occurred in the gastric tube..
1361. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Verification of our therapeutic criterion for acute cholecystitis
"perform a subemergency laparoscopic cholecystectomy when a patient is judged to be able to tolerate general anesthesia"--the experience in a single community hospital., Unknown Journal, 104, 10, 339-343, 2013.01, Our current therapeutic criterion for acute cholecystitis is: Perform a subemergency laparoscopic cholecystectomy (LC) when a patient is judged to be able to tolerate general anesthesia. The aim of the current study was to verify whether this criterion is justified. The outcomes of 21 cases of LC for acute cholecystitis performed between April 2011 and September 2013 were retrospectively analyzed. Subemergency LC was performed according to the aforementioned criterion (Subemergency group; n = 16). Patient who was judged to be unable to tolerate general anesthesia underwent percutaneous transhepatic gallbladder drainage (PTGBD) first, then LC after the patients' condition became stable (PTGBD group; n = 5). There is no conversion to open surgery throughout the study period. The mean of the total hospital stays in the Subemergency group was significantly shorter than that in the PTGBD group (11.5 +/- 5.3 vs. 30.4 +/- 8.5 days). Although two patients in the Subemergency group, who had already needed oxygen administration preoperatively, suffered postoperative respiratory failure, they completely recovered. On the other hand, there is no postoperative complication in the PTGBD group. Subemergency LC could be safely performed when surgeons as well as anesthesiologists judged a patient to be able to tolerate general anesthesia, which significantly shorten hospital stays compared to elective LC after PTGBD. However, elective LC after PTGBD is an absolutely safer therapeutic option in treating unstable patients..
1362. Tetsuo Ikeda, Tomohiko Akahoshi, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Koshi Mimori, Masayuki Watanabe, Makoto Hashizume, Yoshihiko Maehara, [Optimum hepatic parenchymal dissection to prevent bile leak
a comparative study using electrosurgical and stapling devices in swine]., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 507-514, 2013.01, Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma..
1363. Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara, Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma
Report of a case, Surgery today, 10.1007/s00595-012-0332-4, 42, 12, 1210-1214, 2012.12, The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection..
1364. Takashi Motomura, Ken Shirabe, Norihiro Furusyo, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tomohiko Akahoshi, Morimasa Tomikawa, Takasuke Fukuhara, Jun Hayashi, Yoshihiko Maehara, Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype, BMC Gastroenterology, 10.1186/1471-230X-12-158, 12, 2012.11, Background: IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.Methods: Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.Results: Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.Conclusions: IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype..
1365. Takashi Motomura, Yuki Ono, Ken Shirabe, Takasuke Fukuhara, Hideyuki Konishi, Yohei Mano, Takeo Toshima, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Neither MICA nor DEPDC5 genetic polymorphisms correlate with hepatocellular carcinoma recurrence following hepatectomy, HPB Surgery, 10.1155/2012/185496, 2012, 2012.11, Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7 in MICA GG allele carriers, 38.7 in GA, and 20.8 in AA, respectively (P = 0.72). The five-year RFS rate was 23.8 in DEPDC5 TT allele carriers and 31.8 in TG/GG, respectively (P = 0.47). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers (P 0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages..
1366. Yuji Soejima, Toru Ikegami, Hideki Ijichi, Tetsuo Ikeda, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hiroshi Matsuura, Kenichiro Okadome, Yoshihiko Maehara, Technical evolution of laparoscopic hepatic resection
a single institutional experience., Unknown Journal, 103, 11, 226-232, 2012.11, Laparoscopic hepatic resection (LHR) is still a challenging and developing surgical modality because of technical difficulty and a lack of training opportunities and experience. In this study, we present the results of our initial experiences of LHR, focusing on technical evolution in the management of LHR. Between April 2011 and March 2012, a total of 12 LHRs were performed. The first 5 of these LHRs were performed under laparoscopic assistance (hybrid-LHR), while the last 7 LHRs were performed totally laparoscopically (pure-LHR). Indications for LHR were hepatocellular carcinoma (n = 9) and metastatic liver cancer (n = 3). LHR procedures consisted of partial resection (n = 2), left lateral segmentectomy (n = 2), and left lobectomy (n = 1) in the hybrid-LHR group, and partial resection (n = 4), left lateral segmentectomy (n = 2), and right lobectomy (n = 1) in the pure-LHR group. Operative outcomes were compared between the groups and technical modifications were evaluated. The mean operative time, blood loss, and length of hospital stay in the hybrid- and pure-LHR groups were 3.8 and 6.1 hours, 220 and 611 ml, and 9.4 and 7.4 days, respectively. There were no postoperative complications in both groups. Tumor margins were negative in all cases. LHR is a feasible and effective procedure for patients with various types of liver tumors, although technical challenges still need to be overcome..
1367. Shohei Yoshiya, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31826969e6, 94, 9, 947-952, 2012.11, BACKGROUND: Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. METHODS: A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. RESULTS: The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). CONCLUSIONS: Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group..
1368. Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Authors' reply to "female-to-male match predicted poor survival following living donor liver transplantation-some issues needed to be clarified", Transplantation, 10.1097/TP.0b013e3182654d56, 94, 6, e36, 2012.09.
1369. Toru Ikegami, Ken Shirabe, Rumi Matono, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Etiologies, risk factors, and outcomes of bacterial pneumonia after living donor liver transplantation, Liver Transplantation, 10.1002/lt.23483, 18, 9, 1060-1068, 2012.09, The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short-term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram-negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P = 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post-LDLT pneumonia was associated with the following post-LDLT events: the prolonged use of mechanical ventilation (≥3 days), a prolonged stay in the intensive care unit (≥7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed-onset pneumonia, which occurred at least 10 days after transplantation (n = 15), and it was significantly associated with graft dysfunction. A combination of broad-spectrum antibiotics and aminoglycosides provided cover for most gram-negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad-spectrum antibiotics. Delayed-onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed..
1370. Hideaki Uchiyama, Hiroto Kayashima, Rumi Matono, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Toshiharu Matsuura, Tomoaki Taguchi, Yoshihiko Maehara, Relevance of HLA compatibility in living donor liver transplantation
The double-edged sword associated with the patient outcome, Clinical Transplantation, 10.1111/ctr.12019, 26, 5, E522-E529, 2012.09, HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA-A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host-versus-graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft-versus-host disease (GVHD) was also analyzed. No recipients with recipient-against-donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with "R→D MM 0" together with "donor-against-recipient MM 3" died of fatal GVHD. HLA compatibility in LDLT not only affected the long-term acceptance of graft livers but also the risk of fatal GVHD..
1371. Mizue Matsuo, Toru Ikegami, Kazutoyo Morita, Hiroko Yano, Naotaka Hashimoto, Hiroto Kayashima, Toshirou Masuda, Naoko Kondou, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, [A case of successful multi-venous reconstruction using recipient's jugular vein in right lobe-living donor liver transplantation]., Unknown Journal, 103, 9, 186-190, 2012.09, In right lobe-living donor liver transplantation (RT-LDLT), hepatic venous reconstruction of the graft is essential to prevent posttansplant graft congestion and have a good outcome. The patient was a 56-year-old man who had decompensated liver cirrhosis secondary hepatitis C with massive ascites, jaundice and hepatic encephalopathy. He underwent LDLT using his son's right lobe graft. Preoperative simulation by 3D-CT volumetry revealed that the right lobe graft needed multi-venous reconstruction for right inferior hepatic vein (RIHV) and middle hepatic venous tributaries. Preoperative CT scan revealed that the recipient had portal venous thrombus and stenosis, which meant that the recipient's explanted portal vein (EPV) was not suitable for the venous reconstruction of the right lobe graft. Therefore, the recipient's internal and external jugular veins (IJV and EJV) were procured for venous reconstruction. The multiple veins of the right lobe graft were reconstructed to have single co-orifice at the backtable, and the co-orifice was anastomosed to inferior vena cava in short time. The recipient discharged on postoperative day 22 with good venous patency. In RT-LDLT unavailable for recipient's EPV, recipient's IJV and EJV grafts are very useful for multi-venous reconstruction..
1372. Kazuki Takeishi, Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Takashi Motomura, Toru Ikegami, Tomoharu Yoshizumi, Fumio Sakane, Yoshihiko Maehara, Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras-Raf-MEK-ERK pathway, Journal of Hepatology, 10.1016/j.jhep.2012.02.026, 57, 1, 77-83, 2012.07, Background & Aims: Diacylglycerol kinases (DGKs) were recently recognized as key regulators in cell signaling pathways. We investigated whether DGKα is involved in human hepatocellular carcinoma (HCC) progression. Methods: We silenced or overexpressed DGKα in HCC cells and assessed its effect on tumor progression. DGKα expression in 95 surgical samples was analyzed by immunohistochemistry, and the expression status of each sample was correlated with clinicopathological features. Results: DGKα was detected in various HCC cell lines but at very low levels in the normal liver. Knockdown of DGKα significantly suppressed cell proliferation and invasion. Overexpression of wild type (WT) DGKα, but not its kinase-dead (KD) mutant, significantly enhanced cell proliferation. DGKα knockdown impaired MEK and ERK phosphorylation, but did not inhibit Ras activation in HCC cells. In a xenograft model, WT DGKα overexpression significantly enhanced tumor growth compared to the control, but KD DGKα mutant had no effect. Immunohistochemical studies showed that DGKα was expressed in cancerous tissue, but not in adjacent non-cancerous hepatocytes. High DGKα expression (≥20%) was associated with high Ki67 expression (p <0.05) and a high rate of HCC recurrence (p = 0.033) following surgery. In multivariate analyses, high DGKα expression was an independent factor for determining HCC recurrence after surgery. Conclusions: DGKα is involved in HCC progression by activation of the MAPK pathway. DGKα could be a novel target for HCC therapeutics as well as a prognostic marker..
1373. Yuji Soejima, K. Shirabe, A. Taketomi, T. Yoshizumi, H. Uchiyama, T. Ikegami, M. Ninomiya, N. Harada, H. Ijichi, Y. Maehara, Left lobe living donor liver transplantation in adults, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04022.x, 12, 7, 1877-1885, 2012.07, Adult left lobe (LL) living donor liver transplantation (LDLT) has not generally been recognized as a feasible procedure because of the problem of graft size. The objectives of this study were to assess the feasibility and short- and long-term results of adult LL LDLT in comparison with right lobe (RL) LDLT. Data on 200 consecutive LL LDLTs, including five retransplants, were retrospectively compared with those of 112 RL LDLTs, in terms of survival, complications and donor morbidity. The mean graft weight to standard volume ratio of LL grafts was 38.7% whereas that of RL grafts was 47.6% (p < 0.0001). The 1-, 5- and 10-year patient survival rates of LL LDLT were 85.6%, 77.9% and 69.5%, respectively, which were comparable to those of RL LDLT (89.8%, 71.3% and 70.7%, respectively). The incidence of small-for-size syndromewas higher in LL LDLT (19.5%) than in RL LDLT (7.1%) (p < 0.01). The overall donor morbidity rates were comparable between LL (36.0%) and RL (34.8%), whereas postoperative liver function tests and hospital stay were significantly better (p < 0.0001) in LL donors. In conclusion, adult LL LDLT has comparable outcomes to that of RL LDLT. LL LDLT is viable and is the first choice in adult LDLT..
1374. Toru Ikegami, K. Shirabe, T. Yoshizumi, S. Aishima, Y. A. Taketomi, Y. Soejima, H. Uchiyama, H. Kayashima, T. Toshima, Y. Maehara, Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04052.x, 12, 7, 1886-1897, 2012.07, The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult-to-adult LDLT grafts without anatomical, immunological or hepatitis-related issueswere included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH-20) was used to characterize PGD. DFH-20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH-20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PTINR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH-20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH-20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality..
1375. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Use of an internal jugular vein graft for middle hepatic vein tributary reconstruction in right-lobe living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31825b75b6, 94, 2, e17-e18, 2012.07.
1376. Yoko Zaitsu, Toru Ikegami, Toshirou Masuda, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, [A successful case of living donor liver transplantation performed in 7 hours for sub acute fulminant hepatitis]., Fukuoka igaku zasshi = Hukuoka acta medica, 103, 7, 145-149, 2012.07, Living donor liver transplantation (LDLT) is the ultimate cure for fulminant hepatitis. Successful outcomes rely on the precise evaluation of the reversibility of hepatic encephalopathy, and a swift execution of necessary examination of both the donor and the recipient. The case was a 63-years old woman, presented with fever and loss of appetite. She was hospitalized for acute hepatitis and treated at a nearby hospital. She was transferred to the tertiary hospital for the acute deterioration of her liver function on the 7th day after the emergence of the initial symptoms. On the 10th day, she showed Grade 2 encephalopathy and underwent plasma exchange. She was transported to our hospital for possible LDLT on the 11th day. CT scan on arrival showed severe atrophy of her liver and no definite brain edema despite acutely deteriorating encephalopathy (Grade 3). LDLT was launched after 7 hours from her transport. She was discharged from the intensive care unit on the 6th day and was discharged without severe complications on 42th day after the LDLT..
1377. Noboru Harada, Ken Shirabe, Hideki Ijichi, Rumi Matono, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Yoshihiko Maehara, Acoustic radiation force impulse imaging predicts postoperative ascites resulting from curative hepatic resection for hepatocellular carcinoma, Surgery (United States), 10.1016/j.surg.2011.12.035, 151, 6, 837-843, 2012.06, Background: Measurement of liver stiffness using Virtual Touch Tissue Quantification (VTTQ) based on acoustic radiation force impulse imaging reflects the degree of hepatic fibrosis and reserve. This prospective study investigated how well the VTTQ value predicts the development of postoperative complications before curative hepatic resection for hepatocellular carcinoma (HCC). Methods: The study enrolled 50 consecutive patients between February 2009 and October 2010 whose preoperative VTTQ values were determined before they underwent curative hepatic resection for HCC. We assessed the relationship between postoperative complications and VTTQ values. Results: The study included 41 (82%) patients with chronic hepatitis and 9 (18%) with nonviral cirrhosis. The mean VTTQ value was 1.60 (m/sec), which correlated with the fibrosis stage (P =.0058). The VTTQ value was the only variable correlated with postoperative ascites that did not respond to pharmacologic treatment and required invasive management. Univariate and subsequent multivariate analyses revealed that the preoperative VTTQ value was the only independent risk factor for predicting the development of postoperative ascites (cutoff, 1.68 cm/sec; P =.007; odds ratio, 76.481). The area under the receiver operating characteristic curve for the diagnosis of postoperative ascites using VTTQ values was 0.90, whereas those using the aspartate transaminase-to-platelet ratio index and indocyanine green retention rate at 15 minutes values were 0.68 and 0.55, respectively. Conclusion: These data suggest that the VTTQ value is a reliable surrogate marker for predicting postoperative ascites before curative hepatic resection for HCC..
1378. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Shohei Yoshiya, Takeo Toshima, Takashi Motomura, Yuji Soejima, Hideaki Uchiyama, Yoshihiko Maehara, En bloc stapling division of the gastroesophageal vessels controlling portal hemodynamic status in living donor liver transplantation, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.02.016, 214, 6, e53-e56, 2012.06.
1379. T. Yoshizumi, K. Shirabe, T. Ikegami, H. Kayashima, N. Yamashita, K. Morita, T. Masuda, N. Hashimoto, A. Taketomi, Y. Soejima, Y. Maehara, Impact of human T cell leukemia virus type 1 in living donor liver transplantation, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04037.x, 12, 6, 1479-1485, 2012.06, Human T cell leukemia virus type 1 (HTLV-1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV-1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV-1 status in living donor liver transplantation (LDLT). Twenty-six of 329 (7.9%) HTLV-1 carriers underwent primary LDLT. One recipient negative for HTLV-1 before LDLT received a graft from an HTLV-1 positive donor. Eight donors were HTLV-1 positive. Twenty-seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV-1 positive donors and two from negative donors. The 1-, 3- and 5-year HTLV-1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score ≥ 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV-1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development. The authors investigate the impact of human T cell leukemia virus type 1 in living donor liver transplantation and find that fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score > 15 are risk factors for T cell leukemia development See editorial by Kaul on page 1365..
1380. Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Kazutoyo Morita, Naotaka Hashimoto, Hiroto Kayashima, Tohru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihko Maehara, The long-term outcomes of patients with hepatocellular carcinoma after living donor liver transplantation
A comparison of right and left lobe grafts, Surgery today, 10.1007/s00595-011-0086-4, 42, 6, 559-564, 2012.06, Purpose The feasibility of living donor liver transplantation (LDLT) using left lobe (LL) grafts has been demonstrated. However, the long-term outcome of the hepatocellular carcinoma (HCC) patients with LL grafts has not been elucidated. The aim of this study was to analyze the long-term outcomes after LDLT for HCC according to the graft type. Methods A retrospective analysis was performed evaluating the outcomes of LL graft recipients (n = 82) versus recipients of RL grafts (n = 46). The analysis endpoints were the overall and recurrence-free survival after LDLT. The demographics of both recipients and donors, and the tumor characteristics associated with the graft type were also analyzed. Results The graft volume (436 ± 74 g), as well as the graft volume-standard liver volume rate (38.3 ± 6.2%) of the LL graft group were significantly decreased as compared to those of the RL graft group (569 ± 82 g, 46.3 ± 6.7%; P>0.01). The 1-, 3-, 5- and 7-year overall survival rates of the LL graft group were 88.2, 80.2, 75.7 and 72.4%, respectively, which were not significantly different compared to those of the RL graft group (95.4, 87.3, 87.3 and 87.3%). The recurrence-free survival rates of the LL graft group (89.1% at 1 year, 78.8% at 3 years, 75.8% at 5 years and 70.3% at 7 years) were similar to those of the RL graft group (88.6, 88.6, 88.6 and 88.6%). The mean peak postoperative total bilirubin levels and duration of hospital stay after surgery for the LL grafting donors were significantly decreased as compared to those of the RL grafting donors (P>0.01). The rate of severe complications (over Clavien's IIIa) associated with LL graft procurement was 6.2%, which was lower than that in the RL graft group (15.6%). Conclusions The long-term outcomes in the HCC patients with LL grafts were similar to those of patients receiving RL grafts, and the outcomes of the donors of LL grafts were more favorable. Therefore, LL grafts should be considered when selecting LDLT for HCC to ensure donor safety..
1381. Takeo Toshima, Ken Shirabe, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Outcome of hepatectomy for hepatocellular carcinoma in patients with renal dysfunction, HPB, 10.1111/j.1477-2574.2012.00452.x, 14, 5, 317-324, 2012.05, Objectives: There are few reports on the efficacy of hepatectomy for hepatocellular carcinoma (HCC) in patients with renal dysfunction (RD). This study aimed to clarify the validity of hepatectomy for treating HCC in RD patients, and to compare postoperative courses in RD and non-RD patients. Methods: The clinical features of 722 HCC patients who underwent curative hepatectomy between 1986 and 2009 were retrospectively reviewed. Seventeen patients (2.4%) with preoperative serum creatinine levels of >2.0 mg/dl were defined as the RD group, and, of these, seven who did not receive preoperative haemodialysis were defined as borderline patients. Clinicopathological characteristics and postoperative outcomes were compared between the RD group (n= 17) and the non-RD group (n= 705). The postoperative courses of borderline patients were reviewed in detail. Results: Overall survival (P= 0.177) and disease-free survival (P= 0.942) after hepatectomy did not differ significantly between the groups. Incidences of massive ascites (35.3% vs. 14.3%; P= 0.034) and pleural effusion (52.9% vs. 17.6%; P= 0.001), defined as massive effusion (ME), were significantly higher in the RD group than in the non-RD group. Hypoalbuminaemia (≤2.8 g/dl; P= 0.031), heavy blood loss (≥1000 ml; P= 0.012) and intraoperative blood transfusion (P= 0.007) were risk factors for ME. Among the borderline patients, serum creatinine values were not increased immediately after surgery and four patients underwent haemodialysis. Conclusions: Preoperative hypoalbuminaemia, heavy blood loss and blood transfusion are independent risk factors for ME in RD patients. Preoperative improvement of anaemia and reduction of blood loss by meticulous surgical techniques may prevent ME in RD patients who require hepatectomy for HCC..
1382. Takeo Toshima, Akinobu Taketomi, Toru Ikegami, Takasuke Fukuhara, Hiroto Kayashima, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, V5-drainage-preserved right lobe grafts improve graft congestion for living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3182488bd8, 93, 9, 929-935, 2012.05, Background: Right lobe (RL) grafts without middle hepatic vein for living donor liver transplantation (LDLT) result in congestion of recipients' livers and sometimes in unfavorable postoperative course. This study aimed to evaluate the feasibility of our new V5-drainage-preserved RL (VP-RL) graft. Methods: Based on a review of 49 donors' livers in a retrospective study using three-dimensional reconstruction-computed tomography volumetry, hepatic vein draining segment 4 (V4) anatomy was classified into three types: inferior V4 dominant (A); superior V4 dominant (B); and umbilical vein to left hepatic vein dominant (C). Differences in functional graft volume (GV) and remnant liver volume (RV) between VP-RL and modified RL (M-RL) grafts with all three types were evaluated. In a prospective study of actual 15 LDLT, the outcome of venous reconstruction and postoperative parameters with VP-RL grafts compared with M-RL grafts was analyzed. Results: In the retrospective study using three-dimensional reconstruction-computed tomography volumetry, in types B and C, functional GV of VP-RL was larger than that of M-RL (P<0.05) without impaired donors' functional RV, whereas functional RV in VP-RL was significantly decreased in type A (P<0.05). In the prospective study of actual 15 LDLT, using VP-RL with types B and C, size and number of venous reconstructions, and functional GV and postoperative parameters, such as postoperative serum total bilirubin levels and ascites volume, were significantly improved compared with those using M-RL (P<0.05). Conclusions: Using preoperative V4 anatomical classification, VP-RL graft procurement is a valuable strategy in RL-LDLT to improve postoperative course of both recipients and donors..
1383. Rumi Matono, Shohei Yoshiya, Takashi Motomura, Takeo Toshima, Hiroto Kayashima, Toshiro Masuda, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Factors linked to longterm survival of patients with hepatocellular carcinoma accompanied by tumour thrombus in the major portal vein after surgical resection, HPB, 10.1111/j.1477-2574.2011.00436.x, 14, 4, 247-253, 2012.04, Objectives: The prognosis in patients with hepatocellular carcinoma (HCC) accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this study was to clarify the factors linked to survival of >5 years after hepatectomy in HCC patients with MPVTT. Methods: Twenty-nine HCC patients with MPVTT were divided into two groups comprising, respectively, patients who survived >5 years after hepatectomy (survivors, n = 5) and those who did not (non-survivors, n = 24). The two groups were compared. Results: Overall survival rates at 1, 3 and 5 years were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had recurrences of HCC in which the number of recurrent nodules was under four. Three (21.4%) of the 14 non-survivors who underwent curative resection experienced recurrences of HCC and all of them demonstrated fewer than four recurrent nodules (P = 0.0114). Local therapy, such as radiofrequency ablation and resection of recurrence, had more often been used in survivors than in non-survivors (P = 0.0364). Conclusions: Although surgical outcomes in patients with HCC accompanied by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the number of recurrent nodules is less than four, local therapy should be selected with the aim of achieving 5-year survival..
1384. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Tomoharu Yoshizumi, Mizuki Ninomiya, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Bacterial sepsis after living donor liver transplantation
The impact of early enteral nutrition, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2011.12.001, 214, 3, 288-295, 2012.03, Background: Bacterial sepsis is a significant problem that must be addressed after living donor liver transplantation (LDLT). Study Design: A retrospective analysis of 346 adult-to-adult LDLT patients was performed. Results: Forty-six patients (13.3%) experienced bacterial sepsis, with primary and secondary origins in 23.9% and 76.1%, respectively. Gram-negative bacteria accounted for 71.7% of the bacteria isolated. The 2-year cumulative graft survival rate in patients with bacterial sepsis was 45.7%. Patients with bacterial sepsis secondary to pneumonia (n = 12) had poorer 2-year graft survival rates (16.7%) than did those with primary or other types of secondary sepsis (p = 0.004). Multivariate analysis showed that intraoperative massive blood loss >10L (p < 0.001) and no enteral feeding started within 48 hours after transplantation (p = 0.005) were significant risk factors for bacterial sepsis. Among patients who received enteral nutrition, the incidences of bacterial sepsis in patients who received enteral nutrition within 48 hours (n = 135) or later than 48 hours (n = 57) were 5.9% and 21.0%, respectively (p = 0.002). The incidence of early graft loss was 8-fold higher in recipients with massive intraoperative blood loss without early enteral nutrition (p < 0.001). Conclusions: Early enteral nutrition was associated with significantly reduced risk of developing bacterial sepsis after LDLT..
1385. Takashi Motomura, Erina Koga, Akinobu Taketomi, Takasuke Fukuhara, Yohei Mano, Jun Muto, Hideyuki Konishi, Takeo Toshima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype, Hepatology Research, 10.1111/j.1872-034X.2011.00927.x, 42, 3, 288-295, 2012.03, Aim: A genetic polymorphism of inosine triphosphate pyrophosphatase (ITPA) has been associated with pegylated-interferon/ribavirin (PEG-IFN/RBV)-induced anemia in chronic hepatitis C patients. However, correlation of the genetic variant with anemia following liver transplantation has not been determined. Methods: Sixty-three hepatitis C virus (HCV)-positive patients who underwent liver transplantation and PEG-IFN/RBV therapy were enrolled. The rs1127354 was determined for each individual. Results: There was no relationship with anemia or RBV dosage in patients carrying the CC allele (CC group, n=43) and those carrying the CA allele (CA group, n=20). The incidence of hemoglobin (Hb) decline >3g/dL (CC: 4.7%, CA: 0%) was relatively low, whereas the incidence of Hb levels <10g/dL (CC: 18.6%, CA: 30.0%) was high. Univariate analysis revealed that splenectomy inversely correlated with Hb levels <10g/dL at 4weeks (P=0.04). Among the 22 patients who did not undergo splenectomy, the incidence of Hb levels <10g/dL tended to be lower in the seven patients carrying the CA allele (28.6%) than in the 15 patients with the CC allele (60.0%). Conclusion: The ITPA genetic polymorphism does not correlate with post-transplant PEG-IFN/RBV-induced anemia. Splenectomy is useful in preventing anemia regardless of the ITPA genotype..
1386. Jun Muto, Yohei Mano, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Additional resection of the pancreas body prevents postoperative pancreas fistula in patients with portal annular pancreas who undergo pancreaticoduodenectomy, Case Reports in Gastroenterology, 10.1159/000335210, 6, 1, 131-134, 2012.01, Portal annular pancreas (PAP) is a rare variant in which the uncinate process of the pancreas extends to the dorsal surface of the pancreas body and surrounds the portal vein or superior mesenteric vein.Upon pancreaticoduodenectomy (PD), when the pancreas is cut at the neck, two cut surfaces are created. Thus, the cut surface of the pancreas becomes larger than usual and the dorsal cut surface is behind the portal vein, therefore pancreatic fistula after PD has been reported frequently. We planned subtotal stomach-preserving PD in a 45-year-old woman with underlying insulinoma of the pancreas head. When the pancreas head was dissected, the uncinate process was extended and fused to the dorsal surface of the pancreas body. Additional resection of the pancreas body 1 cm distal to the pancreas tail to the left side of the original resection line was performed. The new cut surface became one and pancreaticojejunostomy was performed as usual. No postoperative complications such as pancreatic fistula occurred. Additional resection of the pancreas body may be a standardized procedure in patients with PAP in cases of pancreas cut surface reconstruction..
1387. Hideaki Uchiyama, Ken Shirabe, Masaru Morita, Yoshihiro Kakeji, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Noboru Harada, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Expanding the applications of microvascular surgical techniques to digestive surgeries
A technical review, Surgery today, 10.1007/s00595-011-0032-5, 42, 2, 111-120, 2012.01, In living donor liver transplantation (LDLT), it is considered safer to reconstruct hepatic arteries (HAs) under a microscope than under conventional loupe magnification, because graft HA stumps are generally thin and short with an average diameter of approximately 2 mm. We first applied microvascular surgical techniques to HA reconstruction for LDLT in 1996. In most cases, we use a disposable double-clip to secure the graft and recipient arteries, and interrupted 8-0 nonabsorbable monofilament sutures. We next started performing resection and reconstruction of the right HA in a surgery for hilar cholangioma using the same technique as in LDLT. Lately, we have started applying microvascular surgical techniques to various digestive surgeries; namely, supercharge and superdrainage in esophageal surgery, vascular reconstruction in free jejunal interposition grafts for cervical esophageal cancer, resection and reconstruction of spontaneous HA aneurysms, jejunal artery reconstruction for spontaneous superior mesenteric artery dissections, and so forth. Mastering this technique is time consuming. However, once a surgeon masters the technique it has almost unlimited applications, and most vital vessels can be safely reconstructed using this method. We herein provide a technical review of the application of microvascular surgical techniques for various digestive surgeries..
1388. Tomoharu Yoshizumi, Ken Shirabe, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Masanori Yoshimatsu, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Risk factors that increase mortality after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e318238dacd, 93, 1, 93-98, 2012.01, BACKGROUND.: Female liver to male recipient is a well-accepted risk factor for graft loss in cadaveric liver transplantation. However, gender matching is infeasible because of an insufficient number of available donors. No studies have been performed on the role of gender in the field of living donor liver transplantation. This report investigates the effect of gender mismatch on the outcome of living donor liver transplantation. METHODS.: A total of 335 patients and donors were classified into four groups according to the following gender combinations: male donor to male recipient group (n=104), male donor to female recipient group (n=120), female donor to male recipient (FM) group (n=59), and female donor to female recipient group (n=52). Patient and graft survival were compared among the groups. We performed a multivariable analysis to identify the factors associated with patient mortality. RESULTS.: The 1-, 3-, 5-, and 10-year patient survival rates in the FM group were 80.6%, 66.8%, 61.8%, and 47.7%, respectively. The FM group showed significantly shorter patient survival compared with the other three groups. Independent risk factors for patient mortality were: FM group (P=0.006), pretransplant diabetes mellitus (P=0.001), and a model for end-stage liver disease score more than or equal to 20 (P=0.004). CONCLUSIONS.: Male recipients of transplants from female donors, pretransplant diabetes mellitus, and a model for end-stage liver disease score more than or equal to 20 have poor survival rates..
1389. Ken Shirabe, Yohei Mano, Jun Muto, Rumi Matono, Takashi Motomura, Takeo Toshima, Kazuki Takeishi, Hidekaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Masaru Morita, Shunichi Tsujitani, Yoshihisa Sakaguchi, Yoshihiko Maehara, Role of tumor-associated macrophages in the progression of hepatocellular carcinoma, Surgery today, 10.1007/s00595-011-0058-8, 42, 1, 1-7, 2012.01, Recent studies have shown that the tumor microenvironment plays an important role in cancer progression. Tumor-associated macrophages (TAMs), in particular, have been found to be associated with tumor progression. Macrophages have multiple biological roles, including antigen presentation, target cell cytotoxicity, removal of foreign bodies, tissue remodeling, regulation of inflammation, induction of immunity, thrombosis, and endocytosis. Recent immunological studies have identified two distinct states of polarized macrophage activation: the classically activated (M1) and the alternatively activated (M2) macrophage phenotypes. Bacterial moieties such as lipopolysaccharides and the Th1 cytokine interferon-γ polarize macrophages toward the M1 phenotype. The M2 polarization was discovered as a response to the Th2 cytokine interleukin-4. In general, M2 macrophages exert immunoregulatory activity, participate in polarized Th2 responses, and aid tumor progression. TAMs have recently been found to play an important role in hepatocellular carcinoma (HCC) progression. Based on the properties of TAMs, obtained from pathological examination of resected specimens, we have identified new therapeutic approaches, involving the targeting of TAMs with adjuvant therapy after hepatic resection for HCC. This review discusses the roles of TAM in HCC progression and the possibility of new therapies targeting TAMs..
1390. Toru Ikegami, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yoshihiko Maehara, The impact of renal replacement therapy before or after living donor liver transplantation, Clinical Transplantation, 10.1111/j.1399-0012.2011.01450.x, 26, 1, 143-148, 2012.01, Introduction: The impact of renal replacement therapy (RRT) in living donor liver transplantation (LDLT) has not yet been investigated. Methods: Among 253 LDLT patients, RRT was started before (RRT-Pre, n=9), or after (RRT-Post, n=27) LDLT. The clinical outcomes were reviewed. Results: The one-yr graft survival rate was 94.1% without RRT, and 63.9% and in those with RRT (p<0.0001). Among the RRT patients, the RRT-Pre patients exhibited acute liver failure, hepatorenal syndrome and high model for end-stage liver disease score (35±12), whereas the RRT-Post patients had sepsis as a comorbidity. The one-yr graft survival rate was 100.0% in the RRT-Pre patients vs. 51.9% in the RRT-Post patients (p<0.01). The duration of RRT was significantly shorter in the RRT-Pre patients than that in the RRT-Post patients (5.3±2.1 vs. 17.8±14.1d, p=0.02). The mean duration between starting RRT and LDLT was 2.1±0.7d in the Pre-RRT patients. Conclusion: The RRT-Pre patients had excellent outcomes because the severe condition was primarily treated by LDLT after short-term pre-transplant RRT. Post-transplant uncontrollable sepsis was the major cause of graft loss in patients who receive RRT after LDLT..
1391. Akinobu Taketomi, Kazuki Takeishi, Yohei Mano, Takeo Toshima, Takashi Motomura, Shinichi Aishima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Total resection of the right hepatic vein drainage area with the aid of three-dimensional computed tomography, Surgery today, 10.1007/s00595-011-0021-8, 42, 1, 46-51, 2012.01, Purpose: We analyzed the feasibility and safety of our preliminary surgical approach for total hepatic resection of the right hepatic vein drainage area (THR-RHV) with the aid of three-dimensional computed tomography (3D-CT) guidance. Methods: Clinical findings and 3D-CT volumetry results were investigated in five patients who underwent THR-RHV for a hepatic malignant tumor close to the right hepatic vein (RHV). Results: The mean estimated remnant liver volume after a conventional right lobectomy was 474 ml, whereas that after THR-RHV was 614 ml, indicating that 140 ml (13.8%) of additional liver volume had been preserved by performing THR-RHV. The median operative time, mean ischemic time, and mean blood loss during surgery were 406 min, 51 min, and 587 ml, respectively. Histological examinations confirmed a negative surgical margin in all five patients. The mean liver volume estimated by 3D-CT was 458 ml, whereas the mean actual resected liver volume was 468 g, resulting in a mean error ratio of 3.1%. Conclusions: THR-RHV allowed for a higher remnant liver volume than that after conventional right lobectomy of the liver, and proved feasible with acceptable perioperative results. This technique thus promotes both safety and curability for patients with a tumor close to the RHV..
1392. Eisuke Kawakubo, Yuji Soejima, Eigorou Yamanouchi, Mizuki Ninomiya, Hiroto Kayashima, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Case of magnetic compression anastomosis with double-balloon enteroscopy for biliary obstruction after living donor liver translationn, Japanese Journal of Gastroenterological Surgery, 10.5833/jjgs.44.1404, 44, 11, 1404-1410, 2011.12, Biliary anastomotic strictures are one of the most significant postoperative complications after living donor liver transplantations (LDLT), which develop in about 10-30% of recipients. Various modalities have been reported to treat these complications with an acceptable success rate. Herein, we present a case of complete anastomotic obstruction of hepaticojejunostomy, for which a successful magnetic compression anastomosis (MCA) was performed. The patient was a 56-year-old man who was given a diagnosis of biliary anastomotic strictures 9 months after LDLT. Conservative treatment, including percutaneous transhepatic biliary drainage (PTBD), was initially undertaken, however, re canalization of the bile duct anastomosis could not be obtained. An MCA was performed 3 months after the initial PTBD, which resulted in a success. In conclusion, MCA is a safe and very effective method to treat complete anastomotic strictures after LDLT..
1393. Tetsuo Ikeda, Yusuke Yonemura, Naoyuki Ueda, Akira Kabashima, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yosihiro Kakeji, Masaru Morita, Shunichi Tsujitani, Yoshihiko Maehara, Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic glissonian approach and a modified hanging maneuver to minimize intraoperative bleeding, Surgery today, 10.1007/s00595-010-4479-6, 41, 12, 1592-1598, 2011.12, Purpose: Although laparoscopic liver resection has been widely adopted, performing a pure laparoscopic right hepatectomy remains a challenging procedure. The aim of this report is to evaluate the efficiency of a pure laparoscopic right hepatectomy (PLRH) in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver. Methods: Pure laparoscopic right hepatectomy was performed in the semi-prone position with the use of an intrahepatic Glissonian approach and modified hanging maneuver for patients with primary liver cancer (n = 3) and metastatic liver cancer (n = 1). Results: The intraoperative total blood loss was only 95-140 g (mean: 126.2 g). None of the patients required a blood transfusion, and no serious complications were encountered. The durations of the surgeries ranged from were 308 to 445 min (mean: 394.8 min). The postoperative hospital stay was 8-11 days (mean 9.5 days). Conclusion: Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver is thus considered to be a safe modality, which minimizes intraoperative bleeding..
1394. Hideaki Uchiyama, Yohei Mano, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Ken Shirabe, Yoshihiko Maehara, Kinetics of anti-blood type isoagglutinin titers and B lymphocytes in ABO-incompatible living donor liver transplantation with rituximab and plasma exchange, Transplantation, 10.1097/TP.0b013e318231e9f8, 92, 10, 1134-1139, 2011.11, Background. A novel immunosuppression protocol using rituximab and plasma exchange treatment was developed for ABO-incompatible living donor liver transplantation (ABO-I LDLT). The aim of this study was to investigate the kinetics of anti-blood type isoagglutinin titers and the number of blood B lymphocytes in ABO-I LDLT with the new protocol and their impact on the outcomes after ABO-I LDLT. Methods. Fifteen patients underwent ABO-I LDLT plus splenectomy with the new protocol between November 2005 and December 2010, and their data were retrospectively analyzed. Results. CD19-positive lymphocytes in the blood rapidly disappeared after rituximab treatment and began to recover approximately 6 months later. Anti-blood type isoagglutinin titers were lowered by pretransplant plasma exchange (2 3∼2 12→2 1∼2 8). Although the anti-donor blood type isoagglutinin titers remained consistently low after transplantation in comparison to the pretreatment levels, they persisted long after LDLT, whereas posttransplant biopsy specimens showed sustained A/B antigens on the graft livers. ABO-I hepatitis C virus-positive patients were prone to acceleration of hepatitis C viremia and cytomegalovirus antigenemia in comparison to the control patients. Conclusions. Although the new protocol for ABO-I LDLT yielded great success with 100% graft survival, the acceptable anti-blood type isoagglutinin titers just before LDLT, and its application to hepatitis C-positive patients must be determined..
1395. Toru Ikegami, Ken Shirabe, Kazutoyo Morita, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Hiroto Kayashima, Naotaka Hashimoto, Yoshihiko Maehara, Minimal hilar dissection prevents biliary anastomotic stricture after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3182336073, 92, 10, 1147-1151, 2011.11, Background. We introduced a new technique called minimal hilar dissection (Min-HD) technique in living donor liver transplantation (LDLT) to keep vascular networks around the recipient's bile duct. The aim of this study is to investigate whether the Min-HD technique could prevent biliary anastomotic stricture (BAS) after LDLT with duct-to-duct biliary reconstruction. Methods. An analysis of 214 adult-to-adult LDLT grafts (left lobe, n=135; right lobe, n=76; posterior segment, n=3) with duct-to-duct biliary reconstruction was performed. Results. There were 46 cases with BAS. The incidence of BAS was 32.1% in the conventional technique group (n=84) and 14.6% in the Min-HD technique group (n=130, P=0.003). Multivariate regression analysis regarding BAS was carried out and detected hepatic artery flow less than 50 mL/min (P=0.002), not using the Min-HD technique (P=0.011), biliary anastomotic leakage (BAL, P=0.027) and ductoplasty (P=0.039) for the significant risk factors for BAS. The incidence BAL was 11.9% in the conventional technique group and 0.7% in the Min-HD technique group (P=0.002). No other factors showed an impact on the occurrence of BAL. The treatments for BAS were performed by endoscopic or percutaneous procedures. The cumulative completion rate of the treatment after developing BAS was 45.1% and 78.6% at 1-and 3-year, respectively. The median period for treating BAS was 10.8 months. Conclusion. The Min-HD technique is a rational surgical method, and it has the potential for preventing BAS and BAL after duct-to duct biliary reconstruction in LDLT..
1396. Ken Shirabe, Takeo Toshima, Akinobu Taketomi, Kennichi Taguchi, Tomoharu Yoshizumi, Hideaki Uchiyama, Norifumi Harimoto, Kiyoshi Kajiyama, Akinori Egashira, Yoshihiko Maehara, Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan, Liver International, 10.1111/j.1478-3231.2011.02572.x, 31, 9, 1366-1372, 2011.10, Background & aims: Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC. Methods: Hepatocyte AFB1-DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non-B non-C hepatocellular carcinoma (NBNC HCC). Results: AFB1-DNA adducts were detected in hepatocyte nuclei in 18/279 patients (6%), including13/83 patients (16%) with NBNC HCC and 5/51 patients (10%) expressing hepatitis B surface antigen. None of the patients with HCV Ab (n=136) were positive for AFB1-DNA. The incidence of the G-T transversion and mutations in exon 7 of TP53 in patients with AFB1-DNA adducts were significantly higher in patients with than in patients without AFB1-DNA adducts. All three patients with the codon 249 AGG-AGT mutation had AFB1-DNA adducts. Conclusion: Although exposure to AFB1 is thought to be low in Japan, it is still associated with hepatocarcinogenesis, particularly in NBNC HCC and hepatitis B individuals..
1397. Toru Ikegami, Takashi Maeda, Hiroto Kayashima, Eiji Oki, Tomoharu Yoshizumi, Yoshihisa Sakaguchi, Yasushi Toh, Ken Shirabe, Yoshihiko Maehara, Soft coagulation, polyglycolic acid felt, and fibrin glue for prevention of pancreatic fistula after distal pancreatectomy, Surgery today, 10.1007/s00595-010-4433-7, 41, 9, 1224-1227, 2011.09, Purpose: To evaluate the effectiveness of using soft coagulation followed by the application of polyglycolic acid (PGA) felt and fibrin glue to prevent pancreatic fistula (PF) after distal pancreatectomy (DP). Methods: A soft coagulation system was applied on the cut surface of the pancreas after ligating the main pancreatic duct, followed by the application of layers of PGA felt and fibrin glue on the layers, to prevent the development of a PF after DP. Results: This technique was applied in nine patients, with mean drain amylase levels of 372 ± 296, 185 ± 209, 54 ± 40, and 47 ± 34 IU/l on days 1, 3, 5, and 7, respectively, after DP. Only one patient (11.1%) showed a Grade A PF on day 3 after surgery; none of the other patients developed a fistula. Conclusions: This technique is an effective prophylactic measure to prevent the development of a PF after DP..
1398. Mizuki Ninomiya, Ken Shirabe, Hideki Ijichi, Takeo Toshima, Noboru Harada, Hideaki Uchiyama, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Temporal changes in the stiffness of the remnant liver and spleen after donor hepatectomy as assessed by acoustic radiation force impulse
A preliminary study, Hepatology Research, 10.1111/j.1872-034X.2011.00809.x, 41, 6, 579-586, 2011.06, Aim: Virtual touch tissue quantification (VTTQ) is an implementation of ultrasound acoustic radiation force impulse imaging that provides numerical measurements of tissue stiffness. We have evaluated the temporal changes of the remnant liver and spleen after living donor hepatectomy with special reference to the differences between right and left liver donation. Methods: Nineteen living donors who received right lobectomy (small remnant liver [SRL] group; n=7) or extended left and caudate lobectomy (large remnant liver [LRL] group; n=12) were enrolled. They underwent measurement of liver and spleen VTTQ before and after donor surgery. Results: Virtual touch tissue quantification of the remnant liver increased postoperatively until postoperative day (POD) 3-5, and the values in the SRL group were significantly higher than those in the LRL group at POD 3-9. The values of the spleen also increased after donor surgery and the values in the SRL group were significantly higher than those in the LRL group at POD 3-14. A significant positive correlation between postoperative maximum value of VTTQ and postoperative maximum total bilirubin levels was observed. In liver transplant recipients, there was a significant positive correlation between preoperative spleen VTTQ and the corresponding actual portal venous pressure that was measured at the time of transplant surgery. Conclusion: Stiffness of the remaining liver and spleen in the smaller remnant liver group became harder than that in the larger remnant liver group. Perioperative measurement of liver and spleen VTTQ seems to be a useful means for assessing the physiology of liver regeneration..
1399. T. Motomura, A. Taketomi, T. Fukuhara, Y. Mano, K. Takeishi, T. Toshima, N. Harada, H. Uchiyama, T. Yoshizumi, Y. Soejima, K. Shirabe, Y. Matsuura, Y. Maehara, The impact of IL28B genetic variants on recurrent hepatitis C in liver transplantation
Significant lessons from a dual graft case, American Journal of Transplantation, 10.1111/j.1600-6143.2011.03537.x, 11, 6, 1325-1329, 2011.06, IL28B genetic polymorphism is related to interferon-sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51-year-old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated-interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients. In this dual graft liver transplantation case, each graft with different IL28B genotype showed significantly different pathological findings and viral kinetics after interferon therapy for recurrent hepatitis C..
1400. Takeo Toshima, Ken Shirabe, Kazuki Takeishi, Takashi Motomura, Youhei Mano, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, New method for assessing liver fibrosis based on acoustic radiation force impulse
A special reference to the difference between right and left liver, Journal of gastroenterology, 10.1007/s00535-010-0365-7, 46, 5, 705-711, 2011.05, Background: Virtual touch tissue quantification (VTTQ) based on acoustic radiation force impulse (ARFI) imaging has been developed as a noninvasive bedside method for the assessment of liver stiffness. In this study, we examined the diagnostic performance of ARFI imaging in 103 patients, focusing on the difference in VTTQ values between the right and left liver lobes. Methods: We evaluated VTTQ values of the right and left lobes in 79 patients with chronic liver disease who underwent histological examination of liver fibrosis and in 24 healthy volunteers. The diagnostic accuracy of VTTQ was compared with several serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index. Results: The VTTQ values (meters per second) in the right and left lobes were 1.61 ± 0.51 and 1.90 ± 0.68, respectively, and the difference was statistically significant (P < 0.0001). The VTTQ values in both liver lobes were correlated significantly with histological fibrosis grades (P < 0.001). The standard deviations of the VTTQ values in the right lobe were significantly lower than those in the left lobe (P < 0.001). The area under the receiver-operating characteristic curve for the diagnosis of fibrosis (F ≥ 3) using VTTQ values in both liver lobes was superior to serum markers, especially in the right lobe. Conclusions: VTTQ is an accurate and reliable tool for the assessment of liver fibrosis. VTTQ of the right lobe was more accurate for diagnosing liver fibrosis than in the left lobe..
1401. Naotaka Hashimoto, Tomohiko Akahoshi, Tetsuya Shoji, Morimasa Tomikawa, Norifumi Tsutsumi, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Successful treatment for hepatic encephalopathy aggravated by portal vein thrombosis with balloon-occluded retrograde transvenous obliteration, Case Reports in Gastroenterology, 10.1159/000330287, 5, 2, 366-371, 2011.05, This report presents the case of a 78-year-old female with hepatic encephalopathy due to an inferior mesenteric venous-inferior vena cava shunt. She developed hepatocellular carcinoma affected by hepatitis C virus-related cirrhosis and underwent posterior sectionectomy. Portal vein thrombosis developed and the portal trunk was narrowed after hepatectomy. Portal vein thrombosis resulted in high portal pressure and increased blood flow in an inferior mesenteric venous-inferior vena cava shunt, and hepatic encephalopathy with hyperammonemia was aggravated. The hepatic encephalopathy aggravated by portal vein thrombosis was successfully treated by balloon-occluded retrograde transvenous obliteration via a right transjugular venous approach without the development of other collateral vessels..
1402. Mami Kanamoto, Mitsuo Shimada, Yuji Morine, Tomoharu Yoshizumi, Satoru Imura, Toru Ikegami, Hiroki Mori, Yusuke Arakawa, Beneficial effects of follistatin in hepatic ischemia-reperfusion injuries in rats, Digestive Diseases and Sciences, 10.1007/s10620-010-1401-4, 56, 4, 1075-1081, 2011.04, Background: Ischemia-reperfusion injury has been demonstrated in a variety of clinical settings. The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. Follistatin, an activin-binding protein, binds to activins and subsequently blocks their action. It was reported that blockade of the action of activin with administration of follistatin accelerates recovery from ischemia renal injury. This study was conducted to investigate the involvement of the activin-follistatin system in hepatic ischemia-reperfusion injury. Methods: Total hepatic ischemia for 30 min was performed followed by reperfusion in a rat model. Rats were divided into two groups: a follistatin group and a control group. Follistatin (1 μg/body), which is an activin-binding protein, was administered at the time of reperfusion. Results: Though 80% of animals survived in the follistatin group, four of five animals died in the control group within 3 days after reperfusion (p < 0.05). AST was significantly lower at 3 h after reperfusion in the follistatin group (p < 0.05). LDH was also lower at 6 h after reperfusion in the follistatin group (p < 0.05). Follistatin inhibited the mRNA expression of the βA subunit of activin. Moreover, the expression of IL-6, which is an inflammatory cytokine, was suppressed at 6 h after reperfusion in the follistatin group (p < 0.05). Conclusions: The present study demonstrated that treatment with follistatin reduced the expression of IL-6 and activin resulting in beneficial support for hepatic ischemia-reperfusion injuries..
1403. Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Toru Ikegami, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yoshihiko Maehara, Living donor liver transplantation in patients who have received pretransplant treatment for hepatocellular carcinoma, Transplantation, 10.1097/TP.0b013e318210de92, 91, 8, e61-e62, 2011.04.
1404. Ken Shirabe, Takashi Motomura, Jun Muto, Takeo Toshima, Rumi Matono, Yohei Mano, Kazuki Takeishi, Hideki Ijichi, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Tumor-infiltrating lymphocytes and hepatocellular carcinoma
Pathology and clinical management, International Journal of Clinical Oncology, 10.1007/s10147-010-0131-0, 15, 6, 552-558, 2010.12, The presence of tumor-infiltrating lymphocytes (TILs) in hepatocellular carcinoma (HCC) is relatively rare. The prognosis of patients with HCC and marked TILs is better than that of patients with HCC without TILs. TILs in HCC tissues are mainly T cells, and previous reports suggested that TILs might be important antitumor effector cells. TILs have been extensively analyzed, and subpopulations of CD3+, CD4+, and CD8+ T cells are often present in HCC. Some studies have reported that the percentage of CD8+ T cells, which might have cytotoxic activity, is decreased in tumors with TILs, as compared with noncancerous tissues. Although the antitumor effects of TILs seem to be impaired in HCCs, the underlying mechanism has remained unclear until quite recently. Pathological and in vitro studies have now shown that regulatory T cells play important roles in the deterioration of the antitumor effects of TILs. The aim of this review is to introduce recent pathological findings for TILs in HCC and to evaluate new therapeutic strategies in this field..
1405. T. Ikegami, Y. Soejima, K. Shirabe, A. Taketomi, T. Yoshizumi, H. Uchiyama, T. Fukuhara, T. Ikeda, Y. Maehara, Evolving strategies to prevent biliary strictures after living donor liver transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2010.07.091, 42, 9, 3624-3629, 2010.11, Introduction The optimal surgical technique has not been elucidated that reduces the occurrence of biliary strictures after living donor liver transplantation (LDLT). Method We performed retrospective analysis of 193 consecutive LDLTs, including 78 right and 115 left lobe grafts. An external biliary stent was used for all of the cases. Results The overall 1-, 3-, and 5-year biliary stricturefree survival rates were 87.5%, 85.3%, and 85.3%, respectively. The 1- and 3-year biliary stricturefree survival rates for duct-to-duct reconstruction were 86.9% and 84.9%, and those for hepaticojejunostomy were 90.1% and 80.8%, respectively. A multivariate analysis revealed that the original number of graft bile ducts greater than the number of external stents, right lobe grafts, bile leaks, and recipient age older than 60 years represented the significant risk factors (P < .05) to develop a biliary stricture after LDLT. All cases with biliary strictures (n = 61) were initially managed nonsurgically, but 4 patients ultimately required interventions. Conclusions Biliary reconstruction in LDLT using an appropriate number of external stents resulted in fairly acceptable outcomes. However, not only the proper use of stents or graft selection, but also nonsurgical factors, are important factors that determine the incidence of biliary strictures after LDLT..
1406. Akinobu Taketomi, Takasuke Fukuhara, Kazutoyo Morita, Hiroto Kayashima, Mizuki Ninomiya, Yoichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihko Maehara, Improved results of a surgical resection for the recurrence of hepatocellular carcinoma after living donor liver transplantation, Annals of Surgical Oncology, 10.1245/s10434-010-0999-y, 17, 9, 2283-2289, 2010.09, Purpose: This study was designed to analyze the clinical outcomes of the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and to evaluate the efficacy of a surgical resection in treating such a recurrence. Methods: A total of 101 adult LDLT recipients with HCC between 1996 and 2007, including 17 who had recurrent HCC, were reviewed. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics, laboratory valuables, and tumor characteristics were analyzed. Any medical or surgical treatments that had been administered for any recurrence also were considered. Results: The mean duration until the initial recurrence after LDLT and the mean duration until death after the initial recurrence were 12.9 months and 12.0 months, respectively. A univariate analysis showed that gender, interferon therapy, early posttransplant tumor recurrence, and eligibility for a surgical resection all had a beneficial impact on survival from tumor recurrence. A surgical resection of tumor relapse was the most important variable in our study, and therefore the patients were divided into two groups: surgical therapy group (n = 9), and nonsurgical therapy group (n = 7). Interestingly, the overall survival rates of the surgical group were significantly better than those of the nonsurgical group and were similar to that of the patients without HCC recurrence. Conclusions: Surgical therapy might be useful for patients who experience a recurrence of HCC after LDLT to improve their outcome, when such treatment is available..
1407. Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Natsumi Yamashita, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Mizuki Ninomiya, Yoshihiko Maehara, Living donor liver transplantation in patients older than 60 years, Transplantation, 10.1097/TP.0b013e3181e81b2d, 90, 4, 433-437, 2010.08, Background. Living donor liver transplantation (LDLT) has been performed in adult patients. However, there are a few reports on how recipient age affects the outcome of LDLT. This study assessed LDLT outcome in patients aged 60 years or older. Methods. A total of 267 patients were enrolled and classified into two groups: those younger than 60 years (younger group, n=210) and those aged 60 years or older (older group, n=57). The 6-month and 1-, 3-, and 5-year patient survivals and the incidence of complications were compared. Multivariate analysis was performed to identify the risk factors. Results. Fifty-five of 57 (96.5%) donors in the older group were younger than 50 years (range 25-47 years), whereas only 177 of 210 (84.3%) donors in the younger group were younger than 50 years (P<0.0001). The 6-month and 1-, 3-, and 5-year patient survival rates of the older group were 92.9%, 85.3%, 72.7%, and 70.3%, respectively, whereas those of the younger group were 87.4%, 85.8%, 80.2%, and 78.2%, respectively. Neither difference was significant. A multivariate analysis revealed that the presence of diabetes, lack of hepatocellular carcinoma, and Model for End-Stage Liver Disease (MELD) Score more than or equal to 20 were independent risk factors for survival less than 1 year after LDLT (P=0.0003, P=0.014, and P=0.041, respectively). Another multivariate analysis revealed that the lack of consanguinity, MELD Score more than or equal to 20, and male recipient were independent risk factors for death 1 year or more after LDLT (P=0.004, P=0.005, and P=0.015, respectively). Conclusion. Recipient age did not affect LDLT outcome when patients with MELD Score less than 20 received grafts from consanguineous donors..
1408. Tomonobu Gion, Akinobu Taketomi, Ken Shirabe, Hirofumi Hasegawa, Takayuki Hamatsu, Yo Ichi Yamashita, Keishi Sugimachi, Tomoharu Yoshizumi, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, The role of serum interleukin-8 in hepatic resections, Surgery today, 10.1007/s00595-008-4086-y, 40, 6, 543-548, 2010.06, Purpose: Interleukin-8 (IL-8) is a neutrophil chemotactic factor, which is associated with some inflammatory diseases and various types of surgical stress. The aim of this study was to investigate whether the early postoperative serum IL-8 level may potentially be a new indicator of a surgical stress in patients undergoing a hepatic resection. Methods: The serum IL-8 levels were measured in 37 patients who underwent a hepatectomy. The serum IL-8 levels were serially measured using an enzyme-linked immunosorbent assay both before and after a hepatic resection. In addition, the correlation between the postoperative IL-8 value and several clinical variables were examined. Results: The mean level of IL-8 significantly increased immediately after the operation (P < 0.01 vs before the operation) and decreased on the first postoperative day (POD 1, P < 0.05 vs after the operation). The early postoperative IL-8 levels positively correlated with the length of the procedure (r = 0.383; P < 0.05), the estimated blood loss (r = 0.483; P < 0.01) and the serum bilirubin level on POD 1 (r = 0.390; P < 0.05), and inversely correlated with the white blood cell counts (r = -0.388; P < 0.05) and lymphocyte counts on POD 1 (r = -0.424; P < 0.05). In a comparison of the postoperative IL-8 levels with the surgical factors, there was a significant difference in the extension of the resection (P < 0.05) and in blood transfusion. The patients with a fever of more than 38°C showed higher levels of IL-8 immediately after the operation than those without fever (P < 0.01). Conclusions: The early postoperative serum IL-8 level was found to correlate with the degree of the severity of surgery in patients undergoing a hepatic resection, and it is also considered to be a new indicator of surgical stress and liver injury..
1409. Takasuke Fukuhara, Toru Ikegami, Kazutoyo Morita, Kenji Umeda, Shigeru Ueda, Shigeyuki Nagata, Keishi Sugimachi, Tomonobu Gion, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Impact of preoperative serum sodium concentration in living donor liver transplantatio, Journal of Gastroenterology and Hepatology (Australia), 10.1111/j.1440-1746.2009.06162.x, 25, 5, 978-984, 2010.05, Background and Aims: The importance of hyponatremia in deceased donor liver transplantation (DDLT) has been recently discussed frequently. However, its impact on the outcomes in living donor liver transplantation (LDLT) has not yet been elucidated. The current study was designed to demonstrate the impact of pre-transplant sodium concentration on postoperative clinical outcomes. Methods: One hundred and thirty-four patients who underwent LDLT for end-stage liver diseases were examined to evaluate the significance of pre-transplant hyponatremia (Na ≤ 130 mEq/L) on the short-term clinical outcomes and the efficacy of the Model for End-Stage Liver Disease and serum sodium (MELD-Na) score using the sodium concentration and original MELD score. Results: The preoperative sodium and MELD score for all patients were 133.9 mEq/L (range: 109-142) and 16.2 (range: 6-38), respectively. According to a multivariate analysis, not only the MELD score (P = 0.030) but also the sodium concentration (P = 0.005) were found to be significant predictive factors for short-term graft survival. Preoperative hyponatremia was a significant risk factor for the occurrence of sepsis (P < 0.001), renal dysfunction (P < 0.001) and encephalopathy (P = 0.026). The MELD-Na score was 19.6 (range: 6-51) and the area under the receiver-operator curve of that (c-statistics: 0.867) was higher than MELD score and sodium concentration (c-statistics: 0.820 and 0.842, respectively). Conclusion: Preoperative hyponatremia was a significant risk for postoperative complications and short-term graft loss. The addition of sodium concentration to MELD score might therefore be an effective predictor for post-transplant short-term mortality in LDLT..
1410. Keishi Sugimachi, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Yo Ichi Yamashita, Kenji Umeda, Kazutoyo Morita, Yoshihiko Maehara, Successful curative extracorporeal hepatic resection for far-advanced hepatocellular carcinoma in an adolescent patient, Liver Transplantation, 10.1002/lt.22051, 16, 5, 685-687, 2010.05.
1411. Yuuta Kasagi, Koji Yamazaki, Akihiko Nakashima, Takeshi Yamana, Nami Yamashita, Hiroto Kayashima, Yuji Hoshino, Mayumi Ishida, Tomoharu Yoshizumi, Noriaki Sadanaga, Atsushi Fukuda, Hiroshi Matsuura, Kenichiro Okadome, Chondroblastic osteosarcoma arising from the pleura
Report of a case, Surgery today, 10.1007/s00595-009-3995-8, 39, 12, 1064-1067, 2009.12, Extraskeletal osteosarcoma is an uncommon malignant neoplasm. The origin of osteosarcoma in the pleura is extremely rare, with only four such cases so far documented in the literature to the best of our knowledge. We herein report the case of a 64-year-old Japanese man in whom a left pneumonectomy and pleurectomy were carried out to remove a huge tumor. The pathological examination confi rmed a diagnosis of chondroblastic osteosarcoma that had originally arisen from the pleura..
1412. T. Ikegami, A. Taketomi, Y. Soejima, T. Yoshizumi, T. Fukuhara, K. Kotoh, S. Shimoda, M. Kato, Y. Maehara, The Benefits of Interferon Treatment in Patients Without Sustained Viral Response After Living Donor Liver Transplantation for Hepatitis C, Transplantation Proceedings, 10.1016/j.transproceed.2009.08.070, 41, 10, 4246-4252, 2009.12, Although it has been recognized that interferon (IFN) treatment is crucial for recurrent hepatitis C after liver transplantation, its benefits have not been determined among patients without a sustained viral response (SVR). Methods: Eighty patients who received IFN plus ribavirin treatment after living donor liver transplantation were grouped as follows: group I (n = 18) SVR; group II (n = 25) no-SVR but viral response [VR] positive; Group III (n = 13) no-VR but biochemical response [BR] positive; and group IV (n = 24) no-VR and no-BR. Results: In groups II and III, not only the histological activity grade and fibrosis stage, but also the serum parameters including transaminases and type IV collagen were stable for 3 years after induction of IFN-based treatment. In group I, the activity grade and fibrosis stage significantly improved (P < .01). In group IV, the fibrosis stage significantly deteriorated (P < .01); the serum transaminases and type IV collagen were significantly higher than the other groups (P < .01). The mean duration of IFN treatment was significantly longer among group II (96 weeks) compared with the other cohorts (P < .05). The 5-year graft survival rate in groups II (91%) and III (100%) were comparable to those of group I (100%); group IV (62%) was significantly lower than the other groups (P < .05). Conclusion: IFN treatment was beneficial even among subjects with IFN-dependent VR or BR, although they did not achieve SVR..
1413. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Tashiharu Salbara, Takashi Nishizaki, Yoshihiko Maehara, Recurrent familial hypobetalipoproteinemia-induced nonalcoholic fatty liver disease after living donor liver transplantation, Liver Transplantation, 10.1002/lt.21766, 15, 7, 806-809, 2009.08, Familial hypobetalipoproteinemia (FHBL) is one of the causes of nonalcoholic steatohepatitis (NASH) and a codominant disorder. Patients heterozygous for FHBL may be asymptomatic, although they demonstrate low plasma levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Here we report a nonobese 54-year-old man with decompensated liver cirrhosis who underwent living donor liver transplantation with his son as the donor. Low albuminemia and refractory ascites persisted after transplantation. A biopsy specimen obtained 11 months after liver transplantation revealed severe steatosis and fibrosis, and recurrent NASH was diagnosed on the basis of pathological findings. Both the patient's and donor's laboratory tests demonstrated low LDL cholesterol and apolipoprotein levels. Because mutations in messenger RNAs of microsomal triglyceride transfer protein and apolipoprotein B genes were excluded neither in the recipient nor in the donor, both were clinically diagnosed as being heterozygous for FHBL. We successfully treated the recipient with heterozygous FHBL-induced recurrent NASH after liver transplantation using our diet and exercise programs..
1414. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Tomohiro Iguchi, Naotaka Hashimoto, Yoshihiko Maehara, Rituximab, IVIG, and plasma exchange without graft local infusion treatment
A new protocol in ABO incompatible living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3181adcae6, 88, 3, 303-307, 2009.08, BACKGROUND. Although graft local infusion (GLI) treatment via the portal vein or the hepatic artery has been the pivotal strategy in ABO incompatible (ABOi) living donor liver transplantation (LDLT) in Japan, the procedure is associated with a high rate of catheter-associated complications. METHODS. A new ABOi-LDLT protocol has been implemented using rituximab, intravenous immune globulin (IVIG), plasma exchange (PE), and splenectomy, without using GLI, on four patients, since 2007. Three other patients, treated before 2007, received GLI. RESULTS. Three of the four patients with liver cirrhosis received rituximab over 3 weeks before LDLT, followed by PEs and post-LDLT IVIG, resulting in no rebound elevation of the isoagglutinin titers. The remaining patient, with fulminant hepatitis, received rituximab 3 days before the LDLT, resulting in antibody-mediated rejection, successfully treated by IVIG and PE. All four patients that were treated with the new protocol are alive, 26, 8, 6, and 5 months after ABOi-LDLT with normal liver function. Two of the three other patients with GLI, before 2007, had catheter-associated complications, including one graft loss. CONCLUSION. The new ABOi-LDLT protocol using rituximab, IVIG, and PE, without the use of GLI, therefore seems to be a safe and an effective treatment modality..
1415. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Shigeyuki Nagata, Yoshihiko Maehara, Potential risk in using hepatic veins of a native liver for reconstructing accessory veins in right lobe living donor graft, Transplantation, 10.1097/TP.0b013e3181aae502, 88, 1, 143-144, 2009.07.
1416. T. Yoshizumi, Y. Ikeda, Y. Kaneda, K. Sueishi, Ex Vivo Transfer of Nuclear Factor-κB Decoy Ameliorates Hepatic Cold Ischemia/Reperfusion Injury, Transplantation Proceedings, 10.1016/j.transproceed.2008.10.101, 41, 5, 1504-1507, 2009.06, Cold ischemia/reperfusion injury of the hepatic graft has been attributed to the release of various inflammatory cytokines. Specific inhibition of these cytokines may improve viability of the hepatic graft upon reperfusion. Herein we have assessed the efficacy of cis element decoy against nuclear factor-κB binding site delivery to the hepatic tissue in a rodent liver transplantation model. At 8 hours after reperfusion of the liver, significant reduction was noted in the livers treated with decoy in the release of cytosolic enzymes from the hepatocytes and in serum tumor necrosis factor α (P < .05). The neutrophilic infiltration into the hepatic grafts was significantly suppressed in the livers treated with decoy oligodeoxynucleotides (ODNs). Decoy ODNs against nuclear factor-κB binding site delivery improved the viability of the hepatic graft against cold ischemia/reperfusion injury in the rodent liver transplantation model..
1417. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hirofumi Kawanaka, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Hypersplenism after living donor liver transplantation, Hepato-gastroenterology, 56, 91-92, 778-782, 2009.05, Background/Aims: It has not determined whether post-transplant persistent hypersplenism (PTPH) occurs after living donor liver transplantation (LDLT). Methodology: One hundred and ninety-four patients who survived more than 6 months after LDLTs were examined for the evaluation to determine the incidence of PTPH (leukocyte counts <3,500/μL and/or platelet counts <7.5×104/μL). In addition, 154 patients without a splenectomy were evaluated for the risk factors for PTPH. Results: The incidence of PTPH was 20.1% (n=31/154), and the occurrence ranged between 1.1 and 9.9 years after the LDLT, with the mean follow-up periods of 3.3±2.5 years. Multivariate analysis showed that portal pressure >30mmHg at the time of the laparotomy (p<0.01) and post-LDLT small for size syndrome (p<0.01) are risk factors for PTPH. For those with severe portal hypertension (>30 mmHg at laparotomy), the splenectomy tended to give better survival rate (p=0.09) without increasing the rate of septic complications. Conclusions: Hypersplenism did persist in a proportion of patients after LDLT. A high-risk for PTPH, especially severe portal hypertension, may be an indication for a splenectomy during LDLT in order to achieve uncomplicated post-transplant recovery..
1418. Yusuke Arakawa, Mitsuo Shimada, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Hirohumi Kanemura, Beneficial effects of splenectomy on massive hepatectomy model in rats, Hepatology Research, 10.1111/j.1872-034X.2008.00469.x, 39, 4, 391-397, 2009.04, Aim: Possible spleno-hepatic relationships during hepatectomy remain unclear. The purpose of this study was to investigate the impact of splenectomy during massive hepatectomy in rats. Methods: Rats were divided into the following two groups: 90% hepatectomy (Hx group), hepatectomy with splenectomy (Hx+Sp group). The following parameters were evaluated; survival rate, biochemical parameters, quantitative RT-PCR for hemeoxygenase-1 (HO-1) and tumor necrosing factor α (TNFα), immunohistochemical staining for HO-1, proliferating cell nuclear antigen labeling index and liver weights. Results: The survival rate after massive hepatectomy significantly improved in Hx+Sp group as well as serum biochemical parameters, compared with Hx group (P < 0.05). HO-1 positive hepatocytes and its mRNA expression significantly increased and TNFα mRNA expression significantly decreased in Hx+Sp group compared with Hx group (P < 0.05). Moreover, liver regeneration was significantly accelerated at 48 and 72 h after hepatectomy in Hx+Sp group. Conclusions: Splenectomy had beneficial effects on massive hepatectomy by ameliorating liver injuries and promoting preferable liver regeneration..
1419. Toru Ikegami, Mitsuo Shimada, Satoru Imura, Yuji Soejima, Tomoharu Yoshizumi, Jun Hanaoka, Yuji Morine, Yoshihiko Maehara, The changes of the medial right lobe, transplanted with left lobe liver graft from living donors, Transplantation, 10.1097/TP.0b013e318195c2a3, 87, 5, 698-703, 2009.03, Background. Procurement of left lobe (LL) living donor graft with medial right lobe (mRL) might be an innovative technique. Methods. The grafts were procured from a living donor, exposing the right anterior Glissonean pedicles, after confirmation of the demarcation line by test-clamping of the right Glissonean pedicle. Based on serial computed tomography, the increase in the graft volume (GV) after addition of mRL and changes in volumes were evaluated. Results. The addition of mRL (n=7) increased GV by 48±9 g, which corresponded to a 4% increase in GV-to-standard liver volume ratio. After transplantation, mRL volume has increased in all cases. The regeneration rate of the mRL and other LL segments 1 month after transplantation was 61%±18% and 146%±15%, respectively. Viable hepatic parenchyma with marginal bile duct dilatations in transplanted mRL was observed in all the cases. Marginal enhancement was observed in those cases with promoted regeneration of transplanted mRL. In the cranial part of the mRL, portal branching from the left portal vein, over the middle hepatic vein, was observed in all cases. Conclusion. This technique affords an increase in GV in living donor LL procurement, and should increases the application of LL grafts in living donor liver transplantation..
1420. Toru Ikegami, Takeo Toshima, Kazuki Takeishi, Yuji Soejima, Hirofumi Kawanaka, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Bloodless Splenectomy During Liver Transplantation for Terminal Liver Diseases with Portal Hypertension, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2008.10.034, 208, 2, e1-e4, 2009.02.
1421. Akinobu Taketomi, Hiroto Kayashima, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, Donor risk in adult-to-adult living donor liver transplantation
Impact of left lobe graft, Transplantation, 10.1097/TP.0b013e3181943d46, 87, 3, 445-450, 2009.02, Background.: To ensure donor safety in adult-to-adult living donor liver transplantation, we established a selection criterion for donors in which left lobe (LL) was the first choice of graft. Methods.: Two hundred six consecutive donors were retrospectively studied. Donors were divided into two groups according to graft type: LL graft (n=137) and right lobe (RL) graft (n=69). Results.: Although mean intraoperative blood loss of LL was significantly increased compared with RL, mean peak postoperative total bilirubin levels and duration of hospital stay after surgery were significantly less for LL than RL (P<0.05). No donor died or suffered a life-threatening complication during the study period. The overall complication rate was 34.0%, including biliary complications in 5.3%. The number of biliary complications was four (2.9%) in LL and seven (10.1%) in RL (P<0.05). Logistic regression analysis revealed that only graft type (LL vs. RL) is significantly related to the occurrence of biliary complications (odds ratio 0.11; P=0.0012). The cumulative overall graft survival rates in the recipients with LL were not significantly different from that in the recipients with RL. Conclusions.: LL grafting should be considered favorably when selecting donors for adult-to-adult living donor liver transplantation..
1422. Akinobu Taketomi, Kensaku Sanefuji, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uhciyama, Toru Ikegami, Noboru Harada, Yoichi Yamashita, Keishi Sugimachi, Hiroto Kayashima, Tomohiro Iguchi, Yoshihko Maehara, Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3181943bee, 87, 4, 531-537, 2009.02, BACKGROUNDS.: Because many patients who did not meet the Milan criteria have survived long after undergoing living donor liver transplantation (LDLT), extended criteria for recipient with hepatocellular carcinoma (HCC) are therefore considered to be necessary. METHODS AND RESULTS.: A total of 90 consecutive adult LDLT recipients with HCC between 1996 and 2007 were reviewed. The recurrence-free survival rates of all 90 patients were 86.0%, 81.3%, and 81.3% at 1, 3, and 5 years, respectively. Fourteen of 90 patients developed a recurrence of tumor after the LDLT. The tumor recurrences were diagnosed within 1 year after the LDLT in 11 (78.6%) patients. In a multivariate analysis, both the tumor size of less than 5 cm (P=0.0202) and the des-gamma-carboxy prothrombin (DCP) level of less than 300 mAU/mL (P=0.0001) were found to be favorable independent factors for the recurrence of HCC after LDLT. Therefore, the authors devised new selection criteria for HCC patients (a tumor size of <5 cm or a DCP of <300 mAU/mL). The 1-, 3-, and 5-year overall or recurrence-free survival rates of the 85 patients who met the new criteria were 92.3%, 85.9%, and 82.7%, or 90.5%, 87.0%, and 87.0%, respectively, which were significantly different from those of the five patients who did not meet the new criteria (P<0.0001). CONCLUSIONS.: A combination of two factors, namely the tumor size and the DCP level, was found to be useful for expanding the selection of LDLT candidates for HCC..
1423. Kensaku Sanefuji, Hiroto Kayashima, Tomohiro Iguchi, Keishi Sugimachi, Yo Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Takashi Nishizaki, Akinobu Taketomi, Yoshihiko Maehara, Characterization of hepatocellular carcinoma developed after achieving sustained virological response to interferon therapy for hepatitis C, Journal of Surgical Oncology, 10.1002/jso.21176, 99, 1, 32-37, 2009.01, Background: Interferon (IFN) reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). However, HCC develops in the some patients who have achieved a sustained virological response (SVR). The aim of this study was to clarify the features and prognosis of SVR patients who developed HCC. Materials and Methods: Twenty-six patients who underwent curative hepatectomy for initial HCC after IFN therapy were closely investigated. Twenty patients who were seropositive for HCV-RNA (non-SVR), and a further 6 patients who achieved SVRs (SVR) were included. We analyzed the clinicopathological features, immunological expression levels of p53 and whether HCV-RNA is present in the excised liver. Results: The liver functions of the SVR group were almost better than those of the non-SVR group. However, there was no significant difference in pathological features, surgical factors and prognosis between the groups. In one case with SVR out of eight specimens tested was HCV-RNA detected in the non-cancerous tissue. Immunohistochemistry revealed overexpression of p53 in eight HCCs (100%) from SVR patients. Conclusion: Recurrent HCC still developed after the curative hepatectomy, even if viral elimination had been successful. And molecular alterations in hepatocarcinogenesis of SVR patients might be different from those of CHC patients..
1424. Yuji Soejima, Takasuke Fukuhara, Kazutoyo Morita, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara, A simple hilar dissection technique preserving maximum blood supply to the bile duct in living donor liver transplantation, Transplantation, 10.1097/TP.0b013e318188d4dc, 86, 10, 1468-1469, 2008.11, Duct-to-duct reconstruction is associated with a higher incidence in biliary strictures in living donor liver transplantation (LDLT). However, a standard dissection technique for the recipient's bile duct has not been established. Here, we describe a simple bile duct dissection technique preserving maximum vascular integrity during total hepatectomy of the recipient. The present technique might facilitate duct-to-duct bile duct reconstruction in both right and left lobe LDLT and, thus, contribute to reduce biliary complications such as biliary strictures. We believe that this technique can be a standard in the field of LDLT..
1425. Takuya Tokunaga, Toru Ikegami, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Hisamitsu Shinohara, Mitsuo Shimada, Beneficial effects of fluvastatin on liver microcirculation and regeneration after massive hepatectomy in rats, Digestive Diseases and Sciences, 10.1007/s10620-008-0241-y, 53, 11, 2989-2994, 2008.11, Fluvastatin, the first entirely synthetic statin, has a significant cholesterol-lowing effect comparable with other statins. In addition, it has been shown to inhibit oxidative stress and improve vascular endothelial function. The aim of this study was to clarify the pretreatment effects of fluvastatin on liver function after massive hepatectomy in rats. Six-week-old male Wister rats were divided into two groups: a fluvastatin group (group F), pretreated with oral administration of fluvastatin (20 mg/kg per day) for 2 days before 90% hepatectomy; and a control group (group C), pretreated with vehicle for 2 days before hepatectomy. Animals were sacrificed at 0, 12, 24, 48, and 72 h after hepatectomy. The liver regeneration rate, liver function tests, and hepatic stellate cell activation were examined. The liver regeneration rate in group F was significantly higher at 72 h after hepatectomy (P < 0.05). The serum level of total bilirubin in group F was significantly lower at 48 h after hepatectomy (P < 0.05). Sinusoidal area in group F was maintained histologically. Furthermore, the expression of alpha smooth-muscle actin (α-SMA) protein in the liver was inhibited in group F at 48 h after hepatectomy. This study demonstrated the beneficial effects of fluvastatin in a lethal massive hepatectomy model using rats, with improved hepatic regeneration and microcirculations, by inhibiting the activation of hepatic stellate cells..
1426. Toru Ikegami, Akinobu Taketomi, Ryuji Ohta, Yiji Soejima, Tomoharu Yoshizumi, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, The risks of HBV infection after liver transplantation from HBc antibody positive donor to HBs antibody positive recipient, Hepato-gastroenterology, 55, 88, 2162-2165, 2008.11, The rate of de novo hepatitis B infection, after liver transplantation from a hepatitis B core antibody (HBcAb) (+) donor to a surface antibody (HBsAb) (+) recipient bas not yet elucidated. Four recipients with HBsAb (+) and HBcAb, (+), who received living donor grafts from HBcAb (+) donors were herein reviewed. They received lamivudine monotherapy: three patients with HBsAb titer >10 IU/L did not demonstrate the onset of HBsAg, whereas one patient with HBsAb titer <10 IU/L developed hepatitis B antigen (HBsAg) 4 years after transplantation. An HBsAb (+) patient with a titer of >10 IU/L is therefore considered not to require combination therapy when receiving an HBcAb (+) liver graft. However, a great deal of caution is necessary in patients with a negative or low HBsAb titers <10 IU/L..
1427. Y. Soejima, S. Ueda, K. Sanefuji, H. Kayashima, T. Yoshizumi, T. Ikegami, Y. Yamashita, K. Sugimachi, T. Iguchi, A. Taketomi, Y. Maehara, Sequential pancreaticoduodenectomy after living donor liver transplantation for cholagiocacinoma, American Journal of Transplantation, 10.1111/j.1600-6143.2008.02346.x, 8, 10, 2158-2162, 2008.10, Liver transplantation (LT) for patients with primary sclerosing cholangitis (PSC) is often contraindicated due to concomitant occurrence of cholangiocarcinoma (CC). Cases of simultaneous pancreaticoduodenectomy (PD) with LT have been sporadically reported; however, the applicability of such an invasive procedure to patients with CC has not been validated. We report here a case of sequential PD performed 44 days after a successful living donor liver transplantation (LDLT) using a left lobe graft. Although a clear pancreatic juice leakage through the drain persisted for days after surgery, the patient recovered from the complication and was discharged 32 days after the procedure. Currently, 1 year after LDLT, the patient is doing well with no evidence of recurrence. In conclusion, a sequential PD following LDLT is a safe and feasible option to treat CC complicating PSC. Long-term follow-up and accumulation of cases are necessary to evaluate the effectiveness of this procedure for this complicated disease..
1428. Hiroto Kayashima, Akinobu Taketomi, Yusuke Yonemura, Hideki Ijichi, Noboru Harada, Tomoharu Yoshizumi, Yuji Soejima, Kengo Yoshimitsu, Yoshihiko Maehara, Accuracy of an age-adjusted formula in assessing the graft volume in liver donor liver transplantation, Liver Transplantation, 10.1002/lt.21547, 14, 9, 1366-1371, 2008.09, In living donor liver transplantation, the estimated graft volume (GV) from young donors tends to be overestimated. One reason for this error may be a decrease in GV due to dehydration by University of Wisconsin (UW) solution. The aim of this study was to clarify (1) the usefulness of an age-adjusted formula and (2) the correlation between the decrease in GV and donor age. First, we created the age-adjusted formula using regression analysis retrospectively in 167 donors, and we evaluated the difference in the error ratio of GV from the age-adjusted formula and 3-dimensional computed tomography (3D-CT) prospectively in 49 donors. Second, we measured intraoperative GV both before and after flushing with UW solution and calculated the decrease ratio, and we then evaluated the difference in the decrease ratio between young donors and older donors prospectively in 41 donors. The age-adjusted formula was created as follows: age-adjusted GV = 70.767 + (0.703 × GV estimated with 3D-CT volumetry) + (1.298 × donor age). The mean error ratio for the age-adjusted formula (9.6%) was significantly lower than that from 3D-CT (14.0%). The mean decrease ratio in all 41 donors was 5.4%, and that in young donors (6.9%) was significantly higher than that in older donors (4.4%). In conclusion, although younger donor age is a major factor for estimation errors in hepatic volumetry, our age-adjusted formula is very useful in reducing the error in estimating GV..
1429. Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Noboru Harada, Yo Ichi Yamashita, Hirofumi Kawanaka, Takashi Nishizak, Yoshihiko Maehara, The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft, Transplant International, 10.1111/j.1432-2277.2008.00678.x, 21, 9, 833-842, 2008.09, Small-for-size (SFS) graft syndrome is one of the major causes of graft loss in living donor liver transplantation (LDLT). We examined whether splenectomy is beneficial for overcoming SFS graft syndrome in LDLT. The patients were classified into two groups: the Sp (-) group (n = 69), in which splenectomy was not performed, and the Sp (+) group (n = 44), in which it was. The incidence of SFS graft syndrome was investigated. Risk factors of SFS graft syndrome were identified by univariate- and multivariate analysis. To clarify whether splenectomy is beneficial for patients with a SFS graft, subgroup analysis was performed for patients who had a graft weight-to-standard liver weight (GW-SLW) ratio of 40% or less (n = 50). Thirty-one of 113 patients developed SFS graft syndrome. A multivariate analysis identified that having a male donor was an independent risk factor of SFS graft syndrome. SFS graft syndrome occurred in 11 of 50 patients with a GW-SLW ratio <40%, and Sp (-) was an independent risk factor for the occurrence of SFS graft syndrome in patients (P = 0.014). Simultaneous splenectomy is favorable for overcoming SFS graft syndrome in LDLT patients with a GW-SLW of 40% or less..
1430. Toru Ikegami, Mitsuo Shimada, Satoru Imura, Tomoharu Yoshizumi, Yusuke Arakawa, Takuya Tokunaga, Yuji Morine, Hirofumi Kanemura, The timing of liver transplantation after primary hepatectomy for hepatocellular carcinoma
A special reference to recurrence pattern and milan criteria, Transplantation, 10.1097/TP.0b013e3181814de2, 86, 5, 641-646, 2008.09, INTRODUCTION.: Hepatic resection (HR) is commonly applied as first-line treatment of hepatocellular carcinoma (HCC) even in the era of liver transplantation (LT). METHODS.: Outcomes and detailed recurrence pattern of 80 patients, who underwent curative HR for HCC were examined referring to Milan criteria. RESULTS.: (I) After HR for HCCs exceeding Milan criteria (n=41), recurrence within the criteria was observed in 13 patients (group-A) and recurrence not-meeting the criteria was observed in 22 patients (group-B). group-A showed better 3-year recurrence-free survival rate than group-B (85.7% vs. 23.9%, P<0.05). Tumor size more than or equal to 6 cm was identified as the significant factor for having recurrence as in group-A pattern (P<0.05). Among the patients in group-A, re-recurrence after treating recurrent HCC was observed in eight patients (61.5%) with increased rate of extra-Milan criteria recurrence at 12 months from the initial recurrence. (II) After HR for HCCs meeting Milan criteria (n=39), recurrences within the criteria was observed in 15 patients (group-C) and recurrence not-meeting the criteria was observed in five patients (group-D). The 3-year recurrence-free survival rate was 62.8% in group-C and 40.0% in group-D (P<0.05). Increased rate of extra-Milan re-recurrence was observed later than 12 months from the recurrence in group-C. CONCLUSIONS.: For HCCs not meeting Milan criteria, secondary LT after primary HR could be applied for a proportion of cases with less aggressiveness. For those meeting Milan criteria, primary LT should be the first therapeutic option. However, secondary LT could be offered for those with re-recurrence within criteria after primary HR..
1431. Satoru Imura, Mitsuo Shimada, Kotaro Miyake, Tetsuya Ikemoto, Yuji Marine, Tomoharu Yoshizumi, A new technique to acquire additional liver volume for left lobe graft in living donor liver transplantation, Hepato-gastroenterology, 55, 85, 1206-1210, 2008.07, Background/Aims: Left lobe graft is an ideal option to minimize potential risk for the donor in adult living-donor liver transplantation (LDLT). However, its use is restricted due to size limitations. The purpose of this study was to determine the impact of a new technique for the acquisition of additional liver volume for left lobe graft. Methodology: Three donors underwent left hepatic lobectomy by exploiting a new technique as follows: a demarcation line was marked by clamping the right first Glisson's pedicle. A parenchymal transection plane was located 1cm right side from the demarcation line and just on the left side of the right anterior Glisson's pedicle. A part of the anterior segment added to the left lobe graft by this procedure belonged to right anterior segment by preoperative CT. The preoperative volumetry of the liver was performed using the 3D-CT software, which was able to calculate total liver volume and the volume of each vessel's territories. Additional liver volume was calculated by preoperative CT scan and defined as part of the perfusion area by the right anterior portal branch. Blood perfusion of the additional liver area was postoperatively assessed by dynamic CT, and graft outcome was also evaluated. Results: An additional gain ranged from 40mL to 51mL (mean 41.8mL). GV/SLV was 35.7, 60.0, and 41.0%. The rate of additional volume in GV/SLV ranged from 7.2-8.4% (mean 7.6%). All grafts functioned well. The CT scan performed on early postoperative period confirmed excellent blood perfusion the additional segment. No complication attributable to small-for-size graft was noted. Conclusions: This new technique for left lobe graft harvesting proved a promising approach to gain additional volume, thereby avoiding small-for-size graft in adult LDLT..
1432. Tomoharu Yoshizumi, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hiroto Kayashima, Yo Ichi Yamashita, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, Graft size, donor age, and patient status are the indicators of early graft function after living donor liver transplantation, Liver Transplantation, 10.1002/lt.21462, 14, 7, 1007-1013, 2008.07, No reliable model for predicting early graft function and patient survival after living donor liver transplantation (LDLT) exists. The aim of this study was to establish a new formula for predicting early graft function and prognosis using technetium-99m galactosyl-human serum albumin (Tc-GSA) liver scintigraphy. The ratio of the hepatic uptake ratio of Tc-GSA to the clearance index of Tc-GSA (LHL/HH) was determined 7 days after LDLT. There were 22 patients with a ratio greater than 1.3 and 6 patients with a ratio less than 1.3. Graft function on the 14th postoperative day (POD) was compared between the 2 groups. A new formula to predict the LHL/HH score was established as follows: LHL/HH (predictive score) = 0.011 × graft weight (%) - 0.016 × donor age - 0.008 × Model for End-Stage Liver Disease score - 0. 15 × shunt (if present) + 1.757 (r2 = 0.497, P < 0.01). This predicted LHL/HH ratio was compared to the graft function on POD 14 for 110 LDLT patients. The total bilirubin JB) and prothrombin time international normalized ratio (PT-INR) in the group with an LHL/HH score ≥ 1.3 were lower than those in the group with an LHL/HH score < 1.3. The TB, PT-INR, and volume of ascites in the group with a predictive score ≥ 1.3 (n = 86) were lower than those in the group with a score < 1.3 (n = 24). The 6-month survival probability was improved in the group with a predictive score ≥ 1.3. In conclusion, this preoperative calculated LHL/HH score is correlated with graft function and short-term prognosis. Thus, this predictive model may allow transplant surgeons to use a living donor left lobe graft with greater confidence..
1433. Toru Ikegami, Yuji Soejima, Ryuji Ohta, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Yoshihiko Maehara, Living donor liver transplantation for hepatitis B associated liver diseases
A 10-year experience in a single center, Hepato-gastroenterology, 55, 85, 1445-1449, 2008.07, Background/Aims: Hepatic failure associated with hepatitis B virus (HBV) is one of the main indications for living donor liver transplantation (LDLT). Methodology: Twenty-nine LDLTs, including liver cirrhosis due to HBV (LC-B) (n=17) and fulminant hepatitis B (FH-B) (n=12) were reviewed. Prophylaxis for reinfection was performed with a combination of lamivudine, or hepatitis B immune globulin (HBIG) or adefovir, depending on the viral status. The changes in serological markers, recurrence and survival rate were examined. Results: There were 3 patients with re-emergencies of HBV surface antigen (HBsAg): suspension of HBIG for giving vaccination for HBV (n=1), HBsAg positive donor (n=1) and non-compliance for HBIG (n=1). All patients with YMDD mutants (n=9), except the case with HBsAg positive donor (n=1), were successfully protected by the triple therapy of lamivudine, adefovir and HBIG. No graft loss was due to the recurrence of HBV. Conclusion: The basic strategy using a combination of HBIG and antiviral agents gave acceptable long-term outcomes for LDLT for HBV associated liver diseases. The close monitoring of HBV viral status after transplantation is still crucial in managing these patients..
1434. T. Ikegami, A. Taketomi, R. Ohta, Y. Soejima, T. Yoshizumi, M. Shimada, Y. Maehara, Donor Age in Living Donor Liver Transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2008.02.084, 40, 5, 1471-1475, 2008.06, Background: We sought to elucidate the influence of donor age in living donor liver transplantation (LDLT) using either left lobe (LL) or right lobe (RL) grafts. Methods: Recipients (n = 232) were categorized as: group O/LL (LL, donor age >50, n = 20); group Y/LL (LL, donor age ≤50, n = 140); Group O/RL (RL, donor age >50, n = 12); and group Y/RL (RL, donor age ≤50, n = 61). We compared post-LDLT graft functions. Results: Among LL LDLT, the incidence of small-for-size syndrome was significantly greater for group O/LL compared with group Y/LL (60.0% vs 16.3%, P < .01). However, the cumulative 5-year graft survivals were 73.8% in group O and 76.7% in group Y without substantial difference. In RL LDLT, the post-LDLT morbidity and mortality were similar for group O/RL and group Y/RL. Conclusion: Partial liver grafts, even though LL grafts, from older donors can be used safely with caution in LDLT..
1435. T. Yoshizumi, A. Taketomi, H. Kayashima, Y. Yonemura, N. Harada, H. Ijichi, Y. Soejima, T. Nishizaki, Y. Maehara, Estimation of Standard Liver Volume for Japanese Adults, Transplantation Proceedings, 10.1016/j.transproceed.2008.02.082, 40, 5, 1456-1460, 2008.06, Introduction: Accurate pretransplant estimation of the recipient's standard liver volume (SLV) is important. The purpose of this study was to compare reported formulas for clinical estimation of liver volume among Japanese adults. Methods: We reviewed data on 70 healthy adults (46 men, 24 women, ages 20 to 65 years old) evaluated for living donor liver transplantation. Liver volume (LV) was measured using two- or three-dimensional computed tomography volumetry (CTV). The formulas of DeLand (LV = 1020 × body surface area [BSA] - 220), Urata (LV = 706.2 × BSA + 2.4), Noda (LV = 50.12 × BW0.78), Heinemann (LV = 1072.8 × BSA - 345.7), Vauthey (LV = 18.51 × BW + 191.8) and Yoshizumi (LV = 772 × BSA) were applied to estimate LV. We calculated the differences for individual donors betwen CTV and LV estimated by each formula. Results: Mean LVs as estimated by the formulae of DeLand and Heinemann et al were significantly greater (P < .01) than the mean CTV, while LV estimated by the formula of Urata was significantly less (P < .05) than the CTV. The formulas of DeLand and Heinemann overestimated LV, while the formula of Urata underestimated it. The formulae of Noda et al and Yoshizumi et al tended to underestimate the LV when the CTV was greater than 1600 cm3. When the Yoshizumi formula was applied, the number of donors with an acceptable difference (±15%) between CTV and estimated LV was 55 (78.6%). Conclusions: The Yoshizumi formula was applicable, especially for patients with a BSA < 2.0, whereas the well-known Urata formula made LV underestimates..
1436. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Characteristics of biliary reconstruction using a T-tube as compared with other methods in left-lobe adult living-donor liver transplantation, Journal of Hepato-Biliary-Pancreatic Surgery, 10.1007/s00534-007-1259-9, 15, 3, 346-347, 2008.05.
1437. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Shinji Itoh, Yo Ichi Yamashita, Yoshihiko Maehara, Hilar anatomical variations in living-donor liver transplantation using right-lobe grafts, Digestive surgery, 10.1159/000121907, 25, 2, 117-123, 2008.05, Background: Living-donor liver transplantation using a right-lobe graft has increased the frequency of hilar anatomical variations despite its advantage of a larger graft volume. Methods: Sixty-seven living-donor liver transplantations using right-lobe grafts are reviewed, regarding the surgical anatomy of hilar vascular and biliary systems. Results: The portal anatomy was classified into four types. The incidence of double portal vein was 6.0% (n = 4), and for such cases a unified orifice (n = 1) or a Y-graft (n = 3) was used for reconstruction. The arterial system was classified into five types. The incidence of arterial complications was 6.0% (n = 4), all of which occurred in cases where the graft artery was connected to the recipient's right hepatic artery. The biliary system was classified into four types. The incidence of a double bile duct was 7.5% (n = 5), and that of a unified one was 29.8% (n = 20). Hepaticojejunostomy was more prone to biliary sepsis (25.0%) and bile leakage (18.8%) than duct-to-duct connection (0 and 2%, respectively). Conclusion: Hilar anatomical variations in right-lobe living-donor liver transplantation could be managed after preoperative detailed evaluation of the graft and intraoperative appropriate surgical decision and techniques..
1438. Yuji Soejima, Naoyuki Ueda, Takasuke Fukuhara, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara, One-step venous reconstruction for a right lobe graft with multiple venous orifices in living donor liver transplantation, Liver Transplantation, 10.1002/lt.21401, 14, 5, 706-708, 2008.05.
1439. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoshihiko Maehara, Stenotrophomonas maltophilia bacteremia after living donor liver transplantation
Report of a case, Surgery today, 10.1007/s00595-007-3622-5, 38, 5, 469-472, 2008.05, Stenotrophomonas maltophilia (previously named Xanthomonas maltophilia) is an aerobic, nonfermentive, Gram-negative bacillus that is widespread in the environment. It is considered to be an organism with a limited pathogenic potential, which is rarely capable of causing diseases in humans other than in those who are in an immunocompromised state. In this study, we outline the case of a patient with Stenotrophomonas maltophilia bacteremia after living donor liver transplantation, which showed the clinical signs of severe sepsis and was resistant to almost all antibiotics. However, we successfully treated the patient with the antibiotics trimethoprim-sulfamethoxazole (TMP/SMX) and minocycline hydrochloride (MINO), and performed endotoxin-absorbing therapy using polymyxin B (PMX) to remove the endotoxin from Gramnegative bacillus as well as continuous hemodiafiltration (CHDF) to remove inflammatory cytokines. To the best of our knowledge, this is the first report on the treatment of Stenotrophomonas maltophilia bacteremia after living donor liver transplantation..
1440. Kotaro Miyake, Tomoharu Yoshizumi, Satoru Imura, Koji Sugimoto, Erdenebulgan Batmunkh, Hirofumi Kanemura, Yuji Morine, Mitsuo Shimada, Expression of hypoxia-inducible factor-1α, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma
Correlation with poor prognosis with possible regulation, Pancreas, 10.1097/MPA.0b013e31815f2c2a, 36, 3, e1-e9, 2008.04, OBJECTIVES: Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor that plays an important role in tumor growth and metastasis. Inhibition of histone deacetylase shows a marked inhibition of HIF-1α expression; however, the association between HIF-1α and histone deacetylase 1 (HDAC1), metastasis-associated protein 1 (MTA1) is not fully understood. METHODS: Hypoxia-inducible factor 1α, HDAC1, and MTA1 expressions were detected by immunohistochemistry in 39 pancreatic carcinoma patients. The correlations between the expression of HIF-1α, HDAC1, or MTA1 and clinical features and the prognosis were analyzed. RESULTS: Hypoxia-inducible factor 1α, HDAC1, and MTA1 positive stainings were found in 41%, 56%, and 31%, respectively. There was no correlation between HIF-1α, HDAC1, or MTA1 expression levels and any clinical parameters. The survival rate for patients with HIF-1α and HDAC1-positive stainings were significantly lower than for patients with HIF-1α and HDAC1-negative stainings. The MTA1 overexpression group did not have a significantly lower prognosis than the MTA1 underexpression group. The survival rate for the HDAC1(+)/MTA1(2-3) group was significantly lower than for the other groups. CONCLUSIONS: These results suggest that HIF-1α expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis for pancreatic carcinoma and indicates that HIF-1α and HDAC1/MTA1 are a promising therapeutic target in pancreatic carcinoma treatment..
1441. Yuji Soejima, Makoto Meguro, Akinobu Taketomi, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Shinji Ito, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara, Left lobe living donor liver transplantation in an adult patient with situs inversus
Technical considerations, Transplant International, 10.1111/j.1432-2277.2007.00607.x, 21, 4, 384-389, 2008.04, Situs inversus (SI) is a rare congenital disorder involving a complete mirror image of the thoracic and abdominal organs. Living donor liver transplantation (LDLT) in SI cases poses particular challenges on account of its technical complexity, and only a few cases have been reported. Here, we present an adult with SI who was managed successfully by LDLT using a left lobe graft. Some technical modifications, including triangulated anastomosis of the hepatic vein, were required but no vascular graft was necessary. Graft function and vascular integrity were excellent throughout the postoperative course, although sepsis secondary to wound infection with methicillin-resistant Staphylococcus aureus developed. In conclusion, LDLT using a left lobe graft is a feasible procedure for patients with SI, even for adults. Therefore, this condition, while rare, should not be a contraindication for LDLT. Meticulous preoperative simulation and planning of the vascular reconstruction are important steps in LDLT for this rare anomaly..
1442. Y. Soejima, A. Taketomi, T. Ikegami, T. Yoshizumi, H. Uchiyama, Y. Yamashita, M. Meguro, N. Harada, M. Shimada, Y. Maehara, Living donor liver transplantation using dual grafts from two donors
A feasible option to overcome small-for-size graft problems?, American Journal of Transplantation, 10.1111/j.1600-6143.2008.02153.x, 8, 4, 887-892, 2008.04, Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small-for-size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large-size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small-for-size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small-for-size graft problems without increasing independent donor risks..
1443. Shigeyuki Nagata, Mitsuo Shimada, Yuji Soejima, Takashi Nishizaki, Tomoharu Yoshizumi, Yoshihiko Maehara, Adult-to-adult living donor liver transplantation in severe portosystemic shunt cases, Hepato-gastroenterology, 55, 82-83, 666-669, 2008.03, To date, the need for spontaneous portosystemic shunt division during adult-to-adult living donor liver transplantation (LDLT) remains unknown. This study reports 2 patients with large portosystemic shunts who required LDLT. The first patient was a 40-year-old male with liver cirrhosis due to hepatitis C. The angiogram showed splenosystemic shunts with hepatopetal flow. Shunt occlusion was not performed after implanting a small-size graft because sufficient portal blood flow was observed. On the first postoperative day, portal blood flow was not detected; therefore shunt occlusion was performed and the portal blood flow was restored. The second patient was a 51-year-old female with primary biliary cirrhosis. Marked collateral circulation with hepatofugal flow was observed. Shunt occlusion was performed after implanting a medium-size graft. Postsurgery, hepatopetal portal blood flow was observed and the postoperative course was satisfactory. These cases demonstrate that large portosystemic shunts should be ligated to maintain adequate portal blood flow that corresponds to the graft volume..
1444. Shinji Shimoda, Kenichi Harada, Hiroaki Niiro, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Koichi Tsuneyama, Minoru Nakamura, Atsumasa Komori, Kiyoshi Migita, Yasuni Nakanuma, Hiromi Ishibashi, Carlo Selmi, M. Eric Gershwin, Biliary epithelial cells and primary biliary cirrhosis
The role of liver-infiltrating mononuclear cells, Hepatology, 10.1002/hep.22102, 47, 3, 958-965, 2008.03, Primary biliary cirrhosis (PBC) is characterized by the highly selective autoimmune injury of small intrahepatic bile ducts, despite widespread distribution of mitochondrial autoantigens. On this basis, it has been suggested that the targeted biliary epithelial cells (BECs) play an active role in the perpetuation of autoimmunity by attracting immune cells via chemokine secretion. To address this issue, we challenged BECs from patients with PBC and controls using multiple Toll-like receptor (TLR) ligands as well as autologous liver-infiltrating mononuclear cells (LMNCs) with subsequent measurement of BEC phenotype and chemokine production and LMNC chemotaxis by quantifying specific chemokines. Our data reflect that BECs from PBC patients and controls express similar levels of TLR subtypes, CD40, and human leukocyte antigen DRα (HLA-DRα) and produce equivalent amounts of chemokines in our experimental conditions. Interestingly, however, BEC-expressed chemokines elicit enhanced transmigration of PBC LMNCs compared with controls. Furthermore, the addition of autologous LMNCs to PBC BECs led to the production of higher levels of chemokines and enhanced the expression of CD40 and HLA-DRα. Conclusion: We submit that the proinflammatory activity of BECs in PBC is secondary to the intervention of LMNCs and is not determined per se. These data support the hypothesis that BECs are in fact "innocent victims" of autoimmune injury and that the adaptive immune response is critical in PBC..
1445. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiko Maehara, Hiroyuki Kuwano, Is an elderly recipient a risk for living donor adult liver transplantation?, Hepato-gastroenterology, 55, 82-83, 653-656, 2008.03, Background/Aims: In cadaveric liver transplantation, it has been reported that elderly recipients over 60 years are at risk because of high incidence of complication and malignancy. However, in living-donor adult liver transplantation (LDALT), it is unclear whether the elderly recipient is risky or not risky. In this study, the outcome after LDALT of elderly patients has been evaluated. Methodology: One hundred twenty two consecutive LDALT recipients were studied. The recipients were divided into an elderly group (older than 60 yrs, n=21), and a control group (younger than 60 yrs, n=101). Comparative examination of background factors, postoperative complications and de novo malignancy was carried out. Results: Elderly patients more frequently received transplantation for hepatocellular carcinoma. Pretransplant liver damage such as Child-Pugh, MELD or bilirubin level was same among the groups. There was no significant difference in posttransplant complications except renal failure. Postoperative renal failure (postoperative creatinine level over 2mg/dL) occurred in 29% (n=5) of the elderly group vs. 8% (n=6) of the control group. De novo malignancy occurred in 1 case (lung) in the elderly group and 1 case (Vater) in the control group. In the control group, the 1, 3 and 5 year patient survival rates were 78.5%, 73.1% and 71.4%, respectively. And in the elderly group, the 1, 3 and 5 year patient survival rates were 85.7%, 81.0% and 70.8%, respectively. Conclusions: It may be, we concluded that living donor adult liver transplantation is good treatment for end stage liver diseases in elderly recipients over 60 years. However caution should be taken in the administration of medicine, including immunosuppressants or antibiotics, do to a propensity for postoperative renal failure in elderly recipients..
1446. Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Yo Ichi Yamashita, Yoshihiko Maehara, Liver transplantation for hepatocellular carcinoma, Journal of Hepato-Biliary-Pancreatic Surgery, 10.1007/s00534-007-1296-4, 15, 2, 124-130, 2008.03, The role of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) has evolved over the past two decades, and transplantation has become one of the few curative treatment modalities for patients with HCC. Early results were poor, but the current restrictive selection criteria can yield excellent results. This review will discuss recent issues in the field, including (1) factors affecting the recurrence of HCC after LT; (2) the effect of downstaging HCC before LT, including transarterial catheter chemoembolization (TACE) and radiofrequency ablation (RFA); and (3) living-donor versus deceased-donor liver transplantation for HCC patients. The most important factors that have been described to affect LT survival include the tumor size, vascular invasion, and the degree of tumor differentiation. Recently, tumor markers, including alpha-fetoprotein and des-gamma carboxy prothrombin, were reported as predictors of HCC recurrence after LT. Furthermore, the experience accumulated with locoregional therapies such as TACE and RFA as bridging procedures to LT, along with the reduced waiting time under the HCC-adjusted MELD (model for endstage liver disease) system for organ allocation has led to improved outcomes. With the recent advances in adult living-donor liver transplantation (LDLT), there may be a marked change in the role of liver transplantation for hepatic malignancies, in particular for HCC..
1447. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Kensaku Sanefuji, Hiroto Kayashima, Mitsuo Shimada, Yoshihiko Maehara, Living Donor Liver Transplantation for Acute Liver Failure
A 10-Year Experience in a Single Center, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2007.08.018, 206, 3, 412-418, 2008.03, Background: Living donor liver transplantation has become an accepted treatment for various terminal liver diseases. Study Design: Forty-two living donor liver transplantations performed for acute liver failure during a 10-year period at Kyushu University Hospital were reviewed. Results: Causes of liver failure included hepatitis B (n = 12), hepatitis C (n = 1), autoimmune hepatitis (n = 2), Wilson's disease (n = 3), and unknown causes (n = 24). The graft types were: left lobe (n = 33), right lobe (n = 8), and lateral segment (n = 1). The mean graft volume to standard liver volume ratios were 42.2 ± 9.2% in left lobe grafts and 50.5 ± 3.9% in right lobe grafts (p < 0.05). Extubation was significantly delayed in grade IV encephalopathy patients (73.7 ± 18.2 hours) compared with patients with other grades (p < 0.01 to grades I and II, p < 0.05 to grade III). All other patients, except one with a subarachnoid hemorrhage, had complete neurologic recovery after transplantation. The 1- and 10-year survival rates were 77.6% and 65.5%, respectively, for grafts, and 80.0% and 68.2%, respectively, for patients. Conclusions: Outcomes of living donor liver transplantation for acute liver failure are fairly acceptable despite severe general conditions and emergent transplant settings. Living donor liver transplantation is now among the currently accepted life-saving treatments of choice for acute liver failure, although innovative medical treatments for this disease entity are still anticipated..
1448. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Living donor liver transplantation for fulminant hepatic failure from ABO-incompatible donors [1], Transplant International, 10.1111/j.1432-2277.2007.00588.x, 21, 3, 284-285, 2008.03.
1449. Tomoharu Yoshizumi, Akinobu Taketomi, Hiroto Kayashima, Noboru Harada, Hideaki Uchiyama, Yo Ichi Yamashita, Toru Ikegami, Yuji Soejima, Takashi Nishizaki, Mitsuo Shimada, Yoshihiko Maehara, Successful treatment for a patient with hemophagocytic syndrome after a small-for-size graft liver transplantation, Hepato-gastroenterology, 55, 82-83, 359-362, 2008.03, Hemophagocytic syndrome (HPS) is a hematological disorder caused by activated T lymphocytes, which leads to the proliferation of stimulated macrophages that phagocytose and destroy circulating blood elements and their precursors within bone marrow, and lead to the further production of inflammatory cytokines. Living donor liver transplantation (LDLT) between adults has been performed to compensate for the shortage of available organs. There have been some reports concerning HPS after LDLT; however, its prognosis is disappointingly poor. In particular, there is no report of treated HPS developed after LDLT using small-for-size left lobe grafts. We herein report a case of HPS in a 63-year old woman who underwent LDLT using left lobe graft weighing only 330g. The HPS was diagnosed on postoperative day 13, and was successfully treated using a combination of intravenous immunoglobulin, granulocyte colony stimulating factor, conversion of calcineurin inhibitor and steroid pulse. The trigger of HPS may not only be systemic infection, but also hypercytokinemia caused by various factors. HPS is a fatal complication in immunologically compromised patients; however, early and accurate diagnosis could lead to an adequate treatment and improve the outcome..
1450. Mami Kanamoto, Tomoharu Yoshizumi, Toru Ikegami, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Nobuya Sano, Mitsuo Shimada, Cholangiolocellular carcinoma containing hepatocellular carcinoma and cholangiocellular carcinoma, extremely rare tumor of the liver
A case report, Journal of Medical Investigation, 10.2152/jmi.55.161, 55, 1-2, 161-165, 2008.02, Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor which was first defined by Steiner, et al. in 1957 (1). CLC is thought to be derived from Hering's canal because tumor glands of CLC are morphologically similar to cholangioles. Recently, Theise, et al. reported that Hering's canal might be composed of hepatic stem cells (3). In addition, CLC sometimes contains a hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC) component within the tumor. Those findings suggest that CLC might originate from hepatic stem cells. On the other hand, because of its low frequency, clinicopatholigical features of CLC have not been fully clarified yet. We herein report a case of a 71-year old man with CLC. Based on preoperative imagings, the hepatic tumor was diagnosed as HCC, and he underwent a partial hepatectomy. The tumor contained both a HCC and CCC-like area. In immunohistochemistry, cytokeratin (CK) 7, CK20, CAM5.2 was positive, and CK19 was negative, therefore the tumor was diagnosed as CLC. The diagnostic criteria have not been described clearly, so CLC is difficult to diagnose preoperatively. Further studies are needed to clarify the clinical and clinicopatholigical features of CLC..
1451. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Yo Ichi Yamashita, Shinji Itoh, Yosuke Kuroda, Yoshihiko Maehara, Assessment of graft fibrosis by transient elastography in patients with recurrent hepatitis C after living donor liver transplantation, Transplantation, 10.1097/01.tp.0000297248.18483.16, 85, 1, 69-74, 2008.01, BACKGROUND. Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness and therefore can be a promising tool to evaluate liver fibrosis and avoid liver biopsy. We prospectively assessed the performance of transient elastography in patients with recurrent hepatitis C virus after living donor liver transplantation, in comparison with the surrogate serum markers. METHODS. Fifty-six patients with recurrent hepatitis C virus after living donor liver transplantation, who underwent both liver biopsy and transient elastography were included in this study. The grade of liver fibrosis (the Scheuer classification) obtained by biopsy was compared to liver stiffness measured by the transient elastography. RESULTS. The fibrosis grades were as follows: F0, n=22; F1, n=13; F2, n=9; F3, n=7; and F4, n=5. Liver stiffness values ranged from 2.9 to 72.0 kPa. The optimal cutoff values were 8.8 kPa for F≥1, 9.9 kPa for F≥2, 15.4 kPa for F≥3, and 26.5 kPa for F≥4. The area under the receiver operator characteristic curve for the diagnosis of fibrosis (F≥2) by transient elastography was 0.92, while that by hyaluronic acid, type 4 collagen, alanine aminotransferase, and the aspartate transaminase to platelets ratio index were 0.52, 0.62, 0.64, and 0.70, respectively. CONCLUSIONS. These data suggest that transient elastography is a simple, noninvasive and reliable tool to assess liver fibrosis in patients with recurrent hepatitis C virus after living donor liver transplantation..
1452. Nao Kinjo, Hirofumi Kawanaka, Morimasa Tomikawa, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Shohei Yamaguchi, Daisuke Yoshida, Yoshihiko Maehara, B-RTO for ectopic variceal bleeding after living donor liver transplantation, Hepato-gastroenterology, 55, 81, 241-243, 2008.01, Gastrointestinal bleeding (GIB) is a serious gastroenterological complication after orthotropic liver transplantation, as well as living donor liver transplantation (LDLT). Although ectopic varices are rare causes of GIB, they may lead to life-threatening bleeding and it is difficult to diagnose them. We herein report a rare case of a jejunal variceal bleeding in a recipient five years after LDLT for primary sclerosing cholangitis with successful result by balloon-occluded retrograde transvenous obliteration (B-RTO)..
