Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Tomoharu Yoshizumi Last modified date:2021.05.11

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


Papers
1. 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.
2. 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, 2020.06.
3. 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..
4. 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, 2020.06, 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..
5. 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..
6. 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..
7. Kazuki Takeishi, Toru Ikegami, Tomoharu Yoshizumi, Nao Fujimori, Masaki Mori, Reply, Liver Transplantation, 10.1002/lt.25725, 26, 5, 727-728, 2020.05.
8. 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..
9. 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..
10. 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, 2020.05, 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..
11. 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.
12. 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..
13. 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..
14. 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..
15. 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..
16. 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..
17. 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..
18. 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.
19. 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.
20. 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..
21. 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..
22. 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, 2020.04, 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..
23. 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..
24. 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.
25. 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..
26. 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..
27. 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..
28. 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, 2020.04, 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..
29. 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.
30. 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..
31. 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..
32. 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.
33. 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..
34. 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..
35. 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..
36. 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.
37. 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, 2020.02, BACKGROUND: 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. METHOD: 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 (sPD-L1). RESULTS: Compared with PD-L1-negative HCC patients (n=311), PD-L1-positive HCC patients (n=76) showed significantly worse overall survival (multivariate HR, 2.502; 95% CI, 1.716-3.649; P<0.0001). The presence of tumor-infiltrating CD8-positive T cells was significantly correlated with longer overall survival (multivariate HR, 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 overall survival (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 was significantly higher in PD-L1 positive group than in PD-L1 negative group (p=0.0158). CONCLUSIONS: Our large cohort study showed that PD-L1 expression in cancer cells was associated with a poor clinical outcome and vascular formation in HCC patients. Additionally, 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..
38. 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, 2020.02, 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..
39. 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..
40. 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.
41. 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..
42. 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..
43. 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..
44. 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..
45. 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..
46. 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..
47. 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..
48. 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..
49. 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..
50. 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.
51. 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..
52. 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..
53. 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..
54. 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..
55. 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..
56. 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..
57. 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..
58. 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..
59. 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..
60. 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..
61. 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..
62. 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..
63. 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..
64. 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..
65. 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..
66. 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..
67. 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..
68. 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..
69. 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..
70. 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..
71. 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..
72. 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..
73. 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..
74. 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.
75. 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.
76. 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.
77. 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..
78. 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.
79. 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.
80. 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..
81. 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..
82. 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..
83. 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..
84. 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..
85. 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..
86. 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..
87. 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..
88. 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.
89. 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..
90. 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..
91. 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..
92. 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..
93. 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..
94. 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.
95. 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..
96. 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..
97. 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..
98. 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.
99. 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..
100. 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..
101. 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..
102. 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..
103. 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..
104. 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.
105. 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..
106. 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..
107. 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..
108. 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..
109. 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..
110. 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..
111. 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..
112. 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..
113. 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..
114. 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..
115. 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..
116. 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..
117. 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..
118. 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..
119. 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..
120. 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..
121. 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..
122. 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..
123. 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..
124. 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..
125. 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..
126. 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..
127. 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..
128. 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.
129. 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..
130. 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..
131. 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..
132. 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..
133. 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..
134. 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..
135. Frequency and Characteristics of Occult Hepatitis B Infection Among Hepatocellular Carcinoma Patients in Japan..
136. Frequency and Characteristics of Occult Hepatitis B Infection Among Hepatocellular Carcinoma Patients in Japan..
137. 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..
138. 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..
139. 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..
140. 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..
141. 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..
142. 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..
143. 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)..
144. 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..
145. 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..
146. 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..
147. 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..
148. 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..
149. 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..
150. 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..
151. 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..
152. 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.
153. 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..
154. 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..
155. 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..
156. 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..
157. 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..
158. 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..
159. 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..
160. 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.
161. 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.
162. 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..
163. 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..
164. 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..
165. 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..
166. 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..
167. 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..
168. 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..
169. 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..
170. 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..
171. 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..
172. 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..
173. 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..
174. 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..
175. 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..
176. 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..
177. 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..
178. 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..
179. 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..
180. 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..
181. 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..
182. 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..
183. 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..
184. 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.
185. 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..
186. 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..
187. 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.
188. 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.
189. 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..
190. 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..
191. 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..
192. 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..
193. 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..
194. 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..
195. 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..
196. 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..
197. 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..
198. 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..
199. 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..
200. 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..
201. 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..
202. 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..
203. 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..
204. 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..
205. 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..
206. 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..
207. 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..
208. 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..
209. 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..
210. 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..
211. 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..
212. 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..
213. 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..
214. 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..
215. 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..
216. 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..
217. 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..
218. 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..
219. 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.
220. 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.
221. 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.
222. 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..
223. 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..
224. 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..
225. 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..
226. 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..
227. 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..
228. 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..
229. 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..
230. 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..
231. 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..
232. 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..
233. 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..
234. 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..
235. 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..
236. 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..
237. 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.
238. 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..
239. 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..
240. 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..
241. 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.
242. 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..
243. 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..
244. 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..
245. Takeshi Kurihara, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Reply, Liver Transplantation, 10.1002/lt.24648, 22, 12, 2016.12.
246. 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..
247. 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..
248. 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..
249. 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..
250. 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..
251. 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..
252. 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..
253. 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..
254. 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..
255. 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..
256. 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..
257. 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.
258. 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..
259. 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..
260. 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..
261. 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..
262. 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.
263. 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..
264. 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..
265. 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..
266. 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..
267. 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..
268. 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..
269. 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..
270. 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..
271. 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..
272. 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..
273. 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..
274. 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..
275. 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..
276. 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..
277. 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..
278. 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..
279. 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..
280. 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..
281. 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..
282. 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..
283. 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..
284. 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..
285. 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..
286. [CURRENT STATUS OF HEPATOBILIARY PANCREATIC SURGERY FOR ELDERLY PATIENTS]..
287. 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..
288. 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.
289. 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..
290. 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..
291. 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.
292. 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..
293. 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.
294. 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..
295. 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..
296. 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..
297. 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..
298. 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..
299. Tomoharu Yoshizumi, Living Donor Liver Transplantation for Hepatocellular Carcinoma within Milan Criteria in the Present Era., Anticancer Res, 36, 1, 439-445, 2016.01.
300. 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..
301. 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..
302. 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..
303. 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..
304. 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..
305. 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..
306. 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..
307. 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..
308. 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..
309. 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..
310. 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..
311. 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..
312. 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..
313. 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..
314. 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..
315. 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.
316. 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/)..
317. 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.
318. 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.
319. 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..
320. 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.
321. 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..
322. 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.
323. 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.
324. 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..
325. 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..
326. 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..
327. 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..
328. 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.
329. 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..
330. 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..
331. 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..
332. 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..
333. 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..
334. 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..
335. 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..
336. 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..
337. 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..
338. 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..
339. 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..
340. 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.
341. 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.
342. 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..
343. 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..
344. 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..
345. 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..
346. 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..
347. 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.
348. 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..
349. 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..
350. 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..
351. 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..
352. 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..
353. 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..
354. 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..
355. 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.
356. 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..
357. 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..
358. 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..
359. 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..
360. 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.
361. 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.
362. 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.
363. 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..
364. 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..
365. 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..
366. 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..
367. 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..
368. 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..
369. 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..
370. 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..
371. 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..
372. 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..
373. 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..
374. 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..
375. 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..
376. 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..
377. 吉住 朋晴, Selection of a right posterior sector graft for living donor liver transplantation, Liver Transplantation, 20, 9, 1089-1096, 2014.09.
378. 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..
379. 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..
380. 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..
381. 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.
382. 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..
383. 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..
384. 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.
385. 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..
386. 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..
387. 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..
388. 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..
389. 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..
390. 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..
391. 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..
392. 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..
393. 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..
394. 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..
395. 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..
396. 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..
397. 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..
398. 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..
399. 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..
400. 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..
401. 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..
402. 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..
403. 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..
404. 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..
405. 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.
406. 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.
407. 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..
408. 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..
409. 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..
410. Toru Ikegami, Tomoharu Yoshizumi, Yo-ichi Yamashita, Noboru Harada, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Obstructing Spontaneous Major Shunt Vessels Is or Might Not Be Mandatory in Living Donor Liver Transplantation: The Authors' Reply, TRANSPLANTATION, 10.1097/TP.0000000000000096, 97, 9, E53-E53, 2014.05.
411. Toru Ikegami, Tomoharu Yoshizumi, Yo-Ichi Yamashita, Noboru Harada, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Obstructing spontaneous major shunt vessels is or might not be mandatory in living donor liver transplantation: the authors' reply., Transplantation, 10.1097/TP.0000000000000096, 97, 9, e53, 2014.05.
412. Tomoharu Yoshizumi, Decreased immunoglobulin G levels after living donor liver transplantation is a risk factor for bacterial infection and sepsis, Transplant Infectious Disease, 16, 2, 225-231, 2014.04.
413. Yoshihiro Nagao, Tomohiko Akahoshi, Hideo Uehara, Naotaka Hashimoto, Nao Kinjo, Hirofumi Kawanaka, Morimasa Tomikawa, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuuji Soejima, Ken Shirabe, Yoshihiko Maehara, Balloon-occluded retrograde transvenous obliteration is feasible for prolonged portosystemic shunts after living donor liver transplantation, Surgery today, 10.1007/s00595-013-0535-3, 44, 4, 633-639, 2014.04, Purposes: The purpose of our study was to evaluate the efficacy of balloon-occluded retrograde transvenous obliteration (B-RTO) in patients after living donor liver transplantation (LDLT). Methods: Five patients with gastric varices (GVx) and/or liver dysfunction who were treated with B-RTO from January 2001 to December 2007 were enrolled in this study (GVx, n = 2; liver dysfunction, n = 1; both, n = 2). The eradication rate of the GVx, portal vein hemodynamics and improvement of liver function were evaluated. Results: B-RTO was performed successfully, and the GVx disappeared or decreased markedly in all patients. Recurrence of GVx was not observed during the follow-up. Significantly increased portal vein inflow and improved liver function were observed in all patients. Conclusions: B-RTO may be an effective treatment for patients after LDLT to prevent bleeding from GVx or to modulate portal vein inflow that is reduced by prolonged large portosystemic shunts..
414. Toru Ikegami, Yuki Bekki, Daisuke Imai, Tomoharu Yoshizumi, Mizuki Ninomiya, Hiromitsu Hayashi, Yo Ichi Yamashita, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Clinical outcomes of living donor liver transplantation for patients 65 years old or older with preserved performance status, Liver Transplantation, 10.1002/lt.23825, 20, 4, 408-415, 2014.04, The purpose of this study was to determine the outcomes of living donor liver transplantation (LDLT) for elderly recipients. We reviewed 411 adult-to-adult LDLT cases, including 46 recipients who were 65 years old or older and 365 recipients who were less than 65 years old. The elderly group had a higher proportion of females (P=0.04) and a smaller body surface area (P<0.001) and more frequently underwent transplantation because of hepatitis C (P<0.001) or hepatocellular carcinoma (P<0.001). Elderly patients had less advanced liver disease with lower Model for End-Stage Liver Disease (MELD) scores (P=0.02) and preserved health without the need for prolonged hospitalization (P<0.01). The transplanted graft volume/standard liver volume ratios were similar for the 2 groups (P=0.22). The elderly group had fewer episodes of acute rejection (P=0.03) but had more neuropsychiatric complications (P=0.01). The 5- and 10-year graft survival rates were comparable for the elderly group (89.8% and 77.8%, respectively) and the younger group (79.4% and 72.9%, respectively; P=0.21). Seven recipients were 70 years old or older, and they had a mean MELD score of 15.6±5.2; 6 of these patients were treated as outpatients before LDLT. All were alive after LDLT and showed good compliance with medical management with a mean follow-up of 5.7±3.0 years. In conclusion, LDLT can be safely performed and has acceptable long-term outcomes for low-risk elderly recipients with preserved performance status..
415. Kensuke Kudou, Mizuki Ninomiya, Tomohiro Iguchi, Norifumi Harimoto, Shinji Itoh, Noboru Harada, Kazuki Takeishi, Yo Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Cystic liver infection after living donor liver transplantation
A case report, Case Reports in Gastroenterology, 10.1159/000363375, 8, 2, 169-174, 2014.04, There are no reports of cystic liver infection after liver transplantation. Herein, we report a rare case of cystic liver graft infection after living donor liver transplantation (LDLT). The patient was a 24-year-old man with primary sclerosing cholangitis who underwent right lobe graft LDLT. Preoperative abdominal computed tomography (CT) revealed a liver cyst at segment 8 of the donor liver. Biliary reconstruction was performed with hepaticojejunostomy. The postoperative course was uneventful until the patient developed a high fever and abdominal pain 15 months after LDLT. Abdominal contrast CT revealed abscess formation. Percutaneous drainage of the cyst was performed and purulent liquid was drained. The fever gradually subsided after treatment. On follow-up CT, the size of the infected liver cyst was decreased. Clinicians should be aware of the potential for cystic liver infection when using grafts with liver cysts, particularly when biliary reconstruction is performed with hepaticojejunostomy..
416. T. Yoshizumi, K. Shirabe, T. Ikegami, N. Yamashita, Y. Mano, S. Yoshiya, R. Matono, N. Harimoto, H. Uchiyama, T. Toshima, Y. Maehara, Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis, Transplant Infectious Disease, 10.1111/tid.12188, 16, 2, 225-231, 2014.04, Background: Several studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT). Methods: Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3 months after LDLT were analyzed. Results: Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively. Conclusions: Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis..
417. Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Frequent plasma cell hepatitis during telaprevir-based triple therapy for hepatitis C after liver transplantation, Journal of Hepatology, 10.1016/j.jhep.2013.10.037, 60, 4, 894-896, 2014.04.
418. Toshiro Masuda, Ken Shirabe, Toru Ikegami, Norifumi Harimoto, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Tetsuo Ikeda, Hideo Baba, Yoshihiko Maehara, Sarcopenia is a prognostic factor in living donor liver transplantation, Liver Transplantation, 10.1002/lt.23811, 20, 4, 401-407, 2014.04, The aims of this study were to investigate sarcopenia as a novel predictor of mortality and sepsis after living donor liver transplantation (LDLT) and to evaluate the effects of early enteral nutrition on patients with sarcopenia. Two hundred four patients undergoing preoperative computed tomography within the month before LDLT were retrospectively evaluated. The lengths of the major and minor axes of the psoas muscle were simply measured at the caudal end of the third lumbar vertebra, and the area of the psoas muscle was calculated. A psoas muscle area lower than the 5th percentile for healthy donors of each sex was defined as sarcopenia. Ninety-six of the 204 patients (47.1%), including 58.3% (60/103) of the male patients and 35.6% (36/101) of the female patients, were diagnosed with sarcopenia. Sarcopenia was independently and significantly associated with overall survival: there was an approximately 2-fold higher risk of death for patients with sarcopenia versus patients without sarcopenia (hazard ratio = 2.06, P = 0.047). Sarcopenia was an independent predictor of postoperative sepsis (hazard ratio = 5.31, P = 0.009). Other independent predictors were a younger recipient age (P < 0.001) and a higher body mass index (P = 0.02). Early enteral nutrition within the first 48 hours after LDLT was performed for 24.2% in 2003-2007 and for 100% in 2008-2011, and the incidence of postoperative sepsis for patients with sarcopenia (n = 96) was 28.2% (11/39) in 2003-2007 and 10.5% (6/57) in 2008-2011 (P = 0.03). In conclusion, sarcopenia is an independent predictor of mortality and sepsis after LDLT. The incidence of postoperative sepsis was reduced even in patients with sarcopenia after the routine application of early enteral nutrition. Liver Transpl 20:401-407, 2014..
419. Daisuke Matsuda, Takeo Toshima, Toru Ikegami, Norifumi Harimoto, Yo Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Thrombotic microangiopathy caused by severe graft dysfunction after living donor liver transplantation
Report of a case, Clinical Journal of Gastroenterology, 10.1007/s12328-013-0446-2, 7, 2, 159-163, 2014.04, Thrombotic microangiopathy (TMA) is a life-threatening complication after transplantation including liver transplantation, and its typical clinical picture is characterized by hemolytic anemia, thrombocytopenia, renal dysfunction, neurological abnormalities, and fever. We report the case of a 56-year-old female with end-stage liver disease who underwent living donor liver transplantation (LDLT), and whose postoperative course was characterized by renal failure and progressive hyperbilirubinemia. Two weeks after LDLT, she started to show progressive thrombocytopenia, anemia, oliguria, and encephalopathy. From these clinical manifestations, she was diagnosed as having TMA and underwent plasma exchanges with continuous hemodialysis under temporary holding calcineurin inhibitors. The patient promptly responded to the treatment, with improved hematological, hepatic, and renal conditions, and was discharged from hospital a month later in a stable condition. We describe this case of TMA after LDLT with poor graft function and extensively review the disease in liver transplant recipients..
