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Tomoharu Yoshizumi Last modified date：2022.05.16

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


Papers
1. 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, 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..
2. 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, 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..
3. 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..
4. 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..
5. 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..
6. 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..
7. 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..
8. 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..
9. 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..
10. 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, 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..
11. 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, 2021.07.
12. 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.
13. 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..
14. 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, 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..
15. 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..
16. 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..
17. 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, 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..
18. 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..
19. 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..
20. 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..
21. 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.
22. 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..
23. 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..
24. 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..
25. 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..
26. 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, 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..
27. 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, 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..
28. 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..
29. 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, 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..
30. 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..
31. 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..
32. 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..
33. 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..
34. 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, 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..
35. 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..
36. 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, 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..
37. 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..
38. 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..
39. 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..
40. 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..
41. 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..
42. 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..
43. 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, 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..
44. 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..
45. 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..
46. 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..
47. 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..
48. 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..
49. 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..
50. 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.
51. 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.
52. 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..
53. 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..
54. 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..
55. 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..
56. 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.
57. 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, 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..
58. 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..
59. 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..
60. 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..
61. 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..
62. 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..
63. 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..
64. 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..
65. 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..
66. 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.
67. 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, 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..
68. 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..
69. 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..
70. 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..
71. 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.
72. 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..
73. 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..
74. 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..
75. 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..
76. 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..
77. 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..
78. 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..
79. 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..
80. 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..
81. 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..
82. 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..
83. 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..
84. Kazuki Takeishi, Toru Ikegami, Tomoharu Yoshizumi, Nao Fujimori, Masaki Mori, Reply, Liver Transplantation, 10.1002/lt.25725, 26, 5, 727-728, 2020.05.
85. 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..
86. 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..
87. 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.
88. 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..
89. 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..
90. 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..
91. 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..
92. 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..
93. 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..
94. 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.
95. 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.
96. 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..
97. 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..
98. 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..
99. 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.
100. 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..
101. 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..
102. 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..
103. 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.
104. 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..
105. 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..
106. 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.
107. 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..
108. 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..
109. 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..
110. 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.
111. 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..
112. 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.
113. 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..
114. 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..
115. 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..
116. 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..
117. 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..
118. 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..
119. 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..
120. 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..
121. 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..
122. 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.
123. 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..
124. 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..
125. 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..
126. 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..
127. 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..
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, 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..
129. 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..
130. 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..
131. 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..
132. 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..
133. 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..
134. 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..
135. 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..
136. 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..
137. 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..
138. 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..
139. 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..
140. 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.
141. 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.
142. 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.
143. 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..
144. 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..
145. 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..
146. 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..
147. 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..
148. 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.
149. 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..
150. 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.
151. 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.
152. 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.
153. 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..
154. 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.
155. 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.
156. 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, 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..
157. 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..
158. 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..
159. 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..
160. 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..
161. 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..
162. 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..
163. 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..
164. 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.
165. 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..
166. 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..
167. 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..
168. 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..
169. 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..
170. 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.
171. 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..
172. 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..
173. 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..
174. 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.
175. 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..
176. 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..
177. 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..
178. 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..
179. 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..
180. 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.
181. 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..
182. 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..
183. 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..
184. 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..
185. 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..
186. 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..
187. 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..
188. 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..
189. 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..
190. 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..
191. 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..
192. 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.
193. 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..
194. 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..
195. 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..
196. 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..
197. 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..
198. 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..
199. 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..
200. 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..
201. 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..
202. 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).
203. 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.
204. 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.
205. 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..
206. 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..
207. 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..
208. 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.
209. 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..
210. 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..
211. 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..
212. 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..
213. 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..
214. 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..
215. Frequency and Characteristics of Occult Hepatitis B Infection Among Hepatocellular Carcinoma Patients in Japan..
216. Frequency and Characteristics of Occult Hepatitis B Infection Among Hepatocellular Carcinoma Patients in Japan..
217. 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.
218. 【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.
219. 【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.
220. 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.
221. 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..
222. 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..
223. 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..
224. 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..
225. 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..
226. 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.
227. 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..
228. 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)..
229. 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..
230. 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..
231. 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..
232. 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..
233. 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..
234. 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..
235. 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..
236. 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..
237. 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..
238. 【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.
239. 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.
240. 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..
241. 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..
242. 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..
243. 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..
244. 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..
245. 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..
246. 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.
247. 【肝癌-診断・治療の最新知見-】 肝癌の治療 肝移植.
248. 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..
249. 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.
250. 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.
251. 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..
252. 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..
253. 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.
254. 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.
255. 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..
256. 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..
257. 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..
258. 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..
259. 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..
260. 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..
261. 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..
262. 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..
263. 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..
264. 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..
265. 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..
266. 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..
267. 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..
268. 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..
269. 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..
270. 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..
271. 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..
272. 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..
273. 【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.
274. 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。.
275. 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..
276. 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..
277. 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.
278. 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.
279. 【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.
280. 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.
281. 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..