1453. Kazutoyo Morita, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Naotaka Hashimoto, Yohei Mano, Tatsunori Miyata, Yuji Soejima, Yoshihiko Maehara, Feasible isolated liver transplantation for a cirrhotic patient on chronic hemodialysis, Case Reports in Gastroenterology, 10.1159/000354140, 7, 2, 299-303, 2013.01, End-stage liver and kidney disease (ELKD) is an indication for deceased donor simultaneous liver-kidney transplantation. Although a few cases of living donor liver-kidney transplantation have been reported, the invasiveness remains to be discussed. Living donor liver transplantation (LDLT) is an alternative choice for ELKD, but has never been reported. Here, we report a case of successful LDLT for a patient with ELKD on hemodialysis. The patient was a 63-year-old male and had decompensated hepatitis C cirrhosis with seronegativity for hepatitis C virus. He had non-diabetic end-stage renal failure and had been on hemodialysis for 3 years. He was in good general condition except for hepatic and renal failure. The living donor was his 58-year-old healthy wife. A right lobe graft was transplanted to the recipient under continuous hemodiafiltration (CHDF) and extracorporeal veno-venous bypass. CHDF was continued until postoperative day 4, at which point CHDF was converted to hemodialysis. His posttransplant course was good and he was discharged on postoperative day 36. To the best of our knowledge, this is the first report of LDLT for a patient on chronic hemodialysis. Therefore, being on hemodialysis is not a contraindication for LDLT. LDLT is feasible for a patient with ELKD on hemodialysis..
1454. Hiroto Kayashima, Ken Shirabe, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Liver regeneration and venous collateral formation in the right lobe living-donor remnant
Segmental volumetric analysis and three-dimensional visualization, Transplantation, 10.1097/TP.0b013e31827147d8, 95, 2, 353-360, 2013.01, BACKGROUND: In left lobe (LL) living-donor liver transplantation (LDLT), hepatic venous congestion (HVC) caused by ligation of the middle hepatic vein tributaries is unavoidable in the right lobe (RL) donor remnant. METHODS: To clarify the impact of HVC on liver regeneration and venous collateral formation (VCF), we used three-dimensional computed tomography to examine the volumes of total/segmental liver and HVC and the degree of VCF; preoperative data were compared with data obtained on postoperative day (POD) 35 in 13 LL LDLT donors. RESULTS: On POD 35, the congestion rate decreased from 32.5% to 1.6% and the total liver regeneration rate was 81.7%. Preoperatively, the anterior sector-to-RL volume ratio was significantly lower, and the posterior sector-to-RL volume ratio was significantly higher than postoperatively (56.7% vs. 52.9%, P<0.01, and 36.9% vs. 41.5%, P<0.01, respectively). There was no correlation between degree of HVC and liver regeneration. Obvious VCF was found in five (38.5%) cases. The RL and posterior sector volume per square meter of body surface area in the VCF group were significantly lower than that in the non-VCF group (412 cm/m vs. 492 cm/m, P<0.01, and 140 cm/m vs. 190 cm/m, P<0.01, respectively). The preoperative congestion rate and liver regeneration rate were not significantly different between the groups. CONCLUSIONS: Reconstruction of the middle hepatic vein tributaries in the RL donor remnant might not be necessary in LL LDLT, because the HVC improved dramatically by POD 35 regardless of the development of VCF..
1455. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Mirror image hepatectomy in a patient with situs inversus totalis., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 430-434, 2013.01, Hepatectomy in a patient with situs inversus patient is technically challenging because of its complete mirror image anatomy, especially for a tumor located deep in the liver. Incorrectly identifying intrahepatic vessels and biliary system would lead to serious complications. We experienced a hepatectomy for a tumor in a patient with situs inversus totalis with referring to computer-generated mirror images. A 66-year-old female patient with situs inversus totalis was diagnosed with hepatocellular carcinoma, 5 cm in diameter, centrally located just above the hepatic hilum compressing the right and left hepatic duct. The liver infected with hepatitis C was cirrhotic with a moderate amount of ascites. We preoperatively created several diagrams of the mirror image anatomy and made plans for how to resect this tumor, presupposing the patient had an ordinary anatomy. The tumor was successfully enucleated with referring to these diagrams. The operation time was 454 minutes. Five units of fresh frozen plasma was transfused intraoperatively. Although she suffered refractory ascites which needed repeated paracentesis, she managed to leave the hospital two months after the operation. Creating a mirror image anatomy enables surgeons to safely perform a complex hepatectomy in a patient with situs inversus totalis..
1456. Takashi Motomura, Ken Shirabe, Yohei Mano, Jun Muto, Takeo Toshima, Yuichiro Umemoto, Takasuke Fukuhara, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment, Journal of Hepatology, 10.1016/j.jhep.2012.08.017, 58, 1, 58-64, 2013.01, Background & Aims: Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Preoperative neutrophil-lymphocyte ratio (NLR) is a predictor of patient prognosis, but its mechanism has never been clarified. Methods: We assessed outcomes in 158 patients who had undergone living-donor liver transplantation (LDLT) for HCC. Recurrence-free survival (RFS) was determined in patients with high (≥4) and low (<4) NLR. Levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68, and CD163 were measured. Results: The 5-year RFS rate was significantly lower in patients with high (n = 26) than with low (n = 132) NLR (30.3% vs. 89.0%, p <0.0001), in patients with high (n = 15) than with low (n = 79) NLR who met the MC (73.6% vs. 100%, p = 0.0008) and in patients with high (n = 11) than with low (n = 53) NLR who exceeded the MC (0% vs. 76.1%, p = 0.0002). Tumor expression of VEGF, IL8, IL-17, CD68, and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 levels were significantly higher in the high-NLR group (p = 0.01 each). The density of peritumoral CD163 correlated with the density of peritumoral IL-17-producing cells (p = 0.04) and was significantly higher in the high-NLR group (p = 0.005). Conclusions: NLR predicts outcomes after LDLT for HCC via the inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC..
1457. Keiji Yoshinaga, Hiroshi Saeki, Eiji Oki, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Prognostic markers for immunochemotherapy using tegafur -uracil (UFT) and protein-bound polysaccharide K (PSK)., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 549-558, 2013.01, We previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels. 98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years. There were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant. Serum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary..
1458. Hiroshi Saeki, Eiji Oki, Yasuo Tsuda, Koji Ando, Yukiharu Hiyoshi, Shuhei Ito, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Relevance of totally laparoscopic gastrectomy for patients with advanced gastric cancer., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 405-412, 2013.01, Although the use of laparoscopic gastrectomy for gastric cancer has been widespread, it has remained controversial whether it can be applied for the patients with advanced gastric cancer. The aim of this study was to clarify the safety and usefulness of totally laparoscopic gastrectomy for patients with advanced gastric cancer. Totally laparoscopic gastrectomy was applied for a total of 38 patients with pStage IB-III advanced gastric cancer at our institute. The surgical and long-term results were analyzed in those patients. Twenty-seven patents underwent distal gastrectomy and 11 patients underwent total gastrectomy. The mean number of dissected lymph nodes was 41 (range, 16-87). The mean length of the operation and amount of blood loss was 324 min and 123 ml, respectively. Two cases of postoperative bleeding were noted, while neither anastomosis-related complications nor in-hospital death was observed. The follow-up period after surgery was 8-72 months. Postoperative recurrence was observed in 6 patients (peritoneal dissemination: 3 patients, pleural dissemination: 1 patient, liver metastasis: 1 patient, ovarian metastasis: 1 patient). The overall survival rates at 1, 3 and 5 years were 94.7%, 76.3% and 76.3%, respectively. Totally laparoscopic gastrectomy is safe and can lead to satisfactory long-term outcomes in cases of advanced gastric cancer. Prospective controlled studies are warranted to confirm our findings..
1459. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo Ichi Yamashita, Tetsuo Ikeda, Hirofumi Kawanaka, Keishi Sugimachi, Koshi Mimori, Masayuki Watanabe, Masaru Morita, Eiji Oki, Hiroshi Saeki, Yoshihiko Maehara, Rex shunt for portal vein thrombosis after adult living donor liver transplantation., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 464-468, 2013.01, Portal vein thrombosis (PVT) after liver transplantation is a relatively common but serious complication which could lead to portal hypertension or a direct graft loss. A "Rex" shunt created between the superior mesenteric vein (SMV) and the umbilical portion of the left portal vein can be a useful option to treat PVT after pediatric liver transplantation, however, its application to adult patients has not been reported so far because appropriate vein grafts are hardly available. Herein we present a case of PVT after left lobe living donor liver transplantation (LDLT) who underwent the procedure using the own inferior jugular vein and the gonadal vein as a shunt graft. The shunt was patent immediately after the procedure but was thrombosed 2 days after probably due to the insufficient inflow from the SMV and the absence of anticoagulation therapy, for which emergent thrombectomy and ligation of the significant hepatofugal collateral veins followed by full anti-coagulation therapy were performed. The shunt remains open at 8 month after the procedure with a normal anmonia level and liver function. In conclusion, the Rex shunt using recipient's autologous vein grafts is a feasible and valuable option for adult patients to treat PVT after LDLT..
1460. Masayuki Watanabe, Koki Matsuura, Hideo Baba, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Yoshihiko Maehara, Thoracoscopic pericardial drainage for gastric tube ulcer penetrated into the pericardium., Unknown Journal, 104, 10, 389-393, 2013.01, Peptic ulcer occurring in the gastric conduit for esophageal reconstruction sometimes penetrates into the mediastinal structures. We herein reported a case of pericardial penetration of gastric tube ulcer successfully treated with thoracoscopic pericardial drainage. A 66-year-old Japanese man, who had undergone esophagectomy for esophageal cancer 20 months before, visited our emergency room complaining severe back pain. Computed tomography revealed gastric tube ulcer penetrated into the pericardial space. Thoracoscopic pericardiotomy and drainage was performed and the patient made an uneventful recovery. Thoracoscopic pericardial drainage is useful to manage acute pyogenic pericarditis due to penetration of peptic ulcer which occurred in the gastric tube..
1461. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Verification of our therapeutic criterion for acute cholecystitis
"perform a subemergency laparoscopic cholecystectomy when a patient is judged to be able to tolerate general anesthesia"--the experience in a single community hospital., Unknown Journal, 104, 10, 339-343, 2013.01, Our current therapeutic criterion for acute cholecystitis is: Perform a subemergency laparoscopic cholecystectomy (LC) when a patient is judged to be able to tolerate general anesthesia. The aim of the current study was to verify whether this criterion is justified. The outcomes of 21 cases of LC for acute cholecystitis performed between April 2011 and September 2013 were retrospectively analyzed. Subemergency LC was performed according to the aforementioned criterion (Subemergency group; n = 16). Patient who was judged to be unable to tolerate general anesthesia underwent percutaneous transhepatic gallbladder drainage (PTGBD) first, then LC after the patients' condition became stable (PTGBD group; n = 5). There is no conversion to open surgery throughout the study period. The mean of the total hospital stays in the Subemergency group was significantly shorter than that in the PTGBD group (11.5 +/- 5.3 vs. 30.4 +/- 8.5 days). Although two patients in the Subemergency group, who had already needed oxygen administration preoperatively, suffered postoperative respiratory failure, they completely recovered. On the other hand, there is no postoperative complication in the PTGBD group. Subemergency LC could be safely performed when surgeons as well as anesthesiologists judged a patient to be able to tolerate general anesthesia, which significantly shorten hospital stays compared to elective LC after PTGBD. However, elective LC after PTGBD is an absolutely safer therapeutic option in treating unstable patients..
1462. Tetsuo Ikeda, Tomohiko Akahoshi, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Koshi Mimori, Masayuki Watanabe, Makoto Hashizume, Yoshihiko Maehara, [Optimum hepatic parenchymal dissection to prevent bile leak
a comparative study using electrosurgical and stapling devices in swine]., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 507-514, 2013.01, Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma..
1463. Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara, Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma
Report of a case, Surgery today, 10.1007/s00595-012-0332-4, 42, 12, 1210-1214, 2012.12, The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection..
1464. Takashi Motomura, Ken Shirabe, Norihiro Furusyo, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tomohiko Akahoshi, Morimasa Tomikawa, Takasuke Fukuhara, Jun Hayashi, Yoshihiko Maehara, Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype, BMC Gastroenterology, 10.1186/1471-230X-12-158, 12, 2012.11, Background: IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.Methods: Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.Results: Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.Conclusions: IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype..
1465. Takashi Motomura, Yuki Ono, Ken Shirabe, Takasuke Fukuhara, Hideyuki Konishi, Yohei Mano, Takeo Toshima, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Neither MICA nor DEPDC5 genetic polymorphisms correlate with hepatocellular carcinoma recurrence following hepatectomy, HPB Surgery, 10.1155/2012/185496, 2012, 2012.11, Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7 in MICA GG allele carriers, 38.7 in GA, and 20.8 in AA, respectively (P = 0.72). The five-year RFS rate was 23.8 in DEPDC5 TT allele carriers and 31.8 in TG/GG, respectively (P = 0.47). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers (P 0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages..
1466. Yuji Soejima, Toru Ikegami, Hideki Ijichi, Tetsuo Ikeda, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hiroshi Matsuura, Kenichiro Okadome, Yoshihiko Maehara, Technical evolution of laparoscopic hepatic resection
a single institutional experience., Unknown Journal, 103, 11, 226-232, 2012.11, Laparoscopic hepatic resection (LHR) is still a challenging and developing surgical modality because of technical difficulty and a lack of training opportunities and experience. In this study, we present the results of our initial experiences of LHR, focusing on technical evolution in the management of LHR. Between April 2011 and March 2012, a total of 12 LHRs were performed. The first 5 of these LHRs were performed under laparoscopic assistance (hybrid-LHR), while the last 7 LHRs were performed totally laparoscopically (pure-LHR). Indications for LHR were hepatocellular carcinoma (n = 9) and metastatic liver cancer (n = 3). LHR procedures consisted of partial resection (n = 2), left lateral segmentectomy (n = 2), and left lobectomy (n = 1) in the hybrid-LHR group, and partial resection (n = 4), left lateral segmentectomy (n = 2), and right lobectomy (n = 1) in the pure-LHR group. Operative outcomes were compared between the groups and technical modifications were evaluated. The mean operative time, blood loss, and length of hospital stay in the hybrid- and pure-LHR groups were 3.8 and 6.1 hours, 220 and 611 ml, and 9.4 and 7.4 days, respectively. There were no postoperative complications in both groups. Tumor margins were negative in all cases. LHR is a feasible and effective procedure for patients with various types of liver tumors, although technical challenges still need to be overcome..
1467. Shohei Yoshiya, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31826969e6, 94, 9, 947-952, 2012.11, BACKGROUND: Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. METHODS: A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. RESULTS: The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). CONCLUSIONS: Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group..
1468. Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Authors' reply to "female-to-male match predicted poor survival following living donor liver transplantation-some issues needed to be clarified", Transplantation, 10.1097/TP.0b013e3182654d56, 94, 6, e36, 2012.09.
1469. Toru Ikegami, Ken Shirabe, Rumi Matono, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Etiologies, risk factors, and outcomes of bacterial pneumonia after living donor liver transplantation, Liver Transplantation, 10.1002/lt.23483, 18, 9, 1060-1068, 2012.09, The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short-term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram-negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P = 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post-LDLT pneumonia was associated with the following post-LDLT events: the prolonged use of mechanical ventilation (≥3 days), a prolonged stay in the intensive care unit (≥7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed-onset pneumonia, which occurred at least 10 days after transplantation (n = 15), and it was significantly associated with graft dysfunction. A combination of broad-spectrum antibiotics and aminoglycosides provided cover for most gram-negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad-spectrum antibiotics. Delayed-onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed..
1470. Hideaki Uchiyama, Hiroto Kayashima, Rumi Matono, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Toshiharu Matsuura, Tomoaki Taguchi, Yoshihiko Maehara, Relevance of HLA compatibility in living donor liver transplantation
The double-edged sword associated with the patient outcome, Clinical Transplantation, 10.1111/ctr.12019, 26, 5, E522-E529, 2012.09, HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA-A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host-versus-graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft-versus-host disease (GVHD) was also analyzed. No recipients with recipient-against-donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with "R→D MM 0" together with "donor-against-recipient MM 3" died of fatal GVHD. HLA compatibility in LDLT not only affected the long-term acceptance of graft livers but also the risk of fatal GVHD..
1471. Mizue Matsuo, Toru Ikegami, Kazutoyo Morita, Hiroko Yano, Naotaka Hashimoto, Hiroto Kayashima, Toshirou Masuda, Naoko Kondou, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, [A case of successful multi-venous reconstruction using recipient's jugular vein in right lobe-living donor liver transplantation]., Unknown Journal, 103, 9, 186-190, 2012.09, In right lobe-living donor liver transplantation (RT-LDLT), hepatic venous reconstruction of the graft is essential to prevent posttansplant graft congestion and have a good outcome. The patient was a 56-year-old man who had decompensated liver cirrhosis secondary hepatitis C with massive ascites, jaundice and hepatic encephalopathy. He underwent LDLT using his son's right lobe graft. Preoperative simulation by 3D-CT volumetry revealed that the right lobe graft needed multi-venous reconstruction for right inferior hepatic vein (RIHV) and middle hepatic venous tributaries. Preoperative CT scan revealed that the recipient had portal venous thrombus and stenosis, which meant that the recipient's explanted portal vein (EPV) was not suitable for the venous reconstruction of the right lobe graft. Therefore, the recipient's internal and external jugular veins (IJV and EJV) were procured for venous reconstruction. The multiple veins of the right lobe graft were reconstructed to have single co-orifice at the backtable, and the co-orifice was anastomosed to inferior vena cava in short time. The recipient discharged on postoperative day 22 with good venous patency. In RT-LDLT unavailable for recipient's EPV, recipient's IJV and EJV grafts are very useful for multi-venous reconstruction..
1472. Kazuki Takeishi, Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Takashi Motomura, Toru Ikegami, Tomoharu Yoshizumi, Fumio Sakane, Yoshihiko Maehara, Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras-Raf-MEK-ERK pathway, Journal of Hepatology, 10.1016/j.jhep.2012.02.026, 57, 1, 77-83, 2012.07, Background & Aims: Diacylglycerol kinases (DGKs) were recently recognized as key regulators in cell signaling pathways. We investigated whether DGKα is involved in human hepatocellular carcinoma (HCC) progression. Methods: We silenced or overexpressed DGKα in HCC cells and assessed its effect on tumor progression. DGKα expression in 95 surgical samples was analyzed by immunohistochemistry, and the expression status of each sample was correlated with clinicopathological features. Results: DGKα was detected in various HCC cell lines but at very low levels in the normal liver. Knockdown of DGKα significantly suppressed cell proliferation and invasion. Overexpression of wild type (WT) DGKα, but not its kinase-dead (KD) mutant, significantly enhanced cell proliferation. DGKα knockdown impaired MEK and ERK phosphorylation, but did not inhibit Ras activation in HCC cells. In a xenograft model, WT DGKα overexpression significantly enhanced tumor growth compared to the control, but KD DGKα mutant had no effect. Immunohistochemical studies showed that DGKα was expressed in cancerous tissue, but not in adjacent non-cancerous hepatocytes. High DGKα expression (≥20%) was associated with high Ki67 expression (p <0.05) and a high rate of HCC recurrence (p = 0.033) following surgery. In multivariate analyses, high DGKα expression was an independent factor for determining HCC recurrence after surgery. Conclusions: DGKα is involved in HCC progression by activation of the MAPK pathway. DGKα could be a novel target for HCC therapeutics as well as a prognostic marker..
1473. Yuji Soejima, K. Shirabe, A. Taketomi, T. Yoshizumi, H. Uchiyama, T. Ikegami, M. Ninomiya, N. Harada, H. Ijichi, Y. Maehara, Left lobe living donor liver transplantation in adults, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04022.x, 12, 7, 1877-1885, 2012.07, Adult left lobe (LL) living donor liver transplantation (LDLT) has not generally been recognized as a feasible procedure because of the problem of graft size. The objectives of this study were to assess the feasibility and short- and long-term results of adult LL LDLT in comparison with right lobe (RL) LDLT. Data on 200 consecutive LL LDLTs, including five retransplants, were retrospectively compared with those of 112 RL LDLTs, in terms of survival, complications and donor morbidity. The mean graft weight to standard volume ratio of LL grafts was 38.7% whereas that of RL grafts was 47.6% (p < 0.0001). The 1-, 5- and 10-year patient survival rates of LL LDLT were 85.6%, 77.9% and 69.5%, respectively, which were comparable to those of RL LDLT (89.8%, 71.3% and 70.7%, respectively). The incidence of small-for-size syndromewas higher in LL LDLT (19.5%) than in RL LDLT (7.1%) (p < 0.01). The overall donor morbidity rates were comparable between LL (36.0%) and RL (34.8%), whereas postoperative liver function tests and hospital stay were significantly better (p < 0.0001) in LL donors. In conclusion, adult LL LDLT has comparable outcomes to that of RL LDLT. LL LDLT is viable and is the first choice in adult LDLT..
1474. Toru Ikegami, K. Shirabe, T. Yoshizumi, S. Aishima, Y. A. Taketomi, Y. Soejima, H. Uchiyama, H. Kayashima, T. Toshima, Y. Maehara, Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04052.x, 12, 7, 1886-1897, 2012.07, The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult-to-adult LDLT grafts without anatomical, immunological or hepatitis-related issueswere included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH-20) was used to characterize PGD. DFH-20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH-20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PTINR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH-20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH-20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality..
1475. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Use of an internal jugular vein graft for middle hepatic vein tributary reconstruction in right-lobe living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31825b75b6, 94, 2, e17-e18, 2012.07.
1476. Yoko Zaitsu, Toru Ikegami, Toshirou Masuda, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, [A successful case of living donor liver transplantation performed in 7 hours for sub acute fulminant hepatitis]., Fukuoka igaku zasshi = Hukuoka acta medica, 103, 7, 145-149, 2012.07, Living donor liver transplantation (LDLT) is the ultimate cure for fulminant hepatitis. Successful outcomes rely on the precise evaluation of the reversibility of hepatic encephalopathy, and a swift execution of necessary examination of both the donor and the recipient. The case was a 63-years old woman, presented with fever and loss of appetite. She was hospitalized for acute hepatitis and treated at a nearby hospital. She was transferred to the tertiary hospital for the acute deterioration of her liver function on the 7th day after the emergence of the initial symptoms. On the 10th day, she showed Grade 2 encephalopathy and underwent plasma exchange. She was transported to our hospital for possible LDLT on the 11th day. CT scan on arrival showed severe atrophy of her liver and no definite brain edema despite acutely deteriorating encephalopathy (Grade 3). LDLT was launched after 7 hours from her transport. She was discharged from the intensive care unit on the 6th day and was discharged without severe complications on 42th day after the LDLT..
1477. Noboru Harada, Ken Shirabe, Hideki Ijichi, Rumi Matono, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Yoshihiko Maehara, Acoustic radiation force impulse imaging predicts postoperative ascites resulting from curative hepatic resection for hepatocellular carcinoma, Surgery (United States), 10.1016/j.surg.2011.12.035, 151, 6, 837-843, 2012.06, Background: Measurement of liver stiffness using Virtual Touch Tissue Quantification (VTTQ) based on acoustic radiation force impulse imaging reflects the degree of hepatic fibrosis and reserve. This prospective study investigated how well the VTTQ value predicts the development of postoperative complications before curative hepatic resection for hepatocellular carcinoma (HCC). Methods: The study enrolled 50 consecutive patients between February 2009 and October 2010 whose preoperative VTTQ values were determined before they underwent curative hepatic resection for HCC. We assessed the relationship between postoperative complications and VTTQ values. Results: The study included 41 (82%) patients with chronic hepatitis and 9 (18%) with nonviral cirrhosis. The mean VTTQ value was 1.60 (m/sec), which correlated with the fibrosis stage (P =.0058). The VTTQ value was the only variable correlated with postoperative ascites that did not respond to pharmacologic treatment and required invasive management. Univariate and subsequent multivariate analyses revealed that the preoperative VTTQ value was the only independent risk factor for predicting the development of postoperative ascites (cutoff, 1.68 cm/sec; P =.007; odds ratio, 76.481). The area under the receiver operating characteristic curve for the diagnosis of postoperative ascites using VTTQ values was 0.90, whereas those using the aspartate transaminase-to-platelet ratio index and indocyanine green retention rate at 15 minutes values were 0.68 and 0.55, respectively. Conclusion: These data suggest that the VTTQ value is a reliable surrogate marker for predicting postoperative ascites before curative hepatic resection for HCC..
1478. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Shohei Yoshiya, Takeo Toshima, Takashi Motomura, Yuji Soejima, Hideaki Uchiyama, Yoshihiko Maehara, En bloc stapling division of the gastroesophageal vessels controlling portal hemodynamic status in living donor liver transplantation, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.02.016, 214, 6, e53-e56, 2012.06.
1479. T. Yoshizumi, K. Shirabe, T. Ikegami, H. Kayashima, N. Yamashita, K. Morita, T. Masuda, N. Hashimoto, A. Taketomi, Y. Soejima, Y. Maehara, Impact of human T cell leukemia virus type 1 in living donor liver transplantation, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04037.x, 12, 6, 1479-1485, 2012.06, Human T cell leukemia virus type 1 (HTLV-1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV-1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV-1 status in living donor liver transplantation (LDLT). Twenty-six of 329 (7.9%) HTLV-1 carriers underwent primary LDLT. One recipient negative for HTLV-1 before LDLT received a graft from an HTLV-1 positive donor. Eight donors were HTLV-1 positive. Twenty-seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV-1 positive donors and two from negative donors. The 1-, 3- and 5-year HTLV-1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score ≥ 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV-1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development. The authors investigate the impact of human T cell leukemia virus type 1 in living donor liver transplantation and find that fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score > 15 are risk factors for T cell leukemia development See editorial by Kaul on page 1365..
1480. Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Kazutoyo Morita, Naotaka Hashimoto, Hiroto Kayashima, Tohru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihko Maehara, The long-term outcomes of patients with hepatocellular carcinoma after living donor liver transplantation
A comparison of right and left lobe grafts, Surgery today, 10.1007/s00595-011-0086-4, 42, 6, 559-564, 2012.06, Purpose The feasibility of living donor liver transplantation (LDLT) using left lobe (LL) grafts has been demonstrated. However, the long-term outcome of the hepatocellular carcinoma (HCC) patients with LL grafts has not been elucidated. The aim of this study was to analyze the long-term outcomes after LDLT for HCC according to the graft type. Methods A retrospective analysis was performed evaluating the outcomes of LL graft recipients (n = 82) versus recipients of RL grafts (n = 46). The analysis endpoints were the overall and recurrence-free survival after LDLT. The demographics of both recipients and donors, and the tumor characteristics associated with the graft type were also analyzed. Results The graft volume (436 ± 74 g), as well as the graft volume-standard liver volume rate (38.3 ± 6.2%) of the LL graft group were significantly decreased as compared to those of the RL graft group (569 ± 82 g, 46.3 ± 6.7%; P>0.01). The 1-, 3-, 5- and 7-year overall survival rates of the LL graft group were 88.2, 80.2, 75.7 and 72.4%, respectively, which were not significantly different compared to those of the RL graft group (95.4, 87.3, 87.3 and 87.3%). The recurrence-free survival rates of the LL graft group (89.1% at 1 year, 78.8% at 3 years, 75.8% at 5 years and 70.3% at 7 years) were similar to those of the RL graft group (88.6, 88.6, 88.6 and 88.6%). The mean peak postoperative total bilirubin levels and duration of hospital stay after surgery for the LL grafting donors were significantly decreased as compared to those of the RL grafting donors (P>0.01). The rate of severe complications (over Clavien's IIIa) associated with LL graft procurement was 6.2%, which was lower than that in the RL graft group (15.6%). Conclusions The long-term outcomes in the HCC patients with LL grafts were similar to those of patients receiving RL grafts, and the outcomes of the donors of LL grafts were more favorable. Therefore, LL grafts should be considered when selecting LDLT for HCC to ensure donor safety..
1481. Takeo Toshima, Ken Shirabe, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Outcome of hepatectomy for hepatocellular carcinoma in patients with renal dysfunction, HPB, 10.1111/j.1477-2574.2012.00452.x, 14, 5, 317-324, 2012.05, Objectives: There are few reports on the efficacy of hepatectomy for hepatocellular carcinoma (HCC) in patients with renal dysfunction (RD). This study aimed to clarify the validity of hepatectomy for treating HCC in RD patients, and to compare postoperative courses in RD and non-RD patients. Methods: The clinical features of 722 HCC patients who underwent curative hepatectomy between 1986 and 2009 were retrospectively reviewed. Seventeen patients (2.4%) with preoperative serum creatinine levels of >2.0 mg/dl were defined as the RD group, and, of these, seven who did not receive preoperative haemodialysis were defined as borderline patients. Clinicopathological characteristics and postoperative outcomes were compared between the RD group (n= 17) and the non-RD group (n= 705). The postoperative courses of borderline patients were reviewed in detail. Results: Overall survival (P= 0.177) and disease-free survival (P= 0.942) after hepatectomy did not differ significantly between the groups. Incidences of massive ascites (35.3% vs. 14.3%; P= 0.034) and pleural effusion (52.9% vs. 17.6%; P= 0.001), defined as massive effusion (ME), were significantly higher in the RD group than in the non-RD group. Hypoalbuminaemia (≤2.8 g/dl; P= 0.031), heavy blood loss (≥1000 ml; P= 0.012) and intraoperative blood transfusion (P= 0.007) were risk factors for ME. Among the borderline patients, serum creatinine values were not increased immediately after surgery and four patients underwent haemodialysis. Conclusions: Preoperative hypoalbuminaemia, heavy blood loss and blood transfusion are independent risk factors for ME in RD patients. Preoperative improvement of anaemia and reduction of blood loss by meticulous surgical techniques may prevent ME in RD patients who require hepatectomy for HCC..
1482. Takeo Toshima, Akinobu Taketomi, Toru Ikegami, Takasuke Fukuhara, Hiroto Kayashima, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, V5-drainage-preserved right lobe grafts improve graft congestion for living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3182488bd8, 93, 9, 929-935, 2012.05, Background: Right lobe (RL) grafts without middle hepatic vein for living donor liver transplantation (LDLT) result in congestion of recipients' livers and sometimes in unfavorable postoperative course. This study aimed to evaluate the feasibility of our new V5-drainage-preserved RL (VP-RL) graft. Methods: Based on a review of 49 donors' livers in a retrospective study using three-dimensional reconstruction-computed tomography volumetry, hepatic vein draining segment 4 (V4) anatomy was classified into three types: inferior V4 dominant (A); superior V4 dominant (B); and umbilical vein to left hepatic vein dominant (C). Differences in functional graft volume (GV) and remnant liver volume (RV) between VP-RL and modified RL (M-RL) grafts with all three types were evaluated. In a prospective study of actual 15 LDLT, the outcome of venous reconstruction and postoperative parameters with VP-RL grafts compared with M-RL grafts was analyzed. Results: In the retrospective study using three-dimensional reconstruction-computed tomography volumetry, in types B and C, functional GV of VP-RL was larger than that of M-RL (P<0.05) without impaired donors' functional RV, whereas functional RV in VP-RL was significantly decreased in type A (P<0.05). In the prospective study of actual 15 LDLT, using VP-RL with types B and C, size and number of venous reconstructions, and functional GV and postoperative parameters, such as postoperative serum total bilirubin levels and ascites volume, were significantly improved compared with those using M-RL (P<0.05). Conclusions: Using preoperative V4 anatomical classification, VP-RL graft procurement is a valuable strategy in RL-LDLT to improve postoperative course of both recipients and donors..
1483. Rumi Matono, Shohei Yoshiya, Takashi Motomura, Takeo Toshima, Hiroto Kayashima, Toshiro Masuda, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Factors linked to longterm survival of patients with hepatocellular carcinoma accompanied by tumour thrombus in the major portal vein after surgical resection, HPB, 10.1111/j.1477-2574.2011.00436.x, 14, 4, 247-253, 2012.04, Objectives: The prognosis in patients with hepatocellular carcinoma (HCC) accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this study was to clarify the factors linked to survival of >5 years after hepatectomy in HCC patients with MPVTT. Methods: Twenty-nine HCC patients with MPVTT were divided into two groups comprising, respectively, patients who survived >5 years after hepatectomy (survivors, n = 5) and those who did not (non-survivors, n = 24). The two groups were compared. Results: Overall survival rates at 1, 3 and 5 years were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had recurrences of HCC in which the number of recurrent nodules was under four. Three (21.4%) of the 14 non-survivors who underwent curative resection experienced recurrences of HCC and all of them demonstrated fewer than four recurrent nodules (P = 0.0114). Local therapy, such as radiofrequency ablation and resection of recurrence, had more often been used in survivors than in non-survivors (P = 0.0364). Conclusions: Although surgical outcomes in patients with HCC accompanied by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the number of recurrent nodules is less than four, local therapy should be selected with the aim of achieving 5-year survival..
1484. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Tomoharu Yoshizumi, Mizuki Ninomiya, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Bacterial sepsis after living donor liver transplantation
The impact of early enteral nutrition, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2011.12.001, 214, 3, 288-295, 2012.03, Background: Bacterial sepsis is a significant problem that must be addressed after living donor liver transplantation (LDLT). Study Design: A retrospective analysis of 346 adult-to-adult LDLT patients was performed. Results: Forty-six patients (13.3%) experienced bacterial sepsis, with primary and secondary origins in 23.9% and 76.1%, respectively. Gram-negative bacteria accounted for 71.7% of the bacteria isolated. The 2-year cumulative graft survival rate in patients with bacterial sepsis was 45.7%. Patients with bacterial sepsis secondary to pneumonia (n = 12) had poorer 2-year graft survival rates (16.7%) than did those with primary or other types of secondary sepsis (p = 0.004). Multivariate analysis showed that intraoperative massive blood loss >10L (p < 0.001) and no enteral feeding started within 48 hours after transplantation (p = 0.005) were significant risk factors for bacterial sepsis. Among patients who received enteral nutrition, the incidences of bacterial sepsis in patients who received enteral nutrition within 48 hours (n = 135) or later than 48 hours (n = 57) were 5.9% and 21.0%, respectively (p = 0.002). The incidence of early graft loss was 8-fold higher in recipients with massive intraoperative blood loss without early enteral nutrition (p < 0.001). Conclusions: Early enteral nutrition was associated with significantly reduced risk of developing bacterial sepsis after LDLT..
1485. Takashi Motomura, Erina Koga, Akinobu Taketomi, Takasuke Fukuhara, Yohei Mano, Jun Muto, Hideyuki Konishi, Takeo Toshima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype, Hepatology Research, 10.1111/j.1872-034X.2011.00927.x, 42, 3, 288-295, 2012.03, Aim: A genetic polymorphism of inosine triphosphate pyrophosphatase (ITPA) has been associated with pegylated-interferon/ribavirin (PEG-IFN/RBV)-induced anemia in chronic hepatitis C patients. However, correlation of the genetic variant with anemia following liver transplantation has not been determined. Methods: Sixty-three hepatitis C virus (HCV)-positive patients who underwent liver transplantation and PEG-IFN/RBV therapy were enrolled. The rs1127354 was determined for each individual. Results: There was no relationship with anemia or RBV dosage in patients carrying the CC allele (CC group, n=43) and those carrying the CA allele (CA group, n=20). The incidence of hemoglobin (Hb) decline >3g/dL (CC: 4.7%, CA: 0%) was relatively low, whereas the incidence of Hb levels <10g/dL (CC: 18.6%, CA: 30.0%) was high. Univariate analysis revealed that splenectomy inversely correlated with Hb levels <10g/dL at 4weeks (P=0.04). Among the 22 patients who did not undergo splenectomy, the incidence of Hb levels <10g/dL tended to be lower in the seven patients carrying the CA allele (28.6%) than in the 15 patients with the CC allele (60.0%). Conclusion: The ITPA genetic polymorphism does not correlate with post-transplant PEG-IFN/RBV-induced anemia. Splenectomy is useful in preventing anemia regardless of the ITPA genotype..
1486. Jun Muto, Yohei Mano, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Additional resection of the pancreas body prevents postoperative pancreas fistula in patients with portal annular pancreas who undergo pancreaticoduodenectomy, Case Reports in Gastroenterology, 10.1159/000335210, 6, 1, 131-134, 2012.01, Portal annular pancreas (PAP) is a rare variant in which the uncinate process of the pancreas extends to the dorsal surface of the pancreas body and surrounds the portal vein or superior mesenteric vein.Upon pancreaticoduodenectomy (PD), when the pancreas is cut at the neck, two cut surfaces are created. Thus, the cut surface of the pancreas becomes larger than usual and the dorsal cut surface is behind the portal vein, therefore pancreatic fistula after PD has been reported frequently. We planned subtotal stomach-preserving PD in a 45-year-old woman with underlying insulinoma of the pancreas head. When the pancreas head was dissected, the uncinate process was extended and fused to the dorsal surface of the pancreas body. Additional resection of the pancreas body 1 cm distal to the pancreas tail to the left side of the original resection line was performed. The new cut surface became one and pancreaticojejunostomy was performed as usual. No postoperative complications such as pancreatic fistula occurred. Additional resection of the pancreas body may be a standardized procedure in patients with PAP in cases of pancreas cut surface reconstruction..
1487. Hideaki Uchiyama, Ken Shirabe, Masaru Morita, Yoshihiro Kakeji, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Noboru Harada, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Expanding the applications of microvascular surgical techniques to digestive surgeries
A technical review, Surgery today, 10.1007/s00595-011-0032-5, 42, 2, 111-120, 2012.01, In living donor liver transplantation (LDLT), it is considered safer to reconstruct hepatic arteries (HAs) under a microscope than under conventional loupe magnification, because graft HA stumps are generally thin and short with an average diameter of approximately 2 mm. We first applied microvascular surgical techniques to HA reconstruction for LDLT in 1996. In most cases, we use a disposable double-clip to secure the graft and recipient arteries, and interrupted 8-0 nonabsorbable monofilament sutures. We next started performing resection and reconstruction of the right HA in a surgery for hilar cholangioma using the same technique as in LDLT. Lately, we have started applying microvascular surgical techniques to various digestive surgeries; namely, supercharge and superdrainage in esophageal surgery, vascular reconstruction in free jejunal interposition grafts for cervical esophageal cancer, resection and reconstruction of spontaneous HA aneurysms, jejunal artery reconstruction for spontaneous superior mesenteric artery dissections, and so forth. Mastering this technique is time consuming. However, once a surgeon masters the technique it has almost unlimited applications, and most vital vessels can be safely reconstructed using this method. We herein provide a technical review of the application of microvascular surgical techniques for various digestive surgeries..
1488. Tomoharu Yoshizumi, Ken Shirabe, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Masanori Yoshimatsu, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Risk factors that increase mortality after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e318238dacd, 93, 1, 93-98, 2012.01, BACKGROUND.: Female liver to male recipient is a well-accepted risk factor for graft loss in cadaveric liver transplantation. However, gender matching is infeasible because of an insufficient number of available donors. No studies have been performed on the role of gender in the field of living donor liver transplantation. This report investigates the effect of gender mismatch on the outcome of living donor liver transplantation. METHODS.: A total of 335 patients and donors were classified into four groups according to the following gender combinations: male donor to male recipient group (n=104), male donor to female recipient group (n=120), female donor to male recipient (FM) group (n=59), and female donor to female recipient group (n=52). Patient and graft survival were compared among the groups. We performed a multivariable analysis to identify the factors associated with patient mortality. RESULTS.: The 1-, 3-, 5-, and 10-year patient survival rates in the FM group were 80.6%, 66.8%, 61.8%, and 47.7%, respectively. The FM group showed significantly shorter patient survival compared with the other three groups. Independent risk factors for patient mortality were: FM group (P=0.006), pretransplant diabetes mellitus (P=0.001), and a model for end-stage liver disease score more than or equal to 20 (P=0.004). CONCLUSIONS.: Male recipients of transplants from female donors, pretransplant diabetes mellitus, and a model for end-stage liver disease score more than or equal to 20 have poor survival rates..
1489. Ken Shirabe, Yohei Mano, Jun Muto, Rumi Matono, Takashi Motomura, Takeo Toshima, Kazuki Takeishi, Hidekaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Masaru Morita, Shunichi Tsujitani, Yoshihisa Sakaguchi, Yoshihiko Maehara, Role of tumor-associated macrophages in the progression of hepatocellular carcinoma, Surgery today, 10.1007/s00595-011-0058-8, 42, 1, 1-7, 2012.01, Recent studies have shown that the tumor microenvironment plays an important role in cancer progression. Tumor-associated macrophages (TAMs), in particular, have been found to be associated with tumor progression. Macrophages have multiple biological roles, including antigen presentation, target cell cytotoxicity, removal of foreign bodies, tissue remodeling, regulation of inflammation, induction of immunity, thrombosis, and endocytosis. Recent immunological studies have identified two distinct states of polarized macrophage activation: the classically activated (M1) and the alternatively activated (M2) macrophage phenotypes. Bacterial moieties such as lipopolysaccharides and the Th1 cytokine interferon-γ polarize macrophages toward the M1 phenotype. The M2 polarization was discovered as a response to the Th2 cytokine interleukin-4. In general, M2 macrophages exert immunoregulatory activity, participate in polarized Th2 responses, and aid tumor progression. TAMs have recently been found to play an important role in hepatocellular carcinoma (HCC) progression. Based on the properties of TAMs, obtained from pathological examination of resected specimens, we have identified new therapeutic approaches, involving the targeting of TAMs with adjuvant therapy after hepatic resection for HCC. This review discusses the roles of TAM in HCC progression and the possibility of new therapies targeting TAMs..
1490. Toru Ikegami, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yoshihiko Maehara, The impact of renal replacement therapy before or after living donor liver transplantation, Clinical Transplantation, 10.1111/j.1399-0012.2011.01450.x, 26, 1, 143-148, 2012.01, Introduction: The impact of renal replacement therapy (RRT) in living donor liver transplantation (LDLT) has not yet been investigated. Methods: Among 253 LDLT patients, RRT was started before (RRT-Pre, n=9), or after (RRT-Post, n=27) LDLT. The clinical outcomes were reviewed. Results: The one-yr graft survival rate was 94.1% without RRT, and 63.9% and in those with RRT (p<0.0001). Among the RRT patients, the RRT-Pre patients exhibited acute liver failure, hepatorenal syndrome and high model for end-stage liver disease score (35±12), whereas the RRT-Post patients had sepsis as a comorbidity. The one-yr graft survival rate was 100.0% in the RRT-Pre patients vs. 51.9% in the RRT-Post patients (p<0.01). The duration of RRT was significantly shorter in the RRT-Pre patients than that in the RRT-Post patients (5.3±2.1 vs. 17.8±14.1d, p=0.02). The mean duration between starting RRT and LDLT was 2.1±0.7d in the Pre-RRT patients. Conclusion: The RRT-Pre patients had excellent outcomes because the severe condition was primarily treated by LDLT after short-term pre-transplant RRT. Post-transplant uncontrollable sepsis was the major cause of graft loss in patients who receive RRT after LDLT..
1491. Akinobu Taketomi, Kazuki Takeishi, Yohei Mano, Takeo Toshima, Takashi Motomura, Shinichi Aishima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Total resection of the right hepatic vein drainage area with the aid of three-dimensional computed tomography, Surgery today, 10.1007/s00595-011-0021-8, 42, 1, 46-51, 2012.01, Purpose: We analyzed the feasibility and safety of our preliminary surgical approach for total hepatic resection of the right hepatic vein drainage area (THR-RHV) with the aid of three-dimensional computed tomography (3D-CT) guidance. Methods: Clinical findings and 3D-CT volumetry results were investigated in five patients who underwent THR-RHV for a hepatic malignant tumor close to the right hepatic vein (RHV). Results: The mean estimated remnant liver volume after a conventional right lobectomy was 474 ml, whereas that after THR-RHV was 614 ml, indicating that 140 ml (13.8%) of additional liver volume had been preserved by performing THR-RHV. The median operative time, mean ischemic time, and mean blood loss during surgery were 406 min, 51 min, and 587 ml, respectively. Histological examinations confirmed a negative surgical margin in all five patients. The mean liver volume estimated by 3D-CT was 458 ml, whereas the mean actual resected liver volume was 468 g, resulting in a mean error ratio of 3.1%. Conclusions: THR-RHV allowed for a higher remnant liver volume than that after conventional right lobectomy of the liver, and proved feasible with acceptable perioperative results. This technique thus promotes both safety and curability for patients with a tumor close to the RHV..
1492. Eisuke Kawakubo, Yuji Soejima, Eigorou Yamanouchi, Mizuki Ninomiya, Hiroto Kayashima, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Case of magnetic compression anastomosis with double-balloon enteroscopy for biliary obstruction after living donor liver translationn, Japanese Journal of Gastroenterological Surgery, 10.5833/jjgs.44.1404, 44, 11, 1404-1410, 2011.12, Biliary anastomotic strictures are one of the most significant postoperative complications after living donor liver transplantations (LDLT), which develop in about 10-30% of recipients. Various modalities have been reported to treat these complications with an acceptable success rate. Herein, we present a case of complete anastomotic obstruction of hepaticojejunostomy, for which a successful magnetic compression anastomosis (MCA) was performed. The patient was a 56-year-old man who was given a diagnosis of biliary anastomotic strictures 9 months after LDLT. Conservative treatment, including percutaneous transhepatic biliary drainage (PTBD), was initially undertaken, however, re canalization of the bile duct anastomosis could not be obtained. An MCA was performed 3 months after the initial PTBD, which resulted in a success. In conclusion, MCA is a safe and very effective method to treat complete anastomotic strictures after LDLT..
1493. Tetsuo Ikeda, Yusuke Yonemura, Naoyuki Ueda, Akira Kabashima, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yosihiro Kakeji, Masaru Morita, Shunichi Tsujitani, Yoshihiko Maehara, Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic glissonian approach and a modified hanging maneuver to minimize intraoperative bleeding, Surgery today, 10.1007/s00595-010-4479-6, 41, 12, 1592-1598, 2011.12, Purpose: Although laparoscopic liver resection has been widely adopted, performing a pure laparoscopic right hepatectomy remains a challenging procedure. The aim of this report is to evaluate the efficiency of a pure laparoscopic right hepatectomy (PLRH) in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver. Methods: Pure laparoscopic right hepatectomy was performed in the semi-prone position with the use of an intrahepatic Glissonian approach and modified hanging maneuver for patients with primary liver cancer (n = 3) and metastatic liver cancer (n = 1). Results: The intraoperative total blood loss was only 95-140 g (mean: 126.2 g). None of the patients required a blood transfusion, and no serious complications were encountered. The durations of the surgeries ranged from were 308 to 445 min (mean: 394.8 min). The postoperative hospital stay was 8-11 days (mean 9.5 days). Conclusion: Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver is thus considered to be a safe modality, which minimizes intraoperative bleeding..
1494. Hideaki Uchiyama, Yohei Mano, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Ken Shirabe, Yoshihiko Maehara, Kinetics of anti-blood type isoagglutinin titers and B lymphocytes in ABO-incompatible living donor liver transplantation with rituximab and plasma exchange, Transplantation, 10.1097/TP.0b013e318231e9f8, 92, 10, 1134-1139, 2011.11, Background. A novel immunosuppression protocol using rituximab and plasma exchange treatment was developed for ABO-incompatible living donor liver transplantation (ABO-I LDLT). The aim of this study was to investigate the kinetics of anti-blood type isoagglutinin titers and the number of blood B lymphocytes in ABO-I LDLT with the new protocol and their impact on the outcomes after ABO-I LDLT. Methods. Fifteen patients underwent ABO-I LDLT plus splenectomy with the new protocol between November 2005 and December 2010, and their data were retrospectively analyzed. Results. CD19-positive lymphocytes in the blood rapidly disappeared after rituximab treatment and began to recover approximately 6 months later. Anti-blood type isoagglutinin titers were lowered by pretransplant plasma exchange (2 3∼2 12→2 1∼2 8). Although the anti-donor blood type isoagglutinin titers remained consistently low after transplantation in comparison to the pretreatment levels, they persisted long after LDLT, whereas posttransplant biopsy specimens showed sustained A/B antigens on the graft livers. ABO-I hepatitis C virus-positive patients were prone to acceleration of hepatitis C viremia and cytomegalovirus antigenemia in comparison to the control patients. Conclusions. Although the new protocol for ABO-I LDLT yielded great success with 100% graft survival, the acceptable anti-blood type isoagglutinin titers just before LDLT, and its application to hepatitis C-positive patients must be determined..
1495. Toru Ikegami, Ken Shirabe, Kazutoyo Morita, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Hiroto Kayashima, Naotaka Hashimoto, Yoshihiko Maehara, Minimal hilar dissection prevents biliary anastomotic stricture after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3182336073, 92, 10, 1147-1151, 2011.11, Background. We introduced a new technique called minimal hilar dissection (Min-HD) technique in living donor liver transplantation (LDLT) to keep vascular networks around the recipient's bile duct. The aim of this study is to investigate whether the Min-HD technique could prevent biliary anastomotic stricture (BAS) after LDLT with duct-to-duct biliary reconstruction. Methods. An analysis of 214 adult-to-adult LDLT grafts (left lobe, n=135; right lobe, n=76; posterior segment, n=3) with duct-to-duct biliary reconstruction was performed. Results. There were 46 cases with BAS. The incidence of BAS was 32.1% in the conventional technique group (n=84) and 14.6% in the Min-HD technique group (n=130, P=0.003). Multivariate regression analysis regarding BAS was carried out and detected hepatic artery flow less than 50 mL/min (P=0.002), not using the Min-HD technique (P=0.011), biliary anastomotic leakage (BAL, P=0.027) and ductoplasty (P=0.039) for the significant risk factors for BAS. The incidence BAL was 11.9% in the conventional technique group and 0.7% in the Min-HD technique group (P=0.002). No other factors showed an impact on the occurrence of BAL. The treatments for BAS were performed by endoscopic or percutaneous procedures. The cumulative completion rate of the treatment after developing BAS was 45.1% and 78.6% at 1-and 3-year, respectively. The median period for treating BAS was 10.8 months. Conclusion. The Min-HD technique is a rational surgical method, and it has the potential for preventing BAS and BAL after duct-to duct biliary reconstruction in LDLT..
1496. Ken Shirabe, Takeo Toshima, Akinobu Taketomi, Kennichi Taguchi, Tomoharu Yoshizumi, Hideaki Uchiyama, Norifumi Harimoto, Kiyoshi Kajiyama, Akinori Egashira, Yoshihiko Maehara, Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan, Liver International, 10.1111/j.1478-3231.2011.02572.x, 31, 9, 1366-1372, 2011.10, Background & aims: Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC. Methods: Hepatocyte AFB1-DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non-B non-C hepatocellular carcinoma (NBNC HCC). Results: AFB1-DNA adducts were detected in hepatocyte nuclei in 18/279 patients (6%), including13/83 patients (16%) with NBNC HCC and 5/51 patients (10%) expressing hepatitis B surface antigen. None of the patients with HCV Ab (n=136) were positive for AFB1-DNA. The incidence of the G-T transversion and mutations in exon 7 of TP53 in patients with AFB1-DNA adducts were significantly higher in patients with than in patients without AFB1-DNA adducts. All three patients with the codon 249 AGG-AGT mutation had AFB1-DNA adducts. Conclusion: Although exposure to AFB1 is thought to be low in Japan, it is still associated with hepatocarcinogenesis, particularly in NBNC HCC and hepatitis B individuals..
1497. Toru Ikegami, Takashi Maeda, Hiroto Kayashima, Eiji Oki, Tomoharu Yoshizumi, Yoshihisa Sakaguchi, Yasushi Toh, Ken Shirabe, Yoshihiko Maehara, Soft coagulation, polyglycolic acid felt, and fibrin glue for prevention of pancreatic fistula after distal pancreatectomy, Surgery today, 10.1007/s00595-010-4433-7, 41, 9, 1224-1227, 2011.09, Purpose: To evaluate the effectiveness of using soft coagulation followed by the application of polyglycolic acid (PGA) felt and fibrin glue to prevent pancreatic fistula (PF) after distal pancreatectomy (DP). Methods: A soft coagulation system was applied on the cut surface of the pancreas after ligating the main pancreatic duct, followed by the application of layers of PGA felt and fibrin glue on the layers, to prevent the development of a PF after DP. Results: This technique was applied in nine patients, with mean drain amylase levels of 372 ± 296, 185 ± 209, 54 ± 40, and 47 ± 34 IU/l on days 1, 3, 5, and 7, respectively, after DP. Only one patient (11.1%) showed a Grade A PF on day 3 after surgery; none of the other patients developed a fistula. Conclusions: This technique is an effective prophylactic measure to prevent the development of a PF after DP..
1498. Mizuki Ninomiya, Ken Shirabe, Hideki Ijichi, Takeo Toshima, Noboru Harada, Hideaki Uchiyama, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Temporal changes in the stiffness of the remnant liver and spleen after donor hepatectomy as assessed by acoustic radiation force impulse
A preliminary study, Hepatology Research, 10.1111/j.1872-034X.2011.00809.x, 41, 6, 579-586, 2011.06, Aim: Virtual touch tissue quantification (VTTQ) is an implementation of ultrasound acoustic radiation force impulse imaging that provides numerical measurements of tissue stiffness. We have evaluated the temporal changes of the remnant liver and spleen after living donor hepatectomy with special reference to the differences between right and left liver donation. Methods: Nineteen living donors who received right lobectomy (small remnant liver [SRL] group; n=7) or extended left and caudate lobectomy (large remnant liver [LRL] group; n=12) were enrolled. They underwent measurement of liver and spleen VTTQ before and after donor surgery. Results: Virtual touch tissue quantification of the remnant liver increased postoperatively until postoperative day (POD) 3-5, and the values in the SRL group were significantly higher than those in the LRL group at POD 3-9. The values of the spleen also increased after donor surgery and the values in the SRL group were significantly higher than those in the LRL group at POD 3-14. A significant positive correlation between postoperative maximum value of VTTQ and postoperative maximum total bilirubin levels was observed. In liver transplant recipients, there was a significant positive correlation between preoperative spleen VTTQ and the corresponding actual portal venous pressure that was measured at the time of transplant surgery. Conclusion: Stiffness of the remaining liver and spleen in the smaller remnant liver group became harder than that in the larger remnant liver group. Perioperative measurement of liver and spleen VTTQ seems to be a useful means for assessing the physiology of liver regeneration..
1499. T. Motomura, A. Taketomi, T. Fukuhara, Y. Mano, K. Takeishi, T. Toshima, N. Harada, H. Uchiyama, T. Yoshizumi, Y. Soejima, K. Shirabe, Y. Matsuura, Y. Maehara, The impact of IL28B genetic variants on recurrent hepatitis C in liver transplantation
Significant lessons from a dual graft case, American Journal of Transplantation, 10.1111/j.1600-6143.2011.03537.x, 11, 6, 1325-1329, 2011.06, IL28B genetic polymorphism is related to interferon-sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51-year-old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated-interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients. In this dual graft liver transplantation case, each graft with different IL28B genotype showed significantly different pathological findings and viral kinetics after interferon therapy for recurrent hepatitis C..
1500. Takeo Toshima, Ken Shirabe, Kazuki Takeishi, Takashi Motomura, Youhei Mano, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, New method for assessing liver fibrosis based on acoustic radiation force impulse
A special reference to the difference between right and left liver, Journal of gastroenterology, 10.1007/s00535-010-0365-7, 46, 5, 705-711, 2011.05, Background: Virtual touch tissue quantification (VTTQ) based on acoustic radiation force impulse (ARFI) imaging has been developed as a noninvasive bedside method for the assessment of liver stiffness. In this study, we examined the diagnostic performance of ARFI imaging in 103 patients, focusing on the difference in VTTQ values between the right and left liver lobes. Methods: We evaluated VTTQ values of the right and left lobes in 79 patients with chronic liver disease who underwent histological examination of liver fibrosis and in 24 healthy volunteers. The diagnostic accuracy of VTTQ was compared with several serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index. Results: The VTTQ values (meters per second) in the right and left lobes were 1.61 ± 0.51 and 1.90 ± 0.68, respectively, and the difference was statistically significant (P < 0.0001). The VTTQ values in both liver lobes were correlated significantly with histological fibrosis grades (P < 0.001). The standard deviations of the VTTQ values in the right lobe were significantly lower than those in the left lobe (P < 0.001). The area under the receiver-operating characteristic curve for the diagnosis of fibrosis (F ≥ 3) using VTTQ values in both liver lobes was superior to serum markers, especially in the right lobe. Conclusions: VTTQ is an accurate and reliable tool for the assessment of liver fibrosis. VTTQ of the right lobe was more accurate for diagnosing liver fibrosis than in the left lobe..
1501. Naotaka Hashimoto, Tomohiko Akahoshi, Tetsuya Shoji, Morimasa Tomikawa, Norifumi Tsutsumi, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Successful treatment for hepatic encephalopathy aggravated by portal vein thrombosis with balloon-occluded retrograde transvenous obliteration, Case Reports in Gastroenterology, 10.1159/000330287, 5, 2, 366-371, 2011.05, This report presents the case of a 78-year-old female with hepatic encephalopathy due to an inferior mesenteric venous-inferior vena cava shunt. She developed hepatocellular carcinoma affected by hepatitis C virus-related cirrhosis and underwent posterior sectionectomy. Portal vein thrombosis developed and the portal trunk was narrowed after hepatectomy. Portal vein thrombosis resulted in high portal pressure and increased blood flow in an inferior mesenteric venous-inferior vena cava shunt, and hepatic encephalopathy with hyperammonemia was aggravated. The hepatic encephalopathy aggravated by portal vein thrombosis was successfully treated by balloon-occluded retrograde transvenous obliteration via a right transjugular venous approach without the development of other collateral vessels..
1502. Mami Kanamoto, Mitsuo Shimada, Yuji Morine, Tomoharu Yoshizumi, Satoru Imura, Toru Ikegami, Hiroki Mori, Yusuke Arakawa, Beneficial effects of follistatin in hepatic ischemia-reperfusion injuries in rats, Digestive Diseases and Sciences, 10.1007/s10620-010-1401-4, 56, 4, 1075-1081, 2011.04, Background: Ischemia-reperfusion injury has been demonstrated in a variety of clinical settings. The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. Follistatin, an activin-binding protein, binds to activins and subsequently blocks their action. It was reported that blockade of the action of activin with administration of follistatin accelerates recovery from ischemia renal injury. This study was conducted to investigate the involvement of the activin-follistatin system in hepatic ischemia-reperfusion injury. Methods: Total hepatic ischemia for 30 min was performed followed by reperfusion in a rat model. Rats were divided into two groups: a follistatin group and a control group. Follistatin (1 μg/body), which is an activin-binding protein, was administered at the time of reperfusion. Results: Though 80% of animals survived in the follistatin group, four of five animals died in the control group within 3 days after reperfusion (p < 0.05). AST was significantly lower at 3 h after reperfusion in the follistatin group (p < 0.05). LDH was also lower at 6 h after reperfusion in the follistatin group (p < 0.05). Follistatin inhibited the mRNA expression of the βA subunit of activin. Moreover, the expression of IL-6, which is an inflammatory cytokine, was suppressed at 6 h after reperfusion in the follistatin group (p < 0.05). Conclusions: The present study demonstrated that treatment with follistatin reduced the expression of IL-6 and activin resulting in beneficial support for hepatic ischemia-reperfusion injuries..
1503. Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Toru Ikegami, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yoshihiko Maehara, Living donor liver transplantation in patients who have received pretransplant treatment for hepatocellular carcinoma, Transplantation, 10.1097/TP.0b013e318210de92, 91, 8, e61-e62, 2011.04.
1504. Ken Shirabe, Takashi Motomura, Jun Muto, Takeo Toshima, Rumi Matono, Yohei Mano, Kazuki Takeishi, Hideki Ijichi, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Tumor-infiltrating lymphocytes and hepatocellular carcinoma
Pathology and clinical management, International Journal of Clinical Oncology, 10.1007/s10147-010-0131-0, 15, 6, 552-558, 2010.12, The presence of tumor-infiltrating lymphocytes (TILs) in hepatocellular carcinoma (HCC) is relatively rare. The prognosis of patients with HCC and marked TILs is better than that of patients with HCC without TILs. TILs in HCC tissues are mainly T cells, and previous reports suggested that TILs might be important antitumor effector cells. TILs have been extensively analyzed, and subpopulations of CD3+, CD4+, and CD8+ T cells are often present in HCC. Some studies have reported that the percentage of CD8+ T cells, which might have cytotoxic activity, is decreased in tumors with TILs, as compared with noncancerous tissues. Although the antitumor effects of TILs seem to be impaired in HCCs, the underlying mechanism has remained unclear until quite recently. Pathological and in vitro studies have now shown that regulatory T cells play important roles in the deterioration of the antitumor effects of TILs. The aim of this review is to introduce recent pathological findings for TILs in HCC and to evaluate new therapeutic strategies in this field..
1505. T. Ikegami, Y. Soejima, K. Shirabe, A. Taketomi, T. Yoshizumi, H. Uchiyama, T. Fukuhara, T. Ikeda, Y. Maehara, Evolving strategies to prevent biliary strictures after living donor liver transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2010.07.091, 42, 9, 3624-3629, 2010.11, Introduction The optimal surgical technique has not been elucidated that reduces the occurrence of biliary strictures after living donor liver transplantation (LDLT). Method We performed retrospective analysis of 193 consecutive LDLTs, including 78 right and 115 left lobe grafts. An external biliary stent was used for all of the cases. Results The overall 1-, 3-, and 5-year biliary stricturefree survival rates were 87.5%, 85.3%, and 85.3%, respectively. The 1- and 3-year biliary stricturefree survival rates for duct-to-duct reconstruction were 86.9% and 84.9%, and those for hepaticojejunostomy were 90.1% and 80.8%, respectively. A multivariate analysis revealed that the original number of graft bile ducts greater than the number of external stents, right lobe grafts, bile leaks, and recipient age older than 60 years represented the significant risk factors (P < .05) to develop a biliary stricture after LDLT. All cases with biliary strictures (n = 61) were initially managed nonsurgically, but 4 patients ultimately required interventions. Conclusions Biliary reconstruction in LDLT using an appropriate number of external stents resulted in fairly acceptable outcomes. However, not only the proper use of stents or graft selection, but also nonsurgical factors, are important factors that determine the incidence of biliary strictures after LDLT..
1506. Akinobu Taketomi, Takasuke Fukuhara, Kazutoyo Morita, Hiroto Kayashima, Mizuki Ninomiya, Yoichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihko Maehara, Improved results of a surgical resection for the recurrence of hepatocellular carcinoma after living donor liver transplantation, Annals of Surgical Oncology, 10.1245/s10434-010-0999-y, 17, 9, 2283-2289, 2010.09, Purpose: This study was designed to analyze the clinical outcomes of the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and to evaluate the efficacy of a surgical resection in treating such a recurrence. Methods: A total of 101 adult LDLT recipients with HCC between 1996 and 2007, including 17 who had recurrent HCC, were reviewed. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics, laboratory valuables, and tumor characteristics were analyzed. Any medical or surgical treatments that had been administered for any recurrence also were considered. Results: The mean duration until the initial recurrence after LDLT and the mean duration until death after the initial recurrence were 12.9 months and 12.0 months, respectively. A univariate analysis showed that gender, interferon therapy, early posttransplant tumor recurrence, and eligibility for a surgical resection all had a beneficial impact on survival from tumor recurrence. A surgical resection of tumor relapse was the most important variable in our study, and therefore the patients were divided into two groups: surgical therapy group (n = 9), and nonsurgical therapy group (n = 7). Interestingly, the overall survival rates of the surgical group were significantly better than those of the nonsurgical group and were similar to that of the patients without HCC recurrence. Conclusions: Surgical therapy might be useful for patients who experience a recurrence of HCC after LDLT to improve their outcome, when such treatment is available..
1507. Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Natsumi Yamashita, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Mizuki Ninomiya, Yoshihiko Maehara, Living donor liver transplantation in patients older than 60 years, Transplantation, 10.1097/TP.0b013e3181e81b2d, 90, 4, 433-437, 2010.08, Background. Living donor liver transplantation (LDLT) has been performed in adult patients. However, there are a few reports on how recipient age affects the outcome of LDLT. This study assessed LDLT outcome in patients aged 60 years or older. Methods. A total of 267 patients were enrolled and classified into two groups: those younger than 60 years (younger group, n=210) and those aged 60 years or older (older group, n=57). The 6-month and 1-, 3-, and 5-year patient survivals and the incidence of complications were compared. Multivariate analysis was performed to identify the risk factors. Results. Fifty-five of 57 (96.5%) donors in the older group were younger than 50 years (range 25-47 years), whereas only 177 of 210 (84.3%) donors in the younger group were younger than 50 years (P<0.0001). The 6-month and 1-, 3-, and 5-year patient survival rates of the older group were 92.9%, 85.3%, 72.7%, and 70.3%, respectively, whereas those of the younger group were 87.4%, 85.8%, 80.2%, and 78.2%, respectively. Neither difference was significant. A multivariate analysis revealed that the presence of diabetes, lack of hepatocellular carcinoma, and Model for End-Stage Liver Disease (MELD) Score more than or equal to 20 were independent risk factors for survival less than 1 year after LDLT (P=0.0003, P=0.014, and P=0.041, respectively). Another multivariate analysis revealed that the lack of consanguinity, MELD Score more than or equal to 20, and male recipient were independent risk factors for death 1 year or more after LDLT (P=0.004, P=0.005, and P=0.015, respectively). Conclusion. Recipient age did not affect LDLT outcome when patients with MELD Score less than 20 received grafts from consanguineous donors..
1508. Tomonobu Gion, Akinobu Taketomi, Ken Shirabe, Hirofumi Hasegawa, Takayuki Hamatsu, Yo Ichi Yamashita, Keishi Sugimachi, Tomoharu Yoshizumi, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, The role of serum interleukin-8 in hepatic resections, Surgery today, 10.1007/s00595-008-4086-y, 40, 6, 543-548, 2010.06, Purpose: Interleukin-8 (IL-8) is a neutrophil chemotactic factor, which is associated with some inflammatory diseases and various types of surgical stress. The aim of this study was to investigate whether the early postoperative serum IL-8 level may potentially be a new indicator of a surgical stress in patients undergoing a hepatic resection. Methods: The serum IL-8 levels were measured in 37 patients who underwent a hepatectomy. The serum IL-8 levels were serially measured using an enzyme-linked immunosorbent assay both before and after a hepatic resection. In addition, the correlation between the postoperative IL-8 value and several clinical variables were examined. Results: The mean level of IL-8 significantly increased immediately after the operation (P < 0.01 vs before the operation) and decreased on the first postoperative day (POD 1, P < 0.05 vs after the operation). The early postoperative IL-8 levels positively correlated with the length of the procedure (r = 0.383; P < 0.05), the estimated blood loss (r = 0.483; P < 0.01) and the serum bilirubin level on POD 1 (r = 0.390; P < 0.05), and inversely correlated with the white blood cell counts (r = -0.388; P < 0.05) and lymphocyte counts on POD 1 (r = -0.424; P < 0.05). In a comparison of the postoperative IL-8 levels with the surgical factors, there was a significant difference in the extension of the resection (P < 0.05) and in blood transfusion. The patients with a fever of more than 38°C showed higher levels of IL-8 immediately after the operation than those without fever (P < 0.01). Conclusions: The early postoperative serum IL-8 level was found to correlate with the degree of the severity of surgery in patients undergoing a hepatic resection, and it is also considered to be a new indicator of surgical stress and liver injury..
1509. Takasuke Fukuhara, Toru Ikegami, Kazutoyo Morita, Kenji Umeda, Shigeru Ueda, Shigeyuki Nagata, Keishi Sugimachi, Tomonobu Gion, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Impact of preoperative serum sodium concentration in living donor liver transplantatio, Journal of Gastroenterology and Hepatology (Australia), 10.1111/j.1440-1746.2009.06162.x, 25, 5, 978-984, 2010.05, Background and Aims: The importance of hyponatremia in deceased donor liver transplantation (DDLT) has been recently discussed frequently. However, its impact on the outcomes in living donor liver transplantation (LDLT) has not yet been elucidated. The current study was designed to demonstrate the impact of pre-transplant sodium concentration on postoperative clinical outcomes. Methods: One hundred and thirty-four patients who underwent LDLT for end-stage liver diseases were examined to evaluate the significance of pre-transplant hyponatremia (Na ≤ 130 mEq/L) on the short-term clinical outcomes and the efficacy of the Model for End-Stage Liver Disease and serum sodium (MELD-Na) score using the sodium concentration and original MELD score. Results: The preoperative sodium and MELD score for all patients were 133.9 mEq/L (range: 109-142) and 16.2 (range: 6-38), respectively. According to a multivariate analysis, not only the MELD score (P = 0.030) but also the sodium concentration (P = 0.005) were found to be significant predictive factors for short-term graft survival. Preoperative hyponatremia was a significant risk factor for the occurrence of sepsis (P < 0.001), renal dysfunction (P < 0.001) and encephalopathy (P = 0.026). The MELD-Na score was 19.6 (range: 6-51) and the area under the receiver-operator curve of that (c-statistics: 0.867) was higher than MELD score and sodium concentration (c-statistics: 0.820 and 0.842, respectively). Conclusion: Preoperative hyponatremia was a significant risk for postoperative complications and short-term graft loss. The addition of sodium concentration to MELD score might therefore be an effective predictor for post-transplant short-term mortality in LDLT..
1510. Keishi Sugimachi, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Yo Ichi Yamashita, Kenji Umeda, Kazutoyo Morita, Yoshihiko Maehara, Successful curative extracorporeal hepatic resection for far-advanced hepatocellular carcinoma in an adolescent patient, Liver Transplantation, 10.1002/lt.22051, 16, 5, 685-687, 2010.05.
1511. Yuuta Kasagi, Koji Yamazaki, Akihiko Nakashima, Takeshi Yamana, Nami Yamashita, Hiroto Kayashima, Yuji Hoshino, Mayumi Ishida, Tomoharu Yoshizumi, Noriaki Sadanaga, Atsushi Fukuda, Hiroshi Matsuura, Kenichiro Okadome, Chondroblastic osteosarcoma arising from the pleura
Report of a case, Surgery today, 10.1007/s00595-009-3995-8, 39, 12, 1064-1067, 2009.12, Extraskeletal osteosarcoma is an uncommon malignant neoplasm. The origin of osteosarcoma in the pleura is extremely rare, with only four such cases so far documented in the literature to the best of our knowledge. We herein report the case of a 64-year-old Japanese man in whom a left pneumonectomy and pleurectomy were carried out to remove a huge tumor. The pathological examination confi rmed a diagnosis of chondroblastic osteosarcoma that had originally arisen from the pleura..
1512. T. Ikegami, A. Taketomi, Y. Soejima, T. Yoshizumi, T. Fukuhara, K. Kotoh, S. Shimoda, M. Kato, Y. Maehara, The Benefits of Interferon Treatment in Patients Without Sustained Viral Response After Living Donor Liver Transplantation for Hepatitis C, Transplantation Proceedings, 10.1016/j.transproceed.2009.08.070, 41, 10, 4246-4252, 2009.12, Although it has been recognized that interferon (IFN) treatment is crucial for recurrent hepatitis C after liver transplantation, its benefits have not been determined among patients without a sustained viral response (SVR). Methods: Eighty patients who received IFN plus ribavirin treatment after living donor liver transplantation were grouped as follows: group I (n = 18) SVR; group II (n = 25) no-SVR but viral response [VR] positive; Group III (n = 13) no-VR but biochemical response [BR] positive; and group IV (n = 24) no-VR and no-BR. Results: In groups II and III, not only the histological activity grade and fibrosis stage, but also the serum parameters including transaminases and type IV collagen were stable for 3 years after induction of IFN-based treatment. In group I, the activity grade and fibrosis stage significantly improved (P < .01). In group IV, the fibrosis stage significantly deteriorated (P < .01); the serum transaminases and type IV collagen were significantly higher than the other groups (P < .01). The mean duration of IFN treatment was significantly longer among group II (96 weeks) compared with the other cohorts (P < .05). The 5-year graft survival rate in groups II (91%) and III (100%) were comparable to those of group I (100%); group IV (62%) was significantly lower than the other groups (P < .05). Conclusion: IFN treatment was beneficial even among subjects with IFN-dependent VR or BR, although they did not achieve SVR..
1513. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Tashiharu Salbara, Takashi Nishizaki, Yoshihiko Maehara, Recurrent familial hypobetalipoproteinemia-induced nonalcoholic fatty liver disease after living donor liver transplantation, Liver Transplantation, 10.1002/lt.21766, 15, 7, 806-809, 2009.08, Familial hypobetalipoproteinemia (FHBL) is one of the causes of nonalcoholic steatohepatitis (NASH) and a codominant disorder. Patients heterozygous for FHBL may be asymptomatic, although they demonstrate low plasma levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Here we report a nonobese 54-year-old man with decompensated liver cirrhosis who underwent living donor liver transplantation with his son as the donor. Low albuminemia and refractory ascites persisted after transplantation. A biopsy specimen obtained 11 months after liver transplantation revealed severe steatosis and fibrosis, and recurrent NASH was diagnosed on the basis of pathological findings. Both the patient's and donor's laboratory tests demonstrated low LDL cholesterol and apolipoprotein levels. Because mutations in messenger RNAs of microsomal triglyceride transfer protein and apolipoprotein B genes were excluded neither in the recipient nor in the donor, both were clinically diagnosed as being heterozygous for FHBL. We successfully treated the recipient with heterozygous FHBL-induced recurrent NASH after liver transplantation using our diet and exercise programs..
1514. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Tomohiro Iguchi, Naotaka Hashimoto, Yoshihiko Maehara, Rituximab, IVIG, and plasma exchange without graft local infusion treatment
A new protocol in ABO incompatible living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3181adcae6, 88, 3, 303-307, 2009.08, BACKGROUND. Although graft local infusion (GLI) treatment via the portal vein or the hepatic artery has been the pivotal strategy in ABO incompatible (ABOi) living donor liver transplantation (LDLT) in Japan, the procedure is associated with a high rate of catheter-associated complications. METHODS. A new ABOi-LDLT protocol has been implemented using rituximab, intravenous immune globulin (IVIG), plasma exchange (PE), and splenectomy, without using GLI, on four patients, since 2007. Three other patients, treated before 2007, received GLI. RESULTS. Three of the four patients with liver cirrhosis received rituximab over 3 weeks before LDLT, followed by PEs and post-LDLT IVIG, resulting in no rebound elevation of the isoagglutinin titers. The remaining patient, with fulminant hepatitis, received rituximab 3 days before the LDLT, resulting in antibody-mediated rejection, successfully treated by IVIG and PE. All four patients that were treated with the new protocol are alive, 26, 8, 6, and 5 months after ABOi-LDLT with normal liver function. Two of the three other patients with GLI, before 2007, had catheter-associated complications, including one graft loss. CONCLUSION. The new ABOi-LDLT protocol using rituximab, IVIG, and PE, without the use of GLI, therefore seems to be a safe and an effective treatment modality..
1515. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Shigeyuki Nagata, Yoshihiko Maehara, Potential risk in using hepatic veins of a native liver for reconstructing accessory veins in right lobe living donor graft, Transplantation, 10.1097/TP.0b013e3181aae502, 88, 1, 143-144, 2009.07.
1516. T. Yoshizumi, Y. Ikeda, Y. Kaneda, K. Sueishi, Ex Vivo Transfer of Nuclear Factor-κB Decoy Ameliorates Hepatic Cold Ischemia/Reperfusion Injury, Transplantation Proceedings, 10.1016/j.transproceed.2008.10.101, 41, 5, 1504-1507, 2009.06, Cold ischemia/reperfusion injury of the hepatic graft has been attributed to the release of various inflammatory cytokines. Specific inhibition of these cytokines may improve viability of the hepatic graft upon reperfusion. Herein we have assessed the efficacy of cis element decoy against nuclear factor-κB binding site delivery to the hepatic tissue in a rodent liver transplantation model. At 8 hours after reperfusion of the liver, significant reduction was noted in the livers treated with decoy in the release of cytosolic enzymes from the hepatocytes and in serum tumor necrosis factor α (P < .05). The neutrophilic infiltration into the hepatic grafts was significantly suppressed in the livers treated with decoy oligodeoxynucleotides (ODNs). Decoy ODNs against nuclear factor-κB binding site delivery improved the viability of the hepatic graft against cold ischemia/reperfusion injury in the rodent liver transplantation model..
1517. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hirofumi Kawanaka, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Hypersplenism after living donor liver transplantation, Hepato-gastroenterology, 56, 91-92, 778-782, 2009.05, Background/Aims: It has not determined whether post-transplant persistent hypersplenism (PTPH) occurs after living donor liver transplantation (LDLT). Methodology: One hundred and ninety-four patients who survived more than 6 months after LDLTs were examined for the evaluation to determine the incidence of PTPH (leukocyte counts <3,500/μL and/or platelet counts <7.5×104/μL). In addition, 154 patients without a splenectomy were evaluated for the risk factors for PTPH. Results: The incidence of PTPH was 20.1% (n=31/154), and the occurrence ranged between 1.1 and 9.9 years after the LDLT, with the mean follow-up periods of 3.3±2.5 years. Multivariate analysis showed that portal pressure >30mmHg at the time of the laparotomy (p<0.01) and post-LDLT small for size syndrome (p<0.01) are risk factors for PTPH. For those with severe portal hypertension (>30 mmHg at laparotomy), the splenectomy tended to give better survival rate (p=0.09) without increasing the rate of septic complications. Conclusions: Hypersplenism did persist in a proportion of patients after LDLT. A high-risk for PTPH, especially severe portal hypertension, may be an indication for a splenectomy during LDLT in order to achieve uncomplicated post-transplant recovery..
1518. Yusuke Arakawa, Mitsuo Shimada, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Hirohumi Kanemura, Beneficial effects of splenectomy on massive hepatectomy model in rats, Hepatology Research, 10.1111/j.1872-034X.2008.00469.x, 39, 4, 391-397, 2009.04, Aim: Possible spleno-hepatic relationships during hepatectomy remain unclear. The purpose of this study was to investigate the impact of splenectomy during massive hepatectomy in rats. Methods: Rats were divided into the following two groups: 90% hepatectomy (Hx group), hepatectomy with splenectomy (Hx+Sp group). The following parameters were evaluated; survival rate, biochemical parameters, quantitative RT-PCR for hemeoxygenase-1 (HO-1) and tumor necrosing factor α (TNFα), immunohistochemical staining for HO-1, proliferating cell nuclear antigen labeling index and liver weights. Results: The survival rate after massive hepatectomy significantly improved in Hx+Sp group as well as serum biochemical parameters, compared with Hx group (P < 0.05). HO-1 positive hepatocytes and its mRNA expression significantly increased and TNFα mRNA expression significantly decreased in Hx+Sp group compared with Hx group (P < 0.05). Moreover, liver regeneration was significantly accelerated at 48 and 72 h after hepatectomy in Hx+Sp group. Conclusions: Splenectomy had beneficial effects on massive hepatectomy by ameliorating liver injuries and promoting preferable liver regeneration..
1519. Toru Ikegami, Mitsuo Shimada, Satoru Imura, Yuji Soejima, Tomoharu Yoshizumi, Jun Hanaoka, Yuji Morine, Yoshihiko Maehara, The changes of the medial right lobe, transplanted with left lobe liver graft from living donors, Transplantation, 10.1097/TP.0b013e318195c2a3, 87, 5, 698-703, 2009.03, Background. Procurement of left lobe (LL) living donor graft with medial right lobe (mRL) might be an innovative technique. Methods. The grafts were procured from a living donor, exposing the right anterior Glissonean pedicles, after confirmation of the demarcation line by test-clamping of the right Glissonean pedicle. Based on serial computed tomography, the increase in the graft volume (GV) after addition of mRL and changes in volumes were evaluated. Results. The addition of mRL (n=7) increased GV by 48±9 g, which corresponded to a 4% increase in GV-to-standard liver volume ratio. After transplantation, mRL volume has increased in all cases. The regeneration rate of the mRL and other LL segments 1 month after transplantation was 61%±18% and 146%±15%, respectively. Viable hepatic parenchyma with marginal bile duct dilatations in transplanted mRL was observed in all the cases. Marginal enhancement was observed in those cases with promoted regeneration of transplanted mRL. In the cranial part of the mRL, portal branching from the left portal vein, over the middle hepatic vein, was observed in all cases. Conclusion. This technique affords an increase in GV in living donor LL procurement, and should increases the application of LL grafts in living donor liver transplantation..
1520. Toru Ikegami, Takeo Toshima, Kazuki Takeishi, Yuji Soejima, Hirofumi Kawanaka, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Bloodless Splenectomy During Liver Transplantation for Terminal Liver Diseases with Portal Hypertension, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2008.10.034, 208, 2, e1-e4, 2009.02.
1521. Akinobu Taketomi, Hiroto Kayashima, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, Donor risk in adult-to-adult living donor liver transplantation
Impact of left lobe graft, Transplantation, 10.1097/TP.0b013e3181943d46, 87, 3, 445-450, 2009.02, Background.: To ensure donor safety in adult-to-adult living donor liver transplantation, we established a selection criterion for donors in which left lobe (LL) was the first choice of graft. Methods.: Two hundred six consecutive donors were retrospectively studied. Donors were divided into two groups according to graft type: LL graft (n=137) and right lobe (RL) graft (n=69). Results.: Although mean intraoperative blood loss of LL was significantly increased compared with RL, mean peak postoperative total bilirubin levels and duration of hospital stay after surgery were significantly less for LL than RL (P<0.05). No donor died or suffered a life-threatening complication during the study period. The overall complication rate was 34.0%, including biliary complications in 5.3%. The number of biliary complications was four (2.9%) in LL and seven (10.1%) in RL (P<0.05). Logistic regression analysis revealed that only graft type (LL vs. RL) is significantly related to the occurrence of biliary complications (odds ratio 0.11; P=0.0012). The cumulative overall graft survival rates in the recipients with LL were not significantly different from that in the recipients with RL. Conclusions.: LL grafting should be considered favorably when selecting donors for adult-to-adult living donor liver transplantation..
1522. Akinobu Taketomi, Kensaku Sanefuji, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uhciyama, Toru Ikegami, Noboru Harada, Yoichi Yamashita, Keishi Sugimachi, Hiroto Kayashima, Tomohiro Iguchi, Yoshihko Maehara, Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3181943bee, 87, 4, 531-537, 2009.02, BACKGROUNDS.: Because many patients who did not meet the Milan criteria have survived long after undergoing living donor liver transplantation (LDLT), extended criteria for recipient with hepatocellular carcinoma (HCC) are therefore considered to be necessary. METHODS AND RESULTS.: A total of 90 consecutive adult LDLT recipients with HCC between 1996 and 2007 were reviewed. The recurrence-free survival rates of all 90 patients were 86.0%, 81.3%, and 81.3% at 1, 3, and 5 years, respectively. Fourteen of 90 patients developed a recurrence of tumor after the LDLT. The tumor recurrences were diagnosed within 1 year after the LDLT in 11 (78.6%) patients. In a multivariate analysis, both the tumor size of less than 5 cm (P=0.0202) and the des-gamma-carboxy prothrombin (DCP) level of less than 300 mAU/mL (P=0.0001) were found to be favorable independent factors for the recurrence of HCC after LDLT. Therefore, the authors devised new selection criteria for HCC patients (a tumor size of <5 cm or a DCP of <300 mAU/mL). The 1-, 3-, and 5-year overall or recurrence-free survival rates of the 85 patients who met the new criteria were 92.3%, 85.9%, and 82.7%, or 90.5%, 87.0%, and 87.0%, respectively, which were significantly different from those of the five patients who did not meet the new criteria (P<0.0001). CONCLUSIONS.: A combination of two factors, namely the tumor size and the DCP level, was found to be useful for expanding the selection of LDLT candidates for HCC..
1523. Kensaku Sanefuji, Hiroto Kayashima, Tomohiro Iguchi, Keishi Sugimachi, Yo Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Takashi Nishizaki, Akinobu Taketomi, Yoshihiko Maehara, Characterization of hepatocellular carcinoma developed after achieving sustained virological response to interferon therapy for hepatitis C, Journal of Surgical Oncology, 10.1002/jso.21176, 99, 1, 32-37, 2009.01, Background: Interferon (IFN) reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). However, HCC develops in the some patients who have achieved a sustained virological response (SVR). The aim of this study was to clarify the features and prognosis of SVR patients who developed HCC. Materials and Methods: Twenty-six patients who underwent curative hepatectomy for initial HCC after IFN therapy were closely investigated. Twenty patients who were seropositive for HCV-RNA (non-SVR), and a further 6 patients who achieved SVRs (SVR) were included. We analyzed the clinicopathological features, immunological expression levels of p53 and whether HCV-RNA is present in the excised liver. Results: The liver functions of the SVR group were almost better than those of the non-SVR group. However, there was no significant difference in pathological features, surgical factors and prognosis between the groups. In one case with SVR out of eight specimens tested was HCV-RNA detected in the non-cancerous tissue. Immunohistochemistry revealed overexpression of p53 in eight HCCs (100%) from SVR patients. Conclusion: Recurrent HCC still developed after the curative hepatectomy, even if viral elimination had been successful. And molecular alterations in hepatocarcinogenesis of SVR patients might be different from those of CHC patients..
1524. Yuji Soejima, Takasuke Fukuhara, Kazutoyo Morita, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara, A simple hilar dissection technique preserving maximum blood supply to the bile duct in living donor liver transplantation, Transplantation, 10.1097/TP.0b013e318188d4dc, 86, 10, 1468-1469, 2008.11, Duct-to-duct reconstruction is associated with a higher incidence in biliary strictures in living donor liver transplantation (LDLT). However, a standard dissection technique for the recipient's bile duct has not been established. Here, we describe a simple bile duct dissection technique preserving maximum vascular integrity during total hepatectomy of the recipient. The present technique might facilitate duct-to-duct bile duct reconstruction in both right and left lobe LDLT and, thus, contribute to reduce biliary complications such as biliary strictures. We believe that this technique can be a standard in the field of LDLT..
1525. Takuya Tokunaga, Toru Ikegami, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Hisamitsu Shinohara, Mitsuo Shimada, Beneficial effects of fluvastatin on liver microcirculation and regeneration after massive hepatectomy in rats, Digestive Diseases and Sciences, 10.1007/s10620-008-0241-y, 53, 11, 2989-2994, 2008.11, Fluvastatin, the first entirely synthetic statin, has a significant cholesterol-lowing effect comparable with other statins. In addition, it has been shown to inhibit oxidative stress and improve vascular endothelial function. The aim of this study was to clarify the pretreatment effects of fluvastatin on liver function after massive hepatectomy in rats. Six-week-old male Wister rats were divided into two groups: a fluvastatin group (group F), pretreated with oral administration of fluvastatin (20 mg/kg per day) for 2 days before 90% hepatectomy; and a control group (group C), pretreated with vehicle for 2 days before hepatectomy. Animals were sacrificed at 0, 12, 24, 48, and 72 h after hepatectomy. The liver regeneration rate, liver function tests, and hepatic stellate cell activation were examined. The liver regeneration rate in group F was significantly higher at 72 h after hepatectomy (P < 0.05). The serum level of total bilirubin in group F was significantly lower at 48 h after hepatectomy (P < 0.05). Sinusoidal area in group F was maintained histologically. Furthermore, the expression of alpha smooth-muscle actin (α-SMA) protein in the liver was inhibited in group F at 48 h after hepatectomy. This study demonstrated the beneficial effects of fluvastatin in a lethal massive hepatectomy model using rats, with improved hepatic regeneration and microcirculations, by inhibiting the activation of hepatic stellate cells..
1526. Toru Ikegami, Akinobu Taketomi, Ryuji Ohta, Yiji Soejima, Tomoharu Yoshizumi, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, The risks of HBV infection after liver transplantation from HBc antibody positive donor to HBs antibody positive recipient, Hepato-gastroenterology, 55, 88, 2162-2165, 2008.11, The rate of de novo hepatitis B infection, after liver transplantation from a hepatitis B core antibody (HBcAb) (+) donor to a surface antibody (HBsAb) (+) recipient bas not yet elucidated. Four recipients with HBsAb (+) and HBcAb, (+), who received living donor grafts from HBcAb (+) donors were herein reviewed. They received lamivudine monotherapy: three patients with HBsAb titer >10 IU/L did not demonstrate the onset of HBsAg, whereas one patient with HBsAb titer <10 IU/L developed hepatitis B antigen (HBsAg) 4 years after transplantation. An HBsAb (+) patient with a titer of >10 IU/L is therefore considered not to require combination therapy when receiving an HBcAb (+) liver graft. However, a great deal of caution is necessary in patients with a negative or low HBsAb titers <10 IU/L..
1527. Y. Soejima, S. Ueda, K. Sanefuji, H. Kayashima, T. Yoshizumi, T. Ikegami, Y. Yamashita, K. Sugimachi, T. Iguchi, A. Taketomi, Y. Maehara, Sequential pancreaticoduodenectomy after living donor liver transplantation for cholagiocacinoma, American Journal of Transplantation, 10.1111/j.1600-6143.2008.02346.x, 8, 10, 2158-2162, 2008.10, Liver transplantation (LT) for patients with primary sclerosing cholangitis (PSC) is often contraindicated due to concomitant occurrence of cholangiocarcinoma (CC). Cases of simultaneous pancreaticoduodenectomy (PD) with LT have been sporadically reported; however, the applicability of such an invasive procedure to patients with CC has not been validated. We report here a case of sequential PD performed 44 days after a successful living donor liver transplantation (LDLT) using a left lobe graft. Although a clear pancreatic juice leakage through the drain persisted for days after surgery, the patient recovered from the complication and was discharged 32 days after the procedure. Currently, 1 year after LDLT, the patient is doing well with no evidence of recurrence. In conclusion, a sequential PD following LDLT is a safe and feasible option to treat CC complicating PSC. Long-term follow-up and accumulation of cases are necessary to evaluate the effectiveness of this procedure for this complicated disease..
1528. Hiroto Kayashima, Akinobu Taketomi, Yusuke Yonemura, Hideki Ijichi, Noboru Harada, Tomoharu Yoshizumi, Yuji Soejima, Kengo Yoshimitsu, Yoshihiko Maehara, Accuracy of an age-adjusted formula in assessing the graft volume in liver donor liver transplantation, Liver Transplantation, 10.1002/lt.21547, 14, 9, 1366-1371, 2008.09, In living donor liver transplantation, the estimated graft volume (GV) from young donors tends to be overestimated. One reason for this error may be a decrease in GV due to dehydration by University of Wisconsin (UW) solution. The aim of this study was to clarify (1) the usefulness of an age-adjusted formula and (2) the correlation between the decrease in GV and donor age. First, we created the age-adjusted formula using regression analysis retrospectively in 167 donors, and we evaluated the difference in the error ratio of GV from the age-adjusted formula and 3-dimensional computed tomography (3D-CT) prospectively in 49 donors. Second, we measured intraoperative GV both before and after flushing with UW solution and calculated the decrease ratio, and we then evaluated the difference in the decrease ratio between young donors and older donors prospectively in 41 donors. The age-adjusted formula was created as follows: age-adjusted GV = 70.767 + (0.703 × GV estimated with 3D-CT volumetry) + (1.298 × donor age). The mean error ratio for the age-adjusted formula (9.6%) was significantly lower than that from 3D-CT (14.0%). The mean decrease ratio in all 41 donors was 5.4%, and that in young donors (6.9%) was significantly higher than that in older donors (4.4%). In conclusion, although younger donor age is a major factor for estimation errors in hepatic volumetry, our age-adjusted formula is very useful in reducing the error in estimating GV..
1529. Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Noboru Harada, Yo Ichi Yamashita, Hirofumi Kawanaka, Takashi Nishizak, Yoshihiko Maehara, The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft, Transplant International, 10.1111/j.1432-2277.2008.00678.x, 21, 9, 833-842, 2008.09, Small-for-size (SFS) graft syndrome is one of the major causes of graft loss in living donor liver transplantation (LDLT). We examined whether splenectomy is beneficial for overcoming SFS graft syndrome in LDLT. The patients were classified into two groups: the Sp (-) group (n = 69), in which splenectomy was not performed, and the Sp (+) group (n = 44), in which it was. The incidence of SFS graft syndrome was investigated. Risk factors of SFS graft syndrome were identified by univariate- and multivariate analysis. To clarify whether splenectomy is beneficial for patients with a SFS graft, subgroup analysis was performed for patients who had a graft weight-to-standard liver weight (GW-SLW) ratio of 40% or less (n = 50). Thirty-one of 113 patients developed SFS graft syndrome. A multivariate analysis identified that having a male donor was an independent risk factor of SFS graft syndrome. SFS graft syndrome occurred in 11 of 50 patients with a GW-SLW ratio <40%, and Sp (-) was an independent risk factor for the occurrence of SFS graft syndrome in patients (P = 0.014). Simultaneous splenectomy is favorable for overcoming SFS graft syndrome in LDLT patients with a GW-SLW of 40% or less..
1530. Toru Ikegami, Mitsuo Shimada, Satoru Imura, Tomoharu Yoshizumi, Yusuke Arakawa, Takuya Tokunaga, Yuji Morine, Hirofumi Kanemura, The timing of liver transplantation after primary hepatectomy for hepatocellular carcinoma
A special reference to recurrence pattern and milan criteria, Transplantation, 10.1097/TP.0b013e3181814de2, 86, 5, 641-646, 2008.09, INTRODUCTION.: Hepatic resection (HR) is commonly applied as first-line treatment of hepatocellular carcinoma (HCC) even in the era of liver transplantation (LT). METHODS.: Outcomes and detailed recurrence pattern of 80 patients, who underwent curative HR for HCC were examined referring to Milan criteria. RESULTS.: (I) After HR for HCCs exceeding Milan criteria (n=41), recurrence within the criteria was observed in 13 patients (group-A) and recurrence not-meeting the criteria was observed in 22 patients (group-B). group-A showed better 3-year recurrence-free survival rate than group-B (85.7% vs. 23.9%, P<0.05). Tumor size more than or equal to 6 cm was identified as the significant factor for having recurrence as in group-A pattern (P<0.05). Among the patients in group-A, re-recurrence after treating recurrent HCC was observed in eight patients (61.5%) with increased rate of extra-Milan criteria recurrence at 12 months from the initial recurrence. (II) After HR for HCCs meeting Milan criteria (n=39), recurrences within the criteria was observed in 15 patients (group-C) and recurrence not-meeting the criteria was observed in five patients (group-D). The 3-year recurrence-free survival rate was 62.8% in group-C and 40.0% in group-D (P<0.05). Increased rate of extra-Milan re-recurrence was observed later than 12 months from the recurrence in group-C. CONCLUSIONS.: For HCCs not meeting Milan criteria, secondary LT after primary HR could be applied for a proportion of cases with less aggressiveness. For those meeting Milan criteria, primary LT should be the first therapeutic option. However, secondary LT could be offered for those with re-recurrence within criteria after primary HR..
1531. Satoru Imura, Mitsuo Shimada, Kotaro Miyake, Tetsuya Ikemoto, Yuji Marine, Tomoharu Yoshizumi, A new technique to acquire additional liver volume for left lobe graft in living donor liver transplantation, Hepato-gastroenterology, 55, 85, 1206-1210, 2008.07, Background/Aims: Left lobe graft is an ideal option to minimize potential risk for the donor in adult living-donor liver transplantation (LDLT). However, its use is restricted due to size limitations. The purpose of this study was to determine the impact of a new technique for the acquisition of additional liver volume for left lobe graft. Methodology: Three donors underwent left hepatic lobectomy by exploiting a new technique as follows: a demarcation line was marked by clamping the right first Glisson's pedicle. A parenchymal transection plane was located 1cm right side from the demarcation line and just on the left side of the right anterior Glisson's pedicle. A part of the anterior segment added to the left lobe graft by this procedure belonged to right anterior segment by preoperative CT. The preoperative volumetry of the liver was performed using the 3D-CT software, which was able to calculate total liver volume and the volume of each vessel's territories. Additional liver volume was calculated by preoperative CT scan and defined as part of the perfusion area by the right anterior portal branch. Blood perfusion of the additional liver area was postoperatively assessed by dynamic CT, and graft outcome was also evaluated. Results: An additional gain ranged from 40mL to 51mL (mean 41.8mL). GV/SLV was 35.7, 60.0, and 41.0%. The rate of additional volume in GV/SLV ranged from 7.2-8.4% (mean 7.6%). All grafts functioned well. The CT scan performed on early postoperative period confirmed excellent blood perfusion the additional segment. No complication attributable to small-for-size graft was noted. Conclusions: This new technique for left lobe graft harvesting proved a promising approach to gain additional volume, thereby avoiding small-for-size graft in adult LDLT..
1532. Tomoharu Yoshizumi, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hiroto Kayashima, Yo Ichi Yamashita, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, Graft size, donor age, and patient status are the indicators of early graft function after living donor liver transplantation, Liver Transplantation, 10.1002/lt.21462, 14, 7, 1007-1013, 2008.07, No reliable model for predicting early graft function and patient survival after living donor liver transplantation (LDLT) exists. The aim of this study was to establish a new formula for predicting early graft function and prognosis using technetium-99m galactosyl-human serum albumin (Tc-GSA) liver scintigraphy. The ratio of the hepatic uptake ratio of Tc-GSA to the clearance index of Tc-GSA (LHL/HH) was determined 7 days after LDLT. There were 22 patients with a ratio greater than 1.3 and 6 patients with a ratio less than 1.3. Graft function on the 14th postoperative day (POD) was compared between the 2 groups. A new formula to predict the LHL/HH score was established as follows: LHL/HH (predictive score) = 0.011 × graft weight (%) - 0.016 × donor age - 0.008 × Model for End-Stage Liver Disease score - 0. 15 × shunt (if present) + 1.757 (r2 = 0.497, P < 0.01). This predicted LHL/HH ratio was compared to the graft function on POD 14 for 110 LDLT patients. The total bilirubin JB) and prothrombin time international normalized ratio (PT-INR) in the group with an LHL/HH score ≥ 1.3 were lower than those in the group with an LHL/HH score < 1.3. The TB, PT-INR, and volume of ascites in the group with a predictive score ≥ 1.3 (n = 86) were lower than those in the group with a score < 1.3 (n = 24). The 6-month survival probability was improved in the group with a predictive score ≥ 1.3. In conclusion, this preoperative calculated LHL/HH score is correlated with graft function and short-term prognosis. Thus, this predictive model may allow transplant surgeons to use a living donor left lobe graft with greater confidence..
1533. Toru Ikegami, Yuji Soejima, Ryuji Ohta, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Yoshihiko Maehara, Living donor liver transplantation for hepatitis B associated liver diseases
A 10-year experience in a single center, Hepato-gastroenterology, 55, 85, 1445-1449, 2008.07, Background/Aims: Hepatic failure associated with hepatitis B virus (HBV) is one of the main indications for living donor liver transplantation (LDLT). Methodology: Twenty-nine LDLTs, including liver cirrhosis due to HBV (LC-B) (n=17) and fulminant hepatitis B (FH-B) (n=12) were reviewed. Prophylaxis for reinfection was performed with a combination of lamivudine, or hepatitis B immune globulin (HBIG) or adefovir, depending on the viral status. The changes in serological markers, recurrence and survival rate were examined. Results: There were 3 patients with re-emergencies of HBV surface antigen (HBsAg): suspension of HBIG for giving vaccination for HBV (n=1), HBsAg positive donor (n=1) and non-compliance for HBIG (n=1). All patients with YMDD mutants (n=9), except the case with HBsAg positive donor (n=1), were successfully protected by the triple therapy of lamivudine, adefovir and HBIG. No graft loss was due to the recurrence of HBV. Conclusion: The basic strategy using a combination of HBIG and antiviral agents gave acceptable long-term outcomes for LDLT for HBV associated liver diseases. The close monitoring of HBV viral status after transplantation is still crucial in managing these patients..
1534. T. Ikegami, A. Taketomi, R. Ohta, Y. Soejima, T. Yoshizumi, M. Shimada, Y. Maehara, Donor Age in Living Donor Liver Transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2008.02.084, 40, 5, 1471-1475, 2008.06, Background: We sought to elucidate the influence of donor age in living donor liver transplantation (LDLT) using either left lobe (LL) or right lobe (RL) grafts. Methods: Recipients (n = 232) were categorized as: group O/LL (LL, donor age >50, n = 20); group Y/LL (LL, donor age ≤50, n = 140); Group O/RL (RL, donor age >50, n = 12); and group Y/RL (RL, donor age ≤50, n = 61). We compared post-LDLT graft functions. Results: Among LL LDLT, the incidence of small-for-size syndrome was significantly greater for group O/LL compared with group Y/LL (60.0% vs 16.3%, P < .01). However, the cumulative 5-year graft survivals were 73.8% in group O and 76.7% in group Y without substantial difference. In RL LDLT, the post-LDLT morbidity and mortality were similar for group O/RL and group Y/RL. Conclusion: Partial liver grafts, even though LL grafts, from older donors can be used safely with caution in LDLT..
1535. T. Yoshizumi, A. Taketomi, H. Kayashima, Y. Yonemura, N. Harada, H. Ijichi, Y. Soejima, T. Nishizaki, Y. Maehara, Estimation of Standard Liver Volume for Japanese Adults, Transplantation Proceedings, 10.1016/j.transproceed.2008.02.082, 40, 5, 1456-1460, 2008.06, Introduction: Accurate pretransplant estimation of the recipient's standard liver volume (SLV) is important. The purpose of this study was to compare reported formulas for clinical estimation of liver volume among Japanese adults. Methods: We reviewed data on 70 healthy adults (46 men, 24 women, ages 20 to 65 years old) evaluated for living donor liver transplantation. Liver volume (LV) was measured using two- or three-dimensional computed tomography volumetry (CTV). The formulas of DeLand (LV = 1020 × body surface area [BSA] - 220), Urata (LV = 706.2 × BSA + 2.4), Noda (LV = 50.12 × BW0.78), Heinemann (LV = 1072.8 × BSA - 345.7), Vauthey (LV = 18.51 × BW + 191.8) and Yoshizumi (LV = 772 × BSA) were applied to estimate LV. We calculated the differences for individual donors betwen CTV and LV estimated by each formula. Results: Mean LVs as estimated by the formulae of DeLand and Heinemann et al were significantly greater (P < .01) than the mean CTV, while LV estimated by the formula of Urata was significantly less (P < .05) than the CTV. The formulas of DeLand and Heinemann overestimated LV, while the formula of Urata underestimated it. The formulae of Noda et al and Yoshizumi et al tended to underestimate the LV when the CTV was greater than 1600 cm3. When the Yoshizumi formula was applied, the number of donors with an acceptable difference (±15%) between CTV and estimated LV was 55 (78.6%). Conclusions: The Yoshizumi formula was applicable, especially for patients with a BSA < 2.0, whereas the well-known Urata formula made LV underestimates..
1536. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Characteristics of biliary reconstruction using a T-tube as compared with other methods in left-lobe adult living-donor liver transplantation, Journal of Hepato-Biliary-Pancreatic Surgery, 10.1007/s00534-007-1259-9, 15, 3, 346-347, 2008.05.
1537. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Shinji Itoh, Yo Ichi Yamashita, Yoshihiko Maehara, Hilar anatomical variations in living-donor liver transplantation using right-lobe grafts, Digestive surgery, 10.1159/000121907, 25, 2, 117-123, 2008.05, Background: Living-donor liver transplantation using a right-lobe graft has increased the frequency of hilar anatomical variations despite its advantage of a larger graft volume. Methods: Sixty-seven living-donor liver transplantations using right-lobe grafts are reviewed, regarding the surgical anatomy of hilar vascular and biliary systems. Results: The portal anatomy was classified into four types. The incidence of double portal vein was 6.0% (n = 4), and for such cases a unified orifice (n = 1) or a Y-graft (n = 3) was used for reconstruction. The arterial system was classified into five types. The incidence of arterial complications was 6.0% (n = 4), all of which occurred in cases where the graft artery was connected to the recipient's right hepatic artery. The biliary system was classified into four types. The incidence of a double bile duct was 7.5% (n = 5), and that of a unified one was 29.8% (n = 20). Hepaticojejunostomy was more prone to biliary sepsis (25.0%) and bile leakage (18.8%) than duct-to-duct connection (0 and 2%, respectively). Conclusion: Hilar anatomical variations in right-lobe living-donor liver transplantation could be managed after preoperative detailed evaluation of the graft and intraoperative appropriate surgical decision and techniques..
1538. Yuji Soejima, Naoyuki Ueda, Takasuke Fukuhara, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara, One-step venous reconstruction for a right lobe graft with multiple venous orifices in living donor liver transplantation, Liver Transplantation, 10.1002/lt.21401, 14, 5, 706-708, 2008.05.
1539. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoshihiko Maehara, Stenotrophomonas maltophilia bacteremia after living donor liver transplantation
Report of a case, Surgery today, 10.1007/s00595-007-3622-5, 38, 5, 469-472, 2008.05, Stenotrophomonas maltophilia (previously named Xanthomonas maltophilia) is an aerobic, nonfermentive, Gram-negative bacillus that is widespread in the environment. It is considered to be an organism with a limited pathogenic potential, which is rarely capable of causing diseases in humans other than in those who are in an immunocompromised state. In this study, we outline the case of a patient with Stenotrophomonas maltophilia bacteremia after living donor liver transplantation, which showed the clinical signs of severe sepsis and was resistant to almost all antibiotics. However, we successfully treated the patient with the antibiotics trimethoprim-sulfamethoxazole (TMP/SMX) and minocycline hydrochloride (MINO), and performed endotoxin-absorbing therapy using polymyxin B (PMX) to remove the endotoxin from Gramnegative bacillus as well as continuous hemodiafiltration (CHDF) to remove inflammatory cytokines. To the best of our knowledge, this is the first report on the treatment of Stenotrophomonas maltophilia bacteremia after living donor liver transplantation..
1540. Kotaro Miyake, Tomoharu Yoshizumi, Satoru Imura, Koji Sugimoto, Erdenebulgan Batmunkh, Hirofumi Kanemura, Yuji Morine, Mitsuo Shimada, Expression of hypoxia-inducible factor-1α, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma
Correlation with poor prognosis with possible regulation, Pancreas, 10.1097/MPA.0b013e31815f2c2a, 36, 3, e1-e9, 2008.04, OBJECTIVES: Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor that plays an important role in tumor growth and metastasis. Inhibition of histone deacetylase shows a marked inhibition of HIF-1α expression; however, the association between HIF-1α and histone deacetylase 1 (HDAC1), metastasis-associated protein 1 (MTA1) is not fully understood. METHODS: Hypoxia-inducible factor 1α, HDAC1, and MTA1 expressions were detected by immunohistochemistry in 39 pancreatic carcinoma patients. The correlations between the expression of HIF-1α, HDAC1, or MTA1 and clinical features and the prognosis were analyzed. RESULTS: Hypoxia-inducible factor 1α, HDAC1, and MTA1 positive stainings were found in 41%, 56%, and 31%, respectively. There was no correlation between HIF-1α, HDAC1, or MTA1 expression levels and any clinical parameters. The survival rate for patients with HIF-1α and HDAC1-positive stainings were significantly lower than for patients with HIF-1α and HDAC1-negative stainings. The MTA1 overexpression group did not have a significantly lower prognosis than the MTA1 underexpression group. The survival rate for the HDAC1(+)/MTA1(2-3) group was significantly lower than for the other groups. CONCLUSIONS: These results suggest that HIF-1α expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis for pancreatic carcinoma and indicates that HIF-1α and HDAC1/MTA1 are a promising therapeutic target in pancreatic carcinoma treatment..
1541. Yuji Soejima, Makoto Meguro, Akinobu Taketomi, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Shinji Ito, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara, Left lobe living donor liver transplantation in an adult patient with situs inversus
Technical considerations, Transplant International, 10.1111/j.1432-2277.2007.00607.x, 21, 4, 384-389, 2008.04, Situs inversus (SI) is a rare congenital disorder involving a complete mirror image of the thoracic and abdominal organs. Living donor liver transplantation (LDLT) in SI cases poses particular challenges on account of its technical complexity, and only a few cases have been reported. Here, we present an adult with SI who was managed successfully by LDLT using a left lobe graft. Some technical modifications, including triangulated anastomosis of the hepatic vein, were required but no vascular graft was necessary. Graft function and vascular integrity were excellent throughout the postoperative course, although sepsis secondary to wound infection with methicillin-resistant Staphylococcus aureus developed. In conclusion, LDLT using a left lobe graft is a feasible procedure for patients with SI, even for adults. Therefore, this condition, while rare, should not be a contraindication for LDLT. Meticulous preoperative simulation and planning of the vascular reconstruction are important steps in LDLT for this rare anomaly..
1542. Y. Soejima, A. Taketomi, T. Ikegami, T. Yoshizumi, H. Uchiyama, Y. Yamashita, M. Meguro, N. Harada, M. Shimada, Y. Maehara, Living donor liver transplantation using dual grafts from two donors
A feasible option to overcome small-for-size graft problems?, American Journal of Transplantation, 10.1111/j.1600-6143.2008.02153.x, 8, 4, 887-892, 2008.04, Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small-for-size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large-size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small-for-size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small-for-size graft problems without increasing independent donor risks..
1543. Shigeyuki Nagata, Mitsuo Shimada, Yuji Soejima, Takashi Nishizaki, Tomoharu Yoshizumi, Yoshihiko Maehara, Adult-to-adult living donor liver transplantation in severe portosystemic shunt cases, Hepato-gastroenterology, 55, 82-83, 666-669, 2008.03, To date, the need for spontaneous portosystemic shunt division during adult-to-adult living donor liver transplantation (LDLT) remains unknown. This study reports 2 patients with large portosystemic shunts who required LDLT. The first patient was a 40-year-old male with liver cirrhosis due to hepatitis C. The angiogram showed splenosystemic shunts with hepatopetal flow. Shunt occlusion was not performed after implanting a small-size graft because sufficient portal blood flow was observed. On the first postoperative day, portal blood flow was not detected; therefore shunt occlusion was performed and the portal blood flow was restored. The second patient was a 51-year-old female with primary biliary cirrhosis. Marked collateral circulation with hepatofugal flow was observed. Shunt occlusion was performed after implanting a medium-size graft. Postsurgery, hepatopetal portal blood flow was observed and the postoperative course was satisfactory. These cases demonstrate that large portosystemic shunts should be ligated to maintain adequate portal blood flow that corresponds to the graft volume..
1544. Shinji Shimoda, Kenichi Harada, Hiroaki Niiro, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Koichi Tsuneyama, Minoru Nakamura, Atsumasa Komori, Kiyoshi Migita, Yasuni Nakanuma, Hiromi Ishibashi, Carlo Selmi, M. Eric Gershwin, Biliary epithelial cells and primary biliary cirrhosis
The role of liver-infiltrating mononuclear cells, Hepatology, 10.1002/hep.22102, 47, 3, 958-965, 2008.03, Primary biliary cirrhosis (PBC) is characterized by the highly selective autoimmune injury of small intrahepatic bile ducts, despite widespread distribution of mitochondrial autoantigens. On this basis, it has been suggested that the targeted biliary epithelial cells (BECs) play an active role in the perpetuation of autoimmunity by attracting immune cells via chemokine secretion. To address this issue, we challenged BECs from patients with PBC and controls using multiple Toll-like receptor (TLR) ligands as well as autologous liver-infiltrating mononuclear cells (LMNCs) with subsequent measurement of BEC phenotype and chemokine production and LMNC chemotaxis by quantifying specific chemokines. Our data reflect that BECs from PBC patients and controls express similar levels of TLR subtypes, CD40, and human leukocyte antigen DRα (HLA-DRα) and produce equivalent amounts of chemokines in our experimental conditions. Interestingly, however, BEC-expressed chemokines elicit enhanced transmigration of PBC LMNCs compared with controls. Furthermore, the addition of autologous LMNCs to PBC BECs led to the production of higher levels of chemokines and enhanced the expression of CD40 and HLA-DRα. Conclusion: We submit that the proinflammatory activity of BECs in PBC is secondary to the intervention of LMNCs and is not determined per se. These data support the hypothesis that BECs are in fact "innocent victims" of autoimmune injury and that the adaptive immune response is critical in PBC..
1545. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiko Maehara, Hiroyuki Kuwano, Is an elderly recipient a risk for living donor adult liver transplantation?, Hepato-gastroenterology, 55, 82-83, 653-656, 2008.03, Background/Aims: In cadaveric liver transplantation, it has been reported that elderly recipients over 60 years are at risk because of high incidence of complication and malignancy. However, in living-donor adult liver transplantation (LDALT), it is unclear whether the elderly recipient is risky or not risky. In this study, the outcome after LDALT of elderly patients has been evaluated. Methodology: One hundred twenty two consecutive LDALT recipients were studied. The recipients were divided into an elderly group (older than 60 yrs, n=21), and a control group (younger than 60 yrs, n=101). Comparative examination of background factors, postoperative complications and de novo malignancy was carried out. Results: Elderly patients more frequently received transplantation for hepatocellular carcinoma. Pretransplant liver damage such as Child-Pugh, MELD or bilirubin level was same among the groups. There was no significant difference in posttransplant complications except renal failure. Postoperative renal failure (postoperative creatinine level over 2mg/dL) occurred in 29% (n=5) of the elderly group vs. 8% (n=6) of the control group. De novo malignancy occurred in 1 case (lung) in the elderly group and 1 case (Vater) in the control group. In the control group, the 1, 3 and 5 year patient survival rates were 78.5%, 73.1% and 71.4%, respectively. And in the elderly group, the 1, 3 and 5 year patient survival rates were 85.7%, 81.0% and 70.8%, respectively. Conclusions: It may be, we concluded that living donor adult liver transplantation is good treatment for end stage liver diseases in elderly recipients over 60 years. However caution should be taken in the administration of medicine, including immunosuppressants or antibiotics, do to a propensity for postoperative renal failure in elderly recipients..