420. Toru Ikegami, Yuki Bekki, Daisuke Imai, Tomoharu Yoshizumi, Mizuki Ninomiya, Hiromitsu Hayashi, Yo-Ichi Yamashita, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Clinical outcomes of living donor liver transplantation for patients 65 years old or older with preserved performance status., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23825, 20, 4, 408-15, 2014.04, The purpose of this study was to determine the outcomes of living donor liver transplantation (LDLT) for elderly recipients. We reviewed 411 adult-to-adult LDLT cases, including 46 recipients who were 65 years old or older and 365 recipients who were less than 65 years old. The elderly group had a higher proportion of females (P = 0.04) and a smaller body surface area (P < 0.001) and more frequently underwent transplantation because of hepatitis C (P < 0.001) or hepatocellular carcinoma (P < 0.001). Elderly patients had less advanced liver disease with lower Model for End-Stage Liver Disease (MELD) scores (P = 0.02) and preserved health without the need for prolonged hospitalization (P < 0.01). The transplanted graft volume/standard liver volume ratios were similar for the 2 groups (P = 0.22). The elderly group had fewer episodes of acute rejection (P = 0.03) but had more neuropsychiatric complications (P = 0.01). The 5- and 10-year graft survival rates were comparable for the elderly group (89.8% and 77.8%, respectively) and the younger group (79.4% and 72.9%, respectively; P = 0.21). Seven recipients were 70 years old or older, and they had a mean MELD score of 15.6 ± 5.2; 6 of these patients were treated as outpatients before LDLT. All were alive after LDLT and showed good compliance with medical management with a mean follow-up of 5.7 ± 3.0 years. In conclusion, LDLT can be safely performed and has acceptable long-term outcomes for low-risk elderly recipients with preserved performance status..
421. T. Yoshizumi, K. Shirabe, T. Ikegami, N. Yamashita, Y. Mano, S. Yoshiya, R. Matono, N. Harimoto, H. Uchiyama, T. Toshima, Y. Maehara, Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis, TRANSPLANT INFECTIOUS DISEASE, 10.1111/tid.12188, 16, 2, 225-231, 2014.04, BackgroundSeveral studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT).
MethodsBlood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650mg/dL within 7days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3months after LDLT were analyzed.
ResultsFifty (28.2%) recipients experienced bacterial infection within 3months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15mmHg were independent risk factors for developing bacterial infection within 3months of LDLT (P < 0.0001 P=0.0008, and P=0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3months. Hypogammaglobulinemia, operative time >14h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P=0.009, P=0.001, P=0.003, and P=0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively.
ConclusionsHypogammaglobulinemia within 7days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis..
422. Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Frequent plasma cell hepatitis during telaprevir-based triple therapy for hepatitis C after liver transplantation., Journal of hepatology, 10.1016/j.jhep.2013.10.037, 60, 4, 894-6, 2014.04.
423. Toru Ikegami, Huanlin Wang, Tomoharu Yoshizumi, Takeo Toshima, Shinichi Aishima, Takasuke Fukuhara, Norihiro Furusyo, Kazuhiro Kotoh, Shinji Shimoda, Ken Shirabe, Yoshihiko Maehara, Strategies to treat interferon-induced graft dysfunction after living donor liver transplantation for hepatitis C., Hepatology international, 10.1007/s12072-013-9496-2, 8, 2, 285-92, 2014.04, PURPOSE: Interferon-induced graft dysfunction (IGD) is a poorly defined, unrecognized, but potentially serious condition for patients receiving antiviral drugs after liver transplantation for hepatitis C. METHODS: We evaluated the characteristics of 80 patients who received pegylated interferon-based antiviral treatment for hepatitis C after living donor liver transplantation (LDLT). RESULTS: Eight patients experienced IGD either during (n = 6) or after completing (n = 2) antiviral treatment. Pathological diagnosis included acute cellular rejection (ACR, n = 1), plasma cell hepatitis (PCH, n = 2), PCH plus ACR (n = 3), and chronic rejection (CR, n = 2). One patient with CR initially presented with PCH plus ACR and the other presented with ACR; both had apparent cholestasis. The six patients with ACR or PCH without cholestasis were successfully treated by discontinuing antiviral treatment and increasing immunosuppression, including steroids. By contrast, both of the patients with CR and cholestasis experienced graft loss, despite aggressive treatment. Univariate analysis showed that pegylated interferon-α2a-based treatment (75 vs. 26.4 %, p < 0.01) was the only significant factor for IGD, and was associated with decreased 5-year graft survival (93.4 vs. 71.4 %, p = 0.04). CONCLUSIONS: IGD is a serious condition during or even after antiviral treatment for hepatitis C after LDLT. Early recognition, diagnosis, discontinuation of interferon, and introduction of steroid-based treatment may help to save the graft..
424. Daisuke Matsuda, Takeo Toshima, Toru Ikegami, Norifumi Harimoto, Yo-Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Thrombotic microangiopathy caused by severe graft dysfunction after living donor liver transplantation: report of a case., Clinical journal of gastroenterology, 10.1007/s12328-013-0446-2, 7, 2, 159-63, 2014.04, Thrombotic microangiopathy (TMA) is a life-threatening complication after transplantation including liver transplantation, and its typical clinical picture is characterized by hemolytic anemia, thrombocytopenia, renal dysfunction, neurological abnormalities, and fever. We report the case of a 56-year-old female with end-stage liver disease who underwent living donor liver transplantation (LDLT), and whose postoperative course was characterized by renal failure and progressive hyperbilirubinemia. Two weeks after LDLT, she started to show progressive thrombocytopenia, anemia, oliguria, and encephalopathy. From these clinical manifestations, she was diagnosed as having TMA and underwent plasma exchanges with continuous hemodialysis under temporary holding calcineurin inhibitors. The patient promptly responded to the treatment, with improved hematological, hepatic, and renal conditions, and was discharged from hospital a month later in a stable condition. We describe this case of TMA after LDLT with poor graft function and extensively review the disease in liver transplant recipients..
425. Tomoharu Yoshizumi, Skeletal muscle area correlates with body surface area in healthy adults, Hepatology Research, 44, 3, 313-318, 2014.03.
426. Tomoharu Yoshizumi, Re-evaluation of the predictive score for 6-month graft survival in living donor liver transplantation in the modern era., Liver Transplantation, 20, 3, 323-332, 2014.03.
427. Tomoharu Yoshizumi, Toru Ikegami, Yuki Bekki, Mizuki Ninomiya, Hideaki Uchiyama, Tomohiro Iguchi, Yo Ichi Yamashita, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Re-evaluation of the predictive score for 6-month graft survival in living donor liver transplantation in the modern era, Liver Transplantation, 10.1002/lt.23804, 20, 3, 323-332, 2014.03, The limitations of donor age, graft size, and the Model for End-Stage Liver Disease (MELD) score have not been apparent in living donor liver transplantation (LDLT). Our team developed a formula for predicting graft survival after LDLT; the formula includes the graft weight, donor age, MELD score, and portosystemic shunt status. The aims of this study were to re-evaluate the reliability of our formula and to assess whether our modified treatment strategy has improved 6-month graft survival. Two hundred seventeen patients were allocated into 2 groups: patients with predictive scores ≥ 1.30 (n = 162) and patients with predictive scores < 1.30 (n = 55). The latter group was also divided into subgroups of patients with scores of 1.15 to 1.30 (n = 37) and patients with scores < 1.15 (n = 18). Survival rates for patients with scores < 1.30 were significantly worse than rates for patients with scores ≥ 1.30 (P = 0.006). Survival rates for patients with scores < 1.15 were significantly worse than rates for patients with scores of 1.15 to <1.30 (P < 0.001). A multivariate analysis showed that a predictive score < 1.15 (odds ratio = 7.87, P = 0.006) and a body mass index ≥ 30 kg/m 2 (odds ratio = 13.3, P < 0.001) were independent risk factors for 6-month graft mortality. In conclusion, predictive scores reliably predict 6-month graft survival and could allow a widening of the safe ranges for donor ages and graft sizes..
428. Tomoharu Yoshizumi, Ken Shirabe, Hidekazu Nakagawara, Toru Ikegami, Norifumi Harimoto, Takeo Toshima, Yo ichi Yamashita, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara, Skeletal muscle area correlates with body surface area in healthy adults, Hepatology Research, 10.1111/hepr.12119, 44, 3, 313-318, 2014.03, Aim: Depletion of skeletal muscle mass (sarcopenia) predicts survival in patients with cancer or liver cirrhosis. Recently, many reports have used computed tomography (CT) to measure muscle area to define sarcopenia. However, the definition of sarcopenia using CT has not been fully determined. The aim of this study was to establish formulae to calculate the standard area of skeletal muscle. Methods: Forty-five healthy adults (24 men and 21 women, aged 21-66 years) who wished to donate part of their liver for transplantation underwent CT. Cross-sectional areas (cm2) of skeletal muscle were measured at the caudal end of the third lumbar vertebra. Regression analysis was performed to establish formulae to calculate the standard area of skeletal muscle. A validation conducted on 30 other healthy adults was performed to check the accuracy of formulae. Results: Men had a median skeletal muscle area of 155.0cm2 (range, 114.0-203.0), compared with 111.7cm2 (range, 89.8-139.3) in women (P<0.001). Furthermore, skeletal muscle area significantly correlated with body surface area (BSA) in men (P<0.0001, r2=0.60) and women (P<0.0001, r2=0.78). The formulae to calculate skeletal muscle area were 126.9×BSA-66.2 in men and 125.6×BSA-81.1 in women. The estimated muscle area significantly correlated with actual muscle area in men (P=0.003, r2=0.64) and women (P=0.0001, r2=0.70). Conclusion: Sarcopenia can be defined by the difference between measured data and calculated data using our new formulae..
429. Tomoharu Yoshizumi, Ken Shirabe, Hidekazu Nakagawara, Toru Ikegami, Norifumi Harimoto, Takeo Toshima, Yo-Ichi Yamashita, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara, Skeletal muscle area correlates with body surface area in healthy adults., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/hepr.12119, 44, 3, 313-8, 2014.03, AIM: Depletion of skeletal muscle mass (sarcopenia) predicts survival in patients with cancer or liver cirrhosis. Recently, many reports have used computed tomography (CT) to measure muscle area to define sarcopenia. However, the definition of sarcopenia using CT has not been fully determined. The aim of this study was to establish formulae to calculate the standard area of skeletal muscle. METHODS: Forty-five healthy adults (24 men and 21 women, aged 21-66 years) who wished to donate part of their liver for transplantation underwent CT. Cross-sectional areas (cm(2) ) of skeletal muscle were measured at the caudal end of the third lumbar vertebra. Regression analysis was performed to establish formulae to calculate the standard area of skeletal muscle. A validation conducted on 30 other healthy adults was performed to check the accuracy of formulae. RESULTS: Men had a median skeletal muscle area of 155.0 cm(2) (range, 114.0-203.0), compared with 111.7 cm(2) (range, 89.8-139.3) in women (P < 0.001). Furthermore, skeletal muscle area significantly correlated with body surface area (BSA) in men (P < 0.0001, r(2)  = 0.60) and women (P < 0.0001, r(2)  = 0.78). The formulae to calculate skeletal muscle area were 126.9 × BSA - 66.2 in men and 125.6 × BSA - 81.1 in women. The estimated muscle area significantly correlated with actual muscle area in men (P = 0.003, r(2)  = 0.64) and women (P = 0.0001, r(2)  = 0.70). CONCLUSION: Sarcopenia can be defined by the difference between measured data and calculated data using our new formulae..
430. [Case report of introducing MMF and steroids as an immunosuppressive therapy after living-donor liver transplantation for a patient with the diabetic nephropathy]..
431. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Tomoharu Yoshizumi, Yo Ichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, A high MELD score, combined with the presence of hepatitis C, is associated with a poor prognosis in living donor liver transplantation, Surgery today, 10.1007/s00595-013-0523-7, 44, 2, 233-240, 2014.02, Purpose: The feasibility of performing living donor liver transplantation (LDLT) for patients with high end-stage liver disease (MELD) scores needs to be assessed. Methods: A total of 357 patients who underwent LDLT were included in this analysis. Results: Overall, 46 patients had high MELD scores (≥25) and their graft survival was similar to that in patients with low MELD scores (<25; n = 311; p = 0.395). However, among patients with high MELD scores, a multivariate analysis showed that the presence of hepatitis C (p = 0.013) and LDLT in Era-I (p = 0.036) was significantly associated with a poorer prognosis. Among patients with hepatitis C (n = 155), the 5-year graft survival rate was significantly lower in patients with high MELD scores (33.7 %, p < 0.001) than in patients with low MELD scores. The 5-year graft survival rate was significantly lower in patients in Era-I (n = 119) compared with those in Era-II/III when stratified by low (73.0 vs. 82.5 %, p = 0.040) and high (55.0 vs. 86.1 %, p = 0.023) MELD scores. Among the patients with high MELD scores, those with hepatitis C and LDLT in Era-I had the worst 5-year graft survival rate (14.3, p < 0.001). Conclusion: The graft outcomes in patients with high MELD scores and the presence of hepatitis C were found to be particularly poor..
432. Toru Ikegami, Daisuke Imai, Huanlin Wang, Tomoharu Yoshizumi, Yo Ichi Yamashita, Mizuki Ninomiya, Tomohiro Iguchi, Yuki Bekki, Ken Shirabe, Yoshihiko Maehara, D-MELD as a predictor of early graft mortality in adult-to-adult living-donor liver transplantation, Transplantation, 10.1097/01.TP.0000435696.23525.d0, 97, 4, 457-462, 2014.02, BACKGROUND: Ensuring a good match between donor and recipient is critically important to achieve acceptable graft outcomes after living-donor liver transplantation (LDLT). Our objective was to evaluate the product of donor age and Model for End-stage Liver Disease score (D-MELD) as a predictor of graft survival after LDLT. METHODS: We retrospectively evaluated the records of 355 adults who underwent LDLT for chronic liver disease and explored the relationship between D-MELD and graft outcome. RESULTS: High MELD score and advanced donor age were significantly associated with graft survival; D-MELD had the strongest association with in-hospital mortality. Receiver operating characteristic curve analysis showed that a D-MELD score of 462 had the highest sensitivity for predicting in-hospital mortality. Patients were allocated to three groups based on D-MELD (Class A [≤449; n=142], Class B [450-899; n=163], and Class C [≥900; n=50]) and were found to have stratified cumulative 2-year graft survivals of 94.1%, 85.3%, and 63.1%, respectively (P<0.01). Although D-MELD Class C patients had larger graft volume-to-standard liver volume ratio (P<0.01) and received right lobe grafts more often (P<0.01), they still exhibited significantly higher rates of primary graft dysfunction (P<0.01) and in-hospital mortality (P<0.01). Outcomes in D-MELD Class C were significantly worse in hepatitis C-positive patients (P<0.05). CONCLUSIONS: The D-MELD score is a simple and reliable predictor of early graft survival that assists the matching of donors and recipients in LDLT in adults..
433. H. Uchiyama, K. Shirabe, H. Nakagawara, T. Ikegami, T. Toshima, Y. Soejima, T. Yoshizumi, Y. I. Yamashita, N. Harimoto, T. Ikeda, Y. Maehara, Revisiting the safety of living liver donors by reassessing 441 donor hepatectomies
Is a larger hepatectomy complication-prone?, American Journal of Transplantation, 10.1111/ajt.12559, 14, 2, 367-374, 2014.02, Donor safety is of paramount importance in performing living donor liver transplantation (LDLT). We retrospectively reviewed donor medical records to confirm whether larger donor hepatectomy is absolutely complication-prone. A total of 441 living donor hepatectomies were performed between October 1996 and July 2012 in our institute, which were divided into three eras (Era I, October 1996 to March 2004; Era II, April 2004 to March 2008; Era III, April 2008 to July 2012) and the incidences of postoperative complications were compared among the three types of hepatectomy - right hepatectomy (RH), left hepatectomy (LH) and left lateral segmentectomy (LLS). Although severe complications (Clavien's grade 3 or more) frequently occurred in RH in Eras I and II (15.4% and 10.7%, respectively), the incidence in Era III decreased to the comparable level observed in LH and LLS (5.4% in RH, 2.3% in LH and 5.3% in LLS). The incidence of postoperative complications did not relate to the type of hepatectomy selected in the latest era. Since most complications after hepatectomy were considered preventable, step-by-step meticulous surgical procedures are a prerequisite for further assuring donor safety irrespective of the type of hepatectomy selected. The authors reassess 441 donor hepatectomies and find that with cumulative experiences, right hepatectomies are no longer complication-prone compared to left hepatectomies or left lateral segmentectomies. See editorial by Roll and Roberts on page 251..
434. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Tomoharu Yoshizumi, Yo-Ichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, A high MELD score, combined with the presence of hepatitis C, is associated with a poor prognosis in living donor liver transplantation., Surgery today, 10.1007/s00595-013-0523-7, 44, 2, 233-40, 2014.02, PURPOSE: The feasibility of performing living donor liver transplantation (LDLT) for patients with high end-stage liver disease (MELD) scores needs to be assessed. METHODS: A total of 357 patients who underwent LDLT were included in this analysis. RESULTS: Overall, 46 patients had high MELD scores (≥ 25) and their graft survival was similar to that in patients with low MELD scores (<25; n = 311; p = 0.395). However, among patients with high MELD scores, a multivariate analysis showed that the presence of hepatitis C (p = 0.013) and LDLT in Era-I (p = 0.036) was significantly associated with a poorer prognosis. Among patients with hepatitis C (n = 155), the 5-year graft survival rate was significantly lower in patients with high MELD scores (33.7 %, p < 0.001) than in patients with low MELD scores. The 5-year graft survival rate was significantly lower in patients in Era-I (n = 119) compared with those in Era-II/III when stratified by low (73.0 vs. 82.5 %, p = 0.040) and high (55.0 vs. 86.1 %, p = 0.023) MELD scores. Among the patients with high MELD scores, those with hepatitis C and LDLT in Era-I had the worst 5-year graft survival rate (14.3, p < 0.001). CONCLUSION: The graft outcomes in patients with high MELD scores and the presence of hepatitis C were found to be particularly poor..
435. H. Uchiyama, K. Shirabe, H. Nakagawara, T. Ikegami, T. Toshima, Y. Soejima, T. Yoshizumi, Y.‐I. Yamashita, N. Harimoto, T. Ikeda, Y. Maehara, Revisiting the Safety of Living Liver Donors by Reassessing 441 Donor Hepatectomies: Is a Larger Hepatectomy Complication‐Prone?, American Journal of Transplantation, 10.1111/ajt.12559, 14, 2, 367-374, 2014.02.