282. 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..
283. 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.
284. 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.
285. 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..
286. 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.
287. 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..
288. 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..
289. 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..
290. 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..
291. 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..
292. 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..
293. 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.
294. 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..
295. 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..
296. 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..
297. 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..
298. 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..
299. 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..
300. 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..
301. 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..
302. 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..
303. 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..
304. 脳死肝移植へのBrigeとしてのHigh-Flow CHDFの有効性.
305. 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..
306. 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..
307. 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..
308. 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..
309. 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..
310. 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..
311. 【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.
312. 【激変する肝疾患診療の現状】 肝移植の現況と問題点.
313. 【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.
314. 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).
315. 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.
316. 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..
317. 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..
318. 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..
319. 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..
320. 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..
321. 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..
322. 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..
323. 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.
324. 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.
325. 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.
326. 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..
327. 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..
328. 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..
329. 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..
330. 【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).
331. 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..
332. 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..
333. 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..
334. 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..
335. 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..
336. 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..
337. 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..
338. 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..
339. 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..
340. 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..
341. 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..
342. 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.
343. 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..
344. 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..
345. 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..
346. 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.
347. 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..
348. 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..
349. 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..
350. Takeshi Kurihara, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Reply, Liver Transplantation, 10.1002/lt.24648, 22, 12, 2016.12.
351. 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..
352. 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..
353. 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..
354. 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..
355. 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..
356. 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..
357. 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..
358. 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..
359. 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..
360. 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..
361. 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..
362. 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.
363. 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..
364. 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..
365. 【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.
366. 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..
367. 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..
368. 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.
369. 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..
370. 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..
371. 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.
372. 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。.
373. 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..
374. 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..
375. 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..
376. 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..
377. 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..
378. 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.
379. 【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).
380. 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.
381. 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.
382. 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.
383. 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.
384. 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.
385. 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..
386. 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..
387. 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..
388. 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..
389. 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.
390. 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..
391. 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..
392. 【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.
393. 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.
394. 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.
395. 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.
396. 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..
397. 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..
398. 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..
399. 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..
400. ICG蛍光法による術中肝静脈還流域ナビゲーション.
401. 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, 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).
402. 切除不能膵癌に対するFOLFORINOX療法の有効性と安全性の検討.
403. 地方中核都市における我々のリクルート戦略.
404. 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.
405. 成人生体肝移植における長期予後因子の検討.
406. 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.
407. 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.
408. 生体肝移植におけるERAS概念を取り入れた術後管理.
409. 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.
410. 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.
411. 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.
412. 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.
413. 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.
414. 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.
415. 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.
416. 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.
417. 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..
418. 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..
419. 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..
420. 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..
421. 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.
422. 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.
423. 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.
424. 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.
425. サルコペニアと外科.
426. 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.
427. 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.
428. 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.
429. 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.
430. 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.
431. 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).
432. 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..
433. 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..
434. 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..
435. 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..
436. [CURRENT STATUS OF HEPATOBILIARY PANCREATIC SURGERY FOR ELDERLY PATIENTS]..
437. 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.
438. 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..
439. 【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).
440. 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.
441. 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。.
442. 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。.
443. 肝細胞癌切除患者におけるInflammation-based prognostic scoreと骨格筋量の相関.
444. 食道静脈瘤合併肝細胞癌の手術成績の検討.
445. 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..
446. 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.
447. 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..
448. 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..
449. 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.
450. 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..
451. 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..
452. 【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).
453. 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.
454. 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.
455. 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。.
456. 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.
457. 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.
458. 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.
459. 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.
460. 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.
461. 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.
462. 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.
463. 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.
464. 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.
465. 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.
466. 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.
467. 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..
468. 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..
469. 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..
470. 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..
471. 【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.
472. 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.
473. 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..
474. 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..
475. 【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).
476. 【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.
477. Tomoharu Yoshizumi, Living Donor Liver Transplantation for Hepatocellular Carcinoma within Milan Criteria in the Present Era., Anticancer Res, 36, 1, 439-445, 2016.01.
478. 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..
479. 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..
480. 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..
481. 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..
482. 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..
483. 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..
484. 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..
485. 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..
486. 【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).
487. 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..
488. 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..
489. 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..
490. 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..
491. 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..
492. 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..
493. 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..
494. 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..
495. 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..
496. 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.
497. 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..
498. 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..
499. 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..
500. 【肝炎ウイルスA to E】 B型肝炎 肝移植後のHBV再感染予防.
501. 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).
502. 肝細胞癌に対する腹腔鏡下肝切除術の治療成績.
503. 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.
504. 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.
505. 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.
506. 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..
507. 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.
508. 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/)..
509. 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.
510. 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.
511. 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.
512. 【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).
513. 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.
514. 消化器外科セミナー サルコペニアの概念とその対策.
515. 生体肝移植後E型肝炎持続感染が確認された1例.
516. C型肝炎に対する肝移植 本邦の経験と今後の潮流.
517. HBV関連生体肝移植後のHBV再発因子の解析.
518. 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.