1546. Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Yo Ichi Yamashita, Yoshihiko Maehara, Liver transplantation for hepatocellular carcinoma, Journal of Hepato-Biliary-Pancreatic Surgery, 10.1007/s00534-007-1296-4, 15, 2, 124-130, 2008.03, The role of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) has evolved over the past two decades, and transplantation has become one of the few curative treatment modalities for patients with HCC. Early results were poor, but the current restrictive selection criteria can yield excellent results. This review will discuss recent issues in the field, including (1) factors affecting the recurrence of HCC after LT; (2) the effect of downstaging HCC before LT, including transarterial catheter chemoembolization (TACE) and radiofrequency ablation (RFA); and (3) living-donor versus deceased-donor liver transplantation for HCC patients. The most important factors that have been described to affect LT survival include the tumor size, vascular invasion, and the degree of tumor differentiation. Recently, tumor markers, including alpha-fetoprotein and des-gamma carboxy prothrombin, were reported as predictors of HCC recurrence after LT. Furthermore, the experience accumulated with locoregional therapies such as TACE and RFA as bridging procedures to LT, along with the reduced waiting time under the HCC-adjusted MELD (model for endstage liver disease) system for organ allocation has led to improved outcomes. With the recent advances in adult living-donor liver transplantation (LDLT), there may be a marked change in the role of liver transplantation for hepatic malignancies, in particular for HCC..
1547. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Kensaku Sanefuji, Hiroto Kayashima, Mitsuo Shimada, Yoshihiko Maehara, Living Donor Liver Transplantation for Acute Liver Failure
A 10-Year Experience in a Single Center, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2007.08.018, 206, 3, 412-418, 2008.03, Background: Living donor liver transplantation has become an accepted treatment for various terminal liver diseases. Study Design: Forty-two living donor liver transplantations performed for acute liver failure during a 10-year period at Kyushu University Hospital were reviewed. Results: Causes of liver failure included hepatitis B (n = 12), hepatitis C (n = 1), autoimmune hepatitis (n = 2), Wilson's disease (n = 3), and unknown causes (n = 24). The graft types were: left lobe (n = 33), right lobe (n = 8), and lateral segment (n = 1). The mean graft volume to standard liver volume ratios were 42.2 ± 9.2% in left lobe grafts and 50.5 ± 3.9% in right lobe grafts (p < 0.05). Extubation was significantly delayed in grade IV encephalopathy patients (73.7 ± 18.2 hours) compared with patients with other grades (p < 0.01 to grades I and II, p < 0.05 to grade III). All other patients, except one with a subarachnoid hemorrhage, had complete neurologic recovery after transplantation. The 1- and 10-year survival rates were 77.6% and 65.5%, respectively, for grafts, and 80.0% and 68.2%, respectively, for patients. Conclusions: Outcomes of living donor liver transplantation for acute liver failure are fairly acceptable despite severe general conditions and emergent transplant settings. Living donor liver transplantation is now among the currently accepted life-saving treatments of choice for acute liver failure, although innovative medical treatments for this disease entity are still anticipated..
1548. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Living donor liver transplantation for fulminant hepatic failure from ABO-incompatible donors [1], Transplant International, 10.1111/j.1432-2277.2007.00588.x, 21, 3, 284-285, 2008.03.
1549. Tomoharu Yoshizumi, Akinobu Taketomi, Hiroto Kayashima, Noboru Harada, Hideaki Uchiyama, Yo Ichi Yamashita, Toru Ikegami, Yuji Soejima, Takashi Nishizaki, Mitsuo Shimada, Yoshihiko Maehara, Successful treatment for a patient with hemophagocytic syndrome after a small-for-size graft liver transplantation, Hepato-gastroenterology, 55, 82-83, 359-362, 2008.03, Hemophagocytic syndrome (HPS) is a hematological disorder caused by activated T lymphocytes, which leads to the proliferation of stimulated macrophages that phagocytose and destroy circulating blood elements and their precursors within bone marrow, and lead to the further production of inflammatory cytokines. Living donor liver transplantation (LDLT) between adults has been performed to compensate for the shortage of available organs. There have been some reports concerning HPS after LDLT; however, its prognosis is disappointingly poor. In particular, there is no report of treated HPS developed after LDLT using small-for-size left lobe grafts. We herein report a case of HPS in a 63-year old woman who underwent LDLT using left lobe graft weighing only 330g. The HPS was diagnosed on postoperative day 13, and was successfully treated using a combination of intravenous immunoglobulin, granulocyte colony stimulating factor, conversion of calcineurin inhibitor and steroid pulse. The trigger of HPS may not only be systemic infection, but also hypercytokinemia caused by various factors. HPS is a fatal complication in immunologically compromised patients; however, early and accurate diagnosis could lead to an adequate treatment and improve the outcome..
1550. Mami Kanamoto, Tomoharu Yoshizumi, Toru Ikegami, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Nobuya Sano, Mitsuo Shimada, Cholangiolocellular carcinoma containing hepatocellular carcinoma and cholangiocellular carcinoma, extremely rare tumor of the liver
A case report, Journal of Medical Investigation, 10.2152/jmi.55.161, 55, 1-2, 161-165, 2008.02, Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor which was first defined by Steiner, et al. in 1957 (1). CLC is thought to be derived from Hering's canal because tumor glands of CLC are morphologically similar to cholangioles. Recently, Theise, et al. reported that Hering's canal might be composed of hepatic stem cells (3). In addition, CLC sometimes contains a hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC) component within the tumor. Those findings suggest that CLC might originate from hepatic stem cells. On the other hand, because of its low frequency, clinicopatholigical features of CLC have not been fully clarified yet. We herein report a case of a 71-year old man with CLC. Based on preoperative imagings, the hepatic tumor was diagnosed as HCC, and he underwent a partial hepatectomy. The tumor contained both a HCC and CCC-like area. In immunohistochemistry, cytokeratin (CK) 7, CK20, CAM5.2 was positive, and CK19 was negative, therefore the tumor was diagnosed as CLC. The diagnostic criteria have not been described clearly, so CLC is difficult to diagnose preoperatively. Further studies are needed to clarify the clinical and clinicopatholigical features of CLC..
1551. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Yo Ichi Yamashita, Shinji Itoh, Yosuke Kuroda, Yoshihiko Maehara, Assessment of graft fibrosis by transient elastography in patients with recurrent hepatitis C after living donor liver transplantation, Transplantation, 10.1097/01.tp.0000297248.18483.16, 85, 1, 69-74, 2008.01, BACKGROUND. Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness and therefore can be a promising tool to evaluate liver fibrosis and avoid liver biopsy. We prospectively assessed the performance of transient elastography in patients with recurrent hepatitis C virus after living donor liver transplantation, in comparison with the surrogate serum markers. METHODS. Fifty-six patients with recurrent hepatitis C virus after living donor liver transplantation, who underwent both liver biopsy and transient elastography were included in this study. The grade of liver fibrosis (the Scheuer classification) obtained by biopsy was compared to liver stiffness measured by the transient elastography. RESULTS. The fibrosis grades were as follows: F0, n=22; F1, n=13; F2, n=9; F3, n=7; and F4, n=5. Liver stiffness values ranged from 2.9 to 72.0 kPa. The optimal cutoff values were 8.8 kPa for F≥1, 9.9 kPa for F≥2, 15.4 kPa for F≥3, and 26.5 kPa for F≥4. The area under the receiver operator characteristic curve for the diagnosis of fibrosis (F≥2) by transient elastography was 0.92, while that by hyaluronic acid, type 4 collagen, alanine aminotransferase, and the aspartate transaminase to platelets ratio index were 0.52, 0.62, 0.64, and 0.70, respectively. CONCLUSIONS. These data suggest that transient elastography is a simple, noninvasive and reliable tool to assess liver fibrosis in patients with recurrent hepatitis C virus after living donor liver transplantation..
1552. Nao Kinjo, Hirofumi Kawanaka, Morimasa Tomikawa, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Shohei Yamaguchi, Daisuke Yoshida, Yoshihiko Maehara, B-RTO for ectopic variceal bleeding after living donor liver transplantation, Hepato-gastroenterology, 55, 81, 241-243, 2008.01, Gastrointestinal bleeding (GIB) is a serious gastroenterological complication after orthotropic liver transplantation, as well as living donor liver transplantation (LDLT). Although ectopic varices are rare causes of GIB, they may lead to life-threatening bleeding and it is difficult to diagnose them. We herein report a rare case of a jejunal variceal bleeding in a recipient five years after LDLT for primary sclerosing cholangitis with successful result by balloon-occluded retrograde transvenous obliteration (B-RTO)..
1553. Kazutoyo Morita, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Naotaka Hashimoto, Yohei Mano, Tatsunori Miyata, Yuji Soejima, Yoshihiko Maehara, Feasible isolated liver transplantation for a cirrhotic patient on chronic hemodialysis, Case Reports in Gastroenterology, 10.1159/000354140, 7, 2, 299-303, 2013.01, End-stage liver and kidney disease (ELKD) is an indication for deceased donor simultaneous liver-kidney transplantation. Although a few cases of living donor liver-kidney transplantation have been reported, the invasiveness remains to be discussed. Living donor liver transplantation (LDLT) is an alternative choice for ELKD, but has never been reported. Here, we report a case of successful LDLT for a patient with ELKD on hemodialysis. The patient was a 63-year-old male and had decompensated hepatitis C cirrhosis with seronegativity for hepatitis C virus. He had non-diabetic end-stage renal failure and had been on hemodialysis for 3 years. He was in good general condition except for hepatic and renal failure. The living donor was his 58-year-old healthy wife. A right lobe graft was transplanted to the recipient under continuous hemodiafiltration (CHDF) and extracorporeal veno-venous bypass. CHDF was continued until postoperative day 4, at which point CHDF was converted to hemodialysis. His posttransplant course was good and he was discharged on postoperative day 36. To the best of our knowledge, this is the first report of LDLT for a patient on chronic hemodialysis. Therefore, being on hemodialysis is not a contraindication for LDLT. LDLT is feasible for a patient with ELKD on hemodialysis..
1554. Hiroto Kayashima, Ken Shirabe, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Liver regeneration and venous collateral formation in the right lobe living-donor remnant
Segmental volumetric analysis and three-dimensional visualization, Transplantation, 10.1097/TP.0b013e31827147d8, 95, 2, 353-360, 2013.01, BACKGROUND: In left lobe (LL) living-donor liver transplantation (LDLT), hepatic venous congestion (HVC) caused by ligation of the middle hepatic vein tributaries is unavoidable in the right lobe (RL) donor remnant. METHODS: To clarify the impact of HVC on liver regeneration and venous collateral formation (VCF), we used three-dimensional computed tomography to examine the volumes of total/segmental liver and HVC and the degree of VCF; preoperative data were compared with data obtained on postoperative day (POD) 35 in 13 LL LDLT donors. RESULTS: On POD 35, the congestion rate decreased from 32.5% to 1.6% and the total liver regeneration rate was 81.7%. Preoperatively, the anterior sector-to-RL volume ratio was significantly lower, and the posterior sector-to-RL volume ratio was significantly higher than postoperatively (56.7% vs. 52.9%, P<0.01, and 36.9% vs. 41.5%, P<0.01, respectively). There was no correlation between degree of HVC and liver regeneration. Obvious VCF was found in five (38.5%) cases. The RL and posterior sector volume per square meter of body surface area in the VCF group were significantly lower than that in the non-VCF group (412 cm/m vs. 492 cm/m, P<0.01, and 140 cm/m vs. 190 cm/m, P<0.01, respectively). The preoperative congestion rate and liver regeneration rate were not significantly different between the groups. CONCLUSIONS: Reconstruction of the middle hepatic vein tributaries in the RL donor remnant might not be necessary in LL LDLT, because the HVC improved dramatically by POD 35 regardless of the development of VCF..
1555. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Mirror image hepatectomy in a patient with situs inversus totalis., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 430-434, 2013.01, Hepatectomy in a patient with situs inversus patient is technically challenging because of its complete mirror image anatomy, especially for a tumor located deep in the liver. Incorrectly identifying intrahepatic vessels and biliary system would lead to serious complications. We experienced a hepatectomy for a tumor in a patient with situs inversus totalis with referring to computer-generated mirror images. A 66-year-old female patient with situs inversus totalis was diagnosed with hepatocellular carcinoma, 5 cm in diameter, centrally located just above the hepatic hilum compressing the right and left hepatic duct. The liver infected with hepatitis C was cirrhotic with a moderate amount of ascites. We preoperatively created several diagrams of the mirror image anatomy and made plans for how to resect this tumor, presupposing the patient had an ordinary anatomy. The tumor was successfully enucleated with referring to these diagrams. The operation time was 454 minutes. Five units of fresh frozen plasma was transfused intraoperatively. Although she suffered refractory ascites which needed repeated paracentesis, she managed to leave the hospital two months after the operation. Creating a mirror image anatomy enables surgeons to safely perform a complex hepatectomy in a patient with situs inversus totalis..
1556. Takashi Motomura, Ken Shirabe, Yohei Mano, Jun Muto, Takeo Toshima, Yuichiro Umemoto, Takasuke Fukuhara, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment, Journal of Hepatology, 10.1016/j.jhep.2012.08.017, 58, 1, 58-64, 2013.01, Background & Aims: Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Preoperative neutrophil-lymphocyte ratio (NLR) is a predictor of patient prognosis, but its mechanism has never been clarified. Methods: We assessed outcomes in 158 patients who had undergone living-donor liver transplantation (LDLT) for HCC. Recurrence-free survival (RFS) was determined in patients with high (≥4) and low (<4) NLR. Levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68, and CD163 were measured. Results: The 5-year RFS rate was significantly lower in patients with high (n = 26) than with low (n = 132) NLR (30.3% vs. 89.0%, p <0.0001), in patients with high (n = 15) than with low (n = 79) NLR who met the MC (73.6% vs. 100%, p = 0.0008) and in patients with high (n = 11) than with low (n = 53) NLR who exceeded the MC (0% vs. 76.1%, p = 0.0002). Tumor expression of VEGF, IL8, IL-17, CD68, and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 levels were significantly higher in the high-NLR group (p = 0.01 each). The density of peritumoral CD163 correlated with the density of peritumoral IL-17-producing cells (p = 0.04) and was significantly higher in the high-NLR group (p = 0.005). Conclusions: NLR predicts outcomes after LDLT for HCC via the inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC..
1557. Keiji Yoshinaga, Hiroshi Saeki, Eiji Oki, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Prognostic markers for immunochemotherapy using tegafur -uracil (UFT) and protein-bound polysaccharide K (PSK)., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 549-558, 2013.01, We previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels. 98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years. There were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant. Serum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary..
1558. Hiroshi Saeki, Eiji Oki, Yasuo Tsuda, Koji Ando, Yukiharu Hiyoshi, Shuhei Ito, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Relevance of totally laparoscopic gastrectomy for patients with advanced gastric cancer., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 405-412, 2013.01, Although the use of laparoscopic gastrectomy for gastric cancer has been widespread, it has remained controversial whether it can be applied for the patients with advanced gastric cancer. The aim of this study was to clarify the safety and usefulness of totally laparoscopic gastrectomy for patients with advanced gastric cancer. Totally laparoscopic gastrectomy was applied for a total of 38 patients with pStage IB-III advanced gastric cancer at our institute. The surgical and long-term results were analyzed in those patients. Twenty-seven patents underwent distal gastrectomy and 11 patients underwent total gastrectomy. The mean number of dissected lymph nodes was 41 (range, 16-87). The mean length of the operation and amount of blood loss was 324 min and 123 ml, respectively. Two cases of postoperative bleeding were noted, while neither anastomosis-related complications nor in-hospital death was observed. The follow-up period after surgery was 8-72 months. Postoperative recurrence was observed in 6 patients (peritoneal dissemination: 3 patients, pleural dissemination: 1 patient, liver metastasis: 1 patient, ovarian metastasis: 1 patient). The overall survival rates at 1, 3 and 5 years were 94.7%, 76.3% and 76.3%, respectively. Totally laparoscopic gastrectomy is safe and can lead to satisfactory long-term outcomes in cases of advanced gastric cancer. Prospective controlled studies are warranted to confirm our findings..
1559. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo Ichi Yamashita, Tetsuo Ikeda, Hirofumi Kawanaka, Keishi Sugimachi, Koshi Mimori, Masayuki Watanabe, Masaru Morita, Eiji Oki, Hiroshi Saeki, Yoshihiko Maehara, Rex shunt for portal vein thrombosis after adult living donor liver transplantation., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 464-468, 2013.01, Portal vein thrombosis (PVT) after liver transplantation is a relatively common but serious complication which could lead to portal hypertension or a direct graft loss. A "Rex" shunt created between the superior mesenteric vein (SMV) and the umbilical portion of the left portal vein can be a useful option to treat PVT after pediatric liver transplantation, however, its application to adult patients has not been reported so far because appropriate vein grafts are hardly available. Herein we present a case of PVT after left lobe living donor liver transplantation (LDLT) who underwent the procedure using the own inferior jugular vein and the gonadal vein as a shunt graft. The shunt was patent immediately after the procedure but was thrombosed 2 days after probably due to the insufficient inflow from the SMV and the absence of anticoagulation therapy, for which emergent thrombectomy and ligation of the significant hepatofugal collateral veins followed by full anti-coagulation therapy were performed. The shunt remains open at 8 month after the procedure with a normal anmonia level and liver function. In conclusion, the Rex shunt using recipient's autologous vein grafts is a feasible and valuable option for adult patients to treat PVT after LDLT..
1560. Masayuki Watanabe, Koki Matsuura, Hideo Baba, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Yoshihiko Maehara, Thoracoscopic pericardial drainage for gastric tube ulcer penetrated into the pericardium., Unknown Journal, 104, 10, 389-393, 2013.01, Peptic ulcer occurring in the gastric conduit for esophageal reconstruction sometimes penetrates into the mediastinal structures. We herein reported a case of pericardial penetration of gastric tube ulcer successfully treated with thoracoscopic pericardial drainage. A 66-year-old Japanese man, who had undergone esophagectomy for esophageal cancer 20 months before, visited our emergency room complaining severe back pain. Computed tomography revealed gastric tube ulcer penetrated into the pericardial space. Thoracoscopic pericardiotomy and drainage was performed and the patient made an uneventful recovery. Thoracoscopic pericardial drainage is useful to manage acute pyogenic pericarditis due to penetration of peptic ulcer which occurred in the gastric tube..
1561. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Verification of our therapeutic criterion for acute cholecystitis
"perform a subemergency laparoscopic cholecystectomy when a patient is judged to be able to tolerate general anesthesia"--the experience in a single community hospital., Unknown Journal, 104, 10, 339-343, 2013.01, Our current therapeutic criterion for acute cholecystitis is: Perform a subemergency laparoscopic cholecystectomy (LC) when a patient is judged to be able to tolerate general anesthesia. The aim of the current study was to verify whether this criterion is justified. The outcomes of 21 cases of LC for acute cholecystitis performed between April 2011 and September 2013 were retrospectively analyzed. Subemergency LC was performed according to the aforementioned criterion (Subemergency group; n = 16). Patient who was judged to be unable to tolerate general anesthesia underwent percutaneous transhepatic gallbladder drainage (PTGBD) first, then LC after the patients' condition became stable (PTGBD group; n = 5). There is no conversion to open surgery throughout the study period. The mean of the total hospital stays in the Subemergency group was significantly shorter than that in the PTGBD group (11.5 +/- 5.3 vs. 30.4 +/- 8.5 days). Although two patients in the Subemergency group, who had already needed oxygen administration preoperatively, suffered postoperative respiratory failure, they completely recovered. On the other hand, there is no postoperative complication in the PTGBD group. Subemergency LC could be safely performed when surgeons as well as anesthesiologists judged a patient to be able to tolerate general anesthesia, which significantly shorten hospital stays compared to elective LC after PTGBD. However, elective LC after PTGBD is an absolutely safer therapeutic option in treating unstable patients..
1562. Tetsuo Ikeda, Tomohiko Akahoshi, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Koshi Mimori, Masayuki Watanabe, Makoto Hashizume, Yoshihiko Maehara, [Optimum hepatic parenchymal dissection to prevent bile leak
a comparative study using electrosurgical and stapling devices in swine]., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 507-514, 2013.01, Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma..
1563. Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara, Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma
Report of a case, Surgery today, 10.1007/s00595-012-0332-4, 42, 12, 1210-1214, 2012.12, The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection..
1564. Takashi Motomura, Ken Shirabe, Norihiro Furusyo, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tomohiko Akahoshi, Morimasa Tomikawa, Takasuke Fukuhara, Jun Hayashi, Yoshihiko Maehara, Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype, BMC Gastroenterology, 10.1186/1471-230X-12-158, 12, 2012.11, Background: IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.Methods: Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.Results: Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.Conclusions: IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype..
1565. Takashi Motomura, Yuki Ono, Ken Shirabe, Takasuke Fukuhara, Hideyuki Konishi, Yohei Mano, Takeo Toshima, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Neither MICA nor DEPDC5 genetic polymorphisms correlate with hepatocellular carcinoma recurrence following hepatectomy, HPB Surgery, 10.1155/2012/185496, 2012, 2012.11, Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7 in MICA GG allele carriers, 38.7 in GA, and 20.8 in AA, respectively (P = 0.72). The five-year RFS rate was 23.8 in DEPDC5 TT allele carriers and 31.8 in TG/GG, respectively (P = 0.47). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers (P 0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages..
1566. Yuji Soejima, Toru Ikegami, Hideki Ijichi, Tetsuo Ikeda, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hiroshi Matsuura, Kenichiro Okadome, Yoshihiko Maehara, Technical evolution of laparoscopic hepatic resection
a single institutional experience., Unknown Journal, 103, 11, 226-232, 2012.11, Laparoscopic hepatic resection (LHR) is still a challenging and developing surgical modality because of technical difficulty and a lack of training opportunities and experience. In this study, we present the results of our initial experiences of LHR, focusing on technical evolution in the management of LHR. Between April 2011 and March 2012, a total of 12 LHRs were performed. The first 5 of these LHRs were performed under laparoscopic assistance (hybrid-LHR), while the last 7 LHRs were performed totally laparoscopically (pure-LHR). Indications for LHR were hepatocellular carcinoma (n = 9) and metastatic liver cancer (n = 3). LHR procedures consisted of partial resection (n = 2), left lateral segmentectomy (n = 2), and left lobectomy (n = 1) in the hybrid-LHR group, and partial resection (n = 4), left lateral segmentectomy (n = 2), and right lobectomy (n = 1) in the pure-LHR group. Operative outcomes were compared between the groups and technical modifications were evaluated. The mean operative time, blood loss, and length of hospital stay in the hybrid- and pure-LHR groups were 3.8 and 6.1 hours, 220 and 611 ml, and 9.4 and 7.4 days, respectively. There were no postoperative complications in both groups. Tumor margins were negative in all cases. LHR is a feasible and effective procedure for patients with various types of liver tumors, although technical challenges still need to be overcome..
1567. Shohei Yoshiya, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31826969e6, 94, 9, 947-952, 2012.11, BACKGROUND: Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. METHODS: A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. RESULTS: The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). CONCLUSIONS: Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group..
1568. Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Authors' reply to "female-to-male match predicted poor survival following living donor liver transplantation-some issues needed to be clarified", Transplantation, 10.1097/TP.0b013e3182654d56, 94, 6, e36, 2012.09.
1569. Toru Ikegami, Ken Shirabe, Rumi Matono, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Etiologies, risk factors, and outcomes of bacterial pneumonia after living donor liver transplantation, Liver Transplantation, 10.1002/lt.23483, 18, 9, 1060-1068, 2012.09, The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short-term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram-negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P = 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post-LDLT pneumonia was associated with the following post-LDLT events: the prolonged use of mechanical ventilation (≥3 days), a prolonged stay in the intensive care unit (≥7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed-onset pneumonia, which occurred at least 10 days after transplantation (n = 15), and it was significantly associated with graft dysfunction. A combination of broad-spectrum antibiotics and aminoglycosides provided cover for most gram-negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad-spectrum antibiotics. Delayed-onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed..
1570. Hideaki Uchiyama, Hiroto Kayashima, Rumi Matono, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Toshiharu Matsuura, Tomoaki Taguchi, Yoshihiko Maehara, Relevance of HLA compatibility in living donor liver transplantation
The double-edged sword associated with the patient outcome, Clinical Transplantation, 10.1111/ctr.12019, 26, 5, E522-E529, 2012.09, HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA-A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host-versus-graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft-versus-host disease (GVHD) was also analyzed. No recipients with recipient-against-donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with "R→D MM 0" together with "donor-against-recipient MM 3" died of fatal GVHD. HLA compatibility in LDLT not only affected the long-term acceptance of graft livers but also the risk of fatal GVHD..
1571. Mizue Matsuo, Toru Ikegami, Kazutoyo Morita, Hiroko Yano, Naotaka Hashimoto, Hiroto Kayashima, Toshirou Masuda, Naoko Kondou, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, [A case of successful multi-venous reconstruction using recipient's jugular vein in right lobe-living donor liver transplantation]., Unknown Journal, 103, 9, 186-190, 2012.09, In right lobe-living donor liver transplantation (RT-LDLT), hepatic venous reconstruction of the graft is essential to prevent posttansplant graft congestion and have a good outcome. The patient was a 56-year-old man who had decompensated liver cirrhosis secondary hepatitis C with massive ascites, jaundice and hepatic encephalopathy. He underwent LDLT using his son's right lobe graft. Preoperative simulation by 3D-CT volumetry revealed that the right lobe graft needed multi-venous reconstruction for right inferior hepatic vein (RIHV) and middle hepatic venous tributaries. Preoperative CT scan revealed that the recipient had portal venous thrombus and stenosis, which meant that the recipient's explanted portal vein (EPV) was not suitable for the venous reconstruction of the right lobe graft. Therefore, the recipient's internal and external jugular veins (IJV and EJV) were procured for venous reconstruction. The multiple veins of the right lobe graft were reconstructed to have single co-orifice at the backtable, and the co-orifice was anastomosed to inferior vena cava in short time. The recipient discharged on postoperative day 22 with good venous patency. In RT-LDLT unavailable for recipient's EPV, recipient's IJV and EJV grafts are very useful for multi-venous reconstruction..
1572. Kazuki Takeishi, Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Takashi Motomura, Toru Ikegami, Tomoharu Yoshizumi, Fumio Sakane, Yoshihiko Maehara, Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras-Raf-MEK-ERK pathway, Journal of Hepatology, 10.1016/j.jhep.2012.02.026, 57, 1, 77-83, 2012.07, Background & Aims: Diacylglycerol kinases (DGKs) were recently recognized as key regulators in cell signaling pathways. We investigated whether DGKα is involved in human hepatocellular carcinoma (HCC) progression. Methods: We silenced or overexpressed DGKα in HCC cells and assessed its effect on tumor progression. DGKα expression in 95 surgical samples was analyzed by immunohistochemistry, and the expression status of each sample was correlated with clinicopathological features. Results: DGKα was detected in various HCC cell lines but at very low levels in the normal liver. Knockdown of DGKα significantly suppressed cell proliferation and invasion. Overexpression of wild type (WT) DGKα, but not its kinase-dead (KD) mutant, significantly enhanced cell proliferation. DGKα knockdown impaired MEK and ERK phosphorylation, but did not inhibit Ras activation in HCC cells. In a xenograft model, WT DGKα overexpression significantly enhanced tumor growth compared to the control, but KD DGKα mutant had no effect. Immunohistochemical studies showed that DGKα was expressed in cancerous tissue, but not in adjacent non-cancerous hepatocytes. High DGKα expression (≥20%) was associated with high Ki67 expression (p <0.05) and a high rate of HCC recurrence (p = 0.033) following surgery. In multivariate analyses, high DGKα expression was an independent factor for determining HCC recurrence after surgery. Conclusions: DGKα is involved in HCC progression by activation of the MAPK pathway. DGKα could be a novel target for HCC therapeutics as well as a prognostic marker..
1573. Yuji Soejima, K. Shirabe, A. Taketomi, T. Yoshizumi, H. Uchiyama, T. Ikegami, M. Ninomiya, N. Harada, H. Ijichi, Y. Maehara, Left lobe living donor liver transplantation in adults, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04022.x, 12, 7, 1877-1885, 2012.07, Adult left lobe (LL) living donor liver transplantation (LDLT) has not generally been recognized as a feasible procedure because of the problem of graft size. The objectives of this study were to assess the feasibility and short- and long-term results of adult LL LDLT in comparison with right lobe (RL) LDLT. Data on 200 consecutive LL LDLTs, including five retransplants, were retrospectively compared with those of 112 RL LDLTs, in terms of survival, complications and donor morbidity. The mean graft weight to standard volume ratio of LL grafts was 38.7% whereas that of RL grafts was 47.6% (p < 0.0001). The 1-, 5- and 10-year patient survival rates of LL LDLT were 85.6%, 77.9% and 69.5%, respectively, which were comparable to those of RL LDLT (89.8%, 71.3% and 70.7%, respectively). The incidence of small-for-size syndromewas higher in LL LDLT (19.5%) than in RL LDLT (7.1%) (p < 0.01). The overall donor morbidity rates were comparable between LL (36.0%) and RL (34.8%), whereas postoperative liver function tests and hospital stay were significantly better (p < 0.0001) in LL donors. In conclusion, adult LL LDLT has comparable outcomes to that of RL LDLT. LL LDLT is viable and is the first choice in adult LDLT..
1574. Toru Ikegami, K. Shirabe, T. Yoshizumi, S. Aishima, Y. A. Taketomi, Y. Soejima, H. Uchiyama, H. Kayashima, T. Toshima, Y. Maehara, Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04052.x, 12, 7, 1886-1897, 2012.07, The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult-to-adult LDLT grafts without anatomical, immunological or hepatitis-related issueswere included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH-20) was used to characterize PGD. DFH-20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH-20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PTINR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH-20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH-20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality..
1575. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Use of an internal jugular vein graft for middle hepatic vein tributary reconstruction in right-lobe living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31825b75b6, 94, 2, e17-e18, 2012.07.
1576. Yoko Zaitsu, Toru Ikegami, Toshirou Masuda, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, [A successful case of living donor liver transplantation performed in 7 hours for sub acute fulminant hepatitis]., Fukuoka igaku zasshi = Hukuoka acta medica, 103, 7, 145-149, 2012.07, Living donor liver transplantation (LDLT) is the ultimate cure for fulminant hepatitis. Successful outcomes rely on the precise evaluation of the reversibility of hepatic encephalopathy, and a swift execution of necessary examination of both the donor and the recipient. The case was a 63-years old woman, presented with fever and loss of appetite. She was hospitalized for acute hepatitis and treated at a nearby hospital. She was transferred to the tertiary hospital for the acute deterioration of her liver function on the 7th day after the emergence of the initial symptoms. On the 10th day, she showed Grade 2 encephalopathy and underwent plasma exchange. She was transported to our hospital for possible LDLT on the 11th day. CT scan on arrival showed severe atrophy of her liver and no definite brain edema despite acutely deteriorating encephalopathy (Grade 3). LDLT was launched after 7 hours from her transport. She was discharged from the intensive care unit on the 6th day and was discharged without severe complications on 42th day after the LDLT..
1577. Noboru Harada, Ken Shirabe, Hideki Ijichi, Rumi Matono, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Yoshihiko Maehara, Acoustic radiation force impulse imaging predicts postoperative ascites resulting from curative hepatic resection for hepatocellular carcinoma, Surgery (United States), 10.1016/j.surg.2011.12.035, 151, 6, 837-843, 2012.06, Background: Measurement of liver stiffness using Virtual Touch Tissue Quantification (VTTQ) based on acoustic radiation force impulse imaging reflects the degree of hepatic fibrosis and reserve. This prospective study investigated how well the VTTQ value predicts the development of postoperative complications before curative hepatic resection for hepatocellular carcinoma (HCC). Methods: The study enrolled 50 consecutive patients between February 2009 and October 2010 whose preoperative VTTQ values were determined before they underwent curative hepatic resection for HCC. We assessed the relationship between postoperative complications and VTTQ values. Results: The study included 41 (82%) patients with chronic hepatitis and 9 (18%) with nonviral cirrhosis. The mean VTTQ value was 1.60 (m/sec), which correlated with the fibrosis stage (P =.0058). The VTTQ value was the only variable correlated with postoperative ascites that did not respond to pharmacologic treatment and required invasive management. Univariate and subsequent multivariate analyses revealed that the preoperative VTTQ value was the only independent risk factor for predicting the development of postoperative ascites (cutoff, 1.68 cm/sec; P =.007; odds ratio, 76.481). The area under the receiver operating characteristic curve for the diagnosis of postoperative ascites using VTTQ values was 0.90, whereas those using the aspartate transaminase-to-platelet ratio index and indocyanine green retention rate at 15 minutes values were 0.68 and 0.55, respectively. Conclusion: These data suggest that the VTTQ value is a reliable surrogate marker for predicting postoperative ascites before curative hepatic resection for HCC..
1578. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Shohei Yoshiya, Takeo Toshima, Takashi Motomura, Yuji Soejima, Hideaki Uchiyama, Yoshihiko Maehara, En bloc stapling division of the gastroesophageal vessels controlling portal hemodynamic status in living donor liver transplantation, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.02.016, 214, 6, e53-e56, 2012.06.
1579. T. Yoshizumi, K. Shirabe, T. Ikegami, H. Kayashima, N. Yamashita, K. Morita, T. Masuda, N. Hashimoto, A. Taketomi, Y. Soejima, Y. Maehara, Impact of human T cell leukemia virus type 1 in living donor liver transplantation, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04037.x, 12, 6, 1479-1485, 2012.06, Human T cell leukemia virus type 1 (HTLV-1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV-1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV-1 status in living donor liver transplantation (LDLT). Twenty-six of 329 (7.9%) HTLV-1 carriers underwent primary LDLT. One recipient negative for HTLV-1 before LDLT received a graft from an HTLV-1 positive donor. Eight donors were HTLV-1 positive. Twenty-seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV-1 positive donors and two from negative donors. The 1-, 3- and 5-year HTLV-1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score ≥ 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV-1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development. The authors investigate the impact of human T cell leukemia virus type 1 in living donor liver transplantation and find that fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score > 15 are risk factors for T cell leukemia development See editorial by Kaul on page 1365..
1580. Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Kazutoyo Morita, Naotaka Hashimoto, Hiroto Kayashima, Tohru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihko Maehara, The long-term outcomes of patients with hepatocellular carcinoma after living donor liver transplantation
A comparison of right and left lobe grafts, Surgery today, 10.1007/s00595-011-0086-4, 42, 6, 559-564, 2012.06, Purpose The feasibility of living donor liver transplantation (LDLT) using left lobe (LL) grafts has been demonstrated. However, the long-term outcome of the hepatocellular carcinoma (HCC) patients with LL grafts has not been elucidated. The aim of this study was to analyze the long-term outcomes after LDLT for HCC according to the graft type. Methods A retrospective analysis was performed evaluating the outcomes of LL graft recipients (n = 82) versus recipients of RL grafts (n = 46). The analysis endpoints were the overall and recurrence-free survival after LDLT. The demographics of both recipients and donors, and the tumor characteristics associated with the graft type were also analyzed. Results The graft volume (436 ± 74 g), as well as the graft volume-standard liver volume rate (38.3 ± 6.2%) of the LL graft group were significantly decreased as compared to those of the RL graft group (569 ± 82 g, 46.3 ± 6.7%; P>0.01). The 1-, 3-, 5- and 7-year overall survival rates of the LL graft group were 88.2, 80.2, 75.7 and 72.4%, respectively, which were not significantly different compared to those of the RL graft group (95.4, 87.3, 87.3 and 87.3%). The recurrence-free survival rates of the LL graft group (89.1% at 1 year, 78.8% at 3 years, 75.8% at 5 years and 70.3% at 7 years) were similar to those of the RL graft group (88.6, 88.6, 88.6 and 88.6%). The mean peak postoperative total bilirubin levels and duration of hospital stay after surgery for the LL grafting donors were significantly decreased as compared to those of the RL grafting donors (P>0.01). The rate of severe complications (over Clavien's IIIa) associated with LL graft procurement was 6.2%, which was lower than that in the RL graft group (15.6%). Conclusions The long-term outcomes in the HCC patients with LL grafts were similar to those of patients receiving RL grafts, and the outcomes of the donors of LL grafts were more favorable. Therefore, LL grafts should be considered when selecting LDLT for HCC to ensure donor safety..
1581. Takeo Toshima, Ken Shirabe, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Outcome of hepatectomy for hepatocellular carcinoma in patients with renal dysfunction, HPB, 10.1111/j.1477-2574.2012.00452.x, 14, 5, 317-324, 2012.05, Objectives: There are few reports on the efficacy of hepatectomy for hepatocellular carcinoma (HCC) in patients with renal dysfunction (RD). This study aimed to clarify the validity of hepatectomy for treating HCC in RD patients, and to compare postoperative courses in RD and non-RD patients. Methods: The clinical features of 722 HCC patients who underwent curative hepatectomy between 1986 and 2009 were retrospectively reviewed. Seventeen patients (2.4%) with preoperative serum creatinine levels of >2.0 mg/dl were defined as the RD group, and, of these, seven who did not receive preoperative haemodialysis were defined as borderline patients. Clinicopathological characteristics and postoperative outcomes were compared between the RD group (n= 17) and the non-RD group (n= 705). The postoperative courses of borderline patients were reviewed in detail. Results: Overall survival (P= 0.177) and disease-free survival (P= 0.942) after hepatectomy did not differ significantly between the groups. Incidences of massive ascites (35.3% vs. 14.3%; P= 0.034) and pleural effusion (52.9% vs. 17.6%; P= 0.001), defined as massive effusion (ME), were significantly higher in the RD group than in the non-RD group. Hypoalbuminaemia (≤2.8 g/dl; P= 0.031), heavy blood loss (≥1000 ml; P= 0.012) and intraoperative blood transfusion (P= 0.007) were risk factors for ME. Among the borderline patients, serum creatinine values were not increased immediately after surgery and four patients underwent haemodialysis. Conclusions: Preoperative hypoalbuminaemia, heavy blood loss and blood transfusion are independent risk factors for ME in RD patients. Preoperative improvement of anaemia and reduction of blood loss by meticulous surgical techniques may prevent ME in RD patients who require hepatectomy for HCC..
1582. Takeo Toshima, Akinobu Taketomi, Toru Ikegami, Takasuke Fukuhara, Hiroto Kayashima, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, V5-drainage-preserved right lobe grafts improve graft congestion for living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3182488bd8, 93, 9, 929-935, 2012.05, Background: Right lobe (RL) grafts without middle hepatic vein for living donor liver transplantation (LDLT) result in congestion of recipients' livers and sometimes in unfavorable postoperative course. This study aimed to evaluate the feasibility of our new V5-drainage-preserved RL (VP-RL) graft. Methods: Based on a review of 49 donors' livers in a retrospective study using three-dimensional reconstruction-computed tomography volumetry, hepatic vein draining segment 4 (V4) anatomy was classified into three types: inferior V4 dominant (A); superior V4 dominant (B); and umbilical vein to left hepatic vein dominant (C). Differences in functional graft volume (GV) and remnant liver volume (RV) between VP-RL and modified RL (M-RL) grafts with all three types were evaluated. In a prospective study of actual 15 LDLT, the outcome of venous reconstruction and postoperative parameters with VP-RL grafts compared with M-RL grafts was analyzed. Results: In the retrospective study using three-dimensional reconstruction-computed tomography volumetry, in types B and C, functional GV of VP-RL was larger than that of M-RL (P<0.05) without impaired donors' functional RV, whereas functional RV in VP-RL was significantly decreased in type A (P<0.05). In the prospective study of actual 15 LDLT, using VP-RL with types B and C, size and number of venous reconstructions, and functional GV and postoperative parameters, such as postoperative serum total bilirubin levels and ascites volume, were significantly improved compared with those using M-RL (P<0.05). Conclusions: Using preoperative V4 anatomical classification, VP-RL graft procurement is a valuable strategy in RL-LDLT to improve postoperative course of both recipients and donors..
1583. Rumi Matono, Shohei Yoshiya, Takashi Motomura, Takeo Toshima, Hiroto Kayashima, Toshiro Masuda, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Factors linked to longterm survival of patients with hepatocellular carcinoma accompanied by tumour thrombus in the major portal vein after surgical resection, HPB, 10.1111/j.1477-2574.2011.00436.x, 14, 4, 247-253, 2012.04, Objectives: The prognosis in patients with hepatocellular carcinoma (HCC) accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this study was to clarify the factors linked to survival of >5 years after hepatectomy in HCC patients with MPVTT. Methods: Twenty-nine HCC patients with MPVTT were divided into two groups comprising, respectively, patients who survived >5 years after hepatectomy (survivors, n = 5) and those who did not (non-survivors, n = 24). The two groups were compared. Results: Overall survival rates at 1, 3 and 5 years were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had recurrences of HCC in which the number of recurrent nodules was under four. Three (21.4%) of the 14 non-survivors who underwent curative resection experienced recurrences of HCC and all of them demonstrated fewer than four recurrent nodules (P = 0.0114). Local therapy, such as radiofrequency ablation and resection of recurrence, had more often been used in survivors than in non-survivors (P = 0.0364). Conclusions: Although surgical outcomes in patients with HCC accompanied by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the number of recurrent nodules is less than four, local therapy should be selected with the aim of achieving 5-year survival..
1584. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Tomoharu Yoshizumi, Mizuki Ninomiya, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Bacterial sepsis after living donor liver transplantation
The impact of early enteral nutrition, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2011.12.001, 214, 3, 288-295, 2012.03, Background: Bacterial sepsis is a significant problem that must be addressed after living donor liver transplantation (LDLT). Study Design: A retrospective analysis of 346 adult-to-adult LDLT patients was performed. Results: Forty-six patients (13.3%) experienced bacterial sepsis, with primary and secondary origins in 23.9% and 76.1%, respectively. Gram-negative bacteria accounted for 71.7% of the bacteria isolated. The 2-year cumulative graft survival rate in patients with bacterial sepsis was 45.7%. Patients with bacterial sepsis secondary to pneumonia (n = 12) had poorer 2-year graft survival rates (16.7%) than did those with primary or other types of secondary sepsis (p = 0.004). Multivariate analysis showed that intraoperative massive blood loss >10L (p < 0.001) and no enteral feeding started within 48 hours after transplantation (p = 0.005) were significant risk factors for bacterial sepsis. Among patients who received enteral nutrition, the incidences of bacterial sepsis in patients who received enteral nutrition within 48 hours (n = 135) or later than 48 hours (n = 57) were 5.9% and 21.0%, respectively (p = 0.002). The incidence of early graft loss was 8-fold higher in recipients with massive intraoperative blood loss without early enteral nutrition (p < 0.001). Conclusions: Early enteral nutrition was associated with significantly reduced risk of developing bacterial sepsis after LDLT..
1585. Takashi Motomura, Erina Koga, Akinobu Taketomi, Takasuke Fukuhara, Yohei Mano, Jun Muto, Hideyuki Konishi, Takeo Toshima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype, Hepatology Research, 10.1111/j.1872-034X.2011.00927.x, 42, 3, 288-295, 2012.03, Aim: A genetic polymorphism of inosine triphosphate pyrophosphatase (ITPA) has been associated with pegylated-interferon/ribavirin (PEG-IFN/RBV)-induced anemia in chronic hepatitis C patients. However, correlation of the genetic variant with anemia following liver transplantation has not been determined. Methods: Sixty-three hepatitis C virus (HCV)-positive patients who underwent liver transplantation and PEG-IFN/RBV therapy were enrolled. The rs1127354 was determined for each individual. Results: There was no relationship with anemia or RBV dosage in patients carrying the CC allele (CC group, n=43) and those carrying the CA allele (CA group, n=20). The incidence of hemoglobin (Hb) decline >3g/dL (CC: 4.7%, CA: 0%) was relatively low, whereas the incidence of Hb levels <10g/dL (CC: 18.6%, CA: 30.0%) was high. Univariate analysis revealed that splenectomy inversely correlated with Hb levels <10g/dL at 4weeks (P=0.04). Among the 22 patients who did not undergo splenectomy, the incidence of Hb levels <10g/dL tended to be lower in the seven patients carrying the CA allele (28.6%) than in the 15 patients with the CC allele (60.0%). Conclusion: The ITPA genetic polymorphism does not correlate with post-transplant PEG-IFN/RBV-induced anemia. Splenectomy is useful in preventing anemia regardless of the ITPA genotype..
1586. Jun Muto, Yohei Mano, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Additional resection of the pancreas body prevents postoperative pancreas fistula in patients with portal annular pancreas who undergo pancreaticoduodenectomy, Case Reports in Gastroenterology, 10.1159/000335210, 6, 1, 131-134, 2012.01, Portal annular pancreas (PAP) is a rare variant in which the uncinate process of the pancreas extends to the dorsal surface of the pancreas body and surrounds the portal vein or superior mesenteric vein.Upon pancreaticoduodenectomy (PD), when the pancreas is cut at the neck, two cut surfaces are created. Thus, the cut surface of the pancreas becomes larger than usual and the dorsal cut surface is behind the portal vein, therefore pancreatic fistula after PD has been reported frequently. We planned subtotal stomach-preserving PD in a 45-year-old woman with underlying insulinoma of the pancreas head. When the pancreas head was dissected, the uncinate process was extended and fused to the dorsal surface of the pancreas body. Additional resection of the pancreas body 1 cm distal to the pancreas tail to the left side of the original resection line was performed. The new cut surface became one and pancreaticojejunostomy was performed as usual. No postoperative complications such as pancreatic fistula occurred. Additional resection of the pancreas body may be a standardized procedure in patients with PAP in cases of pancreas cut surface reconstruction..
1587. Hideaki Uchiyama, Ken Shirabe, Masaru Morita, Yoshihiro Kakeji, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Noboru Harada, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Expanding the applications of microvascular surgical techniques to digestive surgeries
A technical review, Surgery today, 10.1007/s00595-011-0032-5, 42, 2, 111-120, 2012.01, In living donor liver transplantation (LDLT), it is considered safer to reconstruct hepatic arteries (HAs) under a microscope than under conventional loupe magnification, because graft HA stumps are generally thin and short with an average diameter of approximately 2 mm. We first applied microvascular surgical techniques to HA reconstruction for LDLT in 1996. In most cases, we use a disposable double-clip to secure the graft and recipient arteries, and interrupted 8-0 nonabsorbable monofilament sutures. We next started performing resection and reconstruction of the right HA in a surgery for hilar cholangioma using the same technique as in LDLT. Lately, we have started applying microvascular surgical techniques to various digestive surgeries; namely, supercharge and superdrainage in esophageal surgery, vascular reconstruction in free jejunal interposition grafts for cervical esophageal cancer, resection and reconstruction of spontaneous HA aneurysms, jejunal artery reconstruction for spontaneous superior mesenteric artery dissections, and so forth. Mastering this technique is time consuming. However, once a surgeon masters the technique it has almost unlimited applications, and most vital vessels can be safely reconstructed using this method. We herein provide a technical review of the application of microvascular surgical techniques for various digestive surgeries..
1588. Tomoharu Yoshizumi, Ken Shirabe, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Masanori Yoshimatsu, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Risk factors that increase mortality after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e318238dacd, 93, 1, 93-98, 2012.01, BACKGROUND.: Female liver to male recipient is a well-accepted risk factor for graft loss in cadaveric liver transplantation. However, gender matching is infeasible because of an insufficient number of available donors. No studies have been performed on the role of gender in the field of living donor liver transplantation. This report investigates the effect of gender mismatch on the outcome of living donor liver transplantation. METHODS.: A total of 335 patients and donors were classified into four groups according to the following gender combinations: male donor to male recipient group (n=104), male donor to female recipient group (n=120), female donor to male recipient (FM) group (n=59), and female donor to female recipient group (n=52). Patient and graft survival were compared among the groups. We performed a multivariable analysis to identify the factors associated with patient mortality. RESULTS.: The 1-, 3-, 5-, and 10-year patient survival rates in the FM group were 80.6%, 66.8%, 61.8%, and 47.7%, respectively. The FM group showed significantly shorter patient survival compared with the other three groups. Independent risk factors for patient mortality were: FM group (P=0.006), pretransplant diabetes mellitus (P=0.001), and a model for end-stage liver disease score more than or equal to 20 (P=0.004). CONCLUSIONS.: Male recipients of transplants from female donors, pretransplant diabetes mellitus, and a model for end-stage liver disease score more than or equal to 20 have poor survival rates..
1589. Ken Shirabe, Yohei Mano, Jun Muto, Rumi Matono, Takashi Motomura, Takeo Toshima, Kazuki Takeishi, Hidekaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Masaru Morita, Shunichi Tsujitani, Yoshihisa Sakaguchi, Yoshihiko Maehara, Role of tumor-associated macrophages in the progression of hepatocellular carcinoma, Surgery today, 10.1007/s00595-011-0058-8, 42, 1, 1-7, 2012.01, Recent studies have shown that the tumor microenvironment plays an important role in cancer progression. Tumor-associated macrophages (TAMs), in particular, have been found to be associated with tumor progression. Macrophages have multiple biological roles, including antigen presentation, target cell cytotoxicity, removal of foreign bodies, tissue remodeling, regulation of inflammation, induction of immunity, thrombosis, and endocytosis. Recent immunological studies have identified two distinct states of polarized macrophage activation: the classically activated (M1) and the alternatively activated (M2) macrophage phenotypes. Bacterial moieties such as lipopolysaccharides and the Th1 cytokine interferon-γ polarize macrophages toward the M1 phenotype. The M2 polarization was discovered as a response to the Th2 cytokine interleukin-4. In general, M2 macrophages exert immunoregulatory activity, participate in polarized Th2 responses, and aid tumor progression. TAMs have recently been found to play an important role in hepatocellular carcinoma (HCC) progression. Based on the properties of TAMs, obtained from pathological examination of resected specimens, we have identified new therapeutic approaches, involving the targeting of TAMs with adjuvant therapy after hepatic resection for HCC. This review discusses the roles of TAM in HCC progression and the possibility of new therapies targeting TAMs..
1590. Toru Ikegami, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yoshihiko Maehara, The impact of renal replacement therapy before or after living donor liver transplantation, Clinical Transplantation, 10.1111/j.1399-0012.2011.01450.x, 26, 1, 143-148, 2012.01, Introduction: The impact of renal replacement therapy (RRT) in living donor liver transplantation (LDLT) has not yet been investigated. Methods: Among 253 LDLT patients, RRT was started before (RRT-Pre, n=9), or after (RRT-Post, n=27) LDLT. The clinical outcomes were reviewed. Results: The one-yr graft survival rate was 94.1% without RRT, and 63.9% and in those with RRT (p<0.0001). Among the RRT patients, the RRT-Pre patients exhibited acute liver failure, hepatorenal syndrome and high model for end-stage liver disease score (35±12), whereas the RRT-Post patients had sepsis as a comorbidity. The one-yr graft survival rate was 100.0% in the RRT-Pre patients vs. 51.9% in the RRT-Post patients (p<0.01). The duration of RRT was significantly shorter in the RRT-Pre patients than that in the RRT-Post patients (5.3±2.1 vs. 17.8±14.1d, p=0.02). The mean duration between starting RRT and LDLT was 2.1±0.7d in the Pre-RRT patients. Conclusion: The RRT-Pre patients had excellent outcomes because the severe condition was primarily treated by LDLT after short-term pre-transplant RRT. Post-transplant uncontrollable sepsis was the major cause of graft loss in patients who receive RRT after LDLT..
1591. Akinobu Taketomi, Kazuki Takeishi, Yohei Mano, Takeo Toshima, Takashi Motomura, Shinichi Aishima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Total resection of the right hepatic vein drainage area with the aid of three-dimensional computed tomography, Surgery today, 10.1007/s00595-011-0021-8, 42, 1, 46-51, 2012.01, Purpose: We analyzed the feasibility and safety of our preliminary surgical approach for total hepatic resection of the right hepatic vein drainage area (THR-RHV) with the aid of three-dimensional computed tomography (3D-CT) guidance. Methods: Clinical findings and 3D-CT volumetry results were investigated in five patients who underwent THR-RHV for a hepatic malignant tumor close to the right hepatic vein (RHV). Results: The mean estimated remnant liver volume after a conventional right lobectomy was 474 ml, whereas that after THR-RHV was 614 ml, indicating that 140 ml (13.8%) of additional liver volume had been preserved by performing THR-RHV. The median operative time, mean ischemic time, and mean blood loss during surgery were 406 min, 51 min, and 587 ml, respectively. Histological examinations confirmed a negative surgical margin in all five patients. The mean liver volume estimated by 3D-CT was 458 ml, whereas the mean actual resected liver volume was 468 g, resulting in a mean error ratio of 3.1%. Conclusions: THR-RHV allowed for a higher remnant liver volume than that after conventional right lobectomy of the liver, and proved feasible with acceptable perioperative results. This technique thus promotes both safety and curability for patients with a tumor close to the RHV..
1592. Eisuke Kawakubo, Yuji Soejima, Eigorou Yamanouchi, Mizuki Ninomiya, Hiroto Kayashima, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Case of magnetic compression anastomosis with double-balloon enteroscopy for biliary obstruction after living donor liver translationn, Japanese Journal of Gastroenterological Surgery, 10.5833/jjgs.44.1404, 44, 11, 1404-1410, 2011.12, Biliary anastomotic strictures are one of the most significant postoperative complications after living donor liver transplantations (LDLT), which develop in about 10-30% of recipients. Various modalities have been reported to treat these complications with an acceptable success rate. Herein, we present a case of complete anastomotic obstruction of hepaticojejunostomy, for which a successful magnetic compression anastomosis (MCA) was performed. The patient was a 56-year-old man who was given a diagnosis of biliary anastomotic strictures 9 months after LDLT. Conservative treatment, including percutaneous transhepatic biliary drainage (PTBD), was initially undertaken, however, re canalization of the bile duct anastomosis could not be obtained. An MCA was performed 3 months after the initial PTBD, which resulted in a success. In conclusion, MCA is a safe and very effective method to treat complete anastomotic strictures after LDLT..
1593. Tetsuo Ikeda, Yusuke Yonemura, Naoyuki Ueda, Akira Kabashima, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yosihiro Kakeji, Masaru Morita, Shunichi Tsujitani, Yoshihiko Maehara, Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic glissonian approach and a modified hanging maneuver to minimize intraoperative bleeding, Surgery today, 10.1007/s00595-010-4479-6, 41, 12, 1592-1598, 2011.12, Purpose: Although laparoscopic liver resection has been widely adopted, performing a pure laparoscopic right hepatectomy remains a challenging procedure. The aim of this report is to evaluate the efficiency of a pure laparoscopic right hepatectomy (PLRH) in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver. Methods: Pure laparoscopic right hepatectomy was performed in the semi-prone position with the use of an intrahepatic Glissonian approach and modified hanging maneuver for patients with primary liver cancer (n = 3) and metastatic liver cancer (n = 1). Results: The intraoperative total blood loss was only 95-140 g (mean: 126.2 g). None of the patients required a blood transfusion, and no serious complications were encountered. The durations of the surgeries ranged from were 308 to 445 min (mean: 394.8 min). The postoperative hospital stay was 8-11 days (mean 9.5 days). Conclusion: Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver is thus considered to be a safe modality, which minimizes intraoperative bleeding..
1594. Hideaki Uchiyama, Yohei Mano, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Ken Shirabe, Yoshihiko Maehara, Kinetics of anti-blood type isoagglutinin titers and B lymphocytes in ABO-incompatible living donor liver transplantation with rituximab and plasma exchange, Transplantation, 10.1097/TP.0b013e318231e9f8, 92, 10, 1134-1139, 2011.11, Background. A novel immunosuppression protocol using rituximab and plasma exchange treatment was developed for ABO-incompatible living donor liver transplantation (ABO-I LDLT). The aim of this study was to investigate the kinetics of anti-blood type isoagglutinin titers and the number of blood B lymphocytes in ABO-I LDLT with the new protocol and their impact on the outcomes after ABO-I LDLT. Methods. Fifteen patients underwent ABO-I LDLT plus splenectomy with the new protocol between November 2005 and December 2010, and their data were retrospectively analyzed. Results. CD19-positive lymphocytes in the blood rapidly disappeared after rituximab treatment and began to recover approximately 6 months later. Anti-blood type isoagglutinin titers were lowered by pretransplant plasma exchange (2 3∼2 12→2 1∼2 8). Although the anti-donor blood type isoagglutinin titers remained consistently low after transplantation in comparison to the pretreatment levels, they persisted long after LDLT, whereas posttransplant biopsy specimens showed sustained A/B antigens on the graft livers. ABO-I hepatitis C virus-positive patients were prone to acceleration of hepatitis C viremia and cytomegalovirus antigenemia in comparison to the control patients. Conclusions. Although the new protocol for ABO-I LDLT yielded great success with 100% graft survival, the acceptable anti-blood type isoagglutinin titers just before LDLT, and its application to hepatitis C-positive patients must be determined..
1595. Toru Ikegami, Ken Shirabe, Kazutoyo Morita, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Hiroto Kayashima, Naotaka Hashimoto, Yoshihiko Maehara, Minimal hilar dissection prevents biliary anastomotic stricture after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3182336073, 92, 10, 1147-1151, 2011.11, Background. We introduced a new technique called minimal hilar dissection (Min-HD) technique in living donor liver transplantation (LDLT) to keep vascular networks around the recipient's bile duct. The aim of this study is to investigate whether the Min-HD technique could prevent biliary anastomotic stricture (BAS) after LDLT with duct-to-duct biliary reconstruction. Methods. An analysis of 214 adult-to-adult LDLT grafts (left lobe, n=135; right lobe, n=76; posterior segment, n=3) with duct-to-duct biliary reconstruction was performed. Results. There were 46 cases with BAS. The incidence of BAS was 32.1% in the conventional technique group (n=84) and 14.6% in the Min-HD technique group (n=130, P=0.003). Multivariate regression analysis regarding BAS was carried out and detected hepatic artery flow less than 50 mL/min (P=0.002), not using the Min-HD technique (P=0.011), biliary anastomotic leakage (BAL, P=0.027) and ductoplasty (P=0.039) for the significant risk factors for BAS. The incidence BAL was 11.9% in the conventional technique group and 0.7% in the Min-HD technique group (P=0.002). No other factors showed an impact on the occurrence of BAL. The treatments for BAS were performed by endoscopic or percutaneous procedures. The cumulative completion rate of the treatment after developing BAS was 45.1% and 78.6% at 1-and 3-year, respectively. The median period for treating BAS was 10.8 months. Conclusion. The Min-HD technique is a rational surgical method, and it has the potential for preventing BAS and BAL after duct-to duct biliary reconstruction in LDLT..
1596. Ken Shirabe, Takeo Toshima, Akinobu Taketomi, Kennichi Taguchi, Tomoharu Yoshizumi, Hideaki Uchiyama, Norifumi Harimoto, Kiyoshi Kajiyama, Akinori Egashira, Yoshihiko Maehara, Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan, Liver International, 10.1111/j.1478-3231.2011.02572.x, 31, 9, 1366-1372, 2011.10, Background & aims: Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC. Methods: Hepatocyte AFB1-DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non-B non-C hepatocellular carcinoma (NBNC HCC). Results: AFB1-DNA adducts were detected in hepatocyte nuclei in 18/279 patients (6%), including13/83 patients (16%) with NBNC HCC and 5/51 patients (10%) expressing hepatitis B surface antigen. None of the patients with HCV Ab (n=136) were positive for AFB1-DNA. The incidence of the G-T transversion and mutations in exon 7 of TP53 in patients with AFB1-DNA adducts were significantly higher in patients with than in patients without AFB1-DNA adducts. All three patients with the codon 249 AGG-AGT mutation had AFB1-DNA adducts. Conclusion: Although exposure to AFB1 is thought to be low in Japan, it is still associated with hepatocarcinogenesis, particularly in NBNC HCC and hepatitis B individuals..
1597. Toru Ikegami, Takashi Maeda, Hiroto Kayashima, Eiji Oki, Tomoharu Yoshizumi, Yoshihisa Sakaguchi, Yasushi Toh, Ken Shirabe, Yoshihiko Maehara, Soft coagulation, polyglycolic acid felt, and fibrin glue for prevention of pancreatic fistula after distal pancreatectomy, Surgery today, 10.1007/s00595-010-4433-7, 41, 9, 1224-1227, 2011.09, Purpose: To evaluate the effectiveness of using soft coagulation followed by the application of polyglycolic acid (PGA) felt and fibrin glue to prevent pancreatic fistula (PF) after distal pancreatectomy (DP). Methods: A soft coagulation system was applied on the cut surface of the pancreas after ligating the main pancreatic duct, followed by the application of layers of PGA felt and fibrin glue on the layers, to prevent the development of a PF after DP. Results: This technique was applied in nine patients, with mean drain amylase levels of 372 ± 296, 185 ± 209, 54 ± 40, and 47 ± 34 IU/l on days 1, 3, 5, and 7, respectively, after DP. Only one patient (11.1%) showed a Grade A PF on day 3 after surgery; none of the other patients developed a fistula. Conclusions: This technique is an effective prophylactic measure to prevent the development of a PF after DP..
1598. Mizuki Ninomiya, Ken Shirabe, Hideki Ijichi, Takeo Toshima, Noboru Harada, Hideaki Uchiyama, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Temporal changes in the stiffness of the remnant liver and spleen after donor hepatectomy as assessed by acoustic radiation force impulse
A preliminary study, Hepatology Research, 10.1111/j.1872-034X.2011.00809.x, 41, 6, 579-586, 2011.06, Aim: Virtual touch tissue quantification (VTTQ) is an implementation of ultrasound acoustic radiation force impulse imaging that provides numerical measurements of tissue stiffness. We have evaluated the temporal changes of the remnant liver and spleen after living donor hepatectomy with special reference to the differences between right and left liver donation. Methods: Nineteen living donors who received right lobectomy (small remnant liver [SRL] group; n=7) or extended left and caudate lobectomy (large remnant liver [LRL] group; n=12) were enrolled. They underwent measurement of liver and spleen VTTQ before and after donor surgery. Results: Virtual touch tissue quantification of the remnant liver increased postoperatively until postoperative day (POD) 3-5, and the values in the SRL group were significantly higher than those in the LRL group at POD 3-9. The values of the spleen also increased after donor surgery and the values in the SRL group were significantly higher than those in the LRL group at POD 3-14. A significant positive correlation between postoperative maximum value of VTTQ and postoperative maximum total bilirubin levels was observed. In liver transplant recipients, there was a significant positive correlation between preoperative spleen VTTQ and the corresponding actual portal venous pressure that was measured at the time of transplant surgery. Conclusion: Stiffness of the remaining liver and spleen in the smaller remnant liver group became harder than that in the larger remnant liver group. Perioperative measurement of liver and spleen VTTQ seems to be a useful means for assessing the physiology of liver regeneration..
1599. T. Motomura, A. Taketomi, T. Fukuhara, Y. Mano, K. Takeishi, T. Toshima, N. Harada, H. Uchiyama, T. Yoshizumi, Y. Soejima, K. Shirabe, Y. Matsuura, Y. Maehara, The impact of IL28B genetic variants on recurrent hepatitis C in liver transplantation
Significant lessons from a dual graft case, American Journal of Transplantation, 10.1111/j.1600-6143.2011.03537.x, 11, 6, 1325-1329, 2011.06, IL28B genetic polymorphism is related to interferon-sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51-year-old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated-interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients. In this dual graft liver transplantation case, each graft with different IL28B genotype showed significantly different pathological findings and viral kinetics after interferon therapy for recurrent hepatitis C..
1600. Takeo Toshima, Ken Shirabe, Kazuki Takeishi, Takashi Motomura, Youhei Mano, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, New method for assessing liver fibrosis based on acoustic radiation force impulse
A special reference to the difference between right and left liver, Journal of gastroenterology, 10.1007/s00535-010-0365-7, 46, 5, 705-711, 2011.05, Background: Virtual touch tissue quantification (VTTQ) based on acoustic radiation force impulse (ARFI) imaging has been developed as a noninvasive bedside method for the assessment of liver stiffness. In this study, we examined the diagnostic performance of ARFI imaging in 103 patients, focusing on the difference in VTTQ values between the right and left liver lobes. Methods: We evaluated VTTQ values of the right and left lobes in 79 patients with chronic liver disease who underwent histological examination of liver fibrosis and in 24 healthy volunteers. The diagnostic accuracy of VTTQ was compared with several serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index. Results: The VTTQ values (meters per second) in the right and left lobes were 1.61 ± 0.51 and 1.90 ± 0.68, respectively, and the difference was statistically significant (P < 0.0001). The VTTQ values in both liver lobes were correlated significantly with histological fibrosis grades (P < 0.001). The standard deviations of the VTTQ values in the right lobe were significantly lower than those in the left lobe (P < 0.001). The area under the receiver-operating characteristic curve for the diagnosis of fibrosis (F ≥ 3) using VTTQ values in both liver lobes was superior to serum markers, especially in the right lobe. Conclusions: VTTQ is an accurate and reliable tool for the assessment of liver fibrosis. VTTQ of the right lobe was more accurate for diagnosing liver fibrosis than in the left lobe..
1601. Naotaka Hashimoto, Tomohiko Akahoshi, Tetsuya Shoji, Morimasa Tomikawa, Norifumi Tsutsumi, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Successful treatment for hepatic encephalopathy aggravated by portal vein thrombosis with balloon-occluded retrograde transvenous obliteration, Case Reports in Gastroenterology, 10.1159/000330287, 5, 2, 366-371, 2011.05, This report presents the case of a 78-year-old female with hepatic encephalopathy due to an inferior mesenteric venous-inferior vena cava shunt. She developed hepatocellular carcinoma affected by hepatitis C virus-related cirrhosis and underwent posterior sectionectomy. Portal vein thrombosis developed and the portal trunk was narrowed after hepatectomy. Portal vein thrombosis resulted in high portal pressure and increased blood flow in an inferior mesenteric venous-inferior vena cava shunt, and hepatic encephalopathy with hyperammonemia was aggravated. The hepatic encephalopathy aggravated by portal vein thrombosis was successfully treated by balloon-occluded retrograde transvenous obliteration via a right transjugular venous approach without the development of other collateral vessels..
1602. Mami Kanamoto, Mitsuo Shimada, Yuji Morine, Tomoharu Yoshizumi, Satoru Imura, Toru Ikegami, Hiroki Mori, Yusuke Arakawa, Beneficial effects of follistatin in hepatic ischemia-reperfusion injuries in rats, Digestive Diseases and Sciences, 10.1007/s10620-010-1401-4, 56, 4, 1075-1081, 2011.04, Background: Ischemia-reperfusion injury has been demonstrated in a variety of clinical settings. The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. Follistatin, an activin-binding protein, binds to activins and subsequently blocks their action. It was reported that blockade of the action of activin with administration of follistatin accelerates recovery from ischemia renal injury. This study was conducted to investigate the involvement of the activin-follistatin system in hepatic ischemia-reperfusion injury. Methods: Total hepatic ischemia for 30 min was performed followed by reperfusion in a rat model. Rats were divided into two groups: a follistatin group and a control group. Follistatin (1 μg/body), which is an activin-binding protein, was administered at the time of reperfusion. Results: Though 80% of animals survived in the follistatin group, four of five animals died in the control group within 3 days after reperfusion (p < 0.05). AST was significantly lower at 3 h after reperfusion in the follistatin group (p < 0.05). LDH was also lower at 6 h after reperfusion in the follistatin group (p < 0.05). Follistatin inhibited the mRNA expression of the βA subunit of activin. Moreover, the expression of IL-6, which is an inflammatory cytokine, was suppressed at 6 h after reperfusion in the follistatin group (p < 0.05). Conclusions: The present study demonstrated that treatment with follistatin reduced the expression of IL-6 and activin resulting in beneficial support for hepatic ischemia-reperfusion injuries..
1603. Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Toru Ikegami, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yoshihiko Maehara, Living donor liver transplantation in patients who have received pretransplant treatment for hepatocellular carcinoma, Transplantation, 10.1097/TP.0b013e318210de92, 91, 8, e61-e62, 2011.04.
1604. Ken Shirabe, Takashi Motomura, Jun Muto, Takeo Toshima, Rumi Matono, Yohei Mano, Kazuki Takeishi, Hideki Ijichi, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Tumor-infiltrating lymphocytes and hepatocellular carcinoma
Pathology and clinical management, International Journal of Clinical Oncology, 10.1007/s10147-010-0131-0, 15, 6, 552-558, 2010.12, The presence of tumor-infiltrating lymphocytes (TILs) in hepatocellular carcinoma (HCC) is relatively rare. The prognosis of patients with HCC and marked TILs is better than that of patients with HCC without TILs. TILs in HCC tissues are mainly T cells, and previous reports suggested that TILs might be important antitumor effector cells. TILs have been extensively analyzed, and subpopulations of CD3+, CD4+, and CD8+ T cells are often present in HCC. Some studies have reported that the percentage of CD8+ T cells, which might have cytotoxic activity, is decreased in tumors with TILs, as compared with noncancerous tissues. Although the antitumor effects of TILs seem to be impaired in HCCs, the underlying mechanism has remained unclear until quite recently. Pathological and in vitro studies have now shown that regulatory T cells play important roles in the deterioration of the antitumor effects of TILs. The aim of this review is to introduce recent pathological findings for TILs in HCC and to evaluate new therapeutic strategies in this field..
1605. T. Ikegami, Y. Soejima, K. Shirabe, A. Taketomi, T. Yoshizumi, H. Uchiyama, T. Fukuhara, T. Ikeda, Y. Maehara, Evolving strategies to prevent biliary strictures after living donor liver transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2010.07.091, 42, 9, 3624-3629, 2010.11, Introduction The optimal surgical technique has not been elucidated that reduces the occurrence of biliary strictures after living donor liver transplantation (LDLT). Method We performed retrospective analysis of 193 consecutive LDLTs, including 78 right and 115 left lobe grafts. An external biliary stent was used for all of the cases. Results The overall 1-, 3-, and 5-year biliary stricturefree survival rates were 87.5%, 85.3%, and 85.3%, respectively. The 1- and 3-year biliary stricturefree survival rates for duct-to-duct reconstruction were 86.9% and 84.9%, and those for hepaticojejunostomy were 90.1% and 80.8%, respectively. A multivariate analysis revealed that the original number of graft bile ducts greater than the number of external stents, right lobe grafts, bile leaks, and recipient age older than 60 years represented the significant risk factors (P < .05) to develop a biliary stricture after LDLT. All cases with biliary strictures (n = 61) were initially managed nonsurgically, but 4 patients ultimately required interventions. Conclusions Biliary reconstruction in LDLT using an appropriate number of external stents resulted in fairly acceptable outcomes. However, not only the proper use of stents or graft selection, but also nonsurgical factors, are important factors that determine the incidence of biliary strictures after LDLT..
1606. Akinobu Taketomi, Takasuke Fukuhara, Kazutoyo Morita, Hiroto Kayashima, Mizuki Ninomiya, Yoichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihko Maehara, Improved results of a surgical resection for the recurrence of hepatocellular carcinoma after living donor liver transplantation, Annals of Surgical Oncology, 10.1245/s10434-010-0999-y, 17, 9, 2283-2289, 2010.09, Purpose: This study was designed to analyze the clinical outcomes of the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and to evaluate the efficacy of a surgical resection in treating such a recurrence. Methods: A total of 101 adult LDLT recipients with HCC between 1996 and 2007, including 17 who had recurrent HCC, were reviewed. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics, laboratory valuables, and tumor characteristics were analyzed. Any medical or surgical treatments that had been administered for any recurrence also were considered. Results: The mean duration until the initial recurrence after LDLT and the mean duration until death after the initial recurrence were 12.9 months and 12.0 months, respectively. A univariate analysis showed that gender, interferon therapy, early posttransplant tumor recurrence, and eligibility for a surgical resection all had a beneficial impact on survival from tumor recurrence. A surgical resection of tumor relapse was the most important variable in our study, and therefore the patients were divided into two groups: surgical therapy group (n = 9), and nonsurgical therapy group (n = 7). Interestingly, the overall survival rates of the surgical group were significantly better than those of the nonsurgical group and were similar to that of the patients without HCC recurrence. Conclusions: Surgical therapy might be useful for patients who experience a recurrence of HCC after LDLT to improve their outcome, when such treatment is available..
1607. Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Natsumi Yamashita, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Mizuki Ninomiya, Yoshihiko Maehara, Living donor liver transplantation in patients older than 60 years, Transplantation, 10.1097/TP.0b013e3181e81b2d, 90, 4, 433-437, 2010.08, Background. Living donor liver transplantation (LDLT) has been performed in adult patients. However, there are a few reports on how recipient age affects the outcome of LDLT. This study assessed LDLT outcome in patients aged 60 years or older. Methods. A total of 267 patients were enrolled and classified into two groups: those younger than 60 years (younger group, n=210) and those aged 60 years or older (older group, n=57). The 6-month and 1-, 3-, and 5-year patient survivals and the incidence of complications were compared. Multivariate analysis was performed to identify the risk factors. Results. Fifty-five of 57 (96.5%) donors in the older group were younger than 50 years (range 25-47 years), whereas only 177 of 210 (84.3%) donors in the younger group were younger than 50 years (P<0.0001). The 6-month and 1-, 3-, and 5-year patient survival rates of the older group were 92.9%, 85.3%, 72.7%, and 70.3%, respectively, whereas those of the younger group were 87.4%, 85.8%, 80.2%, and 78.2%, respectively. Neither difference was significant. A multivariate analysis revealed that the presence of diabetes, lack of hepatocellular carcinoma, and Model for End-Stage Liver Disease (MELD) Score more than or equal to 20 were independent risk factors for survival less than 1 year after LDLT (P=0.0003, P=0.014, and P=0.041, respectively). Another multivariate analysis revealed that the lack of consanguinity, MELD Score more than or equal to 20, and male recipient were independent risk factors for death 1 year or more after LDLT (P=0.004, P=0.005, and P=0.015, respectively). Conclusion. Recipient age did not affect LDLT outcome when patients with MELD Score less than 20 received grafts from consanguineous donors..
1608. Tomonobu Gion, Akinobu Taketomi, Ken Shirabe, Hirofumi Hasegawa, Takayuki Hamatsu, Yo Ichi Yamashita, Keishi Sugimachi, Tomoharu Yoshizumi, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, The role of serum interleukin-8 in hepatic resections, Surgery today, 10.1007/s00595-008-4086-y, 40, 6, 543-548, 2010.06, Purpose: Interleukin-8 (IL-8) is a neutrophil chemotactic factor, which is associated with some inflammatory diseases and various types of surgical stress. The aim of this study was to investigate whether the early postoperative serum IL-8 level may potentially be a new indicator of a surgical stress in patients undergoing a hepatic resection. Methods: The serum IL-8 levels were measured in 37 patients who underwent a hepatectomy. The serum IL-8 levels were serially measured using an enzyme-linked immunosorbent assay both before and after a hepatic resection. In addition, the correlation between the postoperative IL-8 value and several clinical variables were examined. Results: The mean level of IL-8 significantly increased immediately after the operation (P < 0.01 vs before the operation) and decreased on the first postoperative day (POD 1, P < 0.05 vs after the operation). The early postoperative IL-8 levels positively correlated with the length of the procedure (r = 0.383; P < 0.05), the estimated blood loss (r = 0.483; P < 0.01) and the serum bilirubin level on POD 1 (r = 0.390; P < 0.05), and inversely correlated with the white blood cell counts (r = -0.388; P < 0.05) and lymphocyte counts on POD 1 (r = -0.424; P < 0.05). In a comparison of the postoperative IL-8 levels with the surgical factors, there was a significant difference in the extension of the resection (P < 0.05) and in blood transfusion. The patients with a fever of more than 38°C showed higher levels of IL-8 immediately after the operation than those without fever (P < 0.01). Conclusions: The early postoperative serum IL-8 level was found to correlate with the degree of the severity of surgery in patients undergoing a hepatic resection, and it is also considered to be a new indicator of surgical stress and liver injury..
1609. Takasuke Fukuhara, Toru Ikegami, Kazutoyo Morita, Kenji Umeda, Shigeru Ueda, Shigeyuki Nagata, Keishi Sugimachi, Tomonobu Gion, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Impact of preoperative serum sodium concentration in living donor liver transplantatio, Journal of Gastroenterology and Hepatology (Australia), 10.1111/j.1440-1746.2009.06162.x, 25, 5, 978-984, 2010.05, Background and Aims: The importance of hyponatremia in deceased donor liver transplantation (DDLT) has been recently discussed frequently. However, its impact on the outcomes in living donor liver transplantation (LDLT) has not yet been elucidated. The current study was designed to demonstrate the impact of pre-transplant sodium concentration on postoperative clinical outcomes. Methods: One hundred and thirty-four patients who underwent LDLT for end-stage liver diseases were examined to evaluate the significance of pre-transplant hyponatremia (Na ≤ 130 mEq/L) on the short-term clinical outcomes and the efficacy of the Model for End-Stage Liver Disease and serum sodium (MELD-Na) score using the sodium concentration and original MELD score. Results: The preoperative sodium and MELD score for all patients were 133.9 mEq/L (range: 109-142) and 16.2 (range: 6-38), respectively. According to a multivariate analysis, not only the MELD score (P = 0.030) but also the sodium concentration (P = 0.005) were found to be significant predictive factors for short-term graft survival. Preoperative hyponatremia was a significant risk factor for the occurrence of sepsis (P < 0.001), renal dysfunction (P < 0.001) and encephalopathy (P = 0.026). The MELD-Na score was 19.6 (range: 6-51) and the area under the receiver-operator curve of that (c-statistics: 0.867) was higher than MELD score and sodium concentration (c-statistics: 0.820 and 0.842, respectively). Conclusion: Preoperative hyponatremia was a significant risk for postoperative complications and short-term graft loss. The addition of sodium concentration to MELD score might therefore be an effective predictor for post-transplant short-term mortality in LDLT..
1610. Keishi Sugimachi, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Yo Ichi Yamashita, Kenji Umeda, Kazutoyo Morita, Yoshihiko Maehara, Successful curative extracorporeal hepatic resection for far-advanced hepatocellular carcinoma in an adolescent patient, Liver Transplantation, 10.1002/lt.22051, 16, 5, 685-687, 2010.05.
1611. Yuuta Kasagi, Koji Yamazaki, Akihiko Nakashima, Takeshi Yamana, Nami Yamashita, Hiroto Kayashima, Yuji Hoshino, Mayumi Ishida, Tomoharu Yoshizumi, Noriaki Sadanaga, Atsushi Fukuda, Hiroshi Matsuura, Kenichiro Okadome, Chondroblastic osteosarcoma arising from the pleura
Report of a case, Surgery today, 10.1007/s00595-009-3995-8, 39, 12, 1064-1067, 2009.12, Extraskeletal osteosarcoma is an uncommon malignant neoplasm. The origin of osteosarcoma in the pleura is extremely rare, with only four such cases so far documented in the literature to the best of our knowledge. We herein report the case of a 64-year-old Japanese man in whom a left pneumonectomy and pleurectomy were carried out to remove a huge tumor. The pathological examination confi rmed a diagnosis of chondroblastic osteosarcoma that had originally arisen from the pleura..
1612. T. Ikegami, A. Taketomi, Y. Soejima, T. Yoshizumi, T. Fukuhara, K. Kotoh, S. Shimoda, M. Kato, Y. Maehara, The Benefits of Interferon Treatment in Patients Without Sustained Viral Response After Living Donor Liver Transplantation for Hepatitis C, Transplantation Proceedings, 10.1016/j.transproceed.2009.08.070, 41, 10, 4246-4252, 2009.12, Although it has been recognized that interferon (IFN) treatment is crucial for recurrent hepatitis C after liver transplantation, its benefits have not been determined among patients without a sustained viral response (SVR). Methods: Eighty patients who received IFN plus ribavirin treatment after living donor liver transplantation were grouped as follows: group I (n = 18) SVR; group II (n = 25) no-SVR but viral response [VR] positive; Group III (n = 13) no-VR but biochemical response [BR] positive; and group IV (n = 24) no-VR and no-BR. Results: In groups II and III, not only the histological activity grade and fibrosis stage, but also the serum parameters including transaminases and type IV collagen were stable for 3 years after induction of IFN-based treatment. In group I, the activity grade and fibrosis stage significantly improved (P < .01). In group IV, the fibrosis stage significantly deteriorated (P < .01); the serum transaminases and type IV collagen were significantly higher than the other groups (P < .01). The mean duration of IFN treatment was significantly longer among group II (96 weeks) compared with the other cohorts (P < .05). The 5-year graft survival rate in groups II (91%) and III (100%) were comparable to those of group I (100%); group IV (62%) was significantly lower than the other groups (P < .05). Conclusion: IFN treatment was beneficial even among subjects with IFN-dependent VR or BR, although they did not achieve SVR..
1613. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Tashiharu Salbara, Takashi Nishizaki, Yoshihiko Maehara, Recurrent familial hypobetalipoproteinemia-induced nonalcoholic fatty liver disease after living donor liver transplantation, Liver Transplantation, 10.1002/lt.21766, 15, 7, 806-809, 2009.08, Familial hypobetalipoproteinemia (FHBL) is one of the causes of nonalcoholic steatohepatitis (NASH) and a codominant disorder. Patients heterozygous for FHBL may be asymptomatic, although they demonstrate low plasma levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Here we report a nonobese 54-year-old man with decompensated liver cirrhosis who underwent living donor liver transplantation with his son as the donor. Low albuminemia and refractory ascites persisted after transplantation. A biopsy specimen obtained 11 months after liver transplantation revealed severe steatosis and fibrosis, and recurrent NASH was diagnosed on the basis of pathological findings. Both the patient's and donor's laboratory tests demonstrated low LDL cholesterol and apolipoprotein levels. Because mutations in messenger RNAs of microsomal triglyceride transfer protein and apolipoprotein B genes were excluded neither in the recipient nor in the donor, both were clinically diagnosed as being heterozygous for FHBL. We successfully treated the recipient with heterozygous FHBL-induced recurrent NASH after liver transplantation using our diet and exercise programs..
1614. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Tomohiro Iguchi, Naotaka Hashimoto, Yoshihiko Maehara, Rituximab, IVIG, and plasma exchange without graft local infusion treatment
A new protocol in ABO incompatible living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3181adcae6, 88, 3, 303-307, 2009.08, BACKGROUND. Although graft local infusion (GLI) treatment via the portal vein or the hepatic artery has been the pivotal strategy in ABO incompatible (ABOi) living donor liver transplantation (LDLT) in Japan, the procedure is associated with a high rate of catheter-associated complications. METHODS. A new ABOi-LDLT protocol has been implemented using rituximab, intravenous immune globulin (IVIG), plasma exchange (PE), and splenectomy, without using GLI, on four patients, since 2007. Three other patients, treated before 2007, received GLI. RESULTS. Three of the four patients with liver cirrhosis received rituximab over 3 weeks before LDLT, followed by PEs and post-LDLT IVIG, resulting in no rebound elevation of the isoagglutinin titers. The remaining patient, with fulminant hepatitis, received rituximab 3 days before the LDLT, resulting in antibody-mediated rejection, successfully treated by IVIG and PE. All four patients that were treated with the new protocol are alive, 26, 8, 6, and 5 months after ABOi-LDLT with normal liver function. Two of the three other patients with GLI, before 2007, had catheter-associated complications, including one graft loss. CONCLUSION. The new ABOi-LDLT protocol using rituximab, IVIG, and PE, without the use of GLI, therefore seems to be a safe and an effective treatment modality..
1615. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Shigeyuki Nagata, Yoshihiko Maehara, Potential risk in using hepatic veins of a native liver for reconstructing accessory veins in right lobe living donor graft, Transplantation, 10.1097/TP.0b013e3181aae502, 88, 1, 143-144, 2009.07.
1616. T. Yoshizumi, Y. Ikeda, Y. Kaneda, K. Sueishi, Ex Vivo Transfer of Nuclear Factor-κB Decoy Ameliorates Hepatic Cold Ischemia/Reperfusion Injury, Transplantation Proceedings, 10.1016/j.transproceed.2008.10.101, 41, 5, 1504-1507, 2009.06, Cold ischemia/reperfusion injury of the hepatic graft has been attributed to the release of various inflammatory cytokines. Specific inhibition of these cytokines may improve viability of the hepatic graft upon reperfusion. Herein we have assessed the efficacy of cis element decoy against nuclear factor-κB binding site delivery to the hepatic tissue in a rodent liver transplantation model. At 8 hours after reperfusion of the liver, significant reduction was noted in the livers treated with decoy in the release of cytosolic enzymes from the hepatocytes and in serum tumor necrosis factor α (P < .05). The neutrophilic infiltration into the hepatic grafts was significantly suppressed in the livers treated with decoy oligodeoxynucleotides (ODNs). Decoy ODNs against nuclear factor-κB binding site delivery improved the viability of the hepatic graft against cold ischemia/reperfusion injury in the rodent liver transplantation model..
1617. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hirofumi Kawanaka, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Hypersplenism after living donor liver transplantation, Hepato-gastroenterology, 56, 91-92, 778-782, 2009.05, Background/Aims: It has not determined whether post-transplant persistent hypersplenism (PTPH) occurs after living donor liver transplantation (LDLT). Methodology: One hundred and ninety-four patients who survived more than 6 months after LDLTs were examined for the evaluation to determine the incidence of PTPH (leukocyte counts <3,500/μL and/or platelet counts <7.5×104/μL). In addition, 154 patients without a splenectomy were evaluated for the risk factors for PTPH. Results: The incidence of PTPH was 20.1% (n=31/154), and the occurrence ranged between 1.1 and 9.9 years after the LDLT, with the mean follow-up periods of 3.3±2.5 years. Multivariate analysis showed that portal pressure >30mmHg at the time of the laparotomy (p<0.01) and post-LDLT small for size syndrome (p<0.01) are risk factors for PTPH. For those with severe portal hypertension (>30 mmHg at laparotomy), the splenectomy tended to give better survival rate (p=0.09) without increasing the rate of septic complications. Conclusions: Hypersplenism did persist in a proportion of patients after LDLT. A high-risk for PTPH, especially severe portal hypertension, may be an indication for a splenectomy during LDLT in order to achieve uncomplicated post-transplant recovery..
1618. Yusuke Arakawa, Mitsuo Shimada, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Hirohumi Kanemura, Beneficial effects of splenectomy on massive hepatectomy model in rats, Hepatology Research, 10.1111/j.1872-034X.2008.00469.x, 39, 4, 391-397, 2009.04, Aim: Possible spleno-hepatic relationships during hepatectomy remain unclear. The purpose of this study was to investigate the impact of splenectomy during massive hepatectomy in rats. Methods: Rats were divided into the following two groups: 90% hepatectomy (Hx group), hepatectomy with splenectomy (Hx+Sp group). The following parameters were evaluated; survival rate, biochemical parameters, quantitative RT-PCR for hemeoxygenase-1 (HO-1) and tumor necrosing factor α (TNFα), immunohistochemical staining for HO-1, proliferating cell nuclear antigen labeling index and liver weights. Results: The survival rate after massive hepatectomy significantly improved in Hx+Sp group as well as serum biochemical parameters, compared with Hx group (P < 0.05). HO-1 positive hepatocytes and its mRNA expression significantly increased and TNFα mRNA expression significantly decreased in Hx+Sp group compared with Hx group (P < 0.05). Moreover, liver regeneration was significantly accelerated at 48 and 72 h after hepatectomy in Hx+Sp group. Conclusions: Splenectomy had beneficial effects on massive hepatectomy by ameliorating liver injuries and promoting preferable liver regeneration..
1619. Toru Ikegami, Mitsuo Shimada, Satoru Imura, Yuji Soejima, Tomoharu Yoshizumi, Jun Hanaoka, Yuji Morine, Yoshihiko Maehara, The changes of the medial right lobe, transplanted with left lobe liver graft from living donors, Transplantation, 10.1097/TP.0b013e318195c2a3, 87, 5, 698-703, 2009.03, Background. Procurement of left lobe (LL) living donor graft with medial right lobe (mRL) might be an innovative technique. Methods. The grafts were procured from a living donor, exposing the right anterior Glissonean pedicles, after confirmation of the demarcation line by test-clamping of the right Glissonean pedicle. Based on serial computed tomography, the increase in the graft volume (GV) after addition of mRL and changes in volumes were evaluated. Results. The addition of mRL (n=7) increased GV by 48±9 g, which corresponded to a 4% increase in GV-to-standard liver volume ratio. After transplantation, mRL volume has increased in all cases. The regeneration rate of the mRL and other LL segments 1 month after transplantation was 61%±18% and 146%±15%, respectively. Viable hepatic parenchyma with marginal bile duct dilatations in transplanted mRL was observed in all the cases. Marginal enhancement was observed in those cases with promoted regeneration of transplanted mRL. In the cranial part of the mRL, portal branching from the left portal vein, over the middle hepatic vein, was observed in all cases. Conclusion. This technique affords an increase in GV in living donor LL procurement, and should increases the application of LL grafts in living donor liver transplantation..
1620. Toru Ikegami, Takeo Toshima, Kazuki Takeishi, Yuji Soejima, Hirofumi Kawanaka, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Bloodless Splenectomy During Liver Transplantation for Terminal Liver Diseases with Portal Hypertension, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2008.10.034, 208, 2, e1-e4, 2009.02.
1621. Akinobu Taketomi, Hiroto Kayashima, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, Donor risk in adult-to-adult living donor liver transplantation
Impact of left lobe graft, Transplantation, 10.1097/TP.0b013e3181943d46, 87, 3, 445-450, 2009.02, Background.: To ensure donor safety in adult-to-adult living donor liver transplantation, we established a selection criterion for donors in which left lobe (LL) was the first choice of graft. Methods.: Two hundred six consecutive donors were retrospectively studied. Donors were divided into two groups according to graft type: LL graft (n=137) and right lobe (RL) graft (n=69). Results.: Although mean intraoperative blood loss of LL was significantly increased compared with RL, mean peak postoperative total bilirubin levels and duration of hospital stay after surgery were significantly less for LL than RL (P<0.05). No donor died or suffered a life-threatening complication during the study period. The overall complication rate was 34.0%, including biliary complications in 5.3%. The number of biliary complications was four (2.9%) in LL and seven (10.1%) in RL (P<0.05). Logistic regression analysis revealed that only graft type (LL vs. RL) is significantly related to the occurrence of biliary complications (odds ratio 0.11; P=0.0012). The cumulative overall graft survival rates in the recipients with LL were not significantly different from that in the recipients with RL. Conclusions.: LL grafting should be considered favorably when selecting donors for adult-to-adult living donor liver transplantation..
1622. Akinobu Taketomi, Kensaku Sanefuji, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uhciyama, Toru Ikegami, Noboru Harada, Yoichi Yamashita, Keishi Sugimachi, Hiroto Kayashima, Tomohiro Iguchi, Yoshihko Maehara, Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3181943bee, 87, 4, 531-537, 2009.02, BACKGROUNDS.: Because many patients who did not meet the Milan criteria have survived long after undergoing living donor liver transplantation (LDLT), extended criteria for recipient with hepatocellular carcinoma (HCC) are therefore considered to be necessary. METHODS AND RESULTS.: A total of 90 consecutive adult LDLT recipients with HCC between 1996 and 2007 were reviewed. The recurrence-free survival rates of all 90 patients were 86.0%, 81.3%, and 81.3% at 1, 3, and 5 years, respectively. Fourteen of 90 patients developed a recurrence of tumor after the LDLT. The tumor recurrences were diagnosed within 1 year after the LDLT in 11 (78.6%) patients. In a multivariate analysis, both the tumor size of less than 5 cm (P=0.0202) and the des-gamma-carboxy prothrombin (DCP) level of less than 300 mAU/mL (P=0.0001) were found to be favorable independent factors for the recurrence of HCC after LDLT. Therefore, the authors devised new selection criteria for HCC patients (a tumor size of <5 cm or a DCP of <300 mAU/mL). The 1-, 3-, and 5-year overall or recurrence-free survival rates of the 85 patients who met the new criteria were 92.3%, 85.9%, and 82.7%, or 90.5%, 87.0%, and 87.0%, respectively, which were significantly different from those of the five patients who did not meet the new criteria (P<0.0001). CONCLUSIONS.: A combination of two factors, namely the tumor size and the DCP level, was found to be useful for expanding the selection of LDLT candidates for HCC..
1623. Kensaku Sanefuji, Hiroto Kayashima, Tomohiro Iguchi, Keishi Sugimachi, Yo Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Takashi Nishizaki, Akinobu Taketomi, Yoshihiko Maehara, Characterization of hepatocellular carcinoma developed after achieving sustained virological response to interferon therapy for hepatitis C, Journal of Surgical Oncology, 10.1002/jso.21176, 99, 1, 32-37, 2009.01, Background: Interferon (IFN) reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). However, HCC develops in the some patients who have achieved a sustained virological response (SVR). The aim of this study was to clarify the features and prognosis of SVR patients who developed HCC. Materials and Methods: Twenty-six patients who underwent curative hepatectomy for initial HCC after IFN therapy were closely investigated. Twenty patients who were seropositive for HCV-RNA (non-SVR), and a further 6 patients who achieved SVRs (SVR) were included. We analyzed the clinicopathological features, immunological expression levels of p53 and whether HCV-RNA is present in the excised liver. Results: The liver functions of the SVR group were almost better than those of the non-SVR group. However, there was no significant difference in pathological features, surgical factors and prognosis between the groups. In one case with SVR out of eight specimens tested was HCV-RNA detected in the non-cancerous tissue. Immunohistochemistry revealed overexpression of p53 in eight HCCs (100%) from SVR patients. Conclusion: Recurrent HCC still developed after the curative hepatectomy, even if viral elimination had been successful. And molecular alterations in hepatocarcinogenesis of SVR patients might be different from those of CHC patients..
1624. Yuji Soejima, Takasuke Fukuhara, Kazutoyo Morita, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara, A simple hilar dissection technique preserving maximum blood supply to the bile duct in living donor liver transplantation, Transplantation, 10.1097/TP.0b013e318188d4dc, 86, 10, 1468-1469, 2008.11, Duct-to-duct reconstruction is associated with a higher incidence in biliary strictures in living donor liver transplantation (LDLT). However, a standard dissection technique for the recipient's bile duct has not been established. Here, we describe a simple bile duct dissection technique preserving maximum vascular integrity during total hepatectomy of the recipient. The present technique might facilitate duct-to-duct bile duct reconstruction in both right and left lobe LDLT and, thus, contribute to reduce biliary complications such as biliary strictures. We believe that this technique can be a standard in the field of LDLT..
1625. Takuya Tokunaga, Toru Ikegami, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Hisamitsu Shinohara, Mitsuo Shimada, Beneficial effects of fluvastatin on liver microcirculation and regeneration after massive hepatectomy in rats, Digestive Diseases and Sciences, 10.1007/s10620-008-0241-y, 53, 11, 2989-2994, 2008.11, Fluvastatin, the first entirely synthetic statin, has a significant cholesterol-lowing effect comparable with other statins. In addition, it has been shown to inhibit oxidative stress and improve vascular endothelial function. The aim of this study was to clarify the pretreatment effects of fluvastatin on liver function after massive hepatectomy in rats. Six-week-old male Wister rats were divided into two groups: a fluvastatin group (group F), pretreated with oral administration of fluvastatin (20 mg/kg per day) for 2 days before 90% hepatectomy; and a control group (group C), pretreated with vehicle for 2 days before hepatectomy. Animals were sacrificed at 0, 12, 24, 48, and 72 h after hepatectomy. The liver regeneration rate, liver function tests, and hepatic stellate cell activation were examined. The liver regeneration rate in group F was significantly higher at 72 h after hepatectomy (P < 0.05). The serum level of total bilirubin in group F was significantly lower at 48 h after hepatectomy (P < 0.05). Sinusoidal area in group F was maintained histologically. Furthermore, the expression of alpha smooth-muscle actin (α-SMA) protein in the liver was inhibited in group F at 48 h after hepatectomy. This study demonstrated the beneficial effects of fluvastatin in a lethal massive hepatectomy model using rats, with improved hepatic regeneration and microcirculations, by inhibiting the activation of hepatic stellate cells..
1626. Toru Ikegami, Akinobu Taketomi, Ryuji Ohta, Yiji Soejima, Tomoharu Yoshizumi, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, The risks of HBV infection after liver transplantation from HBc antibody positive donor to HBs antibody positive recipient, Hepato-gastroenterology, 55, 88, 2162-2165, 2008.11, The rate of de novo hepatitis B infection, after liver transplantation from a hepatitis B core antibody (HBcAb) (+) donor to a surface antibody (HBsAb) (+) recipient bas not yet elucidated. Four recipients with HBsAb (+) and HBcAb, (+), who received living donor grafts from HBcAb (+) donors were herein reviewed. They received lamivudine monotherapy: three patients with HBsAb titer >10 IU/L did not demonstrate the onset of HBsAg, whereas one patient with HBsAb titer <10 IU/L developed hepatitis B antigen (HBsAg) 4 years after transplantation. An HBsAb (+) patient with a titer of >10 IU/L is therefore considered not to require combination therapy when receiving an HBcAb (+) liver graft. However, a great deal of caution is necessary in patients with a negative or low HBsAb titers <10 IU/L..
1627. Y. Soejima, S. Ueda, K. Sanefuji, H. Kayashima, T. Yoshizumi, T. Ikegami, Y. Yamashita, K. Sugimachi, T. Iguchi, A. Taketomi, Y. Maehara, Sequential pancreaticoduodenectomy after living donor liver transplantation for cholagiocacinoma, American Journal of Transplantation, 10.1111/j.1600-6143.2008.02346.x, 8, 10, 2158-2162, 2008.10, Liver transplantation (LT) for patients with primary sclerosing cholangitis (PSC) is often contraindicated due to concomitant occurrence of cholangiocarcinoma (CC). Cases of simultaneous pancreaticoduodenectomy (PD) with LT have been sporadically reported; however, the applicability of such an invasive procedure to patients with CC has not been validated. We report here a case of sequential PD performed 44 days after a successful living donor liver transplantation (LDLT) using a left lobe graft. Although a clear pancreatic juice leakage through the drain persisted for days after surgery, the patient recovered from the complication and was discharged 32 days after the procedure. Currently, 1 year after LDLT, the patient is doing well with no evidence of recurrence. In conclusion, a sequential PD following LDLT is a safe and feasible option to treat CC complicating PSC. Long-term follow-up and accumulation of cases are necessary to evaluate the effectiveness of this procedure for this complicated disease..
1628. Hiroto Kayashima, Akinobu Taketomi, Yusuke Yonemura, Hideki Ijichi, Noboru Harada, Tomoharu Yoshizumi, Yuji Soejima, Kengo Yoshimitsu, Yoshihiko Maehara, Accuracy of an age-adjusted formula in assessing the graft volume in liver donor liver transplantation, Liver Transplantation, 10.1002/lt.21547, 14, 9, 1366-1371, 2008.09, In living donor liver transplantation, the estimated graft volume (GV) from young donors tends to be overestimated. One reason for this error may be a decrease in GV due to dehydration by University of Wisconsin (UW) solution. The aim of this study was to clarify (1) the usefulness of an age-adjusted formula and (2) the correlation between the decrease in GV and donor age. First, we created the age-adjusted formula using regression analysis retrospectively in 167 donors, and we evaluated the difference in the error ratio of GV from the age-adjusted formula and 3-dimensional computed tomography (3D-CT) prospectively in 49 donors. Second, we measured intraoperative GV both before and after flushing with UW solution and calculated the decrease ratio, and we then evaluated the difference in the decrease ratio between young donors and older donors prospectively in 41 donors. The age-adjusted formula was created as follows: age-adjusted GV = 70.767 + (0.703 × GV estimated with 3D-CT volumetry) + (1.298 × donor age). The mean error ratio for the age-adjusted formula (9.6%) was significantly lower than that from 3D-CT (14.0%). The mean decrease ratio in all 41 donors was 5.4%, and that in young donors (6.9%) was significantly higher than that in older donors (4.4%). In conclusion, although younger donor age is a major factor for estimation errors in hepatic volumetry, our age-adjusted formula is very useful in reducing the error in estimating GV..
1629. Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Noboru Harada, Yo Ichi Yamashita, Hirofumi Kawanaka, Takashi Nishizak, Yoshihiko Maehara, The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft, Transplant International, 10.1111/j.1432-2277.2008.00678.x, 21, 9, 833-842, 2008.09, Small-for-size (SFS) graft syndrome is one of the major causes of graft loss in living donor liver transplantation (LDLT). We examined whether splenectomy is beneficial for overcoming SFS graft syndrome in LDLT. The patients were classified into two groups: the Sp (-) group (n = 69), in which splenectomy was not performed, and the Sp (+) group (n = 44), in which it was. The incidence of SFS graft syndrome was investigated. Risk factors of SFS graft syndrome were identified by univariate- and multivariate analysis. To clarify whether splenectomy is beneficial for patients with a SFS graft, subgroup analysis was performed for patients who had a graft weight-to-standard liver weight (GW-SLW) ratio of 40% or less (n = 50). Thirty-one of 113 patients developed SFS graft syndrome. A multivariate analysis identified that having a male donor was an independent risk factor of SFS graft syndrome. SFS graft syndrome occurred in 11 of 50 patients with a GW-SLW ratio <40%, and Sp (-) was an independent risk factor for the occurrence of SFS graft syndrome in patients (P = 0.014). Simultaneous splenectomy is favorable for overcoming SFS graft syndrome in LDLT patients with a GW-SLW of 40% or less..
1630. Toru Ikegami, Mitsuo Shimada, Satoru Imura, Tomoharu Yoshizumi, Yusuke Arakawa, Takuya Tokunaga, Yuji Morine, Hirofumi Kanemura, The timing of liver transplantation after primary hepatectomy for hepatocellular carcinoma
A special reference to recurrence pattern and milan criteria, Transplantation, 10.1097/TP.0b013e3181814de2, 86, 5, 641-646, 2008.09, INTRODUCTION.: Hepatic resection (HR) is commonly applied as first-line treatment of hepatocellular carcinoma (HCC) even in the era of liver transplantation (LT). METHODS.: Outcomes and detailed recurrence pattern of 80 patients, who underwent curative HR for HCC were examined referring to Milan criteria. RESULTS.: (I) After HR for HCCs exceeding Milan criteria (n=41), recurrence within the criteria was observed in 13 patients (group-A) and recurrence not-meeting the criteria was observed in 22 patients (group-B). group-A showed better 3-year recurrence-free survival rate than group-B (85.7% vs. 23.9%, P<0.05). Tumor size more than or equal to 6 cm was identified as the significant factor for having recurrence as in group-A pattern (P<0.05). Among the patients in group-A, re-recurrence after treating recurrent HCC was observed in eight patients (61.5%) with increased rate of extra-Milan criteria recurrence at 12 months from the initial recurrence. (II) After HR for HCCs meeting Milan criteria (n=39), recurrences within the criteria was observed in 15 patients (group-C) and recurrence not-meeting the criteria was observed in five patients (group-D). The 3-year recurrence-free survival rate was 62.8% in group-C and 40.0% in group-D (P<0.05). Increased rate of extra-Milan re-recurrence was observed later than 12 months from the recurrence in group-C. CONCLUSIONS.: For HCCs not meeting Milan criteria, secondary LT after primary HR could be applied for a proportion of cases with less aggressiveness. For those meeting Milan criteria, primary LT should be the first therapeutic option. However, secondary LT could be offered for those with re-recurrence within criteria after primary HR..
1631. Satoru Imura, Mitsuo Shimada, Kotaro Miyake, Tetsuya Ikemoto, Yuji Marine, Tomoharu Yoshizumi, A new technique to acquire additional liver volume for left lobe graft in living donor liver transplantation, Hepato-gastroenterology, 55, 85, 1206-1210, 2008.07, Background/Aims: Left lobe graft is an ideal option to minimize potential risk for the donor in adult living-donor liver transplantation (LDLT). However, its use is restricted due to size limitations. The purpose of this study was to determine the impact of a new technique for the acquisition of additional liver volume for left lobe graft. Methodology: Three donors underwent left hepatic lobectomy by exploiting a new technique as follows: a demarcation line was marked by clamping the right first Glisson's pedicle. A parenchymal transection plane was located 1cm right side from the demarcation line and just on the left side of the right anterior Glisson's pedicle. A part of the anterior segment added to the left lobe graft by this procedure belonged to right anterior segment by preoperative CT. The preoperative volumetry of the liver was performed using the 3D-CT software, which was able to calculate total liver volume and the volume of each vessel's territories. Additional liver volume was calculated by preoperative CT scan and defined as part of the perfusion area by the right anterior portal branch. Blood perfusion of the additional liver area was postoperatively assessed by dynamic CT, and graft outcome was also evaluated. Results: An additional gain ranged from 40mL to 51mL (mean 41.8mL). GV/SLV was 35.7, 60.0, and 41.0%. The rate of additional volume in GV/SLV ranged from 7.2-8.4% (mean 7.6%). All grafts functioned well. The CT scan performed on early postoperative period confirmed excellent blood perfusion the additional segment. No complication attributable to small-for-size graft was noted. Conclusions: This new technique for left lobe graft harvesting proved a promising approach to gain additional volume, thereby avoiding small-for-size graft in adult LDLT..
1632. Tomoharu Yoshizumi, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hiroto Kayashima, Yo Ichi Yamashita, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, Graft size, donor age, and patient status are the indicators of early graft function after living donor liver transplantation, Liver Transplantation, 10.1002/lt.21462, 14, 7, 1007-1013, 2008.07, No reliable model for predicting early graft function and patient survival after living donor liver transplantation (LDLT) exists. The aim of this study was to establish a new formula for predicting early graft function and prognosis using technetium-99m galactosyl-human serum albumin (Tc-GSA) liver scintigraphy. The ratio of the hepatic uptake ratio of Tc-GSA to the clearance index of Tc-GSA (LHL/HH) was determined 7 days after LDLT. There were 22 patients with a ratio greater than 1.3 and 6 patients with a ratio less than 1.3. Graft function on the 14th postoperative day (POD) was compared between the 2 groups. A new formula to predict the LHL/HH score was established as follows: LHL/HH (predictive score) = 0.011 × graft weight (%) - 0.016 × donor age - 0.008 × Model for End-Stage Liver Disease score - 0. 15 × shunt (if present) + 1.757 (r2 = 0.497, P < 0.01). This predicted LHL/HH ratio was compared to the graft function on POD 14 for 110 LDLT patients. The total bilirubin JB) and prothrombin time international normalized ratio (PT-INR) in the group with an LHL/HH score ≥ 1.3 were lower than those in the group with an LHL/HH score < 1.3. The TB, PT-INR, and volume of ascites in the group with a predictive score ≥ 1.3 (n = 86) were lower than those in the group with a score < 1.3 (n = 24). The 6-month survival probability was improved in the group with a predictive score ≥ 1.3. In conclusion, this preoperative calculated LHL/HH score is correlated with graft function and short-term prognosis. Thus, this predictive model may allow transplant surgeons to use a living donor left lobe graft with greater confidence..
1633. Toru Ikegami, Yuji Soejima, Ryuji Ohta, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Yoshihiko Maehara, Living donor liver transplantation for hepatitis B associated liver diseases
A 10-year experience in a single center, Hepato-gastroenterology, 55, 85, 1445-1449, 2008.07, Background/Aims: Hepatic failure associated with hepatitis B virus (HBV) is one of the main indications for living donor liver transplantation (LDLT). Methodology: Twenty-nine LDLTs, including liver cirrhosis due to HBV (LC-B) (n=17) and fulminant hepatitis B (FH-B) (n=12) were reviewed. Prophylaxis for reinfection was performed with a combination of lamivudine, or hepatitis B immune globulin (HBIG) or adefovir, depending on the viral status. The changes in serological markers, recurrence and survival rate were examined. Results: There were 3 patients with re-emergencies of HBV surface antigen (HBsAg): suspension of HBIG for giving vaccination for HBV (n=1), HBsAg positive donor (n=1) and non-compliance for HBIG (n=1). All patients with YMDD mutants (n=9), except the case with HBsAg positive donor (n=1), were successfully protected by the triple therapy of lamivudine, adefovir and HBIG. No graft loss was due to the recurrence of HBV. Conclusion: The basic strategy using a combination of HBIG and antiviral agents gave acceptable long-term outcomes for LDLT for HBV associated liver diseases. The close monitoring of HBV viral status after transplantation is still crucial in managing these patients..
1634. T. Ikegami, A. Taketomi, R. Ohta, Y. Soejima, T. Yoshizumi, M. Shimada, Y. Maehara, Donor Age in Living Donor Liver Transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2008.02.084, 40, 5, 1471-1475, 2008.06, Background: We sought to elucidate the influence of donor age in living donor liver transplantation (LDLT) using either left lobe (LL) or right lobe (RL) grafts. Methods: Recipients (n = 232) were categorized as: group O/LL (LL, donor age >50, n = 20); group Y/LL (LL, donor age ≤50, n = 140); Group O/RL (RL, donor age >50, n = 12); and group Y/RL (RL, donor age ≤50, n = 61). We compared post-LDLT graft functions. Results: Among LL LDLT, the incidence of small-for-size syndrome was significantly greater for group O/LL compared with group Y/LL (60.0% vs 16.3%, P < .01). However, the cumulative 5-year graft survivals were 73.8% in group O and 76.7% in group Y without substantial difference. In RL LDLT, the post-LDLT morbidity and mortality were similar for group O/RL and group Y/RL. Conclusion: Partial liver grafts, even though LL grafts, from older donors can be used safely with caution in LDLT..
1635. T. Yoshizumi, A. Taketomi, H. Kayashima, Y. Yonemura, N. Harada, H. Ijichi, Y. Soejima, T. Nishizaki, Y. Maehara, Estimation of Standard Liver Volume for Japanese Adults, Transplantation Proceedings, 10.1016/j.transproceed.2008.02.082, 40, 5, 1456-1460, 2008.06, Introduction: Accurate pretransplant estimation of the recipient's standard liver volume (SLV) is important. The purpose of this study was to compare reported formulas for clinical estimation of liver volume among Japanese adults. Methods: We reviewed data on 70 healthy adults (46 men, 24 women, ages 20 to 65 years old) evaluated for living donor liver transplantation. Liver volume (LV) was measured using two- or three-dimensional computed tomography volumetry (CTV). The formulas of DeLand (LV = 1020 × body surface area [BSA] - 220), Urata (LV = 706.2 × BSA + 2.4), Noda (LV = 50.12 × BW0.78), Heinemann (LV = 1072.8 × BSA - 345.7), Vauthey (LV = 18.51 × BW + 191.8) and Yoshizumi (LV = 772 × BSA) were applied to estimate LV. We calculated the differences for individual donors betwen CTV and LV estimated by each formula. Results: Mean LVs as estimated by the formulae of DeLand and Heinemann et al were significantly greater (P < .01) than the mean CTV, while LV estimated by the formula of Urata was significantly less (P < .05) than the CTV. The formulas of DeLand and Heinemann overestimated LV, while the formula of Urata underestimated it. The formulae of Noda et al and Yoshizumi et al tended to underestimate the LV when the CTV was greater than 1600 cm3. When the Yoshizumi formula was applied, the number of donors with an acceptable difference (±15%) between CTV and estimated LV was 55 (78.6%). Conclusions: The Yoshizumi formula was applicable, especially for patients with a BSA < 2.0, whereas the well-known Urata formula made LV underestimates..
1636. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Characteristics of biliary reconstruction using a T-tube as compared with other methods in left-lobe adult living-donor liver transplantation, Journal of Hepato-Biliary-Pancreatic Surgery, 10.1007/s00534-007-1259-9, 15, 3, 346-347, 2008.05.
1637. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Shinji Itoh, Yo Ichi Yamashita, Yoshihiko Maehara, Hilar anatomical variations in living-donor liver transplantation using right-lobe grafts, Digestive surgery, 10.1159/000121907, 25, 2, 117-123, 2008.05, Background: Living-donor liver transplantation using a right-lobe graft has increased the frequency of hilar anatomical variations despite its advantage of a larger graft volume. Methods: Sixty-seven living-donor liver transplantations using right-lobe grafts are reviewed, regarding the surgical anatomy of hilar vascular and biliary systems. Results: The portal anatomy was classified into four types. The incidence of double portal vein was 6.0% (n = 4), and for such cases a unified orifice (n = 1) or a Y-graft (n = 3) was used for reconstruction. The arterial system was classified into five types. The incidence of arterial complications was 6.0% (n = 4), all of which occurred in cases where the graft artery was connected to the recipient's right hepatic artery. The biliary system was classified into four types. The incidence of a double bile duct was 7.5% (n = 5), and that of a unified one was 29.8% (n = 20). Hepaticojejunostomy was more prone to biliary sepsis (25.0%) and bile leakage (18.8%) than duct-to-duct connection (0 and 2%, respectively). Conclusion: Hilar anatomical variations in right-lobe living-donor liver transplantation could be managed after preoperative detailed evaluation of the graft and intraoperative appropriate surgical decision and techniques..