436. Takeo Toshima, Ken Shirabe, Toru Ikegami, Tomoharu Yoshizumi, Atsushi Kuno, Akira Togayachi, Masanori Gotoh, Hisashi Narimatsu, Masaaki Korenaga, Masashi Mizokami, Akihito Nishie, Shinichi Aishima, Yoshihiko Maehara, A novel serum marker, glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP), for assessing liver fibrosis, Journal of gastroenterology, 10.1007/s00535-014-0946-y, 50, 1, 76-84, 2014.01, Background: Recently, a novel marker, hyperglycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP), was developed for liver fibrosis using the glycan “sugar chain”-based immunoassay; however, the feasibility of WFA+-M2BP for assessing liver fibrosis has not been proven with clinical samples of hepatitis.
Methods: Serum WFA+-M2BP values were evaluated in 200 patients with chronic liver disease who underwent histological examination of liver fibrosis. The diagnostic accuracy of WFA+-M2BP values was compared with various fibrosis markers, such as ultrasound based-virtual touch tissue quantification (VTTQ), magnetic resonance imaging based-liver-to-major psoas muscle intensity ratio (LMR), and serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index (APRI).
Results: Serum WFA+-M2BP levels in patients with fibrosis grades F0, F1, F2, F3, and F4 had cutoff indices 1.62, 1.82, 3.02, 3.32, and 3.67, respectively, and there were significant differences between fibrosis stages F1 and F2, and between F2 and F3 (P < 0.01). The area under the receiver operating characteristic curves for the diagnosis of fibrosis (F ≥ 3) using serum WFA+-M2BP values (0.812) was almost comparable to that using VTTQ examination (0.814), but was superior to the other surrogate markers, including LMR index (0.766), APRI (0.694), hyaluronic acid (0.683), and type 4 collagen (0.625) (P < 0.01 each).
Conclusions: Serum WFA+-M2BP values based on a glycan-based immunoassay is an accurate, reliable, and reproducible method for the assessment of liver fibrosis. This approach could be clinically feasible for evaluation of beneficial therapy through the quantification of liver fibrosis in hepatitis patients if this measurement application is commercially realized..
437. T. Toshima, T. Ikegami, K. Kimura, N. Harimoto, Y. Yamashita, T. Yoshizumi, Y. Soejima, T. Ikeda, K. Shirabe, Y. Maehara, Application of postoperative model for end-stage liver disease scoring system for evaluating liver graft function after living donor liver transplantation, Transplantation Proceedings, 10.1016/j.transproceed.2013.09.034, 46, 1, 81-86, 2014.01, Background The Model for End-Stage Liver Disease (MELD) score has been validated to predict the mortality rate of patients with various chronic liver diseases on the waiting list for liver transplantation (LT). The aim of this study was to assess the value of the postoperative MELD scoring system as an early postoperative predictor of outcome in patients undergoing living donor LT (LDLT). Methods A retrospective analysis of 217 adult-to-adult LDLT patients was performed. The values of the MELD score on various postoperative days (PODs) as predictors of graft loss within 6 months after LDLT were examined by calculating the areas under the receiver operating characteristic (AUROC) curves. The 6-months graft survival rates were compared between patients with (n = 22) and without (n = 195) graft loss. Univariate and multivariate analyses were performed to identify the factors associated with mortality. Results The MELD score on POD2 was a predictor of graft loss, with an AUROC c-statistic of 0.779, a specificity of 79.5%, and a sensitivity of 68.2% at optimal cutoff, whereas the preoperative MELD score c-statistic was 0.605 with 44.6% sensitivity. Multivariate analyses for postoperative mortality revealed MELD-POD2 ≥19 (odds ratio, 5.601; 95% confidence interval [CI], 1.395-4.508; P =.0009) as an independent predictor of short-term graft loss following LDLT, in addition to preoperative hospitalization status. Later MELD POD scores were also predictive of graft loss. Conclusions The early postoperative MELD scoring system is feasible as an index for prediction of postoperative mortality following LDLT..
438. H. Kawanaka, T. Akahoshi, N. Kinjo, T. Iguchi, M. Ninomiya, Y. I. Yamashita, T. Ikegami, T. Yoshizumi, K. Shirabe, Y. Maehara, Effect of laparoscopic splenectomy on portal haemodynamics in patients with liver cirrhosis and portal hypertension, British Journal of Surgery, 10.1002/bjs.9622, 101, 12, 1585-1593, 2014.01, Background: The effect of splenomegaly in patients with liver cirrhosis and portal hypertension is not fully understood. This study was designed to determine the effect of laparoscopic splenectomy on portal haemodynamics in these patients.
Methods: Patients with liver cirrhosis and portal hypertension who underwent laparoscopic splenectomy in Kyushu University Hospital from January 2006 to March 2009 were evaluated retrospectively. Correlations between splenic size and portal haemodynamics, and changes in portal haemodynamics and in levels of the vasoactive agents endothelin (ET) 1 and nitric oxide metabolites (NOx) before and 7-10 days after laparoscopic splenectomy were analysed.
Results: Portal venous (PV) blood flow, PV cross-sectional area and PV congestion index correlated significantly with splenic size (P <0·050). All three were significantly reduced following splenectomy in 59 patients. The hepatic venous pressure gradient, measured in 18 patients, decreased by 25 per cent after splenectomy (P <0·001). Portal vascular resistance was also reduced, by 21 per cent (P =0·009). The peripheral blood concentration of ET-1 decreased from 2·95 to 2·11 pg/ml (P <0·001), and that of NOx tended to decrease (from 29·2 to 25·0 pg/ml; P =0·068). In hepatic venous blood, the level of ET-1 decreased from 2·37 to 1·83 pg/ml (P =0·006), whereas NOx concentration tended to increase (from 24·5 to 30·9 pg/ml; P =0·067).
Conclusion: In patients with liver cirrhosis and portal hypertension, splenectomy reduced portal venous pressure. A decrease in splanchnic blood flow, by eliminating splenic blood flow, and reduction in intrahepatic vascular resistance, by normalizing hepatic concentrations of ET-1 and NOx, may both have contributed..
439. Toru Ikegami, Tomoharu Yoshizumi, Yo Ichi Yamashita, Noboru Harada, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Obstructing spontaneous major shunt vessels is or might not be mandatory in living donor liver transplantation
The authors' reply, Transplantation, 10.1097/TP.0000000000000096, 97, 9, e53, 2014.01.
440. Daisuke Imai, Toru Ikegami, Takeo Toshima, Tomoharu Yoshizumi, Yo Ichi Yamashita, Mizuki Ninomiya, Norifumi Harimoto, Shinji Itoh, Hideaki Uchiyama, Ken Shirabe, Yoshihiko Maehara, Preemptive thoracic drainage to eradicate postoperative pulmonary complications after living donor liver transplantation, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.09.006, 219, 6, 1134-1142.e2, 2014.01, Background: Thoracic fluid retention after living donor liver transplantation (LDLT) has various negative consequences, including atelectasis, pneumonia, and respiratory distress or failure. Study Design: We analyzed the clinical impact of preemptive thoracic drainage in 177 patients undergoing adult-to-adult LDLT for chronic liver diseases at a single center. Recipients were divided into 2 time periods. The earlier cohort (n = 120) was analyzed for risk factors for postoperative atelectasis retrospectively; the later cohort (n = 57), with a risk factor for postoperative atelectasis, underwent preemptive thoracic drainage prospectively. The incidence of postoperative pulmonary complications was compared between these 2 cohorts. Results: Independent risk factors for atelectasis in earlier cohort were body mass index ≥27 kg/m2 (p < 0.001), performance status ≥3 (p = 0.003) and model for end-stage liver disease score ≥23 (p = 0.005). The rates of atelectasis (21.1% vs 42.5%, p = 0.005) and pneumonia (1.8% vs 10.0%, p = 0.049) were significantly lower in later than in earlier cohort. Moreover, the mean durations of ICU stay (3.6 ± 0.2 days vs 5.7 ± 0.6 days, p = 0.038) and postoperative oxygen support (5.1 ± 0.8 days vs 7.1 ± 0.5 days, p = 0.037) were significantly shorter in the later than in the earlier cohort. There were no significant differences in the incidence of adverse events associated with thoracic drainages between these 2 cohorts. Conclusions: Preemptive thoracic drainage for transplant recipients at high risk of postoperative atelectasis could decrease morbidities after LDLT..
441. Yuichiroh Umemoto, Shinji Okano, Yoshihiro Matsumoto, Hidekazu Nakagawara, Rumi Matono, Shohei Yoshiya, Yo ichi Yamashita, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Mamoru Harada, Shinichi Aishima, Yoshinao Oda, Ken Shirabe, Yoshihiko Maehara, Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy, Journal of gastroenterology, 10.1007/s00535-014-0933-3, 50, 1, 65-75, 2014.01, Methods: We assessed the levels of PD-L1 and HLA class I expression on HCC samples from 80 patients who had undergone hepatectomy at our institution, and evaluated the correlations between PD-L1 and HLA class I expression and patient prognosis.
Background: Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Surgery is potentially curative, but high recurrence rates worsen patient prognosis. The interaction between the proteins programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) is an important immune checkpoint. The significance of PD-L1 expression and human leukocyte antigen class I (HLA class I), recognized by CD8 T cells, in the prognosis of patients with HCC remains to be determined.
Results: High HLA class I expression was correlated with significantly better recurrence-free survival (RFS), but not overall survival (OS). Multivariate analysis showed that high HLA class I expression was an independent predictor of improved RFS. Low expression of PD-L1 on HCC tended to predict better OS, but the difference was not statistically significant. PD-L1 expression on HCC correlated with the number of CD163-positive macrophages and HLA class I expression with CD3-positive cell infiltration. Univariable and multivariable analyses showed that combined PD-L1 low/HLA class I high expression on HCCs was prognostic for improved OS and RFS.
Conclusions: PD-L1 status may be a good predictor of prognosis in HCC patients with high HLA class I expression. Novel therapies targeting the PD-L1/PD-1 pathway may improve the prognosis of patients with HCC..
442. Toru Ikegami, Tomoharu Yoshizumi, Masaki Kato, Satomi Yamamoto, Takasuke Fukuhara, Yoshiharu Matsuura, Shota Nakamura, Shinji Itoh, Ken Shirabe, Yoshihiko Maehara, Reduced-dose telaprevir-based triple antiviral therapy for recurrent hepatitis C after living donor liver transplantation, Transplantation, 10.1097/TP.0000000000000166, 98, 9, 994-999, 2014.01, Introduction. The feasibility of telaprevir-based triple therapy for recurrent hepatitis C after liver transplantation (LT) has not been evaluated in Asian patients. Methods. Eleven Japanese patients received reduced-dose telaprevir (1500 mg) and adjusted-dose cyclosporine after LT. Six patients were nonresponders and three were transient responders to dual therapy. Results. Rapid viral response, early viral response, end of treatment response, and sustained viral response were achieved in 27.3%, 90.9%, 90.9%, and 81.8% of patients, respectively. One patient had viral breakthrough at week 8 with a T54A mutation in NS3. Deep sequence analysis showed that the T54A mutation reverted to wild-type after stopping telaprevir administration. Seven patients developed severe anemia, and six received blood transfusions (4Y20U). Their hemoglobin and estimated glomerular filtration rate remained significantly lower than pretreatment values at 36 weeks after treatment. Four patients developed plasma cell hepatitis after completing telaprevir treatment, and it was treated by increasing the immunosuppressants. Although the cyclosporine level/dose ratio was 2.7 times higher at week 4 than before treatment, it was 0.7 times lower at week 36. Conclusions. Reduced-dosed telaprevir-based triple antiviral therapy achieved a high viral clearance rate in Japanese patients after LT. Major adverse events included severe anemia, renal dysfunction, and plasma cell hepatitis..
443. Tomoharu Yoshizumi, Toru Ikegami, Koichi Kimura, Hideaki Uchiyama, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara, Selection of a right posterior sector graft for living donor liver transplantation, Liver Transplantation, 10.1002/lt.23924, 20, 9, 1089-1096, 2014.01, Right posterior sector (RPS) grafts have been used to overcome graft size discrepancies, the major concern of living donor liver transplantation. Previous studies have reported the volumetry-based selection of RPS grafts without anatomical exclusion. We reviewed our data and established selection criteria for RPS grafts. The procurement of RPS grafts [conventional (n-=-3) and extended (n-=-5)] was performed for 8 of 429 recipients at our center. Extended RPS grafts contained the drainage area of the right hepatic vein. The mean graft weight (GW) according to 3-dimensional computed tomography volumetry was 488 g, and the GW/standard liver weight (SLW) ratio was 42.6%. The mean actual GW was 437 g, and the GW/SLW ratio was 38.4%. One donor exhibited standard bifurcation of the right portal vein (PV) and the left PV, and 2 donors exhibited trifurcation of the left PV, the right anterior portal vein (APV), and the posterior PV. The remaining 5 donors exhibited APV branching from the left PV, which is the most suitable anatomy for RPS grafts. Two recipients died of sepsis or small-for-size graft syndrome. One underwent retransplantation because of an intractable bile leak and fibrosing cholestatic hepatitis. Intractable bile duct (BD) stenosis developed in 4 of the 6 survivors. In conclusion, with the significant complications and potential concerns associated with RPS grafts, these grafts should be used very rarely and with extreme caution. Donors with the standard bifurcation of the PV and the posterior BD running through the dorsal side of the posterior PV are not suitable candidates for RPS grafts. Extended RPS graft procurement is recommended for easier parenchymal transection..
444. Takahiro Tomino, Yo Ichi Yamashita, Tomohiro Iguchi, Shinji Itoh, Mizuki Ninomiya, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Tetsuo Ikeda, Shinichi Aishima, Ken Shirabe, Yoshihiko Maehara, Spontaneous massive necrosis of hepatocellular carcinoma with narrowing and occlusion of the arteries and portal veins, Case Reports in Gastroenterology, 10.1159/000362440, 8, 1, 148-155, 2014.01, We herein present the case of a 77-year-old man who had fever and right hypochondriac pain. He visited his doctor and underwent contrast computed tomography (CT), and he was suspected to have a liver abscess. He received an antibiotic treatment and his symptoms soon disappeared, but the tumor did not get smaller and its density on contrast CT image got stronger. He underwent biopsy and moderately differentiated hepatocellular carcinoma (HCC) was found. Extended left hepatic and caudate lobectomy was performed. Histological examination showed moderately differentiated HCC with narrowing and occlusion both in the arteries and portal veins associated with mild chronic inflammation. The mechanisms of spontaneous regression of HCC, such as immunological reactions and tumor hypoxia, have been proposed. In our case, histological examination showed the same findings. However, the mechanism is complex, and therefore further investigations are essential to elucidate it..
445. Toru Ikegami, Huanlin Wang, Tomoharu Yoshizumi, Takeo Toshima, Shinichi Aishima, Takasuke Fukuhara, Norihiro Furusyo, Kazuhiro Kotoh, Shinji Shimoda, Ken Shirabe, Yoshihiko Maehara, Strategies to treat interferon-induced graft dysfunction after living donor liver transplantation for hepatitis C, Hepatology International, 10.1007/s12072-013-9496-2, 8, 2, 285-292, 2014.01, Purpose: Interferon-induced graft dysfunction (IGD) is a poorly defined, unrecognized, but potentially serious condition for patients receiving antiviral drugs after liver transplantation for hepatitis C. Methods: We evaluated the characteristics of 80 patients who received pegylated interferon-based antiviral treatment for hepatitis C after living donor liver transplantation (LDLT). Results: Eight patients experienced IGD either during (n = 6) or after completing (n = 2) antiviral treatment. Pathological diagnosis included acute cellular rejection (ACR, n = 1), plasma cell hepatitis (PCH, n = 2), PCH plus ACR (n = 3), and chronic rejection (CR, n = 2). One patient with CR initially presented with PCH plus ACR and the other presented with ACR; both had apparent cholestasis. The six patients with ACR or PCH without cholestasis were successfully treated by discontinuing antiviral treatment and increasing immunosuppression, including steroids. By contrast, both of the patients with CR and cholestasis experienced graft loss, despite aggressive treatment. Univariate analysis showed that pegylated interferon-α2a-based treatment (75 vs. 26.4 %, p < 0.01) was the only significant factor for IGD, and was associated with decreased 5-year graft survival (93.4 vs. 71.4 %, p = 0.04). Conclusions: IGD is a serious condition during or even after antiviral treatment for hepatitis C after LDLT. Early recognition, diagnosis, discontinuation of interferon, and introduction of steroid-based treatment may help to save the graft..