519. 当科における生体肝移植における胆管胆管吻合の成績.
520. 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.
521. 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.
522. 生体肝移植後SSIの発症危険因子と予後の検討.
523. 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.
524. 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.
525. 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.
526. 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.
527. 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.
528. 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.
529. 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.
530. 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.
531. 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..
532. 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.
533. 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.
534. 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.
535. 当教室における血液型不適合生体肝移植の長期成績.
536. 成人生体肝移植後における長期予後因子の検討.
537. 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.
538. 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.
539. 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.
540. 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..
541. 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.
542. 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.
543. 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..
544. 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..
545. 【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.
546. 再発肝細胞癌に対する肝移植の治療成績.
547. 小児肝移植におけるウイルス感染の検討.
548. 当科における肝移植後良性一過性高ALP血症5例の検討.
549. 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.
550. 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.
551. 肝静脈波形からみたB-RTOの適応について.
552. 腹腔鏡下または小切開によるドナー肝切除の是非.
553. 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.
554. 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.
555. 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..
556. 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..
557. 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..
558. 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..
559. 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.
560. 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..
561. 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..
562. 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.
563. 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..
564. 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..
565. 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.
566. 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.
567. 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.
568. 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.
569. 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.
570. 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.
571. 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.
572. 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.
573. 膵癌に対するFOLFIRINOXの治療成績と安全性に関する検討.
574. 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.
575. 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..
576. 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..
577. 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..
578. 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.
579. 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..
580. 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..
581. 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.
582. 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..
583. 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).
584. 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.
585. 肝硬変合併肝細胞癌に対する腹腔鏡下肝切除の意義.
586. 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.
587. 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.
588. 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.
589. 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..
590. 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..
591. 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..
592. 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..
593. 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..
594. 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..
595. 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..
596. 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..
597. 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.
598. 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.
599. 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..
600. 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..
601. 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..
602. 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..
603. 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..
604. 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.
605. 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..
606. 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..
607. 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..
608. 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..
609. 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.
610. 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..
611. 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.
612. 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.
613. 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.
614. 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.
615. 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.
616. 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.
617. 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.
618. 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.
619. 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.
620. 肝胆膵 肝臓の再生研究におけるオートファジーの意義.
621. 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.
622. 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.
623. 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.
624. 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.
625. 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.
626. 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..
627. 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.
628. 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..
629. 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。.
630. 【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.
631. 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..
632. 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..
633. 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.
634. 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..
635. 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..
636. 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..
637. 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..
638. 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.
639. 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.
640. 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.
641. 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..
642. 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).
643. 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..
644. 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..
645. 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..
646. 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..
647. 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..
648. 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..
649. 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..
650. 【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).
651. 【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.
652. 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).
653. 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..
654. 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..
655. 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..
656. 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..
657. 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..
658. 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..
659. 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..
660. 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.
661. 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.
662. 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.
663. 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.
664. 【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.
665. 【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).
666. 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.
667. 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.
668. 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.
669. 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.
670. 大腸癌肝転移に対する腹腔鏡下肝切除術の有用性.
671. 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.
672. 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.
673. 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.
674. 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.
675. 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.
676. 吉住 朋晴, Selection of a right posterior sector graft for living donor liver transplantation, Liver Transplantation, 20, 9, 1089-1096, 2014.09.
677. 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..
678. 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..
679. 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..
680. 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.
681. 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..
682. 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..
683. 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.
684. 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..
685. 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..
686. 【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).
687. 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.
688. 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..
689. 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..
690. 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..
691. 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..
692. 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..
693. 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.
694. 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.
695. 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..
696. 小児肝移植におけるサイトメガロウィルス感染.
697. 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.
698. 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.
699. 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).
700. 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.
701. 胆道癌悪性度評価におけるFDG-PET/CTの役割.
702. 脂肪肝ラット温阻血再灌流傷害に関する基礎的研究.
703. 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.
704. 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..
705. 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..
706. 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..
707. 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..
708. 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.
709. 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..
710. 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..
711. 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.
712. 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.
713. 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.
714. 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.
715. 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.
716. 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.
717. 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.
718. 脂肪肝ラット温阻血再灌流傷害に関する基礎的研究.
719. 高齢者に対する生体肝移植の適応と成績.
720. 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..
721. 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..
722. 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..
723. 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..
724. 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..
725. 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..
726. 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..
727. 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..
728. 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..
729. 固形癌におけるProgrammed cell Death 1 Ligand 1(PDL1)発現の生物学的意義.
730. 新開発-Silicone Jacket IrrigatorによるAuto irrigation Modern Bipolar Systemを用いた肝切除術.
731. 生体肝移植ドナー501例から学んだ安全な定型的肝切除.
732. 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.
733. 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.
734. 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.
735. 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.
736. 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.
737. 進行肝癌における炎症マーカーの意義.
738. 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..
739. 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..
740. 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.
741. 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.
742. 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..
743. 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..
744. 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..
745.