1638. Yuji Soejima, Naoyuki Ueda, Takasuke Fukuhara, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara, One-step venous reconstruction for a right lobe graft with multiple venous orifices in living donor liver transplantation, Liver Transplantation, 10.1002/lt.21401, 14, 5, 706-708, 2008.05.
1639. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoshihiko Maehara, Stenotrophomonas maltophilia bacteremia after living donor liver transplantation
Report of a case, Surgery today, 10.1007/s00595-007-3622-5, 38, 5, 469-472, 2008.05, Stenotrophomonas maltophilia (previously named Xanthomonas maltophilia) is an aerobic, nonfermentive, Gram-negative bacillus that is widespread in the environment. It is considered to be an organism with a limited pathogenic potential, which is rarely capable of causing diseases in humans other than in those who are in an immunocompromised state. In this study, we outline the case of a patient with Stenotrophomonas maltophilia bacteremia after living donor liver transplantation, which showed the clinical signs of severe sepsis and was resistant to almost all antibiotics. However, we successfully treated the patient with the antibiotics trimethoprim-sulfamethoxazole (TMP/SMX) and minocycline hydrochloride (MINO), and performed endotoxin-absorbing therapy using polymyxin B (PMX) to remove the endotoxin from Gramnegative bacillus as well as continuous hemodiafiltration (CHDF) to remove inflammatory cytokines. To the best of our knowledge, this is the first report on the treatment of Stenotrophomonas maltophilia bacteremia after living donor liver transplantation..
1640. Kotaro Miyake, Tomoharu Yoshizumi, Satoru Imura, Koji Sugimoto, Erdenebulgan Batmunkh, Hirofumi Kanemura, Yuji Morine, Mitsuo Shimada, Expression of hypoxia-inducible factor-1α, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma
Correlation with poor prognosis with possible regulation, Pancreas, 10.1097/MPA.0b013e31815f2c2a, 36, 3, e1-e9, 2008.04, OBJECTIVES: Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor that plays an important role in tumor growth and metastasis. Inhibition of histone deacetylase shows a marked inhibition of HIF-1α expression; however, the association between HIF-1α and histone deacetylase 1 (HDAC1), metastasis-associated protein 1 (MTA1) is not fully understood. METHODS: Hypoxia-inducible factor 1α, HDAC1, and MTA1 expressions were detected by immunohistochemistry in 39 pancreatic carcinoma patients. The correlations between the expression of HIF-1α, HDAC1, or MTA1 and clinical features and the prognosis were analyzed. RESULTS: Hypoxia-inducible factor 1α, HDAC1, and MTA1 positive stainings were found in 41%, 56%, and 31%, respectively. There was no correlation between HIF-1α, HDAC1, or MTA1 expression levels and any clinical parameters. The survival rate for patients with HIF-1α and HDAC1-positive stainings were significantly lower than for patients with HIF-1α and HDAC1-negative stainings. The MTA1 overexpression group did not have a significantly lower prognosis than the MTA1 underexpression group. The survival rate for the HDAC1(+)/MTA1(2-3) group was significantly lower than for the other groups. CONCLUSIONS: These results suggest that HIF-1α expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis for pancreatic carcinoma and indicates that HIF-1α and HDAC1/MTA1 are a promising therapeutic target in pancreatic carcinoma treatment..
1641. Yuji Soejima, Makoto Meguro, Akinobu Taketomi, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Shinji Ito, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara, Left lobe living donor liver transplantation in an adult patient with situs inversus
Technical considerations, Transplant International, 10.1111/j.1432-2277.2007.00607.x, 21, 4, 384-389, 2008.04, Situs inversus (SI) is a rare congenital disorder involving a complete mirror image of the thoracic and abdominal organs. Living donor liver transplantation (LDLT) in SI cases poses particular challenges on account of its technical complexity, and only a few cases have been reported. Here, we present an adult with SI who was managed successfully by LDLT using a left lobe graft. Some technical modifications, including triangulated anastomosis of the hepatic vein, were required but no vascular graft was necessary. Graft function and vascular integrity were excellent throughout the postoperative course, although sepsis secondary to wound infection with methicillin-resistant Staphylococcus aureus developed. In conclusion, LDLT using a left lobe graft is a feasible procedure for patients with SI, even for adults. Therefore, this condition, while rare, should not be a contraindication for LDLT. Meticulous preoperative simulation and planning of the vascular reconstruction are important steps in LDLT for this rare anomaly..
1642. Y. Soejima, A. Taketomi, T. Ikegami, T. Yoshizumi, H. Uchiyama, Y. Yamashita, M. Meguro, N. Harada, M. Shimada, Y. Maehara, Living donor liver transplantation using dual grafts from two donors
A feasible option to overcome small-for-size graft problems?, American Journal of Transplantation, 10.1111/j.1600-6143.2008.02153.x, 8, 4, 887-892, 2008.04, Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small-for-size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large-size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small-for-size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small-for-size graft problems without increasing independent donor risks..
1643. Shigeyuki Nagata, Mitsuo Shimada, Yuji Soejima, Takashi Nishizaki, Tomoharu Yoshizumi, Yoshihiko Maehara, Adult-to-adult living donor liver transplantation in severe portosystemic shunt cases, Hepato-gastroenterology, 55, 82-83, 666-669, 2008.03, To date, the need for spontaneous portosystemic shunt division during adult-to-adult living donor liver transplantation (LDLT) remains unknown. This study reports 2 patients with large portosystemic shunts who required LDLT. The first patient was a 40-year-old male with liver cirrhosis due to hepatitis C. The angiogram showed splenosystemic shunts with hepatopetal flow. Shunt occlusion was not performed after implanting a small-size graft because sufficient portal blood flow was observed. On the first postoperative day, portal blood flow was not detected; therefore shunt occlusion was performed and the portal blood flow was restored. The second patient was a 51-year-old female with primary biliary cirrhosis. Marked collateral circulation with hepatofugal flow was observed. Shunt occlusion was performed after implanting a medium-size graft. Postsurgery, hepatopetal portal blood flow was observed and the postoperative course was satisfactory. These cases demonstrate that large portosystemic shunts should be ligated to maintain adequate portal blood flow that corresponds to the graft volume..
1644. Shinji Shimoda, Kenichi Harada, Hiroaki Niiro, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Koichi Tsuneyama, Minoru Nakamura, Atsumasa Komori, Kiyoshi Migita, Yasuni Nakanuma, Hiromi Ishibashi, Carlo Selmi, M. Eric Gershwin, Biliary epithelial cells and primary biliary cirrhosis
The role of liver-infiltrating mononuclear cells, Hepatology, 10.1002/hep.22102, 47, 3, 958-965, 2008.03, Primary biliary cirrhosis (PBC) is characterized by the highly selective autoimmune injury of small intrahepatic bile ducts, despite widespread distribution of mitochondrial autoantigens. On this basis, it has been suggested that the targeted biliary epithelial cells (BECs) play an active role in the perpetuation of autoimmunity by attracting immune cells via chemokine secretion. To address this issue, we challenged BECs from patients with PBC and controls using multiple Toll-like receptor (TLR) ligands as well as autologous liver-infiltrating mononuclear cells (LMNCs) with subsequent measurement of BEC phenotype and chemokine production and LMNC chemotaxis by quantifying specific chemokines. Our data reflect that BECs from PBC patients and controls express similar levels of TLR subtypes, CD40, and human leukocyte antigen DRα (HLA-DRα) and produce equivalent amounts of chemokines in our experimental conditions. Interestingly, however, BEC-expressed chemokines elicit enhanced transmigration of PBC LMNCs compared with controls. Furthermore, the addition of autologous LMNCs to PBC BECs led to the production of higher levels of chemokines and enhanced the expression of CD40 and HLA-DRα. Conclusion: We submit that the proinflammatory activity of BECs in PBC is secondary to the intervention of LMNCs and is not determined per se. These data support the hypothesis that BECs are in fact "innocent victims" of autoimmune injury and that the adaptive immune response is critical in PBC..
1645. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiko Maehara, Hiroyuki Kuwano, Is an elderly recipient a risk for living donor adult liver transplantation?, Hepato-gastroenterology, 55, 82-83, 653-656, 2008.03, Background/Aims: In cadaveric liver transplantation, it has been reported that elderly recipients over 60 years are at risk because of high incidence of complication and malignancy. However, in living-donor adult liver transplantation (LDALT), it is unclear whether the elderly recipient is risky or not risky. In this study, the outcome after LDALT of elderly patients has been evaluated. Methodology: One hundred twenty two consecutive LDALT recipients were studied. The recipients were divided into an elderly group (older than 60 yrs, n=21), and a control group (younger than 60 yrs, n=101). Comparative examination of background factors, postoperative complications and de novo malignancy was carried out. Results: Elderly patients more frequently received transplantation for hepatocellular carcinoma. Pretransplant liver damage such as Child-Pugh, MELD or bilirubin level was same among the groups. There was no significant difference in posttransplant complications except renal failure. Postoperative renal failure (postoperative creatinine level over 2mg/dL) occurred in 29% (n=5) of the elderly group vs. 8% (n=6) of the control group. De novo malignancy occurred in 1 case (lung) in the elderly group and 1 case (Vater) in the control group. In the control group, the 1, 3 and 5 year patient survival rates were 78.5%, 73.1% and 71.4%, respectively. And in the elderly group, the 1, 3 and 5 year patient survival rates were 85.7%, 81.0% and 70.8%, respectively. Conclusions: It may be, we concluded that living donor adult liver transplantation is good treatment for end stage liver diseases in elderly recipients over 60 years. However caution should be taken in the administration of medicine, including immunosuppressants or antibiotics, do to a propensity for postoperative renal failure in elderly recipients..
1646. Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Yo Ichi Yamashita, Yoshihiko Maehara, Liver transplantation for hepatocellular carcinoma, Journal of Hepato-Biliary-Pancreatic Surgery, 10.1007/s00534-007-1296-4, 15, 2, 124-130, 2008.03, The role of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) has evolved over the past two decades, and transplantation has become one of the few curative treatment modalities for patients with HCC. Early results were poor, but the current restrictive selection criteria can yield excellent results. This review will discuss recent issues in the field, including (1) factors affecting the recurrence of HCC after LT; (2) the effect of downstaging HCC before LT, including transarterial catheter chemoembolization (TACE) and radiofrequency ablation (RFA); and (3) living-donor versus deceased-donor liver transplantation for HCC patients. The most important factors that have been described to affect LT survival include the tumor size, vascular invasion, and the degree of tumor differentiation. Recently, tumor markers, including alpha-fetoprotein and des-gamma carboxy prothrombin, were reported as predictors of HCC recurrence after LT. Furthermore, the experience accumulated with locoregional therapies such as TACE and RFA as bridging procedures to LT, along with the reduced waiting time under the HCC-adjusted MELD (model for endstage liver disease) system for organ allocation has led to improved outcomes. With the recent advances in adult living-donor liver transplantation (LDLT), there may be a marked change in the role of liver transplantation for hepatic malignancies, in particular for HCC..
1647. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Kensaku Sanefuji, Hiroto Kayashima, Mitsuo Shimada, Yoshihiko Maehara, Living Donor Liver Transplantation for Acute Liver Failure
A 10-Year Experience in a Single Center, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2007.08.018, 206, 3, 412-418, 2008.03, Background: Living donor liver transplantation has become an accepted treatment for various terminal liver diseases. Study Design: Forty-two living donor liver transplantations performed for acute liver failure during a 10-year period at Kyushu University Hospital were reviewed. Results: Causes of liver failure included hepatitis B (n = 12), hepatitis C (n = 1), autoimmune hepatitis (n = 2), Wilson's disease (n = 3), and unknown causes (n = 24). The graft types were: left lobe (n = 33), right lobe (n = 8), and lateral segment (n = 1). The mean graft volume to standard liver volume ratios were 42.2 ± 9.2% in left lobe grafts and 50.5 ± 3.9% in right lobe grafts (p < 0.05). Extubation was significantly delayed in grade IV encephalopathy patients (73.7 ± 18.2 hours) compared with patients with other grades (p < 0.01 to grades I and II, p < 0.05 to grade III). All other patients, except one with a subarachnoid hemorrhage, had complete neurologic recovery after transplantation. The 1- and 10-year survival rates were 77.6% and 65.5%, respectively, for grafts, and 80.0% and 68.2%, respectively, for patients. Conclusions: Outcomes of living donor liver transplantation for acute liver failure are fairly acceptable despite severe general conditions and emergent transplant settings. Living donor liver transplantation is now among the currently accepted life-saving treatments of choice for acute liver failure, although innovative medical treatments for this disease entity are still anticipated..
1648. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Living donor liver transplantation for fulminant hepatic failure from ABO-incompatible donors [1], Transplant International, 10.1111/j.1432-2277.2007.00588.x, 21, 3, 284-285, 2008.03.
1649. Tomoharu Yoshizumi, Akinobu Taketomi, Hiroto Kayashima, Noboru Harada, Hideaki Uchiyama, Yo Ichi Yamashita, Toru Ikegami, Yuji Soejima, Takashi Nishizaki, Mitsuo Shimada, Yoshihiko Maehara, Successful treatment for a patient with hemophagocytic syndrome after a small-for-size graft liver transplantation, Hepato-gastroenterology, 55, 82-83, 359-362, 2008.03, Hemophagocytic syndrome (HPS) is a hematological disorder caused by activated T lymphocytes, which leads to the proliferation of stimulated macrophages that phagocytose and destroy circulating blood elements and their precursors within bone marrow, and lead to the further production of inflammatory cytokines. Living donor liver transplantation (LDLT) between adults has been performed to compensate for the shortage of available organs. There have been some reports concerning HPS after LDLT; however, its prognosis is disappointingly poor. In particular, there is no report of treated HPS developed after LDLT using small-for-size left lobe grafts. We herein report a case of HPS in a 63-year old woman who underwent LDLT using left lobe graft weighing only 330g. The HPS was diagnosed on postoperative day 13, and was successfully treated using a combination of intravenous immunoglobulin, granulocyte colony stimulating factor, conversion of calcineurin inhibitor and steroid pulse. The trigger of HPS may not only be systemic infection, but also hypercytokinemia caused by various factors. HPS is a fatal complication in immunologically compromised patients; however, early and accurate diagnosis could lead to an adequate treatment and improve the outcome..
1650. Mami Kanamoto, Tomoharu Yoshizumi, Toru Ikegami, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Nobuya Sano, Mitsuo Shimada, Cholangiolocellular carcinoma containing hepatocellular carcinoma and cholangiocellular carcinoma, extremely rare tumor of the liver
A case report, Journal of Medical Investigation, 10.2152/jmi.55.161, 55, 1-2, 161-165, 2008.02, Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor which was first defined by Steiner, et al. in 1957 (1). CLC is thought to be derived from Hering's canal because tumor glands of CLC are morphologically similar to cholangioles. Recently, Theise, et al. reported that Hering's canal might be composed of hepatic stem cells (3). In addition, CLC sometimes contains a hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC) component within the tumor. Those findings suggest that CLC might originate from hepatic stem cells. On the other hand, because of its low frequency, clinicopatholigical features of CLC have not been fully clarified yet. We herein report a case of a 71-year old man with CLC. Based on preoperative imagings, the hepatic tumor was diagnosed as HCC, and he underwent a partial hepatectomy. The tumor contained both a HCC and CCC-like area. In immunohistochemistry, cytokeratin (CK) 7, CK20, CAM5.2 was positive, and CK19 was negative, therefore the tumor was diagnosed as CLC. The diagnostic criteria have not been described clearly, so CLC is difficult to diagnose preoperatively. Further studies are needed to clarify the clinical and clinicopatholigical features of CLC..
1651. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Yo Ichi Yamashita, Shinji Itoh, Yosuke Kuroda, Yoshihiko Maehara, Assessment of graft fibrosis by transient elastography in patients with recurrent hepatitis C after living donor liver transplantation, Transplantation, 10.1097/01.tp.0000297248.18483.16, 85, 1, 69-74, 2008.01, BACKGROUND. Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness and therefore can be a promising tool to evaluate liver fibrosis and avoid liver biopsy. We prospectively assessed the performance of transient elastography in patients with recurrent hepatitis C virus after living donor liver transplantation, in comparison with the surrogate serum markers. METHODS. Fifty-six patients with recurrent hepatitis C virus after living donor liver transplantation, who underwent both liver biopsy and transient elastography were included in this study. The grade of liver fibrosis (the Scheuer classification) obtained by biopsy was compared to liver stiffness measured by the transient elastography. RESULTS. The fibrosis grades were as follows: F0, n=22; F1, n=13; F2, n=9; F3, n=7; and F4, n=5. Liver stiffness values ranged from 2.9 to 72.0 kPa. The optimal cutoff values were 8.8 kPa for F≥1, 9.9 kPa for F≥2, 15.4 kPa for F≥3, and 26.5 kPa for F≥4. The area under the receiver operator characteristic curve for the diagnosis of fibrosis (F≥2) by transient elastography was 0.92, while that by hyaluronic acid, type 4 collagen, alanine aminotransferase, and the aspartate transaminase to platelets ratio index were 0.52, 0.62, 0.64, and 0.70, respectively. CONCLUSIONS. These data suggest that transient elastography is a simple, noninvasive and reliable tool to assess liver fibrosis in patients with recurrent hepatitis C virus after living donor liver transplantation..
1652. Nao Kinjo, Hirofumi Kawanaka, Morimasa Tomikawa, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Shohei Yamaguchi, Daisuke Yoshida, Yoshihiko Maehara, B-RTO for ectopic variceal bleeding after living donor liver transplantation, Hepato-gastroenterology, 55, 81, 241-243, 2008.01, Gastrointestinal bleeding (GIB) is a serious gastroenterological complication after orthotropic liver transplantation, as well as living donor liver transplantation (LDLT). Although ectopic varices are rare causes of GIB, they may lead to life-threatening bleeding and it is difficult to diagnose them. We herein report a rare case of a jejunal variceal bleeding in a recipient five years after LDLT for primary sclerosing cholangitis with successful result by balloon-occluded retrograde transvenous obliteration (B-RTO)..
1653. Kazutoyo Morita, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Naotaka Hashimoto, Yohei Mano, Tatsunori Miyata, Yuji Soejima, Yoshihiko Maehara, Feasible isolated liver transplantation for a cirrhotic patient on chronic hemodialysis, Case Reports in Gastroenterology, 10.1159/000354140, 7, 2, 299-303, 2013.01, End-stage liver and kidney disease (ELKD) is an indication for deceased donor simultaneous liver-kidney transplantation. Although a few cases of living donor liver-kidney transplantation have been reported, the invasiveness remains to be discussed. Living donor liver transplantation (LDLT) is an alternative choice for ELKD, but has never been reported. Here, we report a case of successful LDLT for a patient with ELKD on hemodialysis. The patient was a 63-year-old male and had decompensated hepatitis C cirrhosis with seronegativity for hepatitis C virus. He had non-diabetic end-stage renal failure and had been on hemodialysis for 3 years. He was in good general condition except for hepatic and renal failure. The living donor was his 58-year-old healthy wife. A right lobe graft was transplanted to the recipient under continuous hemodiafiltration (CHDF) and extracorporeal veno-venous bypass. CHDF was continued until postoperative day 4, at which point CHDF was converted to hemodialysis. His posttransplant course was good and he was discharged on postoperative day 36. To the best of our knowledge, this is the first report of LDLT for a patient on chronic hemodialysis. Therefore, being on hemodialysis is not a contraindication for LDLT. LDLT is feasible for a patient with ELKD on hemodialysis..
1654. Hiroto Kayashima, Ken Shirabe, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Liver regeneration and venous collateral formation in the right lobe living-donor remnant
Segmental volumetric analysis and three-dimensional visualization, Transplantation, 10.1097/TP.0b013e31827147d8, 95, 2, 353-360, 2013.01, BACKGROUND: In left lobe (LL) living-donor liver transplantation (LDLT), hepatic venous congestion (HVC) caused by ligation of the middle hepatic vein tributaries is unavoidable in the right lobe (RL) donor remnant. METHODS: To clarify the impact of HVC on liver regeneration and venous collateral formation (VCF), we used three-dimensional computed tomography to examine the volumes of total/segmental liver and HVC and the degree of VCF; preoperative data were compared with data obtained on postoperative day (POD) 35 in 13 LL LDLT donors. RESULTS: On POD 35, the congestion rate decreased from 32.5% to 1.6% and the total liver regeneration rate was 81.7%. Preoperatively, the anterior sector-to-RL volume ratio was significantly lower, and the posterior sector-to-RL volume ratio was significantly higher than postoperatively (56.7% vs. 52.9%, P<0.01, and 36.9% vs. 41.5%, P<0.01, respectively). There was no correlation between degree of HVC and liver regeneration. Obvious VCF was found in five (38.5%) cases. The RL and posterior sector volume per square meter of body surface area in the VCF group were significantly lower than that in the non-VCF group (412 cm/m vs. 492 cm/m, P<0.01, and 140 cm/m vs. 190 cm/m, P<0.01, respectively). The preoperative congestion rate and liver regeneration rate were not significantly different between the groups. CONCLUSIONS: Reconstruction of the middle hepatic vein tributaries in the RL donor remnant might not be necessary in LL LDLT, because the HVC improved dramatically by POD 35 regardless of the development of VCF..
1655. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Mirror image hepatectomy in a patient with situs inversus totalis., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 430-434, 2013.01, Hepatectomy in a patient with situs inversus patient is technically challenging because of its complete mirror image anatomy, especially for a tumor located deep in the liver. Incorrectly identifying intrahepatic vessels and biliary system would lead to serious complications. We experienced a hepatectomy for a tumor in a patient with situs inversus totalis with referring to computer-generated mirror images. A 66-year-old female patient with situs inversus totalis was diagnosed with hepatocellular carcinoma, 5 cm in diameter, centrally located just above the hepatic hilum compressing the right and left hepatic duct. The liver infected with hepatitis C was cirrhotic with a moderate amount of ascites. We preoperatively created several diagrams of the mirror image anatomy and made plans for how to resect this tumor, presupposing the patient had an ordinary anatomy. The tumor was successfully enucleated with referring to these diagrams. The operation time was 454 minutes. Five units of fresh frozen plasma was transfused intraoperatively. Although she suffered refractory ascites which needed repeated paracentesis, she managed to leave the hospital two months after the operation. Creating a mirror image anatomy enables surgeons to safely perform a complex hepatectomy in a patient with situs inversus totalis..
1656. Takashi Motomura, Ken Shirabe, Yohei Mano, Jun Muto, Takeo Toshima, Yuichiro Umemoto, Takasuke Fukuhara, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment, Journal of Hepatology, 10.1016/j.jhep.2012.08.017, 58, 1, 58-64, 2013.01, Background & Aims: Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Preoperative neutrophil-lymphocyte ratio (NLR) is a predictor of patient prognosis, but its mechanism has never been clarified. Methods: We assessed outcomes in 158 patients who had undergone living-donor liver transplantation (LDLT) for HCC. Recurrence-free survival (RFS) was determined in patients with high (≥4) and low (<4) NLR. Levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68, and CD163 were measured. Results: The 5-year RFS rate was significantly lower in patients with high (n = 26) than with low (n = 132) NLR (30.3% vs. 89.0%, p <0.0001), in patients with high (n = 15) than with low (n = 79) NLR who met the MC (73.6% vs. 100%, p = 0.0008) and in patients with high (n = 11) than with low (n = 53) NLR who exceeded the MC (0% vs. 76.1%, p = 0.0002). Tumor expression of VEGF, IL8, IL-17, CD68, and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 levels were significantly higher in the high-NLR group (p = 0.01 each). The density of peritumoral CD163 correlated with the density of peritumoral IL-17-producing cells (p = 0.04) and was significantly higher in the high-NLR group (p = 0.005). Conclusions: NLR predicts outcomes after LDLT for HCC via the inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC..
1657. Keiji Yoshinaga, Hiroshi Saeki, Eiji Oki, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Prognostic markers for immunochemotherapy using tegafur -uracil (UFT) and protein-bound polysaccharide K (PSK)., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 549-558, 2013.01, We previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels. 98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years. There were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant. Serum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary..
1658. Hiroshi Saeki, Eiji Oki, Yasuo Tsuda, Koji Ando, Yukiharu Hiyoshi, Shuhei Ito, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Relevance of totally laparoscopic gastrectomy for patients with advanced gastric cancer., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 405-412, 2013.01, Although the use of laparoscopic gastrectomy for gastric cancer has been widespread, it has remained controversial whether it can be applied for the patients with advanced gastric cancer. The aim of this study was to clarify the safety and usefulness of totally laparoscopic gastrectomy for patients with advanced gastric cancer. Totally laparoscopic gastrectomy was applied for a total of 38 patients with pStage IB-III advanced gastric cancer at our institute. The surgical and long-term results were analyzed in those patients. Twenty-seven patents underwent distal gastrectomy and 11 patients underwent total gastrectomy. The mean number of dissected lymph nodes was 41 (range, 16-87). The mean length of the operation and amount of blood loss was 324 min and 123 ml, respectively. Two cases of postoperative bleeding were noted, while neither anastomosis-related complications nor in-hospital death was observed. The follow-up period after surgery was 8-72 months. Postoperative recurrence was observed in 6 patients (peritoneal dissemination: 3 patients, pleural dissemination: 1 patient, liver metastasis: 1 patient, ovarian metastasis: 1 patient). The overall survival rates at 1, 3 and 5 years were 94.7%, 76.3% and 76.3%, respectively. Totally laparoscopic gastrectomy is safe and can lead to satisfactory long-term outcomes in cases of advanced gastric cancer. Prospective controlled studies are warranted to confirm our findings..
1659. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo Ichi Yamashita, Tetsuo Ikeda, Hirofumi Kawanaka, Keishi Sugimachi, Koshi Mimori, Masayuki Watanabe, Masaru Morita, Eiji Oki, Hiroshi Saeki, Yoshihiko Maehara, Rex shunt for portal vein thrombosis after adult living donor liver transplantation., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 464-468, 2013.01, Portal vein thrombosis (PVT) after liver transplantation is a relatively common but serious complication which could lead to portal hypertension or a direct graft loss. A "Rex" shunt created between the superior mesenteric vein (SMV) and the umbilical portion of the left portal vein can be a useful option to treat PVT after pediatric liver transplantation, however, its application to adult patients has not been reported so far because appropriate vein grafts are hardly available. Herein we present a case of PVT after left lobe living donor liver transplantation (LDLT) who underwent the procedure using the own inferior jugular vein and the gonadal vein as a shunt graft. The shunt was patent immediately after the procedure but was thrombosed 2 days after probably due to the insufficient inflow from the SMV and the absence of anticoagulation therapy, for which emergent thrombectomy and ligation of the significant hepatofugal collateral veins followed by full anti-coagulation therapy were performed. The shunt remains open at 8 month after the procedure with a normal anmonia level and liver function. In conclusion, the Rex shunt using recipient's autologous vein grafts is a feasible and valuable option for adult patients to treat PVT after LDLT..
1660. Masayuki Watanabe, Koki Matsuura, Hideo Baba, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Yoshihiko Maehara, Thoracoscopic pericardial drainage for gastric tube ulcer penetrated into the pericardium., Unknown Journal, 104, 10, 389-393, 2013.01, Peptic ulcer occurring in the gastric conduit for esophageal reconstruction sometimes penetrates into the mediastinal structures. We herein reported a case of pericardial penetration of gastric tube ulcer successfully treated with thoracoscopic pericardial drainage. A 66-year-old Japanese man, who had undergone esophagectomy for esophageal cancer 20 months before, visited our emergency room complaining severe back pain. Computed tomography revealed gastric tube ulcer penetrated into the pericardial space. Thoracoscopic pericardiotomy and drainage was performed and the patient made an uneventful recovery. Thoracoscopic pericardial drainage is useful to manage acute pyogenic pericarditis due to penetration of peptic ulcer which occurred in the gastric tube..
1661. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Verification of our therapeutic criterion for acute cholecystitis
"perform a subemergency laparoscopic cholecystectomy when a patient is judged to be able to tolerate general anesthesia"--the experience in a single community hospital., Unknown Journal, 104, 10, 339-343, 2013.01, Our current therapeutic criterion for acute cholecystitis is: Perform a subemergency laparoscopic cholecystectomy (LC) when a patient is judged to be able to tolerate general anesthesia. The aim of the current study was to verify whether this criterion is justified. The outcomes of 21 cases of LC for acute cholecystitis performed between April 2011 and September 2013 were retrospectively analyzed. Subemergency LC was performed according to the aforementioned criterion (Subemergency group; n = 16). Patient who was judged to be unable to tolerate general anesthesia underwent percutaneous transhepatic gallbladder drainage (PTGBD) first, then LC after the patients' condition became stable (PTGBD group; n = 5). There is no conversion to open surgery throughout the study period. The mean of the total hospital stays in the Subemergency group was significantly shorter than that in the PTGBD group (11.5 +/- 5.3 vs. 30.4 +/- 8.5 days). Although two patients in the Subemergency group, who had already needed oxygen administration preoperatively, suffered postoperative respiratory failure, they completely recovered. On the other hand, there is no postoperative complication in the PTGBD group. Subemergency LC could be safely performed when surgeons as well as anesthesiologists judged a patient to be able to tolerate general anesthesia, which significantly shorten hospital stays compared to elective LC after PTGBD. However, elective LC after PTGBD is an absolutely safer therapeutic option in treating unstable patients..
1662. Tetsuo Ikeda, Tomohiko Akahoshi, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Koshi Mimori, Masayuki Watanabe, Makoto Hashizume, Yoshihiko Maehara, [Optimum hepatic parenchymal dissection to prevent bile leak
a comparative study using electrosurgical and stapling devices in swine]., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 507-514, 2013.01, Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma..
1663. Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara, Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma
Report of a case, Surgery today, 10.1007/s00595-012-0332-4, 42, 12, 1210-1214, 2012.12, The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection..
1664. Takashi Motomura, Ken Shirabe, Norihiro Furusyo, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tomohiko Akahoshi, Morimasa Tomikawa, Takasuke Fukuhara, Jun Hayashi, Yoshihiko Maehara, Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype, BMC Gastroenterology, 10.1186/1471-230X-12-158, 12, 2012.11, Background: IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.Methods: Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.Results: Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.Conclusions: IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype..
1665. Takashi Motomura, Yuki Ono, Ken Shirabe, Takasuke Fukuhara, Hideyuki Konishi, Yohei Mano, Takeo Toshima, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Neither MICA nor DEPDC5 genetic polymorphisms correlate with hepatocellular carcinoma recurrence following hepatectomy, HPB Surgery, 10.1155/2012/185496, 2012, 2012.11, Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7 in MICA GG allele carriers, 38.7 in GA, and 20.8 in AA, respectively (P = 0.72). The five-year RFS rate was 23.8 in DEPDC5 TT allele carriers and 31.8 in TG/GG, respectively (P = 0.47). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers (P 0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages..
1666. Yuji Soejima, Toru Ikegami, Hideki Ijichi, Tetsuo Ikeda, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hiroshi Matsuura, Kenichiro Okadome, Yoshihiko Maehara, Technical evolution of laparoscopic hepatic resection
a single institutional experience., Unknown Journal, 103, 11, 226-232, 2012.11, Laparoscopic hepatic resection (LHR) is still a challenging and developing surgical modality because of technical difficulty and a lack of training opportunities and experience. In this study, we present the results of our initial experiences of LHR, focusing on technical evolution in the management of LHR. Between April 2011 and March 2012, a total of 12 LHRs were performed. The first 5 of these LHRs were performed under laparoscopic assistance (hybrid-LHR), while the last 7 LHRs were performed totally laparoscopically (pure-LHR). Indications for LHR were hepatocellular carcinoma (n = 9) and metastatic liver cancer (n = 3). LHR procedures consisted of partial resection (n = 2), left lateral segmentectomy (n = 2), and left lobectomy (n = 1) in the hybrid-LHR group, and partial resection (n = 4), left lateral segmentectomy (n = 2), and right lobectomy (n = 1) in the pure-LHR group. Operative outcomes were compared between the groups and technical modifications were evaluated. The mean operative time, blood loss, and length of hospital stay in the hybrid- and pure-LHR groups were 3.8 and 6.1 hours, 220 and 611 ml, and 9.4 and 7.4 days, respectively. There were no postoperative complications in both groups. Tumor margins were negative in all cases. LHR is a feasible and effective procedure for patients with various types of liver tumors, although technical challenges still need to be overcome..
1667. Shohei Yoshiya, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31826969e6, 94, 9, 947-952, 2012.11, BACKGROUND: Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. METHODS: A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. RESULTS: The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). CONCLUSIONS: Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group..
1668. Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Authors' reply to "female-to-male match predicted poor survival following living donor liver transplantation-some issues needed to be clarified", Transplantation, 10.1097/TP.0b013e3182654d56, 94, 6, e36, 2012.09.
1669. Toru Ikegami, Ken Shirabe, Rumi Matono, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Etiologies, risk factors, and outcomes of bacterial pneumonia after living donor liver transplantation, Liver Transplantation, 10.1002/lt.23483, 18, 9, 1060-1068, 2012.09, The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short-term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram-negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P = 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post-LDLT pneumonia was associated with the following post-LDLT events: the prolonged use of mechanical ventilation (≥3 days), a prolonged stay in the intensive care unit (≥7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed-onset pneumonia, which occurred at least 10 days after transplantation (n = 15), and it was significantly associated with graft dysfunction. A combination of broad-spectrum antibiotics and aminoglycosides provided cover for most gram-negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad-spectrum antibiotics. Delayed-onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed..
1670. Hideaki Uchiyama, Hiroto Kayashima, Rumi Matono, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Toshiharu Matsuura, Tomoaki Taguchi, Yoshihiko Maehara, Relevance of HLA compatibility in living donor liver transplantation
The double-edged sword associated with the patient outcome, Clinical Transplantation, 10.1111/ctr.12019, 26, 5, E522-E529, 2012.09, HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA-A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host-versus-graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft-versus-host disease (GVHD) was also analyzed. No recipients with recipient-against-donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with "R→D MM 0" together with "donor-against-recipient MM 3" died of fatal GVHD. HLA compatibility in LDLT not only affected the long-term acceptance of graft livers but also the risk of fatal GVHD..
1671. Mizue Matsuo, Toru Ikegami, Kazutoyo Morita, Hiroko Yano, Naotaka Hashimoto, Hiroto Kayashima, Toshirou Masuda, Naoko Kondou, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, [A case of successful multi-venous reconstruction using recipient's jugular vein in right lobe-living donor liver transplantation]., Unknown Journal, 103, 9, 186-190, 2012.09, In right lobe-living donor liver transplantation (RT-LDLT), hepatic venous reconstruction of the graft is essential to prevent posttansplant graft congestion and have a good outcome. The patient was a 56-year-old man who had decompensated liver cirrhosis secondary hepatitis C with massive ascites, jaundice and hepatic encephalopathy. He underwent LDLT using his son's right lobe graft. Preoperative simulation by 3D-CT volumetry revealed that the right lobe graft needed multi-venous reconstruction for right inferior hepatic vein (RIHV) and middle hepatic venous tributaries. Preoperative CT scan revealed that the recipient had portal venous thrombus and stenosis, which meant that the recipient's explanted portal vein (EPV) was not suitable for the venous reconstruction of the right lobe graft. Therefore, the recipient's internal and external jugular veins (IJV and EJV) were procured for venous reconstruction. The multiple veins of the right lobe graft were reconstructed to have single co-orifice at the backtable, and the co-orifice was anastomosed to inferior vena cava in short time. The recipient discharged on postoperative day 22 with good venous patency. In RT-LDLT unavailable for recipient's EPV, recipient's IJV and EJV grafts are very useful for multi-venous reconstruction..
1672. Kazuki Takeishi, Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Takashi Motomura, Toru Ikegami, Tomoharu Yoshizumi, Fumio Sakane, Yoshihiko Maehara, Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras-Raf-MEK-ERK pathway, Journal of Hepatology, 10.1016/j.jhep.2012.02.026, 57, 1, 77-83, 2012.07, Background & Aims: Diacylglycerol kinases (DGKs) were recently recognized as key regulators in cell signaling pathways. We investigated whether DGKα is involved in human hepatocellular carcinoma (HCC) progression. Methods: We silenced or overexpressed DGKα in HCC cells and assessed its effect on tumor progression. DGKα expression in 95 surgical samples was analyzed by immunohistochemistry, and the expression status of each sample was correlated with clinicopathological features. Results: DGKα was detected in various HCC cell lines but at very low levels in the normal liver. Knockdown of DGKα significantly suppressed cell proliferation and invasion. Overexpression of wild type (WT) DGKα, but not its kinase-dead (KD) mutant, significantly enhanced cell proliferation. DGKα knockdown impaired MEK and ERK phosphorylation, but did not inhibit Ras activation in HCC cells. In a xenograft model, WT DGKα overexpression significantly enhanced tumor growth compared to the control, but KD DGKα mutant had no effect. Immunohistochemical studies showed that DGKα was expressed in cancerous tissue, but not in adjacent non-cancerous hepatocytes. High DGKα expression (≥20%) was associated with high Ki67 expression (p <0.05) and a high rate of HCC recurrence (p = 0.033) following surgery. In multivariate analyses, high DGKα expression was an independent factor for determining HCC recurrence after surgery. Conclusions: DGKα is involved in HCC progression by activation of the MAPK pathway. DGKα could be a novel target for HCC therapeutics as well as a prognostic marker..
1673. Yuji Soejima, K. Shirabe, A. Taketomi, T. Yoshizumi, H. Uchiyama, T. Ikegami, M. Ninomiya, N. Harada, H. Ijichi, Y. Maehara, Left lobe living donor liver transplantation in adults, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04022.x, 12, 7, 1877-1885, 2012.07, Adult left lobe (LL) living donor liver transplantation (LDLT) has not generally been recognized as a feasible procedure because of the problem of graft size. The objectives of this study were to assess the feasibility and short- and long-term results of adult LL LDLT in comparison with right lobe (RL) LDLT. Data on 200 consecutive LL LDLTs, including five retransplants, were retrospectively compared with those of 112 RL LDLTs, in terms of survival, complications and donor morbidity. The mean graft weight to standard volume ratio of LL grafts was 38.7% whereas that of RL grafts was 47.6% (p < 0.0001). The 1-, 5- and 10-year patient survival rates of LL LDLT were 85.6%, 77.9% and 69.5%, respectively, which were comparable to those of RL LDLT (89.8%, 71.3% and 70.7%, respectively). The incidence of small-for-size syndromewas higher in LL LDLT (19.5%) than in RL LDLT (7.1%) (p < 0.01). The overall donor morbidity rates were comparable between LL (36.0%) and RL (34.8%), whereas postoperative liver function tests and hospital stay were significantly better (p < 0.0001) in LL donors. In conclusion, adult LL LDLT has comparable outcomes to that of RL LDLT. LL LDLT is viable and is the first choice in adult LDLT..
1674. Toru Ikegami, K. Shirabe, T. Yoshizumi, S. Aishima, Y. A. Taketomi, Y. Soejima, H. Uchiyama, H. Kayashima, T. Toshima, Y. Maehara, Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04052.x, 12, 7, 1886-1897, 2012.07, The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult-to-adult LDLT grafts without anatomical, immunological or hepatitis-related issueswere included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH-20) was used to characterize PGD. DFH-20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH-20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PTINR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH-20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH-20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality..
1675. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Use of an internal jugular vein graft for middle hepatic vein tributary reconstruction in right-lobe living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31825b75b6, 94, 2, e17-e18, 2012.07.
1676. Yoko Zaitsu, Toru Ikegami, Toshirou Masuda, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, [A successful case of living donor liver transplantation performed in 7 hours for sub acute fulminant hepatitis]., Fukuoka igaku zasshi = Hukuoka acta medica, 103, 7, 145-149, 2012.07, Living donor liver transplantation (LDLT) is the ultimate cure for fulminant hepatitis. Successful outcomes rely on the precise evaluation of the reversibility of hepatic encephalopathy, and a swift execution of necessary examination of both the donor and the recipient. The case was a 63-years old woman, presented with fever and loss of appetite. She was hospitalized for acute hepatitis and treated at a nearby hospital. She was transferred to the tertiary hospital for the acute deterioration of her liver function on the 7th day after the emergence of the initial symptoms. On the 10th day, she showed Grade 2 encephalopathy and underwent plasma exchange. She was transported to our hospital for possible LDLT on the 11th day. CT scan on arrival showed severe atrophy of her liver and no definite brain edema despite acutely deteriorating encephalopathy (Grade 3). LDLT was launched after 7 hours from her transport. She was discharged from the intensive care unit on the 6th day and was discharged without severe complications on 42th day after the LDLT..
1677. Noboru Harada, Ken Shirabe, Hideki Ijichi, Rumi Matono, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Yoshihiko Maehara, Acoustic radiation force impulse imaging predicts postoperative ascites resulting from curative hepatic resection for hepatocellular carcinoma, Surgery (United States), 10.1016/j.surg.2011.12.035, 151, 6, 837-843, 2012.06, Background: Measurement of liver stiffness using Virtual Touch Tissue Quantification (VTTQ) based on acoustic radiation force impulse imaging reflects the degree of hepatic fibrosis and reserve. This prospective study investigated how well the VTTQ value predicts the development of postoperative complications before curative hepatic resection for hepatocellular carcinoma (HCC). Methods: The study enrolled 50 consecutive patients between February 2009 and October 2010 whose preoperative VTTQ values were determined before they underwent curative hepatic resection for HCC. We assessed the relationship between postoperative complications and VTTQ values. Results: The study included 41 (82%) patients with chronic hepatitis and 9 (18%) with nonviral cirrhosis. The mean VTTQ value was 1.60 (m/sec), which correlated with the fibrosis stage (P =.0058). The VTTQ value was the only variable correlated with postoperative ascites that did not respond to pharmacologic treatment and required invasive management. Univariate and subsequent multivariate analyses revealed that the preoperative VTTQ value was the only independent risk factor for predicting the development of postoperative ascites (cutoff, 1.68 cm/sec; P =.007; odds ratio, 76.481). The area under the receiver operating characteristic curve for the diagnosis of postoperative ascites using VTTQ values was 0.90, whereas those using the aspartate transaminase-to-platelet ratio index and indocyanine green retention rate at 15 minutes values were 0.68 and 0.55, respectively. Conclusion: These data suggest that the VTTQ value is a reliable surrogate marker for predicting postoperative ascites before curative hepatic resection for HCC..
1678. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Shohei Yoshiya, Takeo Toshima, Takashi Motomura, Yuji Soejima, Hideaki Uchiyama, Yoshihiko Maehara, En bloc stapling division of the gastroesophageal vessels controlling portal hemodynamic status in living donor liver transplantation, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.02.016, 214, 6, e53-e56, 2012.06.
1679. T. Yoshizumi, K. Shirabe, T. Ikegami, H. Kayashima, N. Yamashita, K. Morita, T. Masuda, N. Hashimoto, A. Taketomi, Y. Soejima, Y. Maehara, Impact of human T cell leukemia virus type 1 in living donor liver transplantation, American Journal of Transplantation, 10.1111/j.1600-6143.2012.04037.x, 12, 6, 1479-1485, 2012.06, Human T cell leukemia virus type 1 (HTLV-1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV-1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV-1 status in living donor liver transplantation (LDLT). Twenty-six of 329 (7.9%) HTLV-1 carriers underwent primary LDLT. One recipient negative for HTLV-1 before LDLT received a graft from an HTLV-1 positive donor. Eight donors were HTLV-1 positive. Twenty-seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV-1 positive donors and two from negative donors. The 1-, 3- and 5-year HTLV-1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score ≥ 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV-1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development. The authors investigate the impact of human T cell leukemia virus type 1 in living donor liver transplantation and find that fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score > 15 are risk factors for T cell leukemia development See editorial by Kaul on page 1365..
1680. Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Kazutoyo Morita, Naotaka Hashimoto, Hiroto Kayashima, Tohru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihko Maehara, The long-term outcomes of patients with hepatocellular carcinoma after living donor liver transplantation
A comparison of right and left lobe grafts, Surgery today, 10.1007/s00595-011-0086-4, 42, 6, 559-564, 2012.06, Purpose The feasibility of living donor liver transplantation (LDLT) using left lobe (LL) grafts has been demonstrated. However, the long-term outcome of the hepatocellular carcinoma (HCC) patients with LL grafts has not been elucidated. The aim of this study was to analyze the long-term outcomes after LDLT for HCC according to the graft type. Methods A retrospective analysis was performed evaluating the outcomes of LL graft recipients (n = 82) versus recipients of RL grafts (n = 46). The analysis endpoints were the overall and recurrence-free survival after LDLT. The demographics of both recipients and donors, and the tumor characteristics associated with the graft type were also analyzed. Results The graft volume (436 ± 74 g), as well as the graft volume-standard liver volume rate (38.3 ± 6.2%) of the LL graft group were significantly decreased as compared to those of the RL graft group (569 ± 82 g, 46.3 ± 6.7%; P>0.01). The 1-, 3-, 5- and 7-year overall survival rates of the LL graft group were 88.2, 80.2, 75.7 and 72.4%, respectively, which were not significantly different compared to those of the RL graft group (95.4, 87.3, 87.3 and 87.3%). The recurrence-free survival rates of the LL graft group (89.1% at 1 year, 78.8% at 3 years, 75.8% at 5 years and 70.3% at 7 years) were similar to those of the RL graft group (88.6, 88.6, 88.6 and 88.6%). The mean peak postoperative total bilirubin levels and duration of hospital stay after surgery for the LL grafting donors were significantly decreased as compared to those of the RL grafting donors (P>0.01). The rate of severe complications (over Clavien's IIIa) associated with LL graft procurement was 6.2%, which was lower than that in the RL graft group (15.6%). Conclusions The long-term outcomes in the HCC patients with LL grafts were similar to those of patients receiving RL grafts, and the outcomes of the donors of LL grafts were more favorable. Therefore, LL grafts should be considered when selecting LDLT for HCC to ensure donor safety..
1681. Takeo Toshima, Ken Shirabe, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Outcome of hepatectomy for hepatocellular carcinoma in patients with renal dysfunction, HPB, 10.1111/j.1477-2574.2012.00452.x, 14, 5, 317-324, 2012.05, Objectives: There are few reports on the efficacy of hepatectomy for hepatocellular carcinoma (HCC) in patients with renal dysfunction (RD). This study aimed to clarify the validity of hepatectomy for treating HCC in RD patients, and to compare postoperative courses in RD and non-RD patients. Methods: The clinical features of 722 HCC patients who underwent curative hepatectomy between 1986 and 2009 were retrospectively reviewed. Seventeen patients (2.4%) with preoperative serum creatinine levels of >2.0 mg/dl were defined as the RD group, and, of these, seven who did not receive preoperative haemodialysis were defined as borderline patients. Clinicopathological characteristics and postoperative outcomes were compared between the RD group (n= 17) and the non-RD group (n= 705). The postoperative courses of borderline patients were reviewed in detail. Results: Overall survival (P= 0.177) and disease-free survival (P= 0.942) after hepatectomy did not differ significantly between the groups. Incidences of massive ascites (35.3% vs. 14.3%; P= 0.034) and pleural effusion (52.9% vs. 17.6%; P= 0.001), defined as massive effusion (ME), were significantly higher in the RD group than in the non-RD group. Hypoalbuminaemia (≤2.8 g/dl; P= 0.031), heavy blood loss (≥1000 ml; P= 0.012) and intraoperative blood transfusion (P= 0.007) were risk factors for ME. Among the borderline patients, serum creatinine values were not increased immediately after surgery and four patients underwent haemodialysis. Conclusions: Preoperative hypoalbuminaemia, heavy blood loss and blood transfusion are independent risk factors for ME in RD patients. Preoperative improvement of anaemia and reduction of blood loss by meticulous surgical techniques may prevent ME in RD patients who require hepatectomy for HCC..
1682. Takeo Toshima, Akinobu Taketomi, Toru Ikegami, Takasuke Fukuhara, Hiroto Kayashima, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, V5-drainage-preserved right lobe grafts improve graft congestion for living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3182488bd8, 93, 9, 929-935, 2012.05, Background: Right lobe (RL) grafts without middle hepatic vein for living donor liver transplantation (LDLT) result in congestion of recipients' livers and sometimes in unfavorable postoperative course. This study aimed to evaluate the feasibility of our new V5-drainage-preserved RL (VP-RL) graft. Methods: Based on a review of 49 donors' livers in a retrospective study using three-dimensional reconstruction-computed tomography volumetry, hepatic vein draining segment 4 (V4) anatomy was classified into three types: inferior V4 dominant (A); superior V4 dominant (B); and umbilical vein to left hepatic vein dominant (C). Differences in functional graft volume (GV) and remnant liver volume (RV) between VP-RL and modified RL (M-RL) grafts with all three types were evaluated. In a prospective study of actual 15 LDLT, the outcome of venous reconstruction and postoperative parameters with VP-RL grafts compared with M-RL grafts was analyzed. Results: In the retrospective study using three-dimensional reconstruction-computed tomography volumetry, in types B and C, functional GV of VP-RL was larger than that of M-RL (P<0.05) without impaired donors' functional RV, whereas functional RV in VP-RL was significantly decreased in type A (P<0.05). In the prospective study of actual 15 LDLT, using VP-RL with types B and C, size and number of venous reconstructions, and functional GV and postoperative parameters, such as postoperative serum total bilirubin levels and ascites volume, were significantly improved compared with those using M-RL (P<0.05). Conclusions: Using preoperative V4 anatomical classification, VP-RL graft procurement is a valuable strategy in RL-LDLT to improve postoperative course of both recipients and donors..
1683. Rumi Matono, Shohei Yoshiya, Takashi Motomura, Takeo Toshima, Hiroto Kayashima, Toshiro Masuda, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Factors linked to longterm survival of patients with hepatocellular carcinoma accompanied by tumour thrombus in the major portal vein after surgical resection, HPB, 10.1111/j.1477-2574.2011.00436.x, 14, 4, 247-253, 2012.04, Objectives: The prognosis in patients with hepatocellular carcinoma (HCC) accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this study was to clarify the factors linked to survival of >5 years after hepatectomy in HCC patients with MPVTT. Methods: Twenty-nine HCC patients with MPVTT were divided into two groups comprising, respectively, patients who survived >5 years after hepatectomy (survivors, n = 5) and those who did not (non-survivors, n = 24). The two groups were compared. Results: Overall survival rates at 1, 3 and 5 years were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had recurrences of HCC in which the number of recurrent nodules was under four. Three (21.4%) of the 14 non-survivors who underwent curative resection experienced recurrences of HCC and all of them demonstrated fewer than four recurrent nodules (P = 0.0114). Local therapy, such as radiofrequency ablation and resection of recurrence, had more often been used in survivors than in non-survivors (P = 0.0364). Conclusions: Although surgical outcomes in patients with HCC accompanied by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the number of recurrent nodules is less than four, local therapy should be selected with the aim of achieving 5-year survival..
1684. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Tomoharu Yoshizumi, Mizuki Ninomiya, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Bacterial sepsis after living donor liver transplantation
The impact of early enteral nutrition, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2011.12.001, 214, 3, 288-295, 2012.03, Background: Bacterial sepsis is a significant problem that must be addressed after living donor liver transplantation (LDLT). Study Design: A retrospective analysis of 346 adult-to-adult LDLT patients was performed. Results: Forty-six patients (13.3%) experienced bacterial sepsis, with primary and secondary origins in 23.9% and 76.1%, respectively. Gram-negative bacteria accounted for 71.7% of the bacteria isolated. The 2-year cumulative graft survival rate in patients with bacterial sepsis was 45.7%. Patients with bacterial sepsis secondary to pneumonia (n = 12) had poorer 2-year graft survival rates (16.7%) than did those with primary or other types of secondary sepsis (p = 0.004). Multivariate analysis showed that intraoperative massive blood loss >10L (p < 0.001) and no enteral feeding started within 48 hours after transplantation (p = 0.005) were significant risk factors for bacterial sepsis. Among patients who received enteral nutrition, the incidences of bacterial sepsis in patients who received enteral nutrition within 48 hours (n = 135) or later than 48 hours (n = 57) were 5.9% and 21.0%, respectively (p = 0.002). The incidence of early graft loss was 8-fold higher in recipients with massive intraoperative blood loss without early enteral nutrition (p < 0.001). Conclusions: Early enteral nutrition was associated with significantly reduced risk of developing bacterial sepsis after LDLT..
1685. Takashi Motomura, Erina Koga, Akinobu Taketomi, Takasuke Fukuhara, Yohei Mano, Jun Muto, Hideyuki Konishi, Takeo Toshima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype, Hepatology Research, 10.1111/j.1872-034X.2011.00927.x, 42, 3, 288-295, 2012.03, Aim: A genetic polymorphism of inosine triphosphate pyrophosphatase (ITPA) has been associated with pegylated-interferon/ribavirin (PEG-IFN/RBV)-induced anemia in chronic hepatitis C patients. However, correlation of the genetic variant with anemia following liver transplantation has not been determined. Methods: Sixty-three hepatitis C virus (HCV)-positive patients who underwent liver transplantation and PEG-IFN/RBV therapy were enrolled. The rs1127354 was determined for each individual. Results: There was no relationship with anemia or RBV dosage in patients carrying the CC allele (CC group, n=43) and those carrying the CA allele (CA group, n=20). The incidence of hemoglobin (Hb) decline >3g/dL (CC: 4.7%, CA: 0%) was relatively low, whereas the incidence of Hb levels <10g/dL (CC: 18.6%, CA: 30.0%) was high. Univariate analysis revealed that splenectomy inversely correlated with Hb levels <10g/dL at 4weeks (P=0.04). Among the 22 patients who did not undergo splenectomy, the incidence of Hb levels <10g/dL tended to be lower in the seven patients carrying the CA allele (28.6%) than in the 15 patients with the CC allele (60.0%). Conclusion: The ITPA genetic polymorphism does not correlate with post-transplant PEG-IFN/RBV-induced anemia. Splenectomy is useful in preventing anemia regardless of the ITPA genotype..
1686. Jun Muto, Yohei Mano, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Additional resection of the pancreas body prevents postoperative pancreas fistula in patients with portal annular pancreas who undergo pancreaticoduodenectomy, Case Reports in Gastroenterology, 10.1159/000335210, 6, 1, 131-134, 2012.01, Portal annular pancreas (PAP) is a rare variant in which the uncinate process of the pancreas extends to the dorsal surface of the pancreas body and surrounds the portal vein or superior mesenteric vein.Upon pancreaticoduodenectomy (PD), when the pancreas is cut at the neck, two cut surfaces are created. Thus, the cut surface of the pancreas becomes larger than usual and the dorsal cut surface is behind the portal vein, therefore pancreatic fistula after PD has been reported frequently. We planned subtotal stomach-preserving PD in a 45-year-old woman with underlying insulinoma of the pancreas head. When the pancreas head was dissected, the uncinate process was extended and fused to the dorsal surface of the pancreas body. Additional resection of the pancreas body 1 cm distal to the pancreas tail to the left side of the original resection line was performed. The new cut surface became one and pancreaticojejunostomy was performed as usual. No postoperative complications such as pancreatic fistula occurred. Additional resection of the pancreas body may be a standardized procedure in patients with PAP in cases of pancreas cut surface reconstruction..
1687. Hideaki Uchiyama, Ken Shirabe, Masaru Morita, Yoshihiro Kakeji, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Noboru Harada, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Expanding the applications of microvascular surgical techniques to digestive surgeries
A technical review, Surgery today, 10.1007/s00595-011-0032-5, 42, 2, 111-120, 2012.01, In living donor liver transplantation (LDLT), it is considered safer to reconstruct hepatic arteries (HAs) under a microscope than under conventional loupe magnification, because graft HA stumps are generally thin and short with an average diameter of approximately 2 mm. We first applied microvascular surgical techniques to HA reconstruction for LDLT in 1996. In most cases, we use a disposable double-clip to secure the graft and recipient arteries, and interrupted 8-0 nonabsorbable monofilament sutures. We next started performing resection and reconstruction of the right HA in a surgery for hilar cholangioma using the same technique as in LDLT. Lately, we have started applying microvascular surgical techniques to various digestive surgeries; namely, supercharge and superdrainage in esophageal surgery, vascular reconstruction in free jejunal interposition grafts for cervical esophageal cancer, resection and reconstruction of spontaneous HA aneurysms, jejunal artery reconstruction for spontaneous superior mesenteric artery dissections, and so forth. Mastering this technique is time consuming. However, once a surgeon masters the technique it has almost unlimited applications, and most vital vessels can be safely reconstructed using this method. We herein provide a technical review of the application of microvascular surgical techniques for various digestive surgeries..
1688. Tomoharu Yoshizumi, Ken Shirabe, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Masanori Yoshimatsu, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Risk factors that increase mortality after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e318238dacd, 93, 1, 93-98, 2012.01, BACKGROUND.: Female liver to male recipient is a well-accepted risk factor for graft loss in cadaveric liver transplantation. However, gender matching is infeasible because of an insufficient number of available donors. No studies have been performed on the role of gender in the field of living donor liver transplantation. This report investigates the effect of gender mismatch on the outcome of living donor liver transplantation. METHODS.: A total of 335 patients and donors were classified into four groups according to the following gender combinations: male donor to male recipient group (n=104), male donor to female recipient group (n=120), female donor to male recipient (FM) group (n=59), and female donor to female recipient group (n=52). Patient and graft survival were compared among the groups. We performed a multivariable analysis to identify the factors associated with patient mortality. RESULTS.: The 1-, 3-, 5-, and 10-year patient survival rates in the FM group were 80.6%, 66.8%, 61.8%, and 47.7%, respectively. The FM group showed significantly shorter patient survival compared with the other three groups. Independent risk factors for patient mortality were: FM group (P=0.006), pretransplant diabetes mellitus (P=0.001), and a model for end-stage liver disease score more than or equal to 20 (P=0.004). CONCLUSIONS.: Male recipients of transplants from female donors, pretransplant diabetes mellitus, and a model for end-stage liver disease score more than or equal to 20 have poor survival rates..
1689. Ken Shirabe, Yohei Mano, Jun Muto, Rumi Matono, Takashi Motomura, Takeo Toshima, Kazuki Takeishi, Hidekaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Masaru Morita, Shunichi Tsujitani, Yoshihisa Sakaguchi, Yoshihiko Maehara, Role of tumor-associated macrophages in the progression of hepatocellular carcinoma, Surgery today, 10.1007/s00595-011-0058-8, 42, 1, 1-7, 2012.01, Recent studies have shown that the tumor microenvironment plays an important role in cancer progression. Tumor-associated macrophages (TAMs), in particular, have been found to be associated with tumor progression. Macrophages have multiple biological roles, including antigen presentation, target cell cytotoxicity, removal of foreign bodies, tissue remodeling, regulation of inflammation, induction of immunity, thrombosis, and endocytosis. Recent immunological studies have identified two distinct states of polarized macrophage activation: the classically activated (M1) and the alternatively activated (M2) macrophage phenotypes. Bacterial moieties such as lipopolysaccharides and the Th1 cytokine interferon-γ polarize macrophages toward the M1 phenotype. The M2 polarization was discovered as a response to the Th2 cytokine interleukin-4. In general, M2 macrophages exert immunoregulatory activity, participate in polarized Th2 responses, and aid tumor progression. TAMs have recently been found to play an important role in hepatocellular carcinoma (HCC) progression. Based on the properties of TAMs, obtained from pathological examination of resected specimens, we have identified new therapeutic approaches, involving the targeting of TAMs with adjuvant therapy after hepatic resection for HCC. This review discusses the roles of TAM in HCC progression and the possibility of new therapies targeting TAMs..
1690. Toru Ikegami, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yoshihiko Maehara, The impact of renal replacement therapy before or after living donor liver transplantation, Clinical Transplantation, 10.1111/j.1399-0012.2011.01450.x, 26, 1, 143-148, 2012.01, Introduction: The impact of renal replacement therapy (RRT) in living donor liver transplantation (LDLT) has not yet been investigated. Methods: Among 253 LDLT patients, RRT was started before (RRT-Pre, n=9), or after (RRT-Post, n=27) LDLT. The clinical outcomes were reviewed. Results: The one-yr graft survival rate was 94.1% without RRT, and 63.9% and in those with RRT (p<0.0001). Among the RRT patients, the RRT-Pre patients exhibited acute liver failure, hepatorenal syndrome and high model for end-stage liver disease score (35±12), whereas the RRT-Post patients had sepsis as a comorbidity. The one-yr graft survival rate was 100.0% in the RRT-Pre patients vs. 51.9% in the RRT-Post patients (p<0.01). The duration of RRT was significantly shorter in the RRT-Pre patients than that in the RRT-Post patients (5.3±2.1 vs. 17.8±14.1d, p=0.02). The mean duration between starting RRT and LDLT was 2.1±0.7d in the Pre-RRT patients. Conclusion: The RRT-Pre patients had excellent outcomes because the severe condition was primarily treated by LDLT after short-term pre-transplant RRT. Post-transplant uncontrollable sepsis was the major cause of graft loss in patients who receive RRT after LDLT..
1691. Akinobu Taketomi, Kazuki Takeishi, Yohei Mano, Takeo Toshima, Takashi Motomura, Shinichi Aishima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Total resection of the right hepatic vein drainage area with the aid of three-dimensional computed tomography, Surgery today, 10.1007/s00595-011-0021-8, 42, 1, 46-51, 2012.01, Purpose: We analyzed the feasibility and safety of our preliminary surgical approach for total hepatic resection of the right hepatic vein drainage area (THR-RHV) with the aid of three-dimensional computed tomography (3D-CT) guidance. Methods: Clinical findings and 3D-CT volumetry results were investigated in five patients who underwent THR-RHV for a hepatic malignant tumor close to the right hepatic vein (RHV). Results: The mean estimated remnant liver volume after a conventional right lobectomy was 474 ml, whereas that after THR-RHV was 614 ml, indicating that 140 ml (13.8%) of additional liver volume had been preserved by performing THR-RHV. The median operative time, mean ischemic time, and mean blood loss during surgery were 406 min, 51 min, and 587 ml, respectively. Histological examinations confirmed a negative surgical margin in all five patients. The mean liver volume estimated by 3D-CT was 458 ml, whereas the mean actual resected liver volume was 468 g, resulting in a mean error ratio of 3.1%. Conclusions: THR-RHV allowed for a higher remnant liver volume than that after conventional right lobectomy of the liver, and proved feasible with acceptable perioperative results. This technique thus promotes both safety and curability for patients with a tumor close to the RHV..
1692. Eisuke Kawakubo, Yuji Soejima, Eigorou Yamanouchi, Mizuki Ninomiya, Hiroto Kayashima, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Case of magnetic compression anastomosis with double-balloon enteroscopy for biliary obstruction after living donor liver translationn, Japanese Journal of Gastroenterological Surgery, 10.5833/jjgs.44.1404, 44, 11, 1404-1410, 2011.12, Biliary anastomotic strictures are one of the most significant postoperative complications after living donor liver transplantations (LDLT), which develop in about 10-30% of recipients. Various modalities have been reported to treat these complications with an acceptable success rate. Herein, we present a case of complete anastomotic obstruction of hepaticojejunostomy, for which a successful magnetic compression anastomosis (MCA) was performed. The patient was a 56-year-old man who was given a diagnosis of biliary anastomotic strictures 9 months after LDLT. Conservative treatment, including percutaneous transhepatic biliary drainage (PTBD), was initially undertaken, however, re canalization of the bile duct anastomosis could not be obtained. An MCA was performed 3 months after the initial PTBD, which resulted in a success. In conclusion, MCA is a safe and very effective method to treat complete anastomotic strictures after LDLT..
1693. Tetsuo Ikeda, Yusuke Yonemura, Naoyuki Ueda, Akira Kabashima, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yosihiro Kakeji, Masaru Morita, Shunichi Tsujitani, Yoshihiko Maehara, Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic glissonian approach and a modified hanging maneuver to minimize intraoperative bleeding, Surgery today, 10.1007/s00595-010-4479-6, 41, 12, 1592-1598, 2011.12, Purpose: Although laparoscopic liver resection has been widely adopted, performing a pure laparoscopic right hepatectomy remains a challenging procedure. The aim of this report is to evaluate the efficiency of a pure laparoscopic right hepatectomy (PLRH) in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver. Methods: Pure laparoscopic right hepatectomy was performed in the semi-prone position with the use of an intrahepatic Glissonian approach and modified hanging maneuver for patients with primary liver cancer (n = 3) and metastatic liver cancer (n = 1). Results: The intraoperative total blood loss was only 95-140 g (mean: 126.2 g). None of the patients required a blood transfusion, and no serious complications were encountered. The durations of the surgeries ranged from were 308 to 445 min (mean: 394.8 min). The postoperative hospital stay was 8-11 days (mean 9.5 days). Conclusion: Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver is thus considered to be a safe modality, which minimizes intraoperative bleeding..
1694. Hideaki Uchiyama, Yohei Mano, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Ken Shirabe, Yoshihiko Maehara, Kinetics of anti-blood type isoagglutinin titers and B lymphocytes in ABO-incompatible living donor liver transplantation with rituximab and plasma exchange, Transplantation, 10.1097/TP.0b013e318231e9f8, 92, 10, 1134-1139, 2011.11, Background. A novel immunosuppression protocol using rituximab and plasma exchange treatment was developed for ABO-incompatible living donor liver transplantation (ABO-I LDLT). The aim of this study was to investigate the kinetics of anti-blood type isoagglutinin titers and the number of blood B lymphocytes in ABO-I LDLT with the new protocol and their impact on the outcomes after ABO-I LDLT. Methods. Fifteen patients underwent ABO-I LDLT plus splenectomy with the new protocol between November 2005 and December 2010, and their data were retrospectively analyzed. Results. CD19-positive lymphocytes in the blood rapidly disappeared after rituximab treatment and began to recover approximately 6 months later. Anti-blood type isoagglutinin titers were lowered by pretransplant plasma exchange (2 3∼2 12→2 1∼2 8). Although the anti-donor blood type isoagglutinin titers remained consistently low after transplantation in comparison to the pretreatment levels, they persisted long after LDLT, whereas posttransplant biopsy specimens showed sustained A/B antigens on the graft livers. ABO-I hepatitis C virus-positive patients were prone to acceleration of hepatitis C viremia and cytomegalovirus antigenemia in comparison to the control patients. Conclusions. Although the new protocol for ABO-I LDLT yielded great success with 100% graft survival, the acceptable anti-blood type isoagglutinin titers just before LDLT, and its application to hepatitis C-positive patients must be determined..
1695. Toru Ikegami, Ken Shirabe, Kazutoyo Morita, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Hiroto Kayashima, Naotaka Hashimoto, Yoshihiko Maehara, Minimal hilar dissection prevents biliary anastomotic stricture after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3182336073, 92, 10, 1147-1151, 2011.11, Background. We introduced a new technique called minimal hilar dissection (Min-HD) technique in living donor liver transplantation (LDLT) to keep vascular networks around the recipient's bile duct. The aim of this study is to investigate whether the Min-HD technique could prevent biliary anastomotic stricture (BAS) after LDLT with duct-to-duct biliary reconstruction. Methods. An analysis of 214 adult-to-adult LDLT grafts (left lobe, n=135; right lobe, n=76; posterior segment, n=3) with duct-to-duct biliary reconstruction was performed. Results. There were 46 cases with BAS. The incidence of BAS was 32.1% in the conventional technique group (n=84) and 14.6% in the Min-HD technique group (n=130, P=0.003). Multivariate regression analysis regarding BAS was carried out and detected hepatic artery flow less than 50 mL/min (P=0.002), not using the Min-HD technique (P=0.011), biliary anastomotic leakage (BAL, P=0.027) and ductoplasty (P=0.039) for the significant risk factors for BAS. The incidence BAL was 11.9% in the conventional technique group and 0.7% in the Min-HD technique group (P=0.002). No other factors showed an impact on the occurrence of BAL. The treatments for BAS were performed by endoscopic or percutaneous procedures. The cumulative completion rate of the treatment after developing BAS was 45.1% and 78.6% at 1-and 3-year, respectively. The median period for treating BAS was 10.8 months. Conclusion. The Min-HD technique is a rational surgical method, and it has the potential for preventing BAS and BAL after duct-to duct biliary reconstruction in LDLT..
1696. Ken Shirabe, Takeo Toshima, Akinobu Taketomi, Kennichi Taguchi, Tomoharu Yoshizumi, Hideaki Uchiyama, Norifumi Harimoto, Kiyoshi Kajiyama, Akinori Egashira, Yoshihiko Maehara, Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan, Liver International, 10.1111/j.1478-3231.2011.02572.x, 31, 9, 1366-1372, 2011.10, Background & aims: Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC. Methods: Hepatocyte AFB1-DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non-B non-C hepatocellular carcinoma (NBNC HCC). Results: AFB1-DNA adducts were detected in hepatocyte nuclei in 18/279 patients (6%), including13/83 patients (16%) with NBNC HCC and 5/51 patients (10%) expressing hepatitis B surface antigen. None of the patients with HCV Ab (n=136) were positive for AFB1-DNA. The incidence of the G-T transversion and mutations in exon 7 of TP53 in patients with AFB1-DNA adducts were significantly higher in patients with than in patients without AFB1-DNA adducts. All three patients with the codon 249 AGG-AGT mutation had AFB1-DNA adducts. Conclusion: Although exposure to AFB1 is thought to be low in Japan, it is still associated with hepatocarcinogenesis, particularly in NBNC HCC and hepatitis B individuals..
1697. Toru Ikegami, Takashi Maeda, Hiroto Kayashima, Eiji Oki, Tomoharu Yoshizumi, Yoshihisa Sakaguchi, Yasushi Toh, Ken Shirabe, Yoshihiko Maehara, Soft coagulation, polyglycolic acid felt, and fibrin glue for prevention of pancreatic fistula after distal pancreatectomy, Surgery today, 10.1007/s00595-010-4433-7, 41, 9, 1224-1227, 2011.09, Purpose: To evaluate the effectiveness of using soft coagulation followed by the application of polyglycolic acid (PGA) felt and fibrin glue to prevent pancreatic fistula (PF) after distal pancreatectomy (DP). Methods: A soft coagulation system was applied on the cut surface of the pancreas after ligating the main pancreatic duct, followed by the application of layers of PGA felt and fibrin glue on the layers, to prevent the development of a PF after DP. Results: This technique was applied in nine patients, with mean drain amylase levels of 372 ± 296, 185 ± 209, 54 ± 40, and 47 ± 34 IU/l on days 1, 3, 5, and 7, respectively, after DP. Only one patient (11.1%) showed a Grade A PF on day 3 after surgery; none of the other patients developed a fistula. Conclusions: This technique is an effective prophylactic measure to prevent the development of a PF after DP..
1698. Mizuki Ninomiya, Ken Shirabe, Hideki Ijichi, Takeo Toshima, Noboru Harada, Hideaki Uchiyama, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Temporal changes in the stiffness of the remnant liver and spleen after donor hepatectomy as assessed by acoustic radiation force impulse
A preliminary study, Hepatology Research, 10.1111/j.1872-034X.2011.00809.x, 41, 6, 579-586, 2011.06, Aim: Virtual touch tissue quantification (VTTQ) is an implementation of ultrasound acoustic radiation force impulse imaging that provides numerical measurements of tissue stiffness. We have evaluated the temporal changes of the remnant liver and spleen after living donor hepatectomy with special reference to the differences between right and left liver donation. Methods: Nineteen living donors who received right lobectomy (small remnant liver [SRL] group; n=7) or extended left and caudate lobectomy (large remnant liver [LRL] group; n=12) were enrolled. They underwent measurement of liver and spleen VTTQ before and after donor surgery. Results: Virtual touch tissue quantification of the remnant liver increased postoperatively until postoperative day (POD) 3-5, and the values in the SRL group were significantly higher than those in the LRL group at POD 3-9. The values of the spleen also increased after donor surgery and the values in the SRL group were significantly higher than those in the LRL group at POD 3-14. A significant positive correlation between postoperative maximum value of VTTQ and postoperative maximum total bilirubin levels was observed. In liver transplant recipients, there was a significant positive correlation between preoperative spleen VTTQ and the corresponding actual portal venous pressure that was measured at the time of transplant surgery. Conclusion: Stiffness of the remaining liver and spleen in the smaller remnant liver group became harder than that in the larger remnant liver group. Perioperative measurement of liver and spleen VTTQ seems to be a useful means for assessing the physiology of liver regeneration..
1699. T. Motomura, A. Taketomi, T. Fukuhara, Y. Mano, K. Takeishi, T. Toshima, N. Harada, H. Uchiyama, T. Yoshizumi, Y. Soejima, K. Shirabe, Y. Matsuura, Y. Maehara, The impact of IL28B genetic variants on recurrent hepatitis C in liver transplantation
Significant lessons from a dual graft case, American Journal of Transplantation, 10.1111/j.1600-6143.2011.03537.x, 11, 6, 1325-1329, 2011.06, IL28B genetic polymorphism is related to interferon-sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51-year-old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated-interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients. In this dual graft liver transplantation case, each graft with different IL28B genotype showed significantly different pathological findings and viral kinetics after interferon therapy for recurrent hepatitis C..
1700. Takeo Toshima, Ken Shirabe, Kazuki Takeishi, Takashi Motomura, Youhei Mano, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, New method for assessing liver fibrosis based on acoustic radiation force impulse
A special reference to the difference between right and left liver, Journal of gastroenterology, 10.1007/s00535-010-0365-7, 46, 5, 705-711, 2011.05, Background: Virtual touch tissue quantification (VTTQ) based on acoustic radiation force impulse (ARFI) imaging has been developed as a noninvasive bedside method for the assessment of liver stiffness. In this study, we examined the diagnostic performance of ARFI imaging in 103 patients, focusing on the difference in VTTQ values between the right and left liver lobes. Methods: We evaluated VTTQ values of the right and left lobes in 79 patients with chronic liver disease who underwent histological examination of liver fibrosis and in 24 healthy volunteers. The diagnostic accuracy of VTTQ was compared with several serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index. Results: The VTTQ values (meters per second) in the right and left lobes were 1.61 ± 0.51 and 1.90 ± 0.68, respectively, and the difference was statistically significant (P < 0.0001). The VTTQ values in both liver lobes were correlated significantly with histological fibrosis grades (P < 0.001). The standard deviations of the VTTQ values in the right lobe were significantly lower than those in the left lobe (P < 0.001). The area under the receiver-operating characteristic curve for the diagnosis of fibrosis (F ≥ 3) using VTTQ values in both liver lobes was superior to serum markers, especially in the right lobe. Conclusions: VTTQ is an accurate and reliable tool for the assessment of liver fibrosis. VTTQ of the right lobe was more accurate for diagnosing liver fibrosis than in the left lobe..
1701. Naotaka Hashimoto, Tomohiko Akahoshi, Tetsuya Shoji, Morimasa Tomikawa, Norifumi Tsutsumi, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Successful treatment for hepatic encephalopathy aggravated by portal vein thrombosis with balloon-occluded retrograde transvenous obliteration, Case Reports in Gastroenterology, 10.1159/000330287, 5, 2, 366-371, 2011.05, This report presents the case of a 78-year-old female with hepatic encephalopathy due to an inferior mesenteric venous-inferior vena cava shunt. She developed hepatocellular carcinoma affected by hepatitis C virus-related cirrhosis and underwent posterior sectionectomy. Portal vein thrombosis developed and the portal trunk was narrowed after hepatectomy. Portal vein thrombosis resulted in high portal pressure and increased blood flow in an inferior mesenteric venous-inferior vena cava shunt, and hepatic encephalopathy with hyperammonemia was aggravated. The hepatic encephalopathy aggravated by portal vein thrombosis was successfully treated by balloon-occluded retrograde transvenous obliteration via a right transjugular venous approach without the development of other collateral vessels..
1702. Mami Kanamoto, Mitsuo Shimada, Yuji Morine, Tomoharu Yoshizumi, Satoru Imura, Toru Ikegami, Hiroki Mori, Yusuke Arakawa, Beneficial effects of follistatin in hepatic ischemia-reperfusion injuries in rats, Digestive Diseases and Sciences, 10.1007/s10620-010-1401-4, 56, 4, 1075-1081, 2011.04, Background: Ischemia-reperfusion injury has been demonstrated in a variety of clinical settings. The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. Follistatin, an activin-binding protein, binds to activins and subsequently blocks their action. It was reported that blockade of the action of activin with administration of follistatin accelerates recovery from ischemia renal injury. This study was conducted to investigate the involvement of the activin-follistatin system in hepatic ischemia-reperfusion injury. Methods: Total hepatic ischemia for 30 min was performed followed by reperfusion in a rat model. Rats were divided into two groups: a follistatin group and a control group. Follistatin (1 μg/body), which is an activin-binding protein, was administered at the time of reperfusion. Results: Though 80% of animals survived in the follistatin group, four of five animals died in the control group within 3 days after reperfusion (p < 0.05). AST was significantly lower at 3 h after reperfusion in the follistatin group (p < 0.05). LDH was also lower at 6 h after reperfusion in the follistatin group (p < 0.05). Follistatin inhibited the mRNA expression of the βA subunit of activin. Moreover, the expression of IL-6, which is an inflammatory cytokine, was suppressed at 6 h after reperfusion in the follistatin group (p < 0.05). Conclusions: The present study demonstrated that treatment with follistatin reduced the expression of IL-6 and activin resulting in beneficial support for hepatic ischemia-reperfusion injuries..
1703. Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Toru Ikegami, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yoshihiko Maehara, Living donor liver transplantation in patients who have received pretransplant treatment for hepatocellular carcinoma, Transplantation, 10.1097/TP.0b013e318210de92, 91, 8, e61-e62, 2011.04.
1704. Ken Shirabe, Takashi Motomura, Jun Muto, Takeo Toshima, Rumi Matono, Yohei Mano, Kazuki Takeishi, Hideki Ijichi, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Tumor-infiltrating lymphocytes and hepatocellular carcinoma
Pathology and clinical management, International Journal of Clinical Oncology, 10.1007/s10147-010-0131-0, 15, 6, 552-558, 2010.12, The presence of tumor-infiltrating lymphocytes (TILs) in hepatocellular carcinoma (HCC) is relatively rare. The prognosis of patients with HCC and marked TILs is better than that of patients with HCC without TILs. TILs in HCC tissues are mainly T cells, and previous reports suggested that TILs might be important antitumor effector cells. TILs have been extensively analyzed, and subpopulations of CD3+, CD4+, and CD8+ T cells are often present in HCC. Some studies have reported that the percentage of CD8+ T cells, which might have cytotoxic activity, is decreased in tumors with TILs, as compared with noncancerous tissues. Although the antitumor effects of TILs seem to be impaired in HCCs, the underlying mechanism has remained unclear until quite recently. Pathological and in vitro studies have now shown that regulatory T cells play important roles in the deterioration of the antitumor effects of TILs. The aim of this review is to introduce recent pathological findings for TILs in HCC and to evaluate new therapeutic strategies in this field..
1705. T. Ikegami, Y. Soejima, K. Shirabe, A. Taketomi, T. Yoshizumi, H. Uchiyama, T. Fukuhara, T. Ikeda, Y. Maehara, Evolving strategies to prevent biliary strictures after living donor liver transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2010.07.091, 42, 9, 3624-3629, 2010.11, Introduction The optimal surgical technique has not been elucidated that reduces the occurrence of biliary strictures after living donor liver transplantation (LDLT). Method We performed retrospective analysis of 193 consecutive LDLTs, including 78 right and 115 left lobe grafts. An external biliary stent was used for all of the cases. Results The overall 1-, 3-, and 5-year biliary stricturefree survival rates were 87.5%, 85.3%, and 85.3%, respectively. The 1- and 3-year biliary stricturefree survival rates for duct-to-duct reconstruction were 86.9% and 84.9%, and those for hepaticojejunostomy were 90.1% and 80.8%, respectively. A multivariate analysis revealed that the original number of graft bile ducts greater than the number of external stents, right lobe grafts, bile leaks, and recipient age older than 60 years represented the significant risk factors (P < .05) to develop a biliary stricture after LDLT. All cases with biliary strictures (n = 61) were initially managed nonsurgically, but 4 patients ultimately required interventions. Conclusions Biliary reconstruction in LDLT using an appropriate number of external stents resulted in fairly acceptable outcomes. However, not only the proper use of stents or graft selection, but also nonsurgical factors, are important factors that determine the incidence of biliary strictures after LDLT..
1706. Akinobu Taketomi, Takasuke Fukuhara, Kazutoyo Morita, Hiroto Kayashima, Mizuki Ninomiya, Yoichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihko Maehara, Improved results of a surgical resection for the recurrence of hepatocellular carcinoma after living donor liver transplantation, Annals of Surgical Oncology, 10.1245/s10434-010-0999-y, 17, 9, 2283-2289, 2010.09, Purpose: This study was designed to analyze the clinical outcomes of the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and to evaluate the efficacy of a surgical resection in treating such a recurrence. Methods: A total of 101 adult LDLT recipients with HCC between 1996 and 2007, including 17 who had recurrent HCC, were reviewed. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics, laboratory valuables, and tumor characteristics were analyzed. Any medical or surgical treatments that had been administered for any recurrence also were considered. Results: The mean duration until the initial recurrence after LDLT and the mean duration until death after the initial recurrence were 12.9 months and 12.0 months, respectively. A univariate analysis showed that gender, interferon therapy, early posttransplant tumor recurrence, and eligibility for a surgical resection all had a beneficial impact on survival from tumor recurrence. A surgical resection of tumor relapse was the most important variable in our study, and therefore the patients were divided into two groups: surgical therapy group (n = 9), and nonsurgical therapy group (n = 7). Interestingly, the overall survival rates of the surgical group were significantly better than those of the nonsurgical group and were similar to that of the patients without HCC recurrence. Conclusions: Surgical therapy might be useful for patients who experience a recurrence of HCC after LDLT to improve their outcome, when such treatment is available..
1707. Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Natsumi Yamashita, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Mizuki Ninomiya, Yoshihiko Maehara, Living donor liver transplantation in patients older than 60 years, Transplantation, 10.1097/TP.0b013e3181e81b2d, 90, 4, 433-437, 2010.08, Background. Living donor liver transplantation (LDLT) has been performed in adult patients. However, there are a few reports on how recipient age affects the outcome of LDLT. This study assessed LDLT outcome in patients aged 60 years or older. Methods. A total of 267 patients were enrolled and classified into two groups: those younger than 60 years (younger group, n=210) and those aged 60 years or older (older group, n=57). The 6-month and 1-, 3-, and 5-year patient survivals and the incidence of complications were compared. Multivariate analysis was performed to identify the risk factors. Results. Fifty-five of 57 (96.5%) donors in the older group were younger than 50 years (range 25-47 years), whereas only 177 of 210 (84.3%) donors in the younger group were younger than 50 years (P<0.0001). The 6-month and 1-, 3-, and 5-year patient survival rates of the older group were 92.9%, 85.3%, 72.7%, and 70.3%, respectively, whereas those of the younger group were 87.4%, 85.8%, 80.2%, and 78.2%, respectively. Neither difference was significant. A multivariate analysis revealed that the presence of diabetes, lack of hepatocellular carcinoma, and Model for End-Stage Liver Disease (MELD) Score more than or equal to 20 were independent risk factors for survival less than 1 year after LDLT (P=0.0003, P=0.014, and P=0.041, respectively). Another multivariate analysis revealed that the lack of consanguinity, MELD Score more than or equal to 20, and male recipient were independent risk factors for death 1 year or more after LDLT (P=0.004, P=0.005, and P=0.015, respectively). Conclusion. Recipient age did not affect LDLT outcome when patients with MELD Score less than 20 received grafts from consanguineous donors..
1708. Tomonobu Gion, Akinobu Taketomi, Ken Shirabe, Hirofumi Hasegawa, Takayuki Hamatsu, Yo Ichi Yamashita, Keishi Sugimachi, Tomoharu Yoshizumi, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, The role of serum interleukin-8 in hepatic resections, Surgery today, 10.1007/s00595-008-4086-y, 40, 6, 543-548, 2010.06, Purpose: Interleukin-8 (IL-8) is a neutrophil chemotactic factor, which is associated with some inflammatory diseases and various types of surgical stress. The aim of this study was to investigate whether the early postoperative serum IL-8 level may potentially be a new indicator of a surgical stress in patients undergoing a hepatic resection. Methods: The serum IL-8 levels were measured in 37 patients who underwent a hepatectomy. The serum IL-8 levels were serially measured using an enzyme-linked immunosorbent assay both before and after a hepatic resection. In addition, the correlation between the postoperative IL-8 value and several clinical variables were examined. Results: The mean level of IL-8 significantly increased immediately after the operation (P < 0.01 vs before the operation) and decreased on the first postoperative day (POD 1, P < 0.05 vs after the operation). The early postoperative IL-8 levels positively correlated with the length of the procedure (r = 0.383; P < 0.05), the estimated blood loss (r = 0.483; P < 0.01) and the serum bilirubin level on POD 1 (r = 0.390; P < 0.05), and inversely correlated with the white blood cell counts (r = -0.388; P < 0.05) and lymphocyte counts on POD 1 (r = -0.424; P < 0.05). In a comparison of the postoperative IL-8 levels with the surgical factors, there was a significant difference in the extension of the resection (P < 0.05) and in blood transfusion. The patients with a fever of more than 38°C showed higher levels of IL-8 immediately after the operation than those without fever (P < 0.01). Conclusions: The early postoperative serum IL-8 level was found to correlate with the degree of the severity of surgery in patients undergoing a hepatic resection, and it is also considered to be a new indicator of surgical stress and liver injury..
1709. Takasuke Fukuhara, Toru Ikegami, Kazutoyo Morita, Kenji Umeda, Shigeru Ueda, Shigeyuki Nagata, Keishi Sugimachi, Tomonobu Gion, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Impact of preoperative serum sodium concentration in living donor liver transplantatio, Journal of Gastroenterology and Hepatology (Australia), 10.1111/j.1440-1746.2009.06162.x, 25, 5, 978-984, 2010.05, Background and Aims: The importance of hyponatremia in deceased donor liver transplantation (DDLT) has been recently discussed frequently. However, its impact on the outcomes in living donor liver transplantation (LDLT) has not yet been elucidated. The current study was designed to demonstrate the impact of pre-transplant sodium concentration on postoperative clinical outcomes. Methods: One hundred and thirty-four patients who underwent LDLT for end-stage liver diseases were examined to evaluate the significance of pre-transplant hyponatremia (Na ≤ 130 mEq/L) on the short-term clinical outcomes and the efficacy of the Model for End-Stage Liver Disease and serum sodium (MELD-Na) score using the sodium concentration and original MELD score. Results: The preoperative sodium and MELD score for all patients were 133.9 mEq/L (range: 109-142) and 16.2 (range: 6-38), respectively. According to a multivariate analysis, not only the MELD score (P = 0.030) but also the sodium concentration (P = 0.005) were found to be significant predictive factors for short-term graft survival. Preoperative hyponatremia was a significant risk factor for the occurrence of sepsis (P < 0.001), renal dysfunction (P < 0.001) and encephalopathy (P = 0.026). The MELD-Na score was 19.6 (range: 6-51) and the area under the receiver-operator curve of that (c-statistics: 0.867) was higher than MELD score and sodium concentration (c-statistics: 0.820 and 0.842, respectively). Conclusion: Preoperative hyponatremia was a significant risk for postoperative complications and short-term graft loss. The addition of sodium concentration to MELD score might therefore be an effective predictor for post-transplant short-term mortality in LDLT..
1710. Keishi Sugimachi, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Yo Ichi Yamashita, Kenji Umeda, Kazutoyo Morita, Yoshihiko Maehara, Successful curative extracorporeal hepatic resection for far-advanced hepatocellular carcinoma in an adolescent patient, Liver Transplantation, 10.1002/lt.22051, 16, 5, 685-687, 2010.05.
1711. Yuuta Kasagi, Koji Yamazaki, Akihiko Nakashima, Takeshi Yamana, Nami Yamashita, Hiroto Kayashima, Yuji Hoshino, Mayumi Ishida, Tomoharu Yoshizumi, Noriaki Sadanaga, Atsushi Fukuda, Hiroshi Matsuura, Kenichiro Okadome, Chondroblastic osteosarcoma arising from the pleura
Report of a case, Surgery today, 10.1007/s00595-009-3995-8, 39, 12, 1064-1067, 2009.12, Extraskeletal osteosarcoma is an uncommon malignant neoplasm. The origin of osteosarcoma in the pleura is extremely rare, with only four such cases so far documented in the literature to the best of our knowledge. We herein report the case of a 64-year-old Japanese man in whom a left pneumonectomy and pleurectomy were carried out to remove a huge tumor. The pathological examination confi rmed a diagnosis of chondroblastic osteosarcoma that had originally arisen from the pleura..
1712. T. Ikegami, A. Taketomi, Y. Soejima, T. Yoshizumi, T. Fukuhara, K. Kotoh, S. Shimoda, M. Kato, Y. Maehara, The Benefits of Interferon Treatment in Patients Without Sustained Viral Response After Living Donor Liver Transplantation for Hepatitis C, Transplantation Proceedings, 10.1016/j.transproceed.2009.08.070, 41, 10, 4246-4252, 2009.12, Although it has been recognized that interferon (IFN) treatment is crucial for recurrent hepatitis C after liver transplantation, its benefits have not been determined among patients without a sustained viral response (SVR). Methods: Eighty patients who received IFN plus ribavirin treatment after living donor liver transplantation were grouped as follows: group I (n = 18) SVR; group II (n = 25) no-SVR but viral response [VR] positive; Group III (n = 13) no-VR but biochemical response [BR] positive; and group IV (n = 24) no-VR and no-BR. Results: In groups II and III, not only the histological activity grade and fibrosis stage, but also the serum parameters including transaminases and type IV collagen were stable for 3 years after induction of IFN-based treatment. In group I, the activity grade and fibrosis stage significantly improved (P < .01). In group IV, the fibrosis stage significantly deteriorated (P < .01); the serum transaminases and type IV collagen were significantly higher than the other groups (P < .01). The mean duration of IFN treatment was significantly longer among group II (96 weeks) compared with the other cohorts (P < .05). The 5-year graft survival rate in groups II (91%) and III (100%) were comparable to those of group I (100%); group IV (62%) was significantly lower than the other groups (P < .05). Conclusion: IFN treatment was beneficial even among subjects with IFN-dependent VR or BR, although they did not achieve SVR..
1713. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Tashiharu Salbara, Takashi Nishizaki, Yoshihiko Maehara, Recurrent familial hypobetalipoproteinemia-induced nonalcoholic fatty liver disease after living donor liver transplantation, Liver Transplantation, 10.1002/lt.21766, 15, 7, 806-809, 2009.08, Familial hypobetalipoproteinemia (FHBL) is one of the causes of nonalcoholic steatohepatitis (NASH) and a codominant disorder. Patients heterozygous for FHBL may be asymptomatic, although they demonstrate low plasma levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Here we report a nonobese 54-year-old man with decompensated liver cirrhosis who underwent living donor liver transplantation with his son as the donor. Low albuminemia and refractory ascites persisted after transplantation. A biopsy specimen obtained 11 months after liver transplantation revealed severe steatosis and fibrosis, and recurrent NASH was diagnosed on the basis of pathological findings. Both the patient's and donor's laboratory tests demonstrated low LDL cholesterol and apolipoprotein levels. Because mutations in messenger RNAs of microsomal triglyceride transfer protein and apolipoprotein B genes were excluded neither in the recipient nor in the donor, both were clinically diagnosed as being heterozygous for FHBL. We successfully treated the recipient with heterozygous FHBL-induced recurrent NASH after liver transplantation using our diet and exercise programs..
1714. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Tomohiro Iguchi, Naotaka Hashimoto, Yoshihiko Maehara, Rituximab, IVIG, and plasma exchange without graft local infusion treatment
A new protocol in ABO incompatible living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3181adcae6, 88, 3, 303-307, 2009.08, BACKGROUND. Although graft local infusion (GLI) treatment via the portal vein or the hepatic artery has been the pivotal strategy in ABO incompatible (ABOi) living donor liver transplantation (LDLT) in Japan, the procedure is associated with a high rate of catheter-associated complications. METHODS. A new ABOi-LDLT protocol has been implemented using rituximab, intravenous immune globulin (IVIG), plasma exchange (PE), and splenectomy, without using GLI, on four patients, since 2007. Three other patients, treated before 2007, received GLI. RESULTS. Three of the four patients with liver cirrhosis received rituximab over 3 weeks before LDLT, followed by PEs and post-LDLT IVIG, resulting in no rebound elevation of the isoagglutinin titers. The remaining patient, with fulminant hepatitis, received rituximab 3 days before the LDLT, resulting in antibody-mediated rejection, successfully treated by IVIG and PE. All four patients that were treated with the new protocol are alive, 26, 8, 6, and 5 months after ABOi-LDLT with normal liver function. Two of the three other patients with GLI, before 2007, had catheter-associated complications, including one graft loss. CONCLUSION. The new ABOi-LDLT protocol using rituximab, IVIG, and PE, without the use of GLI, therefore seems to be a safe and an effective treatment modality..
1715. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Shigeyuki Nagata, Yoshihiko Maehara, Potential risk in using hepatic veins of a native liver for reconstructing accessory veins in right lobe living donor graft, Transplantation, 10.1097/TP.0b013e3181aae502, 88, 1, 143-144, 2009.07.
1716. T. Yoshizumi, Y. Ikeda, Y. Kaneda, K. Sueishi, Ex Vivo Transfer of Nuclear Factor-κB Decoy Ameliorates Hepatic Cold Ischemia/Reperfusion Injury, Transplantation Proceedings, 10.1016/j.transproceed.2008.10.101, 41, 5, 1504-1507, 2009.06, Cold ischemia/reperfusion injury of the hepatic graft has been attributed to the release of various inflammatory cytokines. Specific inhibition of these cytokines may improve viability of the hepatic graft upon reperfusion. Herein we have assessed the efficacy of cis element decoy against nuclear factor-κB binding site delivery to the hepatic tissue in a rodent liver transplantation model. At 8 hours after reperfusion of the liver, significant reduction was noted in the livers treated with decoy in the release of cytosolic enzymes from the hepatocytes and in serum tumor necrosis factor α (P < .05). The neutrophilic infiltration into the hepatic grafts was significantly suppressed in the livers treated with decoy oligodeoxynucleotides (ODNs). Decoy ODNs against nuclear factor-κB binding site delivery improved the viability of the hepatic graft against cold ischemia/reperfusion injury in the rodent liver transplantation model..
1717. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hirofumi Kawanaka, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Hypersplenism after living donor liver transplantation, Hepato-gastroenterology, 56, 91-92, 778-782, 2009.05, Background/Aims: It has not determined whether post-transplant persistent hypersplenism (PTPH) occurs after living donor liver transplantation (LDLT). Methodology: One hundred and ninety-four patients who survived more than 6 months after LDLTs were examined for the evaluation to determine the incidence of PTPH (leukocyte counts <3,500/μL and/or platelet counts <7.5×104/μL). In addition, 154 patients without a splenectomy were evaluated for the risk factors for PTPH. Results: The incidence of PTPH was 20.1% (n=31/154), and the occurrence ranged between 1.1 and 9.9 years after the LDLT, with the mean follow-up periods of 3.3±2.5 years. Multivariate analysis showed that portal pressure >30mmHg at the time of the laparotomy (p<0.01) and post-LDLT small for size syndrome (p<0.01) are risk factors for PTPH. For those with severe portal hypertension (>30 mmHg at laparotomy), the splenectomy tended to give better survival rate (p=0.09) without increasing the rate of septic complications. Conclusions: Hypersplenism did persist in a proportion of patients after LDLT. A high-risk for PTPH, especially severe portal hypertension, may be an indication for a splenectomy during LDLT in order to achieve uncomplicated post-transplant recovery..
1718. Yusuke Arakawa, Mitsuo Shimada, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Hirohumi Kanemura, Beneficial effects of splenectomy on massive hepatectomy model in rats, Hepatology Research, 10.1111/j.1872-034X.2008.00469.x, 39, 4, 391-397, 2009.04, Aim: Possible spleno-hepatic relationships during hepatectomy remain unclear. The purpose of this study was to investigate the impact of splenectomy during massive hepatectomy in rats. Methods: Rats were divided into the following two groups: 90% hepatectomy (Hx group), hepatectomy with splenectomy (Hx+Sp group). The following parameters were evaluated; survival rate, biochemical parameters, quantitative RT-PCR for hemeoxygenase-1 (HO-1) and tumor necrosing factor α (TNFα), immunohistochemical staining for HO-1, proliferating cell nuclear antigen labeling index and liver weights. Results: The survival rate after massive hepatectomy significantly improved in Hx+Sp group as well as serum biochemical parameters, compared with Hx group (P < 0.05). HO-1 positive hepatocytes and its mRNA expression significantly increased and TNFα mRNA expression significantly decreased in Hx+Sp group compared with Hx group (P < 0.05). Moreover, liver regeneration was significantly accelerated at 48 and 72 h after hepatectomy in Hx+Sp group. Conclusions: Splenectomy had beneficial effects on massive hepatectomy by ameliorating liver injuries and promoting preferable liver regeneration..
1719. Toru Ikegami, Mitsuo Shimada, Satoru Imura, Yuji Soejima, Tomoharu Yoshizumi, Jun Hanaoka, Yuji Morine, Yoshihiko Maehara, The changes of the medial right lobe, transplanted with left lobe liver graft from living donors, Transplantation, 10.1097/TP.0b013e318195c2a3, 87, 5, 698-703, 2009.03, Background. Procurement of left lobe (LL) living donor graft with medial right lobe (mRL) might be an innovative technique. Methods. The grafts were procured from a living donor, exposing the right anterior Glissonean pedicles, after confirmation of the demarcation line by test-clamping of the right Glissonean pedicle. Based on serial computed tomography, the increase in the graft volume (GV) after addition of mRL and changes in volumes were evaluated. Results. The addition of mRL (n=7) increased GV by 48±9 g, which corresponded to a 4% increase in GV-to-standard liver volume ratio. After transplantation, mRL volume has increased in all cases. The regeneration rate of the mRL and other LL segments 1 month after transplantation was 61%±18% and 146%±15%, respectively. Viable hepatic parenchyma with marginal bile duct dilatations in transplanted mRL was observed in all the cases. Marginal enhancement was observed in those cases with promoted regeneration of transplanted mRL. In the cranial part of the mRL, portal branching from the left portal vein, over the middle hepatic vein, was observed in all cases. Conclusion. This technique affords an increase in GV in living donor LL procurement, and should increases the application of LL grafts in living donor liver transplantation..
1720. Toru Ikegami, Takeo Toshima, Kazuki Takeishi, Yuji Soejima, Hirofumi Kawanaka, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Bloodless Splenectomy During Liver Transplantation for Terminal Liver Diseases with Portal Hypertension, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2008.10.034, 208, 2, e1-e4, 2009.02.
1721. Akinobu Taketomi, Hiroto Kayashima, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, Donor risk in adult-to-adult living donor liver transplantation
Impact of left lobe graft, Transplantation, 10.1097/TP.0b013e3181943d46, 87, 3, 445-450, 2009.02, Background.: To ensure donor safety in adult-to-adult living donor liver transplantation, we established a selection criterion for donors in which left lobe (LL) was the first choice of graft. Methods.: Two hundred six consecutive donors were retrospectively studied. Donors were divided into two groups according to graft type: LL graft (n=137) and right lobe (RL) graft (n=69). Results.: Although mean intraoperative blood loss of LL was significantly increased compared with RL, mean peak postoperative total bilirubin levels and duration of hospital stay after surgery were significantly less for LL than RL (P<0.05). No donor died or suffered a life-threatening complication during the study period. The overall complication rate was 34.0%, including biliary complications in 5.3%. The number of biliary complications was four (2.9%) in LL and seven (10.1%) in RL (P<0.05). Logistic regression analysis revealed that only graft type (LL vs. RL) is significantly related to the occurrence of biliary complications (odds ratio 0.11; P=0.0012). The cumulative overall graft survival rates in the recipients with LL were not significantly different from that in the recipients with RL. Conclusions.: LL grafting should be considered favorably when selecting donors for adult-to-adult living donor liver transplantation..
1722. Akinobu Taketomi, Kensaku Sanefuji, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uhciyama, Toru Ikegami, Noboru Harada, Yoichi Yamashita, Keishi Sugimachi, Hiroto Kayashima, Tomohiro Iguchi, Yoshihko Maehara, Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation, Transplantation, 10.1097/TP.0b013e3181943bee, 87, 4, 531-537, 2009.02, BACKGROUNDS.: Because many patients who did not meet the Milan criteria have survived long after undergoing living donor liver transplantation (LDLT), extended criteria for recipient with hepatocellular carcinoma (HCC) are therefore considered to be necessary. METHODS AND RESULTS.: A total of 90 consecutive adult LDLT recipients with HCC between 1996 and 2007 were reviewed. The recurrence-free survival rates of all 90 patients were 86.0%, 81.3%, and 81.3% at 1, 3, and 5 years, respectively. Fourteen of 90 patients developed a recurrence of tumor after the LDLT. The tumor recurrences were diagnosed within 1 year after the LDLT in 11 (78.6%) patients. In a multivariate analysis, both the tumor size of less than 5 cm (P=0.0202) and the des-gamma-carboxy prothrombin (DCP) level of less than 300 mAU/mL (P=0.0001) were found to be favorable independent factors for the recurrence of HCC after LDLT. Therefore, the authors devised new selection criteria for HCC patients (a tumor size of <5 cm or a DCP of <300 mAU/mL). The 1-, 3-, and 5-year overall or recurrence-free survival rates of the 85 patients who met the new criteria were 92.3%, 85.9%, and 82.7%, or 90.5%, 87.0%, and 87.0%, respectively, which were significantly different from those of the five patients who did not meet the new criteria (P<0.0001). CONCLUSIONS.: A combination of two factors, namely the tumor size and the DCP level, was found to be useful for expanding the selection of LDLT candidates for HCC..
1723. Kensaku Sanefuji, Hiroto Kayashima, Tomohiro Iguchi, Keishi Sugimachi, Yo Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Takashi Nishizaki, Akinobu Taketomi, Yoshihiko Maehara, Characterization of hepatocellular carcinoma developed after achieving sustained virological response to interferon therapy for hepatitis C, Journal of Surgical Oncology, 10.1002/jso.21176, 99, 1, 32-37, 2009.01, Background: Interferon (IFN) reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). However, HCC develops in the some patients who have achieved a sustained virological response (SVR). The aim of this study was to clarify the features and prognosis of SVR patients who developed HCC. Materials and Methods: Twenty-six patients who underwent curative hepatectomy for initial HCC after IFN therapy were closely investigated. Twenty patients who were seropositive for HCV-RNA (non-SVR), and a further 6 patients who achieved SVRs (SVR) were included. We analyzed the clinicopathological features, immunological expression levels of p53 and whether HCV-RNA is present in the excised liver. Results: The liver functions of the SVR group were almost better than those of the non-SVR group. However, there was no significant difference in pathological features, surgical factors and prognosis between the groups. In one case with SVR out of eight specimens tested was HCV-RNA detected in the non-cancerous tissue. Immunohistochemistry revealed overexpression of p53 in eight HCCs (100%) from SVR patients. Conclusion: Recurrent HCC still developed after the curative hepatectomy, even if viral elimination had been successful. And molecular alterations in hepatocarcinogenesis of SVR patients might be different from those of CHC patients..
1724. Yuji Soejima, Takasuke Fukuhara, Kazutoyo Morita, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara, A simple hilar dissection technique preserving maximum blood supply to the bile duct in living donor liver transplantation, Transplantation, 10.1097/TP.0b013e318188d4dc, 86, 10, 1468-1469, 2008.11, Duct-to-duct reconstruction is associated with a higher incidence in biliary strictures in living donor liver transplantation (LDLT). However, a standard dissection technique for the recipient's bile duct has not been established. Here, we describe a simple bile duct dissection technique preserving maximum vascular integrity during total hepatectomy of the recipient. The present technique might facilitate duct-to-duct bile duct reconstruction in both right and left lobe LDLT and, thus, contribute to reduce biliary complications such as biliary strictures. We believe that this technique can be a standard in the field of LDLT..
1725. Takuya Tokunaga, Toru Ikegami, Tomoharu Yoshizumi, Satoru Imura, Yuji Morine, Hisamitsu Shinohara, Mitsuo Shimada, Beneficial effects of fluvastatin on liver microcirculation and regeneration after massive hepatectomy in rats, Digestive Diseases and Sciences, 10.1007/s10620-008-0241-y, 53, 11, 2989-2994, 2008.11, Fluvastatin, the first entirely synthetic statin, has a significant cholesterol-lowing effect comparable with other statins. In addition, it has been shown to inhibit oxidative stress and improve vascular endothelial function. The aim of this study was to clarify the pretreatment effects of fluvastatin on liver function after massive hepatectomy in rats. Six-week-old male Wister rats were divided into two groups: a fluvastatin group (group F), pretreated with oral administration of fluvastatin (20 mg/kg per day) for 2 days before 90% hepatectomy; and a control group (group C), pretreated with vehicle for 2 days before hepatectomy. Animals were sacrificed at 0, 12, 24, 48, and 72 h after hepatectomy. The liver regeneration rate, liver function tests, and hepatic stellate cell activation were examined. The liver regeneration rate in group F was significantly higher at 72 h after hepatectomy (P < 0.05). The serum level of total bilirubin in group F was significantly lower at 48 h after hepatectomy (P < 0.05). Sinusoidal area in group F was maintained histologically. Furthermore, the expression of alpha smooth-muscle actin (α-SMA) protein in the liver was inhibited in group F at 48 h after hepatectomy. This study demonstrated the beneficial effects of fluvastatin in a lethal massive hepatectomy model using rats, with improved hepatic regeneration and microcirculations, by inhibiting the activation of hepatic stellate cells..
1726. Toru Ikegami, Akinobu Taketomi, Ryuji Ohta, Yiji Soejima, Tomoharu Yoshizumi, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara, The risks of HBV infection after liver transplantation from HBc antibody positive donor to HBs antibody positive recipient, Hepato-gastroenterology, 55, 88, 2162-2165, 2008.11, The rate of de novo hepatitis B infection, after liver transplantation from a hepatitis B core antibody (HBcAb) (+) donor to a surface antibody (HBsAb) (+) recipient bas not yet elucidated. Four recipients with HBsAb (+) and HBcAb, (+), who received living donor grafts from HBcAb (+) donors were herein reviewed. They received lamivudine monotherapy: three patients with HBsAb titer >10 IU/L did not demonstrate the onset of HBsAg, whereas one patient with HBsAb titer <10 IU/L developed hepatitis B antigen (HBsAg) 4 years after transplantation. An HBsAb (+) patient with a titer of >10 IU/L is therefore considered not to require combination therapy when receiving an HBcAb (+) liver graft. However, a great deal of caution is necessary in patients with a negative or low HBsAb titers <10 IU/L..
1727. Y. Soejima, S. Ueda, K. Sanefuji, H. Kayashima, T. Yoshizumi, T. Ikegami, Y. Yamashita, K. Sugimachi, T. Iguchi, A. Taketomi, Y. Maehara, Sequential pancreaticoduodenectomy after living donor liver transplantation for cholagiocacinoma, American Journal of Transplantation, 10.1111/j.1600-6143.2008.02346.x, 8, 10, 2158-2162, 2008.10, Liver transplantation (LT) for patients with primary sclerosing cholangitis (PSC) is often contraindicated due to concomitant occurrence of cholangiocarcinoma (CC). Cases of simultaneous pancreaticoduodenectomy (PD) with LT have been sporadically reported; however, the applicability of such an invasive procedure to patients with CC has not been validated. We report here a case of sequential PD performed 44 days after a successful living donor liver transplantation (LDLT) using a left lobe graft. Although a clear pancreatic juice leakage through the drain persisted for days after surgery, the patient recovered from the complication and was discharged 32 days after the procedure. Currently, 1 year after LDLT, the patient is doing well with no evidence of recurrence. In conclusion, a sequential PD following LDLT is a safe and feasible option to treat CC complicating PSC. Long-term follow-up and accumulation of cases are necessary to evaluate the effectiveness of this procedure for this complicated disease..
1728. Hiroto Kayashima, Akinobu Taketomi, Yusuke Yonemura, Hideki Ijichi, Noboru Harada, Tomoharu Yoshizumi, Yuji Soejima, Kengo Yoshimitsu, Yoshihiko Maehara, Accuracy of an age-adjusted formula in assessing the graft volume in liver donor liver transplantation, Liver Transplantation, 10.1002/lt.21547, 14, 9, 1366-1371, 2008.09, In living donor liver transplantation, the estimated graft volume (GV) from young donors tends to be overestimated. One reason for this error may be a decrease in GV due to dehydration by University of Wisconsin (UW) solution. The aim of this study was to clarify (1) the usefulness of an age-adjusted formula and (2) the correlation between the decrease in GV and donor age. First, we created the age-adjusted formula using regression analysis retrospectively in 167 donors, and we evaluated the difference in the error ratio of GV from the age-adjusted formula and 3-dimensional computed tomography (3D-CT) prospectively in 49 donors. Second, we measured intraoperative GV both before and after flushing with UW solution and calculated the decrease ratio, and we then evaluated the difference in the decrease ratio between young donors and older donors prospectively in 41 donors. The age-adjusted formula was created as follows: age-adjusted GV = 70.767 + (0.703 × GV estimated with 3D-CT volumetry) + (1.298 × donor age). The mean error ratio for the age-adjusted formula (9.6%) was significantly lower than that from 3D-CT (14.0%). The mean decrease ratio in all 41 donors was 5.4%, and that in young donors (6.9%) was significantly higher than that in older donors (4.4%). In conclusion, although younger donor age is a major factor for estimation errors in hepatic volumetry, our age-adjusted formula is very useful in reducing the error in estimating GV..
1729. Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Noboru Harada, Yo Ichi Yamashita, Hirofumi Kawanaka, Takashi Nishizak, Yoshihiko Maehara, The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft, Transplant International, 10.1111/j.1432-2277.2008.00678.x, 21, 9, 833-842, 2008.09, Small-for-size (SFS) graft syndrome is one of the major causes of graft loss in living donor liver transplantation (LDLT). We examined whether splenectomy is beneficial for overcoming SFS graft syndrome in LDLT. The patients were classified into two groups: the Sp (-) group (n = 69), in which splenectomy was not performed, and the Sp (+) group (n = 44), in which it was. The incidence of SFS graft syndrome was investigated. Risk factors of SFS graft syndrome were identified by univariate- and multivariate analysis. To clarify whether splenectomy is beneficial for patients with a SFS graft, subgroup analysis was performed for patients who had a graft weight-to-standard liver weight (GW-SLW) ratio of 40% or less (n = 50). Thirty-one of 113 patients developed SFS graft syndrome. A multivariate analysis identified that having a male donor was an independent risk factor of SFS graft syndrome. SFS graft syndrome occurred in 11 of 50 patients with a GW-SLW ratio <40%, and Sp (-) was an independent risk factor for the occurrence of SFS graft syndrome in patients (P = 0.014). Simultaneous splenectomy is favorable for overcoming SFS graft syndrome in LDLT patients with a GW-SLW of 40% or less..
1730. Toru Ikegami, Mitsuo Shimada, Satoru Imura, Tomoharu Yoshizumi, Yusuke Arakawa, Takuya Tokunaga, Yuji Morine, Hirofumi Kanemura, The timing of liver transplantation after primary hepatectomy for hepatocellular carcinoma
A special reference to recurrence pattern and milan criteria, Transplantation, 10.1097/TP.0b013e3181814de2, 86, 5, 641-646, 2008.09, INTRODUCTION.: Hepatic resection (HR) is commonly applied as first-line treatment of hepatocellular carcinoma (HCC) even in the era of liver transplantation (LT). METHODS.: Outcomes and detailed recurrence pattern of 80 patients, who underwent curative HR for HCC were examined referring to Milan criteria. RESULTS.: (I) After HR for HCCs exceeding Milan criteria (n=41), recurrence within the criteria was observed in 13 patients (group-A) and recurrence not-meeting the criteria was observed in 22 patients (group-B). group-A showed better 3-year recurrence-free survival rate than group-B (85.7% vs. 23.9%, P<0.05). Tumor size more than or equal to 6 cm was identified as the significant factor for having recurrence as in group-A pattern (P<0.05). Among the patients in group-A, re-recurrence after treating recurrent HCC was observed in eight patients (61.5%) with increased rate of extra-Milan criteria recurrence at 12 months from the initial recurrence. (II) After HR for HCCs meeting Milan criteria (n=39), recurrences within the criteria was observed in 15 patients (group-C) and recurrence not-meeting the criteria was observed in five patients (group-D). The 3-year recurrence-free survival rate was 62.8% in group-C and 40.0% in group-D (P<0.05). Increased rate of extra-Milan re-recurrence was observed later than 12 months from the recurrence in group-C. CONCLUSIONS.: For HCCs not meeting Milan criteria, secondary LT after primary HR could be applied for a proportion of cases with less aggressiveness. For those meeting Milan criteria, primary LT should be the first therapeutic option. However, secondary LT could be offered for those with re-recurrence within criteria after primary HR..