446. Shotaro Kuramitsu, Tomohiro Iguchi, Mizuki Ninomiya, Yo ichi Yamashita, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Hirofumi Kawanaka, Tetsuo Ikeda, Toshiya Furuta, Ryuichiro Tamada, Yoshihiko Maehara, [Case report of introducing MMF and steroids as an immunosuppressive therapy after living-donor liver transplantation for a patient with the diabetic nephropathy]., Fukuoka igaku zasshi = Hukuoka acta medica, 105, 3, 79-83, 2014.01, Calcineurin inhibitor (CNI) combined with mycophenolate mofetil (MMF) and steroid is mainly used as immunosuppressive therapy after the living-donor liver transplantation (LDLT). However, the nephrotoxicity caused by CNI remains a critical problem for patients with chronic renal failure, especially on early postoperative period. A 62-year-old woman with decompensated liver cirrhosis secondary to hepatitis B (Child-Pugh C, MELD score 11 points) and chronic renal failure due to diabetic nephropathy (Cr 1.56 mg/dl, GFR 27 ml/min/1.73 m2) experienced LDLT. During the reconstruction of hepatic vein, the supra-and infra-hepatic vena cava was totally clamped. The estimated right lobe liver graft volume was 540 g, representing 51.3% of the standard liver volume of the recipient. Because of the perioperative renal dysfunction due to diabetic nephropathy and the total clamping the vena cava which induced the congestion kidney, MMF (1500 mg/day) and steroid (250 mg/day converted into predonisolone) were mainly introduced as an immunosuppressive therapy after LDLT. The low-dose CNI, tacrolimus also induced the nephrotoxicity and was given for only a short time. Finally, according to the postoperative renal function, the low-dose CNI, cyclosporin (50 mg/day) was able to be added to the introduced immunosuppressive therapy. After having left the hospital, MMF (1500 mg/day), steroid (20 mg/day converted into predonisolone) and cyclosporin (75 mg/day) continued to be given as the immunosuppressive therapy and neither acute graft rejection nor drug-induced renal dysfunction was occurred. This is a case report of introducing with mainly MMF and steroid as an immunosuppressive therapy after LDLT for a patient with perioperative renal dysfunction..
447. T. Toshima, T. Ikegami, K. Kimura, N. Harimoto, Y. Yamashita, T. Yoshizumi, Y. Soejima, T. Ikeda, K. Shirabe, Y. Maehara, Application of Postoperative Model for End-Stage Liver Disease Scoring System for Evaluating Liver Graft Function After Living Donor Liver Transplantation, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2013.09.034, 46, 1, 81-86, 2014.01, Background. The Model for End-Stage Liver Disease (MELD) score has been validated to predict the mortality rate of patients with various chronic liver diseases on the waiting list for liver transplantation (LT). The aim of this study was to assess the value of the postoperative MELD scoring system as an early postoperative predictor of outcome in patients undergoing living donor LT (LDLT).
Methods. A retrospective analysis of 217 adult-to-adult LDLT patients was performed. The values of the MELD score on various postoperative days (PODs) as predictors of graft loss within 6 months after LDLT were examined by calculating the areas under the receiver operating characteristic (AUROC) curves. The 6-months graft survival rates were compared between patients with (n = 22) and without (n = 195) graft loss. Univariate and multivariate analyses were performed to identify the factors associated with mortality.
Results. The MELD score on POD2 was a predictor of graft loss, with an AUROC c-statistic of 0.779, a specificity of 79.5%, and a sensitivity of 68.2% at optimal cutoff, whereas the preoperative MELD score c-statistic was 0.605 with 44.6% sensitivity. Multivariate analyses for postoperative mortality revealed MELD-POD2 >= 19 (odds ratio, 5.601; 95% confidence interval [CI], 1.395-4.508; P = .0009) as an independent predictor of short-term graft loss following LDLT, in addition to preoperative hospitalization status. Later MELD POD scores were also predictive of graft loss.
Conclusions. The early postoperative MELD scoring system is feasible as an index for prediction of postoperative mortality following LDLT..
448. Takahiro Tomino, Yo-Ichi Yamashita, Tomohiro Iguchi, Shinji Itoh, Mizuki Ninomiya, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Tetsuo Ikeda, Shinichi Aishima, Ken Shirabe, Yoshihiko Maehara, Spontaneous massive necrosis of hepatocellular carcinoma with narrowing and occlusion of the arteries and portal veins., Case reports in gastroenterology, 10.1159/000362440, 8, 1, 148-55, 2014.01, We herein present the case of a 77-year-old man who had fever and right hypochondriac pain. He visited his doctor and underwent contrast computed tomography (CT), and he was suspected to have a liver abscess. He received an antibiotic treatment and his symptoms soon disappeared, but the tumor did not get smaller and its density on contrast CT image got stronger. He underwent biopsy and moderately differentiated hepatocellular carcinoma (HCC) was found. Extended left hepatic and caudate lobectomy was performed. Histological examination showed moderately differentiated HCC with narrowing and occlusion both in the arteries and portal veins associated with mild chronic inflammation. The mechanisms of spontaneous regression of HCC, such as immunological reactions and tumor hypoxia, have been proposed. In our case, histological examination showed the same findings. However, the mechanism is complex, and therefore further investigations are essential to elucidate it..
449. Tomohiro Iguchi, Ken Shirabe, Kentaro Inoue, Shuhei Ito, Takefumi Ohga, Tadahiro Nozoe, Takahiro Ezaki, Tomoharu Yoshizumi, Hideaki Uchiyama, Yuji Soejima, Toru Ikegami, Yo Ichi Yamashita, Hirofumi Kawanaka, Tetsuo Ikeda, Hiroshi Saeki, Masaru Morita, Yoshihiko Maehara, Impact of high preoperative steroid doses on postoperative complications among patients on prolonged preoperative steroid therapy., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 499-506, 2013.12, Corticosteroids are essential to maintain the organic homeostasis. Steroid, glucocorticoid or its synthetic analog is widely used for inflammatory and autoimmune diseases. Prolonged steroid therapy is reported to cause the susceptibility to infection, impaired wound healing and psychoneurosis, however whether the quantity of taking the preoperative steroid is associated the postoperative complication is still unknown. The aim of this study was to elucidate whether the steroid dose in patients on prolonged preoperative steroid therapy is associated postoperative morbidity and mortality. Twenty-five patients taking steroid for various illnesses and underwent the surgery under general anesthesia were selected in this study. The mean +/- standard deviation and the median of the steroid dose converted into hydrocortisone (mg/day) were 39.2 +/- 31.0 and 20, respectively. Of 25 cases, postoperative complications were seen in 10 cases. The postoperative complication was severe based on the grade of Clavien and Dindo by ANOVA as the doses of taking steroid increased (p = 0.0171). The grave postoperative complication classified as Clavien and Dindo grade III occurred with 100% sensitivity and 87% specificity for the steroid dose converted into hydrocortisone > 80 mg/day. Preoperative taking the large amount of steroid (> 80 mg/day) could cause a grave complication. More careful selection of the operative procedure might improve the mobidity rate..
450. Shigeyuki Nagata, Ken Shirabe, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Hideaki Uchiyama, Yo Ichi Yamashita, Hiroshi Saeki, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Tomonobu Gion, Yuji Soejima, Tetsuo Ikeda, Shunichi Tsujitani, Yoshihiko Maehara, Pilot study of preoperative immunonutrition with antioxidants in living donor liver transplantation donors., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 530-538, 2013.12, Previous studies have demonstrated that oxidative stress by mediating the excessive production of reactive oxygen species is involved in tissue damage and organ failure during and after surgery. The impact of the preoperative immunonutrition including antioxidants on the postoperative course of patients undergoing hepatic surgery was investigated in this pilot study. Twenty-three living donor liver transplantation (LDLT) donors were randomly assigned to either an experimental (AO) group, received a commercial supplement enriched with antioxidant nutrients for each of the 5 days immediately prior to surgery while maintaining normal food intake, or a control (CT) group, administered no supplement. Antioxidative capacity was measured by spectrophotometry of patient serum using a free-radical analytical system. The antioxidative capacity of 90.9% patients in the AO group increased after immunonutrition. Compared to the CT group, the AO group was found to have higher antioxidant capacity and transferrin levels; lower WBC, lymphocyte, and neutrophil counts; and briefer duration of postoperative fever during the postsurgical period. No significant differences were found between the 2 groups regarding the nutritional parameters; liver functioning parameters; immunological parameters; intraoperative factors; postoperative outcomes. Preoperative immunonutrition including antioxidants might play a beneficial role in improving postsurgical immunological response but the modest biological advantage was not associated with any significant clinical outcome..
451. Norifumi Harimoto, Ken Shirabe, Hidekazu Nakagawara, Takeo Toshima, Yo Ichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Yoshihiko Maehara, Prognostic factors affecting survival at recurrence of hepatocellular carcinoma after living-donor liver transplantation
With special reference to neutrophil/lymphocyte ratio, Transplantation, 10.1097/TP.0b013e3182a53f2b, 96, 11, 1008-1012, 2013.12, BACKGROUND: In living-donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC), it is important to predict not only who may be susceptible to recurrence but also who may survive longer. The neutrophil/lymphocyte ratio (NLR) is useful to properly assess the patient without decreasing the long-term survival after LDLT. In this study, we investigated the relationship between NLR and prognosis of patients with recurrent HCC after LDLT. METHODS: In total, 167 LDLTs for HCC were enrolled in this study. Clinicopathologic factors for HCC recurrence after LDLT were investigated and prognostic factors were examined with respect to survival. RESULTS: The following factors were found to be significant in patients with HCC recurrence compared with the controls: α-fetoprotein ≧300 ng/mL, des-γ- carboxyprothrombin ≧300 mAU/mL, NLR ≧4, tumor number >3, tumor size ≧5 cm, duration of last treatment of HCC to LDLT <3 months, Milan criteria exceeded, histologic tumor number ≧10, histologic tumor size >5 cm, poor differentiation, presence of histologic vascular invasion, adjuvant chemotherapy, and interferon therapy against patients with hepatitis C virus. Male sex, interferon therapy against patients with hepatitis C virus, α-fetoprotein ≧300 ng/mL at recurrence, NLR ≧4 at recurrence, and nonsurgical resection for recurrent HCC were significantly related to poor prognosis. The 3-year survival rate after recurrence was 0% in patients with NLR ≧4 and 43.6% in patients with NLR <4. NLR was reelevated after LDLT in patients who later died; however, NLR gradually decreased in surviving patients. CONCLUSION: NLR at recurrence is a prognostic factor affecting survival after recurrence in LDLT for HCC..
452. Yo ichi Yamashita, Ken Shirabe, Takeo Toshima, Eiji Tsuijita, Kazuki Takeishi, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara, Risk factors for recurrence after curative resection of hepatitis C-related hepatocellular carcinoma in patients without postoperative interferon therapy, Hepatology Research, 10.1111/hepr.12091, 43, 12, 1313-1320, 2013.12, Aim: Hepatitis C (HC)-related hepatocellular carcinoma (HCC; HC-HCC) is highly recurrent. Methods: From 1995-2007, 183 curative hepatic resections for primary solitary HC-HCC without postoperative interferon therapy were included in this study. The patients were divided into three groups: (i) 2cm or less (n=56); (ii) more than 2cm to less than 5cm (n=79); and (iii) 5cm or more (n=48). Independent risk factors for HC-HCC recurrence for each group were determined. Results: Independent risk factors for recurrence were aspartate aminotransferase or alanine aminotransferase (AST/ALT) of 80IU/L or more (hazard ratio [HR], 2.1; P=0.02) in patients with HCC of 2cm or less, des-γ-carboxy prothrombin of 100mAU/mL or more (HR, 2.5; P=0.02) and AST/ALT of 80IU/L or more (HR, 2.1; P=0.04) in patients with HCC of more than 2cm to less than 5cm, and the presence of macroscopic portal vein tumor thrombus (HR, 2.8; P=0.02) and AST/ALT of 80IU/L or more (HR, 2.1; P=0.04) in patients with HCC of 5cm or more. All 13 late recurrences of 1 year or more after hepatic resection (27.1%) in patients with HCC of 5cm or more were accompanied by AST/ALT of 80IU/L or more. Conclusion: AST/ALT of 80IU/L or more is an independent risk factor for the recurrence of primary solitary HC-HCC after curative resection irrespective of the primary HC-HCC size..
453. Noboru Harada, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Hideaki Uchiyama, Yuji Soejima, Yo Ichi Yamashita, Hiroshi Saeki, Eiji Oki, Hirofumi Kawanaka, Masaru Morita, Tetsuo Ikeda, Hiroshi Matsuura, Kenichiro Okadome, Yoshihiko Maehara, Surgical treatment and adjuvant chemotherapy for patients with biliary tract cancer
single institution experience of 100 patients., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 539-548, 2013.12, Surgery remains the treatment of choice for patients with resectable biliary tract cancer, enhancing the chance of cure and increasing long-term survival. Early recurrence, however, is frequent in patients who have undergone curative resection. To date, no randomized controlled trials have assessed adjuvant chemotherapy in patients with biliary tract cancer. The aim of this study was to evaluate the outcomes of surgical management followed by adjuvant chemotherapy in patients with biliary tract cancer. This study enrolled 100 patients with Union for International Cancer Control (UICC) stages I-IV biliary tract cancer who underwent surgical resection, including 16 who received sequential adjuvant chemotherapy with gemcitabine or S-1. Overall survival (OS), disease-free survival (DFS), and prognostic factors were analyzed. The median duration of follow-up was 12.6 months. Forty-one patients had lymph node metastasis and 81 underwent RO resection. The 1-, 3-, and 5-year OS rates were 80.9%, 48.6%, and 38.3%, respectively, and the 1-, 3-, and 5-year DFS rates were 59.8%, 39.9%, and 24.9%, respectively. Five-year OS rates were similar in patients who did (40.4%) and did not (32.4%) receive adjuvant chemotherapy. The morbidity and mortality rates were 59% and 3%, respectively. Multivariate analysis showed that only lymph node metastasis (p = 0.042) was independently associated with long-term survival. The presence of lymph node metastasis significantly affected long-term survival, whereas adjuvant chemotherapy did not affect outcomes in our patients with resectable biliary tract cancer..
454. Tomoharu Yoshizumi, ikegami Toru, Hideaki Uchiyama, Yo-ichi Yamashita, Harimoto Norifumi, Ken Shirabe, Yoshihiko Maehara, Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma., Transplantation Proceedings, 45, 11, 3310-3313, 2013.11.
455. Hideyuki Konishi, Ken Shirabe, Shohei Yoshiya, Tetsuo Ikeda, Toru Ikegami, Tomoharu Yoshizumi, Ayae Ikawa-Yoshida, Takashi Motomura, Takasuke Fukuhara, Yoshihiko Maehara, Hepatic interferon-gamma-induced protein-10 expression is more strongly associated with liver fibrosis than interleukin-28B single nucleotide polymorphisms in hepatocellular carcinoma resected patients with chronic hepatitis C, Hepatology Research, 10.1111/hepr.12070, 43, 11, 1139-1147, 2013.11, Aim: Single nucleotide polymorphisms (SNP) around IL-28B and interferon (IFN)-stimulated gene (ISG) expression are predictors of response to standard therapy involving IFN for chronic hepatitis C virus (HCV) infection. We analyzed the association between these predictors to improve the prediction of the response to IFN therapy after liver resection for hepatocellular carcinoma (HCC). Methods: Data were collected from 74 patients with HCV-induced HCC. The IL-28B genotype and hepatic ISG mRNA levels were analyzed to clarify their association, focusing on the progression of liver fibrosis. Results: Fifty patients were identified as having major alleles (rs8099917TT) and the remaining 24 patients had minor alleles (rs8099917TG or GG). Hepatic ISG15 expression was lower in the IL-28B major group than that in the IL-28B minor group (P<0.005). IP-10 expression was similar between the IL-28B major and minor groups (P=0.44). IP-10 expression was elevated with advancing stages of liver fibrosis in HCV infected patients (P=0.005). In patients with mild or no fibrosis, the IL-28B major group had lower IP-10 expression than the IL-28B minor group (P=0.02). However, in patients with advanced fibrosis, IP-10 expression was not different between the IL-28B major and minor groups (P=0.66). Conclusion: Hepatic ISG15 expression is associated with IL-28B polymorphisms, while IP-10 is strongly affected by liver fibrosis..
456. Toru Ikegami, Huanlin Wang, Daisuke Imai, Yuki Bekki, Tomoharu Yoshizumi, Yo Ichi Yamashita, Takeo Toshima, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Pathological analysis of opened round ligaments as venous patch grafts in living donor liver transplantation, Liver Transplantation, 10.1002/lt.23716, 19, 11, 1245-1251, 2013.11, Although the round ligament, including the umbilical vein, could be used as a venous graft in living donor liver transplantation (LDLT), no studies have determined its appropriate use on the basis of pathological findings. We prospectively examined 19 LDLT cases in which the donor's round ligament was procured and used as a venous graft. The round ligaments were categorized into 3 types based on the CD31 immunohistochemistry of tissue cross-sections: (I) canalized umbilical veins (n = 7 or 36.8%), (II) capillary umbilical vessels (n = 4 or 21.1%), and (III) occluded umbilical veins (n = 8 or 42.1%). After dilatation and incision, the round ligaments provided patch grafts that were 5.8 ± 0.4 cm long and 1.8 ± 1.2 cm wide. However, histological studies showed the absence of fine intimal layers on the dilated round ligaments after mechanical maneuvers. The ligaments were used to cuff the venous orifices in 15 patients (left lobe, n = 8; right lobe, n = 7) and were used as venous bridges in 4 patients (left lobe, n = 2; right lobe, n = 2). We detected no thrombosis at the implant sites after LDLT. Our pathological findings indicate that opened round ligaments can be used safely as venous patch grafts in LDLT. Liver Transpl 19:1245-1251, 2013..
457. Yoshihiro Matsumoto, Toru Ikegami, Kazutoyo Morita, Tomoharu Yoshizumi, Hiroto Kayashima, Ken Shirabe, Yoshihiko Maehara, Renoportal anastomosis in right lobe living donor liver transplantation
Report of a case, Surgery today, 10.1007/s00595-012-0351-1, 43, 11, 1316-1320, 2013.11, End-stage liver disease is often accompanied by thrombosis of the portal vein and the formation of splanchnic collateral vessels. Successful liver transplantation in such situations is more likely if the surgeon uses a strategy to establish a graft inflow. A 59-year-old male with a decompensated liver secondary to idiopathic portal hypertension underwent living donor liver transplantation (LDLT) using a right lobe liver graft donated from his son. His portal venous trunk was atrophied and a splenorenal shunt drained the mesenteric venous flow into the systemic circulation. LDLT was performed with renoportal anastomosis (RPA) using his right internal jugular vein as an interposed venous graft, without dissecting the collateral vessels. Although he developed temporary functional hyperbilirubinemia, he was discharged from the hospital 23 days after LDLT. This case suggests that RPA is a useful technique to manage patients with an obstructed portal vein and a splenorenal shunt..