1731. Satoru Imura, Mitsuo Shimada, Kotaro Miyake, Tetsuya Ikemoto, Yuji Marine, Tomoharu Yoshizumi, A new technique to acquire additional liver volume for left lobe graft in living donor liver transplantation, Hepato-gastroenterology, 55, 85, 1206-1210, 2008.07, Background/Aims: Left lobe graft is an ideal option to minimize potential risk for the donor in adult living-donor liver transplantation (LDLT). However, its use is restricted due to size limitations. The purpose of this study was to determine the impact of a new technique for the acquisition of additional liver volume for left lobe graft. Methodology: Three donors underwent left hepatic lobectomy by exploiting a new technique as follows: a demarcation line was marked by clamping the right first Glisson's pedicle. A parenchymal transection plane was located 1cm right side from the demarcation line and just on the left side of the right anterior Glisson's pedicle. A part of the anterior segment added to the left lobe graft by this procedure belonged to right anterior segment by preoperative CT. The preoperative volumetry of the liver was performed using the 3D-CT software, which was able to calculate total liver volume and the volume of each vessel's territories. Additional liver volume was calculated by preoperative CT scan and defined as part of the perfusion area by the right anterior portal branch. Blood perfusion of the additional liver area was postoperatively assessed by dynamic CT, and graft outcome was also evaluated. Results: An additional gain ranged from 40mL to 51mL (mean 41.8mL). GV/SLV was 35.7, 60.0, and 41.0%. The rate of additional volume in GV/SLV ranged from 7.2-8.4% (mean 7.6%). All grafts functioned well. The CT scan performed on early postoperative period confirmed excellent blood perfusion the additional segment. No complication attributable to small-for-size graft was noted. Conclusions: This new technique for left lobe graft harvesting proved a promising approach to gain additional volume, thereby avoiding small-for-size graft in adult LDLT..
1732. Tomoharu Yoshizumi, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hiroto Kayashima, Yo Ichi Yamashita, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara, Graft size, donor age, and patient status are the indicators of early graft function after living donor liver transplantation, Liver Transplantation, 10.1002/lt.21462, 14, 7, 1007-1013, 2008.07, No reliable model for predicting early graft function and patient survival after living donor liver transplantation (LDLT) exists. The aim of this study was to establish a new formula for predicting early graft function and prognosis using technetium-99m galactosyl-human serum albumin (Tc-GSA) liver scintigraphy. The ratio of the hepatic uptake ratio of Tc-GSA to the clearance index of Tc-GSA (LHL/HH) was determined 7 days after LDLT. There were 22 patients with a ratio greater than 1.3 and 6 patients with a ratio less than 1.3. Graft function on the 14th postoperative day (POD) was compared between the 2 groups. A new formula to predict the LHL/HH score was established as follows: LHL/HH (predictive score) = 0.011 × graft weight (%) - 0.016 × donor age - 0.008 × Model for End-Stage Liver Disease score - 0. 15 × shunt (if present) + 1.757 (r2 = 0.497, P < 0.01). This predicted LHL/HH ratio was compared to the graft function on POD 14 for 110 LDLT patients. The total bilirubin JB) and prothrombin time international normalized ratio (PT-INR) in the group with an LHL/HH score ≥ 1.3 were lower than those in the group with an LHL/HH score < 1.3. The TB, PT-INR, and volume of ascites in the group with a predictive score ≥ 1.3 (n = 86) were lower than those in the group with a score < 1.3 (n = 24). The 6-month survival probability was improved in the group with a predictive score ≥ 1.3. In conclusion, this preoperative calculated LHL/HH score is correlated with graft function and short-term prognosis. Thus, this predictive model may allow transplant surgeons to use a living donor left lobe graft with greater confidence..
1733. Toru Ikegami, Yuji Soejima, Ryuji Ohta, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Yoshihiko Maehara, Living donor liver transplantation for hepatitis B associated liver diseases
A 10-year experience in a single center, Hepato-gastroenterology, 55, 85, 1445-1449, 2008.07, Background/Aims: Hepatic failure associated with hepatitis B virus (HBV) is one of the main indications for living donor liver transplantation (LDLT). Methodology: Twenty-nine LDLTs, including liver cirrhosis due to HBV (LC-B) (n=17) and fulminant hepatitis B (FH-B) (n=12) were reviewed. Prophylaxis for reinfection was performed with a combination of lamivudine, or hepatitis B immune globulin (HBIG) or adefovir, depending on the viral status. The changes in serological markers, recurrence and survival rate were examined. Results: There were 3 patients with re-emergencies of HBV surface antigen (HBsAg): suspension of HBIG for giving vaccination for HBV (n=1), HBsAg positive donor (n=1) and non-compliance for HBIG (n=1). All patients with YMDD mutants (n=9), except the case with HBsAg positive donor (n=1), were successfully protected by the triple therapy of lamivudine, adefovir and HBIG. No graft loss was due to the recurrence of HBV. Conclusion: The basic strategy using a combination of HBIG and antiviral agents gave acceptable long-term outcomes for LDLT for HBV associated liver diseases. The close monitoring of HBV viral status after transplantation is still crucial in managing these patients..
1734. T. Ikegami, A. Taketomi, R. Ohta, Y. Soejima, T. Yoshizumi, M. Shimada, Y. Maehara, Donor Age in Living Donor Liver Transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2008.02.084, 40, 5, 1471-1475, 2008.06, Background: We sought to elucidate the influence of donor age in living donor liver transplantation (LDLT) using either left lobe (LL) or right lobe (RL) grafts. Methods: Recipients (n = 232) were categorized as: group O/LL (LL, donor age >50, n = 20); group Y/LL (LL, donor age ≤50, n = 140); Group O/RL (RL, donor age >50, n = 12); and group Y/RL (RL, donor age ≤50, n = 61). We compared post-LDLT graft functions. Results: Among LL LDLT, the incidence of small-for-size syndrome was significantly greater for group O/LL compared with group Y/LL (60.0% vs 16.3%, P < .01). However, the cumulative 5-year graft survivals were 73.8% in group O and 76.7% in group Y without substantial difference. In RL LDLT, the post-LDLT morbidity and mortality were similar for group O/RL and group Y/RL. Conclusion: Partial liver grafts, even though LL grafts, from older donors can be used safely with caution in LDLT..
1735. T. Yoshizumi, A. Taketomi, H. Kayashima, Y. Yonemura, N. Harada, H. Ijichi, Y. Soejima, T. Nishizaki, Y. Maehara, Estimation of Standard Liver Volume for Japanese Adults, Transplantation Proceedings, 10.1016/j.transproceed.2008.02.082, 40, 5, 1456-1460, 2008.06, Introduction: Accurate pretransplant estimation of the recipient's standard liver volume (SLV) is important. The purpose of this study was to compare reported formulas for clinical estimation of liver volume among Japanese adults. Methods: We reviewed data on 70 healthy adults (46 men, 24 women, ages 20 to 65 years old) evaluated for living donor liver transplantation. Liver volume (LV) was measured using two- or three-dimensional computed tomography volumetry (CTV). The formulas of DeLand (LV = 1020 × body surface area [BSA] - 220), Urata (LV = 706.2 × BSA + 2.4), Noda (LV = 50.12 × BW0.78), Heinemann (LV = 1072.8 × BSA - 345.7), Vauthey (LV = 18.51 × BW + 191.8) and Yoshizumi (LV = 772 × BSA) were applied to estimate LV. We calculated the differences for individual donors betwen CTV and LV estimated by each formula. Results: Mean LVs as estimated by the formulae of DeLand and Heinemann et al were significantly greater (P < .01) than the mean CTV, while LV estimated by the formula of Urata was significantly less (P < .05) than the CTV. The formulas of DeLand and Heinemann overestimated LV, while the formula of Urata underestimated it. The formulae of Noda et al and Yoshizumi et al tended to underestimate the LV when the CTV was greater than 1600 cm3. When the Yoshizumi formula was applied, the number of donors with an acceptable difference (±15%) between CTV and estimated LV was 55 (78.6%). Conclusions: The Yoshizumi formula was applicable, especially for patients with a BSA < 2.0, whereas the well-known Urata formula made LV underestimates..
1736. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Characteristics of biliary reconstruction using a T-tube as compared with other methods in left-lobe adult living-donor liver transplantation, Journal of Hepato-Biliary-Pancreatic Surgery, 10.1007/s00534-007-1259-9, 15, 3, 346-347, 2008.05.
1737. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Shinji Itoh, Yo Ichi Yamashita, Yoshihiko Maehara, Hilar anatomical variations in living-donor liver transplantation using right-lobe grafts, Digestive surgery, 10.1159/000121907, 25, 2, 117-123, 2008.05, Background: Living-donor liver transplantation using a right-lobe graft has increased the frequency of hilar anatomical variations despite its advantage of a larger graft volume. Methods: Sixty-seven living-donor liver transplantations using right-lobe grafts are reviewed, regarding the surgical anatomy of hilar vascular and biliary systems. Results: The portal anatomy was classified into four types. The incidence of double portal vein was 6.0% (n = 4), and for such cases a unified orifice (n = 1) or a Y-graft (n = 3) was used for reconstruction. The arterial system was classified into five types. The incidence of arterial complications was 6.0% (n = 4), all of which occurred in cases where the graft artery was connected to the recipient's right hepatic artery. The biliary system was classified into four types. The incidence of a double bile duct was 7.5% (n = 5), and that of a unified one was 29.8% (n = 20). Hepaticojejunostomy was more prone to biliary sepsis (25.0%) and bile leakage (18.8%) than duct-to-duct connection (0 and 2%, respectively). Conclusion: Hilar anatomical variations in right-lobe living-donor liver transplantation could be managed after preoperative detailed evaluation of the graft and intraoperative appropriate surgical decision and techniques..
1738. Yuji Soejima, Naoyuki Ueda, Takasuke Fukuhara, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara, One-step venous reconstruction for a right lobe graft with multiple venous orifices in living donor liver transplantation, Liver Transplantation, 10.1002/lt.21401, 14, 5, 706-708, 2008.05.
1739. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoshihiko Maehara, Stenotrophomonas maltophilia bacteremia after living donor liver transplantation
Report of a case, Surgery today, 10.1007/s00595-007-3622-5, 38, 5, 469-472, 2008.05, Stenotrophomonas maltophilia (previously named Xanthomonas maltophilia) is an aerobic, nonfermentive, Gram-negative bacillus that is widespread in the environment. It is considered to be an organism with a limited pathogenic potential, which is rarely capable of causing diseases in humans other than in those who are in an immunocompromised state. In this study, we outline the case of a patient with Stenotrophomonas maltophilia bacteremia after living donor liver transplantation, which showed the clinical signs of severe sepsis and was resistant to almost all antibiotics. However, we successfully treated the patient with the antibiotics trimethoprim-sulfamethoxazole (TMP/SMX) and minocycline hydrochloride (MINO), and performed endotoxin-absorbing therapy using polymyxin B (PMX) to remove the endotoxin from Gramnegative bacillus as well as continuous hemodiafiltration (CHDF) to remove inflammatory cytokines. To the best of our knowledge, this is the first report on the treatment of Stenotrophomonas maltophilia bacteremia after living donor liver transplantation..
1740. Kotaro Miyake, Tomoharu Yoshizumi, Satoru Imura, Koji Sugimoto, Erdenebulgan Batmunkh, Hirofumi Kanemura, Yuji Morine, Mitsuo Shimada, Expression of hypoxia-inducible factor-1α, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma
Correlation with poor prognosis with possible regulation, Pancreas, 10.1097/MPA.0b013e31815f2c2a, 36, 3, e1-e9, 2008.04, OBJECTIVES: Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor that plays an important role in tumor growth and metastasis. Inhibition of histone deacetylase shows a marked inhibition of HIF-1α expression; however, the association between HIF-1α and histone deacetylase 1 (HDAC1), metastasis-associated protein 1 (MTA1) is not fully understood. METHODS: Hypoxia-inducible factor 1α, HDAC1, and MTA1 expressions were detected by immunohistochemistry in 39 pancreatic carcinoma patients. The correlations between the expression of HIF-1α, HDAC1, or MTA1 and clinical features and the prognosis were analyzed. RESULTS: Hypoxia-inducible factor 1α, HDAC1, and MTA1 positive stainings were found in 41%, 56%, and 31%, respectively. There was no correlation between HIF-1α, HDAC1, or MTA1 expression levels and any clinical parameters. The survival rate for patients with HIF-1α and HDAC1-positive stainings were significantly lower than for patients with HIF-1α and HDAC1-negative stainings. The MTA1 overexpression group did not have a significantly lower prognosis than the MTA1 underexpression group. The survival rate for the HDAC1(+)/MTA1(2-3) group was significantly lower than for the other groups. CONCLUSIONS: These results suggest that HIF-1α expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis for pancreatic carcinoma and indicates that HIF-1α and HDAC1/MTA1 are a promising therapeutic target in pancreatic carcinoma treatment..
1741. Yuji Soejima, Makoto Meguro, Akinobu Taketomi, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Shinji Ito, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara, Left lobe living donor liver transplantation in an adult patient with situs inversus
Technical considerations, Transplant International, 10.1111/j.1432-2277.2007.00607.x, 21, 4, 384-389, 2008.04, Situs inversus (SI) is a rare congenital disorder involving a complete mirror image of the thoracic and abdominal organs. Living donor liver transplantation (LDLT) in SI cases poses particular challenges on account of its technical complexity, and only a few cases have been reported. Here, we present an adult with SI who was managed successfully by LDLT using a left lobe graft. Some technical modifications, including triangulated anastomosis of the hepatic vein, were required but no vascular graft was necessary. Graft function and vascular integrity were excellent throughout the postoperative course, although sepsis secondary to wound infection with methicillin-resistant Staphylococcus aureus developed. In conclusion, LDLT using a left lobe graft is a feasible procedure for patients with SI, even for adults. Therefore, this condition, while rare, should not be a contraindication for LDLT. Meticulous preoperative simulation and planning of the vascular reconstruction are important steps in LDLT for this rare anomaly..
1742. Y. Soejima, A. Taketomi, T. Ikegami, T. Yoshizumi, H. Uchiyama, Y. Yamashita, M. Meguro, N. Harada, M. Shimada, Y. Maehara, Living donor liver transplantation using dual grafts from two donors
A feasible option to overcome small-for-size graft problems?, American Journal of Transplantation, 10.1111/j.1600-6143.2008.02153.x, 8, 4, 887-892, 2008.04, Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small-for-size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large-size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small-for-size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small-for-size graft problems without increasing independent donor risks..
1743. Shigeyuki Nagata, Mitsuo Shimada, Yuji Soejima, Takashi Nishizaki, Tomoharu Yoshizumi, Yoshihiko Maehara, Adult-to-adult living donor liver transplantation in severe portosystemic shunt cases, Hepato-gastroenterology, 55, 82-83, 666-669, 2008.03, To date, the need for spontaneous portosystemic shunt division during adult-to-adult living donor liver transplantation (LDLT) remains unknown. This study reports 2 patients with large portosystemic shunts who required LDLT. The first patient was a 40-year-old male with liver cirrhosis due to hepatitis C. The angiogram showed splenosystemic shunts with hepatopetal flow. Shunt occlusion was not performed after implanting a small-size graft because sufficient portal blood flow was observed. On the first postoperative day, portal blood flow was not detected; therefore shunt occlusion was performed and the portal blood flow was restored. The second patient was a 51-year-old female with primary biliary cirrhosis. Marked collateral circulation with hepatofugal flow was observed. Shunt occlusion was performed after implanting a medium-size graft. Postsurgery, hepatopetal portal blood flow was observed and the postoperative course was satisfactory. These cases demonstrate that large portosystemic shunts should be ligated to maintain adequate portal blood flow that corresponds to the graft volume..
1744. Shinji Shimoda, Kenichi Harada, Hiroaki Niiro, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Koichi Tsuneyama, Minoru Nakamura, Atsumasa Komori, Kiyoshi Migita, Yasuni Nakanuma, Hiromi Ishibashi, Carlo Selmi, M. Eric Gershwin, Biliary epithelial cells and primary biliary cirrhosis
The role of liver-infiltrating mononuclear cells, Hepatology, 10.1002/hep.22102, 47, 3, 958-965, 2008.03, Primary biliary cirrhosis (PBC) is characterized by the highly selective autoimmune injury of small intrahepatic bile ducts, despite widespread distribution of mitochondrial autoantigens. On this basis, it has been suggested that the targeted biliary epithelial cells (BECs) play an active role in the perpetuation of autoimmunity by attracting immune cells via chemokine secretion. To address this issue, we challenged BECs from patients with PBC and controls using multiple Toll-like receptor (TLR) ligands as well as autologous liver-infiltrating mononuclear cells (LMNCs) with subsequent measurement of BEC phenotype and chemokine production and LMNC chemotaxis by quantifying specific chemokines. Our data reflect that BECs from PBC patients and controls express similar levels of TLR subtypes, CD40, and human leukocyte antigen DRα (HLA-DRα) and produce equivalent amounts of chemokines in our experimental conditions. Interestingly, however, BEC-expressed chemokines elicit enhanced transmigration of PBC LMNCs compared with controls. Furthermore, the addition of autologous LMNCs to PBC BECs led to the production of higher levels of chemokines and enhanced the expression of CD40 and HLA-DRα. Conclusion: We submit that the proinflammatory activity of BECs in PBC is secondary to the intervention of LMNCs and is not determined per se. These data support the hypothesis that BECs are in fact "innocent victims" of autoimmune injury and that the adaptive immune response is critical in PBC..
1745. Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Yoshihiko Maehara, Hiroyuki Kuwano, Is an elderly recipient a risk for living donor adult liver transplantation?, Hepato-gastroenterology, 55, 82-83, 653-656, 2008.03, Background/Aims: In cadaveric liver transplantation, it has been reported that elderly recipients over 60 years are at risk because of high incidence of complication and malignancy. However, in living-donor adult liver transplantation (LDALT), it is unclear whether the elderly recipient is risky or not risky. In this study, the outcome after LDALT of elderly patients has been evaluated. Methodology: One hundred twenty two consecutive LDALT recipients were studied. The recipients were divided into an elderly group (older than 60 yrs, n=21), and a control group (younger than 60 yrs, n=101). Comparative examination of background factors, postoperative complications and de novo malignancy was carried out. Results: Elderly patients more frequently received transplantation for hepatocellular carcinoma. Pretransplant liver damage such as Child-Pugh, MELD or bilirubin level was same among the groups. There was no significant difference in posttransplant complications except renal failure. Postoperative renal failure (postoperative creatinine level over 2mg/dL) occurred in 29% (n=5) of the elderly group vs. 8% (n=6) of the control group. De novo malignancy occurred in 1 case (lung) in the elderly group and 1 case (Vater) in the control group. In the control group, the 1, 3 and 5 year patient survival rates were 78.5%, 73.1% and 71.4%, respectively. And in the elderly group, the 1, 3 and 5 year patient survival rates were 85.7%, 81.0% and 70.8%, respectively. Conclusions: It may be, we concluded that living donor adult liver transplantation is good treatment for end stage liver diseases in elderly recipients over 60 years. However caution should be taken in the administration of medicine, including immunosuppressants or antibiotics, do to a propensity for postoperative renal failure in elderly recipients..
1746. Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Yo Ichi Yamashita, Yoshihiko Maehara, Liver transplantation for hepatocellular carcinoma, Journal of Hepato-Biliary-Pancreatic Surgery, 10.1007/s00534-007-1296-4, 15, 2, 124-130, 2008.03, The role of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) has evolved over the past two decades, and transplantation has become one of the few curative treatment modalities for patients with HCC. Early results were poor, but the current restrictive selection criteria can yield excellent results. This review will discuss recent issues in the field, including (1) factors affecting the recurrence of HCC after LT; (2) the effect of downstaging HCC before LT, including transarterial catheter chemoembolization (TACE) and radiofrequency ablation (RFA); and (3) living-donor versus deceased-donor liver transplantation for HCC patients. The most important factors that have been described to affect LT survival include the tumor size, vascular invasion, and the degree of tumor differentiation. Recently, tumor markers, including alpha-fetoprotein and des-gamma carboxy prothrombin, were reported as predictors of HCC recurrence after LT. Furthermore, the experience accumulated with locoregional therapies such as TACE and RFA as bridging procedures to LT, along with the reduced waiting time under the HCC-adjusted MELD (model for endstage liver disease) system for organ allocation has led to improved outcomes. With the recent advances in adult living-donor liver transplantation (LDLT), there may be a marked change in the role of liver transplantation for hepatic malignancies, in particular for HCC..
1747. Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Kensaku Sanefuji, Hiroto Kayashima, Mitsuo Shimada, Yoshihiko Maehara, Living Donor Liver Transplantation for Acute Liver Failure
A 10-Year Experience in a Single Center, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2007.08.018, 206, 3, 412-418, 2008.03, Background: Living donor liver transplantation has become an accepted treatment for various terminal liver diseases. Study Design: Forty-two living donor liver transplantations performed for acute liver failure during a 10-year period at Kyushu University Hospital were reviewed. Results: Causes of liver failure included hepatitis B (n = 12), hepatitis C (n = 1), autoimmune hepatitis (n = 2), Wilson's disease (n = 3), and unknown causes (n = 24). The graft types were: left lobe (n = 33), right lobe (n = 8), and lateral segment (n = 1). The mean graft volume to standard liver volume ratios were 42.2 ± 9.2% in left lobe grafts and 50.5 ± 3.9% in right lobe grafts (p < 0.05). Extubation was significantly delayed in grade IV encephalopathy patients (73.7 ± 18.2 hours) compared with patients with other grades (p < 0.01 to grades I and II, p < 0.05 to grade III). All other patients, except one with a subarachnoid hemorrhage, had complete neurologic recovery after transplantation. The 1- and 10-year survival rates were 77.6% and 65.5%, respectively, for grafts, and 80.0% and 68.2%, respectively, for patients. Conclusions: Outcomes of living donor liver transplantation for acute liver failure are fairly acceptable despite severe general conditions and emergent transplant settings. Living donor liver transplantation is now among the currently accepted life-saving treatments of choice for acute liver failure, although innovative medical treatments for this disease entity are still anticipated..
1748. Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Living donor liver transplantation for fulminant hepatic failure from ABO-incompatible donors [1], Transplant International, 10.1111/j.1432-2277.2007.00588.x, 21, 3, 284-285, 2008.03.
1749. Tomoharu Yoshizumi, Akinobu Taketomi, Hiroto Kayashima, Noboru Harada, Hideaki Uchiyama, Yo Ichi Yamashita, Toru Ikegami, Yuji Soejima, Takashi Nishizaki, Mitsuo Shimada, Yoshihiko Maehara, Successful treatment for a patient with hemophagocytic syndrome after a small-for-size graft liver transplantation, Hepato-gastroenterology, 55, 82-83, 359-362, 2008.03, Hemophagocytic syndrome (HPS) is a hematological disorder caused by activated T lymphocytes, which leads to the proliferation of stimulated macrophages that phagocytose and destroy circulating blood elements and their precursors within bone marrow, and lead to the further production of inflammatory cytokines. Living donor liver transplantation (LDLT) between adults has been performed to compensate for the shortage of available organs. There have been some reports concerning HPS after LDLT; however, its prognosis is disappointingly poor. In particular, there is no report of treated HPS developed after LDLT using small-for-size left lobe grafts. We herein report a case of HPS in a 63-year old woman who underwent LDLT using left lobe graft weighing only 330g. The HPS was diagnosed on postoperative day 13, and was successfully treated using a combination of intravenous immunoglobulin, granulocyte colony stimulating factor, conversion of calcineurin inhibitor and steroid pulse. The trigger of HPS may not only be systemic infection, but also hypercytokinemia caused by various factors. HPS is a fatal complication in immunologically compromised patients; however, early and accurate diagnosis could lead to an adequate treatment and improve the outcome..
1750. Mami Kanamoto, Tomoharu Yoshizumi, Toru Ikegami, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Nobuya Sano, Mitsuo Shimada, Cholangiolocellular carcinoma containing hepatocellular carcinoma and cholangiocellular carcinoma, extremely rare tumor of the liver
A case report, Journal of Medical Investigation, 10.2152/jmi.55.161, 55, 1-2, 161-165, 2008.02, Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor which was first defined by Steiner, et al. in 1957 (1). CLC is thought to be derived from Hering's canal because tumor glands of CLC are morphologically similar to cholangioles. Recently, Theise, et al. reported that Hering's canal might be composed of hepatic stem cells (3). In addition, CLC sometimes contains a hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC) component within the tumor. Those findings suggest that CLC might originate from hepatic stem cells. On the other hand, because of its low frequency, clinicopatholigical features of CLC have not been fully clarified yet. We herein report a case of a 71-year old man with CLC. Based on preoperative imagings, the hepatic tumor was diagnosed as HCC, and he underwent a partial hepatectomy. The tumor contained both a HCC and CCC-like area. In immunohistochemistry, cytokeratin (CK) 7, CK20, CAM5.2 was positive, and CK19 was negative, therefore the tumor was diagnosed as CLC. The diagnostic criteria have not been described clearly, so CLC is difficult to diagnose preoperatively. Further studies are needed to clarify the clinical and clinicopatholigical features of CLC..
1751. Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Yo Ichi Yamashita, Shinji Itoh, Yosuke Kuroda, Yoshihiko Maehara, Assessment of graft fibrosis by transient elastography in patients with recurrent hepatitis C after living donor liver transplantation, Transplantation, 10.1097/01.tp.0000297248.18483.16, 85, 1, 69-74, 2008.01, BACKGROUND. Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness and therefore can be a promising tool to evaluate liver fibrosis and avoid liver biopsy. We prospectively assessed the performance of transient elastography in patients with recurrent hepatitis C virus after living donor liver transplantation, in comparison with the surrogate serum markers. METHODS. Fifty-six patients with recurrent hepatitis C virus after living donor liver transplantation, who underwent both liver biopsy and transient elastography were included in this study. The grade of liver fibrosis (the Scheuer classification) obtained by biopsy was compared to liver stiffness measured by the transient elastography. RESULTS. The fibrosis grades were as follows: F0, n=22; F1, n=13; F2, n=9; F3, n=7; and F4, n=5. Liver stiffness values ranged from 2.9 to 72.0 kPa. The optimal cutoff values were 8.8 kPa for F≥1, 9.9 kPa for F≥2, 15.4 kPa for F≥3, and 26.5 kPa for F≥4. The area under the receiver operator characteristic curve for the diagnosis of fibrosis (F≥2) by transient elastography was 0.92, while that by hyaluronic acid, type 4 collagen, alanine aminotransferase, and the aspartate transaminase to platelets ratio index were 0.52, 0.62, 0.64, and 0.70, respectively. CONCLUSIONS. These data suggest that transient elastography is a simple, noninvasive and reliable tool to assess liver fibrosis in patients with recurrent hepatitis C virus after living donor liver transplantation..
1752. Nao Kinjo, Hirofumi Kawanaka, Morimasa Tomikawa, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Shohei Yamaguchi, Daisuke Yoshida, Yoshihiko Maehara, B-RTO for ectopic variceal bleeding after living donor liver transplantation, Hepato-gastroenterology, 55, 81, 241-243, 2008.01, Gastrointestinal bleeding (GIB) is a serious gastroenterological complication after orthotropic liver transplantation, as well as living donor liver transplantation (LDLT). Although ectopic varices are rare causes of GIB, they may lead to life-threatening bleeding and it is difficult to diagnose them. We herein report a rare case of a jejunal variceal bleeding in a recipient five years after LDLT for primary sclerosing cholangitis with successful result by balloon-occluded retrograde transvenous obliteration (B-RTO)..
1753. Akinobu Taketomi, Ken Shirabe, Jun Muto, Shohei Yoshiya, Takashi Motomura, Yohei Mano, Tohru Ikegami, Tomoharu Yoshizumi, Kenji Sugio, Yoshihiko Maehara, A rare point mutation in the Ras oncogene in hepatocellular carcinoma, Surgery today, 10.1007/s00595-012-0462-8, 43, 3, 289-292, 2013.03, Purpose: The Ras gene is one of the oncogenes most frequently detected in human cancers, and codes for three proteins (K-, N-, and H-Ras). The aim of this study was to examine the mutations in codons 12, 13 and 61 of the three Ras genes in cases of human hepatocellular carcinoma (HCC). Methods: Paired samples of HCC and corresponding non-malignant liver tissue were collected from 61 patients who underwent hepatectomy. A dot-blot analysis was used to analyze the products of the polymerase chain reaction (PCR) amplification of codons 12, 13, and 61 of K-, N- and H-Ras for mutations. Results: Only one mutation (K-Ras codon 13; Gly to Asp) was detected among the 61 patients. Interestingly, this patient had a medical history of surgery for both gastric cancer and right lung cancer. No mutations were found in codons 12 and 61 of K-Ras or codons 12, 13 and 61 of the N-Ras and H-Ras genes in any of the HCCs or corresponding non-malignant tissues. Conclusions: These findings indicated that the activation of Ras proto-oncogenes by mutations in codons 12, 13, and 61 does not play a major role in hepatocellular carcinogenesis..
1754. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Tetsuo Ikeda, Yoshihiko Maehara, A simple and secure ligation of the main pancreatic duct in distal pancreatectomy, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.10.021, 216, 3, e23-e25, 2013.03.
1755. Tetsuo Ikeda, Shohei Yoshiya, Takeo Toshima, Norifumi Harimoto, Youichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Laparoscopic distal pancreatectomy preserving the spleen and splenic vessels for benign and low-grade malignant pancreatic neoplasm., Unknown Journal, 104, 3, 54-63, 2013.03, Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) is expected to be less invasive than laparoscopic distal pancreatectomy with splenectomy. However, there are few reports regarding the details of the procedure for LSPDP, and its safety remains unclear. This study aimed to evaluate the feasibility and safety of LSPDP. Six patients underwent LSPDP from March 2009 to February 2013 in our center, and their clinical data and outcomes were reviewed retrospectively. A total of six laparoscopic distal pancreatic resections were attempted in four female and two male patients. All of the operations were successful, with an average operative time of 290.7 min (range: 211-377 min) and an average blood loss of 43.5 g (range: 0-142 g). The mean hospital stay was 11.8 days (range: 9-17days). No obvious pancreatic fistulas occurred, although pseudocysts at the stump of the pancreas were recognized in three patients on CT scans performed at 7 days postoperatively. Postoperative pathological examinations revealed two cases of serous cystadenoma in the body and tail of the pancreas, one case of serous oligocystic adenoma, one case of mucinous cystadenoma, one case of neuroendocrine tumor, and one case of solid-pseudopapillary neoplasm. LSPDP is minimally invasive, safe, and feasible for the management of benign pancreatic tail tumors, with the advantages of earlier recovery and less morbidity from complications..
1756. Yuji Soejima, Jyun Muto, Rumi Matono, Mizuki Ninomiya, Tetsuo Ikeda, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Ken Shirabe, Yoshihiko Maehara, Strategic breakthrough in adult ABO-incompatible living donor liver transplantation
Preliminary results of consecutive seven cases, Clinical Transplantation, 10.1111/ctr.12060, 27, 2, 227-231, 2013.03, ABO-incompatibility is a major obstacle to expanding exiguous donor pools in adult liver transplantation, especially in countries where grafts from deceased donors are uncommon. We present our preliminary results of ABO-incompatible (ABO-I) adult living donor liver transplantation (LDLT) using a new, simple protocol. Seven consecutive cases of ABO-I LDLT were managed by the same protocol including pre-operative administration of a single dose of rituximab (375 mg/m2) followed by three to five sessions of plasma exchange before LDLT without portal infusion therapy. The triple immunosuppression protocol consisted of tacrolimus, mycophenolate mofetil and steroids, with mycophenolate mofetil starting seven d before LDLT. Splenectomy was performed for all cases. All patients are alive (100% survival) with a mean follow-up of 852 d (715-990 d). Neither antibody-mediated nor hyperacute rejection were encountered. There was only one episode of mild acute cellular rejection, for which steroid augmentation was effective. The median preformed isoagglutinin antibody titer before plasma exchange was 256, while the median antibody titer immediately before LDLT was 16. In conclusion, adult ABO-I LDLT results were excellent - comparable or even superior to those of ABO-compatible LDLT. ABO-I adult LDLT has now become a more applicable modality without the need for an appropriate donor..
1757. Toru Ikegami, Ken Shirabe, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Yo Ichi Yamashita, Norifumi Harimoto, Takeo Toshima, Shohei Yoshiya, Tetsuo Ikeda, Yoshihiko Maehara, Strategies for successful left-lobe living donor liver transplantation in 250 consecutive adult cases in a single center, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.11.011, 216, 3, 353-362, 2013.03, Background: Living donor liver transplantation (LDLT) using left-lobe grafts was not generally recognized as feasible due to the problem of graft size. Study Design: We retrospectively evaluated strategies for successful left-lobe LDLT in 250 consecutive cases stratified into 2 eras: Era 1 (n = 121), in which surgical procedures were continually refined, and Era 2 (n = 129), in which established procedures were used. Results: Graft volume (GV) did not affect the incidence of graft function or survival. Era 2 patients had decreased portal vein (PV) pressure at closure (16.0 ± 3.5 mmHg vs 19.1 ± 4.6 mmHg, p < 0.01), increased PV flow/GV (301 ± 125 mL/min/100g vs 391 ± 142 mL/min/100g, p < 0.01), and improved graft survival rate (1-year: 90.6% vs 81.8%. p < 0.01) despite the smaller GV/standard volume (SLV) ratio (36.2% ± 5.2% vs 41.2% ± 8.8%, p < 0.01) compared with Era 1. Patients in Era 2 had lower PV pressure and greater PV flow (y = 598-5.7x, p = 0.02) at any GV/SLV compared with cases in Era 1 (y = 480-4.3x, p < 0.01), representing greater graft compliance. Univariate analysis for graft survival showed that Era 1, Model for End-Stage Liver Disease (MELD) score ≥20, inpatient status, closing portal venous pressure ≥20 mmHg, no splenectomy, and operative blood loss ≥10L were the risk factors for graft loss, and multivariate analysis showed that Era 1 was the only significant factor (p < 0.01). During Era 2, development of primary graft dysfunction was associated with inpatient recipient status (p = 0.02) and donor age ≥45 years (p < 0.01). Conclusions: The outcomes of left-lobe LDLT were improved by accumulated experience and technical developments..
1758. Hiroko Yano, Toru Ikegami, Tomoharu Yoshizumi, Tomohiko Akahoshi, Morimasa Tomikawa, Hideaki Uchiyama, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, [Total laparoscopic splenectomy for a patient with multiple surgeries including living donor liver transplantation]., Unknown Journal, 104, 3, 64-67, 2013.03, The case was a 50 years old female, with history of multiple previous surgeries including living donor liver transplantation for primary biliary cirrhosis, pancreatoduodenectomy for carcinoma in the duodenal papilla Vater, revision of Roux-en-Y anastomosis for intractable cholangitis due to short Roux limb. She was hospitalized this time for decompensated liver cirrhosis due to recurrent cholangitis, with apparent hypersplenism and risky esophageal varices. After a few session of endoscopic treatment for esophageal varices, we applied total laparoscopic splenectomy for hypersplenism in a patient with multiple surgical histories, for seeking better surgical field for safety. The surgery was completed as planned preoperatively under good surgical field..
1759. Tetsuo Ikeda, Yohei Mano, Kazutoyo Morita, Naotaka Hashimoto, Hirohito Kayashima, Atsuro Masuda, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Pure laparoscopic hepatectomy in semiprone position for right hepatic major resection, Journal of Hepato-Biliary-Pancreatic Sciences, 10.1007/s00534-012-0558-y, 20, 2, 145-150, 2013.02, Background: Pure laparoscopic liver resection is technically difficult for tumors located in the dorsal anterior and posterior sectors. We have developed a maneuver to perform pure laparoscopic hepatectomy in the semiprone position which was developed for resecting tumors located in these areas. Methods: The medical records have been reviewed retrospectively in 30 patients who underwent laparoscopic liver resection in the semiprone position for carcinoma in the dorsal anterior or posterior sectors of the right liver between 2008 and 2011. Results: Seventeen liver tumors were primary liver tumors and 13 were colorectal metastases. Of the 30 patients, 11 (36.6 %) underwent major hepatectomy [right hemihepatectomy in 7 (23.3 %) and posterior sectionectomy in 4 (13.3 %)]. Anatomical minor resection, such as S6 or S7 segmentectomy, was performed in five patients (16.6 %). Five patients with liver metastasis underwent a simultaneous laparoscopic resection. There was no mortality, reoperation, or conversion to open procedures. There were no hepatectomy-related complications such as postoperative bleeding, bile leakage, or liver failure. Conclusions: Pure laparoscopic hepatectomy in the semiprone position for tumors present in the dorsal anterior and posterior sectors is feasible and safe. This method expands the indications for laparoscopic liver resection for tumors..
1760. Takeo Toshima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Ken Shirabe, Yoshihiko Maehara, Effect of CD133-positive stem cells in repeated recurrence of hepatocellular carcinoma after liver transplantation
a case report., Unknown Journal, 104, 10, 383-388, 2013.01, Liver transplantation (LT) is currently one of the best available strategies for treating multiple hepatocellular carcinoma (HCC) and decompensated liver cirrhosis. However, patients often undergo HCC recurrence after LT, with most HCC recurrences detected at 1-2 years. CD133 was the first identified member of the prominin family of pentaspan membrane proteins and is a marker of hepatic stem cells. Here, we report a unique case of seven repeated recurrences of HCC in the lungs after LT, with all HCC recurrences resected curatively by a thoracoscopic approach. Pathological examination revealed moderately differentiated HCC identical to that in the original histology of the liver tumor. Interestingly, no CD133 immunoreactivity was observed in cancerous lesions of the primary HCC and the 1st to 2nd recurrences, as indicated by immunohistochemistry. However, CD133 was strongly stained in the cancerous lesions from the 3rd to 7th recurrences. The patient survived and had no recurrence after 9 years of the initial living donor LT. In conclusion, we investigated an evocative case of seven repeated recurrences of HCC in the lungs to elucidate the significance of circulating CD133-positive hepatic stem cells. This case illustrates the need for further research to clarify the mutual effect of CD133-positive hepatic stem cells for the development of new therapeutic strategies..
1761. Tetsuo Ikeda, Tomohiko Akahoshi, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Koshi Mimori, Masayuki Watanabe, Makoto Hashizume, Yoshihiko Maehara, Evaluation of a transection method for distal pancreatectomy
A comparative study on the use of electrosurgical and stapling devices in swine., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 515-522, 2013.01, Despite marked improvements in pancreatic surgery, the high incidence of pancreatic fistula and high morbidity after resection persists. The objective of this study was to evaluate the role of electrosurgical and stapling devices as an alternative to traditional methods of stump closure in an animal model of distal pancreatectomy. Four devices were used for transection of the pancreatic body : a bi-polar thermofusion system attached to an automatic irrigation function (BI, n = 3), a bi-polar tissue sealer (BS, n = 3), an ultrasonic scissor (US, n = 3), and an endoscopic stapling device (ES, n = 3). For each group, burst pressure was tested using an electronic manometer, with a focus on the location (s) of the first disruption (s). Histological examination was performed for the dissected surfaces. The transection line, including staples, was embedded in a polyester resin, and histological examination was performed for these polished sections of the resin. Pressure was significantly higher for BI (P < 0.01) than that for the other devices. In contrast, thermal denaturation of the pancreas parenchyma was observed at a depth of approximately 1 mm from the dissected portion for BS, while it extended beyond 15 mm for BI. The staple line was the first disruption point for all of ES cases. The pellicle of the pancreas is likely to be deficient after a surgical operation. If the pellicle is preserved, the strength of the pellicle may be insufficient for complete closure with high stapling mechanical pressure or the protein coagulation of usually used electrosurgical devices..
1762. Shinji Okano, Haruhiko Kondoh, Takeo Toshima, Hidekazu Nakagawara, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Mamoru Harada, Yasunobu Yoshikai, Yoshihiko Maehara, Fas-deficient fully allogeneic dendritic cells administered via an intratumoral injection route show efficient antitumor effects in murine models., Unknown Journal, 104, 1, 15-26, 2013.01, Dendritic cell (DC)-based immunotherapy is a potent, active and specific cancer immunotherapy, as DCs are preferable professional APCs (pAPCs) that prime the tumor-associated antigen (TAA) -specific CD8+ T-cell response. In DC-based immunotherapy, allogeneic DCs may be an alternative source of DCs for patients in whom it is difficult to obtain a sufficient number of quality-guaranteed, autologous DCs. However, the usefulness of fully allogeneic DCs in DC-based immunotherapy is controversial, and many investigators have failed to demonstrate that fully allogeneic DCs can induce an efficient antitumor effect in various experimental settings. In this study, we found that the injection of Fas-deficient fully allogeneic DCs via an intratumoral injection route exerted efficient antitumor effects, as did syngeneic DCs, but wild-type fully allogeneic DCs did not. Intratumoral injection therapy using Fas-deficient syngeneic DCs does not show superior tumor growth suppression compared to that using wild-type syngeneic DCs, suggesting that the inhibition of functional Fas may be critical for overcoming the unfavorable factor related to allogeneic DCs, especially overcoming the rejection response to alloantigens, in therapy using fully allogeneic DCs. In addition, the intratumoral injection therapy using Fas-deficient fully allogeneic DCs induced the generation of a significant tumor-specific CD8+ T-cell response, which is restricted by a host-derived major histocompatibility antigen. Therefore, intratumoral injection therapy using fully allogeneic DCs of which functional Fas is inhibited may be an alternative in clinical DC-based immunotherapy, under circumstances that do not allow the use of autologous DCs..
1763. Naotaka Hashimoto, Tomohiko Akahoshi, Masahiro Kamori, Morimasa Tomikawa, Daisuke Yoshida, Yoshihiro Nagao, Kazutoyo Morita, Hiroto Kayashima, Toru Ikegami, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Treatment of bleeding rectal varices with transumbilical venous obliteration of the inferior mesenteric vein, Surgical Laparoscopy, Endoscopy and Percutaneous Techniques, 10.1097/SLE.0b013e31828031ec, 23, 3, e134-e137, 2013.06, A 56-year-old male with alcohol-induced liver cirrhosis developed rectal varices. He had a prior history of treatment for esophageal varices with endoscopic variceal ligation. Despite the repeated treatment for rectal varices with endoscopic variceal ligation, endoscopic injection sclerotherapy, and surgery, the bleeding from the rectal varices could not be controlled. Multidetector-row computed tomography and 3D-angiography revealed the hemodynamic profile of the rectal varices. We next approached the rectal varices through the umbilical vein on the abdominal wall, and successfully embolized the varices continuing from the inferior mesenteric vein using coils and a 5% solution of ethanolamine oleate with iopamidol..
1764. Hideki Ijichi, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Youhei Mano, Shinichi Aishima, Koichiro Abe, Hiroshi Honda, Yoshihiko Maehara, Clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography for patients with primary liver cancer with special reference to rare histological types, hepatocellular carcinoma with sarcomatous change and combined hepatocellular and cholangiocarcinoma, Hepatology Research, 10.1111/j.1872-034X.2012.01107.x, 43, 5, 481-487, 2013.05, Aim: The role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis and staging of primary liver cancer has been demonstrated in several reports. However, no preoperative evaluations of sarcomatous hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (cHCC-CC) with FDG-PET have been reported so far. Methods: Fifty-three HCC patients and three cHCC-CC patients who received liver resection or living-donor liver transplantation were enrolled in this study. All 56 patients had undergone preoperative FDG-PET, and a total of 67 HCC and three cHCC-CC were analyzed histologically. The relationship between clinicopathological features and the maximum standardized uptake value (SUVmax) of tumors were evaluated. Results: The detection rate of HCC by FDG-PET was 43.3 %, and the sensitivity of FDG-PET for the detection of HCC was significantly associated with tumor differentiation, tumor size and microvascular invasion. All three cHCC-CC were detected by FDG-PET. The SUVmax values of the three sarcomatous HCC (SUVmax 14.1, 18.6 and 25.0) and the three cHCC-CC (SUVmax 9.9, 12.0 and 13.0) were higher than that of the poorly differentiated HCC (mean SUVmax 5.7±2.3). Conclusion: SUVmax may be a useful diagnostic tool for the preoperative evaluation of the aggressiveness of primary liver cancers such as sarcomatous HCC and cHCC-CC..
1765. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Norihiro Furusyo, Kazuhiro Kotoh, Masaki Kato, Shinji Shimoda, Yuji Soejima, Takashi Motomura, Takasuke Fukuhara, Yoshihiko Maehara, Impact of conversion from pegylated interferon-α2b to interferon-α2a for treating recurrent hepatitis C after liver transplantation, Transplantation, 10.1097/TP.0b013e318283a82e, 95, 6, e38-e42, 2013.05.
1766. Toshiro Masuda, Ken Shirabe, Shohei Yoshiya, Rumi Matono, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Hideo Baba, Yoshihiko Maehara, Nutrition support and infections associated with hepatic resection and liver transplantation in patients with chronic liver disease, Journal of Parenteral and Enteral Nutrition, 10.1177/0148607112456041, 37, 3, 318-326, 2013.05, Malnutrition is common in liver cirrhotic patients who will undergo liver resection or liver transplantation. A precise evaluation of their nutrition status is thus difficult because of the presence of ascites and the edema caused by their impaired protein synthesis. Both perioperative enteral and parenteral nutrition have benefits in reducing the morbidity and mortality of liver surgery, and in general, oral nutrition supplements are recommended. Branched-chain amino acids (BCAAs) promote protein and glycogen synthesis and regulate immune system function. Synbiotics, a combination of pro- and prebiotics, is reported to enhance immune responses. Oral nutrition support with BCAAs, synbiotics, and an immune-enhancing diet have a beneficial effect on preventing the perioperative infections associated with hepatic resection or liver transplantation..
1767. Toru Ikegami, Ken Shirabe, Hidekazu Nakagawara, Tomoharu Yoshizumi, Takeo Toshima, Yuji Soejima, Hideaki Uchiyama, Yo Ichi Yamashita, Norifumi Harimoto, Yoshihiko Maehara, Obstructing spontaneous major shunt vessels is mandatory to keep adequate portal inflow in living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e318288cadc, 95, 10, 1270-1277, 2013.05, BACKGROUND: It has not been addressed whether the major spontaneous portosystemic shunt vessels should be ligated in living-donor liver transplantation (LDLT). METHODS: We performed a retrospective analysis of 324 cases of adult-to-adult LDLT. RESULTS: Factors associated with the presence of major (>10 mm) shunt vessels (n=130) included portal vein (PV) thrombosis (27.7%), lower PV pressure at laparotomy, Child-Pugh class C, and transplantation of right-side grafts. The types of major portosystemic shunt vessels included splenorenal shunts (46.2%), gastroesophageal shunts (26.9%), mesocaval shunts (13.8%), and others (13.1%). Ligation of the major shunt vessels increased PV pressure (mean [SD], from 16.8 [3.9] mm Hg to 18.6 [4.3] mm Hg; P<0.001) and PV flow (mean [SD], from 1.35 [0.67] L/min to 1.67 [0.67] L/min; P<0.001) into the grafts. Post-LDLT computed tomography showed patent major shunts in 14 patients. Nine of such patients (64.3%) with unligated major shunt vessels (undetected shunt vessels, n=5; incomplete ligation, n=2; and the shunt was newly created or left open to maintain high PV pressure after reperfusion, n=3) required secondary interventions. Two of these patients died because of graft dysfunction. PV flow was significantly lower in the nine patients who underwent secondary ligation of the major shunt vessels compared with patients with successful primary ligation (mean [SD], 0.96 [0.34] L/min vs. 1.65 [0.63] L/min; P=0.001). CONCLUSIONS: It is an appropriate option to obstruct the major portosystemic shunt vessels to ensure adequate graft inflow in LDLT..
1768. Shohei Yoshiya, Ken Shirabe, Yoshihiro Matsumoto, Tetsuo Ikeda, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Yoshihiko Maehara, Rendezvous ductoplasty for biliary anastomotic stricture after living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31828a9450, 95, 10, 1278-1283, 2013.05, BACKGROUND: Biliary anastomotic stricture (BAS) after living-donor liver transplantation (LDLT) is difficult to manage. We used rendezvous ductoplasty (RD) to treat BAS after LDLT. METHODS: We retrospectively analyzed 53 patients with BAS after adult-to-adult LDLT with duct-to-duct biliary reconstruction. RESULTS: BAS was classified according to endoscopic retrograde cholangiography findings after normal-pressure contrast injection: type I (n=32) in which the stricture was visualized; type II (n=13) in which the common hepatic duct and graft intrahepatic ducts were visualized, but the stricture was not visualized; or type III (n=8) in which the stricture and graft intrahepatic ducts were not visualized. In right lobe grafts, types II and III occurred more frequently than type I (P=0.0023). Type I had significantly shorter cold ischemic time (76±11 vs. 118±12 min; P=0.0155) and warm ischemic time (38±2 vs. 49±3 min; P=0.0069) than types II and III. The number of attempts to pass the guidewire through the stricture was significantly lower in type I (1.2±0.2 attempts) than type II (2.2±0.2 attempts; P=0.0018) or type III (2.8±0.3 attempts; P<0.0001). The treatment success rate was 78.1% for type I, 38.5% for type II, and 50.0% for type III (P=0.0282). RD was the first successful treatment in a higher proportion of types II and III patients than type I patients (66.7% vs. 6.3%; P<0.0001). Cumulative treatment success rates were not significantly different between the RD and the non-RD groups (P=0.0920). CONCLUSIONS: RD was a useful treatment for difficult cases of BAS after LDLT and achieved successful outcomes..
1769. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Hiroto Kayashima, Yoshihiko Maehara, Use of the SAND balloon catheter in single-incision laparoscopic cholecystectomy for acute cholecystitis., Unknown Journal, 10.1111/ases.12005, 6, 2, 134-136, 2013.05, SILS for acute cholecystitis is technically challenging because of the difficulties in obtaining optical surgical field. A 2-cm incision was made through the umbilicus, a single port and trocars were introduced, and the abdomen was then insufflated. A 5-mm SAND balloon punctured the abdominal wall and then the gallbladder wall. The distal and proximal balloons were inflated to prevent bile leakage, and the bile was aspirated. The collapsed gallbladder was then retracted cephalad, the critical structures were exposed, and the cystic artery and duct were divided. The gallbladder was dissected and removed through the umbilicus, and the abdomen was closed. We performed this procedure in three cases with acute cholecystitis. Operative times were 95, 133 and 244 min, blood loss was 5, 10 and 43 mL, and postoperative hospital stay was 2, 2 and 3 days, respectively. The single-incision laparoscopic approach with the SAND balloon is a feasible technique for acute cholecystitis..
1770. Mikihiro Kohno, Ken Shirabe, Yohei Mano, Jun Muto, Takashi Motomura, Kazuki Takeishi, Takeo Toshima, Masanori Yoshimatsu, Hideki Ijichi, Noboru Harada, Shinichi Aishima, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Granulocyte colony-stimulating-factor-producing hepatocellular carcinoma with extensive sarcomatous changes
Report of a case, Surgery today, 10.1007/s00595-012-0202-0, 43, 4, 439-445, 2013.04, This report describes a rare case of hepatocellular carcinoma (HCC) producing granulocyte colony-stimulating factor (G-CSF). A 46-year-old male with chronic hepatitis B, who presented with fever, general malaise, loss of appetite, and weight loss, had a huge liver mass in the portal region. He had marked granulocytosis and his serum level of G-CSF was elevated. Complete tumor resection was performed, and the pathological assessment of the resected specimen revealed HCC with extensive sarcomatous changes and immunohistochemical staining for G-CSF and G-CSF receptor. Only a few cases of G-CSF-producing HCC have been reported, and this is the first case of G-CSF-producing HCC that also expressed G-CSF receptor..
1771. Yu Saito, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Koji Yamasaki, Noriaki Sadanaga, Hiroshi Matsuura, Kenichiro Okadome, Hepatic artery aneurysm in a patient with hepatitis c liver cirrhosis
Report of a case, Clinical Journal of Gastroenterology, 10.1007/s12328-013-0372-3, 6, 2, 169-172, 2013.04, Visceral artery aneurysms are rare, with an incidence rate of only 0.01-0.2 % in routine autopsies, and hepatic artery aneurysms account for approximately 20 % of these aneurysms. Despite recent advances in therapeutic techniques and diagnostic tools, the management of visceral artery aneurysms remains clinically challenging. We report a case of hepatic artery aneurysm with liver cirrhosis due to hepatitis C in an 81-year-old woman. A computed tomography scan demonstrated a hepatic artery aneurysm 4.4 cm in diameter. She underwent successful aneurysmectomy with vascular anastomosis. A computed tomography scan on postoperative day 7 demonstrated patent hepatic artery. The patient was followed-up for 1 year after surgery and died owing to progressive liver failure. However, she did not show any hepatic artery problem such as hepatic arterial thrombosis or occlusion. We discuss the risk factors of atherosclerosis in patients with liver cirrhosis, and present an overview of the treatment of hepatic artery aneurysms..
1772. Yo Ichi Yamashita, Ken Shirabe, Eiji Tsujita, Kazuki Takeishi, Tetsuo Ikeda, Tomoharu Yoshizumi, Yoshinari Furukawa, Teruyoshi Ishida, Yoshihiko Maehara, Surgical outcomes of pancreaticoduodenectomy for periampullary tumors in elderly patients, Langenbeck's Archives of Surgery, 10.1007/s00423-013-1061-x, 398, 4, 539-545, 2013.04, Backgrounds: Pancreaticoduodenectomy (PD) is an aggressive surgery with considerable operative risks, but offers the only chance for cure in patients with periampullary tumors. A growing number of elderly patients are being offered PD because of the aging of populations in developed countries. We examined surgical outcomes of PD in patients aged 75 years and older (≥75 years). Methods: A retrospective cohort study was performed in 65 consecutive patients who underwent PD for periampullary tumors at a single medical center during the 5 years from 2006 to 2010. We analyzed surgical outcomes such as mortality and morbidity after PD in patients aged ≥75 years (n = 21) compared to those in patients aged <75 years (n = 44). Results: The positive rate of comorbidities such as hypertension was significantly higher in patients aged ≥75 years than in patients aged <75 years (76 vs. 48 %; p = 0.03). The incidence of wound infection was significantly higher in patients aged ≥75 years than in patients aged <75 years (19 vs. 0 %; p < 0.01). However, there was no significant difference in the mortality rate (0 vs. 2 %; p = 0.49) or the overall morbidity rate (33 vs. 32 %; p = 0.90). There was no significant difference in changes in body weight or serum albumin levels during the 3 months after PD between the two groups, but the recovery of serum prealbumin levels from 1 to 3 months after PD in patients aged ≥75 years was significantly delayed compared to that in patients aged <75 years (p = 0.04). There was no statistically significant difference in long-term survival between the two groups. Conclusions: Advanced age alone should not discourage surgeons from offering PD, although nutritional supports after PD for elderly patients aged ≥75 years are needed..
1773. Yasue Kimura, Hiroyuki Matsuda, Hiroshi Saeki, Eiji Oki, Masaru Morita, Keishi Sugimachi, Yo ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Tetsuo Ikeda, Shinichi Tsutsui, Megumu Fujihara, Koshi Mimori, Masayuki Watanabe, Teruyoshi Ishida, Yoshihiko Maehara, Case of early adenosquamous carcinoma of the stomach., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 9, 315-320, 2013.09, Adenosquamous carcinoma of the stomach is very rare; at present, there are only seven published reports. We report here an eighth case involving a 77-year-old Japanese man who was diagnosed with gastric cancer by upper endoscopy and computed tomography (CT). He underwent laparoscopic-assisted distal gastrectomy for early gastric cancer and the resected specimen was diagnosed as adenosquamous carcinoma limited to the submucosal layer. Only one lymph node metastasis was noted. Seven months later, liver metastasis (3 tumors, 15 mm maximum in diameter) was detected by abdominal CT. He was started on chemotherapy with S-1 and cisplatin (CDDP) and is alive 14 months after surgery. Almost all cases of adenosquamous carcinoma of the stomach are diagnosed in advanced stages and carry a very poor prognosis. Most patients with early adenosquamous carcinoma of the stomach survive for 2 or more years without recurrence, however our patient experienced recurrence 7 months after surgery. Therefore, future treatment for recurrent adenosquamous carcinoma of the stomach should be considered..
1774. Koichi Kimura, Toru Ikegami, Yo ichi Yamashita, Hiroshi Saeki, Eiji Oki, Tomoharu Yoshizumi, Hideaki Uchiyama, Hirofumi Kawanaka, Yuji Soejima, Masaru Morita, Ken Shirabe, Tetsuo Ikeda, Yoshihiko Maehara, Rendezvous technique treatment for late-onset biliary leakage after major hepatectomy of a living donor
report of a case., Fukuoka Acta Medica, 104, 9, 309-314, 2013.09, Biliary leakage is a major complication after hepatectomy. We report the case of a living-donor liver transplantation (LDLT) donor with a late-onset bile leak from the trifurcation of the hepatic duct who was successfully treated using rendezvous technique. A 52-year-old man underwent extended left hepatectomy for donation and was discharged on postoperative day (PD) 13. However, he was rehospitalized on PD 26 with severe abdominal pain. Physical examination suggested panperitonitis, and abdominocentesis showed bilious ascites. Emergent laparotomy for biliary leakage and peritonitis was performed. There was bilious ascites in the peritoneal cavity. A biliary fistula was recognized at the trifurcation of B8a, B8b, and B5. Intraoperative transhepatic biliary drainage of each bile duct was performed. Endoscopic transpapillary drainage was performed on PD 24. Finally, external drains were removed and complete internal drainage established on PD 70. The bile leak was considered to be the result of injury from electrocautery device. Appropriate making choices of the electrocautery devices enable us to avoid over thermal injury of the liver surface. Rendezvous bidirectional drainage effectively treated late-onset bile leakage from the trifurcation of a hepatic bile duct..
1775. Eiji Oki, Yoshihisa Sakaguchi, Kippei Ohgaki, Hiroshi Saeki, Toru Ikegami, Kazuhito Minami, Yoichi Yamashita, Yasushi Toh, Yuji Soejima, Kouji Andou, Koshi Mimori, Masayuki Watanabe, Keishi Sugimachi, Hideaki Uchiyama, Tomoharu Yoshizumi, Hirofumi Kawanaka, Masaru Morita, Tetsuo Ikeda, Yoshihiko Maehara, Total laparoscopic distal gastrectomy for elderly patients with gastric cancer., Fukuoka Acta Medica, 104, 9, 290-298, 2013.09, This study evaluated the feasibility of totally laparoscopic distal gastrectomy (TLDG) in elderly patients with gastric cancer. We retrospectively analyzed the data from 138 patients who underwent TLDG from April 2005 to March 2009. Of these 138 patients, 20 were older than 75 years of age, and 118 were 75 years of age or younger. The preoperative respiratory function and American Society of Anesthesiologists (ASA) -physical status were significantly worse in the elderly patients than in the younger patients (P = 0.013). Hypertension and respiratory disease were more common in the elderly patients than in the younger patients (P = 0.032 / P = 0.005). The findings for the following parameters were similar in the two groups: intraoperative blood loss, operation time, severe postoperative complication rate, time required to start a solid diet, and duration of postoperative hospital stay. The rate of major complications was not different between the two groups, although minor complications were more commonly observed in the elderly patients. TLDG was found to be a safe procedure for elderly patients. This method can be used as one of the standard treatments for gastric cancer in elderly patients..
1776. Takeo Toshima, Mitsuo Shimada, Toru Ikegami, Toru Utsunomiya, Tetsuya Ikemoto, Yuji Morine, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Fairly rare spontaneous disappearance of a hepatic artery aneurysm following living donor liver transplantation, Liver Transplantation, 10.1002/lt.23676, 19, 8, 929-930, 2013.08.
1777. Yohei Mano, Ken Shirabe, Yo Ichi Yamashita, Norifumi Harimoto, Eiji Tsujita, Kazuki Takeishi, Shinichi Aishima, Toru Ikegami, Tomoharu Yoshizumi, Takeharu Yamanaka, Yoshihiko Maehara, Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma
A retrospective analysis, Annals of surgery, 10.1097/SLA.0b013e318297ad6b, 258, 2, 301-305, 2013.08, OBJECTIVE:: To clarify the prognostic value of the preoperative blood neutrophil-to-lymphocyte ratio (NLR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). BACKGROUND:: Although a high NLR has been reported to be a predictor of poor survival in patients with various cancers, it has not been extensively examined in patients with HCC. METHODS:: This retrospective study enrolled 958 patients who underwent hepatectomy without preoperative therapy for HCC from 1996 to 2009. Clinicopathological parameters, including NLR, were evaluated to identify predictors of overall and recurrence-free survival after hepatectomy. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. The best cutoff was determined with time-dependent receiver operating characteristic curve. To determine the mechanism of NLR elevation, immunohistological examination using CD163 staining was performed in 150 patients. RESULTS:: Univariate and multivariate analyses showed that NLR was an independent prognostic factor in overall and recurrence-free survival. The best cutoff of NLR was 2.81, and 238 of 958 patients (24.8%) had NLR of more than 2.81. The 5-year survival rate after hepatectomy was 72.9% in patients with NLR less than 2.81 and 51.5% in those with NLR 2.81 or more (P < 0.0001). CD163-positive cell counts were significantly higher in tumors in the group with NLR 2.81 or more than in the group with NLR less than 2.81 (P = 0.0004). CONCLUSIONS:: Our results show that NLR is an independent predictor of survival after hepatectomy in patients with HCC. Accumulation of tumor-associated macrophages in the tumor is associated with a high NLR..
1778. Tomoharu Yoshizumi, Toru Ikegami, Shohei Yoshiya, Takashi Motomura, Yohei Mano, Jun Muto, Tetsuo Ikeda, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma, Hepatology Research, 10.1111/hepr.12016, 43, 7, 709-716, 2013.07, Aim: Hepatocellular carcinoma (HCC) is primarily treated with hepatic resection and/or locoregional therapy. When HCC recurs and further treatment is no longer possible owing to poor liver function, liver transplantation (LT) or living-donor LT (LDLT) is considered. The aim of this study was to clarify risk factors for tumor recurrence after LDLT in patients with recurrent HCC. Methods: The study comprised 104 patients who had undergone LDLT because of end-stage liver disease with recurrent HCC. The recurrence-free survival rates after the LDLT were calculated. Risk factors for tumor recurrence were identified. Results: The 1-, 3- and 5-year recurrence-free survival rates were 89.6%, 80.3% and 78.4%, respectively. By univariate analysis, the factors affecting recurrence-free survival were the sum of the largest tumor size and number of tumors of 8 or more (P<0.0001), des-γ-carboxy prothrombin of more than 300mAU/mL (P = 0.0001), and a neutrophil-to-lymphocyte ratio (NLR) of 4 or more (P = 0.0002), α-fetoprotein of more than 400ng/mL (P = 0.0001) and bilobar tumor distribution (P = 0.046). A multivariate analysis identified independent risk factors for post-LDLT tumor recurrence including the sum of tumor size and number of tumors of 8 or more (P = 0.0004) and an NLR of 4 or more (P = 0.01). The 1- and 3- year recurrence-free survival rates in the recipients who had both risk factors were 30.0% and 15.0%, respectively. Conclusion: LDLT should not be performed for patients who have both independent risk factors after any treatments for HCC..
1779. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Takeo Toshima, Takashi Motomura, Yoshihiko Maehara, One-step reconstruction of the right inferior hepatic veins using auto-venous grafts in living donor liver transplantation, Surgery today, 10.1007/s00595-012-0449-5, 43, 7, 769-776, 2013.07, Purposes: Reconstruction of the right inferior hepatic vein (RIHV) presents a major technical challenge in living donor liver transplantation (LDLT) using right lobe grafts. Methods: We studied 47 right lobe LDLT grafts with RIHV revascularization, comparing one-step reconstruction, performed post-May 2007 (n = 16), with direct anastomosis, performed pre-May 2007 (n = 31). Results: In the one-step reconstruction technique, the internal jugular vein (n = 6), explanted portal vein (n = 5), inferior vena cava (n = 3), and shunt vessels (n = 2) were used as venous patch grafts for unifying the right hepatic vein, RIHVs, and middle hepatic vein tributaries. By 6 months after LDLT, there was no case of occlusion of the reconstructed RIHVs in the one-step reconstruction group, but a cumulative occlusion rate of 18.2 % in the direct anastomosis group. One-step reconstruction required a longer cold ischemic time (182 ± 40 vs. 115 ± 63, p < 0.001) and these patients had higher alanine transaminase values (142 ± 79 vs. 96 ± 46 IU/L, p = 0.024) on postoperative day POD 7. However, the 6-month short-term graft survival rates were 100 % with one-step reconstruction and 83.9 % with direct anastomosis, respectively. Conclusion: One-step reconstruction of the RIHVs using auto-venous grafts is an easy and feasible technique promoting successful right lobe LDLT..
1780. Toru Ikegami, Ken Shirabe, Takasuke Fukuhara, Norihiro Furusyo, Kazuhiro Kotoh, Masaki Kato, Shinji Shimoda, Shinichi Aishima, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Maehara, Early extensive viremia, but not rs8099917 genotype, is the only predictor for cholestatic hepatitis C after living-donor liver transplantation, Hepatology Research, 10.1111/hepr.12003, 43, 6, 621-629, 2013.06, Aim: Cholestatic hepatitis C is one of the most serious but still unaddressed disorders after liver transplantation. Methods: In this study, we analyzed 49 patients who underwent living-donor liver transplantation (LDLT) to treat hepatitis C virus (HCV) infection. Results: Five patients developed cholestatic hepatitis C, with total bilirubin of 15.2±3.1mg/dL at diagnosis 6.2±1.0 weeks after LDLT. Univariate analysis showed that larger graft to standard liver volume ratio, higher HCV RNA titer at 2 weeks, earlier peak HCV RNA titer and cytomegalovirus infection were the significant risk factors. The development of cholestatic hepatitis C was not significantly associated with interleukin-28B genotype (rs8099917); four out of five affected patients had the T/T genotype. Multivariate analysis showed that higher HCV RNA titer at 2 weeks was the only significant factor (P=0.026) for the development of cholestatic hepatitis C. Receiver-operator curve analysis showed that that HCV RNA titer of more than 7.2log10IU/mL was the optimal cut-off for characterizing cholestatic hepatitis C. All of the patients were serum HCV RNA negative after treatment with pegylated interferon and ribavirin and all the patients are alive. Conclusion: Early extensive viremia, but not the rs8099917 genotype, was the only predictor for cholestatic hepatitis C after LDLT..
1781. Ken Shirabe, T. Motomura, K. Takeishi, K. Morita, H. Kayashima, A. Taketomi, T. Ikegami, Y. Soejima, T. Yoshizumi, Y. Maehara, Human early liver regeneration after hepatectomy in patients with hepatocellular carcinoma
Special reference to age, Scandinavian Journal of Surgery, 10.1177/1457496913482250, 102, 2, 101-105, 2013.06, Background and Aims: This study was conducted to clarify the effects of age on human liver regeneration. Patients and Methods: Thirty major hepatectomies, equal to or more than two segmentectomies for hepatocellular carcinoma, were performed. Ages ranged from 37 to 85 years and five octogenarians were included. The early regenerative index was defined: (liver volume after 7 days after hepatectomy - estimated remnant liver volume before hepatectomy)/estimated remnant liver volume, using three-dimensional computed tomographic volumetry. Farnesoid X receptor and forkhead box m1 expression in the liver, which has been reported to age-related decrease of liver regeneration in animal model, were examined using real-time polymerase chain reaction. The patients were divided into two groups: low early regenerative index (n = 15), early regenerative index less than 55% and high early regenerative index (n = 15), early regenerative index equal to or more than 55%. Results: The mean early regenerative index was 57%. Age (R2 = 0.274, P = 0.003) and estimated blood loss (R2 = 0.134, P = 0.0466) were inversely correlated with the early regenerative index, and the expression of farnesoid X receptor and forkhead box m1 was not. The incidence of posthepatectomy liver failure in the low early regenerative index group was higher than that in the high early regenerative index group (P = 0.0421). Conclusions: Age and intraoperative blood loss are inversely correlated with early liver regeneration in humans. In elderly patients, massive blood loss should be avoided in view of liver regeneration..
1782. Noboru Harada, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Katsuhiro Asonuma, Yukihiro Inomata, Yoshihiko Maehara, Intrahepatic artery pseudoaneurysm associated with a metallic biliary stent after living donor liver transplantation
Report of a case, Surgery today, 10.1007/s00595-012-0302-x, 43, 6, 678-681, 2013.06, An intrahepatic artery pseudoaneurysm (IHAA) is a very rare but potentially lethal complication occurring after liver transplantation. This report presents a case of an IHAA associated with a metallic biliary stent after liver transplantation. A 40-year-old male underwent living donor liver transplantation (LDLT) using a left lobe graft. The bile duct reconstruction was performed with Roux-en-Y hepaticojejunostomy. He developed obstructive jaundice 5 years after LDLT, and had biliary stricture of the anastomosis area, therefore, the two metallic biliary stents were finally positioned at the stricture of the biliary tract. He suddenly developed hematemesis 8 years after LDLT, and computerized tomography scan showed an IHAA. Although seven interlocking detachable coils were placed at the neck of the aneurysm, hematemesis recurred 3 days after the initial embolization. Therefore, retransplantation was successfully performed 25 days after the embolization of IHAA using a right lobe graft from his son. In conclusion, metal stent insertion can lead to the fatal complication of HAA. The placement of a metallic stent could have been avoided in this case. Percutaneous metallic stent insertion for biliary stenosis after liver transplantation should therefore only be performed in carefully selected patients..
1783. Toru Ikegami, Huanlin Wang, Daisuke Imai, Yuki Bekki, Tomoharu Yoshizumi, Yo Ichi Yamashita, Takeo Toshima, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Pathological analysis of opened round ligaments as venous patch grafts in living donor liver transplantation, Liver Transplantation, 10.1002/lt.23716, 19, 11, 1245-1251, 2013.11, Although the round ligament, including the umbilical vein, could be used as a venous graft in living donor liver transplantation (LDLT), no studies have determined its appropriate use on the basis of pathological findings. We prospectively examined 19 LDLT cases in which the donor's round ligament was procured and used as a venous graft. The round ligaments were categorized into 3 types based on the CD31 immunohistochemistry of tissue cross-sections: (I) canalized umbilical veins (n = 7 or 36.8%), (II) capillary umbilical vessels (n = 4 or 21.1%), and (III) occluded umbilical veins (n = 8 or 42.1%). After dilatation and incision, the round ligaments provided patch grafts that were 5.8 ± 0.4 cm long and 1.8 ± 1.2 cm wide. However, histological studies showed the absence of fine intimal layers on the dilated round ligaments after mechanical maneuvers. The ligaments were used to cuff the venous orifices in 15 patients (left lobe, n = 8; right lobe, n = 7) and were used as venous bridges in 4 patients (left lobe, n = 2; right lobe, n = 2). We detected no thrombosis at the implant sites after LDLT. Our pathological findings indicate that opened round ligaments can be used safely as venous patch grafts in LDLT. Liver Transpl 19:1245-1251, 2013..
1784. Yoshihiro Matsumoto, Toru Ikegami, Kazutoyo Morita, Tomoharu Yoshizumi, Hiroto Kayashima, Ken Shirabe, Yoshihiko Maehara, Renoportal anastomosis in right lobe living donor liver transplantation
Report of a case, Surgery today, 10.1007/s00595-012-0351-1, 43, 11, 1316-1320, 2013.11, End-stage liver disease is often accompanied by thrombosis of the portal vein and the formation of splanchnic collateral vessels. Successful liver transplantation in such situations is more likely if the surgeon uses a strategy to establish a graft inflow. A 59-year-old male with a decompensated liver secondary to idiopathic portal hypertension underwent living donor liver transplantation (LDLT) using a right lobe liver graft donated from his son. His portal venous trunk was atrophied and a splenorenal shunt drained the mesenteric venous flow into the systemic circulation. LDLT was performed with renoportal anastomosis (RPA) using his right internal jugular vein as an interposed venous graft, without dissecting the collateral vessels. Although he developed temporary functional hyperbilirubinemia, he was discharged from the hospital 23 days after LDLT. This case suggests that RPA is a useful technique to manage patients with an obstructed portal vein and a splenorenal shunt..
1785. Yo Ichi Yamashita, Ken Shirabe, Eiji Tsuijita, Kazuki Takeishi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Tohru Utsunomiya, Yoshihiko Maehara, Third or more repeat hepatectomy for recurrent hepatocellular carcinoma, Surgery (United States), 10.1016/j.surg.2013.04.046, 154, 5, 1038-1045, 2013.11, Background: We sought to evaluate the surgical results of third or more repeat hepatectomy for recurrent hepatocellular carcinoma (HCC). The role of repeat hepatectomy for recurrent HCC, especially in cases with third or more repeat hepatectomy, is controversial. Methods: We performed A retrospective, cohort study to analyze the surgical results of repeat hepatectomy performed at a single medical center from 1989 to 2011. A total of 1,000 hepatectomies for HCC were divided into 3 groups: A first hepatectomy group (n = 791), second hepatectomy group (n = 163), and third or more hepatectomy group (n = 46). Operative results and patient prognoses were compared among the 3 groups. Results: There were no differences in early surgical results such as mortality and morbidity among the 3 groups. The 5-year survival rates after the first, second, and third or more hepatectomy were 67%, 60%, and 43%, respectively (P =.1913). There was a significant difference in disease-free survival among the 3 groups, and the 5-year disease-free survival rates after first, second, and third or more hepatectomy were 37%, 29%, and 18%, respectively (P =.0169). Conclusion: Third or more repeat hepatectomy for recurrent HCC was performed safely and associated with relatively long-term survival. Third or more repeat hepatectomy for recurrent HCC seems justified, but high rate of HCC recurrence remains a problem..
1786. Mizuki Ninomiya, Tetsuo Ikeda, Ken Shirabe, Hiroto Kayashima, Norifumi Harimoto, Tomohiro Iguchi, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hiroshi Saeki, Eiji Oki, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Masaru Morita, Yoshihiko Maehara, Three-dimensional computed tomography image based endovascular treatment for hepatic vein., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 469-472, 2013.11, Along with the expansion of living donor liver transplantation, whereby hepatic venous anastomosis is mandatory, the frequency of hepatic venous stenosis that need interventional treatment is increasing. Due to its anatomical features, there are several pitfalls in the process of endovascular intervention for hepatic vein. Insufficient information of and around the hepatic vein may lead to miss-diagnosis of target lesion. Simulation by using three-dimensional computed tomography images was useful in planning the direction of X-ray projection and, as a consequence, contributed to safe endovascular treatment for hepatic venous stenosis..
1787. T. Yoshizumi, T. Ikegami, T. Toshima, N. Harimoto, H. Uchiyama, Y. Soejima, Y. Yamashita, K. Shirabe, Y. Maehara, Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma, Transplantation Proceedings, 10.1016/j.transproceed.2013.05.001, 45, 9, 3310-3313, 2013.11, We have proposed risk factors for tumor recurrence, such as tumor nodule ≥5 cm and des-gamma-carboxy prothrombin ≥300 mAU/mL after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors for HCC recurrence and mortality within our criteria. We enrolled 152 adult recipients who had undergone LDLT for end-stage liver disease with HCC who met our criteria. The recurrence-free survival rates after LDLT were calculated. Risk factors for tumor recurrence were identified. On univariate analysis, factors affecting recurrence-free survival were pretransplant treatment for HCC, neutrophil-to-lumphocyte ratio (NLR) >4, alpha-fetoprotein ≥400 ng/mL, ≥5 nodules, and bilobar tumor distribution. Multivariate analysis identified that NLR >4 and ≥5 nodules were independent risk factors for tumor recurrence after LDLT (P =.003 and P =.002, respectively). Two-step selection criteria enable selection of patients who have high-risk of tumor recurrence..
1788. Hideki Ijichi, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Ken Shirabe, Yoshihiko Maehara, Recurrent hepatitis B following recurrence of hepatocellular carcinoma after living donor liver transplantation., Unknown Journal, 104, 10, 376-382, 2013.10, Hepatitis B virus (HBV) recurrence after liver transplantation for HBV-associated liver diseases results in decreased patient and graft survival. Herein we have reported two cases of HBV recurrence following relapse of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT). Both cases had LDLT for end-stage liver disease secondary to HBV infection with nodules of HCC exceeding the Milan criteria. HBV prophylaxis using hepatitis B immunoglobulin with nucleos (t) ide analogues were given and HBV DNA levels were consistently undetectable after LDLT. HCC recurred at 5 months and 13 months posttransplant respectively, and chemotherapy and radiation therapy were performed. HBV recurrence occurred during the treatment of HCC. HBV DNA levels increased despite the treatment with anti-HBV agents after HBV recurrence. In hepatitis B surface antigen positive recipients, HBV prophylaxis should be intensified during the treatment of recurrent HCC..
1789. N. Harimoto, K. Shirabe, Y. I. Yamashita, T. Ikegami, T. Yoshizumi, Y. Soejima, T. Ikeda, Y. Maehara, A. Nishie, T. Yamanaka, Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma, British Journal of Surgery, 10.1002/bjs.9258, 100, 11, 1523-1530, 2013.10, Background Sarcopenia was identified recently as a poor prognostic factor in patients with cancer. The present study investigated the effect of sarcopenia on short- and long-term outcomes following partial hepatectomy for hepatocellular carcinoma (HCC), and aimed to identify prognostic factors. Methods Data were collected retrospectively for all consecutive patients who underwent hepatectomy for HCC with curative intent between January 2004 and December 2009. Patients were assigned to one of two groups according to the presence or absence of sarcopenia, assessed by computed tomographic measurement of muscle mass at the level of the third lumbar vertebra. Clinicopathological, surgical outcome and long-term survival data were analysed. Results Sarcopenia was present in 75 (40·3 per cent) of 186 patients, and was significantly correlated with female sex, lower body mass index and liver dysfunction, as indicated by abnormal serum albumin levels and indocyanine green retention test at 15 min values. In patients with, and without sarcopenia, the 5-year overall survival rate was 71 and 83·7 per cent respectively, and the 5-year recurrence-free survival rate was 13 and 33·2 per cent respectively. Multivariable analysis revealed that reduced skeletal muscle mass was predictive of an unfavourable prognosis. Conclusion Sarcopenia was predictive of worse overall survival even when adjusted for other known predictors in patients with HCC after partial hepatectomy..
1790. Norifumi Harimoto, Hiroyuki Matsuyama, Kiyoshi Kajiyama, Takashi Nagaie, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Yoshihiko Maehara, Significance of stroke volume variation during hepatic resection under infrahepatic inferior vena cava and portal triad clamping., Unknown Journal, 104, 10, 362-369, 2013.10, Stroke volume variation (SVV), which is measured by analyzing arterial blood pressure waveform characteristics, is a simple and sensitive indicator of fluid responsiveness. The current retrospective study was to investigate SVV and central venous pressure (CVP) during hepatic resection under clamping of both the infrahepatic inferior vena cava (IVC) and the portal triad. All hepatic resections performed from December 2009 to February 2010 at the Department of Surgery at Iizuka Hospital in Japan were included in this study. Invasive hemodynamic monitoring including CVP and SVV were performed in 14 patients. CVP was significantly lower in patients with blood loss < or = 486 g than in those with blood loss > 486 g. SVV was significantly higher in patients with blood loss < or = 486 g than those with blood loss > 486 g during both IVC clamping and IVC + portal triad clamping. Estimated blood loss was significantly less in the group with SVV values > 18% compared to the group with values < or = 18%. There was a significant correlation between SVV and CVP (R2 = 0.714; P < .01). SVV is a useful indicator of intraoperative blood loss without the monitoring of CVP during hepatic resection under clamping of both the infrahepatic IVC and the portal triad..
1791. Junji Kurashige, Genta Sawada, Yusuke Takahashi, Hidetoshi Eguchi, Tomoya Sudo, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Masayuki Watanabe, Masaki Mori, Hideo Baba, Koshi Mimori, Suppression of MAL gene expression in gastric cancer correlates with metastasis and mortality., Unknown Journal, 104, 10, 344-349, 2013.10, The Myelin and lymphocyte-associated protein gene (MAL), which is located on the long arm of chromosome 2, assigned to the region cen-q13 in humans, has been reported as tumor suppressor in several cancers. The aim of this study was to clarify the clinical significance of MAL gene in gastric cancer. The expression levels of MAL mRNA was examined using 50 resected gastric cancer specimens used by laser microdissected to determine the clinicopathological significance. MAL expression was then examined by real-time quantitative PCR assay, and we analyzed the correlation between MAL expression and clinicopathological factors. In clinicopathologic analysis, the low MAL expression group showed significantly higher incidence of lymph node metastasis than the high expression group (79% and 46%, respectively, p < 0.05). Furthermore, the low MAL expression group had a significantly poorer prognosis than the high expression group (p < 0.05). The MAL gene repression related with lymph node metastasis and poor prognosis in gastric cancer, suggesting that the MAL may be a new candidate node metastasis-suppressor gene for gastric cancer..
1792. Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Koshi Mimori, Keishi Sugimachi, Masayuki Watanabe, Ken Shirabe, Yoshihiko Maehara, Application of splenectomy to decompress portal pressure in left lobe living donor liver transplantation., Fukuoka Acta Medica, 104, 9, 282-289, 2013.09, This study was conducted to evaluate the impact of splenectomy in living donor liver transplantation (LDLT) using left lobe grafts. The two hundred and fifty LDLT cases were divided into two groups: Group-S (n = 98, simultaneous splenectomy) and Group-NS (n = 152). Group-S had significantly increased recipient age (54.5 +/- 10.9 years vs. 46.3 +/- 17.0 years, p < 0.01), advanced liver diseases including Child class C (64.8% vs. 51.5%, p < 0.01), higher model for end-stage liver score (17.8 +/- 8.1 vs. 15.4 +/- 5.8, p < 0.01) and more patients with hospitalized status (67.4% vs. 48.0%, p < 0.01), and smaller graft volume/standard liver volume ratio (36.5 +/- 6.1% vs. 40.2 +/- 8.2%, p < 0.01). In Group-S, splenectomy decreased portal venous (PV) pressure decreased from 23.5 +/- 5.2 mmHg to 19.2 +/- 4.8 mmHg (p < 0.01). Group-S had significantly increased PV pressure at laparotomy (24.9 +/- 5.3 mmHg vs. 22.5 +/- 6.3 mmHg, p < 0.01) and decreased PV pressure at closure (16.4 +/- 3.5 mmHg vs. 18.0 +/- 4.7 mmHg, p < 0.01), compared with Group-NS. On the 14th day after LDLT, Group-S had lower total bilirubin (5.7 +/- 6.5 mg/dl vs. 8.7 +/- 8.9 mg/dl, p < 0.01) and smaller ascites output (0.4 +/- 0.7 L/day vs. 0.7 +/- 0.4 L/day, p = 0.01) than Group-NS. The cumulative 5-year graft survival rate was 86.8% in Group-S and 76.2% in Group-NS (p = 0.03). In conclusion, splenectomy had beneficial impacts on graft outcomes in left-lobe LDLT..
1793. Tomoharu Yoshizumi, Toru Ikegami, Koichi Kimura, Hideaki Uchiyama, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Selection of a right posterior sector graft for living donor liver transplantation, Liver Transplantation, 10.1002/lt.23924, 20, 9, 1089-1096, 2014.01, Right posterior sector (RPS) grafts have been used to overcome graft size discrepancies, the major concern of living donor liver transplantation. Previous studies have reported the volumetry-based selection of RPS grafts without anatomical exclusion. We reviewed our data and established selection criteria for RPS grafts. The procurement of RPS grafts [conventional (n-=-3) and extended (n-=-5)] was performed for 8 of 429 recipients at our center. Extended RPS grafts contained the drainage area of the right hepatic vein. The mean graft weight (GW) according to 3-dimensional computed tomography volumetry was 488 g, and the GW/standard liver weight (SLW) ratio was 42.6%. The mean actual GW was 437 g, and the GW/SLW ratio was 38.4%. One donor exhibited standard bifurcation of the right portal vein (PV) and the left PV, and 2 donors exhibited trifurcation of the left PV, the right anterior portal vein (APV), and the posterior PV. The remaining 5 donors exhibited APV branching from the left PV, which is the most suitable anatomy for RPS grafts. Two recipients died of sepsis or small-for-size graft syndrome. One underwent retransplantation because of an intractable bile leak and fibrosing cholestatic hepatitis. Intractable bile duct (BD) stenosis developed in 4 of the 6 survivors. In conclusion, with the significant complications and potential concerns associated with RPS grafts, these grafts should be used very rarely and with extreme caution. Donors with the standard bifurcation of the PV and the posterior BD running through the dorsal side of the posterior PV are not suitable candidates for RPS grafts. Extended RPS graft procurement is recommended for easier parenchymal transection..
1794. Takahiro Tomino, Yo Ichi Yamashita, Tomohiro Iguchi, Shinji Itoh, Mizuki Ninomiya, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Tetsuo Ikeda, Shinichi Aishima, Ken Shirabe, Yoshihiko Maehara, Spontaneous massive necrosis of hepatocellular carcinoma with narrowing and occlusion of the arteries and portal veins, Case Reports in Gastroenterology, 10.1159/000362440, 8, 1, 148-155, 2014.01, We herein present the case of a 77-year-old man who had fever and right hypochondriac pain. He visited his doctor and underwent contrast computed tomography (CT), and he was suspected to have a liver abscess. He received an antibiotic treatment and his symptoms soon disappeared, but the tumor did not get smaller and its density on contrast CT image got stronger. He underwent biopsy and moderately differentiated hepatocellular carcinoma (HCC) was found. Extended left hepatic and caudate lobectomy was performed. Histological examination showed moderately differentiated HCC with narrowing and occlusion both in the arteries and portal veins associated with mild chronic inflammation. The mechanisms of spontaneous regression of HCC, such as immunological reactions and tumor hypoxia, have been proposed. In our case, histological examination showed the same findings. However, the mechanism is complex, and therefore further investigations are essential to elucidate it..
1795. Toru Ikegami, Huanlin Wang, Tomoharu Yoshizumi, Takeo Toshima, Shinichi Aishima, Takasuke Fukuhara, Norihiro Furusyo, Kazuhiro Kotoh, Shinji Shimoda, Ken Shirabe, Yoshihiko Maehara, Strategies to treat interferon-induced graft dysfunction after living donor liver transplantation for hepatitis C, Hepatology International, 10.1007/s12072-013-9496-2, 8, 2, 285-292, 2014.01, Purpose: Interferon-induced graft dysfunction (IGD) is a poorly defined, unrecognized, but potentially serious condition for patients receiving antiviral drugs after liver transplantation for hepatitis C. Methods: We evaluated the characteristics of 80 patients who received pegylated interferon-based antiviral treatment for hepatitis C after living donor liver transplantation (LDLT). Results: Eight patients experienced IGD either during (n = 6) or after completing (n = 2) antiviral treatment. Pathological diagnosis included acute cellular rejection (ACR, n = 1), plasma cell hepatitis (PCH, n = 2), PCH plus ACR (n = 3), and chronic rejection (CR, n = 2). One patient with CR initially presented with PCH plus ACR and the other presented with ACR; both had apparent cholestasis. The six patients with ACR or PCH without cholestasis were successfully treated by discontinuing antiviral treatment and increasing immunosuppression, including steroids. By contrast, both of the patients with CR and cholestasis experienced graft loss, despite aggressive treatment. Univariate analysis showed that pegylated interferon-α2a-based treatment (75 vs. 26.4 %, p < 0.01) was the only significant factor for IGD, and was associated with decreased 5-year graft survival (93.4 vs. 71.4 %, p = 0.04). Conclusions: IGD is a serious condition during or even after antiviral treatment for hepatitis C after LDLT. Early recognition, diagnosis, discontinuation of interferon, and introduction of steroid-based treatment may help to save the graft..
1796. Shotaro Kuramitsu, Tomohiro Iguchi, Mizuki Ninomiya, Yo ichi Yamashita, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Hirofumi Kawanaka, Tetsuo Ikeda, Toshiya Furuta, Ryuichiro Tamada, Yoshihiko Maehara, [Case report of introducing MMF and steroids as an immunosuppressive therapy after living-donor liver transplantation for a patient with the diabetic nephropathy]., Fukuoka igaku zasshi = Hukuoka acta medica, 105, 3, 79-83, 2014.01, Calcineurin inhibitor (CNI) combined with mycophenolate mofetil (MMF) and steroid is mainly used as immunosuppressive therapy after the living-donor liver transplantation (LDLT). However, the nephrotoxicity caused by CNI remains a critical problem for patients with chronic renal failure, especially on early postoperative period. A 62-year-old woman with decompensated liver cirrhosis secondary to hepatitis B (Child-Pugh C, MELD score 11 points) and chronic renal failure due to diabetic nephropathy (Cr 1.56 mg/dl, GFR 27 ml/min/1.73 m2) experienced LDLT. During the reconstruction of hepatic vein, the supra-and infra-hepatic vena cava was totally clamped. The estimated right lobe liver graft volume was 540 g, representing 51.3% of the standard liver volume of the recipient. Because of the perioperative renal dysfunction due to diabetic nephropathy and the total clamping the vena cava which induced the congestion kidney, MMF (1500 mg/day) and steroid (250 mg/day converted into predonisolone) were mainly introduced as an immunosuppressive therapy after LDLT. The low-dose CNI, tacrolimus also induced the nephrotoxicity and was given for only a short time. Finally, according to the postoperative renal function, the low-dose CNI, cyclosporin (50 mg/day) was able to be added to the introduced immunosuppressive therapy. After having left the hospital, MMF (1500 mg/day), steroid (20 mg/day converted into predonisolone) and cyclosporin (75 mg/day) continued to be given as the immunosuppressive therapy and neither acute graft rejection nor drug-induced renal dysfunction was occurred. This is a case report of introducing with mainly MMF and steroid as an immunosuppressive therapy after LDLT for a patient with perioperative renal dysfunction..
1797. Tomohiro Iguchi, Ken Shirabe, Kentaro Inoue, Shuhei Ito, Takefumi Ohga, Tadahiro Nozoe, Takahiro Ezaki, Tomoharu Yoshizumi, Hideaki Uchiyama, Yuji Soejima, Toru Ikegami, Yo Ichi Yamashita, Hirofumi Kawanaka, Tetsuo Ikeda, Hiroshi Saeki, Masaru Morita, Yoshihiko Maehara, Impact of high preoperative steroid doses on postoperative complications among patients on prolonged preoperative steroid therapy., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 499-506, 2013.12, Corticosteroids are essential to maintain the organic homeostasis. Steroid, glucocorticoid or its synthetic analog is widely used for inflammatory and autoimmune diseases. Prolonged steroid therapy is reported to cause the susceptibility to infection, impaired wound healing and psychoneurosis, however whether the quantity of taking the preoperative steroid is associated the postoperative complication is still unknown. The aim of this study was to elucidate whether the steroid dose in patients on prolonged preoperative steroid therapy is associated postoperative morbidity and mortality. Twenty-five patients taking steroid for various illnesses and underwent the surgery under general anesthesia were selected in this study. The mean +/- standard deviation and the median of the steroid dose converted into hydrocortisone (mg/day) were 39.2 +/- 31.0 and 20, respectively. Of 25 cases, postoperative complications were seen in 10 cases. The postoperative complication was severe based on the grade of Clavien and Dindo by ANOVA as the doses of taking steroid increased (p = 0.0171). The grave postoperative complication classified as Clavien and Dindo grade III occurred with 100% sensitivity and 87% specificity for the steroid dose converted into hydrocortisone > 80 mg/day. Preoperative taking the large amount of steroid (> 80 mg/day) could cause a grave complication. More careful selection of the operative procedure might improve the mobidity rate..
1798. Shigeyuki Nagata, Ken Shirabe, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Hideaki Uchiyama, Yo Ichi Yamashita, Hiroshi Saeki, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Tomonobu Gion, Yuji Soejima, Tetsuo Ikeda, Shunichi Tsujitani, Yoshihiko Maehara, Pilot study of preoperative immunonutrition with antioxidants in living donor liver transplantation donors., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 530-538, 2013.12, Previous studies have demonstrated that oxidative stress by mediating the excessive production of reactive oxygen species is involved in tissue damage and organ failure during and after surgery. The impact of the preoperative immunonutrition including antioxidants on the postoperative course of patients undergoing hepatic surgery was investigated in this pilot study. Twenty-three living donor liver transplantation (LDLT) donors were randomly assigned to either an experimental (AO) group, received a commercial supplement enriched with antioxidant nutrients for each of the 5 days immediately prior to surgery while maintaining normal food intake, or a control (CT) group, administered no supplement. Antioxidative capacity was measured by spectrophotometry of patient serum using a free-radical analytical system. The antioxidative capacity of 90.9% patients in the AO group increased after immunonutrition. Compared to the CT group, the AO group was found to have higher antioxidant capacity and transferrin levels; lower WBC, lymphocyte, and neutrophil counts; and briefer duration of postoperative fever during the postsurgical period. No significant differences were found between the 2 groups regarding the nutritional parameters; liver functioning parameters; immunological parameters; intraoperative factors; postoperative outcomes. Preoperative immunonutrition including antioxidants might play a beneficial role in improving postsurgical immunological response but the modest biological advantage was not associated with any significant clinical outcome..
1799. Norifumi Harimoto, Ken Shirabe, Hidekazu Nakagawara, Takeo Toshima, Yo Ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Yoshihiko Maehara, Prognostic factors affecting survival at recurrence of hepatocellular carcinoma after living-donor liver transplantation
With special reference to neutrophil/lymphocyte ratio, Transplantation, 10.1097/TP.0b013e3182a53f2b, 96, 11, 1008-1012, 2013.12, BACKGROUND: In living-donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC), it is important to predict not only who may be susceptible to recurrence but also who may survive longer. The neutrophil/lymphocyte ratio (NLR) is useful to properly assess the patient without decreasing the long-term survival after LDLT. In this study, we investigated the relationship between NLR and prognosis of patients with recurrent HCC after LDLT. METHODS: In total, 167 LDLTs for HCC were enrolled in this study. Clinicopathologic factors for HCC recurrence after LDLT were investigated and prognostic factors were examined with respect to survival. RESULTS: The following factors were found to be significant in patients with HCC recurrence compared with the controls: α-fetoprotein ≧300 ng/mL, des-γ- carboxyprothrombin ≧300 mAU/mL, NLR ≧4, tumor number >3, tumor size ≧5 cm, duration of last treatment of HCC to LDLT <3 months, Milan criteria exceeded, histologic tumor number ≧10, histologic tumor size >5 cm, poor differentiation, presence of histologic vascular invasion, adjuvant chemotherapy, and interferon therapy against patients with hepatitis C virus. Male sex, interferon therapy against patients with hepatitis C virus, α-fetoprotein ≧300 ng/mL at recurrence, NLR ≧4 at recurrence, and nonsurgical resection for recurrent HCC were significantly related to poor prognosis. The 3-year survival rate after recurrence was 0% in patients with NLR ≧4 and 43.6% in patients with NLR <4. NLR was reelevated after LDLT in patients who later died; however, NLR gradually decreased in surviving patients. CONCLUSION: NLR at recurrence is a prognostic factor affecting survival after recurrence in LDLT for HCC..
1800. Yo ichi Yamashita, Ken Shirabe, Takeo Toshima, Eiji Tsuijita, Kazuki Takeishi, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara, Risk factors for recurrence after curative resection of hepatitis C-related hepatocellular carcinoma in patients without postoperative interferon therapy, Hepatology Research, 10.1111/hepr.12091, 43, 12, 1313-1320, 2013.12, Aim: Hepatitis C (HC)-related hepatocellular carcinoma (HCC; HC-HCC) is highly recurrent. Methods: From 1995-2007, 183 curative hepatic resections for primary solitary HC-HCC without postoperative interferon therapy were included in this study. The patients were divided into three groups: (i) 2cm or less (n=56); (ii) more than 2cm to less than 5cm (n=79); and (iii) 5cm or more (n=48). Independent risk factors for HC-HCC recurrence for each group were determined. Results: Independent risk factors for recurrence were aspartate aminotransferase or alanine aminotransferase (AST/ALT) of 80IU/L or more (hazard ratio [HR], 2.1; P=0.02) in patients with HCC of 2cm or less, des-γ-carboxy prothrombin of 100mAU/mL or more (HR, 2.5; P=0.02) and AST/ALT of 80IU/L or more (HR, 2.1; P=0.04) in patients with HCC of more than 2cm to less than 5cm, and the presence of macroscopic portal vein tumor thrombus (HR, 2.8; P=0.02) and AST/ALT of 80IU/L or more (HR, 2.1; P=0.04) in patients with HCC of 5cm or more. All 13 late recurrences of 1 year or more after hepatic resection (27.1%) in patients with HCC of 5cm or more were accompanied by AST/ALT of 80IU/L or more. Conclusion: AST/ALT of 80IU/L or more is an independent risk factor for the recurrence of primary solitary HC-HCC after curative resection irrespective of the primary HC-HCC size..
1801. Noboru Harada, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yo Ichi Yamashita, Hiroshi Saeki, Eiji Oki, Hirofumi Kawanaka, Masaru Morita, Tetsuo Ikeda, Hiroshi Matsuura, Kenichiro Okadome, Yoshihiko Maehara, Surgical treatment and adjuvant chemotherapy for patients with biliary tract cancer
single institution experience of 100 patients., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 539-548, 2013.12, Surgery remains the treatment of choice for patients with resectable biliary tract cancer, enhancing the chance of cure and increasing long-term survival. Early recurrence, however, is frequent in patients who have undergone curative resection. To date, no randomized controlled trials have assessed adjuvant chemotherapy in patients with biliary tract cancer. The aim of this study was to evaluate the outcomes of surgical management followed by adjuvant chemotherapy in patients with biliary tract cancer. This study enrolled 100 patients with Union for International Cancer Control (UICC) stages I-IV biliary tract cancer who underwent surgical resection, including 16 who received sequential adjuvant chemotherapy with gemcitabine or S-1. Overall survival (OS), disease-free survival (DFS), and prognostic factors were analyzed. The median duration of follow-up was 12.6 months. Forty-one patients had lymph node metastasis and 81 underwent RO resection. The 1-, 3-, and 5-year OS rates were 80.9%, 48.6%, and 38.3%, respectively, and the 1-, 3-, and 5-year DFS rates were 59.8%, 39.9%, and 24.9%, respectively. Five-year OS rates were similar in patients who did (40.4%) and did not (32.4%) receive adjuvant chemotherapy. The morbidity and mortality rates were 59% and 3%, respectively. Multivariate analysis showed that only lymph node metastasis (p = 0.042) was independently associated with long-term survival. The presence of lymph node metastasis significantly affected long-term survival, whereas adjuvant chemotherapy did not affect outcomes in our patients with resectable biliary tract cancer..
1802. Hideyuki Konishi, Ken Shirabe, Shohei Yoshiya, Tetsuo Ikeda, Toru Ikegami, Tomoharu Yoshizumi, Ayae Ikawa-Yoshida, Takashi Motomura, Takasuke Fukuhara, Yoshihiko Maehara, Hepatic interferon-gamma-induced protein-10 expression is more strongly associated with liver fibrosis than interleukin-28B single nucleotide polymorphisms in hepatocellular carcinoma resected patients with chronic hepatitis C, Hepatology Research, 10.1111/hepr.12070, 43, 11, 1139-1147, 2013.11, Aim: Single nucleotide polymorphisms (SNP) around IL-28B and interferon (IFN)-stimulated gene (ISG) expression are predictors of response to standard therapy involving IFN for chronic hepatitis C virus (HCV) infection. We analyzed the association between these predictors to improve the prediction of the response to IFN therapy after liver resection for hepatocellular carcinoma (HCC). Methods: Data were collected from 74 patients with HCV-induced HCC. The IL-28B genotype and hepatic ISG mRNA levels were analyzed to clarify their association, focusing on the progression of liver fibrosis. Results: Fifty patients were identified as having major alleles (rs8099917TT) and the remaining 24 patients had minor alleles (rs8099917TG or GG). Hepatic ISG15 expression was lower in the IL-28B major group than that in the IL-28B minor group (P<0.005). IP-10 expression was similar between the IL-28B major and minor groups (P=0.44). IP-10 expression was elevated with advancing stages of liver fibrosis in HCV infected patients (P=0.005). In patients with mild or no fibrosis, the IL-28B major group had lower IP-10 expression than the IL-28B minor group (P=0.02). However, in patients with advanced fibrosis, IP-10 expression was not different between the IL-28B major and minor groups (P=0.66). Conclusion: Hepatic ISG15 expression is associated with IL-28B polymorphisms, while IP-10 is strongly affected by liver fibrosis..
1803. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Tomoharu Yoshizumi, Yo Ichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, A high MELD score, combined with the presence of hepatitis C, is associated with a poor prognosis in living donor liver transplantation, Surgery today, 10.1007/s00595-013-0523-7, 44, 2, 233-240, 2014.02, Purpose: The feasibility of performing living donor liver transplantation (LDLT) for patients with high end-stage liver disease (MELD) scores needs to be assessed. Methods: A total of 357 patients who underwent LDLT were included in this analysis. Results: Overall, 46 patients had high MELD scores (≥25) and their graft survival was similar to that in patients with low MELD scores (<25; n = 311; p = 0.395). However, among patients with high MELD scores, a multivariate analysis showed that the presence of hepatitis C (p = 0.013) and LDLT in Era-I (p = 0.036) was significantly associated with a poorer prognosis. Among patients with hepatitis C (n = 155), the 5-year graft survival rate was significantly lower in patients with high MELD scores (33.7 %, p < 0.001) than in patients with low MELD scores. The 5-year graft survival rate was significantly lower in patients in Era-I (n = 119) compared with those in Era-II/III when stratified by low (73.0 vs. 82.5 %, p = 0.040) and high (55.0 vs. 86.1 %, p = 0.023) MELD scores. Among the patients with high MELD scores, those with hepatitis C and LDLT in Era-I had the worst 5-year graft survival rate (14.3, p < 0.001). Conclusion: The graft outcomes in patients with high MELD scores and the presence of hepatitis C were found to be particularly poor..
1804. Toru Ikegami, Daisuke Imai, Huanlin Wang, Tomoharu Yoshizumi, Yo Ichi Yamashita, Mizuki Ninomiya, Tomohiro Iguchi, Yuki Bekki, Ken Shirabe, Yoshihiko Maehara, D-MELD as a predictor of early graft mortality in adult-to-adult living-donor liver transplantation, Transplantation, 10.1097/01.TP.0000435696.23525.d0, 97, 4, 457-462, 2014.02, BACKGROUND: Ensuring a good match between donor and recipient is critically important to achieve acceptable graft outcomes after living-donor liver transplantation (LDLT). Our objective was to evaluate the product of donor age and Model for End-stage Liver Disease score (D-MELD) as a predictor of graft survival after LDLT. METHODS: We retrospectively evaluated the records of 355 adults who underwent LDLT for chronic liver disease and explored the relationship between D-MELD and graft outcome. RESULTS: High MELD score and advanced donor age were significantly associated with graft survival; D-MELD had the strongest association with in-hospital mortality. Receiver operating characteristic curve analysis showed that a D-MELD score of 462 had the highest sensitivity for predicting in-hospital mortality. Patients were allocated to three groups based on D-MELD (Class A [≤449; n=142], Class B [450-899; n=163], and Class C [≥900; n=50]) and were found to have stratified cumulative 2-year graft survivals of 94.1%, 85.3%, and 63.1%, respectively (P<0.01). Although D-MELD Class C patients had larger graft volume-to-standard liver volume ratio (P<0.01) and received right lobe grafts more often (P<0.01), they still exhibited significantly higher rates of primary graft dysfunction (P<0.01) and in-hospital mortality (P<0.01). Outcomes in D-MELD Class C were significantly worse in hepatitis C-positive patients (P<0.05). CONCLUSIONS: The D-MELD score is a simple and reliable predictor of early graft survival that assists the matching of donors and recipients in LDLT in adults..
1805. H. Uchiyama, K. Shirabe, H. Nakagawara, T. Ikegami, T. Toshima, Y. Soejima, T. Yoshizumi, Y. I. Yamashita, N. Harimoto, T. Ikeda, Y. Maehara, Revisiting the safety of living liver donors by reassessing 441 donor hepatectomies
Is a larger hepatectomy complication-prone?, American Journal of Transplantation, 10.1111/ajt.12559, 14, 2, 367-374, 2014.02, Donor safety is of paramount importance in performing living donor liver transplantation (LDLT). We retrospectively reviewed donor medical records to confirm whether larger donor hepatectomy is absolutely complication-prone. A total of 441 living donor hepatectomies were performed between October 1996 and July 2012 in our institute, which were divided into three eras (Era I, October 1996 to March 2004; Era II, April 2004 to March 2008; Era III, April 2008 to July 2012) and the incidences of postoperative complications were compared among the three types of hepatectomy - right hepatectomy (RH), left hepatectomy (LH) and left lateral segmentectomy (LLS). Although severe complications (Clavien's grade 3 or more) frequently occurred in RH in Eras I and II (15.4% and 10.7%, respectively), the incidence in Era III decreased to the comparable level observed in LH and LLS (5.4% in RH, 2.3% in LH and 5.3% in LLS). The incidence of postoperative complications did not relate to the type of hepatectomy selected in the latest era. Since most complications after hepatectomy were considered preventable, step-by-step meticulous surgical procedures are a prerequisite for further assuring donor safety irrespective of the type of hepatectomy selected. The authors reassess 441 donor hepatectomies and find that with cumulative experiences, right hepatectomies are no longer complication-prone compared to left hepatectomies or left lateral segmentectomies. See editorial by Roll and Roberts on page 251..
1806. Takeo Toshima, Ken Shirabe, Toru Ikegami, Tomoharu Yoshizumi, Atsushi Kuno, Akira Togayachi, Masanori Gotoh, Hisashi Narimatsu, Masaaki Korenaga, Masashi Mizokami, Akihito Nishie, Shinichi Aishima, Yoshihiko Maehara, A novel serum marker, glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP), for assessing liver fibrosis, Journal of gastroenterology, 10.1007/s00535-014-0946-y, 50, 1, 76-84, 2014.01, Background: Recently, a novel marker, hyperglycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP), was developed for liver fibrosis using the glycan “sugar chain”-based immunoassay; however, the feasibility of WFA+-M2BP for assessing liver fibrosis has not been proven with clinical samples of hepatitis.
Methods: Serum WFA+-M2BP values were evaluated in 200 patients with chronic liver disease who underwent histological examination of liver fibrosis. The diagnostic accuracy of WFA+-M2BP values was compared with various fibrosis markers, such as ultrasound based-virtual touch tissue quantification (VTTQ), magnetic resonance imaging based-liver-to-major psoas muscle intensity ratio (LMR), and serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index (APRI).
Results: Serum WFA+-M2BP levels in patients with fibrosis grades F0, F1, F2, F3, and F4 had cutoff indices 1.62, 1.82, 3.02, 3.32, and 3.67, respectively, and there were significant differences between fibrosis stages F1 and F2, and between F2 and F3 (P < 0.01). The area under the receiver operating characteristic curves for the diagnosis of fibrosis (F ≥ 3) using serum WFA+-M2BP values (0.812) was almost comparable to that using VTTQ examination (0.814), but was superior to the other surrogate markers, including LMR index (0.766), APRI (0.694), hyaluronic acid (0.683), and type 4 collagen (0.625) (P < 0.01 each).
Conclusions: Serum WFA+-M2BP values based on a glycan-based immunoassay is an accurate, reliable, and reproducible method for the assessment of liver fibrosis. This approach could be clinically feasible for evaluation of beneficial therapy through the quantification of liver fibrosis in hepatitis patients if this measurement application is commercially realized..
1807. T. Toshima, T. Ikegami, K. Kimura, N. Harimoto, Y. Yamashita, T. Yoshizumi, Y. Soejima, T. Ikeda, K. Shirabe, Y. Maehara, Application of postoperative model for end-stage liver disease scoring system for evaluating liver graft function after living donor liver transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2013.09.034, 46, 1, 81-86, 2014.01, Background The Model for End-Stage Liver Disease (MELD) score has been validated to predict the mortality rate of patients with various chronic liver diseases on the waiting list for liver transplantation (LT). The aim of this study was to assess the value of the postoperative MELD scoring system as an early postoperative predictor of outcome in patients undergoing living donor LT (LDLT). Methods A retrospective analysis of 217 adult-to-adult LDLT patients was performed. The values of the MELD score on various postoperative days (PODs) as predictors of graft loss within 6 months after LDLT were examined by calculating the areas under the receiver operating characteristic (AUROC) curves. The 6-months graft survival rates were compared between patients with (n = 22) and without (n = 195) graft loss. Univariate and multivariate analyses were performed to identify the factors associated with mortality. Results The MELD score on POD2 was a predictor of graft loss, with an AUROC c-statistic of 0.779, a specificity of 79.5%, and a sensitivity of 68.2% at optimal cutoff, whereas the preoperative MELD score c-statistic was 0.605 with 44.6% sensitivity. Multivariate analyses for postoperative mortality revealed MELD-POD2 ≥19 (odds ratio, 5.601; 95% confidence interval [CI], 1.395-4.508; P =.0009) as an independent predictor of short-term graft loss following LDLT, in addition to preoperative hospitalization status. Later MELD POD scores were also predictive of graft loss. Conclusions The early postoperative MELD scoring system is feasible as an index for prediction of postoperative mortality following LDLT..
1808. H. Kawanaka, T. Akahoshi, N. Kinjo, T. Iguchi, M. Ninomiya, Y. I. Yamashita, T. Ikegami, T. Yoshizumi, K. Shirabe, Y. Maehara, Effect of laparoscopic splenectomy on portal haemodynamics in patients with liver cirrhosis and portal hypertension, British Journal of Surgery, 10.1002/bjs.9622, 101, 12, 1585-1593, 2014.01, Background: The effect of splenomegaly in patients with liver cirrhosis and portal hypertension is not fully understood. This study was designed to determine the effect of laparoscopic splenectomy on portal haemodynamics in these patients.
Methods: Patients with liver cirrhosis and portal hypertension who underwent laparoscopic splenectomy in Kyushu University Hospital from January 2006 to March 2009 were evaluated retrospectively. Correlations between splenic size and portal haemodynamics, and changes in portal haemodynamics and in levels of the vasoactive agents endothelin (ET) 1 and nitric oxide metabolites (NOx) before and 7-10 days after laparoscopic splenectomy were analysed.
Results: Portal venous (PV) blood flow, PV cross-sectional area and PV congestion index correlated significantly with splenic size (P <0·050). All three were significantly reduced following splenectomy in 59 patients. The hepatic venous pressure gradient, measured in 18 patients, decreased by 25 per cent after splenectomy (P <0·001). Portal vascular resistance was also reduced, by 21 per cent (P =0·009). The peripheral blood concentration of ET-1 decreased from 2·95 to 2·11 pg/ml (P <0·001), and that of NOx tended to decrease (from 29·2 to 25·0 pg/ml; P =0·068). In hepatic venous blood, the level of ET-1 decreased from 2·37 to 1·83 pg/ml (P =0·006), whereas NOx concentration tended to increase (from 24·5 to 30·9 pg/ml; P =0·067).
Conclusion: In patients with liver cirrhosis and portal hypertension, splenectomy reduced portal venous pressure. A decrease in splanchnic blood flow, by eliminating splenic blood flow, and reduction in intrahepatic vascular resistance, by normalizing hepatic concentrations of ET-1 and NOx, may both have contributed..
1809. Toru Ikegami, Tomoharu Yoshizumi, Yo Ichi Yamashita, Noboru Harada, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Obstructing spontaneous major shunt vessels is or might not be mandatory in living donor liver transplantation
The authors' reply, Transplantation, 10.1097/TP.0000000000000096, 97, 9, e53, 2014.01.
1810. Daisuke Imai, Toru Ikegami, Takeo Toshima, Tomoharu Yoshizumi, Yo Ichi Yamashita, Mizuki Ninomiya, Norifumi Harimoto, Shinji Itoh, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Preemptive thoracic drainage to eradicate postoperative pulmonary complications after living donor liver transplantation, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.09.006, 219, 6, 1134-1142.e2, 2014.01, Background: Thoracic fluid retention after living donor liver transplantation (LDLT) has various negative consequences, including atelectasis, pneumonia, and respiratory distress or failure. Study Design: We analyzed the clinical impact of preemptive thoracic drainage in 177 patients undergoing adult-to-adult LDLT for chronic liver diseases at a single center. Recipients were divided into 2 time periods. The earlier cohort (n = 120) was analyzed for risk factors for postoperative atelectasis retrospectively; the later cohort (n = 57), with a risk factor for postoperative atelectasis, underwent preemptive thoracic drainage prospectively. The incidence of postoperative pulmonary complications was compared between these 2 cohorts. Results: Independent risk factors for atelectasis in earlier cohort were body mass index ≥27 kg/m2 (p < 0.001), performance status ≥3 (p = 0.003) and model for end-stage liver disease score ≥23 (p = 0.005). The rates of atelectasis (21.1% vs 42.5%, p = 0.005) and pneumonia (1.8% vs 10.0%, p = 0.049) were significantly lower in later than in earlier cohort. Moreover, the mean durations of ICU stay (3.6 ± 0.2 days vs 5.7 ± 0.6 days, p = 0.038) and postoperative oxygen support (5.1 ± 0.8 days vs 7.1 ± 0.5 days, p = 0.037) were significantly shorter in the later than in the earlier cohort. There were no significant differences in the incidence of adverse events associated with thoracic drainages between these 2 cohorts. Conclusions: Preemptive thoracic drainage for transplant recipients at high risk of postoperative atelectasis could decrease morbidities after LDLT..
1811. Yuichiroh Umemoto, Shinji Okano, Yoshihiro Matsumoto, Hidekazu Nakagawara, Rumi Matono, Shohei Yoshiya, Yo ichi Yamashita, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Mamoru Harada, Shinichi Aishima, Yoshinao Oda, Ken Shirabe, Yoshihiko Maehara, Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy, Journal of gastroenterology, 10.1007/s00535-014-0933-3, 50, 1, 65-75, 2014.01, Methods: We assessed the levels of PD-L1 and HLA class I expression on HCC samples from 80 patients who had undergone hepatectomy at our institution, and evaluated the correlations between PD-L1 and HLA class I expression and patient prognosis.
Background: Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Surgery is potentially curative, but high recurrence rates worsen patient prognosis. The interaction between the proteins programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) is an important immune checkpoint. The significance of PD-L1 expression and human leukocyte antigen class I (HLA class I), recognized by CD8 T cells, in the prognosis of patients with HCC remains to be determined.
Results: High HLA class I expression was correlated with significantly better recurrence-free survival (RFS), but not overall survival (OS). Multivariate analysis showed that high HLA class I expression was an independent predictor of improved RFS. Low expression of PD-L1 on HCC tended to predict better OS, but the difference was not statistically significant. PD-L1 expression on HCC correlated with the number of CD163-positive macrophages and HLA class I expression with CD3-positive cell infiltration. Univariable and multivariable analyses showed that combined PD-L1 low/HLA class I high expression on HCCs was prognostic for improved OS and RFS.
Conclusions: PD-L1 status may be a good predictor of prognosis in HCC patients with high HLA class I expression. Novel therapies targeting the PD-L1/PD-1 pathway may improve the prognosis of patients with HCC..
1812. Toru Ikegami, Tomoharu Yoshizumi, Masaki Kato, Satomi Yamamoto, Takasuke Fukuhara, Yoshiharu Matsuura, Shota Nakamura, Shinji Itoh, Ken Shirabe, Yoshihiko Maehara, Reduced-dose telaprevir-based triple antiviral therapy for recurrent hepatitis C after living donor liver transplantation, Transplantation, 10.1097/TP.0000000000000166, 98, 9, 994-999, 2014.01, Introduction. The feasibility of telaprevir-based triple therapy for recurrent hepatitis C after liver transplantation (LT) has not been evaluated in Asian patients. Methods. Eleven Japanese patients received reduced-dose telaprevir (1500 mg) and adjusted-dose cyclosporine after LT. Six patients were nonresponders and three were transient responders to dual therapy. Results. Rapid viral response, early viral response, end of treatment response, and sustained viral response were achieved in 27.3%, 90.9%, 90.9%, and 81.8% of patients, respectively. One patient had viral breakthrough at week 8 with a T54A mutation in NS3. Deep sequence analysis showed that the T54A mutation reverted to wild-type after stopping telaprevir administration. Seven patients developed severe anemia, and six received blood transfusions (4Y20U). Their hemoglobin and estimated glomerular filtration rate remained significantly lower than pretreatment values at 36 weeks after treatment. Four patients developed plasma cell hepatitis after completing telaprevir treatment, and it was treated by increasing the immunosuppressants. Although the cyclosporine level/dose ratio was 2.7 times higher at week 4 than before treatment, it was 0.7 times lower at week 36. Conclusions. Reduced-dosed telaprevir-based triple antiviral therapy achieved a high viral clearance rate in Japanese patients after LT. Major adverse events included severe anemia, renal dysfunction, and plasma cell hepatitis..
1813. Satoshi Ida, Eiji Oki, Koji Ando, Yasue Kimura, Yo ichi Yamashita, Hiroshi Saeki, Toru Ikegami, Tomoharu Yoshizumi, Masayuki Watanabe, Masaru Morita, Ken Shirabe, Tetsuya Kusumoto, Tetsuo Ikeda, Hideo Baba, Yoshihiko Maehara, Pure laparoscopic right-sided hepatectomy in the semi-prone position for synchronous colorectal cancer with liver metastases, Asian journal of endoscopic surgery, 10.1111/ases.12098, 7, 2, 133-137, 2014.05, INTRODUCTION: Simultaneous resection for colorectal cancer and synchronous colorectal liver metastases (SCRLM) has been found to be safe and effective. However, pure laparoscopic simultaneous resection (PULSAR) for primary colorectal cancer and SCRLM is usually difficult, especially in the right lobe of the liver. The purpose of this study was to assess the feasibility of PULSAR for patients with primary colorectal cancer and SCRLM.
METHODS: From January 2008 to December 2012, a total of 10 patients (9 men and 1woman; mean age, 64 years) underwent PULSAR for a primary tumor and SCRLM.
RESULTS: Seven patients (70%) with lesions in the right lobe (segments 6, 7, and 8) successfully underwent resection with a pure laparoscopic procedure while in the left semi-prone position. No patient was converted to conventional open surgery. The mean operative duration, volume of bleeding, and postoperative hospital stay were 606 ± 46 min, 585 ± 145 mL, and 18 ± 3.5 days, respectively. Although a liver abscess developed in one patient, no colonic complications or perioperative death occurred.
CONCLUSION: PULSAR for primary colorectal cancer and SCRLM is a feasible multidisciplinary treatment. Moreover, PULSAR can be safely and effectively performed with the patient in the semi-prone position, even when SCRLM exists in the right lobe of the liver..
1814. Yoshihiro Nagao, Tomohiko Akahoshi, Hideo Uehara, Naotaka Hashimoto, Nao Kinjo, Hirofumi Kawanaka, Morimasa Tomikawa, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuuji Soejima, Ken Shirabe, Yoshihiko Maehara, Balloon-occluded retrograde transvenous obliteration is feasible for prolonged portosystemic shunts after living donor liver transplantation, Surgery today, 10.1007/s00595-013-0535-3, 44, 4, 633-639, 2014.04, Purposes: The purpose of our study was to evaluate the efficacy of balloon-occluded retrograde transvenous obliteration (B-RTO) in patients after living donor liver transplantation (LDLT). Methods: Five patients with gastric varices (GVx) and/or liver dysfunction who were treated with B-RTO from January 2001 to December 2007 were enrolled in this study (GVx, n = 2; liver dysfunction, n = 1; both, n = 2). The eradication rate of the GVx, portal vein hemodynamics and improvement of liver function were evaluated. Results: B-RTO was performed successfully, and the GVx disappeared or decreased markedly in all patients. Recurrence of GVx was not observed during the follow-up. Significantly increased portal vein inflow and improved liver function were observed in all patients. Conclusions: B-RTO may be an effective treatment for patients after LDLT to prevent bleeding from GVx or to modulate portal vein inflow that is reduced by prolonged large portosystemic shunts..
1815. Toru Ikegami, Yuki Bekki, Daisuke Imai, Tomoharu Yoshizumi, Mizuki Ninomiya, Hiromitsu Hayashi, Yo Ichi Yamashita, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Clinical outcomes of living donor liver transplantation for patients 65 years old or older with preserved performance status, Liver Transplantation, 10.1002/lt.23825, 20, 4, 408-415, 2014.04, The purpose of this study was to determine the outcomes of living donor liver transplantation (LDLT) for elderly recipients. We reviewed 411 adult-to-adult LDLT cases, including 46 recipients who were 65 years old or older and 365 recipients who were less than 65 years old. The elderly group had a higher proportion of females (P=0.04) and a smaller body surface area (P<0.001) and more frequently underwent transplantation because of hepatitis C (P<0.001) or hepatocellular carcinoma (P<0.001). Elderly patients had less advanced liver disease with lower Model for End-Stage Liver Disease (MELD) scores (P=0.02) and preserved health without the need for prolonged hospitalization (P<0.01). The transplanted graft volume/standard liver volume ratios were similar for the 2 groups (P=0.22). The elderly group had fewer episodes of acute rejection (P=0.03) but had more neuropsychiatric complications (P=0.01). The 5- and 10-year graft survival rates were comparable for the elderly group (89.8% and 77.8%, respectively) and the younger group (79.4% and 72.9%, respectively; P=0.21). Seven recipients were 70 years old or older, and they had a mean MELD score of 15.6±5.2; 6 of these patients were treated as outpatients before LDLT. All were alive after LDLT and showed good compliance with medical management with a mean follow-up of 5.7±3.0 years. In conclusion, LDLT can be safely performed and has acceptable long-term outcomes for low-risk elderly recipients with preserved performance status..
1816. Kensuke Kudou, Mizuki Ninomiya, Tomohiro Iguchi, Norifumi Harimoto, Shinji Itoh, Noboru Harada, Kazuki Takeishi, Yo Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Cystic liver infection after living donor liver transplantation
A case report, Case Reports in Gastroenterology, 10.1159/000363375, 8, 2, 169-174, 2014.04, There are no reports of cystic liver infection after liver transplantation. Herein, we report a rare case of cystic liver graft infection after living donor liver transplantation (LDLT). The patient was a 24-year-old man with primary sclerosing cholangitis who underwent right lobe graft LDLT. Preoperative abdominal computed tomography (CT) revealed a liver cyst at segment 8 of the donor liver. Biliary reconstruction was performed with hepaticojejunostomy. The postoperative course was uneventful until the patient developed a high fever and abdominal pain 15 months after LDLT. Abdominal contrast CT revealed abscess formation. Percutaneous drainage of the cyst was performed and purulent liquid was drained. The fever gradually subsided after treatment. On follow-up CT, the size of the infected liver cyst was decreased. Clinicians should be aware of the potential for cystic liver infection when using grafts with liver cysts, particularly when biliary reconstruction is performed with hepaticojejunostomy..
1817. T. Yoshizumi, K. Shirabe, T. Ikegami, N. Yamashita, Y. Mano, S. Yoshiya, R. Matono, N. Harimoto, H. Uchiyama, T. Toshima, Y. Maehara, Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis, Transplant Infectious Disease, 10.1111/tid.12188, 16, 2, 225-231, 2014.04, Background: Several studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT). Methods: Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3 months after LDLT were analyzed. Results: Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively. Conclusions: Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis..
1818. Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Frequent plasma cell hepatitis during telaprevir-based triple therapy for hepatitis C after liver transplantation, Journal of Hepatology, 10.1016/j.jhep.2013.10.037, 60, 4, 894-896, 2014.04.
1819. Toshiro Masuda, Ken Shirabe, Toru Ikegami, Norifumi Harimoto, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Tetsuo Ikeda, Hideo Baba, Yoshihiko Maehara, Sarcopenia is a prognostic factor in living donor liver transplantation, Liver Transplantation, 10.1002/lt.23811, 20, 4, 401-407, 2014.04, The aims of this study were to investigate sarcopenia as a novel predictor of mortality and sepsis after living donor liver transplantation (LDLT) and to evaluate the effects of early enteral nutrition on patients with sarcopenia. Two hundred four patients undergoing preoperative computed tomography within the month before LDLT were retrospectively evaluated. The lengths of the major and minor axes of the psoas muscle were simply measured at the caudal end of the third lumbar vertebra, and the area of the psoas muscle was calculated. A psoas muscle area lower than the 5th percentile for healthy donors of each sex was defined as sarcopenia. Ninety-six of the 204 patients (47.1%), including 58.3% (60/103) of the male patients and 35.6% (36/101) of the female patients, were diagnosed with sarcopenia. Sarcopenia was independently and significantly associated with overall survival: there was an approximately 2-fold higher risk of death for patients with sarcopenia versus patients without sarcopenia (hazard ratio = 2.06, P = 0.047). Sarcopenia was an independent predictor of postoperative sepsis (hazard ratio = 5.31, P = 0.009). Other independent predictors were a younger recipient age (P < 0.001) and a higher body mass index (P = 0.02). Early enteral nutrition within the first 48 hours after LDLT was performed for 24.2% in 2003-2007 and for 100% in 2008-2011, and the incidence of postoperative sepsis for patients with sarcopenia (n = 96) was 28.2% (11/39) in 2003-2007 and 10.5% (6/57) in 2008-2011 (P = 0.03). In conclusion, sarcopenia is an independent predictor of mortality and sepsis after LDLT. The incidence of postoperative sepsis was reduced even in patients with sarcopenia after the routine application of early enteral nutrition. Liver Transpl 20:401-407, 2014..
1820. Daisuke Matsuda, Takeo Toshima, Toru Ikegami, Norifumi Harimoto, Yo Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Thrombotic microangiopathy caused by severe graft dysfunction after living donor liver transplantation
Report of a case, Clinical Journal of Gastroenterology, 10.1007/s12328-013-0446-2, 7, 2, 159-163, 2014.04, Thrombotic microangiopathy (TMA) is a life-threatening complication after transplantation including liver transplantation, and its typical clinical picture is characterized by hemolytic anemia, thrombocytopenia, renal dysfunction, neurological abnormalities, and fever. We report the case of a 56-year-old female with end-stage liver disease who underwent living donor liver transplantation (LDLT), and whose postoperative course was characterized by renal failure and progressive hyperbilirubinemia. Two weeks after LDLT, she started to show progressive thrombocytopenia, anemia, oliguria, and encephalopathy. From these clinical manifestations, she was diagnosed as having TMA and underwent plasma exchanges with continuous hemodialysis under temporary holding calcineurin inhibitors. The patient promptly responded to the treatment, with improved hematological, hepatic, and renal conditions, and was discharged from hospital a month later in a stable condition. We describe this case of TMA after LDLT with poor graft function and extensively review the disease in liver transplant recipients..
1821. Tomoharu Yoshizumi, Toru Ikegami, Yuki Bekki, Mizuki Ninomiya, Hideaki Uchiyama, Tomohiro Iguchi, Yo Ichi Yamashita, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Re-evaluation of the predictive score for 6-month graft survival in living donor liver transplantation in the modern era, Liver Transplantation, 10.1002/lt.23804, 20, 3, 323-332, 2014.03, The limitations of donor age, graft size, and the Model for End-Stage Liver Disease (MELD) score have not been apparent in living donor liver transplantation (LDLT). Our team developed a formula for predicting graft survival after LDLT; the formula includes the graft weight, donor age, MELD score, and portosystemic shunt status. The aims of this study were to re-evaluate the reliability of our formula and to assess whether our modified treatment strategy has improved 6-month graft survival. Two hundred seventeen patients were allocated into 2 groups: patients with predictive scores ≥ 1.30 (n = 162) and patients with predictive scores < 1.30 (n = 55). The latter group was also divided into subgroups of patients with scores of 1.15 to 1.30 (n = 37) and patients with scores < 1.15 (n = 18). Survival rates for patients with scores < 1.30 were significantly worse than rates for patients with scores ≥ 1.30 (P = 0.006). Survival rates for patients with scores < 1.15 were significantly worse than rates for patients with scores of 1.15 to <1.30 (P < 0.001). A multivariate analysis showed that a predictive score < 1.15 (odds ratio = 7.87, P = 0.006) and a body mass index ≥ 30 kg/m 2 (odds ratio = 13.3, P < 0.001) were independent risk factors for 6-month graft mortality. In conclusion, predictive scores reliably predict 6-month graft survival and could allow a widening of the safe ranges for donor ages and graft sizes..
1822. Tomoharu Yoshizumi, Ken Shirabe, Hidekazu Nakagawara, Toru Ikegami, Norifumi Harimoto, Takeo Toshima, Yo ichi Yamashita, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara, Skeletal muscle area correlates with body surface area in healthy adults, Hepatology Research, 10.1111/hepr.12119, 44, 3, 313-318, 2014.03, Aim: Depletion of skeletal muscle mass (sarcopenia) predicts survival in patients with cancer or liver cirrhosis. Recently, many reports have used computed tomography (CT) to measure muscle area to define sarcopenia. However, the definition of sarcopenia using CT has not been fully determined. The aim of this study was to establish formulae to calculate the standard area of skeletal muscle. Methods: Forty-five healthy adults (24 men and 21 women, aged 21-66 years) who wished to donate part of their liver for transplantation underwent CT. Cross-sectional areas (cm2) of skeletal muscle were measured at the caudal end of the third lumbar vertebra. Regression analysis was performed to establish formulae to calculate the standard area of skeletal muscle. A validation conducted on 30 other healthy adults was performed to check the accuracy of formulae. Results: Men had a median skeletal muscle area of 155.0cm2 (range, 114.0-203.0), compared with 111.7cm2 (range, 89.8-139.3) in women (P<0.001). Furthermore, skeletal muscle area significantly correlated with body surface area (BSA) in men (P<0.0001, r2=0.60) and women (P<0.0001, r2=0.78). The formulae to calculate skeletal muscle area were 126.9×BSA-66.2 in men and 125.6×BSA-81.1 in women. The estimated muscle area significantly correlated with actual muscle area in men (P=0.003, r2=0.64) and women (P=0.0001, r2=0.70). Conclusion: Sarcopenia can be defined by the difference between measured data and calculated data using our new formulae..
1823. Takeo Toshima, Ken Shirabe, Takasuke Fukuhara, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Shinji Okano, Yoshihiko Maehara, Suppression of autophagy during liver regeneration impairs energy charge and hepatocyte senescence in mice, Hepatology, 10.1002/hep.27140, 60, 1, 290-300, 2014.07, Autophagy is a homeostatic mechanism that regulates protein and organelle turnover and uses the amino acids from degraded proteins to produce adenosine 5'-triphosphate (ATP). We investigated the activity of autophagy-associated pathways in liver regeneration after partial hepatectomy (PHx) in liver-specific autophagy-related gene 5 (Atg5) knockout (KO) mice. Liver regeneration was severely impaired by 70% PHx, with a reduction in postoperative mitosis, but a compensating increase in hepatocyte size. PHx induced intracellular adenosine triphosphate and β-oxidation reduction as well as injured cellular mitochondria. Furthermore, PHx in Atg5 KO mice enhanced hepatic accumulation of p62 and ubiquitinated proteins. These results indicated that reorganization of intracellular proteins and organelles during autophagy was impaired in the regenerating liver of these mice. Up-regulation of p21 was associated with hepatocyte senescence, senescence-associated β-galactosidase expression, irreversible growth arrest, and secretion of senescence-associated molecules, including interleukin (IL)-6 and IL-8. Conclusion: These findings indicate that autophagy plays a critical role in liver regeneration and in the preservation of cellular quality, preventing hepatocytes from becoming fully senescent and hypertrophic..
1824. N. Harimoto, T. Ikegami, H. Nakagawara, Y. I. Yamashita, T. Yoshizumi, H. Uchiyama, Y. Soejima, T. Ikeda, K. Shirabe, S. Aishima, Y. Oda, Y. Maehara, Chronic immune-mediated reaction syndrome as the cause of late graft mortality in living-donor liver transplantation for primary biliary cirrhosis, Transplantation Proceedings, 10.1016/j.transproceed.2014.02.021, 46, 5, 1438-1443, 2014.06, Introduction Few studies to date have investigated the causes of late graft mortality after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC). Patients and Methods Fifty-five LDLTs for PBC were retrospectively reviewed. Factors prognostic of graft survival after LDLT were investigated, and histologic findings in patients with late graft loss were assessed. Results The 1-, 5-, and 10-year cumulative graft survival rates were 85.1%, 82.5%, and 66.9%, respectively. Multivariate Cox regression analysis found that male donor and ≥4 HLA mismatches were independently associated with poor graft survival. Among the 13 grafts lost, 5 were lost >1 year after LDLT, including 1 each due to chronic rejection, veno-occlusive disease, and obliterative portal venopathy, and 2 to other causes. Pathologic reviews of the serial biopsy specimens and explanted grafts from these 5 patients, with graft rejections from "chronic immune-mediated reaction syndrome," showed reciprocal changes over time. No patient died of recurrent PBC. Conclusions Male donor and ≥4 HLA mismatches were independent factors associated with poor graft survival. Late graft mortality after LDLT for PBC in some patients was due to chronic immune-mediated reaction syndrome, including chronic rejection, veno-occlusive disease, and obliterative portal venopathy, but not to recurrent PBC..
1825. Shohei Yoshiya, Yukiko Fujimoto, Yuki Bekki, Hideyuki Konishi, Yo ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Impact of epidermal growth factor single-nucleotide polymorphism on recurrence of hepatocellular carcinoma after hepatectomy in patients with chronic hepatitis C virus infection, Cancer Science, 10.1111/cas.12415, 105, 6, 646-650, 2014.06, Epidermal growth factor (EGF) gene single-nucleotide polymorphism (SNP) is associated with an increased risk of hepatic tumors. The study aimed to elucidate the impact of EGF SNP and EGF receptor (EGFR) expression on the recurrence of hepatocellular carcinoma (HCC) after hepatectomy. To examine the impact of EGF SNP and EGFR on recurrent HCC, we retrospectively analyzed 141 HCC patients with chronic hepatitis C virus infection who underwent curative hepatectomy. The EGF *61 GG allele was present in 69 patients (48.9%), AG in 56 (39.7%) and AA in 16 (11.4%). The AA group had a significantly lower rate of intrahepatic metastasis (0% vs 16.5%, P = 0.02), lower serum EGF concentration (26.3 ± 15.9 pg/mL vs 43.4 ± 30.5 pg/mL, P = 0.02) and lower proportion of early recurrence (≤2 years; 28.6% vs 71.2%, P = 0.03) than the AG/GG group. The AA group had significantly higher recurrence-free survival than the AG/GG group (P = 0.04), but there was no significant difference in overall survival between these two groups (P = 0.97). High versus low EGFR expression analyzed by immunohistochemical staining in cancer cells was not significantly associated with overall survival (P = 0.37) or recurrence-free survival (P = 0.39). Therefore, EGF *61 AA was associated with a lower risk of recurrence after curative hepatectomy for HCC in patients with hepatitis C virus infection than other genotypes, but EGFR expression in cancer cells was not significantly associated with prognosis. EGF *61 AA was associated with a lower risk of recurrence after curative hepatectomy for HCC in patients with hepatitis C virus infection than other genotypes. EGFR expression in cancer cells was not significantly associated with prognosis..
1826. H. Konishi, T. Motomura, Y. Matsumoto, N. Harimoto, T. Ikegami, T. Yoshizumi, Y. Soejima, K. Shirabe, T. Fukuhara, Y. Maehara, Interferon-lambda4 genetic polymorphism is associated with the therapy response for hepatitis C virus recurrence after a living donor liver transplant, Journal of Viral Hepatitis, 10.1111/jvh.12154, 21, 6, 397-404, 2014.06, The standard therapy against hepatitis C virus (HCV) recurrence postliver transplantation includes interferon (IFN)α and ribavirin. IFNL4 ss469415590 polymorphism has been reported as a novel predictor of the response to IFN therapy for chronic HCV infection. We examined the impact of IFNL4 polymorphism on the responsiveness to IFN therapy after liver transplantation. Tissue specimens were collected from 80 HCV-infected recipients and 78 liver donors, and their IFNL4 ss469415590 genotype, hepatic IFNL4 and interferon-stimulated genes' mRNA expression levels were examined. The association of the polymorphism and expression levels in terms of the IFN therapy response to HCV recurrence was analysed. Most individuals who had rs8099917 risk alleles also had ss469415590 risk alleles (R2 = 0.9). Sustained virological response (SVR) rates were higher in both liver graft recipients and transplants with ss469415590 TT/TT alleles than in those with the risk ΔG allele (P = 0.003 and P = 0.005, respectively). In recipients with ss469415590 TT/TT, IFNL4 TT mRNA levels showed no significant differences between livers of patients who responded to therapy and those who did not (P = 0.4). In recipients with the risk ΔG allele, IFNL4 ΔG mRNA expression levels were significantly lower in SVR patients than in non-SVR patients (P = 0.02). Hepatic interferon stimulable genes and IFNL4 mRNA expression were correlated. Our findings suggest that analysing the ss469415590 genotype and IFNL4 ΔG expression provides a novel prediction strategy for the possible response to IFN therapy after liver transplantation..
1827. Shohei Yoshiya, Ken Shirabe, Hidekazu Nakagawara, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Yo Ichi Yamashita, Norifumi Harimoto, Akihiro Nishie, Takeharu Yamanaka, Yoshihiko Maehara, Portal vein thrombosis after hepatectomy, World journal of surgery, 10.1007/s00268-013-2440-8, 38, 6, 1491-1497, 2014.06, Background: Although various complications after hepatectomy have been reported, there have been no large studies on postoperative portal vein thrombosis (PVT) as a complication. This study evaluated the incidence, risk factors, and clinical outcomes of PVT after hepatectomy. Methods: The preoperative and postoperative clinical characteristics of patients who underwent hepatectomy were retrospectively analyzed. Results: A total of 208 patients were reviewed. The incidence of PVT after hepatectomy was 9.1 % (n = 19), including main portal vein (MPV) thrombosis (n = 7) and peripheral portal vein (PPV) thrombosis (n = 12). Patients with MPV thrombosis had a significantly higher incidence of right hepatectomy (p < 0.001), larger resection volume (p = 0.003), and longer operation time (p = 0.021) than patients without PVT (n = 189). Multivariate analysis identified right hepatectomy as a significant independent risk factor for MPV thrombosis (odds ratio 108.9; p < 0.001). Patients with PPV thrombosis had a significantly longer duration of Pringle maneuver than patients without PVT (p = 0.002). Among patients who underwent right hepatectomy, those with PVT (n = 6) had a significantly lower early liver regeneration rate than those without PVT (n = 13; p = 0.040), and those with PVT had deterioration of liver function on postoperative day 7. In all patients with MPV thrombosis who received anticoagulation therapy, PVT subsequently resolved. Conclusions: Postoperative PVT after hepatectomy is not rare. It is closely related to delayed recovery of liver function and delayed liver regeneration..
1828. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Yoichi Yamashita, Hirofumi Kawanaka, Tetsuo Ikeda, Masaru Morita, Eiji Oki, Yoshihiko Maehara, Use of living donor liver grafts with double or triple arteries, Transplantation, 10.1097/01.TP.0000442687.33536.c4, 97, 11, 1172-1177, 2014.06, BACKGROUND: Hepatic grafts used in living donor liver transplantation (LDLT) sometimes have two or more arteries, in which surgeons are required to perform complex arterial reconstruction. The aim of the current study was to demonstrate whether selecting living donor liver grafts with double or triple arteries yielded the same outcomes as grafts with a single artery. METHODS: We retrospectively investigated the outcomes of LDLT focusing on the numbers of arteries on grafts. Four hundred forty-six cases of LDLT performed between October 1996 and October 2012 were retrospectively analyzed. The cases were divided into the following three groups according to the number of arteries on a graft: the single (n=331), the double (n=108), and the triple (n=7) groups. RESULTS: Artery-related complications occurred in five cases in the single group, two cases in the double group, and no case in the triple group. Although the overall graft survival was comparable among the three groups, there was a tendency of worsened graft survival and increased incidence of anastomotic biliary stricture after liver transplantation in right hepatic grafts with double arteries. CONCLUSIONS: The use of grafts with double or triple arteries yielded favorable outcomes with minimum artery-related complications compared with grafts with a single artery. However, the use of right hepatic grafts with double arteries is discouraging in the current study..
1829. Takeo Toshima, Ken Shirabe, Yoshihiro Matsumoto, Shohei Yoshiya, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Yoshihiko Maehara, Autophagy enhances hepatocellular carcinoma progression by activation of mitochondrial β-oxidation, Journal of gastroenterology, 10.1007/s00535-013-0835-9, 49, 5, 907-916, 2014.05, Background: Several types of cancers, including hepatocellular carcinoma (HCC), show resistance to hypoxia and nutrient starvation. Autophagy is a means of providing macromolecules for energy generation under such stressed-conditions. The aim of this study was to clarify the role of autophagy in HCC development under hypoxic conditions. Methods: The expression of microtubule-associated protein 1 light chain 3 (LC3), which is a key gene involved in autophagosome formation, was evaluated in human HCC using immunohistochemistry and western blot. The relationship between LC3 and hypoxia-induced factor 1α (HIF1α) expression was examined using real-time PCR. In addition, human HCC cell line Huh7 was treated with pharmacological autophagy-inhibitor and inactive mutant of Atg4B (Atg4B C74A) under hypoxic condition to evaluate the effects of hypoxia-induced autophagy on cell survival, intracellular ATP, and mitochondrial β-oxidation. Results: LC3 was significantly highly expressed in HCC as compared with noncancerous tissues. LC3 expression, correlated with HIF1α expression, was also significantly correlated with tumor size, and only in the context of large tumors, was an independent predictor of HCC recurrence after surgery. In addition, Huh7 treated with autophagy-inhibitor under hypoxia had lower viability, with low levels of intracellular ATP due to impaired mitochondrial β-oxidation. Conclusions: Autophagy in HCC works to promote HIF1α-mediated proliferation through the maintenance of intracellular ATP, depending on the activation of mitochondrial β-oxidation. These findings demonstrated the feasibility of anti-autophagic treatment as a potential curative therapy for HCC, and improved understanding of the factors determining adaptive metabolic responses to hypoxic conditions..
1830. M. Taniguchi, H. Furukawa, T. Kawai, H. Morikawa, K. Morozumi, M. Goto, T. Kondo, A. Aikawa, T. Ito, S. Takahara, M. Nio, N. Kokudo, S. Uemoto, N. Fukushima, K. Yoshida, T. Kenmochi, H. Date, M. Ono, S. Eguchi, T. Shimamura, K. Mizuta, T. Yoshizumi, T. Ueno, Establishment of educational program for multiorgan procurement from deceased donors, Transplantation Proceedings, 10.1016/j.transproceed.2014.02.002, 46, 4, 1071-1073, 2014.05, Introduction Multiorgan procurement is not an easy procedure and requires special technique and training. Since sufficient donors are not available for on-site training in Japan, establishment of the educational program for multiorgan procurement is mandatory. Materials and methods Development of e-learning and simulation using pigs are our main goals. E-learning contains three dimensional computer graphic (3DCG) animations of the multiorgan procurement, explanation of both donor criteria and procurement procedure, and self-assessment examination. To clarify the donor criteria, the risk factors to 3-month survival of the recipients were analyzed in 138 adult cases of liver transplantation. The 3DCG animation for liver procurement was developed, which was used in the lecture prior to the simulation on August 10, 2013. The results of the examination after this lecture (exam 2013) were compared with the results after the lecture without using animation in 2012 (exam 2012). The simulation was performed by 97 trainees divided into 9 teams, and the surveys were conducted. Results The risk factors for early outcome of the recipients were cold ischemia time (≥10 hours), Model for End-stage Liver Disease score (≥20), and donor age (≥55 years). Results of examination showed that overall percentage of the correct answers was significantly higher in exam 2013 than in exam 2012 (48.3% vs 32.7%; P =.0001). The survey after the simulation of multiorgan procurement revealed that most trainees thought that the simulation was useful and should be continued. Conclusion The novel educational program could allow young surgeons to make precise assessments and perform the exact procedure in the multiorgan procurement..
1831. Shohei Yoshiya, Toru Ikegami, Tomoharu Yoshizumi, Huanlin Wang, Noboru Harada, Yo Ichi Yamashita, Akihiro Nishie, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Fairly rare de novo inflammatory pseudotumor in a graft after living donor liver transplantation, Liver Transplantation, 10.1002/lt.23828, 20, 5, 616-618, 2014.05.
1832. Ken Shirabe, Shohei Yoshiya, Tomoharu Yoshizumi, Hideaki Uchiyama, Yuji Soejima, Hirofumi Kawanaka, Toru Ikegami, Yo Ichi Yamashita, Tetsuo Ikeda, Yoshihiko Maehara, Liver transplantation in the patients with hepatocellular carcinoma beyond Milan criteria - With special reference to extended criteria, Journal of Japanese Society of Gastroenterology, 111, 5, 885-891, 2014.05.
1833. Ken Shirabe, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Shinji Itoh, Kazuki Takeishi, Takeo Toshima, Kohichi Kimura, Yoshihiro Matsumoto, Yuki Bekki, Daisuke Imai, Yoichi Yamashita, Hirofumi Kawanaka, Yoshihiko Maehara, Transdisciplinary Approach for Sarcopenia. Clinical significance of sarcopenia in the patients with chronic liver disease, Clinical calcium, 24, 10, 1493-1499, 2014.10, Recently, many studies of the patients with chronic liver disease have focused on sarcopenia. In the patients with chronic liver disease, sarcopenia occurs, because of advanced liver failure and hepatocellular carcinoma (HCC) . In both diseases, sarcopenia is an important prognostic factor. Thus, sarcopenia has been reported to be a predictor for recurrence of HCC and early mortality after liver transplantation. In the patients with HCC, the mechanism of sarcopenia is unknown. In the patients with endostea liver failure, muscle compensates energy breakdown of the liver and muscle atrophy occurs. Further research is necessary to clarify whether nutritional support and muscle training prevent from sarcopenia and as a result, improve survival of the patients with chronic liver disease..
1834. Masanori Yoshimatsu, Ken Shirabe, Yoshihiro Nagao, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Tetsuo Ikeda, Katsunori Tatsugami, Yoshihiko Maehara, A safe combined nephrectomy and right lobectomy using the liver hanging maneuver for huge renal cell carcinoma directly invading the right lobe of the liver
Report of a case, Surgery today, 10.1007/s00595-013-0693-3, 44, 9, 1778-1782, 2014.09, We herein discuss a patient who underwent simultaneous combined right nephrectomy and right lobectomy of the liver. A 64-year-old male was diagnosed with a huge right renal cell carcinoma (RCC), 13 cm in diameter, which was invading directly into the right hepatic lobe. This type of RCC has been rarely reported, and an anterior approach using the liver hanging maneuver was extremely useful during hepatic parenchymal dissection. The liver parenchymal dissection was performed prior to mobilization of the liver, because the mobilization of the right lobe of the liver was impossible. During the hepatic parenchymal resection, the liver was suspended with the tape and transected, and thereafter, retroperitoneal dissection, nephrectomy and right lobectomy of the liver were completed. The patient was discharged from the hospital on the 12th postoperative day with an uneventful clinical course. The anterior approach using the liver hanging maneuver during hepatic parenchymal resection can be safe and feasible for huge RCC invading the right hepatic lobe..
1835. Shinji Itoh, Ken Shirabe, Yoshihiro Matsumoto, Shohei Yoshiya, Jun Muto, Norifumi Harimoto, Yo Ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Akihiro Nishie, Yoshihiko Maehara, Effect of body composition on outcomes after hepatic resection for hepatocellular carcinoma, Annals of Surgical Oncology, 10.1245/s10434-014-3686-6, 21, 9, 3063-3068, 2014.09, Purpose. To evaluate the effect of body composition on outcomes after hepatic resection for patients with hepatocellular carcinoma (HCC). Methods. We performed 190 hepatic resections for HCC and divided the patients into 2 groups on the basis of visceral fat area (VFA), assessed by computed tomographic measurement at the level of the umbilicus, into high VFA (H-VFA) (n = 106) and low VFA (L-VFA) (n = 84) groups. We compared the surgical outcomes between the two groups. Results. L-VFA was significantly correlated with a lower body mass index, sarcopenia, lower serum albumin, and liver cirrhosis. There was no difference in the incidence of postoperative complications and mortality between the 2 groups. Patients in the L-VFA group had a significantly poorer prognosis than those in the H-VFA group in terms of both overall (P = 0.043) and recurrence-free (P = 0.001) survival. The results of multivariate analysis showed that sarcopenia rather than L-VFA was an independent and prognostic indicator after hepatic resection with HCC. Conclusions. Body composition is an important factor affecting cancer outcomes after hepatic resection for HCC in Japan..
1836. Y. Yoshida, T. Ikegami, T. Yoshizumi, T. Toshima, Y. I. Yamashita, S. Yoshiya, K. Shirabe, Y. Maehara, Rs8099917 and viral genotyping as indications for living donor liver transplantation for hepatitis C
A case report, Transplantation Proceedings, 10.1016/j.transproceed.2013.09.059, 46, 7, 2426-2429, 2014.09, Introduction Appropriate antiviral treatment is essential for living donor liver transplantation (LDLT) to be effective for treating hepatitis C. However, it has never been reported that pre-LDLT genetic analyses of both host and virus, with prediction of the outcome of post-LDLT antiviral treatment, indicated LDLT for a borderline case.
Case Report We have reported the case of a 68-year-old woman with liver cirrhosis caused by genotype 1b hepatitis C, a history of ruptured esophageal varices, and adequately controlled minor ascites. Her liver function was classified as Child-Pugh grade B. The donor was a 42-year-old woman with an estimated left lobe graft volume (GV) of 33.8% based on the standard liver volume of the recipient. Molecular analyses used to confirm the indication of LDLT for this combination revealed the following: The rs8099917 genotype was T/T in the donor and recipient, the HCV core protein was double wild type, there were no mutations in the interferon sensitivity-determining region, and 8 mutations were found in the interferon/ribavirin resistance-determining region. LDLT was performed because very high sensitivity to interferon treatment was predicted. Discussion Six months after LDLT and uneventful post-LDLT courses, pegylated interferon-α2a and ribavirin were administered under immunosuppression with cyclosporine and mycophenolate mofetil. This regimen was continued for 48 weeks, resulting in a viral response at 10 weeks and a sustained viral response, as predicted.
Conclusions We have reported the usefulness of molecular analyses of host and viral factors for indicating LDLT to treat hepatitis C in a borderline case..
1837. Toru Ikegami, Ken Shirabe, Yo Ichi Yamashita, Tomoharu Yoshizumi, Norifumi Harimoto, Kazuki Takeishi, Eiji Tsujita, Shinji Itoh, Yoshihiko Maehara, Small upper midline incision for living donor hemi-liver graft procurement in adults, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.04.021, 219, 3, e39-e43, 2014.09.
1838. Tetsuo Ikeda, Takao Toshima, Norifumi Harimoto, Youichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Laparoscopic liver resection in the semiprone position for tumors in the anterosuperior and posterior segments, using a novel dual-handling technique and bipolar irrigation system, Surgical endoscopy, 10.1007/s00464-014-3469-y, 28, 8, 2484-2492, 2014.08, Background: Hepatic tumors in the lower edge and lateral segments are commonly treated by laparoscopic liver resection. Tumors in the anterosuperior and posterior segments are often large and locally invasive, and resection is associated with a higher risk of insufficient surgical margins, massive intraoperative bleeding, and breaching of the tumor. Laparoscopic surgery for such tumors often involves major hepatectomy, including resection of a large volume of normal liver tissue. We developed a novel method of laparoscopic resection of tumors in these segments with the patient in the semiprone position, using a dual-handling technique with an intercostal transthoracic port. The aim of this study was to evaluate the safety and usefulness of our technique. Methods: Of 160 patients who underwent laparoscopic liver resection at our center from June 2008 to May 2013, we retrospectively reviewed those with tumors in the anterosuperior and posterior segments. Patients were placed supine or semilateral during surgery until January 2010 and semiprone from February 2010. Results: Before the introduction of the semiprone position in February 2010, a total of 7 of 40 patients (17.5%) with tumors in the anterosuperior and posterior segments underwent laparoscopic liver resection, and after introduction of the semiprone position, 69 of 120 patients (57.5%) with tumors in the anterosuperior and posterior segments underwent laparoscopic liver resection (P < 0.001). There were no conversions to open surgery, reoperations, or deaths. The semiprone group had a significantly higher proportion of patients who underwent partial resection or segmentectomy of S7 or S8, lower intraoperative blood loss, and shorter hospital stay than the supine group (all P < 0.05). Postoperative complication rates were similar between groups. Conclusions: Laparoscopic liver resection in the semiprone position is safe and increases the number of patients who can be treated by laparoscopic surgery without increasing the frequency of major hepatectomy..
1839. Sho Nishimura, Hiroshi Saeki, Toru Ikegami, Koji Ando, Yo Ichi Yamashita, Eiji Oki, Tomoharu Yoshizumi, Masaru Morita, Ken Shirabe, Yoshihiko Maehara, Living donor liver transplantation followed by total gastrectomy - A two-stage planed operative strategy for early gastric cancer concomitant with decompensated liver cirrhosis, Anticancer research, 34, 8, 4307-4310, 2014.08, Aim: With the recent popularization of living donor liver transplantation (LDLT), providing treatment for comorbidities in LDLT recipients has become important. We report the first case of a patient who was successfully treated with LDLT followed by total gastrectomy for early gastric cancer concomitant with decompensated liver cirrhosis. Case Report: A 64-year-old female was admitted for the treatment of severe liver cirrhosis. The patient's preoperative liver function was evaluated as Child-Pugh classification grade C. Upper gastrointestinal endoscopy revealed early gastric cancer. We first performed LDLT to improve her liver function and coagulopathy. Nineteen days after the LDLT, we performed total gastrectomy. Results: The patient's postoperative course was uneventful and she left our hospital on the 18th day after gastrectomy. The final pathological diagnosis of gastric cancer was Stage IA. Conclusion: Aggressive and adequate surgical strategy including LDLT is effective as curative treatment in patients with controllable malignancy concomitant with severe liver dysfunction..
1840. Yo Ichi Yamashita, Daisuke Imai, Yuki Bekki, Kazuki Takeishi, Eiji Tsujita, Toru Ikegami, Tomoharu Yoshizumi, Tetsuo Ikeda, Ken Shirabe, Teruyoshi Ishida, Yoshihiko Maehara, Surgical outcomes of anatomical resection for solitary recurrent hepatocellular carcinoma, Anticancer research, 34, 8, 4421-4426, 2014.08, Background: For eradicating portal venous tumor extension and intrahepatic metastasis in hepatocellular carcinoma (HCC), anatomical resection is, in theory, preferable. Patients and Methods: We carried-out a retrospective cohort study in 110 patients who underwent curative hepatic resection (anatomical resection; n=20, and limited resection; n=90) for solitary recurrent HCC from 1990-2010. Results: No significant difference was found in short-term surgical results such as mortality, morbidity, and duration of hospital stay between the two groups. Anatomical resection did not influence overall and disease-free survival for all patients with a solitary recurrent HCC. In patients with cancer spread, such as pathological vascular invasion and intrahepatic metastasis (n=61), or with des-ã-carboxy prothrombin (DCP)≥100 mAU/ml (n=73), the disease-free survival rate in the anatomical-resection group was significantly better than that in the limited-resection group (p=0.0452 and p=0.0345, respectively). Conclusion: Anatomical resection should be recommended only for HCC suspected of exhibiting cancer spread as reflected by DCP ≥100 mAU/ml in patients with solitary recurrent HCC..
1841. Koichi Kimura, Toru Ikegami, Yuki Bekki, Mizuki Ninomiya, Yo Ichi Yamashita, Tomoharu Yoshizumi, Shohei Yoshiya, Yuji Soejima, Noboru Harada, Ken Shirabe, Yoshihiko Maehara, Clinical significance of gastrointestinal bleeding after living donor liver transplantation, Transplant International, 10.1111/tri.12325, 27, 7, 705-711, 2014.07, The clinical presentations of gastrointestinal bleeding (GIB) occurring after living donor liver transplantation (LDLT) have not been fully described. We performed a retrospective analysis of 297 LDLT cases. Nineteen patients (6.4%) experienced GIB after LDLT. The etiology of GIB included bleeding at the jejunojejunostomy following hepaticojejunostomy (n = 13), peptic ulcer disease (n = 2), portal hypertensive gastropathy (n = 2), and other causes (n = 2). Hemostasis was achieved in 13 patients (68.4%) by endoscopic (n = 3), surgical (n = 1), or supportive treatments (n = 15), but not in the other six patients. Graft dysfunction (P < 0.001), hepaticojejunostomy (P = 0.01), portal vein pressure at the end of surgery >20 mmHg (P = 0.002), and operative blood loss >10 L (P = 0.004) were risk factors. One-year graft survival rate was significantly lower in patients with GIB than in patients without GIB (P < 0.001). The inhospital mortality rate was 52.6% for patients with GIB, 75.0% for patients with graft dysfunction, and 14.3% for patients without graft dysfunction (P = 0.028). Despite its infrequency after LDLT, GIB has strong correlation with graft dysfunction and inhospital mortality..
1842. Ken Shirabe, Takeo Toshima, Koichi Kimura, Yoichi Yamashita, Tetsuo Ikeda, Toru Ikegami, Tomoharu Yoshizumi, Koichiro Abe, Shinichi Aishima, Yoshihiko Maehara, New scoring system for prediction of microvascular invasion in patients with hepatocellular carcinoma, Liver International, 10.1111/liv.12459, 34, 6, 937-941, 2014.07, Background & Aims: The microvascular invasion of cancer cells (mvi) is a good prognostic factor after hepatic resection (HR) and liver transplantation for hepatocellular carcinoma (HCC). This study aimed to predict mvi in patients with HCC. Methods: We studied 63 hepatectomized patients with HCC who had HCC without any extrahepatic metastases and vascular invasion, which were detected during preoperative evaluation. The preoperative clinicopathological data of these patients were analysed to predict presence of mvi. A scoring system was designed using significant risk factors. This system was applied to another series of 34 patients with HCC who underwent HR, and was evaluated for validation. Results: Tumour size, serum des-gamma-carboxy prothrombin (DCP) levels and the maximum standardized uptake value (SUVmax) on 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography were independent clinical predictors for mvi after multivariate analyses. Tumour size, serum DCP levels, and values of SUVmax were used to plot a receiver operating characteristic curve for predicting mvi. Areas under the curve of tumour size, serum DCP levels and SUV max values, were 0.8652, 0.8027 and 0.7848 respectively. Maximal sensitivity and specificity were obtained when the tumour size was 3.6 cm, SUVmax was 4.2, and the serum DCP level was 101 mAU/ml. A scoring system was designed using these three variables. The sensitivity and specificity of our scoring system were 100% and 90.9%, respectively, in the validation test. Conclusion: Our scoring system for mvi, consisting of tumour size, serum DCP levels, and SUV max, provides a precise prediction of mvi..
1843. K. Takeishi, K. Shirabe, Y. Yoshida, Y. Tsutsui, T. Kurihara, K. Kimura, S. Itoh, N. Harimoto, Y. I. Yamashita, T. Ikegami, T. Yoshizumi, A. Nishie, Y. Maehara, Correlation between portal vein anatomy and bile duct variation in 407 living liver donors, American Journal of Transplantation, 10.1111/ajt.12965, 15, 1, 155-160, 2015.01, Our aim was to determine whether variant bile duct (BD) anatomy is associated with portal vein (PV) and/or hepatic artery (HA) anatomy. We examined the associations between BD anatomy and PV and/or HA anatomy in 407 living donor transplantation donors. We also examined whether the right posterior BD (RPBD) course was associated with the PV and/or HA anatomy. Variant PV, HA and BD anatomies were found in 11%, 25% and 25%, respectively, of 407 donors enrolled in this study. The presence of a variant BD was more frequently associated with a variant PV than with a normal PV (61% vs. 20%, p<0.0001). By contrast, the presence of a variant HA was not associated with a variant BD. A supraportal RPBD was found in 357 donors (88%) and an infraportal RPBD was found in 50 donors (12%). An infraportal RPBD was significantly more common in donors with a variant PV than in donors with a normal PV (30% vs. 10%, p=0.0004). Variant PV, but not variant HA, anatomies were frequently associated with variant BD anatomy. Additionally, an infraportal RPBD was more common in donors with a variant PV than in donors with a normal PV. This study investigating the anatomy of 407 living liver donors indicates that variant portal vein, but not variant hepatic artery, anatomies are frequently associated with variant bile duct anatomy..
1844. Takeo Toshima, Toru Ikegami, Yoshihiro Matsumoto, Shohei Yoshiya, Norifumi Harimoto, Yo ichi Yamashita, Tomoharu Yoshizumi, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, One-step venous reconstruction using the donor’s round ligament in right-lobe living-donor liver transplantation, Surgery today, 10.1007/s00595-014-1004-3, 45, 4, 522-525, 2015.01, We herein report the use of an opened round ligament as a venous patch graft for inferior right hepatic vein (IRHV) reconstruction and anastomosis to the inferior vena cava (IVC) in living-donor liver transplantation (LDLT) using a right-lobe (RL) graft. After laparotomy, the donor’s round ligament was harvested and opened, and the semi-transparent umbilical vein, which was 7.0 cm in length and 3.0 cm in width, was carefully trimmed on the back table for use as a patch graft. The right hepatic vein of the graft was anastomosed to the harvested patch, and the IRHV was anastomosed to an independent hole made in the wall on the other side of the patch, to form a bridged vascular patch for anastomosis to the IVC. The interposition graft filled promptly and provided a good outflow from the posterior segment. This is the first report of venous reconstruction using a donor’s round ligament graft in RL-LDLT..
1845. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Akinobu Taketomi, Yoshihiko Maehara, Small-for-Size Syndrome, Transplantation of the Liver Third Edition, 10.1016/B978-1-4557-0268-8.00055-5, 719-728, 2015.01.
1846. Mizuki Ninomiya, Shinichi Aishima, Tomoharu Yoshizumi, Toru Ikegami, Huanlin Wang, Norifumi Harimoto, Shinji Ito, Hideaki Uchiyama, Yuji Soejima, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Different histological sequelae of immune-mediated graft dysfunction after interferon treatment in transplanted dual grafts from living donors, Liver Transplantation, 10.1002/lt.23996, 20, 12, 1520-1522, 2014.12.
1847. Hideki Ijichi, Ken Shirabe, Yoshihiro Matsumoto, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Kazutoyo Morita, Takeo Toshima, Yohei Mano, Yoshihiko Maehara, Evaluation of graft stiffness using acoustic radiation force impulse imaging after living donor liver transplantation, Clinical Transplantation, 10.1111/ctr.12457, 28, 11, 1256-1262, 2014.11, Acoustic radiation force impulse (ARFI) imaging is an ultrasound-based modality to evaluate tissue stiffness using short-duration acoustic pulses in the region of interest. Virtual touch tissue quantification (VTTQ), which is an implementation of ARFI, allows quantitative assessment of tissue stiffness. Twenty recipients who underwent living donor liver transplantation (LDLT) for chronic liver diseases were enrolled. Graft types included left lobes with the middle hepatic vein and caudate lobes (n = 11), right lobes (n = 7), and right posterior segments (n = 2). They underwent measurement of graft VTTQ during the early post-LDLT period. The VTTQ value level rose after LDLT, reaching a maximum level on postoperative day 4. There were no significant differences in the VTTQ values between the left and right lobe graft types. Significant correlations were observed between the postoperative maximum value of VTTQ and graft volume-to-recipient standard liver volume ratio, portal venous flow to graft volume ratio, and post-LDLT portal venous pressure. The postoperative maximum serum alanine aminotransferase level and ascites fluid production were also significantly correlated with VTTQ. ARFI may be a useful diagnostic tool for the noninvasive and quantitative evaluation of the severity of graft dysfunction after LDLT..
1848. Hirofumi Kawanaka, Tomohiko Akahoshi, Shinji Itoh, Tomohiro Iguchi, Norifumi Harimoto, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Kenji Takenaka, Yoshihiko Maehara, Optimizing risk stratification in portal vein thrombosis after splenectomy and its primary prophylaxis with antithrombin III concentrates and danaparoid sodium in liver cirrhosis with portal hypertension, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.07.939, 219, 5, 865-874, 2014.11, Background Decreased antithrombin III (ATIII) activity and large splenic vein diameter (SVD) are risk factors for portal vein thrombosis (PVT) after splenectomy in liver cirrhosis with portal hypertension. Antithrombin III concentrates can prevent PVT. This study was designed to stratify risks for PVT after splenectomy in cirrhotic patients and to develop prophylactic protocols for PVT.
Study Design In 53 patients (testing cohort), the cutoff level of preoperative ATIII activity (≤60%) was evaluated for administration of ATIII concentrates. Antithrombin III activity and SVD were re-evaluated as criteria for prophylaxis of PVT. In 57 patients (validation cohort), the risk stratification of PVT and prophylactic protocols were validated.
Results In the testing cohort, 10 (19%) of 53 patients had PVT. Risk level of PVT was stratified and prophylactic protocols were developed. Patients at low risk (ATIII activity ≥70% and SVD <10 mm) were not treated; those at high risk (ATIII activity <70% or SVD ≥10 mm) received ATIII concentrates (1,500 U/day) for 3 days; and those at highest risk (SVD ≥15 mm) received ATIII concentrates for 3 days, followed by danaparoid sodium (2,500 U/day) for 14 days and warfarin. In the validation cohort, 0 of 14 low-risk and 2 of 32 high-risk patients had PVT. Although 8 of 11 patients at highest risk had temporary PVT, it disappeared within 3 months postoperatively. Finally, only 2 (3.5%) of 57 patients had PVT.
Conclusions Risk stratification of PVT after splenectomy and prophylaxis with ATIII concentrates and danaparoid sodium dramatically reduced the incidence of PVT..
1849. Noboru Harada, Ken Shirabe, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Hideaki Uchiyama, Yo ichi Yamashita, Mizuki Ninomiya, Hirofumi Kawanaka, Tomohiko Akahoshi, Yoshihiko Maehara, Bacterial sepsis and perioperative nutritional support therapy in living donor liver transplantation, Bacteremia Risk Factors, Treatment and Potential Complications, 115-130, 2014.10, Bacterial sepsis is a frequent occurrence during the first 1-2 months after liver transplantation under immunosuppressive therapy. Despite recent advances in perioperative management and surgical techniques, postoperative mortality and morbidity rates are still associated with infectious complications, such as bacterial sepsis, after liver transplantation. Furthermore, bacterial sepsis is the most frequent cause of in-hospital death after living donor liver transplantation (LDLT). In this chapter, the etiology, outcomes, and risk factors of bacterial sepsis after LDLT are discussed. In addition, we focus on the effect of perioperative nutritional support in LDLT for preventing bacterial sepsis after LDLT. LDLT involves a smaller graft size and scheduled nonemergent surgery compared with deceased donor liver transplantation. A smaller graft size is the main disadvantage of adult-to-adult LDLT because it results in increased portal venous pressure, impaired bowel motility, bacterial translocation, ascites production, and hyperbilirubinemia. In the last 2 decades, nutritional support has been recognized as a vital component for the management of critically ill patients, by delivering preoperative essential substrates and nutrition using enteral feeding, to aid patient recovery. In particular, preoperative branchedchain amino acid supplementation might reduce the incidence of postoperative bacterial sepsis after LDLT. Additionally, early enteral nutrition is associated with a significantly reduced risk of developing bacterial sepsis after LDLT. Therefore, poor nutritional status of pre-transplants can be improved by using nutritional support, and the high infectious status of posttransplants under immunosuppressive therapy can be improved with initiation of early postoperative enteral nutrition. Improved nutrition supports a functional immune system, and reduces septic morbidity and mortality in patients with liver transplantation..
1850. Yo Ichi Yamashita, Yuki Bekki, Daisuke Imai, Toru Ikegami, Tomoharu Yoshizumi, Tetsuo Ikeda, Hirofumi Kawanaka, Akihiro Nishie, Ken Shirabe, Yoshihiko Maehara, Efficacy of postoperative anticoagulation therapy with enoxaparin for portal vein thrombosis after hepatic resection in patients with liver cancer, Thrombosis Research, 10.1016/j.thromres.2014.07.038, 134, 4, 826-831, 2014.10, Backgrounds: Enoxaparin, low-molecular-weight heparin, has become a routine thromboprophylaxis in general surgery. Study design: A retrospective cohort study was performed in 281 patients who underwent hepatic resections for liver cancers from 2011 to 2013. These patients were divided into two groups; an enoxaparin (-) group (n = 228) and an enoxaparin (+) group (n = 53). Short-term surgical results including venous thromboembolism (VTE) and portal vein thrombosis (PVT) were compared. Results: In the enoxaparin (+) group, the patients' age (65 vs. 69 years; p = 0.01) and BMI (22.9 vs. 24.4; p < 0.01) were significantly higher. According to the symptomatic VTE, symptomatic pulmonary embolism occurred in one patient (0.4%) in the enoxaparin (-) group, but the complication rate was not significantly different (p = 0.63). The complication rate of PVT was significantly lower in the enoxaparin (+) group (10 vs. 2%; p = 0.04). The independent risk factors for PVT were an operation time ≥ 300 minutes (Odds ratio 6.66) and non-treatment with enoxaparin (Odds ratio 2.49). Conclusions: Postoperative anticoagulant therapy with enoxaparin could prevent PVT in patients who underwent hepatic resection for liver cancers..
1851. Jun Muto, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Shinichi Aishima, Kousei Ishigami, Yoshikazu Yonemitsu, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara, The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma, Anticancer research, 34, 10, 5313-5320, 2014.10, Aim: The apelin-APJ system regulates angiogenesis, and is overexpressed in several types of cancer. The aim of this study was to clarify the role of the apelin-APJ system in the angiogenesis of hepatocellular carcinoma (HCC). Materials and Methods: Expressions of angiogenic factors and vascular markers were investigated in specimens from 90 HCC patients. A subcutaneous HCC tumor mouse model was treated with the APJ antagonist, F13A, and tumor growth and vascular development were assessed. Results: APJ expression was observed in arteriole-smooth muscle. Higher amounts of APJ+-arteriole and apelin were detected in tumors (p<0.001 for both). APJ+-arteriole and apelin expression were more commonly observed in moderately- and poorly-differentiated than in well-differentiated HCC (p≤0.003). HCC with irregular dilated arteries expressed higher levels of apelin (p=0.012). Tumor growth was inhibited by treatment with F13A (p<0.001), and arterioles were decreased in the treated group (p=0.047), in vivo. Conclusion: Apelin-APJ is overexpressed, and works as a signal for arteriogenesis in HCC..
1852. Hiroto Kayashima, Ken Shirabe, Rumi Matono, Shohei Yoshiya, Kazutoyo Morita, Kenji Umeda, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Three-dimensional computed tomography analysis of variations in the middle hepatic vein tributaries
proposed new classification, Surgery today, 10.1007/s00595-014-0836-1, 44, 11, 2077-2085, 2014.10, Purpose: To evaluate the anatomical variations in the middle hepatic vein tributaries (V5/V8) for determining the reconstruction strategy in right lobe living donor liver transplantation (LDLT).
Methods: The V5/V8 variations were examined in 268 patients and were classified into three and two types, respectively. The reconstruction rate (RR), patency rate (PR) and clinical outcomes were retrospectively evaluated in 46 right lobe LDLT cases.
Results: In terms of V5 variations, the RR and PR were significantly higher for type 2 than type 3 (82.6 vs. 44.4 % and 73.7 vs. 25.0 %, respectively). The alanine aminotransferase level on postoperative day (POD) 5 in the V5 patent group was significantly lower than in the occluded group (123 vs. 191 IU/dL). Regarding V8 variations, the RR and PR were significantly higher for type 1 than type 2 (44.4 vs. 17.6 % and 75.0 vs. 33.3 %, respectively). The aspartate aminotransferase level on POD 3 was significantly lower in the V8 patent group than in the occluded group (50 vs. 121 IU/dL).
Conclusion: For right lobe grafts with single large V5 (type 2) or V8 (type 1) variations, reconstruction is necessary. Our new classification of the MHV tributaries is useful for determining the reconstruction strategy to use in right lobe LDLT..
1853. Kazuki Takeishi, Takashi Maeda, Eiji Tsujita, Yo Ichi Yamashita, Noboru Harada, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Predictors of intrahepatic multiple recurrences after curative hepatectomy for hepatocellular carcinoma, Anticancer research, 35, 5, 3061-3066, 2015.05, Background/Aim: Survival of patients with multiple recurrences (MR) of hepatocellular carcinoma (HCC) is very poor as recurrent tumors are usually aggressive and not amenable to curative resection. The present study aimed to investigate retrospectively predictors of intrahepatic MR of HCC after hepatectomy. Patients and Methods: We reviewed 416 patients who underwent hepatectomy and developed intrahepatic recurrence during the follow-up period. According to the recurrence pattern, the patients were divided into two groups: 83 who had four or more recurrent lesions in the remnant liver were defined as the MR group and the others who constituted the control group. Results: Multivariate analysis showed that micro-intrahepatic metastasis, α-fetoprotein and tumor size were independent risk factors for MR after hepatectomy. The combination of these three independent factors was significantly associated with MR. The recurrence rates within 1 year after hepatectomy of MR and control groups were 53.0% and 27.6%, respectively (p=0.0001). The 5-year overall survival rate of the MR group was 39%, which was significantly less than that of the control group (68%, p<0.0001). Conclusions: MR of HCC was associated with an earlier recurrence and poorer survival after hepatectomy. The combination of three independent factors for MR might help predict MR occurrence during the follow-up period..
1854. Tomoyuki Uchihara, Yo Ichi Yamashita, Wang Hualin, Kazuki Takeishi, Shinji Itoh, Norihumi Harimoto, Tomoharu Yoshizumi, Shinichi Aishima, Ken Shirabe, Hideo Baba, Yoshihiko Maehara, Recurrence 11 years after complete response to gemcitabine, 5-fluorouracil, and cisplatin chemotherapy followed by radiotherapy in a patient with advanced pancreatic cancer
A case report, Anticancer research, 35, 5, 2867-2872, 2015.05, A 63-year-old man diagnosed with locally advanced pancreatic ductal adenocarcinoma (PDAC; stage IIa) was treated with chemotherapy (gemcitabine, 5-fluorouracil and cisplatin) followed by radiotherapy. He had complete response by imaging and relapse-free survival for 11 years. However, he subsequently presented with local tumor recurrence and underwent pancreaticoduodenectomy followed by chemotherapy; a partial response was achieved. As in liver metastasis of colonic cancer, complete response by imaging in PDAC may not mean pathological complete response. We would propose the importance of adjuvant surgery for a patient with PDAC with complete response by imaging after chemoradiotherapy..
1855. Hideyuki Konishi, Ken Shirabe, Hidekazu Nakagawara, Norifumi Harimoto, Yo Ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshinao Oda, Yoshihiko Maehara, Suppression of silent information regulator 1 activity in noncancerous tissues of hepatocellular carcinoma
Possible association with non-B non-C hepatitis pathogenesis, Cancer Science, 10.1111/cas.12653, 106, 5, 542-549, 2015.05, Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase. In mice, mSirt1 deficiency causes the onset of fatty liver via regulation of the hepatic nutrient metabolism pathway. In this study, we demonstrate SIRT1 expression, activity and NAD+ regulation using noncancerous liver tissue specimens from hepatocellular carcinoma patients with non-B non-C (NBNC) hepatitis. SIRT1 expression levels were higher in NBNC patients than in healthy donors, while SIRT1 histone H3K9 deacetylation activity was suppressed in NBNC patients. In the liver of hepatitis patients, decreased NAD+ amounts and its regulatory enzyme nicotinamide phosphoribosyltransferase expression levels were observed, and this led to inhibition of SIRT1 activity. SIRT1 expression was associated with HIF1 protein accumulation in both the NBNC liver and liver cancer cell lines. These results may indicate that the NBNC hepatitis liver is exposed to hypoxic conditions. In HepG2 cells, hypoxia induced inflammatory chemokines, such as CXCL10 and MCP-1. These inductions were suppressed in rich NAD+ condition, and by SIRT1 activator treatment. In conclusion, hepatic SIRT1 activity was repressed in NBNC patients, and normalization of NAD+ amounts and activation of SIRT1 could improve the inflammatory condition in the liver of NBNC hepatitis patients..
1856. N. Harimoto, H. Wang, T. Ikegami, K. Takeishi, S. Itoh, Y. I. Yamashita, T. Yoshizumi, S. Aishima, K. Shirabe, Y. Oda, Y. Maehara, Hepatology
Rare Stevens-Johnson syndrome and vanishing bile duct syndrome induced by acetaminophen, requiring liver transplantation, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.12849, 30, 4, 656, 2015.04.
1857. T. Yoshizumi, S. Itoh, D. Imai, T. Ikegami, M. Ninomiya, T. Iguchi, N. Harimoto, K. Takeishi, Y. Kimura, H. Uchiyama, Y. Soejima, T. Ikeda, H. Kawanaka, K. Shirabe, Y. Maehara, Impact of platelets and serotonin on liver regeneration after living donor hepatectomy, Transplantation Proceedings, 10.1016/j.transproceed.2014.11.050, 47, 3, 683-685, 2015.04, Background Several animal models have revealed that platelet-derived serotonin initiates liver regeneration after hepatectomy. However, there are few reports regarding the effects of serotonin in the clinical setting. The aim of this study was to explore the impact of serotonin and platelets in the early phase after healthy living donor hepatectomy. Study Design Stored samples from 34 living donors who received left lobectomy with caudate lobectomy (LL+C) or right lobectomy (RL) were available in the study. Serum serotonin levels and platelet counts associated with liver regeneration such as whole liver volume and hepatic graft weight (GW) were retrospectively collected from the database and analyzed. Results The remnant liver volume rate of RL grafts was smaller than that of LL+C grafts (45.4% vs 64.7%; P <.001). The regeneration rate at 7 days after surgery did not differ between the 2 groups (123% vs 122%). The serotonin levels and platelet counts decreased after surgery until postoperative day 3, then increased thereafter. The platelet counts and serotonin levels of LL+C donors were significantly higher than those of RL donors. Conclusions Our findings suggest that platelets and serotonin play a pivotal role in initiating liver regeneration in the remnant liver..
1858. Shinji Itoh, Toru Ikegami, Tomoharu Yoshizumi, Huanlin Wang, Kazuki Takeishi, Norifumi Harimoto, Yo Ichi Yamashita, Hirofumi Kawanaka, Shinichi Aishima, Ken Shirabe, Yoshihiko Maehara, Long-term outcome of living-donor liver transplantation for combined hepatocellular-cholangiocarcinoma, Anticancer research, 35, 4, 2475-2476, 2015.04, Background/Aim: Combined hepatocellular-cholangio carcinoma (cHC-CC) is found unexpectedly in explanted or resected liver specimens. The current study evaluated the longterm outcomes of living-donor liver transplantation (LDLT) between patients with cHC-CC and hepatocellular carcinoma (HCC). Patients and Methods: We performed 178 LDLT including 8 patients of pathologically and immunohistochemically diagnosed cHC-CC who all under went LDLT with a preoperative diagnosis of HCC by ima ging study. Results: Out of the 8 patients, 6 were within the Milan criteria and all were within the Kyushu University criteria. The 1-, 5- and 10-year overall survival (OS) and disease-free survival (DFS) rates after LDLT for patients with cHC-CC were 87.5, 72.9 and 48.6% and 85.7, 85.7 and 85.7%, respectively. The OS and DFS between patients with cHC-CC and HCC were not statistically different. Conclusion: LDLT for patients with cHC-CC using the Milan criteria or the Kyushu University criteria, as well as HCC, could have an acceptable long-term outcome..
1859. N. Harimoto, Y. Yoshida, T. Kurihara, K. Takeishi, S. Itoh, N. Harada, E. Tsujita, Y. I. Yamashita, H. Uchiyama, Y. Soejima, T. Ikegami, T. Yoshizumi, H. Kawanaka, T. Ikeda, K. Shirabe, H. Saeki, E. Oki, Y. Kimura, Y. Maehara, Prognostic impact of Des-γ-carboxyl prothrombin in living-donor liver transplantation for recurrent hepatocellular carcinoma, Transplantation Proceedings, 10.1016/j.transproceed.2014.09.178, 47, 3, 703-704, 2015.04, Background Although the Milan criteria are widely accepted for liver transplantation (LT) in patients for hepatocellular carcinoma (HCC), they have not been fully evaluated for salvage LT in patients with recurrent HCC. We have previously reported outcomes of living-donor LT (LDLT) for HCC and identified 2 risk factors affecting recurrence-free survival (RFS): tumor size >5 cm and des-γ-carboxyl prothrombin (DCP) concentration >300 mAU/mL (Kyushu University criteria). This study was designed to clarify risk factors for tumor recurrence after LDLT in patients with recurrent HCC. Methods Outcomes in 114 patients who underwent LDLT for recurrent HCC were analyzed retrospectively. RFS rates after LDLT were calculated, and risk factors for tumor recurrence were identified. Results The 1-, 3-, and 5-year RFS rates after LDLT were 90.6%, 80.4%, and 78.8%, respectively. Univariate analysis showed that tumor recurrence was associated with alpha-fetoprotein concentration ≥300 ng/mL, DCP concentration ≥300 mAU/mL, tumor number ≥4, tumor size ≥5 cm, transarterial chemotherapy before LDLT, duration of last treatment of HCC to LDLT <3 months, bilobar distribution, exceeding Milan criteria, exceeding Kyushu University criteria, poor differentiation, and histologic vascular invasion. Multivariate analysis showed that DCP ≥300 mAU/mL (P =.03) and duration from last treatment to LDLT <3 months (P =.01) were independent predictors of RFS. Conclusions DCP concentration and time between last treatment and LDLT are prognostic of RFS in patients undergoing LDLT for HCC..
1860. K. Takeishi, T. Ikegami, T. Yoshizumi, S. Itoh, N. Harimoto, N. Harada, E. Tsujita, Y. Kimura, Y. Yamashita, K. Saeki, E. Oki, K. Shirabe, Y. Maehara, Thymoglobulin for steroid-resistant immune-mediated graft dysfunction during simeprevir-based antiviral treatment for post-transplantation hepatitis c
Case report, Transplantation Proceedings, 10.1016/j.transproceed.2014.11.056, 47, 3, 794-795, 2015.04, Introduction Immune-mediated graft dysfunction (IGD), a recently established disease entity with unfavourable outcome, is an antigraft immune reaction during interferon-based antiviral treatment for hepatitis C virus (HCV) infection after liver transplantation (LT). We report a case having steroid-resistant acute cellular rejection (ACR) type IGD, which was successfully treated using thymoglobulin. Case Report A 56-year-old woman with recurrent HCV after LT was commenced on antiviral treatment including simeprevir, pegylated-interferon (IFN) 2a, and ribavirin. A negative serum HCV-RNA was confirmed after 4 weeks. After 12 weeks of therapy, severe liver dysfunction developed, despite a constantly negative HCV-RNA. Liver biopsy revealed portal and periportal inflammatory infiltrates including numerous eosinophils, lymphocytes, and bile duct damages, indicating ACR. IFN therapy was ceased, and she was treated with steroid pulse treatment, followed by high-level immunosuppression maintenance. However, ACR was irremediable. Thereafter she was treated with thymoglobulin (75 mg/d for 5 days). Her serum alanine aminotransaminase and total bilirubin levels decreased immediately, and her liver biopsy specimen showed no activity. During these periods of the treatment, the HCV-RNA became positive and the liver enzyme elevated, but other liver function tests still remained within normal range. Conclusion Thymoglobulin could be the best choice in steroid-resistant IGD during antiviral treatment for post-transplantation recurrent hepatitis C..
1861. T. Ikegami, T. Yoshizumi, Y. Soejima, N. Harimoto, S. Itoh, K. Takeishi, H. Uchiyama, H. Kawanaka, Y. I. Yamashita, E. Tsujita, N. Harada, E. Oki, H. Saeki, Y. Kimura, K. Shirabe, Y. Maehara, Triple therapy using direct-acting agents for recurrent hepatitis C after liver transplantation
A single-center experience, Transplantation Proceedings, 10.1016/j.transproceed.2014.10.058, 47, 3, 730-732, 2015.04, Background Hepatitis C viral graft reinfection is almost a universal event after liver transplantation with consequent disease progression. Methods We applied triple therapy (n = 21) with the use of telaprevir (TVR; n = 12) or simeprevir (SVR; n = 9). Results TVR was given at the dose 1,500 mg daily (n = 11) with reduced dose of cyclosporine at 25% to 50%, and SVR was given at the dose 100 mg daily with unadjusted cyclosporine, followed by 12 weeks of dual therapy. The early viral response was achieved in 91.7% (n = 11), end of treatment response rate was 91.7% (n = 11), and sustained viral response rate was 83.3% (n = 10) in the TVR group, and respective rates were 88.9% (n = 8), 77.8% (n = 7), and 77.8% (n = 7) in the SVR group. Although granulocyte colony-stimulating factor was not given in the patients with triple therapy, blood transfusion was performed in 7 cases (58.3%) in the TVR group and 1 case (11.1%) in the SVR group. Interferon-mediated graft dysfunction was observed in 4 cases (33.3%) in the TVR group and 3 cases (33.3%) in the SVR group, respectively. The cumulative viral clearance rates in triple (n = 21) and dual (n = 105) therapy were 95.0% and 18.1% at 12 weeks, and 95.0% and 40.0%, respectively, at 24 weeks (P <.01). Conclusions Although careful monitoring for possible adverse events is required during treatment, triple therapy with the use of direct-acting agents are very effective in treating hepatitis C after liver transplantation..
1862. Mizuki Ninomiya, Ken Shirabe, Marcelo E. Facciuto, Myron E. Schwartz, Sander S. Florman, Tomoharu Yoshizumi, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Yoshihiko Maehara, Comparative study of living and deceased donor liver transplantation as a treatment for hepatocellular carcinoma, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.12.009, 220, 3, 297-304.e3, 2015.03, Background Living donor liver transplantation (LDLT) is an important treatment option for unresectable hepatocellular carcinoma (HCC), but whether recurrence and survival in LDLT differ from those in deceased donor liver transplantation (DDLT) remains controversial. Study Design A retrospective analysis was performed between patients with HCC who underwent LDLT in a Japanese institute (n = 133) and those who underwent DDLT in a United States institute (n = 362). Results Although there was a difference in patient background characteristics (eg, body mass index, donor age, Model for End-Stage Liver Disease [MELD] score), tumor aggressiveness represented by Milan criteria and microscopic vascular invasion were comparable between the 2 groups. The cumulative 5-year recurrence rates of the LDLT group and the DDLT group were similar (14.8% vs 19.0%, p = 0.638), but overall survival in the LDLT group was significantly better than that in the DDLT group (84.2% vs 63.5%, p < 0.0001). Separate multivariate analysis identified different preoperative predictive factors for HCC recurrence (salvage transplantation and Des-gamma-carboxy prothrombin >300 in the LDLT group, beyond Milan criteria in the DDLT group). Combined multivariate analysis of the 2 groups identified recipient's body mass image >30 kg/m2 as an independent risk factor for overall survival; the technique of transplantation (LDLT or DDLT) was not found to be a risk factor. Conclusions When compared between the institutes where LDLT or DDLT were the first treatment choices for unresectable HCC, recurrence rates were comparable. Living donor liver trasplantation is a viable treatment option for unresectable HCC, providing recurrence rates similar to those achieved with DDLT..
1863. Huanlin Wang, Toru Ikegami, Noboru Harada, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Yo Ichi Yamashita, Shinji Itoh, Norifumi Harimoto, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Optimal changes in portal hemodynamics induced by splenectomy during living donor liver transplantation, Surgery today, 10.1007/s00595-014-0999-9, 45, 8, 979-985, 2015.08, Purposes: The purpose of this study was to evaluate the impact of splenectomy in adult-to-adult living donor liver transplantation (LDLT). Methods: Adult-to-adult LDLTs (n = 276) were divided into those with simultaneous splenectomy during LDLT (Splenectomy group, n = 154) and those without (Non-Splenectomy group, n = 122). Results: In the Splenectomy group, splenectomy decreased the portal venous pressure from 24.0 to 19.1 mmHg (p < 0.001). At the end of surgery, the portal venous pressure was significantly lower and the graft compliance was significantly higher in the Splenectomy group compared with the Non-Splenectomy group. The graft portal venous flow was also better in the Splenectomy group (y = 625–5.1x; r2 = 0.08, p < 0.01) than in the Non-Splenectomy group (y = 470–2.9x; r2 = 0.04, p = 0.03). Fourteen days after LDLT, the total bilirubin and ascites output were lower in the Splenectomy group than in the Non-Splenectomy group. Among the patients with hepatitis C, splenectomy was associated with a significantly higher rate of a sustained viral response (59.4 vs. 35.9 %, p = 0.020) than was noted in those without splenectomy (n = 39). There were no patients with post-splenectomy sepsis under vaccination. Conclusions: By decreasing the portal pressure and increasing the graft vascular compliance, splenectomy conferred better graft outcomes in adult-to-adult LDLT.
1864. M. Ninomiya, K. Shirabe, H. Kayashima, T. Ikegami, A. Nishie, N. Harimoto, Y. Yamashita, T. Yoshizumi, H. Uchiyama, Y. Maehara, Functional assessment of the liver with gadolinium-ethoxybenzyl-diethylenetriamine penta-acetate-enhanced MRI in living-donor liver transplantation, British Journal of Surgery, 10.1002/bjs.9820, 102, 8, 944-951, 2015.07, Background A precise estimation of the capacity of the remnant liver following partial liver resection is important. In this study, the regional function of the liver in patients undergoing living-donor liver transplantation was evaluated by gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (EOB)-enhanced MRI, with special reference to the congested region. Methods EOB-MRI analysis was performed before hepatectomy in donors, and 7days after surgery in the donor and recipient. In the hepatocyte phase, from images obtained 15min after Primovist® injection, the signal intensity in each liver segment was measured and divided by the signal intensity of the erector spinae muscle (liver to muscle ratio, LMR) for standardization. Inter-regional differences in LMRs were analysed in donors and recipients. Results Thirty-two living donors and 31 recipients undergoing living-donor liver transplantation were enrolled. In donors, the LMRs of the remnant left lobe were almost equivalent among the liver segments. In the remnant right lobe without the middle hepatic vein, the mean(s.d.) LMR for congested segments (S5 and S8) was significantly lower than that for non-congested segments (S6 and S7): 2·60(0·52) versus 3·64(0·56) respectively (P<0·001). After surgery, values in the non-congested region were almost identical to those in the preoperative donor liver. LMR values in the left and right lobe graft were significantly lower than those in the corresponding segment before donor surgery (P<0·001). Conclusion The function of the congested region secondary to outflow obstruction in the remnant donor liver was approximately 70 per cent of that in the non-congested region. EOB-MRI is a promising tool to assess regional liver function, with good spatial resolution. Estimation of hepatic functional reserve in liver surgery.
1865. Norifumi Harimoto, Tetsuo Ikeda, Kazuki Takeishi, Shinji Itoh, Yo Ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Outcomes after laparoscopic hepatectomy in the semi-prone position for hepatocellular carcinoma located in segment 6,7, or 8, Anticancer research, 35, 7, 4167-4170, 2015.07, Background: This retrospective study investigated outcomes after laparoscopic hepatectomy in the semi-prone position compared to open hepatectomy in the conventional supine position, for HCC (hepatocellular carcinoma) located in segment 6, 7, or 8. Patients and Methods: Patients were divided into two groups according to the surgical approach. The clinicopathological and surgical outcomes were analyzed. Results: There were no significant differences in patient-related or tumor-related factors between the two groups. The laparoscopic-hepatectomy group had significantly less blood loss, fewer postoperative complications, and a shorter hospital stay than the open-hepatectomy group. There were no in-hospital deaths. The postoperative change in the serum C-reactive protein was a significantly larger decrease in the group treated with laparoscopic hepatectomy than that in the open-hepatectomy group. Conclusion: Laparoscopic hepatectomy in the semi-prone position for HCC is safe and minimally invasive, and can reduce intraoperative bleeding, postoperative complications, and hospital stay compared to open hepatectomy..
1866. Qingjiang Hu, Kazuki Takeishi, Yo Ichi Yamashita, Tetsuo Ikeda, Huanlin Wang, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Splenectomy followed by hepatectomy for hepatocellular carcinoma with hypersplenism and portal hypertension caused by macroglobulinemia, Anticancer research, 35, 7, 4077-4082, 2015.07, Aim: To describe a patient with hepatocellular carcinoma (HCC), accompanied by hypersplenism and portal hypertension caused by macroglobulinemia, who underwent splenectomy followed by hepatectomy. Case Report: A 74-year-old man was admitted to our Hospital. He had previously developed primary macroglobulinemia, which had been completely cured by chemotherapy. At admission, he had a low platelet count (52×103/μl), and his liver function was impaired. Imaging showed a 5-cm-sized tumor, an esophageal varix, and splenomegaly, but not liver cirrhosis. The patient underwent splenectomy for hypersplenism and portal hypertension; the weight of his spleen was 2,400 g. After splenectomy, his platelet count increased to 259×103/μl and his liver function was improved. He safely underwent hepatectomy for HCC. The patient was discharged 14 days later without morbidity. Conclusion: These findings suggest that hepatectomy following splenectomy for hypersplenism and portal hypertension caused by macroglobulinemia, may effectively cure HCC in patients with liver dysfunction and thrombocytopenia..
1867. Yo Ichi Yamashita, Yoshihiro Yoshida, Takeshi Kurihara, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Surgical results for recurrent hepatocellular carcinoma after curative hepatectomy
Repeat hepatectomy versus salvage living donor liver transplantation, Liver Transplantation, 10.1002/lt.24111, 21, 7, 961-968, 2015.07, The aims of this study were to evaluate the efficacy of repeat hepatectomy (Hx) and salvage living donor liver transplantation (LDLT) for recurrent hepatocellular carcinoma (HCC). A retrospective cohort study was performed to analyze the surgical results of repeat Hx and salvage LDLT for patients with recurrent HCC within the Milan criteria from 1989 to 2012. A total of 159 patients were divided into 2 groups: a repeat Hx group (n = 146) and a salvage LDLT group (n = 13). Operative results and patient prognoses were compared between the 2 groups. The operative invasiveness, including the operation time (229.1 ±â€‰97.7 versus 862.9 ±â€‰194.4 minutes; P < 0.0001) and blood loss (596.3 ±â€‰764.9 versus 24,690 ±â€‰59,014.4 g; P < 0.0001), were significantly higher in the salvage LDLT group. The early surgical results, such as morbidity (31% versus 62%; P = 0.0111) and the duration of hospital stay (20 ±â€‰22 versus 35 ±â€‰21 days; P = 0.0180), were significantly worse in the salvage LDLT group. There was no significant difference in the overall survival (OS) rate, but the disease-free survival rate of the salvage LDLT group was significantly better (P = 0.0002). The OS rate of patients with grade B liver damage in the repeat Hx group was significantly worse (P < 0.0001), and the 5-year OS rate was quite low, that is, 20% (liver damage A, 77% for the repeat Hx group and 75% for the salvage LDLT group). The prognosis of patients with grade B liver damage after repeat Hx for recurrent HCC is poor, and salvage LDLT would be a potent option for such patients..
1868. Yo Ichi Yamashita, Yoshihiro Yoshida, Takeshi Kurihara, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Surgical results for recurrent hepatocellular carcinoma after curative hepatectomy
Repeat hepatectomy versus salvage living donor liver transplantation, Liver Transplantation, 10.1002/lt.24111, 21, 7, 961-968, 2015.07, The aims of this study were to evaluate the efficacy of repeat hepatectomy (Hx) and salvage living donor liver transplantation (LDLT) for recurrent hepatocellular carcinoma (HCC). A retrospective cohort study was performed to analyze the surgical results of repeat Hx and salvage LDLT for patients with recurrent HCC within the Milan criteria from 1989 to 2012. A total of 159 patients were divided into 2 groups: a repeat Hx group (n = 146) and a salvage LDLT group (n = 13). Operative results and patient prognoses were compared between the 2 groups. The operative invasiveness, including the operation time (229.1 ±â€‰97.7 versus 862.9 ±â€‰194.4 minutes; P < 0.0001) and blood loss (596.3 ±â€‰764.9 versus 24,690 ±â€‰59,014.4 g; P < 0.0001), were significantly higher in the salvage LDLT group. The early surgical results, such as morbidity (31% versus 62%; P = 0.0111) and the duration of hospital stay (20 ±â€‰22 versus 35 ±â€‰21 days; P = 0.0180), were significantly worse in the salvage LDLT group. There was no significant difference in the overall survival (OS) rate, but the disease-free survival rate of the salvage LDLT group was significantly better (P = 0.0002). The OS rate of patients with grade B liver damage in the repeat Hx group was significantly worse (P < 0.0001), and the 5-year OS rate was quite low, that is, 20% (liver damage A, 77% for the repeat Hx group and 75% for the salvage LDLT group). The prognosis of patients with grade B liver damage after repeat Hx for recurrent HCC is poor, and salvage LDLT would be a potent option for such patients..
1869. Daisuke Taniguchi, Norifumi Harimoto, Kazuki Takeishi, Shinji Itoh, Yoichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Hirofumi Kawanaka, Ken Shirabe, Yosuke Morodomi, Tetsuzo Tagawa, Tatsuro Okamoto, Yoshihiko Maehara, Liver transplantation followed by pulmonary resection complicated with end-stage liver cirrhosis
A case report, Anticancer research, 35, 6, 3411-3414, 2015.06, Background: With the recent popularization of living-donor liver transplantation (LDLT), it has become important to provide treatment for comorbidities in recipients. We report the case of a patient who was successfully treated with LDLT, followed by left upper lobectomy for lung cancer concomitant with decompensated liver cirrhosis. Case Report: A 67-year-old female was admitted for treatment for severe liver cirrhosis. The lung cancer was identified preoperatively using computed tomography. We initially performed LDLT to improve liver function and coagulopathy; the patient was discharged postoperatively on day 39 without complication. Three months after LDLT, we performed a left upper lobectomy. Results: The patient's postoperative course was uneventful and she was discharged after 11 days. Conclusion: We conclude that an aggressive and appropriate surgical strategy, including LDLT, is an effective curative treatment in patients with controllable malignancy, concomitant with severe liver dysfunction..
1870. Masahiro Shimokawa, Shinji Itoh, Toru Ikegami, Kazuki Takeishi, Norifumi Harimoto, Yo Ich Yamashita, Tomoharu Yoshizumi, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Local therapy improvement of outcome in a patient with recurrent hepatocellular carcinoma after living donor liver transplantation
A case report, Anticancer research, 35, 6, 3525-3529, 2015.06, We describe a very rare case of recurrent hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT). A 47-year-old female underwent LDLT for HCC within Milan criteria, receiving a left liver lobe from her 38-year-old husband with an incompatible blood type. Thirty months after LDLT, however, enhanced computed tomography (CT) showed a tumor in her left adrenal gland; after another six months, enhanced CT and positron-emission tomography detected a frontal head bone tumor; enhanced CT performed 54 months after LDLT revealed a recurrent HCC in the liver graft. Each of these three tumors was surgically resected. Two months after hepatic partial resection, an enhanced CT showed another HCC in her liver graft, which was treated with local ablation therapy. One year after the last ablation treatment, the recipient is doing well without evidence of recurrence. At the time of detection of each of these tumors, the patient's serum concentration of hepatitis B virus surface antigen was elevated. Pathological examination showed that the resected tumors were moderately differentiated HCCs. Genotyping by microsatellite analysis confirmed their origin to be metastases of the primary HCC..
1871. Tomohiro Iguchi, Ken Shirabe, Shinichi Aishima, Huanlin Wang, Nobuhiro Fujita, Mizuki Ninomiya, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshinao Oda, Yoshihiko Maehara, New pathologic stratification of microvascular invasion in hepatocellular carcinoma
Predicting prognosis after living-donor liver transplantation, Transplantation, 10.1097/TP.0000000000000489, 99, 6, 1236-1242, 2015.06, Background. Vascular invasion of hepatocellular carcinoma (HCC) has a high incidence of recurrence after liver transplantation. Patients with microvascular invasion (MVI) show a high tumor grade; however, some show a good prognosis. This retrospective study aimed to investigate whether the degree of MVI affects prognosis after living-donor liver transplantation. Methods. A total of 142 patients with HCC who had undergone living-donor liver transplantation were histologically evaluated about the number of invaded vessels and the maximum number of invading carcinoma cells. Patients with MVI were classified into two subgroups: high MVI group (n = 38), which showed more than 50 carcinoma cells in the vessels, with multiple invaded vessels; and low MVI group (n = 17), which showed MVI, but not high MVI. Results. Analysis of recurrence-free survival showed that high MVI group had significantly poorer outcomes than the other groups (P < 0.001). High MVI group had significantly higher α-fetoprotein levels, des-γ-carboxy prothrombin levels, number of tumors, a larger tumor size, and a higher percentage of poorly differentiated HCC than non-MVI group. High MVI was an independent prognostic factor for recurrence-free survival (P = 0.030). Among patients exceeding the Milan criteria (n = 61), high MVI group had significantly poorer outcomes than the other groups for recurrence-free survival (P = 0.003). Patients in high MVI group had significantly higher des-γ-carboxy prothrombin levels and a larger tumor size than non-MVI group. High MVI was an independent prognostic factor for recurrence-free survival (P = 0.014). Conclusion. In living-donor liver transplantation for HCC, high MVI is a novel pathologic marker for predicting prognosis..
1872. Shohei Yoshiya, Ken Shirabe, Daisuke Imai, Takeo Toshima, Yo Ichi Yamashita, Toru Ikegami, Shinji Okano, Tomoharu Yoshizumi, Hirofumi Kawanaka, Yoshihiko Maehara, Blockade of the apelin–APJ system promotes mouse liver regeneration by activating Kupffer cells after partial hepatectomy, Journal of gastroenterology, 10.1007/s00535-014-0992-5, 50, 5, 573-582, 2015.05, Background: Liver regeneration after massive hepatectomy or living donor liver transplantation is critical. The apelin–APJ system is involved in the regulation of cardiovascular function, inflammation, fluid homeostasis, the adipo-insular axis, and angiogenesis, but its function in liver regeneration remains unclear. Methods: We investigated the impact of pharmacologic blockade of the apelin–APJ system, using the specific APJ antagonist F13A on liver regeneration after hepatectomy in mice. Results: F13A-treated mice had significantly higher serum concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 than control mice, due to F13A-promoted activation of Kupffer cells. Compared with untreated mice, F13A enhanced the signal transducer and activator of transcription 3 and mitogen-activated protein kinase pathways, stimulated cell-cycle progression, and promoted hepatocyte proliferation and liver regeneration without inducing apoptosis or inflammation in regenerating livers. In vitro, Kupffer cells expressed APJ and were activated directly by F13A treatment, releasing TNF-α and IL-6. Moreover, F13A-treated mice had a higher survival rate than untreated mice in the extended hepatectomy model. Conclusions: F13A treatment promotes early phase liver regeneration after hepatectomy by promoting the activation of Kupffer cells and increasing serum levels of TNF-α and IL-6. F13A treatment may become a therapeutic option to facilitate efficient liver regeneration after liver surgery..
1873. Shinji Shimoda, Satomi Hisamoto, Kenichi Harada, Sho Iwasaka, Yong Chong, Minoru Nakamura, Yuki Bekki, Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yoshihiko Maehara, Xiao Song He, M. Eric Gershwin, Koichi Akashi, Natural killer cells regulate T cell immune responses in primary biliary cirrhosis, Hepatology, 10.1002/hep.28122, 62, 6, 1817-1827, 2015.12, The hallmark of primary biliary cirrhosis (PBC) is the presence of autoreactive T- and B-cell responses that target biliary epithelial cells (BECs). Biliary cell cytotoxicity is dependent upon initiation of innate immune responses followed by chronic adaptive, as well as bystander, mechanisms. Critical to these mechanisms are interactions between natural killer (NK) cells and BECs. We have taken advantage of the ability to isolate relatively pure viable preparations of liver-derived NK cells, BECs, and endothelial cells, and studied interactions between NK cells and BECs and focused on the mechanisms that activate autoreactive T cells, their dependence on interferon (IFN)-γ, and expression of BEC major histocompatibility complex (MHC) class I and II molecules. Here we show that at a high NK/BEC ratio, NK cells are cytotoxic for autologous BECs, but are not dependent on autoantigen, yet still activate autoreactive CD4+ T cells in the presence of antigen presenting cells. In contrast, at a low NK/BEC ratio, BECs are not lysed, but IFN-γ production is induced, which facilitates expression of MHC class I and II molecules on BEC and protects them from lysis upon subsequent exposure to autoreactive NK cells. Furthermore, IFN-γ secreted from NK cells after exposure to autologous BECs is essential for this protective function and enables autoreactive CD4+ T cells to become cytopathic. Conclusions: NK cell-mediated innate immune responses are likely critical at the initial stage of PBC, but also facilitate and maintain the chronic cytopathic effect of autoantigen-specific T cells, essential for progression of disease..
1874. Norifumi Harimoto, Ken Shirabe, Toru Ikegami, Tomoharu Yoshizumi, Takashi Maeda, Kiyoshi Kajiyama, Takeharu Yamanaka, Yoshihiko Maehara, Postoperative complications are predictive of poor prognosis in hepatocellular carcinoma, Journal of Surgical Research, 10.1016/j.jss.2015.06.012, 199, 2, 470-477, 2015.12, Background A retrospective study was performed at some high-volume institutions to clarify the prognostic significance of postoperative complications in patients who had undergone hepatectomy for hepatocellular carcinoma (HCC). No published studies have investigated the relationship between postoperative complications of Clavien-Dindo grade III or more and prognosis in patients who have undergone hepatic resection. Methods Patient data were retrospectively collected for 966 consecutive patients who had undergone hepatectomy for HCC with curative intent between January 2004 and December 2012. The patients were assigned to two groups according to the presence of postoperative complications. Clinicopathologic, surgical outcome, and long-term survival data were analyzed. Results Hospital deaths occurred in nine patients (0.9%). Postoperative complications were identified in 165 patients (17.1%). Compared with patients without complications, patients with complications had significantly larger tumors, more advanced-stage tumors, more poorly differentiated tumors, more intrahepatic metastasis, longer operation time, greater blood loss, more blood transfusion, and more anatomic resection and combined resection. The overall 5-y survival rates were 48.6% in patients with postoperative complications and 73.2% in patients without them. The 5-y recurrence-free survival rates were 23.7% in patients with postoperative complications and 36.7% in patients without them. Multivariate analysis revealed that longer operation time and lower serum albumin level of albumin were independent predictive factors for occurrence of postoperative complications. Conclusions In patients with HCC, posthepatectomy complications are predictive of a worse overall survival, even when adjustments have been made for other known predictors..
1875. Takeo Toshima, Ken Shirabe, Takeshi Kurihara, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Hirofumi Kawanaka, Tetsuo Ikeda, Yoshihiko Maehara, Profile of plasma amino acids values as a predictor of sepsis in patients following living donor liver transplantation
Special reference to sarcopenia and postoperative early nutrition, Hepatology Research, 10.1111/hepr.12484, 45, 12, 1170-1177, 2015.12, Aim: Sarcopenia is an independent predictor of mortality and sepsis after living donor liver transplantation (LDLT). However, the exact mechanisms by which sarcopenia affects poor prognosis or worse immunity against postoperative sepsis are unclear, particularly regarding muscular amino acid metabolism, and the authors aimed to identify the role of plasma amino acids in sarcopenia by retrospective study. Methods: The area of the psoas muscle in 228 recipients of LDLT was retrospectively measured by dynamic computed tomography. Additionally, plasma amino acid levels were measured both pre- and postoperatively. The impact of plasma amino acids for postoperative sepsis and the relationship between sarcopenia and early nutrition after LDLT were analyzed. Results: Among the plasma amino acids, only leucine, isoleucine and glutamine in patients with sarcopenia were significantly lower than those without sarcopenia (each, P<0.05). Multivariate analysis identified the lower plasma glutamine levels as a risk factor of postoperative sepsis after LDLT (odds ratio 5.371, P=0.002). In sarcopenia patients, plasma glutamine levels after LDLT were significantly decreased compared with before LDLT in patients both with and without postoperative early nutrition. However, in non-sarcopenia patients with early nutrition, plasma glutamine levels after LDLT were comparable with those before LDLT. Conclusion: This is the first report to study the profile of plasma amino acid change before and after LDLT. Low preoperative glutamine values were an independent risk factor for predicting postoperative sepsis. The efficacy of postoperative early nutrition may prevent postoperative sepsis by improving glutamine levels..
1876. Sung Kwan Bae, Shinji Shimoda, Toru Ikegami, Tomoharu Yoshizumi, Norifumi Harimoto, Shinji Itoh, Yuji Soejima, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Risk factors for hepatitis B virus recurrence after living donor liver transplantation
A 17-year experience at a single center, Hepatology Research, 10.1111/hepr.12489, 45, 12, 1203-1210, 2015.12, Aim: The incidence of hepatitis B virus (HBV) recurrence after liver transplantation (LT) has been reduced by prophylaxis with hepatitis B immunoglobulin (HBIG) and nucleoside analogs, but the factors associated with HBV recurrence are unclear. The aim of this study was to determine the risk factors associated with HBV recurrence after living donor LT (LDLT). Methods: A retrospective review was performed for 45 patients (28 male and 17 female; median age, 54years) who underwent LDLT for HBV-related liver disease and were followed up for at least 6months between October 1996 and June 2013. The virological data, tumor burden, antiviral therapy and immunosuppressive therapy were evaluated and compared between the HBV recurrence ad non-recurrence groups. Results: Seven of the 45 patients (15.6%) developed post-LT HBV recurrence. The median interval between LDLT and HBV recurrence was 23.7months (range, 0.8-35.9). Three of the seven patients (42.9%) developed recurrence after cessation of HBIG, and three (42.9%) were cases with hepatocellular carcinoma (HCC) recurrence after LDLT. The remaining case underwent transplantation from a donor with positive hepatitis B surface antigen. Based on the univariate and multivariate analyses, HBIG cessation (hazard ratio [HR], 20.17; 95% confidence interval [95% CI], 2.091-194.593; P=0.009) and HCC recurrence (HR, 30.835; 95% CI, 3.132-303.593; P=0.003) were independent risk factors for HBV recurrence after LDLT. Conclusion: In LDLT patients, cessation of HBIG and HCC recurrence were risk factors associated with HBV recurrence, so careful monitoring for serological HBV markers is needed in patients with these factors..
1877. Yo ichi Yamashita, Daisuke Imai, Yuki Bekki, Koichi Kimura, Yoshiriro Matsumoto, Hidekazu Nakagawara, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Shinichi Aishima, Yoshihiko Maehara, Surgical Outcomes of Hepatic Resection for Hepatitis B Virus Surface Antigen-Negative and Hepatitis C Virus Antibody-Negative Hepatocellular Carcinoma, Annals of Surgical Oncology, 10.1245/s10434-014-4261-x, 22, 7, 2279-2285, 2015.12, Background: The incidence of hepatitis B virus surface antigen-negative and hepatitis C virus antibody-negative hepatocellular carcinoma (NBNC-HCC) is gradually increasing. Methods: A retrospective cohort study was performed in 694 patients who underwent curative hepatic resection for primary HCC from January 1990 to December 2011. Results: In the NBNC-HCC group (n = 110), the complication rate of diabetic mellitus (38 %) was significantly higher than that of the B-HCC group (n = 110; 17 %), and their rate of alcohol abuse (38 %) was significantly higher than that of both the B-HCC (26 %) and C-HCC groups (n = 474; 22 %). In the NBNC-HCC group, the tumor diameter (4.5 ± 3.6 cm) was significantly larger than that of the C-HCC group (2.9 ± 1.8 cm), but the rate of histological cirrhosis (37 %) was significantly lower than those of both the B-HCC (67 %) and C-HCC (53 %) groups. There were no significant differences regarding overall and disease-free survival among the three groups. In the NBNC-HCC group, multiple intrahepatic or distant recurrences (25 %) were significantly higher than in the C-HCC group (17 %), and the rate of recurrence more than 2 years after hepatic resection (24 %) was significantly higher than that of the B-HCC group (12 %). Conclusions: The surgical outcomes of patients with NBNC-HCC were not significantly different compared with those of the patients with B-HCC or C-HCC. There was a substantial population with late recurrence among the patients with NBNC-HCC after curative hepatic resection, and thus not only long-term follow-up but also the early establishment of preventive methods for HCC recurrence from NBNC-hepatitis are necessary..
1878. Yuki Inagaki, Yukio Oshiro, Tomohiro Tanaka, Tomoharu Yoshizumi, Hideaki Okajima, Kohei Ishiyama, Chikashi Nakanishi, Masaaki Hidaka, Hiroshi Wada, Taizo Hibi, Kosei Takagi, Masaki Honda, Kaori Kuramitsu, Hideaki Tanaka, Taiji Tohyama, Toshihiko Ikegami, Satoru Imura, Tsuyoshi Shimamura, Yoshimi Nakayama, Taizen Urahashi, Kazumasa Yamagishi, Hiroshi Ohnishi, Shigeo Nagashima, Masaharu Takahashi, Ken Shirabe, Norihiro Kokudo, Hiroaki Okamoto, Nobuhiro Ohkohchi, A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis E in Liver Transplant Recipients in Japan, EBioMedicine, 10.1016/j.ebiom.2015.09.030, 2, 11, 1607-1612, 2015.11, Background: Recently, chronic hepatitis E has been increasingly reported in organ transplant recipients in European countries. In Japan, the prevalence of hepatitis E virus (HEV) infection after transplantation remains unclear, so we conducted a nationwide cross-sectional study to clarify the prevalence of chronic HEV infection in Japanese liver transplant recipients. Methods: A total of 1893 liver transplant recipients in 17 university hospitals in Japan were examined for the presence of immunoglobulin G (IgG), IgM and IgA classes of anti-HEV antibodies, and HEV RNA in serum. Findings: The prevalence of anti-HEV IgG, IgM and IgA class antibodies was 2.9% (54/1893), 0.05% (1/1893) and 0% (0/1893), respectively. Of 1651 patients tested for HEV RNA, two patients (0.12%) were found to be positive and developed chronic infection after liver transplantation. In both cases, HEV RNA was also detected in one of the blood products transfused at the perioperative period. Analysis of the HEV genomes revealed that the HEV isolates obtained from the recipients and the transfused blood products were identical in both cases, indicating transfusion-transmitted HEV infection. Interpretation: The prevalence of HEV antibodies in liver transplant recipients was 2.9%, which is low compared with the healthy population in Japan and with organ transplant recipients in European countries; however, the present study found, for the first time, two Japanese patients with chronic HEV infection that was acquired via blood transfusion during or after liver transplantation..
1879. Hideaki Uchiyama, Kazutoyo Morita, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Kenji Takenaka, Yoshihiko Maehara, Pancreatic Transection Using Tape Sling and Ultrasonic Aspirator Dissection Technique in Pancreaticoduodenectomy and Distal Pancreatectomy, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2015.08.005, 221, 5, e91-e95, 2015.11.
1880. Takeshi Kurihara, Yo Ichi Yamashita, Yoshihiro Yoshida, Kazuki Takeishi, Shinji Itoh, Norifumi Harimoto, Tomoharu Yoshizumi, Ken Shirabe, Tetsuo Ikeda, Yoshihiko Maehara, Indocyanine Green Fluorescent Imaging for Hepatic Resection of the Right Hepatic Vein Drainage Area, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2015.05.009, 221, 3, e49-e53, 2015.09.
1881. Mitsuhiro Yasuda, Toru Ikegami, Daisuke Imai, Huanlin Wang, Yuki Bekki, Shinji Itoh, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, The changes in treatment strategies in ABOi living donor liver transplantation for acute liver failure, Journal of Medical Investigation, 10.2152/jmi.62.184, 62, 3, 184-187, 2015.09, Introduction. Living donor liver transplantation (LDLT) using ABO-incompatible (ABOi) graft for acute liver failure (ALF) is a developing treatment modality. Methods. We reviewed the changes in our treatment strategies in applying ABOi LDLT for FH over our fourteen years of experience. Results. Five patients with ALF received LDLT in adults using ABOi grafts, with different but gradually renewed protocols. The etiologies for acute liver failure included autoimmune hepatitis (n=3) and unknown (n=2). The desensitization protocol for ABOi barrier included Case #1; local infusion (portal vein)+plasma exchange (PE), Case #2; local infusion (hepatic artery)+rituximab+PE, Case #3 and #4; rituximab+PE, and Case #5; rituximab+PE under high-flow continuous hemodiafiltration. Local infusion was abandoned since Case #3, because Case #1 had portal vein thrombosis resulting in graft necrosis and Case #2 had hepatic artery dissection. The patients (Case #2 and #3), who received rituximab within 7 days before LDLT, experienced antibody-mediated rejection. Thus, the most recent protocol for ABOi-LDLT is that rituximab is given 2 weeks before LDLT, followed by high-flow continuous hemodiafiltration to obstacle hepatic encephalopathy until LDLT. The four patients except Case #1 are doing well with good graft function over 3.8±3.7 years. Conclusion. Rituximab-based ABOi-LDLT, most-recently under high-flow hemodiafiltration for treating encephalopathy, is a feasible option for applying LDLT for ALF..
1882. Hirofumi Kawanaka, Tomohiko Akahoshi, Nao Kinjo, Norifumi Harimoto, Shinji Itoh, Norifumi Tsutsumi, Yoshihiro Matsumoto, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Laparoscopic Splenectomy with Technical Standardization and Selection Criteria for Standard or Hand-Assisted Approach in 390 Patients with Liver Cirrhosis and Portal Hypertension, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2015.04.011, 221, 2, 354-366, 2015.08, Background Laparoscopic splenectomy (LS) is still challenging in patients with liver cirrhosis and portal hypertension. This study was designed to establish safe and less invasive LS in patients with liver cirrhosis and portal hypertension. Study Design We analyzed 390 patients with liver cirrhosis and portal hypertension, who underwent LS between 1993 and 2013. Patients were divided into 3 time periods; early (1993 to 2004, n = 106); middle (2005 to 2008, n = 159); and late (2008 to 2013, n = 125). During the middle time period, standardized technique for LS and selection criteria for hand-assisted LS were adopted. Patients with spleen volume ≥ 1,000 mL by CT volumetry, large perisplenic collateral vessels, and/or Child-Pugh score ≥ 9, underwent hand-assisted LS. During the late time period, the selection criteria were refined and patients with spleen volume ≥ 600 mL underwent hand-assisted LS. Results Conversion to open splenectomy decreased (10.4% in the early time period, 1.9% in the middle time period, and 3.2% in the late time period, p = 0.004), median blood loss decreased (300g, 87g, and 98g, respectively, p < 0.001), and the success rate of pure LS tended to improve (87.2%, 89.5%, and 98.0%, respectively, p = 0.110). Mortality was 0% in each time period, Clavien-Dindo grade IIIb or more complications tended to decrease (5.7%, 2.5%, and 0.8%, respectively, p = 0.081), and technique-related complications decreased significantly (10.4%, 3.8%, and 2.4%, respectively, p = 0.014). Conclusions Laparoscopic splenectomy is now a safe and less invasive approach, even in patients with liver cirrhosis and portal hypertension, because of its technical standardization with the refined selection criteria for pure or hand-assisted LS..
1883. Toru Ikegami, Tomoharu Yoshizumi, Yoshihro Yoshida, Takeshi Kurihara, Norifumi Harimoto, Shinji Itoh, Masahiro Shimokawa, Takasuke Fukuhara, Ken Shirabe, Yoshihiko Maehara, Telaprevir versus simeprevir for the treatment of recurrent hepatitis C after living donor liver transplantation, Hepatology Research, 10.1111/hepr.12546, 46, 3, E136-E145, 2016.03, Aim: Our aim was to evaluate the clinical outcomes of telaprevir (TVR)- or simeprevir (SMV)-based triple therapy for recurrent hepatitis C after living donor liver transplantation. Methods: Twenty-six patients received antiviral therapy, consisting of either TVR (n=12) or SMV (n=14) in combination with pegylated interferon and ribavirin, plus cyclosporin. Results: More patients had a dose reduction of the direct-acting agent (36.3% vs 0.0%, P=0.02) or required blood transfusion for anemia (58.3% vs 7.1%, P<0.01) in the TVR group. The cyclosporin trough/dose ratio increased significantly from week 0 to week 4 in the TVR group (1.6±0.4 to 5.1±2.0, P<0.01), but not in the SMV group (1.2±0.3 to 1.3±0.2, P=0.68). The 24-week cumulative viral clearance rate was 91.7% and 85.7% in the TVR and in SMV groups, respectively. The early viral response and sustained viral response rates were 91.7% and 83.3%, respectively, in the TVR group, compared with 85.7% and 64.3%, respectively, in the SMV group. Interferon-mediated graft dysfunction occurred in four and five patients in the TVR and SMV groups, respectively; two patients were treated by oral steroids, five by steroid pulse and two by thymoglobulin, resulting in viral breakthrough in one case. Conclusion: SMV-based triple therapy was associated with fewer adverse events and drug interactions with cyclosporin, and possibly less antiviral properties to TVR. Interferon-mediated graft dysfunction is a significant clinical problem that warrants particular caution following living donor liver transplantation..
1884. Kazuki Takeishi, Takashi Maeda, Yo ichi Yamashita, Eiji Tsujita, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, A Cohort Study for Derivation and Validation of Early Detection of Pancreatic Fistula After Pancreaticoduodenectomy, Journal of Gastrointestinal Surgery, 10.1007/s11605-015-3030-x, 20, 2, 385-391, 2016.02, Background: Pancreatic fistula (PF) remains the most important morbidity after pancreaticoduodenectomy (PD). Early drain removal was recently recommended. However, this is not applicable to all cases because the development of severe PF may not be obvious until a later postoperative day (POD). This study aimed to discover ways to detect clinically relevant PF early during the postoperative stage after PD. Methods: We studied 120 patients who underwent PD. Grades B/C PF classified according to the International Study Group of Pancreatic Surgery guidelines were defined as clinically relevant PF. Logistic regression was used to identify detection factors for clinically relevant PF. Receiver operating characteristic curves were used to identify the optimal cutoff value for clinically relevant PF, and the k-fold cross-validation model to validate the cutoff value. Results: Drain amylase on POD 1 and C-reactive protein (CPR) on POD 2 were independent factors for clinically relevant PF. Drain amylase >1300 IU/l on POD 1 and CRP >12.8 g/dl on POD 2 were the best cutoff values for clinically relevant PF detection and were confirmed by k-fold cross-validation. The sensitivity and specificity values were 79 and 81 %, respectively. Conclusions: Values of drain amylase and CRP combined were useful to distinguish clinically relevant PF..
1885. Hideaki Uchiyama, Ryosuke Minagawa, shinji itoh, Kiyoshi Kajiyama, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Kenji Takenaka, Yoshihiko Maehara, Favorable Outcomes of Hepatectomy for Ruptured Hepatocellular Carcinoma
Retrospective Analysis of Primary R0-Hepatectomized Patients, Anticancer research, 36, 1, 379-385, 2016.01, BACKGROUND/AIM: The rupture of hepatocellular carcinoma (HCC) is defined as a detrimental staging factor. The aim of the present study was to elucidate whether the prognosis of surgical patients with ruptured HCC was truly appalling.
PATIENTS AND METHODS: The data obtained from the medical records of 1,031 patients who underwent primary R0 hepatecomy for HCC between August 2003 and November 2014 at the Department of Surgery and Science, Kyushu University Hospital and its two affiliated hospitals, were retrospectively analyzed. Twenty-seven patients had ruptured HCC.
RESULTS: The recurrence-free and overall survival for patients with ruptured HCC were favorable. All 19 patients with ruptured HCC who experienced recurrence had intrahepatic recurrence, while only three had peritoneal recurrence. The multivariate risk factor analyses showed that rupture itself was not relevant to recurrence-free survival nor to overall patient survival.
CONCLUSION: Rupture itself does not have much relevance to the outcome for patients who undergo hepatectomy..
1886. Shinji Itoh, Ken Shirabe, Shunji Kohnoe, Noriaki Sadanaga, Kiyoshi Kajiyama, Motoyuki Yamagata, Hideaki Anai, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Impact of recombinant human soluble thrombomodulin for disseminated intravascular coagulation, Anticancer research, 36, 5, 2493-2496, 2016.01, Background: Early treatment of disseminated intravascular coagulation (DIC) can be associated with improved early outcomes. We aimed to evaluate the effectiveness of recombinant human soluble thrombomodulin (rTM) administration in patients with peritonitis-induced DIC. Patients and Methods: We treated 39 patients with DIC or pre-DIC caused by peritonitis at the Department of Surgery and Science, Kyushu University, and related facilities between January and December 2013. Results: Patients surviving to 28 days after DIC treatment had significantly better platelet counts, DIC scores, and sequential organ failure assessment scores at 7 days than did those who died earlier than 28 days. Patients receiving rTM had significantly better overall survival rates at 28 days and the results of multivariate analysis showed that rTM administration for DIC treatment was a prognostic indicator of 28-day survival in patients with peritonitis. Conclusion: rTM administration for the treatment of DIC or pre-DIC complicated by peritonitis had acceptable early outcomes..