458. Yo Ichi Yamashita, Ken Shirabe, Eiji Tsuijita, Kazuki Takeishi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Tohru Utsunomiya, Yoshihiko Maehara, Third or more repeat hepatectomy for recurrent hepatocellular carcinoma, Surgery (United States), 10.1016/j.surg.2013.04.046, 154, 5, 1038-1045, 2013.11, Background: We sought to evaluate the surgical results of third or more repeat hepatectomy for recurrent hepatocellular carcinoma (HCC). The role of repeat hepatectomy for recurrent HCC, especially in cases with third or more repeat hepatectomy, is controversial. Methods: We performed A retrospective, cohort study to analyze the surgical results of repeat hepatectomy performed at a single medical center from 1989 to 2011. A total of 1,000 hepatectomies for HCC were divided into 3 groups: A first hepatectomy group (n = 791), second hepatectomy group (n = 163), and third or more hepatectomy group (n = 46). Operative results and patient prognoses were compared among the 3 groups. Results: There were no differences in early surgical results such as mortality and morbidity among the 3 groups. The 5-year survival rates after the first, second, and third or more hepatectomy were 67%, 60%, and 43%, respectively (P =.1913). There was a significant difference in disease-free survival among the 3 groups, and the 5-year disease-free survival rates after first, second, and third or more hepatectomy were 37%, 29%, and 18%, respectively (P =.0169). Conclusion: Third or more repeat hepatectomy for recurrent HCC was performed safely and associated with relatively long-term survival. Third or more repeat hepatectomy for recurrent HCC seems justified, but high rate of HCC recurrence remains a problem..
459. Mizuki Ninomiya, Tetsuo Ikeda, Ken Shirabe, Hiroto Kayashima, Norifumi Harimoto, Tomohiro Iguchi, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hiroshi Saeki, Eiji Oki, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Masaru Morita, Yoshihiko Maehara, Three-dimensional computed tomography image based endovascular treatment for hepatic vein., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 469-472, 2013.11, Along with the expansion of living donor liver transplantation, whereby hepatic venous anastomosis is mandatory, the frequency of hepatic venous stenosis that need interventional treatment is increasing. Due to its anatomical features, there are several pitfalls in the process of endovascular intervention for hepatic vein. Insufficient information of and around the hepatic vein may lead to miss-diagnosis of target lesion. Simulation by using three-dimensional computed tomography images was useful in planning the direction of X-ray projection and, as a consequence, contributed to safe endovascular treatment for hepatic venous stenosis..
460. T. Yoshizumi, T. Ikegami, T. Toshima, N. Harimoto, H. Uchiyama, Y. Soejima, Y. Yamashita, K. Shirabe, Y. Maehara, Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma, Transplantation Proceedings, 10.1016/j.transproceed.2013.05.001, 45, 9, 3310-3313, 2013.11, We have proposed risk factors for tumor recurrence, such as tumor nodule ≥5 cm and des-gamma-carboxy prothrombin ≥300 mAU/mL after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors for HCC recurrence and mortality within our criteria. We enrolled 152 adult recipients who had undergone LDLT for end-stage liver disease with HCC who met our criteria. The recurrence-free survival rates after LDLT were calculated. Risk factors for tumor recurrence were identified. On univariate analysis, factors affecting recurrence-free survival were pretransplant treatment for HCC, neutrophil-to-lumphocyte ratio (NLR) >4, alpha-fetoprotein ≥400 ng/mL, ≥5 nodules, and bilobar tumor distribution. Multivariate analysis identified that NLR >4 and ≥5 nodules were independent risk factors for tumor recurrence after LDLT (P =.003 and P =.002, respectively). Two-step selection criteria enable selection of patients who have high-risk of tumor recurrence..
461. Toru Ikegami, Huanlin Wang, Daisuke Imai, Yuki Bekki, Tomoharu Yoshizumi, Yo-Ichi Yamashita, Takeo Toshima, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Pathological analysis of opened round ligaments as venous patch grafts in living donor liver transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.23716, 19, 11, 1245-51, 2013.11, Although the round ligament, including the umbilical vein, could be used as a venous graft in living donor liver transplantation (LDLT), no studies have determined its appropriate use on the basis of pathological findings. We prospectively examined 19 LDLT cases in which the donor's round ligament was procured and used as a venous graft. The round ligaments were categorized into 3 types based on the CD31 immunohistochemistry of tissue cross-sections: (I) canalized umbilical veins (n = 7 or 36.8%), (II) capillary umbilical vessels (n = 4 or 21.1%), and (III) occluded umbilical veins (n = 8 or 42.1%). After dilatation and incision, the round ligaments provided patch grafts that were 5.8 ± 0.4 cm long and 1.8 ± 1.2 cm wide. However, histological studies showed the absence of fine intimal layers on the dilated round ligaments after mechanical maneuvers. The ligaments were used to cuff the venous orifices in 15 patients (left lobe, n = 8; right lobe, n = 7) and were used as venous bridges in 4 patients (left lobe, n = 2; right lobe, n = 2). We detected no thrombosis at the implant sites after LDLT. Our pathological findings indicate that opened round ligaments can be used safely as venous patch grafts in LDLT..
462. Yo-ichi Yamashita, Ken Shirabe, Eiji Tsuijita, Kazuki Takeishi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Tohru Utsunomiya, Yoshihiko Maehara, Third or more repeat hepatectomy for recurrent hepatocellular carcinoma., Surgery, 10.1016/j.surg.2013.04.046, 154, 5, 1038-45, 2013.11, BACKGROUND: We sought to evaluate the surgical results of third or more repeat hepatectomy for recurrent hepatocellular carcinoma (HCC). The role of repeat hepatectomy for recurrent HCC, especially in cases with third or more repeat hepatectomy, is controversial. METHODS: We performed A retrospective, cohort study to analyze the surgical results of repeat hepatectomy performed at a single medical center from 1989 to 2011. A total of 1,000 hepatectomies for HCC were divided into 3 groups: A first hepatectomy group (n = 791), second hepatectomy group (n = 163), and third or more hepatectomy group (n = 46). Operative results and patient prognoses were compared among the 3 groups. RESULTS: There were no differences in early surgical results such as mortality and morbidity among the 3 groups. The 5-year survival rates after the first, second, and third or more hepatectomy were 67%, 60%, and 43%, respectively (P = .1913). There was a significant difference in disease-free survival among the 3 groups, and the 5-year disease-free survival rates after first, second, and third or more hepatectomy were 37%, 29%, and 18%, respectively (P = .0169). CONCLUSION: Third or more repeat hepatectomy for recurrent HCC was performed safely and associated with relatively long-term survival. Third or more repeat hepatectomy for recurrent HCC seems justified, but high rate of HCC recurrence remains a problem..
463. T. Yoshizumi, T. Ikegami, T. Toshima, N. Harimoto, H. Uchiyama, Y. Soejima, Y. Yamashita, K. Shirabe, Y. Maehara, Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma, Transplantation Proceedings, 10.1016/j.transproceed.2013.05.001, 45, 9, 3310-3313, 2013.11, We have proposed risk factors for tumor recurrence, such as tumor nodule ≥5 cm and des-gamma-carboxy prothrombin ≥300 mAU/mL after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors for HCC recurrence and mortality within our criteria. We enrolled 152 adult recipients who had undergone LDLT for end-stage liver disease with HCC who met our criteria. The recurrence-free survival rates after LDLT were calculated. Risk factors for tumor recurrence were identified. On univariate analysis, factors affecting recurrence-free survival were pretransplant treatment for HCC, neutrophil-to-lumphocyte ratio (NLR) >
4, alpha-fetoprotein ≥400 ng/mL, ≥5 nodules, and bilobar tumor distribution. Multivariate analysis identified that NLR >
4 and ≥5 nodules were independent risk factors for tumor recurrence after LDLT (P =.003 and P =.002, respectively). Two-step selection criteria enable selection of patients who have high-risk of tumor recurrence. © 2013 by Elsevier Inc. All rights reserved..
464. Hideki Ijichi, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Ken Shirabe, Yoshihiko Maehara, Recurrent hepatitis B following recurrence of hepatocellular carcinoma after living donor liver transplantation., Unknown Journal, 104, 10, 376-382, 2013.10, Hepatitis B virus (HBV) recurrence after liver transplantation for HBV-associated liver diseases results in decreased patient and graft survival. Herein we have reported two cases of HBV recurrence following relapse of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT). Both cases had LDLT for end-stage liver disease secondary to HBV infection with nodules of HCC exceeding the Milan criteria. HBV prophylaxis using hepatitis B immunoglobulin with nucleos (t) ide analogues were given and HBV DNA levels were consistently undetectable after LDLT. HCC recurred at 5 months and 13 months posttransplant respectively, and chemotherapy and radiation therapy were performed. HBV recurrence occurred during the treatment of HCC. HBV DNA levels increased despite the treatment with anti-HBV agents after HBV recurrence. In hepatitis B surface antigen positive recipients, HBV prophylaxis should be intensified during the treatment of recurrent HCC..
465. N. Harimoto, K. Shirabe, Y. I. Yamashita, T. Ikegami, T. Yoshizumi, Y. Soejima, T. Ikeda, Y. Maehara, A. Nishie, T. Yamanaka, Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma, British Journal of Surgery, 10.1002/bjs.9258, 100, 11, 1523-1530, 2013.10, Background Sarcopenia was identified recently as a poor prognostic factor in patients with cancer. The present study investigated the effect of sarcopenia on short- and long-term outcomes following partial hepatectomy for hepatocellular carcinoma (HCC), and aimed to identify prognostic factors. Methods Data were collected retrospectively for all consecutive patients who underwent hepatectomy for HCC with curative intent between January 2004 and December 2009. Patients were assigned to one of two groups according to the presence or absence of sarcopenia, assessed by computed tomographic measurement of muscle mass at the level of the third lumbar vertebra. Clinicopathological, surgical outcome and long-term survival data were analysed. Results Sarcopenia was present in 75 (40·3 per cent) of 186 patients, and was significantly correlated with female sex, lower body mass index and liver dysfunction, as indicated by abnormal serum albumin levels and indocyanine green retention test at 15 min values. In patients with, and without sarcopenia, the 5-year overall survival rate was 71 and 83·7 per cent respectively, and the 5-year recurrence-free survival rate was 13 and 33·2 per cent respectively. Multivariable analysis revealed that reduced skeletal muscle mass was predictive of an unfavourable prognosis. Conclusion Sarcopenia was predictive of worse overall survival even when adjusted for other known predictors in patients with HCC after partial hepatectomy..
466. Norifumi Harimoto, Hiroyuki Matsuyama, Kiyoshi Kajiyama, Takashi Nagaie, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Yoshihiko Maehara, Significance of stroke volume variation during hepatic resection under infrahepatic inferior vena cava and portal triad clamping., Unknown Journal, 104, 10, 362-369, 2013.10, Stroke volume variation (SVV), which is measured by analyzing arterial blood pressure waveform characteristics, is a simple and sensitive indicator of fluid responsiveness. The current retrospective study was to investigate SVV and central venous pressure (CVP) during hepatic resection under clamping of both the infrahepatic inferior vena cava (IVC) and the portal triad. All hepatic resections performed from December 2009 to February 2010 at the Department of Surgery at Iizuka Hospital in Japan were included in this study. Invasive hemodynamic monitoring including CVP and SVV were performed in 14 patients. CVP was significantly lower in patients with blood loss < or = 486 g than in those with blood loss > 486 g. SVV was significantly higher in patients with blood loss < or = 486 g than those with blood loss > 486 g during both IVC clamping and IVC + portal triad clamping. Estimated blood loss was significantly less in the group with SVV values > 18% compared to the group with values < or = 18%. There was a significant correlation between SVV and CVP (R2 = 0.714; P < .01). SVV is a useful indicator of intraoperative blood loss without the monitoring of CVP during hepatic resection under clamping of both the infrahepatic IVC and the portal triad..
467. Junji Kurashige, Genta Sawada, Yusuke Takahashi, Hidetoshi Eguchi, Tomoya Sudo, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Masayuki Watanabe, Masaki Mori, Hideo Baba, Koshi Mimori, Suppression of MAL gene expression in gastric cancer correlates with metastasis and mortality., Unknown Journal, 104, 10, 344-349, 2013.10, The Myelin and lymphocyte-associated protein gene (MAL), which is located on the long arm of chromosome 2, assigned to the region cen-q13 in humans, has been reported as tumor suppressor in several cancers. The aim of this study was to clarify the clinical significance of MAL gene in gastric cancer. The expression levels of MAL mRNA was examined using 50 resected gastric cancer specimens used by laser microdissected to determine the clinicopathological significance. MAL expression was then examined by real-time quantitative PCR assay, and we analyzed the correlation between MAL expression and clinicopathological factors. In clinicopathologic analysis, the low MAL expression group showed significantly higher incidence of lymph node metastasis than the high expression group (79% and 46%, respectively, p < 0.05). Furthermore, the low MAL expression group had a significantly poorer prognosis than the high expression group (p < 0.05). The MAL gene repression related with lymph node metastasis and poor prognosis in gastric cancer, suggesting that the MAL may be a new candidate node metastasis-suppressor gene for gastric cancer..
468. N. Harimoto, K. Shirabe, Y. I. Yamashita, T. Ikegami, T. Yoshizumi, Y. Soejima, T. Ikeda, Y. Maehara, A. Nishie, T. Yamanaka, Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma, British Journal of Surgery, 10.1002/bjs.9258, 100, 11, 1523-1530, 2013.10, Background Sarcopenia was identified recently as a poor prognostic factor in patients with cancer. The present study investigated the effect of sarcopenia on short- and long-term outcomes following partial hepatectomy for hepatocellular carcinoma (HCC), and aimed to identify prognostic factors. Methods Data were collected retrospectively for all consecutive patients who underwent hepatectomy for HCC with curative intent between January 2004 and December 2009. Patients were assigned to one of two groups according to the presence or absence of sarcopenia, assessed by computed tomographic measurement of muscle mass at the level of the third lumbar vertebra. Clinicopathological, surgical outcome and long-term survival data were analysed. Results Sarcopenia was present in 75 (40·3 per cent) of 186 patients, and was significantly correlated with female sex, lower body mass index and liver dysfunction, as indicated by abnormal serum albumin levels and indocyanine green retention test at 15 min values. In patients with, and without sarcopenia, the 5-year overall survival rate was 71 and 83·7 per cent respectively, and the 5-year recurrence-free survival rate was 13 and 33·2 per cent respectively. Multivariable analysis revealed that reduced skeletal muscle mass was predictive of an unfavourable prognosis. Conclusion Sarcopenia was predictive of worse overall survival even when adjusted for other known predictors in patients with HCC after partial hepatectomy. © 2013 British Journal of Surgery Society Ltd. Published by John Wiley &
Sons Ltd..
469. Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Koshi Mimori, Keishi Sugimachi, Masayuki Watanabe, Ken Shirabe, Yoshihiko Maehara, Application of splenectomy to decompress portal pressure in left lobe living donor liver transplantation., Fukuoka Acta Medica, 104, 9, 282-289, 2013.09, This study was conducted to evaluate the impact of splenectomy in living donor liver transplantation (LDLT) using left lobe grafts. The two hundred and fifty LDLT cases were divided into two groups: Group-S (n = 98, simultaneous splenectomy) and Group-NS (n = 152). Group-S had significantly increased recipient age (54.5 +/- 10.9 years vs. 46.3 +/- 17.0 years, p < 0.01), advanced liver diseases including Child class C (64.8% vs. 51.5%, p < 0.01), higher model for end-stage liver score (17.8 +/- 8.1 vs. 15.4 +/- 5.8, p < 0.01) and more patients with hospitalized status (67.4% vs. 48.0%, p < 0.01), and smaller graft volume/standard liver volume ratio (36.5 +/- 6.1% vs. 40.2 +/- 8.2%, p < 0.01). In Group-S, splenectomy decreased portal venous (PV) pressure decreased from 23.5 +/- 5.2 mmHg to 19.2 +/- 4.8 mmHg (p < 0.01). Group-S had significantly increased PV pressure at laparotomy (24.9 +/- 5.3 mmHg vs. 22.5 +/- 6.3 mmHg, p < 0.01) and decreased PV pressure at closure (16.4 +/- 3.5 mmHg vs. 18.0 +/- 4.7 mmHg, p < 0.01), compared with Group-NS. On the 14th day after LDLT, Group-S had lower total bilirubin (5.7 +/- 6.5 mg/dl vs. 8.7 +/- 8.9 mg/dl, p < 0.01) and smaller ascites output (0.4 +/- 0.7 L/day vs. 0.7 +/- 0.4 L/day, p = 0.01) than Group-NS. The cumulative 5-year graft survival rate was 86.8% in Group-S and 76.2% in Group-NS (p = 0.03). In conclusion, splenectomy had beneficial impacts on graft outcomes in left-lobe LDLT..
470. Yasue Kimura, Hiroyuki Matsuda, Hiroshi Saeki, Eiji Oki, Masaru Morita, Keishi Sugimachi, Yo ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Tetsuo Ikeda, Shinichi Tsutsui, Megumu Fujihara, Koshi Mimori, Masayuki Watanabe, Teruyoshi Ishida, Yoshihiko Maehara, Case of early adenosquamous carcinoma of the stomach., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 9, 315-320, 2013.09, Adenosquamous carcinoma of the stomach is very rare; at present, there are only seven published reports. We report here an eighth case involving a 77-year-old Japanese man who was diagnosed with gastric cancer by upper endoscopy and computed tomography (CT). He underwent laparoscopic-assisted distal gastrectomy for early gastric cancer and the resected specimen was diagnosed as adenosquamous carcinoma limited to the submucosal layer. Only one lymph node metastasis was noted. Seven months later, liver metastasis (3 tumors, 15 mm maximum in diameter) was detected by abdominal CT. He was started on chemotherapy with S-1 and cisplatin (CDDP) and is alive 14 months after surgery. Almost all cases of adenosquamous carcinoma of the stomach are diagnosed in advanced stages and carry a very poor prognosis. Most patients with early adenosquamous carcinoma of the stomach survive for 2 or more years without recurrence, however our patient experienced recurrence 7 months after surgery. Therefore, future treatment for recurrent adenosquamous carcinoma of the stomach should be considered..
471. Koichi Kimura, Toru Ikegami, Yo ichi Yamashita, Hiroshi Saeki, Eiji Oki, Tomoharu Yoshizumi, Hideaki Uchiyama, Hirofumi Kawanaka, Yuji Soejima, Masaru Morita, Ken Shirabe, Tetsuo Ikeda, Yoshihiko Maehara, Rendezvous technique treatment for late-onset biliary leakage after major hepatectomy of a living donor
report of a case., Fukuoka Acta Medica, 104, 9, 309-314, 2013.09, Biliary leakage is a major complication after hepatectomy. We report the case of a living-donor liver transplantation (LDLT) donor with a late-onset bile leak from the trifurcation of the hepatic duct who was successfully treated using rendezvous technique. A 52-year-old man underwent extended left hepatectomy for donation and was discharged on postoperative day (PD) 13. However, he was rehospitalized on PD 26 with severe abdominal pain. Physical examination suggested panperitonitis, and abdominocentesis showed bilious ascites. Emergent laparotomy for biliary leakage and peritonitis was performed. There was bilious ascites in the peritoneal cavity. A biliary fistula was recognized at the trifurcation of B8a, B8b, and B5. Intraoperative transhepatic biliary drainage of each bile duct was performed. Endoscopic transpapillary drainage was performed on PD 24. Finally, external drains were removed and complete internal drainage established on PD 70. The bile leak was considered to be the result of injury from electrocautery device. Appropriate making choices of the electrocautery devices enable us to avoid over thermal injury of the liver surface. Rendezvous bidirectional drainage effectively treated late-onset bile leakage from the trifurcation of a hepatic bile duct..
472. Eiji Oki, Yoshihisa Sakaguchi, Kippei Ohgaki, Hiroshi Saeki, Toru Ikegami, Kazuhito Minami, Yoichi Yamashita, Yasushi Toh, Yuji Soejima, Kouji Andou, Koshi Mimori, Masayuki Watanabe, Keishi Sugimachi, Hideaki Uchiyama, Tomoharu Yoshizumi, Hirofumi Kawanaka, Masaru Morita, Tetsuo Ikeda, Yoshihiko Maehara, Total laparoscopic distal gastrectomy for elderly patients with gastric cancer., Fukuoka Acta Medica, 104, 9, 290-298, 2013.09, This study evaluated the feasibility of totally laparoscopic distal gastrectomy (TLDG) in elderly patients with gastric cancer. We retrospectively analyzed the data from 138 patients who underwent TLDG from April 2005 to March 2009. Of these 138 patients, 20 were older than 75 years of age, and 118 were 75 years of age or younger. The preoperative respiratory function and American Society of Anesthesiologists (ASA) -physical status were significantly worse in the elderly patients than in the younger patients (P = 0.013). Hypertension and respiratory disease were more common in the elderly patients than in the younger patients (P = 0.032 / P = 0.005). The findings for the following parameters were similar in the two groups: intraoperative blood loss, operation time, severe postoperative complication rate, time required to start a solid diet, and duration of postoperative hospital stay. The rate of major complications was not different between the two groups, although minor complications were more commonly observed in the elderly patients. TLDG was found to be a safe procedure for elderly patients. This method can be used as one of the standard treatments for gastric cancer in elderly patients..
473. Takeo Toshima, Mitsuo Shimada, Toru Ikegami, Toru Utsunomiya, Tetsuya Ikemoto, Yuji Morine, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Fairly rare spontaneous disappearance of a hepatic artery aneurysm following living donor liver transplantation, Liver Transplantation, 10.1002/lt.23676, 19, 8, 929-930, 2013.08.
474. Yohei Mano, Ken Shirabe, Yo Ichi Yamashita, Norifumi Harimoto, Eiji Tsujita, Kazuki Takeishi, Shinichi Aishima, Toru Ikegami, Tomoharu Yoshizumi, Takeharu Yamanaka, Yoshihiko Maehara, Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma
A retrospective analysis, Annals of surgery, 10.1097/SLA.0b013e318297ad6b, 258, 2, 301-305, 2013.08, OBJECTIVE:: To clarify the prognostic value of the preoperative blood neutrophil-to-lymphocyte ratio (NLR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). BACKGROUND:: Although a high NLR has been reported to be a predictor of poor survival in patients with various cancers, it has not been extensively examined in patients with HCC. METHODS:: This retrospective study enrolled 958 patients who underwent hepatectomy without preoperative therapy for HCC from 1996 to 2009. Clinicopathological parameters, including NLR, were evaluated to identify predictors of overall and recurrence-free survival after hepatectomy. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. The best cutoff was determined with time-dependent receiver operating characteristic curve. To determine the mechanism of NLR elevation, immunohistological examination using CD163 staining was performed in 150 patients. RESULTS:: Univariate and multivariate analyses showed that NLR was an independent prognostic factor in overall and recurrence-free survival. The best cutoff of NLR was 2.81, and 238 of 958 patients (24.8%) had NLR of more than 2.81. The 5-year survival rate after hepatectomy was 72.9% in patients with NLR less than 2.81 and 51.5% in those with NLR 2.81 or more (P < 0.0001). CD163-positive cell counts were significantly higher in tumors in the group with NLR 2.81 or more than in the group with NLR less than 2.81 (P = 0.0004). CONCLUSIONS:: Our results show that NLR is an independent predictor of survival after hepatectomy in patients with HCC. Accumulation of tumor-associated macrophages in the tumor is associated with a high NLR..
475. Yoshizumi T, Ikegami T, Yoshiya S, Motomura T, Mano Y, Muto J, Ikeda T, Soejima Y, Shirabe K, Maehara Y, Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma., Hepatology Research, 10.1111, 43, 7, 709-716, 2013.07.
476. Tomoharu Yoshizumi, Toru Ikegami, Shohei Yoshiya, Takashi Motomura, Yohei Mano, Jun Muto, Tetsuo Ikeda, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma, Hepatology Research, 10.1111/hepr.12016, 43, 7, 709-716, 2013.07, Aim: Hepatocellular carcinoma (HCC) is primarily treated with hepatic resection and/or locoregional therapy. When HCC recurs and further treatment is no longer possible owing to poor liver function, liver transplantation (LT) or living-donor LT (LDLT) is considered. The aim of this study was to clarify risk factors for tumor recurrence after LDLT in patients with recurrent HCC. Methods: The study comprised 104 patients who had undergone LDLT because of end-stage liver disease with recurrent HCC. The recurrence-free survival rates after the LDLT were calculated. Risk factors for tumor recurrence were identified. Results: The 1-, 3- and 5-year recurrence-free survival rates were 89.6%, 80.3% and 78.4%, respectively. By univariate analysis, the factors affecting recurrence-free survival were the sum of the largest tumor size and number of tumors of 8 or more (P<0.0001), des-γ-carboxy prothrombin of more than 300mAU/mL (P = 0.0001), and a neutrophil-to-lymphocyte ratio (NLR) of 4 or more (P = 0.0002), α-fetoprotein of more than 400ng/mL (P = 0.0001) and bilobar tumor distribution (P = 0.046). A multivariate analysis identified independent risk factors for post-LDLT tumor recurrence including the sum of tumor size and number of tumors of 8 or more (P = 0.0004) and an NLR of 4 or more (P = 0.01). The 1- and 3- year recurrence-free survival rates in the recipients who had both risk factors were 30.0% and 15.0%, respectively. Conclusion: LDLT should not be performed for patients who have both independent risk factors after any treatments for HCC..
477. Toru Ikegami, Ken Shirabe, Shohei Yoshiya, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Takeo Toshima, Takashi Motomura, Yoshihiko Maehara, One-step reconstruction of the right inferior hepatic veins using auto-venous grafts in living donor liver transplantation, Surgery today, 10.1007/s00595-012-0449-5, 43, 7, 769-776, 2013.07, Purposes: Reconstruction of the right inferior hepatic vein (RIHV) presents a major technical challenge in living donor liver transplantation (LDLT) using right lobe grafts. Methods: We studied 47 right lobe LDLT grafts with RIHV revascularization, comparing one-step reconstruction, performed post-May 2007 (n = 16), with direct anastomosis, performed pre-May 2007 (n = 31). Results: In the one-step reconstruction technique, the internal jugular vein (n = 6), explanted portal vein (n = 5), inferior vena cava (n = 3), and shunt vessels (n = 2) were used as venous patch grafts for unifying the right hepatic vein, RIHVs, and middle hepatic vein tributaries. By 6 months after LDLT, there was no case of occlusion of the reconstructed RIHVs in the one-step reconstruction group, but a cumulative occlusion rate of 18.2 % in the direct anastomosis group. One-step reconstruction required a longer cold ischemic time (182 ± 40 vs. 115 ± 63, p < 0.001) and these patients had higher alanine transaminase values (142 ± 79 vs. 96 ± 46 IU/L, p = 0.024) on postoperative day POD 7. However, the 6-month short-term graft survival rates were 100 % with one-step reconstruction and 83.9 % with direct anastomosis, respectively. Conclusion: One-step reconstruction of the RIHVs using auto-venous grafts is an easy and feasible technique promoting successful right lobe LDLT..
478. Toru Ikegami, Ken Shirabe, Takasuke Fukuhara, Norihiro Furusyo, Kazuhiro Kotoh, Masaki Kato, Shinji Shimoda, Shinichi Aishima, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Maehara, Early extensive viremia, but not rs8099917 genotype, is the only predictor for cholestatic hepatitis C after living-donor liver transplantation, Hepatology Research, 10.1111/hepr.12003, 43, 6, 621-629, 2013.06, Aim: Cholestatic hepatitis C is one of the most serious but still unaddressed disorders after liver transplantation. Methods: In this study, we analyzed 49 patients who underwent living-donor liver transplantation (LDLT) to treat hepatitis C virus (HCV) infection. Results: Five patients developed cholestatic hepatitis C, with total bilirubin of 15.2±3.1mg/dL at diagnosis 6.2±1.0 weeks after LDLT. Univariate analysis showed that larger graft to standard liver volume ratio, higher HCV RNA titer at 2 weeks, earlier peak HCV RNA titer and cytomegalovirus infection were the significant risk factors. The development of cholestatic hepatitis C was not significantly associated with interleukin-28B genotype (rs8099917); four out of five affected patients had the T/T genotype. Multivariate analysis showed that higher HCV RNA titer at 2 weeks was the only significant factor (P=0.026) for the development of cholestatic hepatitis C. Receiver-operator curve analysis showed that that HCV RNA titer of more than 7.2log10IU/mL was the optimal cut-off for characterizing cholestatic hepatitis C. All of the patients were serum HCV RNA negative after treatment with pegylated interferon and ribavirin and all the patients are alive. Conclusion: Early extensive viremia, but not the rs8099917 genotype, was the only predictor for cholestatic hepatitis C after LDLT..
479. Ken Shirabe, T. Motomura, K. Takeishi, K. Morita, H. Kayashima, A. Taketomi, T. Ikegami, Y. Soejima, T. Yoshizumi, Y. Maehara, Human early liver regeneration after hepatectomy in patients with hepatocellular carcinoma
Special reference to age, Scandinavian Journal of Surgery, 10.1177/1457496913482250, 102, 2, 101-105, 2013.06, Background and Aims: This study was conducted to clarify the effects of age on human liver regeneration. Patients and Methods: Thirty major hepatectomies, equal to or more than two segmentectomies for hepatocellular carcinoma, were performed. Ages ranged from 37 to 85 years and five octogenarians were included. The early regenerative index was defined: (liver volume after 7 days after hepatectomy - estimated remnant liver volume before hepatectomy)/estimated remnant liver volume, using three-dimensional computed tomographic volumetry. Farnesoid X receptor and forkhead box m1 expression in the liver, which has been reported to age-related decrease of liver regeneration in animal model, were examined using real-time polymerase chain reaction. The patients were divided into two groups: low early regenerative index (n = 15), early regenerative index less than 55% and high early regenerative index (n = 15), early regenerative index equal to or more than 55%. Results: The mean early regenerative index was 57%. Age (R2 = 0.274, P = 0.003) and estimated blood loss (R2 = 0.134, P = 0.0466) were inversely correlated with the early regenerative index, and the expression of farnesoid X receptor and forkhead box m1 was not. The incidence of posthepatectomy liver failure in the low early regenerative index group was higher than that in the high early regenerative index group (P = 0.0421). Conclusions: Age and intraoperative blood loss are inversely correlated with early liver regeneration in humans. In elderly patients, massive blood loss should be avoided in view of liver regeneration..
480. Noboru Harada, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Katsuhiro Asonuma, Yukihiro Inomata, Yoshihiko Maehara, Intrahepatic artery pseudoaneurysm associated with a metallic biliary stent after living donor liver transplantation
Report of a case, Surgery today, 10.1007/s00595-012-0302-x, 43, 6, 678-681, 2013.06, An intrahepatic artery pseudoaneurysm (IHAA) is a very rare but potentially lethal complication occurring after liver transplantation. This report presents a case of an IHAA associated with a metallic biliary stent after liver transplantation. A 40-year-old male underwent living donor liver transplantation (LDLT) using a left lobe graft. The bile duct reconstruction was performed with Roux-en-Y hepaticojejunostomy. He developed obstructive jaundice 5 years after LDLT, and had biliary stricture of the anastomosis area, therefore, the two metallic biliary stents were finally positioned at the stricture of the biliary tract. He suddenly developed hematemesis 8 years after LDLT, and computerized tomography scan showed an IHAA. Although seven interlocking detachable coils were placed at the neck of the aneurysm, hematemesis recurred 3 days after the initial embolization. Therefore, retransplantation was successfully performed 25 days after the embolization of IHAA using a right lobe graft from his son. In conclusion, metal stent insertion can lead to the fatal complication of HAA. The placement of a metallic stent could have been avoided in this case. Percutaneous metallic stent insertion for biliary stenosis after liver transplantation should therefore only be performed in carefully selected patients..
481. Naotaka Hashimoto, Tomohiko Akahoshi, Masahiro Kamori, Morimasa Tomikawa, Daisuke Yoshida, Yoshihiro Nagao, Kazutoyo Morita, Hiroto Kayashima, Toru Ikegami, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Treatment of bleeding rectal varices with transumbilical venous obliteration of the inferior mesenteric vein, Surgical Laparoscopy, Endoscopy and Percutaneous Techniques, 10.1097/SLE.0b013e31828031ec, 23, 3, e134-e137, 2013.06, A 56-year-old male with alcohol-induced liver cirrhosis developed rectal varices. He had a prior history of treatment for esophageal varices with endoscopic variceal ligation. Despite the repeated treatment for rectal varices with endoscopic variceal ligation, endoscopic injection sclerotherapy, and surgery, the bleeding from the rectal varices could not be controlled. Multidetector-row computed tomography and 3D-angiography revealed the hemodynamic profile of the rectal varices. We next approached the rectal varices through the umbilical vein on the abdominal wall, and successfully embolized the varices continuing from the inferior mesenteric vein using coils and a 5% solution of ethanolamine oleate with iopamidol..
482. K. Shirabe, T. Motomura, K. Takeishi, K. Morita, H. Kayashima, A. Taketomi, T. Ikegami, Y. Soejima, T. Yoshizumi, Y. Maehara, HUMAN EARLY LIVER REGENERATION AFTER HEPATECTOMY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA: SPECIAL REFERENCE TO AGE, SCANDINAVIAN JOURNAL OF SURGERY, 102, 2, 101-105, 2013.06, Background and Aims: This study was conducted to clarify the effects of age on human liver regeneration.
Patients and Methods: Thirty major hepatectomies, equal to or more than two segmentectomies for hepatocellular carcinoma, were performed. Ages ranged from 37 to 85 years and five octogenarians were included. The early regenerative index was defined: (liver volume after 7 days after hepatectomy -estimated remnant liver volume before hepatectomy)/estimated remnant liver volume, using three-dimensional computed tomographic volumetry. Farnesoid X receptor and forkhead box ml expression in the liver, which has been reported to age-related decrease of liver regeneration in animal model, were examined using real-time polymerase chain reaction. The patients were divided into two groups: low early regenerative index (n = 15), early regenerative index less than 55% and high early regenerative index (n = 15), early regenerative index equal to or more than 55%.
Results: The mean early regenerative index was 57%. Age (R-2 = 0.274, P = 0.003) and estimated blood loss (R-2 = 0.134, P = 0.0466) were inversely correlated with the early regenerative index, and the expression of farnesoid X receptor and forkhead box ml was not. The incidence of posthepatectomy liver failure in the low early regenerative index group was higher than that in the high early regenerative index group (P = 0.0421).