1887. Koichi Kimura, Ken Shirabe, Tomoharu Yoshizumi, Kazuki Takeishi, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Shinji Okano, Yoshihiko Maehara, Ischemia-reperfusion injury in fatty liver is mediated by activated NADPH oxidase 2 in rats, Transplantation, 10.1097/TP.0000000000001130, 100, 4, 791-800, 2016.01, Background. Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery, and steatosis is a risk factor for liver damage. Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) contribute to liver dysfunction. Here we examined the role of NOX in I/R injury of fatty livers. Methods. Rats were fed a methionine and cholinedeficient diet to induce a fatty liver. Rats then underwent surgically induced partial hepatic ischemia followed by reperfusion. Results. The overall survival rate after I/R was lower in rats with fatty livers than with normal livers (P < 0.01). Necrotic area and the concentrations of 8-hydroxy-2α-deoxyguanosine (8-OHdG), TNFÁ, and IL-6 were higher in fatty liver tissue than in normal liver tissue (P < 0.01). The number of p47phox-positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 24 hours after reperfusion. The number of TLR-4 positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 4 and 24 hours after reperfusion coupled with a decreased number of high-mobility group box 1-positive hepatocytes. Apocynin significantly improved the survival rate, necrotic area, and concentrations of 8-hydroxy-2α-deoxyguanosine, TNFα, and IL-6 (P < 0.01). The protective effect of apocynin on fatty livers was greater than on normal livers. Conclusions. Ischemia-reperfusion injury was associated with increased high-mobility group box 1, TLR4, and NOX2. Inhibition of NOX activity improved oxidative stress and may prevent I/R injury in fatty liver..
1888. Noboru Harada, Takashi Maeda, Tomoharu Yoshizumi, Tetsuo Ikeda, Hiroto Kayashima, Toru Ikegami, Norifumi Harimoto, Shintaro Takaki, Yoshihiko Maehara, Laparoscopic liver resection is a feasible treatment for patients with hepatocellular carcinoma and portal hypertension, Anticancer research, 36, 7, 3489-3497, 2016.01, Aim: To compare outcomes of patients with primary hepatocellular carcinoma (HCC) and portal hypertension (PHT) who underwent laparoscopic liver resection (LLR), open liver resection (OLR) or radiofrequency ablation (RFA). Patients and Methods: We retrospectively reviewed 88 patients with primary HCC and PHT who underwent LLR (n=20), OLR (n=48) or RFA (n=20) and analyzed their outcomes by treatment group. To reduce selection bias, covariate distributions in groups were adjusted using inverse probability treatment weighting (IPTW). Results: Five-year recurrence-free survival (RFS) was significantly better in the LLR and OLR than in the RFA group both before and after IPTW adjustment. The OLR group had significantly more postoperative complications than the RFA group; however, there was no significant difference in the postoperative complication rate between LLR and RFA groups. Conclusion: LLR may be a feasible treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or advanced hepatocellular carcinoma (A HCC) and PHT..
1889. Tomoharu Yoshizumi, Norifumi Harimoto, Shinji Itoh, Hirohisa Okabe, Koichi Kimura, Hideaki Uchiyama, Toru Ikegami, Tetsuo Ikeda, Yoshihiko Maehara, Living Donor Liver Transplantation for Hepatocellular Carcinoma within Milan Criteria in the Present Era, Anticancer research, 36, 1, 439-445, 2016.01, BACKGROUND: The aim of the present study was to clarify the outcome of living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.
PATIENTS AND METHODS: The study comprised of 197 adult patients. One hundred twenty-nine patients were within Milan criteria. The overall and recurrence-free survival rates after the LDLT were calculated.
RESULTS: The 1-, 5- and 10-year overall survival rates were 94.5%, 89.9% and 88.6%, respectively. The 1-, 5- and 10-year recurrence-free survival rates were 100%, 97.0% and 94.0%, respectively. Four patients had HCC recurrence. The mean neutrophil to lymphocyte ratio (NLR) (6.75 vs. 2.75, p=0.002) or alpha-fetoprotein (AFP) (3,239 vs. 197, p<0.001) of these four recipients was significantly higher compared to that of 125 recipients without HCC recurrence.
CONCLUSION: The outcome of LDLT for patients with HCC within Milan criteria was outstanding. Careful follow-up after LDLT is necessary for patients with high NLR or AFP..
1890. Yo Ichi Yamashita, Tomoharu Yoshizumi, Kengo Fukuzawa, Takashi Nishizaki, Eiji Tsujita, Kiyoshi Kajiyama, Yuji Soejima, Motoyuki Yamagata, Kazuharu Yamamoto, Eisuke Adachi, Keishi Sugimachi, Yasuharu Ikeda, Hideaki Uchiyama, Takashi Maeda, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Yoshihiko Maehara, Surgical results of pancreaticoduodenectomy for pancreatic ductal adenocarcinoma
A multi-institutional retrospective study of 174 patients, Anticancer research, 36, 5, 2407-2412, 2016.01, Background: Postoperative pancreatic fistula (POPF) remains a major complication after pancreaticoduo-denectomy (PD), and the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) after PD is poor. Patients and Methods: A multi-institutional retrospective study was performed in 174 patients who underwent PD for PDAC from 2007 to 2012. The details of clinical data were examined, and risk factors for POPF and poor prognostic factors after PD were identified. Results: POPF occured in 26 patients (15%), and 18 patients (10%) were diagnosed as Grade B/C POPF. The independent risk factors for Grade B/C POPF were body mass index (BMI) ≥25 (Odds Ratio [OR]=21.1, p=0.006) and absence of post-operative enteral nutrition (EN) (OR=10.2, p=0.04). The 1-, 3-, and 5-year overall survivals of patients with PDAC after PD were 76%, 35%, and 18%, respectively. R1/2 operation was identified as the only independent poor prognostic factor (Hazard Ratio=3.66; p=0.0002). Conclusion: Patients with BMI ≥25 should be closely monitored for POPF after PD. Post-operative EN might help prevent POPF. Performing R0 resection is an important goal for ensuring patient survival after PD for PDAC..
1891. Daisuke Imai, Yo ichi Yamashita, Toru Ikegami, Takeo Toshima, Norifumi Harimoto, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Tetsuo Ikeda, Yoshihiko Maehara, A “rendezvous technique” for treating a pancreatic fistula after distal pancreatectomy, Surgery today, 10.1007/s00595-013-0740-0, 45, 1, 96-100, 2015.12, Case presentation: We herein present a case of a pancreatic fistula after DP that was successfully treated with percutaneous pancreatic duct drainage, which was performed using a combined percutaneous and endoscopic approach, named the “rendezvous technique”. In our case, we performed distal pancreatectomy with celiac artery resection for a locally advanced pancreatic body cancer. On postoperative day (POD) 7, the drain amylase level increased up to 37,460 IU/l. Computed tomography (CT) revealed peripancreatic fluid collections. On POD 10, we placed a catheter in the main pancreatic duct using the rendezvous technique. CT on POD 14 revealed a decrease in the size of the peripancreatic fluid collection, and contrast imaging from the drains on POD 22 revealed almost complete disappearance of the fluid collection. We withdrew the pigtail catheter on POD 27 and the percutaneous pancreatic duct drain on POD 36. This patient was discharged from our hospital on POD 40.
Conclusion: We herein report a new approach called the “rendezvous technique” for the management of pancreatic fistulae after DP that can be used instead of a stressful nasopancreatic tube.
Background: Pancreatic fistulae are a major complication of distal pancreatectomy (DP). Some cases of severe pancreatic fistula require invasive procedures. There have been some reports concerning the effectiveness of pancreatic duct drainage through an endoscopic transpapillary approach for pancreatic fistulae..
1892. Kazuki Takeishi, Takashi Maeda, Ken Shirabe, Eiji Tsujita, Yo ichi Yamashita, Norifumi Harimoto, Shinji Itoh, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Clinicopathologic Features and Outcomes of Non-B, Non-C Hepatocellular Carcinoma After Hepatectomy, Annals of Surgical Oncology, 10.1245/s10434-015-4728-4, 22, 1116-1124, 2015.12, Purpose: This retrospective study aimed to investigate the clinical characteristics and long-term outcomes after hepatectomy in patients with non-B, non-C (NBNC) hepatocellular carcinoma (HCC) who were negative for hepatitis B virus surface antigen and anti–hepatitis C virus antibody. Methods: We retrospectively reviewed 666 patients with HCC who underwent hepatectomy. The patients were divided into NBNC-HCC patients [n = 117 (17.6 %)] and hepatitis virus (HV)-HCC patients [n = 547 (82.4 %)]. We compared the clinicopathologic characteristics and long-term outcomes between the 2 groups. Two patients with incomplete virus-marker data were not analyzed. Results: NBNC-HCC patients had better liver function but more advanced and larger HCCs and a high incidence of intrahepatic metastasis compared to HV-HCC patients. Recurrence-free and overall survival were similar in both groups. Multivariate analysis showed that aspartate aminotransferase (AST) and α-fetoprotein were independently associated with disease-free and overall survival in NBNC-HCC patients after hepatectomy. High AST was significantly associated with tumor size and rate of capsule formation with cancer cell infiltration in NBNC-HCC patients, but not with other liver function tests, fibrosis, or necrosis of noncancerous lesions. Conclusions: NBNC-HCC patients have better liver function than HV-HCC patients, despite having more advanced HCC at diagnosis. There were no differences in long-term outcomes after hepatectomy between NBNC-HCC and HV-HCC patients. Preoperative AST and α-fetoprotein were independently associated with the prognosis of NBNC-HCC after hepatectomy. Serum AST levels might be associated with tumor malignancy in NBNC-HCC patients..
1893. Takeshi Kurihara, Tomoharu Yoshizumi, Yoshihiro Yoshida, Toru Ikegami, Shinji Itoh, Norifumi Harimoto, Mizuki Ninomiya, Hideaki Uchiyama, Hirohisa Okabe, Koichi Kimura, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Graft selection strategy in adult-to-adult living donor liver transplantation
When both hemiliver grafts meet volumetric criteria, Liver Transplantation, 10.1002/lt.24431, 22, 7, 914-922, 2016.07, To ensure donor safety in living donor liver transplantation (LDLT), the left and caudate lobe (LL) is the preferred graft choice. However, patient prognosis may still be poor even if graft volume (GV) selection criteria are met. Our aim was to evaluate the effects of right lobe (RL) donation when the LL graft selection criteria are met. Consecutive donors (n = 135) with preoperative LL graft volumetric GV/standard liver volume (SLV) of ≥35% and RL remnant of ≥35% were retrospectively studied. Patients were divided into 2 groups: LL graft and RL graft. Recipient's body surface area (BSA), Model for End-Stage Liver Disease (MELD) score, and the donor's age were higher in the RL group. The donor's BSA and preoperative volumetric GV/SLV of the LL graft were smaller in the RL group. The predicted score (calculated using data for graft size, donor age, MELD score, and the presence of portosystemic shunt, which correlated well with graft function and with 6-month graft survival) of the RL group, was significantly lower if the LL graft were used, but using the actual RL graft improved the score equal to that of the LL group. Six-month and 12-month graft survival rates did not differ between the 2 groups. In patients with a poor prognosis, a larger RL graft improved the predicted score and survival was equal to that of patients who received LL grafts. In conclusion, graft selection by GV, donor age, and recipient MELD score improves outcomes in LDLT. Liver Transplantation 22 914–922 2016 AASLD..
1894. Yo ichi Yamashita, Tomoharu Yoshizumi, Toru Ikegami, Hideaki Uchiyama, Eiji Tsujita, Shinji Itoh, Norifumi Harimoto, Yuji Soejima, Akinobu Taketomi, Hideo Baba, Yoshihiko Maehara, Inquiries About Biomarkers of Acute Liver Failure in Patients Who Underwent Living Donor Liver Transplantation Using a Protein Chip Array, Fukuoka igaku zasshi = Hukuoka acta medica, 107, 7, 131-135, 2016.07, The causative agent of hepatic encephalopathy (HE) has not been identified with certainty. The recovery of consciousness in patients with acute liver failure (ALF) who underwent liver transplantation (LT) is sometimes drastic ; therefore, we thought that the causative agents of HE would change markedly peri-operatively in these patients. We examined the biomarkers including new agents in the serum of patients using the ProteinChip® System 4000 (Ciphergen Biosystems, Yokohama, JAPAN). Sixteen samples were obtained from four patients with ALF who underwent living donor LT (LDLT) at four time points ; pre-operative, one post-operative day (1POD), 3POD, and 7POD. We used three chips made by the Biomek2000 robot. All duplicated samples were assayed and analyzed using the CiphergenExpressTM data manager. We divided the peri-operative changes in the intensity of identified peaks into seven patterns. The number of peaks whose intensity shows significant changes peri-operatively reached 755. Of course, it is difficult to determine each structure in all 755 peaks ; therefore, we should narrow down the candidates for causative agents of HE in further studies. Our own results suggest that many difficulties lie ahead in determining the causative agent of HE..
1895. Shinji Itoh, Tomoharu Yoshizumi, Koichi Kimura, Hirohisa Okabe, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Ken Shirabe, Akihiro Nishie, Yoshihiko Maehara, Effect of sarcopenic obesity on outcomes of living-donor liver transplantation for hepatocellular carcinoma, Anticancer research, 36, 6, 3029-3034, 2016.06, Background/Aim: We aimed to evaluate the effect of body composition on the outcome of living-donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC). Patients and Methods: We performed LDLT in 153 patients with HCC and divided the patients into two groups based on skeletal muscle mass-to-visceral fat area ratio (SVR), as assessed by computed tomography (CT) measurement, namely a low-SVR group (n=38) and a notlow SVR group (n=112). We compared surgical outcomes between the two groups. Results: A low SVR was significantly correlated with a higher body mass index and male sex. No differences were found between the two groups in terms of other factors. The patients in the low-SVR group had a significantly poorer prognosis than those in the notlow SVR group in terms of recurrence-free (p=0.01) and overall (p=0.03) survival. The results of the multivariate analysis showed low SVR to be an independent and prognostic indicator for patients with HCC who had undergone LDLT. Conclusion: Pre-transplant body composition measured by CT is a major determinant of prognosis in LDLT for HCC in Japan..
1896. Tomonari Shimagaki, Tomoharu Yoshizumi, Koichi Kimura, Takashi Motomura, Akihisa Nagatsu, Hirohisa Okabe, Shinji Itoh, Noboru Harada, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Living Donor Liver Transplantation in an Elderly Recipient with Preserved Performance Status
A Case Report, Fukuoka igaku zasshi = Hukuoka acta medica, 107, 6, 115-120, 2016.06, Background: Living donor liver transplantation (LDLT) in an elderly recipient is controversial.
Case presentation: We report a case of LDLT in a 74-year-old female who had decompensated liver cirrhosis and hepatocellular carcinoma (HCC). She was the oldest recipient who received LDLT in Japan ever. She was rejected for LDLT at a nearby hospital because of her age.We decided to perform LDLT because her general condition was good (the Eastern Cooperative Oncology Group (ECOG) performance status 2 ). The surgery was uncomplicated and the postoperative course was uneventful, and the patient was discharged 35 days after the surgery. Currently she is living at home, and she has maintained a good quality of life.
Conclusions: We believe that a recipient in good general condition is capable of undergoing LDLT despite advanced age..
1897. Tomoharu Yoshizumi, Norifumi Harimoto, Shinji Itoh, Toru Ikegami, Hideaki Uchiyama, Tetsuo Ikeda, Yoshihiko Maehara, CURRENT STATUS OF HEPATOBILIARY PANCREATIC SURGERY FOR ELDERLY PATIENTS, Nihon Geka Gakkai zasshi, 117, 3, 174-181, 2016.05, The aging of Japan’s population is becoming pronounced, and hepatobiliary pancreatic surgery for elderly patients is increasingly performed. Elderly patients generally have extensive comorbidities, the risk of malnutrition, and diminished renal, liver, and cardiopulmonary function. Therefore, the indications of surgery should be individually evaluated considering surgical risk, impaired quality of life, and prognosis after surgery. Japanese insurance allows left lateral segmentectomy and partial resection for liver malignancy to be performed by laparoscopic surgery. Laparoscopic surgery may prevent sarcopenia, which is a predictor of survival in patients with various malignancies or those with liver cirrhosis. Elderly patients often develop delirium or severe aspiration pneumonia postoperatively. Interprofessional collaboration for pain control and early mobilization is the key to prevent severe complications in elderly patients. Thirty percent of patients with hepatocellular carcinoma are older than 75 years of age. Morbidity and mortality rates after hepatic resection in the elderly with acceptable cardiopulmonary function are comparable to those in younger individuals with adequate patient selection. Recipient age does not affect the outcome after living-donor liver transplantation (LDLT), as long as patient status is relatively good. Therefore, age alone should not be considered a contraindication for LDLT..
1898. Kazutoyo Morita, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo Ichi Yamashita, Keishi Sugimachi, Norifumi Harimoto, Shinji Itoh, Tetsuo Ikeda, Yoshihiko Maehara, Relevance of microRNA-18a and microRNA-199a-5p to hepatocellular carcinoma recurrence after living donor liver transplantation, Liver Transplantation, 10.1002/lt.24400, 22, 5, 665-676, 2016.05, There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. First, we performed microarray analyses of samples from a liver with primary HCC, a liver that was noncancerous, and a liver that had recurrence-metastasis from 3 patients with posttransplant recurrence. Then we selected miRNAs with consistently altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous livers was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. MicroRNA-18a (miR-18a) expression was increased, and microRNA-199a-5p (miR-199a-5p) expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor, and insulin-like growth factor 2. In conclusion, increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT..
1899. Hirohisa Okabe, Hiroki Kinoshita, Katsunori Imai, Shigeki Nakagawa, Takaaki Higashi, Kota Arima, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Takatoshi Ishiko, Tomoharu Yoshizumi, Toru Beppu, Satdarshan P.S. Monga, Hideo Baba, Yoshihiko Maehara, Diverse basis of β-catenin activation in human hepatocellular carcinoma
Implications in biology and prognosis, PloS one, 10.1371/journal.pone.0152695, 11, 4, 2016.04, Aim: β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ϵ (CK1ϵ) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of β-catenin activation in human HCC. Methods: Gene alteration in exon3 of CTNNB1, gene expression of β-catenin targets such as glutamate synthetase (GS), axin2, lect2 and regucalcin (RGN), and protein expression of β-catenin were examined in 125 human HCC tissues. Results: Sixteen patients (12.8%) showed conventional missense mutations affecting codons 33, 37, 41, and 45. Fifteen additional patients (12.0%) had other missense mutations in codon 32, 34, and 35. Induction of exon3 mutation caused described β-catenin target gene upregulation in HCC cell line. Interestingly, conventional and non-phosphorylation site mutations were equally associated with upregulation of β-catenin target genes. Nuclear localization of β-catenin was associated with poor overall survival (p = 0.0461). Of these patients with nuclear β-catenin localization, loss of described β-catenin target gene upregulation showed significant poorer overall survival than others (p = 0.0001). Conclusion: This study suggests that both conventional and other missense mutations in exon 3 of CTNNB1 lead to β-catenin activation in human HCC. Additionally, the mechanism of nuclear β-catenin localization without upregulation of described β-catenin target genes might be of clinical importance depending on distinct mechanism..
1900. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Koichi Kimura, Hirohisa Okabe, Yoshihiko Maehara, Living donor liver transplantation for intrahepatic arteriovenous fistula with hepatic artery reconstruction using the right gastroepiploic artery, Liver Transplantation, 10.1002/lt.24377, 22, 4, 552-556, 2016.04.
1901. Shinji Itoh, Ken Shirabe, Tomoharu Yoshizumi, Kazuki Takeishi, Norifumi Harimoto, Toru Ikegami, Hirofumi Kawanaka, Akihiro Nishie, Takahide Kamishima, Yoshihiko Maehara, Skeletal muscle mass assessed by computed tomography correlates to muscle strength and physical performance at a liver-related hospital experience, Hepatology Research, 10.1111/hepr.12537, 46, 4, 292-297, 2016.04, Aim: We aimed to evaluate whether skeletal muscle mass measured by computed tomography (CT) or bioelectrical impedance analysis (BIA) correlated to muscle strength and physical performance in liver-related hospital cases. Methods: We prospectively conducted this study in 120 liver-related hospital cases. Skeletal muscle mass was measured by CT scan and BIA. Muscle strength was determined by hand grip strength and physical performance by usual gait speed. Results: Skeletal muscle mass measured using CT significantly correlated to usual gait speed (r2=0.17, P<0.0001) and hand grip strength (r2=0.66, P<0.0001), but the correlations were lower using BIA (r2=0.1, P=0.0005; r2=0.54, P<0.0001). With regard to liver function, the relationship between skeletal muscle mass measured by CT and BIA and two muscle function parameters in the Child-Pugh A group were significant. In contrast, skeletal muscle mass measured by BIA in the Child-Pugh B or C group was not significantly related to usual gait speed. Conclusion: Skeletal muscle mass measured by CT was significantly correlated to hand grip strength and usual gait speed, with higher correlations compared with BIA. Moreover, skeletal muscle mass measured by CT significantly correlated with two muscle functions, even in patients with Child-Pugh B or C..
1902. Hideaki Uchiyama, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Yoshihiko Maehara, Outcomes of adult-to-adult living donor liver transplantation in 321 recipients, Liver Transplantation, 10.1002/lt.24378, 22, 3, 305-315, 2016.03, We conducted a retrospective investigation in order to clarify whether selecting the type of liver graft had an impact on outcomes of adult-to-adult living donor liver transplantation (AALDLT). Data from the medical records of the donors and the recipients of 321 consecutive cases of AALDLT performed between April 2004 and March 2014 were retrospectively analyzed. Our general criteria for selecting the type of liver graft was that a left graft was preferentially selected when the estimated volume of the left graft was ≥35% of the standard liver volume of the recipient, and that a right graft was selected only when the estimated remnant liver volume of the donor was ≥35% of the total liver volume. In this series, 177 left grafts, 136 right grafts, and 8 posterior grafts were used. The left grafts tended to have 2 or more arteries, whereas the right grafts tended to have 2 or more bile duct orifices. The graft survival curves and the incidences of severe complications were comparable between the AALDLT using right grafts and the AALDLT using left grafts. The preoperative estimation of graft size hardly enabled us to predict severe posttransplant complication. Moreover, small-for-size graft syndrome occurred regardless of the estimated graft volumes. Instead, donor age was a significant risk factor for small-for-size graft syndrome. In conclusion, left grafts should be more aggressively used for the sake of donors' safety. The use of hepatic grafts from older donors should be avoided if possible in order to circumvent troublesome posttransplant complications. Liver Transpl 22:305-315, 2016..
1903. Yoshihide Ueda, Toru Ikegami, Akihiko Soyama, Nobuhisa Akamatsu, Masahiro Shinoda, Kohei Ishiyama, Masaki Honda, Shigeru Marubashi, Hideaki Okajima, Tomoharu Yoshizumi, Susumu Eguchi, Norihiro Kokudo, Yuko Kitagawa, Hideki Ohdan, Yukihiro Inomata, Hiroaki Nagano, Ken Shirabe, Shinji Uemoto, Yoshihiko Maehara, Simeprevir or telaprevir with peginterferon and ribavirin for recurrent hepatitis C after living-donor liver transplantation
A Japanese multicenter experience, Hepatology Research, 10.1111/hepr.12684, 46, 13, 1285-1293, 2016.12, Aim: This study aimed to clarify the efficacy and safety of simeprevir, a second-generation NS3/4A inhibitor, with peginterferon and ribavirin for recurrent hepatitis C after liver transplantation. Methods: A retrospective cohort study of living-donor liver transplant recipients with recurrent hepatitis C with the hepatitis C virus genotype 1 treated with either simeprevir- or telaprevir-based triple therapy was carried out at eight Japanese liver transplant centers. Results: Simeprevir- and telaprevir-based triple therapies were given to 79 and 36 patients, respectively. Of the 79 patients treated with simeprevir-based triple therapy, 44 (56%) achieved sustained virological response 12 weeks (SVR12) after treatment ended, and there was no significant difference in the SVR12 between the simeprevir- and telaprevir-based triple therapy groups (69%). The rates of adverse events were not significantly different between the simeprevir- and telaprevir-based triple therapy groups, although the rate of patients who received blood cell transfusion and erythropoietin due to anemia and had renal insufficiency were significantly higher in the telaprevir group than in the simeprevir group. Three baseline factors, the presence of prior dual therapy with peginterferon and ribavirin (P = 0.001), a non-responder to the prior dual therapy (P < 0.001), and male sex (P = 0.040), were identified as significant predictive factors for non-SVR with simeprevir-based triple therapy. Conclusion: Simeprevir-based triple therapy for recurrent hepatitis C after living-donor liver transplantation resulted in a high SVR rate and good tolerability, especially in treatment-naïve patients..
1904. Toru Ikegami, Norifumi Harimoto, Masahiro Shimokawa, Tomoharu Yoshizumi, Hideaki Uchiyama, Shinji Itoh, Norihisa Okabe, Kazuhito Sakata, Akihisa Nagatsu, Yuji Soejima, Yoshihiko Maehara, The learning curves in living donor hemiliver graft procurement using small upper midline incision, Clinical Transplantation, 10.1111/ctr.12850, 30, 12, 1532-1537, 2016.12, The learning curve for performing living donor hemiliver procurement (LDHP) via small upper midline incision (UMI) has not been determined. Living donors (n=101) who underwent LDHP via UMI were included to investigate the learning curve using cumulative sum analysis. The cumulative sum analysis showed that nine cases for right lobe (case #23) and 19 cases for left lobe (case #32 in the whole series) are needed for stable and acceptable surgical outcomes in LDHP via UMI. The established phase (n=69, since case #33) had a significantly shorter operative time, a smaller incision size, and less blood loss than the previous learning phase (n=32, serial case number up to the last 19th left lobe case). Multivariate analysis showed that the learning phase, high body mass index ≥25 kg/m2, and left lobe graft procurement are the factors associated with surgical events including operative blood loss ≥400 mL, operative time ≥300 minutes, or surgical complications ≥Clavien-Dindo grade II. There is an obvious learning curve in performing LDHP via UMI, and 32 cases including both 19 cases for left lobe and nine cases for right lobe are needed for having stable and acceptable surgical outcomes..
1905. H. Okabe, T. Yoshizumi, T. Ikegami, H. Uchiyama, N. Harimoto, S. Itoh, K. Kimura, H. Baba, Y. Maehara, Salvage Splenic Artery Embolization for Saving Falling Living Donor Graft due to Portal Overflow
A Case Report, Transplantation Proceedings, 10.1016/j.transproceed.2016.07.023, 48, 9, 3171-3173, 2016.11, Portal decompression is an approach for reducing portal overflow caused by small-for-size syndrome. We report the case of a patient who recovered from rapidly progressing hyperbilirubinemia caused by a small graft by decompressing portal overflow with splenic artery embolization following a living donor liver transplantation (LDLT). The patient was a 54-year-old man with end-stage liver disease secondary to alcoholic liver cirrhosis; the donor was his 54-year-old wife. The graft volume of the left lobe was 444 mL, which was 34.8% of the standard liver volume (SLV) and insufficient for the recipient; thus, the plan was to use the right lobe for the graft. The patient underwent LDLT with a right lobe graft; the volume to SLV ratio was 39.1%, and the graft-to-recipient-weight ratio was 0.72%. Although portal pressure was low during the operation, the patient eventually developed small-for-size syndrome after LDLT. It was conceivable that because the patient had splenomegaly, portal decompression would be effective. Splenic arterial embolization was performed successfully on postoperative day (POD) 7. The patient's total bilirubin level was increased to 40 mg/dL on POD16. Decreased portal flow, which was shown by ultrasound screening to be “to-and-flo,” increased again on POD23 to one-third of that on POD1. He was discharged without any infectious complications. Additional splenic artery embolization after LDLT may be a convenient option for reducing portal overflow for patients with splenomegaly if the portal decompression was not performed for some reason at the surgery..
1906. Norifumi Harimoto, Tomoharu Yoshizumi, Masahiro Shimokawa, Kazuhito Sakata, Kouichi Kimura, Shinji Itoh, Toru Ikegami, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70 years and older with hepatocellular carcinoma, Hepatology Research, 10.1111/hepr.12674, 46, 12, 1247-1255, 2016.11, Aim: The present study investigated the effect of sarcopenia on short- and long-term surgical outcomes and identified potential prognostic factors for hepatocellular carcinoma (HCC) following hepatectomy among patients 70 years of age and older. Methods: Patient data were retrospectively collected for 296 consecutive patients who underwent hepatectomy for HCC with curative intent. Patients were assigned to two groups according to age (younger than 70 years, and 70 years and older), and the presence of sarcopenia. The clinicopathological, surgical outcome, and long-term survival data were analyzed. Results: Sarcopenia was present in 112 of 296 (37.8%) patients with HCC, and 35% of patients aged 70 years and older. Elderly patients had significantly lower serum albumin levels, prognostic nutrition index, percentage of liver cirrhosis, and histological intrahepatic metastasis compared with patients younger than 70 years. Overall survival and disease-free survival rates in patients with sarcopenia correlated with significantly poor prognosis in the group aged 70 years and older. Multivariate analysis revealed that sarcopenia was predictive of an unfavorable prognosis. Conclusion: This retrospective analysis revealed that sarcopenia was predictive of worse overall survival and recurrence-free survival after hepatectomy in patients 70 years of age and older with HCC..
1907. Yuji Soejima, Tomoaki Taguchi, Maki Sugimoto, Makoto Hayashida, Tomoharu Yoshizumi, Toru Ikegami, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Three-dimensional printing and biotexture modeling for preoperative simulation in living donor liver transplantation for small infants, Liver Transplantation, 10.1002/lt.24516, 22, 11, 1610-1614, 2016.11.
1908. Nobuhiro Fujita, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Ken Shirabe, Tomoharu Yoshizumi, Kazuhiro Kotoh, Norihiro Furusyo, Tomoyuki Hida, Yoshinao Oda, Taisuke Fujioka, Hiroshi Honda, Fibrosis in nonalcoholic fatty liver disease
Noninvasive assessment using computed tomography volumetry, World Journal of Gastroenterology, 10.3748/wjg.v22.i40.8949, 22, 40, 8949-8955, 2016.10, AIM To evaluate the diagnostic performance of computed tomography (CT) volumetry for discriminating the fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). METHODS A total of 38 NAFLD patients were enrolled. On the basis of CT imaging, the volumes of total, left lateral segment (LLS), left medial segment, caudate lobe, and right lobe (RL) of the liver were calculated with a dedicated liver application. The relationship between the volume percentage of each area and fibrosis stage was analyzed using Spearman's rank correlation coefficient. A receiver operating characteristic (ROC) curve analysis was performed to determine the accuracy of CT volumetry for discriminating fibrosis stage. RESULTS The volume percentages of the caudate lobe and the LLS significantly increased with the fibrosis stage (r = 0.815, P < 0.001; and r = 0.465, P = 0.003, respectively). Contrarily, the volume percentage of the RL significantly decreased with fibrosis stage (r = -0.563, P < 0.001). The volume percentage of the caudate lobe had the best diagnostic accuracy for staging fibrosis, and the area under the ROC curve values for discriminating fibrosis stage were as follows: ≥ F1, 0.896; ≥ F2, 0.929; ≥ F3, 0.955; and ≥ F4, 0.923. The best cut-off for advanced fibrosis (F3-F4) was 4.789%, 85.7% sensitivity and 94.1% specificity. CONCLUSION The volume percentage of the caudate lobe calculated by CT volumetry is a useful diagnostic parameter for staging fibrosis in NAFLD patients..
1909. Norifumi Harimoto, Tomoharu Yoshizumi, Tomonari Shimagaki, Akihisa Nagatsu, Takashi Motomura, Noboru Harada, Hirohisa Okabe, Shinji Itoh, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Inflammation-based prognostic score in patients with living donor liver transplantation for hepatocellular carcinoma, Anticancer research, 10.21873/anticanres.11137, 36, 10, 5537-5542, 2016.10, Background: Inflammation-besed prognostic score including neutrophil/lymphocyte ratio (NLR), platelet/ lymphocyte ratio (PLR), modified Glasgow prognostic score (mGPS) and prognostic nutritional index (PNI) have prognostic value in various malignancies. Patients and Methods: We retrospectively investigated their prognostic value in 213 patients with living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). Disease-free survival (DFS) following LDLT was calculated; NLR, PLR, PNI and mGPS values in patients with and without recurrence were compared. Risk factors for HCC recurrence were identified by univariate and multivariate analyses. Results: Both NLR and PLR were significantly increased in patients with recurrence. Multivariate analysis showed that desgamma-carboxy prothrombin (DCP) 300 mAU/ml, NLR 2.66, <3 months between last HCC treatment to LDLT were independent predictors of DFS. Conclusion: Preoperative NLR was an independent, inflammation-based prognostic marker of DFS and was predictive of recurrence following LDLT..
1910. Yoshiki Asayama, Akihiro Nishie, Kousei Ishigami, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Nobuhiro Fujita, Tomoharu Yoshizumi, Tomoyuki Hida, Hiroshi Honda, Histogram analysis of noncancerous liver parenchyma on gadoxetic acid-enhanced MRI
predictive value for liver function and pathology, Abdominal Radiology, 10.1007/s00261-016-0753-4, 41, 9, 1751-1757, 2016.09, Purpose: To clarify whether the heterogeneity of hepatic parenchyma in the hepatobiliary phase on gadoxetic acid-magnetic resonance (MR) imaging is correlated with liver damage. Materials and methods: We retrospectively examined the cases of 98 patients with or without chronic liver disease who underwent gadoxetic acid-enhanced 3T MR imaging before a hepatectomy between December 2010 and October 2014. For the evaluation of the heterogeneity of the signal intensity in the hepatobiliary phase, we placed the region of interest on the hepatic parenchyma, and the skewness and kurtosis were calculated using ImageJ software. A discriminant analysis was performed to examine the routine preoperative laboratory test results including indocyanine green retention at 15 min (ICG-R15), necro-inflammation grade, and liver fibrosis stage according to the METAVIR system: A0/1 (n = 69) and A2 (n = 29); F0/1 (n = 47), F2/3 (n = 31), and F4 (n = 20). Results: The combination of skewness and kurtosis could discriminate the high ICG-R15 (>20) and low (<20) groups (lambda; 0.925, p = 0.025), necro-inflammatory grade (lambda; 0.926, p = 0.026), and fibrosis stage (lambda; 0.752, p < 0.0001) with statistical significance. The difference between the patients with normal values and those with an abnormal platelet count or aspartate transaminase level was also detectable (lambda; 0.901, p < 0.007, and lambda; 0.864, p = 0.001, respectively). Conclusion: Histogram analyses of the hepatobiliary phase of gadoxetic acid-enhanced MR imaging have potential as a biomarker for the assessment of liver function, liver fibrosis, and necro-inflammation..
1911. Hideaki Uchiyama, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Hirohisa Okabe, Koichi Kimura, Yoshihiko Maehara, The use of left grafts with a replaced or accessory left hepatic artery in adult-to-adult living donor liver transplantation
analyses of donor and recipient outcomes, Clinical Transplantation, 10.1111/ctr.12783, 30, 9, 1021-1027, 2016.09, In living donor liver transplantation (LDLT), a left hepatic graft occasionally includes a replaced or accessory left hepatic artery (LHA). The procuring of such grafts requires extensive dissection along the lesser curvature of the stomach to elongate the replaced or accessory LHA on the donor side. On the recipient side, complicated arterial reconstruction is often necessary to use such grafts. We retrospectively reviewed the medical records of 206 adult recipients who underwent LDLT and their respective donors. The recipients and donors were divided into two groups according to the presence of the replaced or accessory LHA. Twenty-five grafts included a replaced or accessory LHA. Only one hepatic artery-related complication was observed in the current series, in which a pseudoaneurysm arose at the site of anastomosis between the donor accessory LHA and the recipient LHA. There was no increase in the incidence of postoperative complications in the donors with a replaced or accessory LHA in comparison with the donors without these arteries. The use of left hepatic grafts that included a replaced LHA or accessory LHA did not have any negative impact on the outcomes on either the donor or the recipient side..
1912. Shinji Itoh, Shunji Kohnoe, Ken Shirabe, Daisuke Yoshida, Hirofumi Kawanaka, Tomoharu Yoshizumi, Toru Ikegami, Yo Ichi Yamashita, Takeshi Kurihara, Yoshihiko Maehara, Validity of hepatic or pancreatic resection for elderly patients aged 85 years or older at a single community hospital in Japan, Anticancer research, 36, 8, 4289-4292, 2016.08, Aim: To evaluate the efficacy of age on the surgical outcomes in hepatic or pancreatic resection. Patients and Methods: We performed 50 hepatic or pancreatic resections in our community hospital and divided them into 2 groups based on age: patients aged 85 years old and patients aged <85 years old. We calculated the Estimation of Physiologic Ability and Surgical Stress (EPASS) score and the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) system and compared the surgical outcome between the two groups. Results: There was no significant difference between the two groups with regard to E-PASS and POSSUM scores. Patients aged 85 years had a significantly higher frequency of anti-platelet agents. The incidence of postoperative complications and mortality in patients 85 years old were comparable to those in patients aged <85 years old. Conclusion: Hepatic or pancreatic resection for elderly patients aged 85 years or older can be safely performed under a given careful patient selection..
1913. Y. Soejima, T. Yoshizumi, T. Ikegami, N. Harimoto, N. Harada, S. Ito, T. Motomura, H. Uchiyama, Y. Maehara, In Situ Procurement of a Recipient's Portal Vein for a Right Lobe Liver Graft With Multiple Venous Orifices
A Case Report, Transplantation Proceedings, 10.1016/j.transproceed.2016.10.028, 49, 1, 172-174, 2017.01, Reconstruction of multiple venous orifices of a right lobe graft is a time-consuming and troublesome procedure in right lobe living-donor liver transplantation. In the current study, we present a new venous reconstruction technique for a right lobe graft with multiple and complex hepatic vein (HV) orifices, in which procurement of the recipient's left portal vein was performed in situ to keep the anhepatic period to a minimum. All of the HV orifices were reconstructed together at the back table, while maintaining patency of the recipient's systemic and splanchnic circulation. A homologous vein graft and veno-venous bypass were not necessary. All HVs were patent during the follow-up and the patient was free from complications. In conclusion, the present technique is readily available for reconstruction of complex and multiple HV tributaries, while avoiding a long anhepatic time and the use of veno-venous bypass..
1914. Masayo Tsukamoto, Yo Ichi Yamashita, Katsunori Imai, Naoki Umezaki, Takanobu Yamao, Hirohisa Okabe, Shigeki Nakagawa, Daisuke Hashimoto, Akira Chikamoto, Takatoshi Ishiko, Tomoharu Yoshizumi, Yoshihiko Maehara, Hideo Baba, Predictors of cure of intrahepatic cholangiocarcinoma after hepatic resection, Anticancer research, 10.21873/anticanres.12164, 37, 12, 6971-6976, 2017.01, Background/Aim: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma, and has a poor prognosis. Surgical resection is the only option for a cure of ICC. Here we attempted to define the cure rate after hepatic resection for ICC and to identify the predictors for a cure. Patients and Methods: Among the 96 patients who underwent R0 resections for primary ICC between 1990 and 2011 at the Kumamoto University Hospital and Kyushu University Hospital, those who were followed for ≥5 years after surgery were enrolled. “Cure” was defined as recurrence-free survival (RFS) of ≥5 years after surgery. Results: A total of 81 patients were eligible. A cure was achieved in 37 patients (45.7%). The 5-year overall survival and RFS rates were 55.0% and 41.7%, respectively. A multivariate logistic regression analysis identified the absence of lymph node metastasis (relative risk (RR) 7.5, p=0.011) and the absence of microvascular invasion (RR 5.5, p=0.0137) as the independent predictors of achieving a cure. Conclusion: R0 resections achieved a cure in 45.7% of this series of ICC patients. The predictors of a cure identified here, i.e., absence of lymph node metastasis and absence of microvascular invasion, could contribute to the selection of patients who are not candidates for adjuvant chemotherapy..
1915. Takeo Toshima, Ken Shirabe, Yoshihiro Matsumoto, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Role of autophagy in liver regeneration, Autophagy Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging Volume 12, 10.1016/B978-0-12-812146-7.00023-8, 451-461, 2017.01, Autophagy regulates protein and organelle turnover and produces adenosine 5'-triphosphate (ATP) by using the amino acids from degraded proteins. We generated liver-specific autophagy-related gene 5 (Atg5)-knockout (KO) mice to investigate the activity of autophagy-associated pathways in liver regeneration after partial hepatectomy (PHx). The proliferation of remnant liver in Atg5 KO mice was severely impaired by 70% PHx with a reduction in postoperative mitosis, but a compensating increase in hepatocyte size. PHx injured cellular mitochondria and induced the intracellular ATP and β-oxidation reduction. Besides, hepatic accumulation of p62 and ubiquitinated proteins were enhanced. These results indicated that the reorganization of intracellular proteins and organelles during autophagy was impaired in the regenerating liver in this setting. Upregulation of p21 was associated with hepatocyte senescence and irreversible growth arrest. In the results, autophagy plays a critical role in regenerating liver and in the preservation of cellular quality by preventing hepatocytes from becoming fully senescent and hypertrophic in liver regeneration..
1916. Toru Ikegami, Tomoharu Yoshizumi, Jyunji Kawasaki, Akihisa Nagatsu, Hideaki Uchiyama, Noboru Harada, Norifumi Harimoto, Shinji Itoh, Takashi Motomura, Yuji Soejima, Yoshihiko Maehara, Surgical resection for lymph node metastasis after liver transplantation for hepatocellular carcinoma, Anticancer research, 10.21873/anticanres.11395, 37, 2, 891-896, 2017.01, Background: Treatment strategies for lymph node (LN) metastasis after liver transplantation (LT) for hepatocellular carcinoma (HCC) have not been studied. Patients and Methods: The treatment modes and outcomes in patients with LN metastasis after LT (n=6) for HCC were reviewed. Results: The mean time from LT to LN recurrence was 2.0±1.3 years, and the locations of the LNs recurrences included the phrenic (n=2), common hepatic artery (n=2), inferior vena cava (n=1) and gastric (n=1) regions. Treatments included surgery alone (n=3), surgery followed by chemoradiation (n=1), radiation followed by chemotherapy (n=1), and chemotherapy, radiation and sorafenib (n=1). Although the patients receiving nonsurgical treatments (n=3) died within 1.2 years, those who underwent surgical removal of the metastatic LNs survived 11.2 years, 4.5 years and 0.8 years, respectively, without any signs of re-recurrence. Conclusion: Surgical resection is the only feasible and potentially curative treatment for LN metastasis after LT for HCC..
1917. Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Shinji Ito, Noboru Harada, Takashi Motomura, Akihisa Nagatsu, Tetsuo Ikeda, Yoshihiko Maehara, Surgical resection of giant pheochromocytomas arising behind the retrohepatic inferior vena cava, Anticancer research, 10.21873/anticanres.11318, 37, 1, 277-280, 2017.01, Background: Surgical resection of retrocaval giant pheochromocytomas (PCs) and of extra-adrenal paragangliomas (EAPs) is a technically challenging procedure but data on these procedures are scarce. The purpose of this study was to present and evaluate our surgical results for such tumors. Patients and Methods: We retrospectively analyzed four consecutive patients who had surgery for giant retro-caval PCs and EAPs in terms of surgical technique, resectability of the tumor, requirement for bypass, and postoperative complications. A laparoscopic approach was not feasible in all cases because of the undesirable location of the tumors. Results: In all cases, the liver was completely mobilized from the right side to expose and control the supra- and infra-hepatic inferior vena cava. Resection of the tumors was feasible for all patients with a minimum titration of blood pressure during surgery. None of the cases required venous bypass. In the patient who had the largest tumor, the infra-hepatic inferior vena cava was transected temporally to obtain direct and maximum exposure of the tumor. None of the patients have had any postoperative complications and all are currently alive without recurrence and use of antihypertensive drugs. Conclusion: Resection of retrocaval giant PCs and EAPs is a safe procedure. Temporal transection of the infra-hepatic inferior vena cava can offer excellent exposure, especially for an extremely large tumor, without compromising hepatic and systemic hemodynamics..
1918. Hideaki Uchiyama, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Hirohisa Okabe, Yuji Soejima, Yoshihiko Maehara, Use of internal jugular vein grafts in reconstructing multiple venous orifices of right hepatic grafts without the middle hepatic vein trunk, Liver Transplantation, 10.1002/lt.24644, 23, 1, 110-116, 2017.01.
1919. Y. Asayama, A. Nishie, K. Ishigami, Y. Ushijima, Y. Takayama, D. Okamoto, N. Fujita, Y. Kubo, S. Aishima, T. Yoshizumi, H. Honda, Fatty change in moderately and poorly differentiated hepatocellular carcinoma on MRI
a possible mechanism related to decreased arterial flow, Clinical Radiology, 10.1016/j.crad.2016.04.020, 71, 12, 1277-1283, 2016.12, Aim To clarify the frequency of fatty change in moderately and poorly differentiated hepatocellular carcinomas (mHCCs and pHCCs) and its relationship to arterial blood flow. Materials and methods One hundred and thirty-six surgically resected HCC lesions were studied. All patients had undergone dynamic magnetic resonance imaging (MRI) with chemical-shift-encoded water–fat imaging (CSI). The presence of fat was identified by a signal drop-off on CSI and confirmed at pathology. Lesions were classified into four groups in the arterial phase; G1, hypointense; G2, isointense; G3, slightly and heterogeneously hyperintense; G4, markedly and homogeneously hyperintense. The number of cumulative arteries (CAs) in the tumours in the pathology examination were counted. Results A fat component was observed significantly more frequently in the pHCCs (13/21; 61.9%) compared to the mHCCs (32/101; 31.7%; p=0.013). The numbers of lesions in each group were as follows: (G1, G2, G3, G4) = (18, 9, 23, 4) in the HCCs with fat; (1, 6, 24, 51) in the HCCs without fat (p<0.001); (5, 5, 18, 4) in the mHCCs with fat; (0, 3, 19, 47) in the mHCCs without fat (p<0.001); (11, 0, 2, 0) in the pHCCs with fat; (0, 2, 3, 3) in the pHCCs without fat (p=0.001). The number of CAs in the fat-containing HCCs (5.5±2.9) was significantly lower than that in the HCCs without fat (10.8±5.3; p<0.001). Conclusion A fat component was more commonly observed in the pHCCs than in the mHCCs. The present results showed a possible mechanism of fatty change in mHCCs and pHCCs in relation to decreased arterial blood supply..
1920. Satomi Hisamoto, Shinji Shimoda, Kenichi Harada, Sho Iwasaka, Shinya Onohara, Yong Chong, Minoru Nakamura, Yuki Bekki, Tomoharu Yoshizumi, Toru Ikegami, Yoshihiko Maehara, Xiao Song He, M. Eric Gershwin, Koichi Akashi, Hydrophobic bile acids suppress expression of AE2 in biliary epithelial cells and induce bile duct inflammation in primary biliary cholangitis, Journal of Autoimmunity, 10.1016/j.jaut.2016.08.006, 75, 150-160, 2016.12, Understanding the mechanisms of chronic inflammation in primary biliary cholangitis (PBC) is essential for successful treatment. Earlier work has demonstrated that patients with PBC have reduced expression of the anion exchanger 2 (AE2) on biliary epithelial cells (BEC) and deletion of AE2 gene has led to a PBC-like disorder in mice. To directly address the role of AE2 in preventing PBC pathogenesis, we took advantage of our ability to isolate human BEC and autologous splenic mononuclear cells (SMC). We studied the influence of hydrophobic bile acids, in particular, glycochenodeoxycholic acid (GCDC), on AE2 expression in BEC and the subsequent impact on the phenotypes of BEC and local inflammatory responses. We demonstrate herein that GCDC reduces AE2 expression in BEC through induction of reactive oxygen species (ROS), which enhances senescence of BEC. In addition, a reduction of AE2 levels by either GCDC or another AE2 inhibitor upregulates expression of CD40 and HLA-DR as well as production of IL-6, IL-8 and CXCL10 from BEC in response to toll like receptor ligands, an effect suppressed by inhibition of ROS. Importantly, reduced AE2 expression enhances the migration of autologous splenic mononuclear cells (SMC) towards BEC. In conclusion, our data highlight a key functional role of AE2 in the maintenance of the normal physiology of BEC and the pathogenic consequences of reduced AE2 expression, including abnormal intrinsic characteristics of BEC and their production of signal molecules that lead to the chronic inflammatory responses in small bile ducts..
1921. Toru Ikegami, Tomoharu Yoshizumi, Kazuhito Sakata, Hideaki Uchiyama, Norifumi Harimoto, Noboru Harada, Shinji Itoh, Akihisa Nagatsu, Yuji Soejima, Yoshihiko Maehara, Left lobe living donor liver transplantation in adults
What is the safety limit?, Liver Transplantation, 10.1002/lt.24611, 22, 12, 1666-1675, 2016.12, Small-for-size syndrome (SFSS) is the most significant cause of graft loss after living donor liver transplantation (LDLT), especially after left lobe (LL) LDLT in adults. The safety limit of applying LL-LDLT in adults without severe SFSS with a high rate of lethality needs to be determined. A total of 207 LL-LDLTs in adults since September 2005 were evaluated to analyze the risk factors for severe SFSS, defined as a serum total bilirubin concentration of ≥20.0 mg/dL after LDLT. Although there were no significant differences in cumulative graft survival after LDLT between medium grafts (graft volume [GV] to standard liver volume [SLV] ratio ≥ 40.0%), small grafts (35.0% ≤ GV/SLV < 40.0%), and extra small grafts (GV/SLV < 35.0%), patients with severe SFSS showed a significantly lower 5-year graft survival rate than those without (42.9% versus 94.3%, respectively; P < 0.001). Multivariate analysis for severe SFSS after LL-LDLT showed that donor age of ≥48 years (P = 0.01), Model for End-Stage Liver Disease (MELD) score of ≥ 19 (P < 0.01), and end portal venous pressure of ≥19 mm Hg (P = 0.04) were the significant and independent factors for severe SFSS after LL-LDLT. Within such high-risk subgroups of patients with a donor age of ≥48 years or MELD score of ≥ 19 before LDLT, operative blood loss volume of ≥8.0 L was a risk factor for severe SFSS. LL-LDLT in adults could be indicated and provide acceptable outcomes for the combinations of donors aged < 48 years and recipients with a MELD score of <19. Smaller grafts might yield acceptable outcomes in appropriately selected donor-recipient combinations. Liver Transplantation 22 1666–1675 2016 AASLD..
1922. Takeshi Kurihara, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Reply, Liver Transplantation, 10.1002/lt.24648, 22, 12, 2016.12.
1923. Fumihiro Shoji, Gouji Toyokawa, Noboru Harada, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tatsuro Okamoto, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Maehara, Surgical treatment and outcome of patients with de novo lung cancer after liver transplantation, Anticancer research, 10.21873/anticanres.11608, 37, 5, 2619-2623, 2017.05, Background: De novo malignancy, including primary lung cancer, is one of the limitations to long-term survival after liver transplantation. The purpose of this study was to describe patients who developed de novo lung cancer after living-donor liver transplantation (LDLT) and investigate their clinicopathological features as well as the feasibility of surgical resection. Patients and Methods: We investigated 554 patients who underwent LDLT. Results: De novo lung cancer after LDLT was observed in five (0.9%) out of 554 studied patients: four men and one woman, aged 61-78 years (mean=67 years). All four men had a smoking history. Clinical stages of de novo lung cancer were stage IA in three patients, and stage IB and IV in one patient each. Three out of five patients underwent pulmonary lobectomy and pathological stage was IA in two patients and IIA in one. All patients who underwent surgery stopped immunosuppressive therapy 1 day preoperatively and restarted on postoperative day 1. There were no serious postoperative complications. All three patients are still alive without any recurrence, with survival ranging from 8 to 29 months, with an average of 16.3 months after diagnosis of lung cancer. Conclusion: Although the study population was small, these results suggest that pulmonary lobectomy of de novo lung cancer after LDLT, even under immunosuppressive conditions, is a feasible procedure and may yield a survival benefit..
1924. Shinji Itoh, Tomoharu Yoshizumi, Ken Shirabe, Koichi Kimura, Hirohisa Okabe, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Akihiro Nishie, Yoshihiko Maehara, Functional remnant liver assessment predicts liver-related morbidity after hepatic resection in patients with hepatocellular carcinoma, Hepatology Research, 10.1111/hepr.12761, 47, 5, 398-404, 2017.04, Aim: We aimed to evaluate whether functional assessment of the future remnant liver is a predictor of postoperative morbidity after hepatic resection in patients with hepatocellular carcinoma (HCC). Methods: One hundred forty-six patients who underwent hepatic resection for HCC were enrolled in this study. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI (EOB-MRI) analysis for functional liver assessment was carried out before hepatic resection. The signal intensity in the remnant liver was measured and divided by the signal intensity of the major psoas muscle (the liver to major psoas muscle ratio, LMR) for standardization. The remnant liver function was calculated using the formula (LMR on the hepatobiliary phase/LMR on the precontrast image). Computed tomography liver volumetry was also carried out. The remnant functional liver was calculated as the remnant liver volume or volumetric rate × remnant liver function by EOB-MRI. Results: Morbidities developed in 19 (13.0%) patients. Morbidities associated with the liver occurred in 7 patients (4.7%). There was no mortality during surgery. Median remnant liver function scores using EOB-MRI and remnant functional liver using volumetric rate or volumetry were 1.82 (range, 1.25–2.96), 155.9 (range, 64.7–285.3), and 1027 (range, 369–2148), respectively. Logistic regression analysis identified the remnant functional liver volume as the only independent predictor for liver-related morbidity. Conclusion: Remnant functional liver volume using computed tomography liver volumetry and EOB-MRI was a significantly useful predictor for liver-related morbidity after hepatic resection in patients with HCC..
1925. Tomohiro Iguchi, Toru Ikegami, Tetsuhiro Fujiyoshi, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Low positive airway pressure without positive end-expiratory pressure decreases blood loss during hepatectomy in living liver donors, Digestive surgery, 10.1159/000447755, 34, 3, 192-196, 2017.04, Background/Aims: Despite the development of strategies to minimize blood loss during hepatectomy challenges remain. Our aim was to determine whether low positive airway pressure (PAP) without positive end-expiratory pressure (PEEP) could minimize blood loss during hepatectomy. Methods: Forty-one living liver donors who underwent extended left lobectomy or right lobectomy between December 2012 and November 2013 were retrospectively analyzed. In the standard PAP group (n = 18), tidal volume was 8-10 ml/kg, respiratory rate was 10-12/min and PEEP was maintained at 5 cm H2O. In the low PAP group (n = 23), tidal volume was reduced to 5 ml/kg, respiratory rate was increased to 15/min and PEEP maintained at 0 cm H2O. Low central venous pressure (CVP) was maintained during surgery in all cases. Results: The low PAP group had significantly less blood loss (p = 0.0075) and shorter operation time (p = 0.0303) than the standard PAP group. In multiple regression analysis, ventilation mode and median CVP were found to be determining factors for blood loss. In no case did the ventilation mode affect perioperative management. Conclusions: Low PAP without PEEP is a safe mechanical ventilation mode that might help minimize blood loss along with CVP monitoring during hepatectomy..
1926. Hideaki Uchiyama, Norifumi Harimoto, Shinji Itoh, Tomoharu Yoshizumi, Toru Ikegami, Yoshihiko Maehara, Pleural Effusion After Hepatectomy for Hepatocellular Carcinoma
Risk Factor Analyses and Its Impact on Oncological Outcomes, World journal of surgery, 10.1007/s00268-016-3826-1, 41, 4, 1089-1099, 2017.04, Background: Although posthepatectomy pleural effusion (PHPE) is a commonly observed phenomenon, its precise etiology and the impact of its emergence on oncological outcomes have still unknown. The aim of the current study was to retrospectively investigate risk factors for PHPE and its impact on oncological outcomes of hepatocellular carcinoma (HCC). Methods: Medical records of 330 patients who underwent primary curative hepatectomy for HCC were reviewed. All 330 patients had CT around day 7 after hepatectomy, and the emergence of PHPE on CT was examined. Presumed 38 risk factors for the emergence of PHPE and already-known 9 risk factors together with PHPE for HCC recurrence and patient death after hepatectomy were analyzed. Results: The overall incidence of PHPE was 54.5% (180/330). One hundred seventy-nine and 38 out of the 180 patients had right-sided PHPE and left-sided PHPE, respectively. The independent risk factors for right-sided PHPE were hepatitis B or C back ground, lower preoperative white blood cell count, larger intraoperative blood loss, longer operation time, subcostal incision, and longer total inflow occlusion time, while the only independent risk factor for left-sided PHPE was longer operation time. Left-sided PHPE was testified to be one of the independent risk factors not only for HCC recurrence but also for patient death. Conclusions: Although the cause of PHPE after hepatectomy might be multifactorial, the emergence of left-sided PHPE is a portent of worse oncological outcomes after curative hepatectomy for HCC and patients with left-sided PHPE need close follow-ups..
1927. Noboru Harada, Tomoharu Yoshizumi, Takashi Maeda, Hiroto Kayashima, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Yoshihiko Maehara, Preoperative pancreatic stiffness by real-time tissue elastography to predict pancreatic fistula after pancreaticoduodenectomy, Anticancer research, 10.21873/anticanres.11529, 37, 4, 1909-1915, 2017.04, Aim: To assess the correlations among pancreatic fibrosis, pancreatic stiffness, and postoperative pancreatic fistula (PF). Patients and Methods: The study population consisted of 17 consecutively enrolled patients who underwent subtotal stomach-preserving pancreaticoduodenectomy (SSPPD). The liver fibrosis (LF) index as pancreatic stiffness was measured by real- time tissue elastography (RTE) before SSPPD. We also obtained the pathological fibrosis assessment of the pancreatic stump after SSPPD. Results: The LF index was significantly correlated with pathological pancreatic stump fibrosis. The LF index of patients without PF was significantly higher than that of patients with PF. The optimal cut-off value of the LF index to predict postoperative PF was defined as an LF index ≤1.91. Multivariate analysis revealed that a preoperative LF index ≤1.91 was an independent predictive factor of postoperative PF. Conclusion: Evaluation of pancreatic stiffness using RTE might be an objective index to estimate pancreatic fibrosis and predict postoperative PF..
1928. Shinji Itoh, Hideaki Uchiyama, Yasuharu Ikeda, Kazutoyo Morita, Noboru Harada, Keishi Sugimachi, Hirofumi Kawanaka, Daisuke Korenaga, Tomoharu Yoshizumi, Kenji Takenaka, Yoshihiko Maehara, Post-hepatectomy refractory ascites in cirrhotic patients with hepatocellular carcinoma
Risk factor analysis to overcome this problematic complication, Anticancer research, 10.21873/anticanres.11459, 37, 3, 1381-1385, 2017.03, Background: Refractory ascites is a serious posthepatectomy complication in cirrhotic patients with hepatocellular carcinoma (HCC). In order to avoid this complication, surgeons should preserve as much liver parenchyma as possible in performing hepatectomy in such patients. However, we still occasionally encounter refractory ascites even after limited or small hepatectomy. The aim of this study was to identify risk factors for post-hepatectomy refractory ascites in cirrhotic patients, focusing on limited or small hepatectomy. Patients and Methods: The data of 73 cirrhotic patients with HCC who underwent limited or small hepatectomy were analyzed. Limited or small hepatectomy was defined as hepatectomy equal to or of less than subsegmentectomy. We compared the clinicopathological factors between patients with and without postoperative refractory ascites. Results: Fourteen cirrhotic patients suffered postoperative refractory ascites. Total cholesterol, duration of operation, duration of Pringle maneuver, resection of segment VII, intraoperative blood loss, and intraoperative blood transfusion were found to be significant risk factors for postoperative refractory ascites in univariate analyses. Multivariate analysis revealed that resection of segment VII was an independent risk factor. Conclusion: Resection of segment VII necessitates extensive dissection of the right triangular or coronary ligaments, which could explain that it was an independent risk factor for posthepatectomy refractory ascites. Surgeons should avoid extensive dissection of these ligaments in order to avoid this detrimental complication..
1929. Takasuke Fukuhara, Satomi Yamamoto, Chikako Ono, Shota Nakamura, Daisuke Motooka, Hiroyuki Mori, Takeshi Kurihara, Asuka Sato, Tomokazu Tamura, Takashi Motomura, Toru Okamoto, Michio Imamura, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Kazuaki Chayama, Yoshiharu Matsuura, Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity, Scientific reports, 10.1038/srep45228, 7, 2017.03, It is well documented that a variety of viral quasispecies are found in the patients with chronic infection of hepatitis C virus (HCV). However, the significance of quasispecies in the specific infectivity to individual cell types remains unknown. In the present study, we analyzed the role of quasispecies of the genotype 2a clone, JFH1 (HCVcc), in specific infectivity to the hepatic cell lines, Huh7.5.1 and Hep3B. HCV RNA was electroporated into Huh7.5.1 cells and Hep3B/miR-122 cells expressing miR-122 at a high level. Then, we adapted the viruses to Huh7 and Hep3B/miR-122 cells by serial passages and termed the resulting viruses HCVcc/Huh7 and HCVcc/Hep3B, respectively. Interestingly, a higher viral load was obtained in the homologous combination of HCVcc/Huh7 in Huh7.5.1 cells or HCVcc/Hep3B in Hep3B/miR-122 cells compared with the heterologous combination. By using a reverse genetics system and deep sequence analysis, we identified several adaptive mutations involved in the high affinity for each cell line, suggesting that quasispecies of HCV participate in cell-specific infectivity..
1930. Daisuke Hashimoto, Akira Chikamoto, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Hideo Baba, Yoshihiko Maehara, A comparative study on the complications of conventional and end-to-side inserting pancreatojejunostomy after pancreaticoduodenectomy, Surgery today, 10.1007/s00595-016-1364-y, 47, 2, 238-244, 2017.02, Purpose: Pancreatico-digestive anastomosis is important in ensuring the safety of pancreaticoduodenectomy. This study compared the postoperative complications of a newly developed method of inserting end-to-side pancreaticojejunostomy with the conventional pancreaticojejunostomy after pancreaticoduodenectomy. Methods: From April 2012 to December 2015, 108 consecutive patients underwent pancreaticoduodenectomy at Kumamoto University Hospital. A modified child’s reconstruction was performed with the inserting or conventional pancreaticojejunostomy. The clinical course and the incidence of postoperative complications were retrospectively evaluated. Results: Five patients were excluded, four who underwent hepato-pancreatoduodenectomy and one who did not require pancreaticojejunostomy because of an atrophic pancreatic remnant. Of the 103 patients that were included in the analysis, 41 and 62 underwent surgery with the inserting and conventional methods, respectively. The incidence of postoperative Clavien–Dindo grade > II complications was similar in the two groups [36.6 % (15/41) vs 27.4 % (17/62)]. However, the rates of grade C postoperative pancreatic fistula [7.3 % (3/41) vs 0 % (0/62) P = 0.030] and re-operation for postoperative complications [14.6 % (6/41) vs 3.2 % (2/62), P = 0.034] were significantly higher in the inserting group than in the conventional group. There were no in-hospital deaths in either group. Conclusions: The conventional pancreaticojejunostomy is safer than the end-to-side inserting pancreaticojejunostomy, as the latter is associated with a risk of severe complications. Improvements in pancreatico-digestive anastomosis techniques are required..
1931. Masahiro Satake, Keiji Matsubayashi, Yuji Hoshi, Rikizo Taira, Yasumi Furui, Norihiro Kokudo, Nobuhisa Akamatsu, Tomoharu Yoshizumi, Nobuhiro Ohkohchi, Hiroaki Okamoto, Masato Miyoshi, Akinori Tamura, Kyoko Fuse, Kenji Tadokoro, Unique clinical courses of transfusion-transmitted hepatitis E in patients with immunosuppression, Transfusion, 10.1111/trf.13994, 57, 2, 280-288, 2017.02, BACKGROUND: The high prevalence of specific immunoglobulin G for hepatitis E virus (HEV) in Japanese people raises the possibility of a high incidence of HEV-viremic blood donors and therefore frequent transfusion-transmitted HEV (TT-HEV). STUDY DESIGN AND METHODS: TT-HEV cases established in Japan through hemovigilance and those published in the literature were collected. Infectivity of HEV-contaminated blood components and disease severity in relation to immunosuppression were investigated. RESULTS: Twenty established TT-HEV cases were recorded over the past 17 years. A lookback study verified that five of 10 patients transfused with known HEV-contaminated blood components acquired HEV infection. The minimal infectious dose of HEV through transfusion was 3.6 × 104 IU. Nine of the 19 TT-HEV cases analyzed had hematologic diseases. Only two cases showed the maximal alanine aminotransferase level of more than 1000 U/L. Two patients with hematologic malignancy and two liver transplant recipients had chronic liver injury of moderate severity. CONCLUSION: The infectivity of HEV-contaminated components was 50%. Immunosuppression likely causes the moderate illness of TT-HEV, but it may lead to the establishment of chronic sequelae. Transfusion recipients, a population that is variably immunosuppressed, are more vulnerable to chronic liver injury as a result of TT-HEV than the general population is as a result of food-borne infection..
1932. Toru Ikegami, Tomonari Shimagaki, Junji Kawasaki, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Norifumi Harimoto, Shinji Itoh, Yuji Soejima, Yoshihiko Maehara, Eversion technique to prevent biliary stricture after living donor liver transplantation in the universal minimal hilar dissection era, Transplantation, 10.1097/TP.0000000000001533, 101, 1, e20-e25, 2017.01, Background. Biliary anastomosis stricture (BAS) is still among the major concerns after living donor liver transplantation (LDLT), even after the technical refinements including the universal use of the blood flow-preserving hilar dissection technique. The aim of this study is to investigate what are still the factors for BAS after LDLT. Methods. An analysis of 279 adult-to-adult LDLT grafts (left lobe, n = 161; right lobe, n = 118) with duct-to-duct biliary reconstruction, since the universal application of minimal hilar dissection technique and gradual introduction of eversion technique, was performed. Results. There were 39 patients with BAS. Univariate analysis showed that a right lobe graft (P = 0.008), multiple bile ducts (P < 0.001), ductoplasty (P < 0.001), not using the eversion technique (P = 0.004) and fewer biliary stents than bile duct orifices (P = 0.002) were among the factors associated with BAS. The 1-year and 5-year BAS survival rates were 17.7% and 21.2% in the noneversion group (n = 134), and 6.2% and 7.9% in the eversion group (n = 145), respectively (P = 0.002). The perioperative factors including graft biliary anatomy were not different between everted (n = 134) and noneverted (n = 145) patients. Conclusions. The application of eversion technique under minimal hilar dissection technique could be a key for preventing BAS in duct-to-duct biliary reconstruction in LDLT..
1933. Yuki Bekki, Tomoharu Yoshizumi, Shinji Shimoda, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Atsushi Kuno, Hisashi Narimatsu, Ken Shirabe, Yoshihiko Maehara, Hepatic stellate cells secreting WFA+-M2BP
Its role in biological interactions with Kupffer cells, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.13708, 32, 7, 1387-1393, 2017.07, Background and Aim: Hepatic stellate cells (HSCs) play a central role in hepatic fibrosis and are regulated by Kupffer cells (KCs). Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) was recently identified as a serum marker for hepatic fibrosis. Although WFA+-M2BP was identified as a ligand of Mac-2, the function of WFA+-M2BP in hepatic fibrosis remains unclear. Methods: Liver specimens were obtained from five patients with cirrhosis, five with chronic hepatitis, and five without hepatic fibrosis. WFA+-M2BP kinetics were evaluated histologically and in subpopulations of liver cells such as HSCs, KCs, endothelial cells, biliary epithelial cells, and hepatocytes in in vitro culture. The function of WFA+-M2BP in activated HSCs was evaluated using immunoblot analysis. Results: Numbers of WFA+-M2BP-positive cells in liver tissues increased with fibrosis stage. There were significant differences in WFA+-M2BP levels between fibrosis stages F0 and F1–2 (P = 0.012) and between fibrosis stages F1–2 and F3–4 (P < 0.001). HSCs were the source of WFA+-M2BP secretion in in vitro cultures of liver cells, as determined by sandwich immunoassay. Cells of the human HSC line LX-2 also secreted WFA+-M2BP. Histologically, tissue sections showed that WFA+-M2BP was located in Mac-2-expressing KCs. In vitro assays showed that exogenous WFA+-M2BP stimulation enhanced Mac-2 expression in KCs and that HSCs co-cultured with KCs increased α-smooth muscle actin expression. Finally, Mac-2-depleted KCs with short interfering RNA had reduced α-smooth muscle actin expression following co-culturing with HSCs. Conclusions: WFA+-M2BP from HSCs induces Mac-2 expression in KCs, which in turn activates HSCs to be fibrogenic..
1934. Noboru Harada, Tomoharu Yoshizumi, Yo Ichi Yamashita, Yuji Soejima, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Yoshihiko Maehara, Impact and prediction of lymph node involvement in patients with intrahepatic cholangiocarcinoma after curative resection, Anticancer research, 10.21873/anticanreS.11751, 37, 7, 3763-3769, 2017.07, Background: The aim of this study was to identify the preoperative predictors of prognosis in patients with intrahepatic cholangiocarcinoma (ICC) undergoing resection. Patients and Methods: We enrolled 90 patients with ICC who underwent surgical resection, including 59 in whom surgery was considered curative, and measured the overall survival (OS), recurrence-free survival (RFS), and other outcomes and potential prognostic factorS. Results: Multivariate Cox proportional hazards analysis showed that tumor in the resection margins (R>0) independently predicted long-term OS in the whole cohort. In the curatively-resected group (R0), lymph node involvement was the only independent predictor of long-term OS. Multiple tumors, perihilar tumor location and serum carcinoembryonic antigen (CEA) concentration >2.2 ng/ml were independent predictors of lymph node involvement before curative resection. Conclusion: Patients with ICC with multiple tumors, perihilar tumors and serum CEA concentration >2.2 ng/ml in association with lymph node involvement may need additional preoperative chemotherapy..
1935. Daisuke Imai, Tomoharu Yoshizumi, Shinji Okano, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Yuji Soejima, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara, The prognostic impact of programmed cell death ligand 1 and human leukocyte antigen class I in pancreatic cancer, Cancer Medicine, 10.1002/cam4.1087, 6, 7, 1614-1626, 2017.07, Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive tumor-microenvironment (TME) that supports the growth of tumors and mediates tumors enabling evasion of the immune system. Expression of programmed cell death ligand 1 (PD-L1) and loss of human leukocyte antigen (HLA) class I on tumor cells are methods by which tumors escape immunosurveillance. We examined immune cell infiltration, the expression of PD-L1 and HLA class I by PDA cells, and the correlation between these immunological factors and clinical prognosis. PDA samples from 36 patients were analyzed for HLA class I, HLA-DR, PD-L1, PD-1, CD4, CD8, CD56, CD68, and FoxP3 expression by immunohistochemistry. The correlations between the expression of HLA class I, HLA-DR, PD-L1 or PD-1 and the pattern of tumor infiltrating immune cells or the patients’ prognosis were assessed. PD-L1 expression correlated with tumor infiltration by CD68+ and FoxP3+ cells. Low HLA class I expression was an only risk factor for poor survival. PD-L1 negative and HLA class I high-expressing PDA was significantly associated with higher numbers of infiltrating CD8+ T cells in the TME, and a better prognosis. Evaluation of both PD-L1 and HLA class I expression by PDA may be a good predictor of prognosis for patients. HLA class I expression by tumor cells should be evaluated when selecting PDA patients who may be eligible for treatment with PD-1/PD-L1 immune checkpoint blockade therapies..
1936. Huanlin Wang, Kenichi Kohashi, Tomoharu Yoshizumi, Yukihiko Okumura, Yuki Tanaka, Masahiro Shimokawa, Takeshi Iwasaki, Shinichi Aishima, Yoshihiko Maehara, Yoshinao Oda, Coexpression of SALL4 with HDAC1 and/or HDAC2 is associated with underexpression of PTEN and poor prognosis in patients with hepatocellular carcinoma, Human Pathology, 10.1016/j.humpath.2017.03.007, 64, 69-75, 2017.06, Spalt-like transcriptional factor 4 (SALL4), a stem marker, is reactivated in several cancers. A previous study has demonstrated that SALL4 interacts with the nucleosome remodeling deacetylase complex, which contains histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2). In this study, we investigated the expression status of SALL4, HDAC1, and HDAC2 and their relationship with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by immunohistochemical analysis of the posthepatectomy specimens of 135 patients with hepatocellular carcinoma who were treated at our hospital. Ninety-two frozen samples were subjected to quantitative reverse-transcription polymerase chain reaction analysis to detect the messenger RNA levels of PTEN. Seventy-six (56%) of 135 patients were positive for SALL4, and this group had a higher prevalence of hepatitis B antigen, a higher value of α-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKAII) and poor histologic differentiation. The 5-year survival rate was significantly lower in the SALL4-positive group. High HDAC1 expression (51%) was correlated with a poor histologic differentiation and a poor prognosis. High HDAC2 expression (46%) was associated with a higher prevalence of hepatitis B antigen positivity, a poor histologic differentiation and higher prevalence of vascular invasion, and a lower 5-year survival rate. Coexpression of SALL4 with HDAC1 and/or HDAC2 was correlated with underexpression of PTEN. Moreover, multivariable analysis revealed that coexpression of SALL4 with HDAC1 and/or HDAC2 was predictive of an unfavorable prognosis. Our data thus suggested that the combination of SALL4, HDAC1, and HDAC2 may provide a potential target for molecular therapy..
1937. T. Motomura, T. Yoshizumi, H. Wang, A. Nagatsu, S. Itoh, N. Harada, N. Harimoto, T. Ikegami, H. Uchiyama, Y. Soejima, Y. Maehara, Duct-to-duct Biliary Reconstruction in Living-donor Liver Transplantation for Primary Sclerosing Cholangitis
Report of a Case, Transplantation Proceedings, 10.1016/j.transproceed.2017.03.069, 49, 5, 1196-1198, 2017.06, Although Roux-en Y hepaticojejunostomy was previously recommended for the biliary reconstruction in liver transplantation for primary sclerosing cholangitis (PSC), some recent reports showed no difference in the graft survival between Roux-en Y and duct-to-duct anastomosis in deceased-donor liver transplantation. On the other hand, considering the risk of recurrence and the short length of the bile duct of the graft, duct-to-duct biliary anastomosis has never been reported in a patient undergoing living-donor liver transplantation (LDLT) for PSC. A 45 year-old male underwent LDLT using a left-lobe graft donated from his brother. Cholangiography showed no lesion in his common bile duct and duct-to-duct anastomosis was chosen for him. Fifteen months later, he suffered cholangitis due to PSC recurrence and endoscopic retrograde cholangiography was performed. The stents were inserted into his B2 and B3, and he remains well. Because of the ability to easily manage biliary complication, duct-to-duct biliary reconstruction may become the first choice in LDLT for PSC without common bile duct lesions..
1938. Toru Ikegami, Tomoharu Yoshizumi, Junji Kawasaki, Tomonari Shimagaki, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Hepatocellular carcinoma developed in a living donor after left lobe donation
a case for caution, Hepatology Research, 10.1111/hepr.12786, 47, 7, 715-718, 2017.06, Although it has been recognized that those who are positive for anti-hepatitis B core antibody (anti-HBcAb) and negative for hepatitis B surface antigen (HBsAg) with normal liver function could be donors for living donor liver transplantation under appropriate prophylaxis, the negative impact of positive HBcAb on such donors themselves has not been reported. We present a case of a living donor with positive HBcAb, who donated his left lobe for his sister with unresectable giant hepatic hemangioma, and the donor himself developed a de novo hepatocellular carcinoma (HCC) 10 years after donation. He had been lost from the follow-up program since 1 year after donation. Imaging studies showed a heterogeneously enhanced mass compatible with HCC, which was 9 cm in size with portal invasion into the anterior portal vein of the remnant liver. Re-laparotomy for hepatectomy with the removal of the tumor thrombus in the anterior portal vein of the remnant liver was carried out, and he is free from recurrence 6 months after surgery on prophylactic sorafenib. At our institute, 58 (9.6%) donors among the 603 living donors were anti-HBcAb positive and anti-HBsAg negative, and we started regular HCC surveillance using sonogram every 6 months for these patients..
1939. A. Nagatsu, T. Yoshizumi, T. Ikegami, N. Harimoto, N. Harada, Y. Soejima, A. Taketomi, Y. Maehara, In Situ Posterior Graft Segmentectomy for Large-for-Size Syndrome in Deceased Donor Liver Transplantation in Adults
A Case Report, Transplantation Proceedings, 10.1016/j.transproceed.2017.03.036, 49, 5, 1199-1201, 2017.06, Large-for-size syndrome (LFSS) is controversial in pediatric living donor liver transplantation patients and is associated with a poor graft outcome. Similar situations in deceased donor liver transplantation (DDLT) in adults have not been reported frequently, and there are no official guidelines worldwide. Deceased donation is extremely limited in Japan, and when a larger liver is allocated for a very sick small recipient in Japan, transplantation with a plan to address LFSS might be necessary. The patient is a 58-year-old female patient who had acute liver failure with coma. The graft-recipient weight ratio (GRWR) was 2.74%. Although the graft was enlarged by reperfusion, the intraoperative Doppler ultrasound, performed after reperfusion, showed sufficient graft in-flow and out-flow. However, when the liver graft was situated appropriately into the right phrenic space supported by the rib cage and diaphragm, the blood flow in the hepatic vein and portal vein was significantly reduced. Graft blood flow did not improve without removing it from the right subphrenic space. Therefore, we decided to perform an in situ graft posterior segmentectomy, so that the graft right lobe was properly accommodated in the patient's right subphrenic space. After the segmentectomy of the graft, an intraoperative Doppler sonogram showed significantly improved blood flow. LFSS could be a significant operative challenge in adult DDLT, especially in areas with limited chances of DDLT. In situ posterior segmentectomy in the demarcated area could be a solution for treating patients with LFSS..
1940. Yoshiki Asayama, Akihiro Nishie, Kousei Ishigami, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Nobuhiro Fujita, Takao Ohtsuka, Tomoharu Yoshizumi, Shinichi Aishima, Yoshinao Oda, Hiroshi Honda, Prognostic significance of contrast-enhanced CT attenuation value in extrahepatic cholangiocarcinoma, European Radiology, 10.1007/s00330-016-4621-y, 27, 6, 2563-2569, 2017.06, Objectives: To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). Methods: This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT − attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT − attenuation value at unenhanced CT)] × 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. Results: The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). Conclusions: The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. Key points: • Dynamic contrast study can evaluate the aggressiveness of extrahepatic cholangiocarcinoma. • A lower washout ratio was an independent prognostic factor for overall survival. • CT can predict survival and inform decisions on surgical options or chemotherapy..
1941. Koichiro Morita, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Nobuhiro Fujita, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Hiroshi Honda, Does apparent diffusion coefficient predict the degree of liver regeneration of donor and recipient after living donor liver transplantation?, European Journal of Radiology, 10.1016/j.ejrad.2017.02.041, 90, 146-151, 2017.05, Objective To elucidate the relationship between the ADCs of the liver graft and the remnant liver and the degree of liver regeneration in LDLT. Materials and methods 15 recipients and 15 corresponding donors underwent magnetic resonance imaging and computed tomography 1–2 weeks after living donor liver transplantation (LDLT). For diffusion-weighted imaging (DWI), a single-shot echo-planar sequence with b-factors of 0, 500, and 1000 s/mm2 was scanned. ADCs of the liver parenchyma were calculated at b factors of 0 and 500 and 1000 (ADC 0–500–1000) or 0 and 500 (ADC 0–500) or 500 and 1000 (ADC 500–1000). The liver volume ratio at LDLT, the mean ADCs and the regeneration rate were compared between the graft and the remnant liver using paired-t tests. Results The mean liver volume ratio of the recipients (41.3 ± 9.8%) tended to be smaller than that of the donors (51.8 ± 13.8%). The mean ADC 0–500 of the remnant liver (1.72 ± 0.33) was significantly higher than that of the graft (1.43 ± 0.32). The regeneration rate of the graft (2.07 ± 0.41) was significantly higher than that of the remnant liver (1.53 ± 0.49). Conclusion ADC 0–500 can describe differences in blood perfusion between liver grafts and the remnant liver according to the degree of liver regeneration..
1942. Hirohisa Okabe, Daisuke Hashimoto, Akira Chikamoto, Morikatsu Yoshida, Katsunobu Taki, Kota Arima, Katsunori Imai, Yoshitaka Tamura, Osamu Ikeda, Takatoshi Ishiko, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Yo ichi Yamashita, Tomoharu Yoshizumi, Toru Beppu, Yasuyuki Yamashita, Hideo Baba, Yoshihiko Maehara, Shape and Enhancement Characteristics of Pancreatic Neuroendocrine Tumor on Preoperative Contrast-enhanced Computed Tomography May be Prognostic Indicators, Annals of Surgical Oncology, 10.1245/s10434-016-5630-4, 24, 5, 1399-1405, 2017.05, Background: Prognostic indicators of the malignant potential of pancreatic neuroendocrine tumors (PNET) are limited. We assessed tumor shape and enhancement pattern on contrast-enhanced computed tomography as predictors of malignant potential. Methods: Sixty cases of PNET patients undergoing curative surgery from 2001 to 2014 were enrolled onto our retrospective study. Preoperative enhanced CTs were assessed, and criteria defined for regularly shaped and enhancing tumors (group 1), and irregularly shaped and/or enhancing tumors (group 2). The relation of tumor shape and enhancement pattern to outcome was assessed. Results: Interobserver agreement was substantial (kappa = 0.74). Group 2 (n = 24) was significantly correlated with synchronous liver metastasis (23 vs. 0 %), lymph node metastasis (36 vs. 3 %), pathologic capsular invasion (68 vs. 8 %), larger tumor size (30 vs. 12 mm), tumor, node, metastasis classification system (TNM) stage III/IV disease (46 vs. 3 %), and histologic grade 2/3 (41 vs. 0 %). Multivariate analysis revealed that tumor grade 2/3 and group 2 criteria correlated with tumor relapse (hazard ratio 6.5 and 13.6, P = 0.0071 and 0.039, respectively), and that only group 2 criteria were independently correlated with poor overall survival (hazard ratio 5.56e + 9, P = 0.0041). Conclusions: Irregular tumor shape/enhancement on preoperative computed tomography is a negative prognostic factor after curative surgery for PNET..
1943. T. Motomura, T. Yoshizumi, M. Ohira, Y. Mano, T. Toshima, S. Itoh, N. Harada, N. Harimoto, T. Ikegami, Y. Soejima, Y. Maehara, Successful Recombinant Thrombomodulin Treatment for Thrombotic Microangiopathy After Liver Transplantation
A Case Report, Transplantation Proceedings, 10.1016/j.transproceed.2017.09.014, 49, 10, 2409-2410, 2017.12, Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare but severe complication after liver transplantation. In contrast to other thrombotic microangiopathies, treatment for TA-TMA has yet to be clarified. A 52-year-old male patient with liver cirrhosis due to hepatitis C underwent split liver transplantation from a deceased donor. His clinical course was without complication until 4 days after transplantation, when he experienced impaired consciousness, hemolytic anemia with fragmented erythrocytes, and marked thrombocytopenia. TA-TMA was diagnosed, and recombinant thrombomodulin was administered for 4 days. The patient's clinical symptoms and laboratory data rapidly improved. He has been followed up for 6 months and has not shown any complications. The pathogenesis of TA-TMA is endothelial damage in the vasculature. Recombinant thrombomodulin, an endothelial cell–protecting agent, is a promising new therapeutic choice for TA-TMA after liver transplantation..
1944. Toru Ikegami, Yoshihide Ueda, Nobuhisa Akamatsu, Kohei Ishiyama, Ryoichi Goto, Akihiko Soyama, Kaori Kuramitsu, Masaki Honda, Masahiro Shinoda, Tomoharu Yoshizumi, Hideaki Okajima, Yuko Kitagawa, Yukihiro Inomata, Yonson Ku, Susumu Eguchi, Akinobu Taketomi, Hideki Ohdan, Norihiro Kokudo, Mitsuo Shimada, Katsuhiko Yanaga, Hiroyuki Furukawa, Shinji Uemoto, Yoshihiko Maehara, Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation
A Japanese multicenter experience, Clinical Transplantation, 10.1111/ctr.13109, 31, 11, 2017.11, The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n = 1) in the NS3, and at L31 (n = 4), Y93 (n = 4), and L31/Y93 (n = 1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n = 12). Univariate analysis showed that a history of SMV (P <.01) and the presence of mutations in NS5A (P =.02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate..
1945. N. Harimoto, T. Yoshizumi, T. Izumi, T. Motomura, N. Harada, S. Itoh, T. Ikegami, H. Uchiyama, Y. Soejima, A. Nishie, T. Kamishima, R. Kusaba, K. Shirabe, Y. Maehara, Clinical Outcomes of Living Liver Transplantation According to the Presence of Sarcopenia as Defined by Skeletal Muscle Mass, Hand Grip, and Gait Speed, Transplantation Proceedings, 10.1016/j.transproceed.2017.09.017, 49, 9, 2144-2152, 2017.11, Background Sarcopenia is an independent predictor of death after living-donor liver transplantation (LDLT). However, the ability of the Asian Working Group for Sarcopenia criteria for sarcopenia (defined as reduced skeletal muscle mass plus low muscle strength) to predict surgical outcomes in patients who have undergone LDLT has not been determined. Methods This study prospectively enrolled 366 patients who underwent LDLT at Kyushu University Hospital. Skeletal muscle area (determined by computed tomography), hand-grip strength, and gait speed were measured in 102 patients before LDLT. We investigated the relationship between sarcopenia and surgical outcomes after LDLT performed in three time periods. Results The number of patients with lower skeletal muscle area has increased to 52.9% in recent years. The incidence of sarcopenia according to the Asian Working Group for Sarcopenia criteria was 23.5% (24/102). Patients with sarcopenia (defined by skeletal muscle area and functional parameters) had significantly lower skeletal muscle area and weaker hand-grip strength than did those without sarcopenia. Compared with non-sarcopenic patients, patients with sarcopenia also had significantly worse liver function, greater estimated blood loss, greater incidence of postoperative complications of Clavien-Dindo grade IV or greater (including amount of ascites on postoperative day 14, total bilirubin on postoperative day 14, and postoperative sepsis), and longer postoperative hospital stay. Multiple logistic regression analysis revealed sarcopenia as a significant predictor of 6-month mortality. Conclusions The combination of skeletal muscle mass and function can predict surgical outcomes in LDLT patients..
1946. T. Shimauchi, K. Yamaura, M. Higashi, K. Abe, T. Yoshizumi, S. Hoka, Fibrinolysis in Living Donor Liver Transplantation Recipients Evaluated Using Thromboelastometry
Impact on Mortality, Transplantation Proceedings, 10.1016/j.transproceed.2017.09.025, 49, 9, 2117-2121, 2017.11, Background Inadequate hemostasis during living donor liver transplantation (LDLT) is mainly due to coagulopathy but may also include fibrinolysis. The purpose of this study was to determine the incidence of fibrinolysis and assess its relevance to mortality in LDLT. Methods The incidence and prognosis of fibrinolysis were retrospectively studied in 76 patients who underwent LDLT between April 2010 and February 2013. Fibrinolysis was evaluated and defined by maximum lysis (ML) >15% within a 60-minute run time using thromboelastometry (ROTEM). Results Fibrinolysis was observed in 19 of the 76 (25%) patients before the anhepatic (pre-anhepatic) phase and was developed in 24 (32%) patients during and after the anhepatic (post-anhepatic) phase. In these 43 patients who had fibrinolysis, spontaneous recovery occurred in 29 patients (73%) within 3 hours after reperfusion of the liver graft. Recovery with tranexamic acid was noted in 2 patients with fibrinolysis in the post-anhepatic phase. Thrombosis in the portal vein and liver artery was noted in 14 patients, and the incidence was significantly greater in patients with post-anhepatic fibrinolysis than in those with pre-anhepatic fibrinolysis (P =.0017). Fibrinolysis that developed in the pre-anhepatic phase was associated with increased 30-day and 6-month mortalities (P =.0003 and.0026, respectively). Conclusions Fibrinolysis existed and developed in a large percentage of patients during LDLT. Thrombosis in the portal vein and hepatic artery was more common in patients with fibrinolysis in the post-anhepatic phase. Fibrinolysis that developed in the pre-anhepatic phase was associated with increased 30-day and 6-month mortalities..
1947. Norifumi Harimoto, Tomoharu Yoshizumi, Kazuhito Sakata, Akihisa Nagatsu, Takashi Motomura, Shinji Itoh, Noboru Harada, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma, World journal of surgery, 10.1007/s00268-017-4097-1, 41, 11, 2805-2812, 2017.11, Background: The Controlling Nutritional Status (CONUT) score is an objective tool widely used to assess nutritional status in patients with inflammatory disease, chronic heart failure, and chronic liver disease. The relationship between CONUT score and prognosis in patients who have undergone hepatic resection, however, has not been evaluated. Methods: Data were retrospectively collected for 357 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent between January 2004 and December 2015. The patients were assigned to two groups, those with preoperative CONUT scores ≤3 (low CONUT score) and >3 (high CONUT score), and their clinicopathological characteristics, surgical outcomes, and long-term survival were compared. Results: Of the 357 patients, 69 (19.3%) had high (>3) and 288 (80.7%) had low (≤3) preoperative CONUT scores. High CONUT score was significantly associated with HCV infection, low serum albumin and cholesterol concentrations, low lymphocyte count, shorter prothrombin time, Child–Pugh B and liver damage B scores, and blood transfusion. Multivariate analysis identified six factors prognostic of poor overall survival (older age, liver damage B score, high CONUT score, poor tumor differentiation, the presence of intrahepatic metastases, and blood transfusion) and five factors prognostic of reduced recurrence-free survival (older age, higher ICGR15, larger tumor size, presence of intrahepatic metastasis, and blood transfusion). Conclusions: In patients with HCC, preoperative CONUT scores are predictive of poorer overall survival, even after adjustments for other known predictors..
1948. Norifumi Harimoto, Tomoharu Yoshizumi, Kazuhito Sakata, Akihisa Nagatsu, Takashi Motomura, Shinji Itoh, Noboru Harada, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Prognostic significance of combined albumin–bilirubin and tumor–node–metastasis staging system in patients who underwent hepatic resection for hepatocellular carcinoma, Hepatology Research, 10.1111/hepr.12868, 47, 12, 1289-1298, 2017.11, Background: In recent years, the establishment of new staging systems for hepatocellular carcinoma (HCC) has been reported worldwide. The system combining albumin–bilirubin (ALBI) with tumor–node–metastasis stage, developed by the Liver Cancer Study Group of Japan, was called the ALBI-T score. Methods: Patient data were retrospectively collected for 357 consecutive patients who had undergone hepatic resection for HCC with curative intent between January 2004 and December 2015. The overall survival and recurrence-free survival were compared by the Kaplan–Meier method, using different staging systems: the Japan integrated staging (JIS), modified JIS, and ALBI-T. Results: Multivariate analysis identified five poor prognostic factors (higher age, poor differentiation, the presence of microvascular invasion, the presence of intrahepatic metastasis, and blood transfusion) that influenced overall survival, and four poor prognostic factors (the presence of intrahepatic metastasis, serum α-fetoprotein level, blood transfusion, and each staging system (JIS, modified JIS, and ALBI-T score)) that influenced recurrence-free survival. Patients for each these three staging system had a significantly worse prognosis regarding recurrence-free survival, but not with overall survival. The modified JIS score showed the lowest Akaike information criteria statistic value, indicating it had the best ability to predict overall survival compared with the other staging systems. Conclusions: This retrospective analysis showed that, in post-hepatectomy patients with HCC, the ALBI-T score is predictive of worse recurrence-free survival, even when adjustments are made for other known predictors. However, modified JIS is better than ALBI-T in predicting overall survival..
1949. Koichiro Yoshimaru, Toshiharu Matsuura, Yoshiaki Kinoshita, Makoto Hayashida, Yoshiaki Takahashi, Yusuke Yanagi, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara, Tomoaki Taguchi, Graft reduction using a powered stapler in pediatric living donor liver transplantation, Pediatric Transplantation, 10.1111/petr.12985, 21, 6, 2017.09, Large-for-size syndrome is defined by inadequate tissue oxygenation, which results in vascular complications and graft compression after abdominal closure in living donor liver transplantation recipients. An accurate graft reduction that matches the optimal liver volume for the recipient is essential. We herein initially present the feasibility and safety of graft reduction using a powered stapler to obtain an optimal graft size. From October 1996 to October 2015, a total of eight graft reductions were performed using a powered stapler (group A; n=4) or by the conventional method using a cavitron ultrasonic surgical aspirator and portal triad suturing (group B; n=4). The background, intraoperative findings and the post-operative outcomes of these eight patients were retrospectively investigated. There were no statistically significant differences in the background of the patients in the two groups. Graft reduction was successfully achieved without any intraoperative complications in group A, whereas intraoperative complications, such as bleeding and bile leakage, occurred in two patients of group B. No post-operative surgical complications were detected on computed tomography; moreover, the serum aspartate aminotransferase level normalized significantly earlier in group A (P<.05). In summary, graft reduction using a powered stapler was feasible and safe in comparison with the conventional method..
1950. Toru Ikegami, Tomoharu Yoshizumi, Hideaki Uchiyama, Yuji Soejima, Noboru Harada, Yoshihiko Maehara, Hepatic artery reconstruction in living donor liver transplantation using surgical loupes
Achieving low rate of hepatic arterial thrombosis in 741 consecutive recipients—tips and tricks to overcome the poor hepatic arterial flow, Liver Transplantation, 10.1002/lt.24798, 23, 8, 1081-1082, 2017.08.
1951. Yoshihide Ueda, Toru Ikegami, Nobuhisa Akamatsu, Akihiko Soyama, Masahiro Shinoda, Ryoichi Goto, Hideaki Okajima, Tomoharu Yoshizumi, Akinobu Taketomi, Yuko Kitagawa, Susumu Eguchi, Norihiro Kokudo, Shinji Uemoto, Yoshihiko Maehara, Treatment with sofosbuvir and ledipasvir without ribavirin for 12 weeks is highly effective for recurrent hepatitis C virus genotype 1b infection after living donor liver transplantation
a Japanese multicenter experience, Journal of gastroenterology, 10.1007/s00535-017-1310-9, 52, 8, 986-991, 2017.08, Background: The optimal therapy for recurrent hepatitis C virus (HCV) infection after liver transplantation has not yet been established. This study aimed to clarify the efficacy and safety of interferon-free therapy with sofosbuvir and ledipasvir without ribavirin for 12 weeks in Japanese patients with HCV genotype 1b infection after living donor liver transplantation. Methods: A cohort study of living donor liver transplant recipients with recurrent HCV genotype 1b infection treated with sofosbuvir (400 mg/day) and ledipasvir (90 mg/day) was performed at six liver transplant centers in Japan. Results: Fifty-four patients were treated with sofosbuvir and ledipasvir. Thirty-eight patients (70%) were treatment experienced, including 17 patients who had undergone prior direct-acting-antiviral-based triple therapy. Ten patients had resistance-associated substitutions at L31 or Y93 in the NS5A region of the HCV genome. Fifty-three patients completed the 12-week treatment protocol; treatment was discontinued in one patient who developed pneumonia at 4 weeks and died thereafter. All 53 patients who completed the treatment regimen achieved a sustained virological response 12 weeks after completion of treatment. Treatment was well tolerated in most patients, but seven patients developed serious adverse events, including hemorrhagic duodenal ulcers (n = 3), infection (n = 2), pleural effusion (n = 1), and alveolar hemorrhage (n = 1). Conclusions: Sofosbuvir and ledipasvir treatment without ribavirin for 12 weeks was highly effective in achieving a sustained virological response in Japanese patients who developed recurrent HCV genotype 1b infection after living donor liver transplantation..
1952. Masakazu Sugiyama, Tomoharu Yoshizumi, Yoshihiro Yoshida, Yuki Bekki, Yoshihiro Matsumoto, Shohei Yoshiya, Takeo Toshima, Toru Ikegami, Shinji Itoh, Norifumi Harimoto, Shinji Okano, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, p62 Promotes Amino Acid Sensitivity of mTOR Pathway and Hepatic Differentiation in Adult Liver Stem/Progenitor Cells, Journal of cellular physiology, 10.1002/jcp.25653, 232, 8, 2112-2124, 2017.08, Autophagy is a homeostatic process regulating turnover of impaired proteins and organelles, and p62 (sequestosome-1, SQSTM1) functions as the autophagic receptor in this process. p62 also functions as a hub for intracellular signaling such as that in the mammalian target of rapamycin (mTOR) pathway. Liver stem/progenitor cells have the potential to differentiate to form hepatocytes or cholangiocytes. In this study, we examined effects of autophagy, p62, and associated signaling on hepatic differentiation. Adult stem/progenitor cells were isolated from the liver of mice with chemically induced liver injury. Effects of autophagy, p62, and related signaling pathways on hepatic differentiation were investigated by silencing the genes for autophagy protein 5 (ATG5) and/or SQSTM1/p62 using small interfering RNAs. Hepatic differentiation was assessed based on increased albumin and hepatocyte nuclear factor 4α, as hepatocyte markers, and decreased cytokeratin 19 and SOX9, as stem/progenitor cell markers. These markers were measured using quantitative RT-PCR, immunofluorescence, and Western blotting. ATG5 silencing decreased active LC3 and increased p62, indicating inhibition of autophagy. Inhibition of autophagy promoted hepatic differentiation in the stem/progenitor cells. Conversely, SQSTM1/p62 silencing impaired hepatic differentiation. A suggested mechanism for p62-dependent hepatic differentiation in our study was activation of the mTOR pathway by amino acids. Amino acid activation of mTOR signaling was enhanced by ATG5 silencing and suppressed by SQSTM1/p62 silencing. Our findings indicated that promoting amino acid sensitivity of the mTOR pathway is dependent on p62 accumulated by inhibition of autophagy and that this process plays an important role in the hepatic differentiation of stem/progenitor cells. J. Cell. Physiol. 232: 2112–2124, 2017..
1953. Kazuki Takeishi, Toru Ikegami, Tomoharu Yoshizumi, Nao Fujimori, Masaki Mori, Reply, Liver Transplantation, 10.1002/lt.25725, 26, 5, 727-728, 2020.05.
1954. Tomoharu Yoshizumi, Masaki Mori, Correction to
Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy (Surgery Today, (2020), 50, 1, (21-29), 10.1007/s00595-019-01881-y), Surgery today, 10.1007/s00595-019-01949-9, 50, 4, 2020.04, The article Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy, written by Tomoharu Yoshizumi and Masaki Mori, was originally published Online First without Open Access. After publication in volume 50, issue 1, page 21–29 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to.
1955. Takahiro Tomino, Hirotada Tajiri, Takaaki Tatsuguchi, Takahiro Shirai, Kounosuke Oisaki, Shigeki Matsunaga, Fumiyuki Sanematsu, Daiji Sakata, Tomoharu Yoshizumi, Yoshihiko Maehara, Motomu Kanai, Jean François Cote, Yoshinori Fukui, Takehito Uruno, DOCK1 inhibition suppresses cancer cell invasion and macropinocytosis induced by self-activating Rac1P29S mutation, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2018.02.073, 497, 1, 298-304, 2018.02, Rac1 is a member of the Rho family of small GTPases that regulates cytoskeletal reorganization, membrane polarization, cell migration and proliferation. Recently, a self-activating mutation of Rac1, Rac1P29S, has been identified as a recurrent somatic mutation frequently found in sun-exposed melanomas, which possesses increased inherent GDP/GTP exchange activity and cell transforming ability. However, the role of cellular Rac1-interacting proteins in the transforming potential of Rac1P29S remains unclear. We found that the catalytic domain of DOCK1, a Rac-specific guanine nucleotide exchange factor (GEF) implicated in malignancy of a variety of cancers, can greatly accelerate the GDP/GTP exchange of Rac1P29S. Enforced expression of Rac1P29S induced matrix invasion and macropinocytosis in wild-type (WT) mouse embryonic fibroblasts (MEFs), but not in DOCK1-deficient MEFs. Consistently, a selective inhibitor of DOCK1 that blocks its GEF function suppressed the invasion and macropinocytosis in WT MEFs expressing Rac1P29S. Human melanoma IGR-1 and breast cancer MDA-MB-157 cells harbor Rac1P29S mutation and express DOCK1 endogenously. Genetic inactivation and pharmacological inhibition of DOCK1 suppressed their invasion and macropinocytosis. Taken together, these results indicate that DOCK1 is a critical regulator of the malignant phenotypes induced by Rac1P29S, and suggest that targeting DOCK1 might be an effective approach to treat cancers associated with Rac1P29S mutation..
1956. Yohei Yamada, Ken Hoshino, Yasushi Fuchimoto, Kentaro Matsubara, Taizo Hibi, Hiroshi Yagi, Yuta Abe, Masahiro Shinoda, Minoru Kitago, Hideaki Obara, Takahito Yagi, Hideaki Okajima, Toshimi Kaido, Shinji Uemoto, Tatsuya Suzuki, Keiichi Kubota, Tomoharu Yoshizumi, Yoshihiko Maehara, Yukihiro Inomata, Yuko Kitagawa, Hiroto Egawa, Tatsuo Kuroda, Rituximab induction to prevent the recurrence of PSC after liver transplantation—the lessons learned from ABO-incompatible living donor liver transplantation, Transplantation Direct, 10.1097/TXD.0000000000000760, 4, 2, 2018.02, Background. Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx. Methods. We conducted a national survey and analyzed the outcome of recipients who underwent ABO-I LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove existing antibodies, and the use of immunosuppression to control humoral immunity. Rituximab was added to the immunosuppression regimen from 2006 onward; 5 patients received rituximab perioperatively. Results. All 7 recipients who underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we found that all 5 recipients from 2006 (who were treated with rituximab) retained an excellent graft function for more than 7 years without any recurrence of PSC. Conclusions. The findings of this study shed light on the efficacy of a novel strategy to prevent the recurrence of PSC and the possible mechanisms provided by rituximab treatment are discussed..
1957. Hirofumi Kawanaka, Tomohiko Akahoshi, Yoshihiro Nagao, Nao Kinjo, Daisuke Yoshida, Yoshihiro Matsumoto, Norifumi Harimoto, Shinji Itoh, Tomoharu Yoshizumi, Yoshihiko Maehara, Customization of laparoscopic gastric devascularization and splenectomy for gastric varices based on CT vascular anatomy, Surgical endoscopy, 10.1007/s00464-017-5646-2, 32, 1, 114-126, 2018.01, Background: Laparoscopic gastric devascularization(Lap GDS) and splenectomy (SPL) for gastric varices is technically challenging because of highly developed collateral vessels and bleeding tendency. We investigated the feasibility of customization of Lap GDS and SPL based on CT vascular anatomy. Methods: We analyzed 61 cirrhotic patients with gastric varices who underwent Lap GDS and SPL between 2006 and 2014. Lap GDS was customized according to the afferent feeding veins (left gastric vein (LGV) and/or posterior gastric vein (PGV)/short gastric vein (SGV)) and efferent drainage veins (gastrorenal shunt and/or gastrophrenic shunt, or numerous retroperitoneal veins) based on CT imaging. Results: Thirty-four patients with efferent drainage veins suitable for balloon-occluded retrograde transvenous obliteration (B-RTO) underwent B-RTO instead of surgical GDS, with subsequent Lap SPL. Among 27 patients with gastric varices unsuitable for B-RTO, 15 patients with PGV/SGV underwent Lap GDS of the greater curvature and SPL, and 12 patients with LGV or LGV/PGV/SGV underwent Lap GDS of the greater and lesser curvature and SPL. The mean operation time was 294 min and mean blood loss was 198 g. There was no mortality or severe morbidity. Gastric varices were eradicated in all 61 patients, with no bleeding or recurrence during a mean follow-up of 55.9 months. The cumulative 3-, 5-, and 7-year survival rates were 92, 82, and 64%, respectively. Conclusions: Lap GDS and SPL customized based on CT vascular anatomy is a safe and effective procedure for treating gastric varices..
1958. N. Harimoto, K. Yugawa, T. Ikegami, M. Ohira, Y. Mano, T. Motomura, T. Toshima, S. Itoh, N. Harada, Y. Soejima, T. Yoshizumi, Y. Maehara, Y. Oda, Hepatobiliary and Pancreatic
Pregnancy induced hepatic veno-occlusive disease requiring liver transplantation, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.13975, 33, 1, 2018.01.
1959. T. Ikegami, T. Yoshizumi, M. Ohira, N. Harada, Y. Soejima, Y. Maehara, Indication of living donor liver transplantation for septuagenarians from double equipoise theory, American Journal of Transplantation, 10.1111/ajt.14446, 18, 1, 278-279, 2018.01.
1960. Shinji Itoh, Tomoharu Yoshizumi, Kazuhisa Sakata, Takashi Motomura, Yohei Mano, Takeo Toshima, Norifumi Harimoto, Noboru Harada, Toru Ikegami, Yuji Soejima, Ryuichi Kusaba, Takahide Kamishima, Akihiro Nishie, Yoshihiko Maehara, Slow Gait Speed Is a Risk Factor for Complications After Hepatic Resection, Journal of Gastrointestinal Surgery, 10.1007/s11605-018-3993-5, 2018.01, Purpose: The aims of this study were to clarify the relationship of gait speed, hand grip strength, and skeletal muscle mass with complications after hepatic resection and to identify risk factors for complications in patients who underwent hepatic resection. Methods: We evaluated the risk factors for complications after hepatic resection in 154 consecutive patients. Preoperative factors included gait speed, hand grip strength, and skeletal muscle mass. The gait speed and hand grip strength of patients were measured by physical therapists, and skeletal muscle mass was measured by computed tomography. Multivariate logistic regression analyses using preoperative factors were performed to assess predictors of the development of complications after hepatic resection. Results: Thirty-three patients (21.4%) developed complications after hepatic resection. These patients had a significantly lower serum albumin level (p = 0.015), slower gait speed (p = 0.007), higher rate of hepatic resection ≥ 2 Couinaud segments (p = 0.014), and lower rate of laparoscopic hepatic resection (p = 0.017) than patients without complications. Multivariate analysis revealed that a gait speed ≤ 1.10 m/s and a serum albumin level of ≤ 4.0 g/dl were independent risk factors for complications after hepatic resection. Conclusions: Slow gait speed and low serum albumin level are significant risk factors for complications after hepatic resection. These data will be helpful for perioperative patient management..
1961. Hideaki Uchiyama, Shinji Itoh, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, Yuji Soejima, Noboru Harada, Kazutoyo Morita, Takeo Toshima, Takashi Motomura, Yoshihiko Maehara, Living donor liver transplantation for hepatocellular carcinoma
results of prospective patient selection by Kyushu University Criteria in 7 years, HPB, 10.1016/j.hpb.2017.08.004, 19, 12, 1082-1090, 2017.12, Background Expanding patient selection beyond the Milan criteria in living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) has long been a matter for debate. We have used the Kyushu University Criteria – maximum tumor diameter <5 cm or des-γ-carboxy prothrombin <300 mAU/ml – in LDLT for HCC since June 2007. The aim of the present study was to present the results of our prospective patient selection by Kyushu University Criteria and to confirm whether or not our criteria were justified. Methods The entire study period was divided into the pre-Kyushu era (July 1999–May 2007) and the Kyushu era (June 2007–November 2014). Eighty-nine and 90 patients underwent LDLT for HCC in the pre-Kyushu era and the Kyushu era, respectively. Results In the pre-Kyushu era, there were significant differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients. In the Kyushu era, however, the differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients disappeared. The 5-year overall patient survival in the Kyushu era was 89.4%. Conclusion Our selection criteria enabled a considerable number of beyond-Milan patients to undergo LDLT without jeopardizing the recurrence-free, and disease-specific, and overall patient survival..
1962. Kousei Ishigami, Akihiro Nishie, Naoki Mochidome, Yoshiki Asayama, Yasuhiro Ushijima, Daisuke Kakihara, Daisuke Okamoto, Nobuhiro Fujita, Takao Ohtsuka, Yoshihiro Miyasaka, Tomoyuki Hida, Tomoharu Yoshizumi, Hiroshi Honda, Mucinous nonneoplastic cyst of the pancreas
CT and MRI appearances, Abdominal Radiology, 10.1007/s00261-017-1204-6, 42, 12, 2827-2834, 2017.12, Purpose: The purpose of this retrospective study was to evaluate imaging features of mucinous nonneoplastic cyst (MNNC) of the pancreas. Materials and methods: Three (0.9%) patients with MNNC of the pancreas were found in 335 surgically resected pancreatic cystic lesions. Three MDCT and two MRI/MRCP studies were retrospectively reviewed. Results: Three cases of MNNC were found in the pancreatic neck, body, and tail, respectively. All the three cases were multilocular without communication with the main pancreatic duct (MPD), although upstream MPD dilatation was seen in two of the three cases. The signal intensity of the cyst fluid was low on T1-weighted, high on T2-weighted, and low on diffusion-weighted images. Cyst wall was thin in two cases, and the remaining case with obstructive pancreatitis showed visible cyst wall enhancement. Conclusion: Imaging findings of MNNC of the pancreas were nonspecific without communication with the MPD. Cyst wall is typically thin without visible enhancement..
1963. Yo ichi Yamashita, Shinichi Aishima, Yosuke Nakao, Tomoharu Yoshizumi, Hiroaki Nagano, Tamotsu Kuroki, Yuko Takami, Takao Ide, Masayuki Ohta, Mitsuhisa Takatsuki, Atsushi Nanashima, Fuminori Ishii, Kenji Kitahara, Satoshi Iino, Toru Beppu, Hideo Baba, Susumu Eguchi, Clinicopathological characteristics of combined hepatocellular cholangiocarcinoma from the viewpoint of patient prognosis after hepatic resection
High rate of early recurrence and its predictors, Hepatology Research, 10.1111/hepr.13507, 2020.01, Aim: Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a very rare subtype of primary liver carcinoma; therefore, its clinicopathological characteristics have not yet been elucidated in detail. The aim of the study was to reveal the clinicopathological characteristics and prognostic factors of cHCC-CCA after hepatic resection (HR). Methods: A total of 124 patients who underwent curative HR for cHCC-CCA between 2000 and 2016 were enrolled in this multi-institutional study conducted by the Kyushu Study Group of Liver Surgery. Clinicopathological analysis was performed from the viewpoint of patient prognosis. Results: A total of 62 patients (50%) had early recurrence within 1.5 years after HR, including 36 patients (58%) with extrahepatic recurrence. In contrast, just four patients (3%) had late recurrence occurring >3 years after HR. The independent predictors of early recurrence were as follows: des-gamma carboxyprothrombin >40 mAU/mL (odds ratio 26.2, P = 0.0117), carbohydrate antigen 19–9>37 IU/l (odds ratio 18.0, P = 0.0200), and poorly differentiated HCC or CCA (odds ratio 11.2, P = 0.0259). Conclusions: Half of the patients with cHCC-CCA had early recurrence after HR. Preoperative elevation of des-gamma carboxyprothrombin or carbohydrate antigen 19–9 and the existence of poorly differentiated components of HCC or CCA in resected specimens are predictors of its early recurrence..
1964. Kyohei Yugawa, Shinji Itoh, Tomoharu Yoshizumi, Shohei Yoshiya, Kazuki Takeishi, Takeo Toshima, Noboru Harada, Toru Ikegami, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Prognostic impact of 8-hydroxy-deoxyguanosine and its repair enzyme 8-hydroxy-deoxyguanosine DNA glycosylase in hepatocellular carcinoma, Pathology International, 10.1111/pin.12952, 2020.01, Hepatocellular carcinoma (HCC) has a poor prognosis in the setting of chronic inflammation and fibrosis, both of which promote nuclear DNA oxidative damage. 8-hydroxy-deoxyguanosine (8-OHdG) DNA glycosylase (OGG1) enhances the repair of 8-OHdG, which is the primary oxidative stress-induced mutation that leads to malignant alterations. This study aims to clarify the relationships between oxidative stress-induced factors and HCC progression. The clinicopathological factors were compared with immunohistochemistry OGG1 and 8-OHdG expressions in 86 resected HCC specimens. High 8-OHdG expression was associated with high serum aspartate transaminase and total bilirubin levels, as well as a low platelet count, compared with low 8-OHdG expression. Histological liver cirrhosis and poor differentiation were more frequent in patients with high 8-OHdG expression than in those with low 8-OHdG expression. The 8-OHdG was negatively correlated with OGG1 expression in HCC patients. Therefore, we classified the patients into two groups, low OGG1/high 8-OHdG group and the other group. The patients with low OGG1/high 8-OHdG expressions had worse prognosis than those with the other expressions. Our results showed that low OGG1/high 8-OHdG expressions in nuclei influence HCC patient outcomes. Evaluating the patterns of OGG1 and 8-OHdG expressions might provide pivotal prognostic biomarkers in patients with HCC..