Conclusions: Age and intraoperative blood loss are inversely correlated with early liver regeneration in humans. In elderly patients, massive blood loss should be avoided in view of liver regeneration..
483. Naotaka Hashimoto, Tomohiko Akahoshi, Masahiro Kamori, Morimasa Tomikawa, Daisuke Yoshida, Yoshihiro Nagao, Kazutoyo Morita, Hiroto Kayashima, Toru Ikegami, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Treatment of bleeding rectal varices with transumbilical venous obliteration of the inferior mesenteric vein., Surgical laparoscopy, endoscopy & percutaneous techniques, 10.1097/SLE.0b013e31828031ec, 23, 3, e134-7, 2013.06, A 56-year-old male with alcohol-induced liver cirrhosis developed rectal varices. He had a prior history of treatment for esophageal varices with endoscopic variceal ligation. Despite the repeated treatment for rectal varices with endoscopic variceal ligation, endoscopic injection sclerotherapy, and surgery, the bleeding from the rectal varices could not be controlled. Multidetector-row computed tomography and 3D-angiography revealed the hemodynamic profile of the rectal varices. We next approached the rectal varices through the umbilical vein on the abdominal wall, and successfully embolized the varices continuing from the inferior mesenteric vein using coils and a 5% solution of ethanolamine oleate with iopamidol..
484. Hideki Ijichi, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Youhei Mano, Shinichi Aishima, Koichiro Abe, Hiroshi Honda, Yoshihiko Maehara, Clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography for patients with primary liver cancer with special reference to rare histological types, hepatocellular carcinoma with sarcomatous change and combined hepatocellular and cholangiocarcinoma, Hepatology Research, 10.1111/j.1872-034X.2012.01107.x, 43, 5, 481-487, 2013.05, Aim: The role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis and staging of primary liver cancer has been demonstrated in several reports. However, no preoperative evaluations of sarcomatous hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (cHCC-CC) with FDG-PET have been reported so far. Methods: Fifty-three HCC patients and three cHCC-CC patients who received liver resection or living-donor liver transplantation were enrolled in this study. All 56 patients had undergone preoperative FDG-PET, and a total of 67 HCC and three cHCC-CC were analyzed histologically. The relationship between clinicopathological features and the maximum standardized uptake value (SUVmax) of tumors were evaluated. Results: The detection rate of HCC by FDG-PET was 43.3 %, and the sensitivity of FDG-PET for the detection of HCC was significantly associated with tumor differentiation, tumor size and microvascular invasion. All three cHCC-CC were detected by FDG-PET. The SUVmax values of the three sarcomatous HCC (SUVmax 14.1, 18.6 and 25.0) and the three cHCC-CC (SUVmax 9.9, 12.0 and 13.0) were higher than that of the poorly differentiated HCC (mean SUVmax 5.7±2.3). Conclusion: SUVmax may be a useful diagnostic tool for the preoperative evaluation of the aggressiveness of primary liver cancers such as sarcomatous HCC and cHCC-CC..
485. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Norihiro Furusyo, Kazuhiro Kotoh, Masaki Kato, Shinji Shimoda, Yuji Soejima, Takashi Motomura, Takasuke Fukuhara, Yoshihiko Maehara, Impact of conversion from pegylated interferon-α2b to interferon-α2a for treating recurrent hepatitis C after liver transplantation, Transplantation, 10.1097/TP.0b013e318283a82e, 95, 6, e38-e42, 2013.05.
486. Toshiro Masuda, Ken Shirabe, Shohei Yoshiya, Rumi Matono, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Hideo Baba, Yoshihiko Maehara, Nutrition support and infections associated with hepatic resection and liver transplantation in patients with chronic liver disease, Journal of Parenteral and Enteral Nutrition, 10.1177/0148607112456041, 37, 3, 318-326, 2013.05, Malnutrition is common in liver cirrhotic patients who will undergo liver resection or liver transplantation. A precise evaluation of their nutrition status is thus difficult because of the presence of ascites and the edema caused by their impaired protein synthesis. Both perioperative enteral and parenteral nutrition have benefits in reducing the morbidity and mortality of liver surgery, and in general, oral nutrition supplements are recommended. Branched-chain amino acids (BCAAs) promote protein and glycogen synthesis and regulate immune system function. Synbiotics, a combination of pro- and prebiotics, is reported to enhance immune responses. Oral nutrition support with BCAAs, synbiotics, and an immune-enhancing diet have a beneficial effect on preventing the perioperative infections associated with hepatic resection or liver transplantation..
487. Toru Ikegami, Ken Shirabe, Hidekazu Nakagawara, Tomoharu Yoshizumi, Takeo Toshima, Yuji Soejima, Hideaki Uchiyama, Yo Ichi Yamashita, Norifumi Harimoto, Yoshihiko Maehara, Obstructing spontaneous major shunt vessels is mandatory to keep adequate portal inflow in living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e318288cadc, 95, 10, 1270-1277, 2013.05, BACKGROUND: It has not been addressed whether the major spontaneous portosystemic shunt vessels should be ligated in living-donor liver transplantation (LDLT). METHODS: We performed a retrospective analysis of 324 cases of adult-to-adult LDLT. RESULTS: Factors associated with the presence of major (>10 mm) shunt vessels (n=130) included portal vein (PV) thrombosis (27.7%), lower PV pressure at laparotomy, Child-Pugh class C, and transplantation of right-side grafts. The types of major portosystemic shunt vessels included splenorenal shunts (46.2%), gastroesophageal shunts (26.9%), mesocaval shunts (13.8%), and others (13.1%). Ligation of the major shunt vessels increased PV pressure (mean [SD], from 16.8 [3.9] mm Hg to 18.6 [4.3] mm Hg; P<0.001) and PV flow (mean [SD], from 1.35 [0.67] L/min to 1.67 [0.67] L/min; P<0.001) into the grafts. Post-LDLT computed tomography showed patent major shunts in 14 patients. Nine of such patients (64.3%) with unligated major shunt vessels (undetected shunt vessels, n=5; incomplete ligation, n=2; and the shunt was newly created or left open to maintain high PV pressure after reperfusion, n=3) required secondary interventions. Two of these patients died because of graft dysfunction. PV flow was significantly lower in the nine patients who underwent secondary ligation of the major shunt vessels compared with patients with successful primary ligation (mean [SD], 0.96 [0.34] L/min vs. 1.65 [0.63] L/min; P=0.001). CONCLUSIONS: It is an appropriate option to obstruct the major portosystemic shunt vessels to ensure adequate graft inflow in LDLT..
488. Shohei Yoshiya, Ken Shirabe, Yoshihiro Matsumoto, Tetsuo Ikeda, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Yoshihiko Maehara, Rendezvous ductoplasty for biliary anastomotic stricture after living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31828a9450, 95, 10, 1278-1283, 2013.05, BACKGROUND: Biliary anastomotic stricture (BAS) after living-donor liver transplantation (LDLT) is difficult to manage. We used rendezvous ductoplasty (RD) to treat BAS after LDLT. METHODS: We retrospectively analyzed 53 patients with BAS after adult-to-adult LDLT with duct-to-duct biliary reconstruction. RESULTS: BAS was classified according to endoscopic retrograde cholangiography findings after normal-pressure contrast injection: type I (n=32) in which the stricture was visualized; type II (n=13) in which the common hepatic duct and graft intrahepatic ducts were visualized, but the stricture was not visualized; or type III (n=8) in which the stricture and graft intrahepatic ducts were not visualized. In right lobe grafts, types II and III occurred more frequently than type I (P=0.0023). Type I had significantly shorter cold ischemic time (76±11 vs. 118±12 min; P=0.0155) and warm ischemic time (38±2 vs. 49±3 min; P=0.0069) than types II and III. The number of attempts to pass the guidewire through the stricture was significantly lower in type I (1.2±0.2 attempts) than type II (2.2±0.2 attempts; P=0.0018) or type III (2.8±0.3 attempts; P<0.0001). The treatment success rate was 78.1% for type I, 38.5% for type II, and 50.0% for type III (P=0.0282). RD was the first successful treatment in a higher proportion of types II and III patients than type I patients (66.7% vs. 6.3%; P<0.0001). Cumulative treatment success rates were not significantly different between the RD and the non-RD groups (P=0.0920). CONCLUSIONS: RD was a useful treatment for difficult cases of BAS after LDLT and achieved successful outcomes..
489. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Hiroto Kayashima, Yoshihiko Maehara, Use of the SAND balloon catheter in single-incision laparoscopic cholecystectomy for acute cholecystitis., Unknown Journal, 10.1111/ases.12005, 6, 2, 134-136, 2013.05, SILS for acute cholecystitis is technically challenging because of the difficulties in obtaining optical surgical field. A 2-cm incision was made through the umbilicus, a single port and trocars were introduced, and the abdomen was then insufflated. A 5-mm SAND balloon punctured the abdominal wall and then the gallbladder wall. The distal and proximal balloons were inflated to prevent bile leakage, and the bile was aspirated. The collapsed gallbladder was then retracted cephalad, the critical structures were exposed, and the cystic artery and duct were divided. The gallbladder was dissected and removed through the umbilicus, and the abdomen was closed. We performed this procedure in three cases with acute cholecystitis. Operative times were 95, 133 and 244 min, blood loss was 5, 10 and 43 mL, and postoperative hospital stay was 2, 2 and 3 days, respectively. The single-incision laparoscopic approach with the SAND balloon is a feasible technique for acute cholecystitis..
490. Hideki Ijichi, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Youhei Mano, Shinichi Aishima, Koichiro Abe, Hiroshi Honda, Yoshihiko Maehara, Clinical usefulness of (18) F-fluorodeoxyglucose positron emission tomography/computed tomography for patients with primary liver cancer with special reference to rare histological types, hepatocellular carcinoma with sarcomatous change and combined hepatocellular and cholangiocarcinoma., Hepatology research : the official journal of the Japan Society of Hepatology, 10.1111/j.1872-034X.2012.01107.x, 43, 5, 481-7, 2013.05, AIM: The role of (18) F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis and staging of primary liver cancer has been demonstrated in several reports. However, no preoperative evaluations of sarcomatous hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (cHCC-CC) with FDG-PET have been reported so far. METHODS: Fifty-three HCC patients and three cHCC-CC patients who received liver resection or living-donor liver transplantation were enrolled in this study. All 56 patients had undergone preoperative FDG-PET, and a total of 67 HCC and three cHCC-CC were analyzed histologically. The relationship between clinicopathological features and the maximum standardized uptake value (SUVmax) of tumors were evaluated. RESULTS: The detection rate of HCC by FDG-PET was 43.3 %, and the sensitivity of FDG-PET for the detection of HCC was significantly associated with tumor differentiation, tumor size and microvascular invasion. All three cHCC-CC were detected by FDG-PET. The SUVmax values of the three sarcomatous HCC (SUVmax 14.1, 18.6 and 25.0) and the three cHCC-CC (SUVmax 9.9, 12.0 and 13.0) were higher than that of the poorly differentiated HCC (mean SUVmax 5.7 ± 2.3). CONCLUSION: SUVmax may be a useful diagnostic tool for the preoperative evaluation of the aggressiveness of primary liver cancers such as sarcomatous HCC and cHCC-CC..
491. Kazutoyo Morita, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Naotaka Hashimoto, Yohei Mano, Tatsunori Miyata, Yuji Soejima, Yoshihiko Maehara, Feasible isolated liver transplantation for a cirrhotic patient on chronic hemodialysis., Case reports in gastroenterology, 10.1159/000354140, 7, 2, 299-303, 2013.05, End-stage liver and kidney disease (ELKD) is an indication for deceased donor simultaneous liver-kidney transplantation. Although a few cases of living donor liver-kidney transplantation have been reported, the invasiveness remains to be discussed. Living donor liver transplantation (LDLT) is an alternative choice for ELKD, but has never been reported. Here, we report a case of successful LDLT for a patient with ELKD on hemodialysis. The patient was a 63-year-old male and had decompensated hepatitis C cirrhosis with seronegativity for hepatitis C virus. He had non-diabetic end-stage renal failure and had been on hemodialysis for 3 years. He was in good general condition except for hepatic and renal failure. The living donor was his 58-year-old healthy wife. A right lobe graft was transplanted to the recipient under continuous hemodiafiltration (CHDF) and extracorporeal veno-venous bypass. CHDF was continued until postoperative day 4, at which point CHDF was converted to hemodialysis. His posttransplant course was good and he was discharged on postoperative day 36. To the best of our knowledge, this is the first report of LDLT for a patient on chronic hemodialysis. Therefore, being on hemodialysis is not a contraindication for LDLT. LDLT is feasible for a patient with ELKD on hemodialysis..
492. Ikegami T, Shirabe K, Yoshizumi T, Furusyo N, Kotoh K, Kato M, Shimoda S, Soejima Y, Motomura T, Fukuhara T, Maehara Y, Impact of conversion from pegylated interferon-α2b to interferon-α2a for treating recurrent hepatitis C after liver transplantation., Transplantation, 10.1097/TP.0b013e318283a82e, 95, 6, e38-e42, 2013.05.
493. Toru Ikegami, Ken Shirabe, Hidekazu Nakagawara, Tomoharu Yoshizumi, Takeo Toshima, Yuji Soejima, Hideaki Uchiyama, Yo-Ichi Yamashita, Norifumi Harimoto, Yoshihiko Maehara, Obstructing spontaneous major shunt vessels is mandatory to keep adequate portal inflow in living-donor liver transplantation., Transplantation, 10.1097/TP.0b013e318288cadc, 95, 10, 1270-7, 2013.05, BACKGROUND: It has not been addressed whether the major spontaneous portosystemic shunt vessels should be ligated in living-donor liver transplantation (LDLT). METHODS: We performed a retrospective analysis of 324 cases of adult-to-adult LDLT. RESULTS: Factors associated with the presence of major (>10 mm) shunt vessels (n=130) included portal vein (PV) thrombosis (27.7%), lower PV pressure at laparotomy, Child-Pugh class C, and transplantation of right-side grafts. The types of major portosystemic shunt vessels included splenorenal shunts (46.2%), gastroesophageal shunts (26.9%), mesocaval shunts (13.8%), and others (13.1%). Ligation of the major shunt vessels increased PV pressure (mean [SD], from 16.8 [3.9] mm Hg to 18.6 [4.3] mm Hg; P<0.001) and PV flow (mean [SD], from 1.35 [0.67] L/min to 1.67 [0.67] L/min; P<0.001) into the grafts. Post-LDLT computed tomography showed patent major shunts in 14 patients. Nine of such patients (64.3%) with unligated major shunt vessels (undetected shunt vessels, n=5; incomplete ligation, n=2; and the shunt was newly created or left open to maintain high PV pressure after reperfusion, n=3) required secondary interventions. Two of these patients died because of graft dysfunction. PV flow was significantly lower in the nine patients who underwent secondary ligation of the major shunt vessels compared with patients with successful primary ligation (mean [SD], 0.96 [0.34] L/min vs. 1.65 [0.63] L/min; P=0.001). CONCLUSIONS: It is an appropriate option to obstruct the major portosystemic shunt vessels to ensure adequate graft inflow in LDLT..
494. Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Hiroto Kayashima, Yoshihiko Maehara, Use of the SAND balloon catheter in single-incision laparoscopic cholecystectomy for acute cholecystitis., Asian journal of endoscopic surgery, 10.1111/ases.12005, 6, 2, 134-6, 2013.05, INTRODUCTION: SILS for acute cholecystitis is technically challenging because of the difficulties in obtaining optical surgical field. MATERIALS AND SURGICAL TECHNIQUE: A 2-cm incision was made through the umbilicus, a single port and trocars were introduced, and the abdomen was then insufflated. A 5-mm SAND balloon punctured the abdominal wall and then the gallbladder wall. The distal and proximal balloons were inflated to prevent bile leakage, and the bile was aspirated. The collapsed gallbladder was then retracted cephalad, the critical structures were exposed, and the cystic artery and duct were divided. The gallbladder was dissected and removed through the umbilicus, and the abdomen was closed. We performed this procedure in three cases with acute cholecystitis. Operative times were 95, 133 and 244 min, blood loss was 5, 10 and 43 mL, and postoperative hospital stay was 2, 2 and 3 days, respectively. DISCUSSION: The single-incision laparoscopic approach with the SAND balloon is a feasible technique for acute cholecystitis..
495. Mikihiro Kohno, Ken Shirabe, Yohei Mano, Jun Muto, Takashi Motomura, Kazuki Takeishi, Takeo Toshima, Masanori Yoshimatsu, Hideki Ijichi, Noboru Harada, Shinichi Aishima, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Granulocyte colony-stimulating-factor-producing hepatocellular carcinoma with extensive sarcomatous changes
Report of a case, Surgery today, 10.1007/s00595-012-0202-0, 43, 4, 439-445, 2013.04, This report describes a rare case of hepatocellular carcinoma (HCC) producing granulocyte colony-stimulating factor (G-CSF). A 46-year-old male with chronic hepatitis B, who presented with fever, general malaise, loss of appetite, and weight loss, had a huge liver mass in the portal region. He had marked granulocytosis and his serum level of G-CSF was elevated. Complete tumor resection was performed, and the pathological assessment of the resected specimen revealed HCC with extensive sarcomatous changes and immunohistochemical staining for G-CSF and G-CSF receptor. Only a few cases of G-CSF-producing HCC have been reported, and this is the first case of G-CSF-producing HCC that also expressed G-CSF receptor..