1965. Kousei Ishigami, Akihiro Nishie, Yoshiki Asayama, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Nobuhiro Fujita, Tomoharu Yoshizumi, Norifumi Harimoto, Takao Ohtsuka, Kohei Nakata, Hiroshi Honda, The prevalence of transpancreatic common hepatic artery and coexisting variant anatomy, Clinical Anatomy, 10.1002/ca.22957, 31, 4, 598-604, 2018.05, We studied the prevalence of the transpancreatic common hepatic artery (tp-CHA) and coexisting variant anatomy. The study group comprised 788 consecutive liver transplant donor candidates who had undergone thin-section multidetector-row computed tomography (MDCT) studies to investigate vascular anatomy. Multiplanar reformatted (MPR) images obtained from the arterial phase were retrospectively reviewed to assess the presence/absence of the tp-CHA. Five cases of tp-CHA with pancreaticobiliary tumors were also included in an investigation of the presence/absence of variant hepatic arteries, celiac stenosis, and circumportal pancreas. Three of the 788 (0.38%) donor candidates had a tp-CHA. Overall, eight tp-CHA cases were assessed for coexisting variant anatomy. Seven of these eight cases had a hepatomesenteric trunk, six had celiac stenosis, and two had a circumportal pancreas. The prevalence of the tp-CHA was 0.38% (approx. one in 260 in normal populations). A tp-CHA can commonly be associated with a hepatomesenteric trunk and celiac stenosis. A circumportal pancreas can also coexist with a tp-CHA. Clin. Anat. 31:598–604, 2018..
1966. Kazuki Takeishi, Hirofumi Kawanaka, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Impact of Splenic Volume and Splenectomy on Prognosis of Hepatocellular Carcinoma Within Milan Criteria After Curative Hepatectomy, World journal of surgery, 10.1007/s00268-017-4232-z, 42, 4, 1120-1128, 2018.04, Background: The prognosis of hepatocellular carcinoma (HCC) with portal hypertension (PH) is very poor. Splenomegaly is considered important evidence of PH. Our aim was to clarify the prognostic value of splenic volume (SV) and the effect of splenectomy on the prognosis of HCC within the Milan criteria after curative hepatectomy. Methods: In this single-center retrospective study, we reviewed 160 patients with HCC that met the Milan criteria, including 138 who had undergone hepatectomy and 22 who had undergone hepatectomy and splenectomy between July 2004 and December 2010. SV was measured by three-dimensional computed tomography and patients allocated to three groups (high SV ≥300 mL; low OpenSPiltSPi300 mL; and splenectomy) to compare post-hepatectomy survival rates. Results: Multivariate analyses showed that SV is an independent prognostic factor for overall and disease-free survival. The overall survival rates at 5 years in the high SV, low SV, and splenectomy groups were 39, 75, and 88%, respectively. The overall survival rate in the high SV group was significantly worse than in the low SV and splenectomy groups (P OpenSPiltSPi 0.001). There was no significant difference between the low SV and splenectomy groups (P = 0.831). Conclusions: High SV is an independent predictor of post-hepatectomy HCC recurrence and overall survival. There is no significant difference in prognosis between low SV and splenectomy groups, even though the latter had high SV. Combined splenectomy with hepatectomy for HCC and PH may improve prognosis and be an appropriate alternative when liver transplantation cannot be performed..
1967. Koichi Kimura, Tomoharu Yoshizumi, Shoichi Inokuchi, Shinji Itoh, Takashi Motomura, Yohei Mano, Takeo Toshima, Noboru Harada, Norifumi Harimoto, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Potential effect of recombinant thrombomodulin on ischemia–reperfusion liver injury in rats, Hepatology Research, 10.1111/hepr.13005, 48, 5, 391-396, 2018.04, Aim: Liver ischemia–reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High-mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage-associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury. Methods: Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1. Results: In rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(−) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(−) group after surgery (P < 0.001). The levels of tumor necrosis factor-α and interleukin-6 in the liver tissue 24 h after surgery were significantly lower in the rTM(+) group than the rTM(−) group (P < 0.001). The plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(−) group (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(−) group (P < 0.001). Conclusions: Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1..
1968. Tomonari Shimagaki, Tomoharu Yoshizumi, Norifumi Harimoto, Sachiyo Yoshio, Yutaka Naito, Yusuke Yamamoto, Takahiro Ochiya, Yoshihiro Yoshida, Tatsuya Kanto, Yoshihiko Maehara, MicroRNA-125b expression and intrahepatic metastasis are predictors for early recurrence after hepatocellular carcinoma resection, Hepatology Research, 10.1111/hepr.12990, 48, 4, 313-321, 2018.03, Aim: Early hepatocellular carcinoma (HCC) recurrence after curative resection is a known poor prognostic factor. We aimed to identify microRNAs associated with recurrence after curative HCC resection. Methods: To identify risk factors for early recurrence and metastasis, 694 patients who underwent primary curative HCC resection were analyzed. We evaluated microRNA expression in cancerous and non-cancerous tissues by microarray and quantitative PCR analyses using 16 HCC samples. We defined patients who had a recurrence within 1 year of resection as the early recurrence (ER) group, patients who had a recurrence within 1–5 years as the late recurrence (LR) group, and patients who did not recur during the 5-year observation period as the no recurrence (NR) group. We examined the relationship between microRNA expression and clinical features. Results: Multivariate analysis revealed that α-fetoprotein >31 ng/mL, tumor size >4 cm, and intrahepatic metastasis (IM) were significant factors. Afterwards, microarray analyses revealed that microRNA (miR)-125b-5p and miR-148a-3p were significantly downregulated in recurrent cases. The ratio of miR-125b-5p expression in cancerous versus non-cancerous tissue (miR-125b ratio), but not miR-148a-3p, was significantly lower in the ER group. Early recurrence was associated with reduced overall survival compared with the LR and NR group. The miR-125b ratio was significantly lower in the ER group than in the LR and NR groups. Multivariate analysis showed that a low miR-125b ratio and IM were independently associated with ER and disease-free survival. Conclusions: Assessing tissue miR-125b-5p expression and IM is useful for stratifying patients at risk of early HCC recurrence after curative resection..
1969. Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Masashi Ohira, Yoshihiko Maehara, Appropriate Use of Stents to Prevent Biliary Complications after Living Donor Liver Transplantation, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2017.10.009, 226, 2, 2018.02.
1970. Shinji Itoh, Tomoharu Yoshizumi, Takahiro Tomino, Akihisa Nagatsu, Takashi Motomura, Noboru Harada, Norifumi Harimoto, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Associations between antibody to hepatitis B core antigen positivity and outcomes in hepatocellular carcinoma patients undergoing hepatic resection, Hepatology Research, 10.1111/hepr.12939, 48, 3, E155-E161, 2018.02, Aim: We aimed to evaluate the effect of antibody to hepatitis B core antigen (HBcAb) positivity on clinical outcomes after hepatic resection in hepatocellular carcinoma (HCC) patients with negative hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb), termed non-B, non-C HCC (NBNC-HCC), or with HCV-related HCC. Methods: Two hundred and sixty-three patients who underwent hepatic resection for HCC and measurements of HBsAg, HCVAb, and HBcAb were enrolled in this study. Results: The percentages of HBcAb positivity were 52.3% (n = 57) and 56.9% (n = 66) in patients with NBNC- and HCV-related HCC, respectively. The proportion of multiple NBNC-HCCs was significantly greater in patients with HBcAb positivity compared to HBcAb negativity (P = 0.028). There were no significant differences in the recurrence-free and overall survival rates between NBNC-HCC patients with HBcAb positivity versus negativity (P = 0.461 and P = 0.190, respectively). Furthermore, for HCV-related HCC patients, there were no significant differences in the baseline factors between patients with positive versus negative HBcAb. The proportion of patients with HBcAb-positive HCV-related HCC who underwent anatomical resection of the liver was significantly greater than that of HBcAb-negative patients, whereas the recurrence-free and overall survival rates were not significantly different (P = 0.158 and P = 0.191, respectively). Conclusion: In our study, the presence of HBcAb had no impact on surgical outcomes after hepatic resection in patients with NBNB- and HCV-related HCC. Occult HBV infection might be associated with hepatocarcinogenesis in patients with NBNC-related HCC..
1971. Yohei Mano, Tomoharu Yoshizumi, Kyohei Yugawa, Masafumi Ohira, Takashi Motomura, Takeo Toshima, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Lymphocyte-to-Monocyte Ratio Is a Predictor of Survival After Liver Transplantation for Hepatocellular Carcinoma, Liver Transplantation, 10.1002/lt.25204, 24, 11, 1603-1611, 2018.11, Recent studies revealed that systemic inflammation was correlated with poorer prognosis in various cancers. We investigated the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients who underwent living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). We retrospectively analyzed the records of 216 patients who underwent LDLT for HCC. Patients were divided into high (n = 126) and low (n = 90) LMR groups. Their clinicopathological parameters and survival times were compared. To determine the mechanisms of the change in the LMR, we performed immunohistochemical analyses of CD3 and CD68 expression. A low LMR was significantly associated with a high Model for End-Stage Liver Disease score; a high Child-Pugh score; elevation of alpha-fetoprotein, des-gamma-carboxyprothrombin, and neutrophil-to-lymphocyte ratio; larger tumor size; more tumors; and poorer prognosis. A low LMR was associated with poor prognosis and represented an independent prognostic factor, particularly among patients beyond the Milan criteria. The ratio of CD3-positive to CD68-positive cells was significantly lower in the low-LMR group. In conclusion, our results show that the LMR was an independent predictor of survival of patients with HCC beyond the Milan criteria who underwent LDLT. The LMR reflected the immune status of the tumor microenvironment..
1972. Toshimi Kaido, Masahiro Shinoda, Yukihiro Inomata, Takahito Yagi, Nobuhisa Akamatsu, Yasutsugu Takada, Hideki Ohdan, Tsuyoshi Shimamura, Yasuhiro Ogura, Susumu Eguchi, Hidetoshi Eguchi, Satoshi Ogata, Tomoharu Yoshizumi, Toshihiko Ikegami, Michio Yamamoto, Satoshi Morita, Shinji Uemoto, Effect of herbal medicine daikenchuto on oral and enteral caloric intake after liver transplantation
A multicenter, randomized controlled trial, Nutrition, 10.1016/j.nut.2018.02.022, 54, 68-75, 2018.10, Objective: Postoperative early oral or enteral intake is a crucial element of the Enhanced Recovery After Surgery (ERAS) protocol. However, normal food intake or enteral feeding cannot be started early in the presence of coexisting bowel dysfunction in patients undergoing liver transplantation (LT). The aim of this multicenter, randomized, double-blinded, placebo-controlled trial was to determine the enhancement effects of the Japanese herbal medicine Daikenchuto (DKT) on oral/enteral caloric intake in patients undergoing LT. Methods: A total of 112 adult patients undergoing LT at 14 Japanese centers were enrolled. The patients were randomly assigned to receive either DKT or placebo from postoperative day (POD) 1 to 14. The primary endpoints were total oral/enteral caloric intake, abdominal distension, and pain on POD 7. The secondary endpoints included sequential changes in total oral/enteral caloric intake after LT, and portal venous flow volume and velocity in the graft. Results: A total of 104 patients (DKT, n = 55; placebo, n = 49) were included in the analyses. There were no significant differences between the two groups in terms of primary endpoints. However, postoperative total oral/enteral caloric intake was significantly accelerated in the DKT group compared with the placebo group (P = 0.023). Moreover, portal venous flow volume (POD 10, 14) and velocity (POD 14) were significantly higher in the DKT group than in the placebo group (P = 0.047, P = 0.025, P = 0.014, respectively). Conclusions: Postoperative administration of DKT may enhance total oral/enteral caloric intake and portal venous flow volume and velocity after LT and favorably contribute to the performance of the ERAS protocol..
1973. Norifumi Harimoto, Tomoharu Yoshizumi, Shoichi Inokuchi, Shinji Itoh, Eisuke Adachi, Yasuharu Ikeda, Hideaki Uchiyama, Tohru Utsunomiya, Kiyoshi Kajiyama, Koichi Kimura, Fumiaki Kishihara, Keishi Sugimachi, Eiji Tsujita, Mizuki Ninomiya, Kengo Fukuzawa, Takashi Maeda, Ken Shirabe, Yoshihiko Maehara, Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma
A Multi-institutional Study, Annals of Surgical Oncology, 10.1245/s10434-018-6672-6, 25, 11, 3316-3323, 2018.10, Background: The Controlling Nutritional Status (CONUT) score is an objective tool that is widely used to assess the nutritional status in patients, including those with cancer. The relationship between the CONUT score and prognosis in patients who have undergone hepatic resection has not been evaluated in a multi-institutional study. Methods: Data were retrospectively collected for 2461 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent at 13 institutions between January 2004 and December 2015. Patients were assigned to two groups: preoperative CONUT scores ≤ 3 (low CONUT score) and ≥ 4 (high CONUT score). Clinicopathological characteristics, surgical outcomes, and long-term survival were compared using propensity score matching analysis. Results: Of the 2461 patients, 540 (21.9%) had high (≥ 4) and 1921 (78.1%) had low (≤ 3) preoperative CONUT scores. Overall, a high CONUT score was significantly associated with older age, female sex, low body mass index, low serum albumin, high serum total bilirubin, low lymphocyte count, low serum cholesterol, shorter prothrombin time, higher indocyanine green retention test at 15 min, Child–Pugh B (vs. A), liver cirrhosis, minor resection, shorter operation time, massive blood loss, blood transfusion, and postoperative complications. After propensity score matching, a higher CONUT score was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS) using multivariate analysis. Conclusions: This retrospective, multi-institutional analysis showed that, in patients who undergo curative hepatectomy for HCC, the preoperative CONUT score is predictive of worse OS and RFS, even after propensity score matching analysis..
1974. Hirohisa Okabe, Tomoharu Yoshizumi, Yo Ichi Yamashita, Katsunori Imai, Hiromitsu Hayashi, Shigeki Nakagawa, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Toru Beppu, Shinichi Aishima, Ken Shirabe, Hideo Baba, Yoshihiko Maehara, Histological architectural classification determines recurrence pattern and prognosis after curative hepatectomy in patients with hepatocellular carcinoma, PloS one, 10.1371/journal.pone.0203856, 13, 9, 2018.09, Aim The clinical impact of pathological classification based on architectural pattern in hepatocellular carcinoma (HCC) remains elusive in spite of its well-known and common feature. Methods The prognostic impact of pathological classification was examined with prospective database. Three hundred and eighty HCC patients who underwent curative hepatectomy as an initial treatment in Kumamoto University were enrolled as a test cohort. The outcome was confirmed with a validation cohort in Kyushu University. Results Macrotrabecular (macro-T) subtype (n = 38) and compact subtype (n = 43) showed similar biological and prognostic features. Both showed higher AFP level and worse overall survival than microrabecular (micro-T) subtype (n = 266). Multivariate analysis for overall survival revealed that DCP 40, multiple tumor and macro-T/compact subtype were associated with poor overall survival (risk ratio = 2.2, 1.6 and 1.6; p = 0.002, 0.020, and 0.047, respectively). Of note, 32% of macro-T/compact subtype showed early recurrence within 1 year, which showed substantially low (5%) 5 year overall survival, whereas 16% of micro-T/PG subtype did. Twenty-one percent of macro-T/compact subtype showed multiple intrahepatic metastases ( 4) or distant metastases, which resulted in non-curative treatment, whereas 5% of micro-T/PG subtype did. In validation cohort, macro-T/compact subtype was an independent predictor of worse overall survival. Conclusion Macro-T/compact subtype is biologically discriminated from micro-T and PG subtypes due to its aggressive features and poor prognosis after curative treatment. Additional treatment with curative hepatectomy on Macro-T/compact subtype should be discussed because of high possibility of systemic residual cancer cell..
1975. Daisuke Imai, Tomoharu Yoshizumi, Kazuhito Sakata, Toru Ikegami, Shinji Itoh, Noboru Harada, Takashi Motomura, Takeo Toshima, Yohei Mano, Yuji Soejima, Yoshihiko Maehara, Long-term Outcomes and Risk Factors after Adult Living Donor Liver Transplantation, Transplantation, 10.1097/TP.0000000000002324, 102, 9, e382-e391, 2018.09, Background Although risk factors for the long-term mortality of liver transplantation are well described, there is a lack of detailed study regarding these factors for adult living donor liver transplantation (LDLT). Methods We retrospectively analyzed 528 adult LDLT recipients in our hospital. The risk factors were analyzed for overall deaths more than 5 years post-LDLT. Results Over the 20-year follow-up, 137 patients died. Patient survival at 1, 3, 5, and 10 years post-LDLT was 87.8%, 81.8%, 79.4%, and 72.8%, respectively. The independent risk factors for more than 5 years post-LDLT overall death were hepatocellular carcinoma recurrence (hazard ratio [HR], 38.9; P < 0.001), lymphoid de novo malignancy (HR, 47.2; P = 0.001), primary sclerosing cholangitis as primary diagnosis (HR, 11.5; P < 0.001), chronic rejection (HR, 6.93; P = 0.006), acute rejection (HR, 2.96; P = 0.017), and bile duct stenosis (HR, 2.30; P = 0.045). Conclusions Not only malignancies and rejection but also bile duct stenosis and primary sclerosing cholangitis had significant impacts on late period post-LDLT mortality..
1976. Noboru Harada, Tomoharu Yoshizumi, Toru Ikegami, Shinji Itoh, Norihiro Furusho, Masaki Kato, Shinji Shimoda, Takasuke Fukuhara, Yuji Soejima, Yoshihiko Maehara, Serum asunaprevir and daclatasvir concentrations and outcomes in patients with recurrent hepatitis C who have undergone living donor liver transplantation, Anticancer research, 10.21873/anticanres.12885, 38, 9, 5513-5520, 2018.09, Background/Aim: This study’s aim was to investigate the safety and effectiveness of asunaprevir and daclatasvir treatment for recurrent hepatitis C virus (HCV) infection in transplant recipients. The study cohort comprised 14 transplant recipients with recurrent hepatitis C who were receiving asunaprevir and daclatasvir. Patients and Methods: Serum concentrations of asunaprevir and daclatasvir, their therapeutic effects, trough concentrations/dose ratios of tacrolimus, and adverse effects were evaluated. Results: Hepatitis C virus was still undetectable in 12 (85.7%) out of 14 patients 12 weeks after completing treatment. One week after starting treatment, asunaprevir concentrations were significantly higher in patients with baseline albumin concentrations ≤3.6 g/dl than in those with baseline albumin concentrations >3.6 g/dl. No marked fluctuations were identified in tacrolimus trough concentrations/dose ratios during the 24 weeks of therapy. Conclusion: Full doses of asunaprevir and daclatasvir-based treatment can be safely and effectively administered to liver transplant recipients for recurrent HCV genotype 1b after living donor liver transplantation (LDLT) with little effect on blood concentrations of tacrolimus..
1977. Norifumi Harimoto, Tomoharu Yoshizumi, Yukiko Fujimoto, Takashi Motomura, Youhei Mano, Takeo Toshima, Shinji Itoh, Noboru Harada, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, Surgery for Hepatocellular Carcinoma in Patients with Child–Pugh B Cirrhosis
Hepatic Resection Versus Living Donor Liver Transplantation, World journal of surgery, 10.1007/s00268-018-4493-1, 42, 8, 2606-2616, 2018.08, Background: Liver transplantation has been established as the optimal treatment for hepatocellular carcinoma in cirrhotic patients, but hepatic resection is also effective in patients with well-preserved liver function. Determining the suitable surgical treatment for patients with Child–Pugh class B cirrhosis is a more difficult challenge. Methods: We retrospectively compared the results of hepatic resection and living donor liver transplantation for hepatocellular carcinoma in 137 patients with Child–Pugh class B cirrhosis. The procedures were performed at Kyushu University Hospital from April 2014 through October 2016. Results: Patients who underwent hepatic resection were significantly older and had better liver function, larger tumor size, smaller number of tumors, and less surgical stress compared with patients who underwent living donor liver transplantation. The overall survival rate and the recurrence-free survival rate in patients with transplantation were significantly better than that in patients with resection. The multivariate analysis showed that recurrent hepatocellular carcinoma and microvascular invasion were significant prognostic factors for both overall and recurrence-free survival in the hepatic resection group. In the group with protein induced by vitamin K absence or antagonist-II ≥300 mAU/mL, both the overall survival curve and the recurrence-free survival curve in patients with living donor liver transplantation were not significantly different from those in patients with hepatic resection. Conclusions: Living donor liver transplantation for hepatocellular carcinoma in patients with Child–Pugh class B cirrhosis was favorable under the condition of protein induced by vitamin K absence or antagonist-II <300 mAU/mL in selected recipients and donors. Hepatic resection for recurrent hepatocellular carcinoma and excessive blood loss should be avoided in patients with Child–Pugh class B cirrhosis..
1978. Jun Muto, Masaya Sugiyama, Ken Shirabe, Motokazu Mukaide, Ikue Kirikae-Muto, Toru Ikegami, Tomoharu Yoshizumi, Yo Ichi Yamashita, Yoshihiko Maehara, Masashi Mizokami, Frequency and characteristics of occult hepatitis b infection among hepatocellular carcinoma patients in japan, Annals of Hepatology, 10.5604/01.3001.0012.0927, 17, 4, 596-603, 2018.07, Introduction and aim. Occult hepatitis B virus (HBV) infection (OBI) represents a state without detectable hepatitis B surface antigen, but positive for HBV DNA. The correlation between OBI and hepatocellular carcinoma (HCC) carcinogenesis is controversial. We studied the frequency and characteristics of OBI among HCC patients and metastatic liver cancer patients. Material and methods. DNA was obtained from tumor and non-tumor tissues from 75 HCC patients (15 chronic hepatitis B (CHB), 39 chronic hepatitis C (CHC), 21 cryptogenic) and 15 metastatic liver cancer patients who underwent liver resection. HBV DNA and covalently-closed circular (ccc) DNA were detected using real-time polymerase chain reaction (PCR), and four HBV DNA regions were detected by nested PCR. Clinicopathological factors were compared between patients with and without OBI. Results. HBV DNA was detected in 14 (93.3%) CHB, five (22.7%) cryptogenic and four (10.3%) CHC patients. cccDNA was detected in 12 (80.0%) CHB, three (14.3%) cryptogenic and two (5.1%) CHC patients. All CHB, eight (38.1%) cryptogenic and ten (25.6%) CHC patients tested positive with nested PCR. No metastatic liver cancer patients were positive for any HBV DNA regions. OBI patients had shorter prothrombin times (P = 0.0055), and lower inflammation activity score in non-tumor liver (P = 0.0274). There were no differences in anti-HBV antibodies. Conclusions. OBI was detected in 38% of cryptogenic and 25.6% of CHC patients. There was no correlation between OBI and anti-HBV antibodies, but fewer patients with OBI had high inflammatory activity, suggesting that factors other than inflammation may be involved in HCC carcinogenesis in patients with OBI..
1979. Hirofumi Watanabe, Yoshiki Asayama, Akihiro Nishie, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Okamoto, Nobuhiro Fujita, Tomoharu Yoshizumi, Yoshinao Oda, Hiroshi Honda, A case of pseudoglandular hepatocellular carcinoma
The usefulness of a multimodal approach, Radiology Case Reports, 10.1016/j.radcr.2018.03.022, 13, 3, 689-692, 2018.06, Hepatocellular carcinoma (HCC) mainly composed of the pseudoglandular pattern is very rare. We present a case of pseudoglandular HCC that was hyperechoic on ultrasound, with strongly high signal intensity on T2-weighted imaging and weak arterial contrast enhancement. Computed tomography hepatic arteriography showed corona enhancement. Radiologists should keep in mind this combination of multimodal radiological findings for pseudoglandular HCC..
1980. Long Bin Jeng, Sung Gyu Lee, Arvinder Singh Soin, Wei Chen Lee, Kyung Suk Suh, Dong Jin Joo, Shinji Uemoto, Jaewon Joh, Tomoharu Yoshizumi, Horng Ren Yang, Gi Won Song, Patricia Lopez, Jossy Kochuparampil, Carole Sips, Shuhei Kaneko, Gary Levy, Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients
12-month results of a randomized multicenter study, American Journal of Transplantation, 10.1111/ajt.14623, 18, 6, 1435-1446, 2018.06, In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference –0.7% (90% CI −5.2%, 3.7%); P <.001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P <.001 for non-inferiority), but not superiority and was similar between groups overall (mean −8.0 vs. −12.1 mL/min/1.73 m2, P =.108), and in patients continuing randomized treatment (−8.0 vs. −13.3 mL/min/1.73 m2, P =.046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432..
1981. Mio Fukuda, Kimitaka Suetsugu, Soichiro Tajima, Yurie Katsube, Hiroyuki Watanabe, Noboru Harada, Tomoharu Yoshizumi, Nobuaki Egashira, Masaki Mori, Satohiro Masuda, Neutrophil gelatinase-associated lipocalin is not associated with tacrolimus-induced acute kidney injury in liver transplant patients who received mycophenolate mofetil with delayed introduction of tacrolimus, International journal of molecular sciences, 10.3390/ijms20123103, 20, 12, 2019.06, Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication. The urinary neutrophil gelatinase-associated lipocalin (NGAL) level has been linked to tacrolimus-induced AKI in patients starting tacrolimus treatment the morning after liver transplantation. Here we tested this association using a diffierent immunosuppression protocol: Mycophenolate mofetil administration beginning on Postoperative Day 1 and tacrolimus administration beginning on Postoperative Day 2 or 3. Urine samples were collected from 26 living donor liver transplant recipients before (Postoperative Day 1) and after (Postoperative Day 7 or 14) tacrolimus administration. NGAL levels were measured via enzyme-linked immunosorbent assays, as were those of three additional urinary biomarkers for kidney diseases: Monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), and human epididymis secretory protein 4 (HE4). HE4 levels after tacrolimus administration were significantly higher in patients who developed AKI (n = 6) than in those who did not (n = 20), whereas NGAL, MCP-1, and L-FABP levels did not differ significantly before or after tacrolimus administration. These findings indicate that NGAL may not be a universal biomarker of AKI in tacrolimus-treated liver transplant recipients. To reduce the likelihood of tacrolimus-induced AKI, our immunosuppression protocol is recommended..
1982. Akihiro Nishie, Sadato Akahori, Yoshiki Asayama, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Kakihara, Tomohiro Nakayama, Yukihisa Takayama, Nobuhiro Fujita, Koichiro Morita, Keisuke Ishimatsu, Seiichiro Takao, Tomoharu Yoshizumi, Kenichi Kohashi, Yuanzhong Li, Hiroshi Honda, Prediction of liver fibrosis using CT under respiratory control
New attempt using deformation vectors obtained by non-rigid registration technique, Anticancer research, 10.21873/anticanres.13257, 39, 3, 1417-1424, 2019.03, Aim: To investigate whether liver fibrosis can be predicted by quantifying the deformity of the liver obtained based on computed tomographic (CT) images scanned under respiratory control. Materials and Methods: For dynamic CT of 47 patients, portal venous and equilibrium phases were scanned during inspiration and expiration, respectively. After rigid registration of the two images, non-rigid registration of the liver was performed, and the amount and direction of each voxel's shift during non-rigid registration was defined as the deformation vector. The correlation of each CT parameter for the obtained deformation vectors with the pathologically-proven degree of liver fibrosis was assessed using Spearman's rank correlation test. Receiver operating characteristic curve analysis was conducted for prediction of liver fibrosis. Results: The standard deviation, coefficient of variance (CV) and skewness were significantly negatively correlated with the degree of liver fibrosis (p=0.030, 0.009 and 0.037, respectively). Of these measures, CV was best correlated and significantly decreased as liver fibrosis progressed (rho=−0.376). CV showed accuracies of 66.0-70.2%, and the areas under curves were 0.654-0.727 for prediction of fibrosis of grade F1 or greater, F2 or greater, F3 or greater and F4 fibrosis. Conclusion: The deformation vector is a potential CT parameter for evaluating liver fibrosis..
1983. K. Kimura, K. Kudo, T. Kurihara, S. Yoshiya, Y. Mano, K. Takeishi, S. Itoh, N. Harada, T. Ikegami, T. Yoshizumi, T. Ikeda, Rendezvous Technique Using Double Balloon Endoscope for Removal of Multiple Intrahepatic Bile Duct Stones in Hepaticojejunostomy After Living Donor Liver Transplant
A Case Report, Transplantation Proceedings, 10.1016/j.transproceed.2018.12.005, 51, 2, 579-584, 2019.03, Cholangitis is a major complication following transplantation. We report a living donor liver transplant (LDLT) patient with cholangitis due to multiple stones in the intrahepatic bile duct during hepaticojejunostomy anastomosis, who was successfully treated with the rendezvous technique using double balloon endoscope. A 64-year-old woman underwent LDLT with right lobe graft and hepaticojejunostomy for Wilson disease. There was bile leakage with biliary peritonitis, which was treated conservatively after transplant. Two years after surgery, she developed reiterated cholangitis due to stenosis of hepaticojejunostomy anastomosis and multiple stones in the intrahepatic bile ducts. Percutaneous transhepatic biliary drainage was performed. The size of the drainage tube was increased, and the anastomotic area was dilated in a stepwise manner using a balloon catheter. The stones were crushed and lithotomy was performed using electronic hydraulic lithotripsy through cholangioscopy. Finally, lithotomy was performed for the remaining stones through endoscopic retrograde cholangiography with the rendezvous technique using the double balloon endoscope. Rendezvous approach with percutaneous transhepatic biliary drainage and double balloon endoscopic retrograde cholangiography was an effective treatment for the multiple intrahepatic stones in hepaticojejunostomy following LDLT with right lobe graft..
1984. Akira Watanabe, Norihumi Harimoto, Kenichiro Araki, Norio Kubo, Takamichi Igarashi, Mariko Tsukagoshi, Norihiro Ishii, Takahiro Yamanaka, Tomoharu Yoshizumi, Ken Shirabe, Absolute neutrophil count predicts postoperative prognosis in mass-forming intrahepatic cholangiocarcinoma, Anticancer research, 10.21873/anticanres.13197, 39, 2, 941-947, 2019.02, Background/Aim: Intrahepatic cholangiocarcinoma (IHCC) is characterized by poor prognosis, and postoperative recurrence remains a problem. Thus, prognostic markers for IHCC are greatly needed. Recently, inflammatory factors were reported to be related to tumor progression and recurrence in various cancers. Therefore, the present study aimed to evaluate the prognostic ability of inflammatory factors. Materials and Methods: Forty-four patients with mass-forming IHCC (m-IHCC) were retrospectively evaluated and the correlations between inflammatory markers, including neutrophil–to–lymphocyte ratio and, modified Glasgow prognostic score, and patient survival were assessed. Results: The absolute neutrophil count (ANC) was significantly higher in the recurrence group than in the non-recurrence group (p=0.00568) and the most significant prognostic factor by multivariate analysis. Poor recurrence-free survival (RFS; p=0.00452) and cancer-specific survival (CSS; p=0.0323) were associated with high neutrophil levels. Moreover, neutrophil infiltration in the tumor site was positively correlated with ANC. Conclusion: ANC is associated with poor RFS, and could be used to predict recurrence in patients with m-IHCC..
1985. Akira Watanabe, Norifumi Harimoto, Kenichiro Araki, Tomoharu Yoshizumi, Kota Arima, Yoichi Yamashita, Hideo Baba, Higuchi Tetsuya, Hiroyuki Kuwano, Ken Shirabe, A new strategy based on fluorodeoxyglucose-positron emission tomography for managing liver metastasis from colorectal cancer, Journal of Surgical Oncology, 10.1002/jso.25250, 118, 7, 1088-1095, 2018.12, Background: Prognostic models are needed to manage liver metastasis from colorectal cancer (CRLM). Thus, we developed an algorithm to guide treatment based on the standardized uptake value (SUV) from fluorodeoxyglucose-positron emission tomography (FDG-PET). Methods: We retrospectively evaluated 148 patients who underwent surgery for CRLM, including 107 cases of primary surgery and 41 cases with preoperative chemotherapy before conversion surgery. We evaluated the prognostic value of perioperative SUV among primary surgery cases, as well as the prognostic value of the SUV change ratio after conversion surgery (postchemotherapy/prechemotherapy SUV). Results: In the primary surgery group, recurrence-free survival (RFS) was independently predicted by an SUV of ≥6.04 (P = 0.042) and ≥4 liver metastases (P = 0.003). The combination of an SUV of ≥6.04 and ≥4 liver metastases was strongly associated with poor RFS (P < 0.001). In the conversion surgery group, the SUV change ratio was associated with tumor size change and pathological response. An SUV change ratio of ≥0.293 was associated with shorter RFS (P = 0.006) and independently predicted RFS (P = 0.026). We established a therapeutic algorithm for managing CRLM based on these results. Conclusion: FDG-PET may be useful for predicting recurrence and prognosis in cases of CRLM, and our algorithm may be useful for managing multiple CRLMs..
1986. Shinkichi Takamori, Kazuki Takada, Tetsuzo Tagawa, Gouji Toyokawa, Fumihiko Hirai, Nami Yamashita, Tatsuro Okamoto, Eiji Oki, Tomoharu Yoshizumi, Yoshinao Oda, Yoshihiko Maehara, Differences in PD-L1 expression on tumor and immune cells between lung metastases and corresponding primary tumors, Surgical Oncology, 10.1016/j.suronc.2018.08.001, 27, 4, 637-641, 2018.12, Background: It has been reported that the tumor microenvironment, including tumor-associated immune cells (ICs) and programmed cell death-ligand 1 (PD-L1) expression, differs between primary and metastatic tumors. This study aimed to elucidate the differences in PD-L1 expression on tumor cells (TCs) and ICs between lung metastases and corresponding primary tumors. Methods: We analyzed paired lesions from 44 patients diagnosed with lung metastases between 2005 and 2017 at Kyushu University. The percentages of PD-L1-positive TCs and ICs in lung metastases and the primary tumor were classified into five categories (0: <1%; 1: 1%–4%; 2: 5%–9%; 3: 10%–49%; and 4: ≥50%). Lesions in which ≥1% of the TCs and ICs were PD-L1-positive were considered positive. Results: The primary cancers included rectal (n = 19), colon (n = 10), liver (n = 10), bile duct (n = 2), stomach (n = 1), gall bladder (n = 1) and breast (n = 1). Discrepancies in PD-L1 expression on TCs and ICs between lung metastases and primary lesions were observed in 5 (11.4%, κ = 0.23) and 9 (20.5%, κ = 0.11) of the 44 cases, respectively. PD-L1 expression on ICs was higher in lung metastases than paired primary tumors (p = 0.026), although the percentage of PD-L1-positive TCs was not significantly different between lung metastases and primary tumors (p = 0.767). Conclusions: There were significant differences in PD-L1 expression on TCs and ICs between lung metastases and primary tumors. Clinicians should be aware of these differences in the tumor microenvironment when treating patients with immunotherapy..
1987. N. Harimoto, H. Nakagawara, K. Shirabe, T. Yoshizumi, S. Itoh, T. Ikegami, Y. Soejima, Y. Maehara, Y. Ishida, C. Tateno, Y. Tanaka, Functional Analysis of Human Hepatocytes Isolated From Chimeric Mouse Liver, Transplantation Proceedings, 10.1016/j.transproceed.2018.06.035, 50, 10, 3858-3862, 2018.12, Chimeric mice with humanized liver were first established by transplanting primary human hepatocytes (PHHs) isolated from a Japanese 27-year-old donor into complementary DNA-urokinase-type plasminogen activator/severe combined immunodeficiency mice. The PHHs from the Japanese donor increased more than 100-fold in the mouse liver, and human hepatocytes purified from the chimeric mouse liver (hcPHs) were successfully transplanted into second-passaged mice. These PHHs and hcPHs can produce human albumin and preserve many liver-specific enzyme genes, which are important for liver function. Interestingly, hepatitis B virus can be infected with these chimeric mice; hepatitis B viral DNA and hepatitis B surface antigen levels were detectable. In conclusion, hcPHs can be an ideal cell source for analysis of human hepatocytes..
1988. Nao Nishida, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Kaname Kojima, Yosuke Kawai, Kazuko Ueno, Hitomi Nakamura, Noriyo Yamashiki, Tomohiro Tanaka, Sumito Tamura, Akira Mori, Shintaro Yagi, Yuji Soejima, Tomoharu Yoshizumi, Mitsuhisa Takatsuki, Atsushi Tanaka, Kenichi Harada, Shinji Shimoda, Atsumasa Komori, Susumu Eguchi, Yoshihiko Maehara, Shinji Uemoto, Norihiro Kokudo, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura, NELFCD and CTSZ loci are associated with jaundice-stage progression in primary biliary cholangitis in the Japanese population, Scientific reports, 10.1038/s41598-018-26369-6, 8, 1, 2018.12, Approximately 10-20% of patients with primary biliary cholangitis (PBC) progress to jaundice stage regardless of treatment with ursodeoxycholic acid and bezafibrate. In this study, we performed a GWAS and a replication study to identify genetic variants associated with jaundice-stage progression in PBC using a total of 1,375 patients (1,202 early-stage and 173 jaundice-stage) in a Japanese population. SNP rs13720, which is located in the 3′UTR of cathepsin Z (CTSZ), showed the strongest association (odds ratio [OR] = 2.15, P = 7.62 × 10-7) with progression to jaundice stage in GWAS. High-density association mapping at the CTSZ and negative elongation factor complex member C/D (NELFCD) loci, which are located within a strong linkage disequilibrium (LD) block, revealed that an intronic SNP of CTSZ, rs163800, was significantly associated with jaundice-stage progression (OR = 2.16, P = 8.57 × 10-8). In addition, eQTL analysis and in silico functional analysis indicated that genotypes of rs163800 or variants in strong LD with rs163800 influence expression levels of both NELFCD and CTSZ mRNA. The present novel findings will contribute to dissect the mechanism of PBC progression and also to facilitate the development of therapies for PBC patients who are resistant to current therapies..
1989. Y. Soejima, T. Yoshizumi, T. Ikegami, N. Harimoto, N. Harada, S. Itoh, T. Toshima, T. Motomura, Y. Mano, M. Ohira, Y. Bekki, Y. Maehara, Real-Time Ultrasound-Guided Thrombectomy for Extensive Portal Vein Thrombosis in Living Donor Liver Transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2018.08.047, 50, 10, 3549-3551, 2018.12, Thrombectomy is a routine or common practice for treating organized portal vein thrombosis (PVT) during liver transplantation. However, this procedure is often performed in a blinded fashion and can result in insufficient thrombectomy or devastating consequences such as injury to the retropancreatic portal vein where prompt repair is very difficult. To overcome these drawbacks for blind thrombectomy, we herein describe a new technique that makes complex thrombectomy safe and easy under direct ultrasound vision. This procedure is readily available and highly reproducible and can be used as the standard procedure for treating extensive PVT..
1990. Takeo Toshima, Tomoharu Yoshizumi, Toru Ikegami, Noboru Harada, Shinji Itoh, Yohei Mano, Takashi Motomura, Yuji Soejima, Yoshihiko Maehara, Impact of osteopenia in liver cirrhosis
Special reference to standard bone mineral density with age, Anticancer research, 10.21873/anticanres.13009, 38, 11, 6465-6471, 2018.11, Background/Aim: Computed tomography (CT) has recently been applied to measure bone mineral density (BMD). However, the definition of osteopenia, which means depletion of BMD, using CT remains controversial. The aim of this study was to establish formulae to calculate standard BMD. Patients and Methods: Fifty healthy donors for liver transplantation underwent CT. BMD was measured as crosssectional average pixel density (Hounsfield units) only in trabecular-bone at Th11 bottom. Validation was performed on another 50 healthy donors to check the accuracy of formulae for standard BMD. Results: Measured BMD was significantly correlated with age in both males and females (p<0.0001). The formulae to calculate standard BMD were 308.82-2.49 × Age in males and 311.84-2.41 × Age in females. Estimated BMD was significantly correlated with measured BMD in males and females (p<0.0001). Conclusion: Osteopenia can be defined by the difference between measured data and calculated data using our new formula based on each age..
1991. Yoshihiko Maehara, Yuji Soejima, Tomoharu Yoshizumi, Naoyuki Kawahara, Eiji Oki, Hiroshi Saeki, Tomohiko Akahoshi, Toru Ikegami, Yo ichi Yamashita, Tadashi Furuyama, Keishi Sugimachi, Noboru Harada, Tetsuzo Tagawa, Norifumi Harimoto, Shinji Itoh, Hideto Sonoda, Koji Ando, Yuichiro Nakashima, Yoshihiro Nagao, Nami Yamashita, Yuta Kasagi, Takafumi Yukaya, Takeshi Kurihara, Ryosuke Tsutsumi, Shinkichi Takamori, Shun Sasaki, Tetsuo Ikeda, Yoshikazu Yonemitsu, Takasuke Fukuhara, Hiroyuki Kitao, Makoto Iimori, Yuki Kataoka, Takeshi Wakasa, Masami Suzuki, Koji Teraishi, Yasuto Yoshida, Masaki Mori, The evolution of surgical treatment for gastrointestinal cancers, International Journal of Clinical Oncology, 10.1007/s10147-019-01499-7, 24, 11, 1333-1349, 2019.11, Introduction: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. Materials and methods, and results: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. Conclusion: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival..
1992. Tatsunori Miyata, Yo Ichi Yamashita, Tomoharu Yoshizumi, Masayuki Shiraishi, Masayuki Ohta, Susumu Eguchi, Shinichi Aishima, Hikaru Fujioka, Hideo Baba, CXCL12 expression in intrahepatic cholangiocarcinoma is associated with metastasis and poor prognosis, Cancer Science, 10.1111/cas.14151, 110, 10, 3197-3203, 2019.10, Intrahepatic cholangiocarcinoma is a rare malignant biliary neoplasm that causes a poor prognosis even after curative hepatectomy. Liver metastasis is the major recurrence pattern of intrahepatic cholangiocarcinoma; therefore, the prevention of liver metastasis is a desirable objective. The aim of this study is to identify gene(s) related to liver metastasis of intrahepatic cholangiocarcinoma and to examine the inhibitory effects on metastasis of intrahepatic cholangiocarcinoma by controlling such gene(s). We collected 3 pairs of intrahepatic cholangiocarcinoma frozen samples, and 36 pairs (primary and metastatic lesions) of intrahepatic cholangiocarcinoma formalin-fixed paraffin-embedded samples, from patients who underwent surgical resection at hospitals related to the Kyushu Study Group of Liver Surgery between 2002 and 2016. We carried out cDNA microarray analyses and immunohistochemistry to identify candidate genes, and evaluated one of them as a therapeutic target using human cholangiocarcinoma cell lines. We identified 4 genes related to liver metastasis using cDNA microarray, and found that CXCL12 was the only gene whose expression was significantly higher in liver metastasis than in primary intrahepatic cholangiocarcinoma by immunohistochemistry (P =.003). In prognosis, patients in the high CXCL12 group showed a significantly poor prognosis in disease-free (P <.0001) and overall survival (P =.0004). By knockdown of CXCL12, we could significantly suppress the invasive and migratory capabilities of 2 human cholangiocarcinoma cell lines. Therefore, CXCL12 might be associated with metastasis and poor prognosis in intrahepatic cholangiocarcinoma..
1993. Tomoharu Yoshizumi, Noboru Harada, Masaki Mori, Biliary Stricture
The Achilles Heel of Pediatric Living Donor Liver Transplantation, Transplantation, 10.1097/TP.0000000000002573, 103, 9, 1758-1759, 2019.09, Since a 1989 report demonstrating successful living donor liver transplantation (LDLT), living donors have been increasingly used to overcome the disparity between organ supply and demand, especially in the cases of pediatric patients. Although short-term graft outcomes after LDLT have improved significantly because of progress in surgical techniques and immunosuppression, biliary stricture (BS) remains the Achilles heel of pediatric LDLT and is the major cause of significant long-term morbidity. BS results in poor quality of life or even in graft loss after LDLT, with a reported incidence of BS after pediatric LDLT of 10% to 35%. The suggested risk factors for BS after LDLT are hepatic arterial thrombosis, bile duct ischemia, acute cellular rejection, older donor age, and ABO incompatibility. Duct-to-duct biliary reconstruction, which enables an endoscopic approach to be attempted after BS, is the preferred technique for LDLT. Endoscopic approaches are less invasive and more convenient for recipients than surgical and percutaneous interventions. However, the major cause of end-stage liver disease in pediatric recipients is biliary atresia, and hepaticojejunostomy is needed to reconstruct the bile duct because of the lack of recipient bile duct. Endoscopic approaches for BS are usually less favorable in patients with hepaticojejunostomy than in those with duct-to-duct biliary reconstruction. Treatment options for BS after hepaticojejunostomy at many centers thus involve interventional radiology or surgical reintervention. Although endoscopic approaches remain controversial in pediatric recipients, several reports have shown them to be safe and less invasive..
1994. Daisuke Imai, Takashi Maeda, Huanlin Wang, Kensaku Sanefuji, Hiroto Kayashima, Shohei Yoshiya, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Tomoharu Yoshizumi, Masaki Mori, Elevation of Mac-2 binding protein glycosylation isomer after hepatectomy is associated with post-hepatectomy liver failure, total Pringle time, and renal dysfunction, Annals of Gastroenterological Surgery, 10.1002/ags3.12271, 3, 5, 515-522, 2019.09, Background: Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum glycomarker used to assess liver fibrosis. However, it has been reported that M2BPGi is likely to reflect other factors not limited to liver fibrosis. Methods: We retrospectively analyzed 79 patients with liver tumors who underwent liver resection. M2BPGi was measured within 1 week before operation and almost 1 month after operation. We introduced a value termed the “ΔM2BPGi ratio” (=M2BPGiafter operation/M2BPGibefore operation), and analyzed factors that influenced the ΔM2BPGi ratio. Results: The median value of the ΔM2BPGi ratio was 1.28 (range, 0.36-5.68). In 64 patients (81.0%), the cutoff index values of M2BPGi were elevated approximately 1 month after operation, especially in patients who experienced post-hepatectomy liver failure (PHLF). Multiple linear regression showed total Pringle time, PHLF grade ≥B, and preoperative value of creatinine were significant predictors of the ΔM2BPGi ratio. The mean values of the ΔM2BPGi ratio were 1.37 ± 0.07, 1.52 ± 0.22, and 2.94 ± 0.30 for PHLF grade 0, grade A, and grade B, respectively, resulting in statistically significant differences by the Kruskal-Wallis test (P = 0.022). Conclusions: Total Pringle time, PHLF grade ≥B, and preoperative creatinine significantly influenced the elevation of M2BPGi almost 1 month after liver resection. This study strongly affirms the previous suggestion that M2BPGi is likely to reflect other factors not limited to liver fibrosis..
1995. Daisuke Imai, Tomoharu Yoshizumi, Shinji Okano, Shinji Itoh, Toru Ikegami, Noboru Harada, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara, IFN-γ Promotes Epithelial-Mesenchymal Transition and the Expression of PD-L1 in Pancreatic Cancer, Journal of Surgical Research, 10.1016/j.jss.2019.02.038, 240, 115-123, 2019.08, Background: Tumor immune reactions not only provide host defense but also accelerate tumor immune escape and phenotype switching. Here, we examined the association of programmed cell death ligand 1 (PD-L1) expression with epithelial-mesenchymal transition (EMT)–associated markers in pancreatic ductal adenocarcinoma (PDA) within the context of the tumor microenvironment. Materials and methods: PDA samples from 36 patients were analyzed for PD-L1, vimentin, E-cadherin, and Snail expressions and for PDA cell and immune cell infiltration. PD-L1 expression and EMT in PDA cell lines under conditions of altering interferon gamma (IFN-γ) signals were also assessed. Results: Immunohistochemistry revealed a significant correlation between vimentin and PD-L1 expression, whereas double staining showed them to be simultaneously expressed by PDA cells. Positive vimentin expression was associated with the infiltration of a lower number of CD8 + T cells and a higher number of FoxP3 + cells and poor patient prognosis (P = 0.03). PDA tumor cells promoted PD-L1 expression and EMT under the presence of IFN-γ which was inhibited by the signal transducer and activator of transcription (STAT)1 small interfering RNA. Conclusions: Strong correlations were observed between PD-L1 expression, EMT, and the immunosuppressive tumor microenvironment. Targeting STAT1 combined with PD-1/PD-L1 immunotherapy may improve outcomes for patients with PDA..
1996. Toru Ikegami, Tomoharu Yoshizumi, Norifumi Harimoto, Masaki Mori, Splenectomy as Flow Modulation Strategy and Risk Factors of De Novo Portal Vein Thrombosis in Adult-to-Adult Living Donor Liver Transplantation, Liver Transplantation, 10.1002/lt.25494, 25, 8, 1281-1283, 2019.08.
1997. Takashi Motomura, Tomoharu Yoshizumi, Yukiko Kosai-Fujimoto, Y. Mano, T. Toshima, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Goichi Yoshimoto, Koichi Akashi, Masaki Mori, Adult T-Cell Leukemia After Deceased Donor Liver Transplantation for Acute Liver Failure
A Case Report, Transplantation Proceedings, 10.1016/j.transproceed.2019.03.031, 51, 6, 1978-1981, 2019.07, Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL); however, the mechanism of its development has yet to be uncovered. A few ATL cases have been reported in HTLV-1-positive recipients after living donor liver transplantation. A 57-year-old HTLV-1-positive Japanese male suffered acute liver failure due to hepatitis B infection. He was transferred to our department to undergo deceased donor liver transplantation (DDLT). Tacrolimus and mycophenolate mofetil were induced for immunosuppression. His clinical outcome was satisfactory. However, he visited his physician 3 years after DDLT reporting abdominal pain and fever. A computed tomography scan showed multiple lymph node enlargement. Lymph node biopsy and his blood sample led to a diagnosis of ATL. He was transferred to the Department of Hematology and Oncology and underwent chemotherapy. To our knowledge, this is the first report of ATL development after DDLT from an HTLV-1-positive recipient. As is the case with our previous report, the current patient had undergone liver transplant for acute liver failure. Unlike living donor liver transplantation, however, DDLT needs no hepatic growth factor for liver regeneration. This finding sheds light on the resolution of the mechanism for the development of ATL from the HTLV-1 carrier..
1998. Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Masaki Mori, Effective and Safe Living Donor Hepatectomy Under Intermittent Inflow Occlusion and Outflow Pressure Control, Journal of Gastrointestinal Surgery, 10.1007/s11605-019-04196-y, 23, 7, 1529-1530, 2019.07.
1999. Yuki Morooka, Koji Umeshita, Akinobu Taketomi, Ken Shirabe, Tomoharu Yoshizumi, Mayumi Yamamoto, Tsuyoshi Shimamura, Akihiko Oshita, Hideki Ohdan, Naoki Kawagishi, Kuniko Hagiwara, Hidetoshi Eguchi, Hiroaki Nagano, Long-term donor quality of life after living donor liver transplantation in Japan, Clinical Transplantation, 10.1111/ctr.13584, 33, 6, 2019.06, Aims: This study examined the long-term quality of life (QOL) of living liver donors (LLDs) in Japan using both generic and LLD-specific instruments. Methods: The sample comprised 374 LLDs from five university hospitals in Japan who underwent surgery more than a year previously. QOL was evaluated using the Short Form-36 health survey (SF-36) and LLD-QOL scale. Results: SF-36 results indicated that the overall long-term QOL of LLDs was significantly better than the Japanese standard. When comparing by donor factors, LLDs whose recipients were children scored higher for “satisfaction” than those whose recipients were adults on the LLD-QOL scale. LLDs with complications had lower QOL for “scars” and “burden” on the LLD-QOL scale but no differences in SF-36 scores. LLDs with longer hospital stay had lower physical QOL on SF-36 and lower QOL for “scars” and “after-effects” on the LLD-QOL scale. LLDs whose recipients have died showed lower mental QOL on SF-36 and lower “satisfaction” and greater “lack of understanding of donor health” on the LLD-QOL scale. Conclusions: Our multicenter study clarified the long-term QOL of LLDs and suggested that donors’ QOL was related to the donors’ and recipients’ ages, donor's complications and hospital stay length, and recipient's prognosis..
2000. Toru Ikegami, Tomoharu Yoshizumi, Norifumi Iseda, Takeo Toshima, Mohamed Elemam Elshawy, Masaki Mori, Reply, Liver Transplantation, 10.1002/lt.25702, 26, 3, 463-464, 2020.03.
2001. Daisuke Imai, Takashi Maeda, Mototsugu Shimokawa, Huanlin Wang, Shohei Yoshiya, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Tomoharu Yoshizumi, Masaki Mori, Prognostic nutritional index is superior as a predictor of prognosis among various inflammation-based prognostic scores in patients with hepatocellular carcinoma after curative resection, Hepatology Research, 10.1111/hepr.13431, 50, 1, 101-109, 2020.01, Aim: There is increasing evidence that inflammation-based prognostic scores are stage-independent predictors of poor outcome in patients with hepatocellular carcinoma (HCC). However, these findings were observed in a small-sized study comparing the prognostic value of these scores for patients after curative resection for HCC. Methods: We retrospectively analyzed 717 consecutive patients with HCC who underwent curative liver resection at Hiroshima Red Cross Hospital & Atomic Bomb Survivors Hospital. Clinicopathological variables including preoperative inflammation-based prognostic scores, such as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Controlling Nutritional Status score, prognostic nutritional index (PNI), and Glasgow Prognostic Score were analyzed. The prognostic value of these scores was compared by the time-dependent receiver operating characteristic curve analyses. Results: The integrate area under the curve of PNI, Controlling Nutritional Status score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and Glasgow Prognostic Score were 0.6751, 0.6435, 0.5845, 0.5276, and 0.5351 for overall survival (OS), respectively, and 0.5955, 0.5694, 0.4692, 0.4873, and 0.5272 for disease-free survival, respectively. Multivariate analyses for prognosis factor in HCC patients showed that PNI was an independent predictor of both OS (HR 0.91, P < 0.001) and disease-free survival (HR 0.94, P < 0.001). When the patients were divided into high and low PNI groups, the patients in the low PNI group had significant poorer OS (P < 0.001) and disease-free survival (P < 0.001), even after background factors were matched between these two groups. Conclusions: PNI is superior to Controlling Nutritional Status score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, or Glasgow Prognostic Score as a predictor of OS and recurrence-free survival in patients with HCC who underwent curative hepatic resection..
2002. A. Watanabe, T. Yoshizumi, N. Harimoto, K. Kogure, T. Ikegami, N. Harada, S. Itoh, K. Takeishi, Y. Mano, S. Yoshiya, A. Morinaga, K. Araki, N. Kubo, M. Mori, K. Shirabe, Right hepatic venous system variation in living donors
a three-dimensional CT analysis, British Journal of Surgery, 10.1002/bjs.11602, 2020.01, Background: The right hepatic venous system consists of the right hepatic vein (RHV) and inferior RHVs (IRHVs). When the right posterior section is used as a graft for liver transplantation, understanding variations and relationships between the RHV and IRHVs is critical for graft venous return and hepatic vein reconstruction. This study aimed to evaluate variations in the hepatic veins and the relationships between them. Methods: The medical records and CT images of patients who underwent hepatectomy as liver donors were assessed retrospectively. The relationship between the veins was evaluated by three-dimensional CT. Results: The configuration of the posterior section was classified into one of eight types based on the RHV and IRHVs in 307 patients. Type 1a (103 of 307), type 1b (139 of 307) and type 2a (40 of 307) accounted for 91·9 per cent of the total. The diameter of the RHV extending towards the inferior vena cava had a significant inverse correlation with that of the IRHV (r2 = –0·615, P < 0·001). Type 1a, which had no IRHVs, had the RHV with the largest diameter; conversely, type 2a, which had a large IRHV, had the RHV with the smallest diameter. Conclusion: The hepatic venous system of the right posterior section was classified into eight types, with an inverse relationship between RHV and IRHV sizes. This information is useful for segment VII resection or when the right liver is used as a transplant graft..
2003. Kazuki Takeishi, Tomoharu Yoshizumi, Shinji Itoh, Kyohei Yugawa, Shohei Yoshiya, Takeo Toshima, Noboru Harada, Toru Ikegami, Akihiro Nishie, Masaki Mori, Surgical Indications for Hepatocellular Carcinoma with Non-hypervascular Hypointense Nodules Detected by Gd-EOB-DTPA-Enhanced MRI, Annals of Surgical Oncology, 10.1245/s10434-020-08419-4, 2020.01, Background: The surgical indication for non-hypervascular hypointense nodules (NHVN) detected incidentally on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) for classical hepatocellular carcinoma (HCC) is unknown. Our aim is to clarify the long-term outcomes in patients with this finding. Methods: We reviewed the cases of 290 HCC patients, including 66 patients with NHVN, who underwent Gd-EOB-MRI prior to hepatectomy, between October 2008 and December 2017 at our center. We divided the patients into three groups: a no-NHVN group, a treated NHVN group, and an untreated NHVN group. Results: There was no significant difference in (RFS) or overall survival (OS) between the no-NHVN and untreated NHVN groups (p = 0.103 and 0.103, respectively). There was no significant difference between these two groups after propensity score matching. Multivariate analyses showed that microscopic intrahepatic metastases and the size of the main classical HCC, the target tumor, were independent prognostic factors of overall survival, but the presence of non-hypervascular hypointense nodules was not. There was no significant difference in RFS or OS between the treated NHVN and untreated NHVN groups (p = 0.158 and 0.109, respectively). Conclusions: Non-hypervascular hypointense nodules detected incidentally on Gd-EOB-MRI associated with targeted hypervascular HCC did not reflect prognosis of HCC after hepatectomy. Surgical procedures for classical enhancing HCC may be performed even if non-hypervascular hypointense nodules adjacent to the targeted HCC cannot be removed completely..
2004. Takuma Izumi, Kazuhito Sakata, Daisuke Okuzaki, Shoichi Inokuchi, Tomokazu Tamura, Daisuke Motooka, Shota Nakamura, Chikako Ono, Masahiro Shimokawa, Yoshiharu Matsuura, Masaki Mori, Takasuke Fukuhara, Tomoharu Yoshizumi, Characterization of human pegivirus infection in liver transplantation recipients, Journal of Medical Virology, 10.1002/jmv.25555, 91, 12, 2093-2100, 2019.12, Approximately 2% of healthy persons are infected with human pegivirus (HPgV). HPgV is transmitted via vertical, sexual, and blood-borne routes. Recently, the association of HPgV infection with the risk of lymphoma was reported. Here, we examined the prevalence of chronic HPgV infection in liver transplantation (LT) recipients and patients with hepatectomy and the influence of HPgV infection after LT on clinical and perioperative factors. We enrolled 313 LT recipients and 187 patients with hepatectomy who received care at the Kyusyu University Hospital between May 1997 and September 2017. Of the 313 recipients and 187 patients enrolled in this study, 44 recipients (14.1%) and 2 patients (1.1%) had HPgV viremia, respectively. There was no significant association between HPgV infection and LT outcomes. Interestingly, one recipient was infected with HPgV during the peritransplant period, which was likely transmitted via blood transfusion because HPgV RNA was detected from the blood bag transfused to the recipient during LT. We reviewed the available literature on the prevalence HPgV infections in other organ-transplanted patients and whether they impacted clinical outcomes. They also had the higher prevalence of HPgV infection, while it appears to be of low or no consequences. In addition, HPgV infection induced the upregulation of interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells. LT recipients had higher HPgV viremia compared to patients with hepatectomy. Although HPgV infection was not associated with LT-related outcomes, it induced ISG expression in recipients..
2005. Toru Ikegami, Tomoharu Yoshizumi, Yuriko Tsutsui, Noboru Harada, Shinji Itoh, Shohei Yoshiya, Daisuke Imai, Hideaki Uchiyama, Masaki Mori, Extensive Thrombectomy as a Legitimate Strategy in Living Donor Liver Transplantation With Advanced Portal Vein Thrombosis, Liver Transplantation, 10.1002/lt.25623, 25, 12, 1768-1777, 2019.12, Management of portal vein thrombosis (PVT), especially advanced PVT involving the superior mesenteric vein (SMV), in living donor liver transplantation (LDLT) is challenging. There were 514 adults who underwent LDLT between 2005 and 2018 included in this retrospective study, and PVT was observed in 67 (13.0%) patients. The LDLT recipients with PVT were characterized by increased portal pressure at laparotomy (26.1 ± 6.0 versus 24.3 ± 5.9 mm Hg; P = 0.03) and at closure (16.8 ± 3.9 versus 15.6 ± 3.6 mm Hg; P = 0.02), increased operative blood loss (14.6 ± 29.7 versus 5.7 ± 6.3 L; P < 0.01), and decreased 1-year graft survival (83.5% versus 92.8%; P = 0.04). Among the 18 patients with atrophic or vanished portal vein on pre-LDLT computed tomography, significant portal atrophy was actually observed only in 1 (5.6%) patient during LDLT surgery. For advanced PVT (n = 7) involving SMV in era 1, we performed nonanatomical inflow reconstruction using interposition grafts, resulting in significant inflow problems in 4 (57.1%) patients. Thus, for the patients with advanced PVT (n = 4) in era 2, we abandoned nonanatomical reconstruction and applied extensive thrombectomy under ultrasound guidance with secure shunt ligation, resulting in no inflow problems and no graft loss. In conclusion, even for advanced PVT involving SMV, extensive thrombectomy under sonogram guidance followed by anatomical inflow reconstruction and shunt ligation is a legitimate strategy in adult LDLT with PVT..
2006. Tomonari Shimagaki, Sachiyo Yoshio, Hironari Kawai, Yuzuru Sakamoto, Hiroyoshi Doi, Michitaka Matsuda, Taizo Mori, Yosuke Osawa, Moto Fukai, Takeshi Yoshida, Yunfei Ma, Tomoyuki Akita, Junko Tanaka, Akinobu Taketomi, Rikinari Hanayama, Tomoharu Yoshizumi, Masaki Mori, Tatsuya Kanto, Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma, Scientific reports, 10.1038/s41598-019-52356-6, 9, 1, 2019.12, Current serum hepatocellular carcinoma (HCC) biomarkers are insufficient for early diagnosis. We aimed to clarify whether serum MFG-E8 can serve as a diagnostic or prognostic biomarker of HCC. Serum MFG-E8 levels of 282 HCC patients, who underwent primary hepatectomy, were examined by ELISA. We also quantified serum MFG-E8 levels in patients with chronic hepatitis (CH), liver cirrhosis (LC), as well as in healthy volunteers (HVs). Serum MFG-E8 levels were significantly lower in HCC patients than in HVs regardless of the etiology of liver disease (3.6 ± 0.1 vs 5.8 ± 0.2 ng/mL, p < 0.0001), and recovered after treatment of HCC. Serum MFG-E8 levels in CH and LC patients were comparable to those in HVs. Serum MFG-E8 could detect HCCs, even α-fetoprotein (AFP)-negative or des-γ-carboxy prothrombin (DCP)-negative HCCs, in CH and LC patients. Our new HCC prediction model using MFG-E8 and DCP (Logit(p) = 2.619 − 0.809 × serum MFG-E8 + 0.0226 × serum DCP) distinguished HCC patients from CH and LC patients with an area under the curve of 0.923, a sensitivity of 81.1%, and a specificity of 89.8%. Futhermore, low preoperative serum MFG-E8 was an independent predictor of poor overall survival. Thus, serum MFG-E8 could serve as a feasible diagnostic and prognostic biomarker for HCC..
2007. Yohei Mano, Sachiyo Yoshio, Hirotaka Shoji, Shimagaki Tomonari, Yoshihiko Aoki, Nobuyoshi Aoyanagi, Toru Okamoto, Yoshiharu Matsuura, Yosuke Osawa, Kiminori Kimura, Kyohei Yugawa, Huanlin Wang, Yoshinao Oda, Tomoharu Yoshizumi, Yoshihiko Maehara, Tatsuya Kanto, Bone morphogenetic protein 4 provides cancer-supportive phenotypes to liver fibroblasts in patients with hepatocellular carcinoma, Journal of gastroenterology, 10.1007/s00535-019-01579-5, 54, 11, 1007-1018, 2019.11, Background: Cancer-associated fibroblasts (CAFs) are essential constituents of cancer-supportive microenvironments. The high incidence of hepatocellular carcinoma (HCC) in advanced fibrosis patients implies that fibroblasts have a promoting effect on HCC development. We aimed to explore the regulators of phenotypes and function of CAFs in the liver. Methods: We established primary cancer-associated fibroblasts (CAFs) and non-cancerous liver fibroblasts (NFs) from 15 patients who underwent HCC resection. We compared phenotypes, capacity of cytokine/chemokine production and gene expression profiles between pairs of CAFs and NFs from the same donors. We examined resected tissue from additional 50 patients with HCC for immunohistochemical analyses. Results: The CAFs expressed more ACTA2 and COL1A1 than the NFs, suggesting that CAFs are more activated phenotype. The CAFs produced larger amounts of IL-6, IL-8 and CCL2 than the NFs, which led to invasiveness of HuH7 in vitro. We found that Bone Morphogenetic Protein-4 (BMP4) is up-regulated in CAFs compared to NFs. The CAF phenotype and function were gained by BMP4 over-expression or recombinant BMP4 given to fibroblasts, all of which decreased with BMP4 knockdown. In tissues obtained from the patients, BMP4-positive cells are mainly observed in encapsulated fibrous lesions and HCC. Positive expression of BMP4 in HCC in resected tissues, not in fibroblasts, was associated with poorer postoperative overall survival in patients with HCC. Conclusion: Endogenous and exogenous BMP4 activate liver fibroblasts to gain capacity of secreting cytokines and enhancing invasiveness of cancer cells in the liver. BMP4 is one of the regulatory factors of CAFs functioning in the microenvironment of HCC..
2008. Kyohei Yugawa, Shinji Itoh, Takeshi Kurihara, Shohei Yoshiya, Yohei Mano, Kazuki Takeishi, Noboru Harada, Toru Ikegami, Yuji Soejima, Masaki Mori, Tomoharu Yoshizumi, Skeletal muscle mass predicts the prognosis of patients with intrahepatic cholangiocarcinoma, American Journal of Surgery, 10.1016/j.amjsurg.2019.03.010, 218, 5, 952-958, 2019.11, Background: We studied the prognostic impact of sarcopenia after hepatic resection for intrahepatic cholangiocarcinoma (ICC). Methods: Sixty-one patients who underwent surgery for ICC during 2000–2017 were analyzed retrospectively. Psoas muscle areas were measured on CT scans at the third lumbar vertebra. Areas less than the sex-specific median were deemed low skeletal muscle masses (SMMs). Results: Low-SMM patients were significantly more often older (p = 0.002) than high-SMM patients, had lower serum albumin (p = 0.004), higher serum C-reactive protein (CRP) (p = 0.002), and higher carbohydrate antigen 19-9 (p < 0.001). Five-year overall survival rates were 72.5% and 17.6% and 5-year recurrence-free survival rates were 58.6% and 21.1%, respectively, in high- and low-SMM patients. Multivariable analysis revealed that low SMM predicted unfavorable prognoses. SMM was associated with immune nutritional status (e.g., prognostic nutritional index, Glasgow prognostic score, CRP/albumin ratio). Conclusion: Low SMM was related to worse surgical outcomes in patients with ICC following hepatic resection..
2009. Kazuki Takeishi, Tomoharu Yoshizumi, Toru Ikegami, Shinji Itoh, Noboru Harada, Nao Fujimori, Takamasa Ohno, Masaki Mori, Transgastric Endoscopic Lumen–Apposing Metal Stents for Intra-abdominal Fluid Collections After Living Donor Liver Transplantation, Liver Transplantation, 10.1002/lt.25707, 26, 4, 598-601, 2020.04.
2010. Shohei Yoshiya, Tomoharu Yoshizumi, Norifumi Iseda, Kazuki Takeishi, Takeo Toshima, Yoshihiro Nagao, Shinji Itoh, Noboru Harada, Toru Ikegami, Masaki Mori, Anastomosis of the Common Hepatic Artery and Round Ligament as Portal Vein Arterialization for Hepatic Artery Occlusion After Deceased Donor Liver Transplantation
A Case Report, Transplantation Proceedings, 10.1016/j.transproceed.2019.12.003, 52, 2, 641-643, 2020.03, Background: Hepatic artery occlusion (HAO) is a life-threatening complication after liver transplantation. We report a case of portal vein arterialization (PVA) with anastomosis of the recipient common hepatic artery (CHA) and a graft of the round ligament to achieve intrahepatic arterial flow. Case presentation: A 57-year-old man had a medical history of decompensated liver cirrhosis secondary to cholestatic liver disease owing to biliary anastomotic stricture after living donor liver transplantation and end-stage renal failure. He underwent deceased donor liver and renal transplantation with anastomosis of the recipient proper hepatic artery and the graft CHA. He experience symptoms from HAO on postoperative day 23 and underwent emergency surgery to re-anastomose the hepatic artery. Despite several instances of re-anastomoses, intrahepatic arterial flow was not able to be achieved and therefore PVA with anastomosis of the recipient CHA and the graft round ligament was performed. Although liver enzyme levels rapidly declined after surgery and the finding of liver infarction was not observed, a large amount of watery stool was observed owing to portal hypertension, which was an adverse effect of PVA. As enhanced computed tomography on POD 31 showed a pseudoaneurysm of the anastomotic site, occlusion with coils was performed to arrest hemorrhage, and a contrast study after coil occlusion showed intrahepatic arterial blood flow via collateral arteries. Thereafter, the patient needed treatment for ischemic biliary duct stenosis and was discharged home on POD 98. Conclusion: PVA using a round ligament for HAO after liver transplantation might play a role as a bridge treatment until retransplantation or maturation of collaterals..
2011. Masaru Harada, Yuichi Honma, Tomoharu Yoshizumi, Keiichiro Kumamoto, Shinji Oe, Noboru Harada, Aya Tanimoto, Kei Yabuki, Tsukasa Karasuyama, Akitoshi Yoneda, Michihiko Shibata, Idiopathic copper toxicosis
is abnormal copper metabolism a primary cause of this disease?, Medical Molecular Morphology, 10.1007/s00795-019-00227-4, 53, 1, 50-55, 2020.03, Idiopathic copper toxicosis (ICT) is characterized by marked copper deposition, Mallory-Denk body (MDB) formation and severe hepatic injury. Although the characteristics are apparently different from Wilson disease, large amounts of copper accumulate in the liver of the patients. We extensively treated a patient with ICT to reduce the body copper, however, the patient needed liver transplantation. Previous liver biopsy revealed high copper content. But extirpated liver contained an extremely small amount of copper, although MDBs and severe inflammation remained. These phenomena suggest abnormal copper metabolism is not the principle cause of ICT but some other abnormality must exist..
2012. Toru Ikegami, Tomoharu Yoshizumi, Takahiro Tomiyama, Shoichi Inokuchi, Masaki Mori, Extensive portal thrombectomy with secure shunt ligation should be more strongly emphasized in the real-world setting, Journal of Hepatology, 10.1016/j.jhep.2019.09.009, 72, 1, 199-201, 2020.01.
2013. Noboru Harada, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Shinji Itoh, Kazuki Takeishi, Takeo Toshima, Yoshihiro Nagao, Shohei Yoshiya, Masaki Mori, Impact of middle hepatic artery reconstruction after living donor liver transplantation using the left lobe, Clinical Transplantation, 10.1111/ctr.13850, 2020.01, Introduction: The aim of this study was to clarify the impact of middle hepatic artery reconstruction on the outcomes of duct-to-duct biliary anastomosis after living donor liver transplantation (LDLT) using the left lobe. Materials and Methods: Among 258 patients who underwent LDLT using the left lobe, 216 patients who underwent hepatic artery reconstruction and one hepatic duct reconstruction with duct-to-duct interrupted anastomosis were divided into three groups: Group A (n = 123), one arterial stump with left hepatic artery reconstruction; Group B (n = 32), two arterial stumps with only left hepatic artery reconstruction; and Group C (n = 61), two arterial stumps with reconstruction of the left and middle hepatic arteries. The outcomes after LDLT were compared among the three groups. Results: No hepatic artery complications occurred. Group B had a significantly greater incidence of anastomotic biliary stricture than Group C. A multivariate analysis with Cox regression revealed that being in Group B was the only significant independent risk factor for postoperative anastomotic biliary stricture after LDLT. Conclusions: Middle and left hepatic artery reconstruction is safe in LDLT and may prevent biliary stricture caused by dual hepatic artery reconstruction when the graft has left and middle hepatic artery stumps..
2014. Tomoharu Yoshizumi, Masaki Mori, Portal flow modulation in living donor liver transplantation
review with a focus on splenectomy, Surgery today, 10.1007/s00595-019-01881-y, 50, 1, 21-29, 2020.01, Small-for-size graft (SFSG) syndrome after living donor liver transplantation (LDLT) is the dysfunction of a small graft, characterized by coagulopathy, cholestasis, ascites, and encephalopathy. It is a serious complication of LDLT and usually triggered by excessive portal flow transmitted to the allograft in the postperfusion setting, resulting in sinusoidal congestion and hemorrhage. Portal overflow injures the liver directly through nutrient excess, endothelial activation, and sinusoidal shear stress, and indirectly through arterial vasoconstriction. These conditions may be attenuated with portal flow modulation. Attempts have been made to control excessive portal flow to the SFSG, including simultaneous splenectomy, splenic artery ligation, hemi-portocaval shunt, and pharmacological manipulation, with positive outcomes. Currently, a donor liver is considered a SFSG when the graft-to-recipient weight ratio is less than 0.8 or the ratio of the graft volume to the standard liver volume is less than 40%. A strategy for transplanting SFSG safely into recipients and avoiding extensive surgery in the living donor could effectively address the donor shortage. We review the literature and assess our current knowledge of and strategies for portal flow modulation in LDLT..
2015. Yusuke Yonemura, Tomoharu Yoshizumi, Shoichi Inokuchi, Yukiko Kosai-Fujimoto, Noboru Harada, Shinji Itoh, Takeo Toshima, Kazuki Takeishi, Shohei Yoshiya, Masaki Mori, Predictor of outcome after living donor liver transplantation for patients with hepatocellular carcinoma beyond the Japan criteria, Annals of Gastroenterological Surgery, 10.1002/ags3.12335, 2020.01, Background: The Japan criteria (JC, maximum tumor size within 5 cm, within five tumor nodules, AFP within 500 ng/mL or within Milan criteria) have been applied to cadaveric liver transplantation (LT) for hepatocellular carcinoma (HCC) and will be used for living donor LT (LDLT) in Japan. The aim of this study was to verify the JC in LDLT and to clarify the risk factor of HCC recurrence and mortality after LDLT beyond the JC. Patients and methods: Adult patients who underwent LDLT for end-stage liver disease with HCC until October 2019 were reviewed retrospectively (n = 246). Patients were divided into two groups according to whether they were within JC (n = 203) or beyond JC (n = 43). Recurrence-free or overall survival rates after LDLT were compared. Univariate and multivariate analyses were performed to identify risk factors of HCC recurrence and HCC-related mortality after LDLT for patients beyond the JC. Results: Patients beyond the JC had significantly poorer 5-year recurrence-free (50.3% vs 95.9%, P <.001) or overall (61.7% vs 98.1%, P <.001) survival rates compared with patients within the JC. A multivariate analysis revealed that des-gamma-carboxy prothrombin (DCP) ≥ 300 mAU/mL (hazard ratio 9.36, 95% CI; 2.41-36.4, P =.001) was an independent risk factor for HCC recurrence and HCC-related mortality (hazard ratio 13.8, 95% CI; 1.92-98.6, P =.01) after LDLT in patients beyond the JC. Conclusion: The outcome of LDLT for patients within the JC was favorable. Patients beyond the JC with DCP ≥ 300 mAU/mL might be contraindicated for LDLT..
2016. Takeo Toshima, Tomoharu Yoshizumi, Yukiko Kosai-Fujimoto, Shoichi Inokuchi, Shohei Yoshiya, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Masaki Mori, Prognostic Impact of Osteopenia in Patients Who Underwent Living Donor Liver Transplantation for Hepatocellular Carcinoma, World journal of surgery, 10.1007/s00268-019-05206-5, 44, 1, 258-267, 2020.01, Background: Osteopenia, loss of bone mineral density (BMD), was recently identified to be independently associated with early marker of deconditioning that precedes sarcopenia in patients with hepatocellular carcinoma (HCC). The aim of this study was to clarify the impact of osteopenia as the risk factor for mortality after living donor liver transplantation (LDLT) compared with already-reported biological markers. Methods: Data were collected retrospectively for all consecutive patients who underwent LDLT for HCC at our institution between January 1998 and December 2015. BMD was evaluated with computed tomographic measurement of pixel density in the midvertebral core of the 11th thoracic vertebra. Data related to clinicopathological parameters and prognosis were analyzed. Results: The median value of BMD was 163.6 Hounsfield units and osteopenia was identified in 103 (53.4%) of the 193 recipients, according to the age-specific formula. In addition to the other tumor burdens, such as tumor numbers ≥5 (HR 2.521, P = 0.027), DCP levels >200 mAU/mL (HR 2.678, P = 0.006), and neutrophil-to-lymphocyte ratio ≥3.01 (HR 2.068, P = 0.025), osteopenia (HR 2.106, P = 0.024) was independent risk factor for mortality by multivariate analysis. Overall survival of the patients who met the two risk factors and more was significantly lower than the others (HR 5.382, P < 0.001). Besides, the calibration plot for the 5-year overall survival using nomogram was predicted very well (C-index 0.746). Conclusions: Preoperative osteopenia was independently associated with post-LDLT mortality among patients with HCC. Moreover, risk score and nomogram with calibration curve were developed to confirm the clinical usefulness of osteopenia for post-LDLT patients..
2017. Kyohei Yugawa, Kenichi Kohashi, Shinji Itoh, Tomoharu Yoshizumi, Ichiro Sakamoto, Hiroyuki Tsutsui, Masaki Mori, Yoshinao Oda, Combined hepatocellular-cholangiocarcinoma after tetralogy of Fallot repair
a case report and review of literature, Pathology Research and Practice, 10.1016/j.prp.2020.152908, 216, 5, 2020.05, Background: Liver fibrosis and cancer are serious hepatic complications for patients with congenital heart diseases. We present a rare case of combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC-CCA) after the repair of tetralogy of Fallot (TOF). Case presentation: A 54-year-old Japanese woman had undergone biventricular repair for TOF at 7 years old. She presented with abdominal distension. Abdominal CT revealed ascites and a 90-mm tumor involving the liver's left lobe. Tumor marker values were: alpha-fetoprotein, 16,208 ng/mL and des-gamma-carboxy prothrombin, 33,920 mAU/mL. The preoperative diagnosis was malignant tumor of the liver (e.g., HCC or intrahepatic CCA). We performed a left lobectomy of the liver. Histopathologically, the tumor was composed of two components growing in trabecular and irregular tubular patterns accompanied by a transitional area; the tumor was diagnosed as cHCC-CCA. The non-cancerous area showed fibrous change mainly surrounding a central vein and sinusoid, expanding toward the portal area without inflammation. Conclusions: We provide the details of our patient's cHCC-CCA that developed from fibrous congestive liver associated with right-sided heart failure after TOF repair, diagnosed based on histopathological features. We discuss liver fibrosis as a hepatic complication and a careful follow-up maneuver for improving the outcomes of patients with chronic hepatic congestion..
2018. Seiichiro Takao, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Kakihara, Tomohiro Nakayama, Nobuhiro Fujita, Koichiro Morita, Keisuke Ishimatsu, Tomoharu Yoshizumi, Toru Ikegami, Masatoshi Kondo, Hiroshi Honda, Improved visualization of a fine intrahepatic biliary duct on drip infusion cholangiography-computed tomography
Impact of knowledge-based iterative model reconstruction, Hepatology Research, 10.1111/hepr.13477, 50, 5, 629-634, 2020.05, Aim: The purpose of this study was to investigate the visualization of fine biliary ducts with knowledge-based iterative model reconstruction (IMR) in low-dose drip infusion computed tomography (CT) cholangiography (DIC-CT) as compared with filtered back projection (FBP) and hybrid iterative reconstruction (iDose4). Methods: A total of 38 patients underwent DIC-CT for living donor liver transplantation. CT was performed approximately 20 min after the end of the infusion of meglumine iotroxate (100 mL). Images were reconstructed using FBP, iDose4, and IMR, and 1-mm slice images at fixed window level and width were prepared for assessment. Two reviewers independently evaluated the quality of visualization of the fine biliary ducts of the caudate lobe (B1) using a 5-point scale. The visualization scores of three reconstructed images were compared using the Kruskal–Wallis test and Mann–Whitney U-test. Results: For reviewer 1, the visualization score of IMR was significantly higher than that of FBP (P = 0.012), and tended to be higher than that of iDose4 (P = 0.078). For reviewer 2, the visualization score of IMR was significantly higher than those of both FBP and iDose4 (P < 0.01). Conclusions: IMR showed better visualization of B1 on DIC-CT than FBP or iDose4. DIC-CT reconstructed with IMR may be useful to the anatomical grasp of biliary tracts in cases of hepatectomy..
2019. Kaori Kuramitsu, Takumi Fukumoto, Hiroto Egawa, Hideki Ohdan, Koji Umeshita, Shinji Uemoto, Taizo Hibi, Mureo Kasahara, Tomoharu Yoshizumi, Koichi Mizuta, Tsuyoshi Shimamura, Hiroyuki Furukawa, A Multicenter Japanese Survey Assessing the Long-term Outcomes of Liver Retransplantation Using Living Donor Grafts, Transplantation, 10.1097/TP.0000000000002958, 104, 4, 754-761, 2020.04, BACKGROUND: Liver transplantation is the most suitable treatment option available for end-stage liver disease. However, some patients require retransplantation, despite medical advances that have led to improved survival. We aimed to compile a definitive, nationwide resource of liver retransplantation data in Japan, seeking to identify the predictors of patient survival posttransplantation. METHODS: Questionnaires were sent to 32 institutions that had conducted 281 retransplantations before 2015. RESULTS: Among the 265 patients included in this study (142 pediatric cases), the average age at primary transplantation was 23 years, and retransplantation was performed after an average of 1468 days. The main indication for retransplantation was graft rejection (95 patients). Living-donor liver transplantation accounted for 94.7% of primary transplantations and 73.2% of retransplantations. Patient survival at 1, 3, or 5 years did not differ by type of transplantation but was better for pediatric (70.8%, 68.3%, and 60.1%, respectively) than for adult (57.2%, 50.4%, and 45.2%, respectively) recipients (P = 0.0003). Small-for-size syndrome, retransplantation within 365 days, and inpatient status at retransplantation were significant predictors of poor survival in pediatric cases. Retransplantation within 365 days and conditions warranting retransplantation were significant predictors of poor survival in adult patients. CONCLUSIONS: In Japan, where >70% of retransplantations are performed using living donors, the indications and timing are different from those in previous reports from other countries, while maintaining comparable survival rates. Considering technical challenges, graft failure within 365 days should be thoroughly restricted to justify the use of living donor..
2020. Masafumi Ohira, Tomoharu Yoshizumi, Kyohei Yugawa, Yukiko Kosai-Fujimoto, Shoichi Inokuchi, Takashi Motomura, Yohei Mano, Takeo Toshima, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Masaki Mori, Association of inflammatory biomarkers with long-term outcomes after curative surgery for mass-forming intrahepatic cholangiocarcinoma, Surgery today, 10.1007/s00595-019-01905-7, 50, 4, 379-388, 2020.04, Purpose: Inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are reportedly predictive of the long-term outcomes of several cancers. We evaluated their correlations with the post-surgical long-term outcomes of patients with mass-forming (MF) intrahepatic cholangiocarcinoma (ICC). Methods: The subjects of this study were 52 patients who underwent hepatic resection for MF-ICC at our hospital. We measured the cutoff values of NLR, LMR and PLR, using receiver operating characteristic curves, and compared the survival rates of patients with high vs. those with low values. We also evaluated a prognostic scoring system based on significant inflammatory biomarkers. Results: The cutoff values for NLR, LMR, and PLR were 1.93, 4.78, and 98, respectively. The high-NLR and low-LMR groups had significantly worse prognoses than the low-NLR and high-LMR groups. We designed a scoring system using the inflammation score (IS) based on NLR and LMR values, stratifying patients into three groups with scores of 0, 1, or 2. The IS was significantly correlated with overall survival (OS), with 5-year survival rates by the IS score of 100% for 0, 61% for 1, and 32% for 2 (P = 0.011). The IS was found to be an independent predictor of OS in multivariate analysis. Conclusions: Our IS scoring system may predict long-term outcomes after surgery for MF-ICC..
2021. Takahiro Nakamura, Mio Fukuda, Ryosuke Matsukane, Kimitaka Suetsugu, Noboru Harada, Tomoharu Yoshizumi, Nobuaki Egashira, Masaki Mori, Satohiro Masuda, Influence of POR*28 polymorphisms on 5*3-associated variations in tacrolimus blood levels at an early stage after liver transplantation, International journal of molecular sciences, 10.3390/ijms21072287, 21, 7, 2020.04, It is well known that the CYP3A5*3 polymorphism is an important marker that correlates with the tacrolimus dose requirement after organ transplantation. Recently, it has been revealed that the POR*28 polymorphism affects the pharmacokinetics of tacrolimus in renal transplant patients. In this study, we examined whether POR*28 as well as CYP3A5*3 polymorphism in Japanese recipients and donors would be another biomarker for the variation of tacrolimus blood levels in the recipients during the first month after living-donor liver transplantation. We enrolled 65 patients treated with tacrolimus, who underwent liver transplantation between July 2016 and January 2019. Genomic DNA was extracted from whole-blood samples, and genotyping was performed to examine the presence of CYP3A5*3 and POR*28 polymorphisms in the recipients and donors. The CYP3A5*3/*3 genotype (defective CYP3A5) of the recipient (standard partial regression coefficient [median C/D ratio of CYP3A5 expressor vs. CYP3A5 non-expressor, p value]: Pod 1–7, β= −0.389 [1.76 vs. 2.73, p < 0.001]; Pod 8–14, β = −0.345 [2.03 vs. 2.83, p < 0.001]; Pod 15–21, β= −0.417 [1.75 vs. 2.94, p < 0.001]; Pod 22–28, β = −0.627 [1.55 vs. 2.90, p < 0.001]) rather than donor (Pod 1–7, β = n/a [1.88 vs. 2.76]; Pod 8–14, β = n/a [1.99 vs. 2.93]; Pod 15–21, β = −0.175 [1.91 vs. 2.94, p = 0.004]; Pod 22–28, β = n/a [1.61 vs. 2.67]) significantly contributed to the increase in the concentration/dose (C/D) ratio of tacrolimus for at least one month after surgery. We found that the tacrolimus C/D ratio significantly decreased from the third week after transplantation when the recipient carried both CYP3A5*1 (functional CYP3A5) and POR*28 (n = 19 [29.2%], median C/D ratio [inter quartile range] = 1.58 [1.39–2.17]), compared with that in the recipients carrying CYP3A5*1 and POR*1/*1 (n = 8 [12.3%], median C/D ratio [inter quartile range] = 2.23 [2.05–3.06]) (p < 0.001). In conclusion, to our knowledge, this is the first report suggesting that the POR*28 polymorphism is another biomarker for the tacrolimus oral dosage after liver transplantation in patients carrying CYP3A5*1 rather than CYP3A5*3/*3..
2022. Yukiko Kosai-Fujimoto, Tomoharu Yoshizumi, Takahiro Tomiyama, Akinari Morinaga, Norifumi Iseda, Shoichi Inokuchi, Kyohei Yugawa, Shohei Yoshiya, Takeo Toshima, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Masaki Mori, Living-Donor Liver Transplantation for Patients With Extrahepatic Malignancy
A Series of 14 Patients in a Single Institution, Transplantation Proceedings, 10.1016/j.transproceed.2019.12.041, 52, 3, 889-893, 2020.04, Extrahepatic malignancy is a relative contraindication for liver transplant in many countries. Nevertheless, the indications for living-donor liver transplantation (LDLT) for such patients vary by institution. Our aim was to reevaluate the indications for LDLT in patients with extrahepatic malignancy. We retrospectively reviewed data for 609 patients who underwent adult LDLT from May 1997 to January 2018 and analyzed patients with a history of extrahepatic malignancies or concurrent malignancies. Fourteen patients had extrahepatic malignancies concurrent with or before LDLT. Malignancies in 9 patients were detected during their systematic screening for LDLT. The mean duration between surgeries was 70 days (range, 20-209 days). Five patients had a history of extrahepatic malignancies before considering LDLT. The estimated 5-year survival rate was 100%. Although the risk and long-term prognosis of patients with extrahepatic malignancy are not well known, such patients can be candidates for LDLT if they undergo curative surgery for the malignancy, and if the prognosis of the malignancy is the same or superior to that of LDLT..
2023. Masahiro Shimokawa, Tomoharu Yoshizumi, Shinji Itoh, Norifumi Iseda, Kazuhito Sakata, Kyohei Yugawa, Takeo Toshima, Noboru Harada, Toru Ikegami, Masaki Mori, Modulation of Nqo1 activity intercepts anoikis resistance and reduces metastatic potential of hepatocellular carcinoma, Cancer Science, 10.1111/cas.14320, 111, 4, 1228-1240, 2020.04, The processing of intracellular reactive oxygen species (ROS) by nuclear factor erythroid-derived 2-like 2 (Nrf2) and NADPH quinone oxidoreductase 1 (Nqo1) is important for tumor metastasis. However, the clinical and biological significance of Nrf2/Nqo1 expression in hepatocellular carcinoma (HCC) remains unclear. We aimed to clarify the clinical importance of Nrf2/Nqo1 expression in HCC and evaluate the association of Nrf2/Nqo1 expression with HCC metastasis. We also evaluated the impact of Nqo1 modulation on HCC metastatic potential. We used spheroids derived from HCC cell lines. In anchorage-independent culture, HCC cells showed increased ROS, leading to the upregulation of Nrf2/Nqo1. Futile stimulation of Nqo1 by β-lapachone induces excessive oxidative stress and dramatically increased anoikis sensitivity, finally diminishing the spheroid formation ability, which was far stronger than depletion of Nqo1. We analyzed 117 cases of primary HCC who underwent curative resection. Overexpression of Nrf2/Nqo1 in primary HCC was associated with tumor size, high α-fetoprotein, and des-γ-carboxy-prothrombin levels. Overexpression of Nrf2/Nqo1 was also associated with multiple intrahepatic recurrences (P =.0073) and was an independent risk factor for poor prognosis (P =.0031). NADPH quinone oxidoreductase 1 plays an important role in anchorage-independent survival, which is essential for survival for circulation and distant metastasis of HCC cells. These results suggest that targeting Nqo1 activity could be a potential strategy for HCC adjuvant therapy..
2024. Takeo Toshima, Tomoharu Yoshizumi, Shoichi Inokuchi, Yukiko Kosai-Fujimoto, Takeshi Kurihara, Shohei Yoshiya, Yohei Mano, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Mototsugu Shimokawa, Yoshihiko Maehara, Masaki Mori, Risk factors for the metabolic syndrome components of hypertension, diabetes mellitus, and dyslipidemia after living donor liver transplantation, HPB, 10.1016/j.hpb.2019.08.008, 22, 4, 511-520, 2020.04, Background: Metabolic syndrome (MS) is the most common long-term complication after liver transplantation, and it has been increasing in incidence. The aim of this study was to clarify the risk factors for each MS component -hypertension, diabetes mellitus, and dyslipidemia-after living-donor liver transplantation (LDLT), including characteristics of living-donors. Methods: Data related to clinicopathological parameters including MS components in 461 consecutive patients who underwent LDLT were analyzed retrospectively. Results: Prevalence of all MS components (hypertension, diabetes mellitus, and dyslipidemia) increased from 9.3%, 16.5%, and 7.2% before LDLT to 44.9%, 45.3%, and 50.8% after LDLT, respectively. By multivariate logistic regression analysis, the three factors, cyclosporine use (OR 2.086, P = 0.001), recipient age (OR 1.036, P = 0.001), and BMI (OR 1.072, P = 0.026) were independent predictors for post-LDLT hypertension. Next, the three factors, male recipient (OR 2.471, P < 0.001), recipient age (OR 1.039, P = 0.002), and donor BMI (OR 1.124, P = 0.012) were independent for post-LDLT diabetes mellitus. The four factors, cyclosporine use (OR 2.015, P = 0.001), prolonged prednisolone use (OR 1.928, P = 0.002), recipient age (OR 1.019, P = 0.037), and GRWR (OR 0.316, P = 0.037) were independent for post-LDLT dyslipidemia as well. Conclusions: Not only recipient-related factors but also donor-related factors were independently associated with each targeted post-LDLT MS component..
2025. Yoshihiro Matsumoto, Tomoharu Yoshizumi, Takeo Toshima, Kazuki Takeishi, Takasuke Fukuhara, Shinji Itoh, Toru Ikegami, Yuji Soejima, Masaki Mori, Ectopic localization of autophagosome in fatty liver is a key factor for liver regeneration, Organogenesis, 10.1080/15476278.2019.1633872, 15, 1, 24-34, 2019.01, Autophagy has a critical role in liver regeneration. However, no studies have demonstrated autophagic flux in the regenerating fatty liver. The aim of this study was to clarify the dynamics of autophagy in the regeneration of the fatty liver. Following 70% partial hepatectomy (PH) in db/db fatty mice, which is a non-alcoholic fatty liver disease (NAFLD) model, we investigated the survival rate and recovery of liver volume. Histological examination of the regenerating liver was examined using electron microscopy. The 7-day survival rate after PH in db/db mice was 20%, which was significantly lower than that in control mice (P<.01). Liver regeneration within 48 h after PH was significantly impaired in db/db mice (P<.05). The number of proliferating cell nuclear antigen (PCNA) positive cells and the expression levels of cell-cycle markers cyclins D, E, and A were lower in db/db mice compared with controls. In the regenerating liver, LC3-II level was higher in db/db mice, but p62 expression was increased and cathepsin D expression, a marker of autophagolysosome proteolysis, was decreased compared with controls. Additionally, electronic microscopy revealed that autophagosomes during liver regeneration in db/db mice were mainly located in lipid droplets. Our findings indicate that the different localization of autophagosomes in db/db mice compared with controls led to impairment of liver regeneration in the fatty liver..
2026. Shohei Yoshiya, Kengo Fukuzawa, Shoichi Inokuchi, Yukiko Kosai-Fujimoto, Kensaku Sanefuji, Kentaro Iwaki, Akira Motohiro, Shinji Itoh, Noboru Harada, Toru Ikegami, Tomoharu Yoshizumi, Masaki Mori, Efficacy of Neoadjuvant Chemotherapy in Distal Pancreatectomy with En Bloc Celiac Axis Resection (DP-CAR) for Locally Advanced Pancreatic Cancer, Journal of Gastrointestinal Surgery, 10.1007/s11605-019-04324-8, 2019.01, Backgrounds: Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is an extended surgical procedure for patients with locally advanced cancer of the pancreatic body and tail. Recently, the usability of neoadjuvant chemotherapy (NAC) in pancreatic cancer was reported. The purpose of this study was to clarify the impact of NAC on surgical outcomes and prognosis in DP-CAR patients. Methods: This study retrospectively reviewed 20 consecutive patients who underwent DP-CAR at a single institution. Results: Eleven of 20 patients (55.0%) received NAC. Their first regimens were gemcitabine (GEM) plus nab-PTX (n = 7, 63.6%), GEM plus S-1 (n = 3, 27.3%), and GEM (n = 1, 9.1%). Although two patients converted to a second regimen, none abandoned NAC due to adverse effects or could not undergo a planned procedure for disease progression. There were no significant differences in intraoperative variables, morbidity, including pancreatic fistula and delayed gastric emptying, and mortality between patients with and without NAC; however, patients with NAC had a significantly lower proportion of arterial invasion (p = 0.025), lymphatic invasion (p < 0.0001), and vascular invasion (p = 0.035). There were no significant differences in the induction rate of adjuvant chemotherapy (p = 0.201). The recurrence-free survival and overall survival rates in patients with NAC were significantly higher than in patients without NAC (p = 0.041 and p = 0.018, respectively). Conclusion: DP-CAR following NAC was associated with a preferable prognosis and had no negative effect on surgical outcomes. Therefore, NAC in DP-CAR patients might be a beneficial and safe therapeutic strategy..
2027. Koichi Kimura, Kensuke Kudo, Tomoharu Yoshizumi, Takeshi Kurihara, Shohei Yoshiya, Yohei Mano, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Tetsuo Ikeda, Electrohydraulic lithotripsy and rendezvous nasal endoscopic cholangiography for common bile duct stone
A case report, World Journal of Clinical Cases, 10.12998/wjcc.v7.i10.1149, 7, 10, 1149-1154, 2019.01, BACKGROUND In patients with large stones in the common bile duct (CBD), advanced treatment modalities are generally needed. Here, we present an interesting case of a huge CBD stone treated with electrohydraulic lithotripsy (EHL) by the percutaneous approach and rendezvous endoscopic retrograde cholangiography (ERC) using a nasal endoscope. CASE SUMMARY A 91-year-old woman underwent ERC for a symptomatic large CBD stone with a diameter of 50 mm. She was referred to our institution after the failure of lithotomy by ERC, and after undergoing percutaneous transhepatic biliary drainage. We attempted to fragment the stone by transhepatic cholangioscopy using EHL. However, the stones were too large and partly soft clay-like for lithotripsy. Next, we attempted lithotomy with ERC and cholangioscopy by the rendezvous technique using a nasal endoscope and achieved complete lithotomy. No complication was observed at the end of this procedure. CONCLUSION Cholangioscopy by rendezvous technique using a nasal endoscope is a feasible and safe endoscopic method for removing huge CBD stones..
2028. Takeo Toshima, Tomoharu Yoshizumi, Masahiro Shimokawa, Toru Ikegami, Noboru Harada, Shinji Itoh, Yohei Mano, Takashi Motomura, Yuji Soejima, Yoshihiko Maehara, Feasibility of All-in-One Venoplasty With a Venous Cuff Using an Opened Round Ligament for the Right Lobe Graft in Living Donor Liver Transplantation, Liver Transplantation, 10.1002/lt.25339, 25, 1, 171-175, 2019.01.
2029. Noboru Harada, Tomoharu Yoshizumi, Hideaki Uchiyama, Yuji Soejima, Toru Ikegami, Shinji Itoh, Impact of hepatic artery size mismatch between donor and recipient on outcomes after living-donor liver transplantation using the right lobe, Clinical Transplantation, 10.1111/ctr.13444, 33, 1, 2019.01, Introduction: The aim of this study was to evaluate the effect of hepatic artery (HA) size mismatch anastomosis on outcomes after living-donor liver transplantation (LDLT). Materials and methods: After excluding 128 patients with the exclusion criteria among 233 LDLTs using the right lobe, 104 LDLT patients were divided into two groups: donor HA diameter that was greater than or equal to the recipient HA diameter (D ≥ R group; n = 79), and donor HA diameter that was smaller than the recipient HA diameter (D < R group; n = 25). Results: Hepatic artery-related complications occurred in only one patient (HA thrombosis; 1.0%) who was in the D < R group. The reconstructed HA flow in the D ≥ R group was significantly greater than that in the D < R group (P = 0.015). There was a higher incidence of anastomotic biliary stricture in the D < R group (32.0%) compared with the D ≥ R group (13.9%, P = 0.022) after LDLT. A multivariate analysis with Cox regression revealed that the HA anastomosis of the D < R group and hepaticojejunostomy were significant independent risk factors for postoperative anastomotic biliary stenosis. Conclusions: Hepatic artery anastomosis with a donor HA diameter smaller than that of the recipient HA might be an independent risk factor for postoperative biliary stenosis after LDLT using the right lobe..
2030. Yo ichi Yamashita, Katsunori Imai, Takayoshi Kaida, Takanobu Yamao, Masayo Tsukamoto, Shigeki Nakagawa, Hirohisa Okabe, Akira Chikamoto, Takatoshi Ishiko, Tomoharu Yoshizumi, Tetsuo Ikeda, Yoshihiko Maehara, Hideo Baba, Multimodal radiofrequency ablation versus laparoscopic hepatic resection for the treatment of primary hepatocellular carcinoma within Milan criteria in severely cirrhotic patients
long-term favorable outcomes over 10 years, Surgical endoscopy, 10.1007/s00464-018-6264-3, 33, 1, 46-51, 2019.01, Background: Less invasiveness is an important consideration for the treatment of hepatocellular carcinoma (HCC) especially in patients with severe cirrhosis. Methods: Between April 2000 and September 2016, 100 patients with liver damage B underwent multimodal radiofrequency ablation (RFA; n = 62) or laparoscopic hepatic resection (Lap-HR; n = 38) for primary HCC as defined by the Milan criteria. We compared the operative outcomes and patients’ survival between the two groups. Results: The RFA group showed worse liver functions as indicated by indocyanine green retention rate (32.9 vs. 22.4%; p < 0.0001) and serum albumin value (3.3 vs. 3.6 g/dl; p = 0.0029). As expected, RFA was less invasive, as indicated by the differences in operation time (166 vs. 288 min.; p < 0.0001) and blood loss (8 vs. 377 g; p < 0.0001). There was no significant difference in the morbidity rate between the two groups; however, the duration of hospital stay of the RFA group was significantly shorter (7 vs. 11 days; p = 0.0002). There were no significant between-group differences regarding overall or disease-free survival. Conclusion: Multimodal RFA for HCC in patients with severe cirrhosis is associated with less invasiveness and shorter hospital stays, with no compromise in the patients’ survival. In patients with severe cirrhosis, it may be time to consider changing the standard treatment for primary HCC within the Milan criteria to multimodal RFA..
2031. Hideaki Uchiyama, Ken Shirabe, Yuki Bekki, Takeo Toshima, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Peritransplant kinetics of Mac-2-binding protein glycosylation isomer levels in living donor liver transplantation
Its implication of posttransplant small-for-size syndrome, Translational Gastroenterology and Hepatology, 10.21037/tgh.2019.05.08, 4, May, 2019.01, Background: Wisteria floribunda agglutinin positive human Mac-2 binding protein glycosylation isomer (M2BPGi) has recently developed as a noninvasive serum marker of liver fibrosis. Liver transplant candidates usually have high serum levels of M2BPGi due to advanced cirrhosis. The aim of the present study was to elucidate the kinetics of serum M2BPGi after liver transplantation and the relationships between the level of M2BPGi and graft function. Methods: Fifteen recipients who underwent living donor liver transplantation (LDLT) between June 2015 and January 2016 and whose pretransplant, postoperative day (POD) 1, POD 3, and POD 7 sera were available for measuring M2BPGi were enrolled in this study. Small-for-size syndrome (SFSS) was defined as the presence of cholestasis (total bilirubin >10 mg/dL) on POD 7 and intractable ascites (>1 L/day on POD 14 or >500 ml/day on POD 28) without other specific causes. Results: The median of pretransplant M2BPGi was 9.75 cutoff index (C.O.I.) (range, 3.04-24.49). There was neither any correlation between pretransplant M2BPGi and Model for End-Stage Liver Disease scores (r=0.416, P=0.123) nor Child-Turcotte-Pugh scores (r=-0.221, P=0.428). The levels of M2BPGi dramatically decreased after LDLT (median; 1.48 on POD 1, 1.47 on POD 3, 1.49 on POD 7). However, serum levels of M2BPGi rose again on POD 7 in some recipients and all 4 recipients with serum levels of M2BPGi exceeding 3.00 C.O.I. succumbed to SFSS later. When the cutoff of M2BPGi on POD 7 for predicting SFSS was determined to be 3.06 according to its receiver operating characteristic curve, both the sensitivity and the specificity for predicting later SFSS were 100%. Conclusions: The levels of M2BPGi dramatically decreased after LDLT. A re-rise of M2BPGi predicted later development of SFSS..
2032. Kazuhito Sakata, Tomoharu Yoshizumi, Takuma Izumi, Masahiro Shimokawa, Shinji Itoh, Toru Ikegami, Noboru Harada, Takeo Toshima, Yohei Mano, Masaki Mori, The role of DNA repair glycosylase OGG1 in intrahepatic cholangiocarcinoma, Anticancer research, 10.21873/anticanres.13465, 39, 6, 3241-3248, 2019.01, Background/Aim: The effects of oxidative stress on various carcinomas were reported in previous studies, but those in intrahepatic cholangiocarcinoma (ICC) have not been fully elucidated. The purpose of this study was, thus, to reveal the effects of oxidative DNA damage and repair enzymes on ICC. Materials and Methods: The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-OHdG DNA glycosylase (OGG1) were immunohistochemically evaluated in specimens resected from 63 patients with ICC. Results: Low OGG1 expression was related to tumour depth T4 (p=0.04), venous invasion (p=0.0005), lymphatic vessel invasion (p=0.03), and perineural invasion (p=0.03). Compared to the high-OGG1-expression group, patients with low OGG1 expression had a significantly poorer prognosis (overall survival: p=0.04, recurrence-free survival: p=0.02). Unlike for OGG1, the expression levels of 8-OHdG showed no association with prognosis. Conclusion: Oxidative DNA damage and DNA repair enzymes may be closely related to ICC progression..
2033. Shohei Yoshiya, Ryosuke Minagawa, Keisuke Kamo, Meidai Kasai, Kenji Taketani, Takafumi Yukaya, Yasue Kimura, Tadashi Koga, Masanori Kai, Kiyoshi Kajiyama, Tomoharu Yoshizumi, Usability of Intraoperative Fluorescence Imaging with Indocyanine Green During Laparoscopic Cholecystectomy After Percutaneous Transhepatic Gallbladder Drainage, World journal of surgery, 10.1007/s00268-018-4760-1, 43, 1, 127-133, 2019.01, Background: Patients with persistent symptoms of acute cholecystitis for >72 h who cannot undergo urgent laparoscopic cholecystectomy (LC) often undergo percutaneous transhepatic gallbladder drainage (PTGBD) and delayed LC. However, intraoperative near-infrared fluorescence with indocyanine green (ICG) has recently become available in various surgical settings. Therefore, we evaluated the usability of intraoperative fluorescence imaging with ICG for LC after PTGBD in patients with acute cholecystitis. Methods: The preoperative and postoperative clinical characteristics of patients who underwent LC after PTGBD were retrospectively analyzed. Results: In total, 130 patients were reviewed. Intraoperative ICG fluorescence imaging was used in 39 (30.0%) patients, and none developed adverse reactions. Patients with ICG fluorescence imaging had a significantly shorter operative time (129 ± 46 vs. 150 ± 56 min, p = 0.0455), markedly lower conversion rate (2.6% vs. 22.0%, p = 0.0017), and lower proportion of subtotal cholecystectomy (0.0% vs. 6.6%, p = 0.0359) than patients without ICG fluorescence imaging. Independent risk factors for conversion to laparotomy during LC after PTGBD were the performance of PTGBD after 48 h from onset (OR 3.52; 95% CI 1.11–12.21; p = 0.0322), an unremoved PTGBD tube on LC (4.48, 1.46–15.00, p = 0.0084), and surgery without ICG (8.00, 1.28–159.47, p = 0.0231). Conclusion: Intraoperative ICG fluorescence imaging produced better surgical outcomes without any adverse reactions. Early performance of PTGBD and intraoperative ICG fluorescence imaging can reduce the surgical difficulties in LC after PTGBD for acute cholecystitis..
2034. Huanlin Wang, Tomoharu Yoshizumi, Shinji Itoh, Toru Ikegami, Noboru Harada, Yoshinao Oda, Masaki Mori, Retroperitoneal schwannoma preoperatively diagnosed as liver metastasis from colon cancer
A case report, International Journal of Surgery Case Reports, 10.1016/j.ijscr.2019.09.031, 64, 31-34, 2019, Background: Retroperitoneal schwannomas are rare. Case presentation: We here report a case of 64-year-old woman who was referred to her local hospital for abdominal pain and found to have a palpable tumor. Computed tomography (CT) and colonoscopy revealed a combination of liver and colon lesions and colon cancer with a large liver metastasis was suspected. After neoadjuvant chemotherapy had proved ineffective for her presumed liver metastasis, the patient was referred to our hospital where we performed a simultaneous right hemicolectomy and extended left hepatic lobectomy. The pathological diagnoses were a colonic adenocarcinoma and retroperitoneal schwannoma immediately adjacent to the liver. Conclusions: Although liver metastasis should be the first provisional diagnosis in patients with advanced colon cancer, retroperitoneal schwannoma should also be suspected in the differential diagnosis of possible liver lesions..
2035. Yoshizumi T, Itoh S, Imai D, Ikegami T, Ninomiya M, Iguchi T, Harimoto N, Takeishi K, Kimura Y, Uchiyama H, Soejima Y, Ikeda T, Kawanaka H, Shirabe K, Maehara Y., Impact of platelets and serotonin on liver regeneration after living donor hepatectomy. , Transplantlantation Proceedings, 10.1016/j.transproceed.2014.11.050., 47, 3, 685-685, 2015.04.
2036. Tomoharu Yoshizumi, Living Donor Liver Transplantation for Hepatocellular Carcinoma within Milan Criteria in the Present Era., Anticancer Res, 36, 1, 439-445, 2016.01.
2037. Tomoharu Yoshizumi, Impact of human T-cell leukemia virus type 1 on living donor liver transplantation: a multi-center study in Japan., J Hepatobiliary Pancreat Sci, 10.1002/jhbp.345, 2016.03.
2038. Tomoharu Yoshizumi, Decreased immunoglobulin G levels after living donor liver transplantation is a risk factor for bacterial infection and sepsis, Transplant Infectious Disease, 16, 2, 225-231, 2014.04.
2039. Tomoharu Yoshizumi, Re-evaluation of the predictive score for 6-month graft survival in living donor liver transplantation in the modern era., Liver Transplantation, 20, 3, 323-332, 2014.03.
2040. Tomoharu Yoshizumi, Skeletal muscle area correlates with body surface area in healthy adults, Hepatology Research, 44, 3, 313-318, 2014.03.
2041. 吉住 朋晴, Selection of a right posterior sector graft for living donor liver transplantation, Liver Transplantation, 20, 9, 1089-1096, 2014.09.
2042. Yoshizumi T, Ikegami T, Yoshiya S, Motomura T, Mano Y, Muto J, Ikeda T, Soejima Y, Shirabe K, Maehara Y, Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma., Hepatology Research, 10.1111, 43, 7, 709-716, 2013.07.
2043. Tomoharu Yoshizumi, ikegami Toru, Hideaki Uchiyama, Yo-ichi Yamashita, Harimoto Norifumi, Ken Shirabe, Yoshihiko Maehara, Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma., Transplantation Proceedings, 45, 11, 3310-3313, 2013.11.
2044. Yoshizumi T, Shirabe K, Taketomi A, Uchiyama H, Harada N, Ijichi H, Yoshimatsu M, Ikegami T, Soejima Y, Maehara Y, Risk factors that increase mortality after living donor liver , Transplantation., 93, 1, 938-938, 2012.01.
2045. Yoshizumi T, Shirabe K, Ikegami T, Kayashima H, Yamashita N, Morita K, Masuda T, Hashimoto N, Taketomi A, Soejima Y, Maehara Y., Impact of human T cell leukemia virus type 1 in living donor liver transplantation., American Journal of Transplantation, 10.1111/j.1600-6143.2012.04037.x. , 12, 6, 1479-85, 2012.06, Human T cell leukemia virus type 1 (HTLV-1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV-1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV-1 status in living donor liver transplantation (LDLT). Twenty-six of 329 (7.9%) HTLV-1 carriers underwent primary LDLT. One recipient negative for HTLV-1 before LDLT received a graft from an HTLV-1 positive donor. Eight donors were HTLV-1 positive. Twenty-seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV-1 positive donors and two from negative donors. The 1-, 3- and 5-year HTLV-1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score ≥ 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV-1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development..
2046. Yoshizumi T, Shirabe K, Soejima Y, Taketomi A, Yamashita N, Ikegami T, Uchiyama H, Kayashima H, Ninomiya M, Maehara Y., Living donor liver transplantation in patients older than 60 years., Transplantation, 90, 433-437, 2010.07.
2047. Yoshizumi T, Shirabe K, Soejima Y, Taketomi A, Ikegami T, Uchiyama H, Harada N, Ijichi H, Maehara Y. , Living Donor Liver Transplantation in Patients who have received pre-transplant treatment for hepatocellular carcinoma. , Transplantation, 91, e61-62, 2011.09.
2048. Yoshizumi T, Taketomi A, Soejima Y, Uchiyama H, Ikegami T, Harada N, Kayashima H, Yamashita Y, Shimada M, Maehara Y., Impact of donor age and recipient status on left lobe graft for living donor adult liver transplantation., Transplant International, 21, 81-88, 2008.01.
2049. Yoshizumi T, Taketomi A, Soejima Y, Ikegami T, Uchiyama H, Kayashima H, Harada N, Yamashita Y, Kawanaka H, Maehara Y., The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft. , Transplant International, 21, 833-842, 2008.04.
2050. Yoshizumi T, Shimada M, Soejima Y, Terashi T, Taketomi A, Maehara Y., Successful pylorus-preserving pancreaticoduodenectomy for a patient with carcinoma of the papilla Vater two years after living donor liver transplantation., Hepatogastroenterology, 54, 941-943, 2007.04.
2051. Yoshizumi T, Taketomi A, Uchiyama H, Harada N, Kayashima H, Yamashita Y, Soejima Y, Shimada M, Maehara Y. , Graft size, donor, age, and patient status are the indicators of early graft function after living donor liver transplantation. , Liver Transplantation, 14, 7, 1007-1013, 2008.07.
2052. Yoshizumi T, Yonemitsu Y, Ikeda Y, Kaneda Y, Yanaga K, Sugimachi K, Sueishi K , Tumor necrosis factor α antisense transfer remarkably improves hepatic graft
viability., Liver International, volume 26, pp 451-6, 2006.04.