496. Yu Saito, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Koji Yamasaki, Noriaki Sadanaga, Hiroshi Matsuura, Kenichiro Okadome, Hepatic artery aneurysm in a patient with hepatitis c liver cirrhosis
Report of a case, Clinical Journal of Gastroenterology, 10.1007/s12328-013-0372-3, 6, 2, 169-172, 2013.04, Visceral artery aneurysms are rare, with an incidence rate of only 0.01-0.2 % in routine autopsies, and hepatic artery aneurysms account for approximately 20 % of these aneurysms. Despite recent advances in therapeutic techniques and diagnostic tools, the management of visceral artery aneurysms remains clinically challenging. We report a case of hepatic artery aneurysm with liver cirrhosis due to hepatitis C in an 81-year-old woman. A computed tomography scan demonstrated a hepatic artery aneurysm 4.4 cm in diameter. She underwent successful aneurysmectomy with vascular anastomosis. A computed tomography scan on postoperative day 7 demonstrated patent hepatic artery. The patient was followed-up for 1 year after surgery and died owing to progressive liver failure. However, she did not show any hepatic artery problem such as hepatic arterial thrombosis or occlusion. We discuss the risk factors of atherosclerosis in patients with liver cirrhosis, and present an overview of the treatment of hepatic artery aneurysms..
497. Yo Ichi Yamashita, Ken Shirabe, Eiji Tsujita, Kazuki Takeishi, Tetsuo Ikeda, Tomoharu Yoshizumi, Yoshinari Furukawa, Teruyoshi Ishida, Yoshihiko Maehara, Surgical outcomes of pancreaticoduodenectomy for periampullary tumors in elderly patients, Langenbeck's Archives of Surgery, 10.1007/s00423-013-1061-x, 398, 4, 539-545, 2013.04, Backgrounds: Pancreaticoduodenectomy (PD) is an aggressive surgery with considerable operative risks, but offers the only chance for cure in patients with periampullary tumors. A growing number of elderly patients are being offered PD because of the aging of populations in developed countries. We examined surgical outcomes of PD in patients aged 75 years and older (≥75 years). Methods: A retrospective cohort study was performed in 65 consecutive patients who underwent PD for periampullary tumors at a single medical center during the 5 years from 2006 to 2010. We analyzed surgical outcomes such as mortality and morbidity after PD in patients aged ≥75 years (n = 21) compared to those in patients aged <75 years (n = 44). Results: The positive rate of comorbidities such as hypertension was significantly higher in patients aged ≥75 years than in patients aged <75 years (76 vs. 48 %; p = 0.03). The incidence of wound infection was significantly higher in patients aged ≥75 years than in patients aged <75 years (19 vs. 0 %; p < 0.01). However, there was no significant difference in the mortality rate (0 vs. 2 %; p = 0.49) or the overall morbidity rate (33 vs. 32 %; p = 0.90). There was no significant difference in changes in body weight or serum albumin levels during the 3 months after PD between the two groups, but the recovery of serum prealbumin levels from 1 to 3 months after PD in patients aged ≥75 years was significantly delayed compared to that in patients aged <75 years (p = 0.04). There was no statistically significant difference in long-term survival between the two groups. Conclusions: Advanced age alone should not discourage surgeons from offering PD, although nutritional supports after PD for elderly patients aged ≥75 years are needed..
498. Yu Saito, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Koji Yamasaki, Noriaki Sadanaga, Hiroshi Matsuura, Kenichiro Okadome, Hepatic artery aneurysm in a patient with hepatitis C liver cirrhosis: report of a case., Clinical journal of gastroenterology, 10.1007/s12328-013-0372-3, 6, 2, 169-72, 2013.04, Visceral artery aneurysms are rare, with an incidence rate of only 0.01-0.2 % in routine autopsies, and hepatic artery aneurysms account for approximately 20 % of these aneurysms. Despite recent advances in therapeutic techniques and diagnostic tools, the management of visceral artery aneurysms remains clinically challenging. We report a case of hepatic artery aneurysm with liver cirrhosis due to hepatitis C in an 81-year-old woman. A computed tomography scan demonstrated a hepatic artery aneurysm 4.4 cm in diameter. She underwent successful aneurysmectomy with vascular anastomosis. A computed tomography scan on postoperative day 7 demonstrated patent hepatic artery. The patient was followed-up for 1 year after surgery and died owing to progressive liver failure. However, she did not show any hepatic artery problem such as hepatic arterial thrombosis or occlusion. We discuss the risk factors of atherosclerosis in patients with liver cirrhosis, and present an overview of the treatment of hepatic artery aneurysms..
499. Akinobu Taketomi, Ken Shirabe, Jun Muto, Shohei Yoshiya, Takashi Motomura, Yohei Mano, Tohru Ikegami, Tomoharu Yoshizumi, Kenji Sugio, Yoshihiko Maehara, A rare point mutation in the Ras oncogene in hepatocellular carcinoma, Surgery today, 10.1007/s00595-012-0462-8, 43, 3, 289-292, 2013.03, Purpose: The Ras gene is one of the oncogenes most frequently detected in human cancers, and codes for three proteins (K-, N-, and H-Ras). The aim of this study was to examine the mutations in codons 12, 13 and 61 of the three Ras genes in cases of human hepatocellular carcinoma (HCC). Methods: Paired samples of HCC and corresponding non-malignant liver tissue were collected from 61 patients who underwent hepatectomy. A dot-blot analysis was used to analyze the products of the polymerase chain reaction (PCR) amplification of codons 12, 13, and 61 of K-, N- and H-Ras for mutations. Results: Only one mutation (K-Ras codon 13; Gly to Asp) was detected among the 61 patients. Interestingly, this patient had a medical history of surgery for both gastric cancer and right lung cancer. No mutations were found in codons 12 and 61 of K-Ras or codons 12, 13 and 61 of the N-Ras and H-Ras genes in any of the HCCs or corresponding non-malignant tissues. Conclusions: These findings indicated that the activation of Ras proto-oncogenes by mutations in codons 12, 13, and 61 does not play a major role in hepatocellular carcinogenesis..
500. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Tetsuo Ikeda, Yoshihiko Maehara, A simple and secure ligation of the main pancreatic duct in distal pancreatectomy, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.10.021, 216, 3, e23-e25, 2013.03.
501. Tetsuo Ikeda, Shohei Yoshiya, Takeo Toshima, Norifumi Harimoto, Youichi Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, Laparoscopic distal pancreatectomy preserving the spleen and splenic vessels for benign and low-grade malignant pancreatic neoplasm., Unknown Journal, 104, 3, 54-63, 2013.03, Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) is expected to be less invasive than laparoscopic distal pancreatectomy with splenectomy. However, there are few reports regarding the details of the procedure for LSPDP, and its safety remains unclear. This study aimed to evaluate the feasibility and safety of LSPDP. Six patients underwent LSPDP from March 2009 to February 2013 in our center, and their clinical data and outcomes were reviewed retrospectively. A total of six laparoscopic distal pancreatic resections were attempted in four female and two male patients. All of the operations were successful, with an average operative time of 290.7 min (range: 211-377 min) and an average blood loss of 43.5 g (range: 0-142 g). The mean hospital stay was 11.8 days (range: 9-17days). No obvious pancreatic fistulas occurred, although pseudocysts at the stump of the pancreas were recognized in three patients on CT scans performed at 7 days postoperatively. Postoperative pathological examinations revealed two cases of serous cystadenoma in the body and tail of the pancreas, one case of serous oligocystic adenoma, one case of mucinous cystadenoma, one case of neuroendocrine tumor, and one case of solid-pseudopapillary neoplasm. LSPDP is minimally invasive, safe, and feasible for the management of benign pancreatic tail tumors, with the advantages of earlier recovery and less morbidity from complications..
502. Yuji Soejima, Jyun Muto, Rumi Matono, Mizuki Ninomiya, Tetsuo Ikeda, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Ken Shirabe, Yoshihiko Maehara, Strategic breakthrough in adult ABO-incompatible living donor liver transplantation
Preliminary results of consecutive seven cases, Clinical Transplantation, 10.1111/ctr.12060, 27, 2, 227-231, 2013.03, ABO-incompatibility is a major obstacle to expanding exiguous donor pools in adult liver transplantation, especially in countries where grafts from deceased donors are uncommon. We present our preliminary results of ABO-incompatible (ABO-I) adult living donor liver transplantation (LDLT) using a new, simple protocol. Seven consecutive cases of ABO-I LDLT were managed by the same protocol including pre-operative administration of a single dose of rituximab (375 mg/m2) followed by three to five sessions of plasma exchange before LDLT without portal infusion therapy. The triple immunosuppression protocol consisted of tacrolimus, mycophenolate mofetil and steroids, with mycophenolate mofetil starting seven d before LDLT. Splenectomy was performed for all cases. All patients are alive (100% survival) with a mean follow-up of 852 d (715-990 d). Neither antibody-mediated nor hyperacute rejection were encountered. There was only one episode of mild acute cellular rejection, for which steroid augmentation was effective. The median preformed isoagglutinin antibody titer before plasma exchange was 256, while the median antibody titer immediately before LDLT was 16. In conclusion, adult ABO-I LDLT results were excellent - comparable or even superior to those of ABO-compatible LDLT. ABO-I adult LDLT has now become a more applicable modality without the need for an appropriate donor..
503. Toru Ikegami, Ken Shirabe, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Yo Ichi Yamashita, Norifumi Harimoto, Takeo Toshima, Shohei Yoshiya, Tetsuo Ikeda, Yoshihiko Maehara, Strategies for successful left-lobe living donor liver transplantation in 250 consecutive adult cases in a single center, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.11.011, 216, 3, 353-362, 2013.03, Background: Living donor liver transplantation (LDLT) using left-lobe grafts was not generally recognized as feasible due to the problem of graft size. Study Design: We retrospectively evaluated strategies for successful left-lobe LDLT in 250 consecutive cases stratified into 2 eras: Era 1 (n = 121), in which surgical procedures were continually refined, and Era 2 (n = 129), in which established procedures were used. Results: Graft volume (GV) did not affect the incidence of graft function or survival. Era 2 patients had decreased portal vein (PV) pressure at closure (16.0 ± 3.5 mmHg vs 19.1 ± 4.6 mmHg, p < 0.01), increased PV flow/GV (301 ± 125 mL/min/100g vs 391 ± 142 mL/min/100g, p < 0.01), and improved graft survival rate (1-year: 90.6% vs 81.8%. p < 0.01) despite the smaller GV/standard volume (SLV) ratio (36.2% ± 5.2% vs 41.2% ± 8.8%, p < 0.01) compared with Era 1. Patients in Era 2 had lower PV pressure and greater PV flow (y = 598-5.7x, p = 0.02) at any GV/SLV compared with cases in Era 1 (y = 480-4.3x, p < 0.01), representing greater graft compliance. Univariate analysis for graft survival showed that Era 1, Model for End-Stage Liver Disease (MELD) score ≥20, inpatient status, closing portal venous pressure ≥20 mmHg, no splenectomy, and operative blood loss ≥10L were the risk factors for graft loss, and multivariate analysis showed that Era 1 was the only significant factor (p < 0.01). During Era 2, development of primary graft dysfunction was associated with inpatient recipient status (p = 0.02) and donor age ≥45 years (p < 0.01). Conclusions: The outcomes of left-lobe LDLT were improved by accumulated experience and technical developments..
504. Hiroko Yano, Toru Ikegami, Tomoharu Yoshizumi, Tomohiko Akahoshi, Morimasa Tomikawa, Hideaki Uchiyama, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara, [Total laparoscopic splenectomy for a patient with multiple surgeries including living donor liver transplantation]., Unknown Journal, 104, 3, 64-67, 2013.03, The case was a 50 years old female, with history of multiple previous surgeries including living donor liver transplantation for primary biliary cirrhosis, pancreatoduodenectomy for carcinoma in the duodenal papilla Vater, revision of Roux-en-Y anastomosis for intractable cholangitis due to short Roux limb. She was hospitalized this time for decompensated liver cirrhosis due to recurrent cholangitis, with apparent hypersplenism and risky esophageal varices. After a few session of endoscopic treatment for esophageal varices, we applied total laparoscopic splenectomy for hypersplenism in a patient with multiple surgical histories, for seeking better surgical field for safety. The surgery was completed as planned preoperatively under good surgical field..
505. Akinobu Taketomi, Ken Shirabe, Jun Muto, Shohei Yoshiya, Takashi Motomura, Yohei Mano, Tohru Ikegami, Tomoharu Yoshizumi, Kenji Sugio, Yoshihiko Maehara, A rare point mutation in the Ras oncogene in hepatocellular carcinoma., Surgery today, 10.1007/s00595-012-0462-8, 43, 3, 289-92, 2013.03, PURPOSE: The Ras gene is one of the oncogenes most frequently detected in human cancers, and codes for three proteins (K-, N-, and H-Ras). The aim of this study was to examine the mutations in codons 12, 13 and 61 of the three Ras genes in cases of human hepatocellular carcinoma (HCC). METHODS: Paired samples of HCC and corresponding non-malignant liver tissue were collected from 61 patients who underwent hepatectomy. A dot-blot analysis was used to analyze the products of the polymerase chain reaction (PCR) amplification of codons 12, 13, and 61 of K-, N- and H-Ras for mutations. RESULTS: Only one mutation (K-Ras codon 13; Gly to Asp) was detected among the 61 patients. Interestingly, this patient had a medical history of surgery for both gastric cancer and right lung cancer. No mutations were found in codons 12 and 61 of K-Ras or codons 12, 13 and 61 of the N-Ras and H-Ras genes in any of the HCCs or corresponding non-malignant tissues. CONCLUSIONS: These findings indicated that the activation of Ras proto-oncogenes by mutations in codons 12, 13, and 61 does not play a major role in hepatocellular carcinogenesis..
506. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Tetsuo Ikeda, Yoshihiko Maehara, A simple and secure ligation of the main pancreatic duct in distal pancreatectomy., Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2012.10.021, 216, 3, e23-5-5, 2013.03.
507. Tetsuo Ikeda, Yohei Mano, Kazutoyo Morita, Naotaka Hashimoto, Hirohito Kayashima, Atsuro Masuda, Toru Ikegami, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara, Pure laparoscopic hepatectomy in semiprone position for right hepatic major resection, Journal of Hepato-Biliary-Pancreatic Sciences, 10.1007/s00534-012-0558-y, 20, 2, 145-150, 2013.02, Background: Pure laparoscopic liver resection is technically difficult for tumors located in the dorsal anterior and posterior sectors. We have developed a maneuver to perform pure laparoscopic hepatectomy in the semiprone position which was developed for resecting tumors located in these areas. Methods: The medical records have been reviewed retrospectively in 30 patients who underwent laparoscopic liver resection in the semiprone position for carcinoma in the dorsal anterior or posterior sectors of the right liver between 2008 and 2011. Results: Seventeen liver tumors were primary liver tumors and 13 were colorectal metastases. Of the 30 patients, 11 (36.6 %) underwent major hepatectomy [right hemihepatectomy in 7 (23.3 %) and posterior sectionectomy in 4 (13.3 %)]. Anatomical minor resection, such as S6 or S7 segmentectomy, was performed in five patients (16.6 %). Five patients with liver metastasis underwent a simultaneous laparoscopic resection. There was no mortality, reoperation, or conversion to open procedures. There were no hepatectomy-related complications such as postoperative bleeding, bile leakage, or liver failure. Conclusions: Pure laparoscopic hepatectomy in the semiprone position for tumors present in the dorsal anterior and posterior sectors is feasible and safe. This method expands the indications for laparoscopic liver resection for tumors..
508. Takeo Toshima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Ken Shirabe, Yoshihiko Maehara, Effect of CD133-positive stem cells in repeated recurrence of hepatocellular carcinoma after liver transplantation
a case report., Unknown Journal, 104, 10, 383-388, 2013.01, Liver transplantation (LT) is currently one of the best available strategies for treating multiple hepatocellular carcinoma (HCC) and decompensated liver cirrhosis. However, patients often undergo HCC recurrence after LT, with most HCC recurrences detected at 1-2 years. CD133 was the first identified member of the prominin family of pentaspan membrane proteins and is a marker of hepatic stem cells. Here, we report a unique case of seven repeated recurrences of HCC in the lungs after LT, with all HCC recurrences resected curatively by a thoracoscopic approach. Pathological examination revealed moderately differentiated HCC identical to that in the original histology of the liver tumor. Interestingly, no CD133 immunoreactivity was observed in cancerous lesions of the primary HCC and the 1st to 2nd recurrences, as indicated by immunohistochemistry. However, CD133 was strongly stained in the cancerous lesions from the 3rd to 7th recurrences. The patient survived and had no recurrence after 9 years of the initial living donor LT. In conclusion, we investigated an evocative case of seven repeated recurrences of HCC in the lungs to elucidate the significance of circulating CD133-positive hepatic stem cells. This case illustrates the need for further research to clarify the mutual effect of CD133-positive hepatic stem cells for the development of new therapeutic strategies..
509. Tetsuo Ikeda, Tomohiko Akahoshi, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Koshi Mimori, Masayuki Watanabe, Makoto Hashizume, Yoshihiko Maehara, Evaluation of a transection method for distal pancreatectomy
A comparative study on the use of electrosurgical and stapling devices in swine., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 515-522, 2013.01, Despite marked improvements in pancreatic surgery, the high incidence of pancreatic fistula and high morbidity after resection persists. The objective of this study was to evaluate the role of electrosurgical and stapling devices as an alternative to traditional methods of stump closure in an animal model of distal pancreatectomy. Four devices were used for transection of the pancreatic body : a bi-polar thermofusion system attached to an automatic irrigation function (BI, n = 3), a bi-polar tissue sealer (BS, n = 3), an ultrasonic scissor (US, n = 3), and an endoscopic stapling device (ES, n = 3). For each group, burst pressure was tested using an electronic manometer, with a focus on the location (s) of the first disruption (s). Histological examination was performed for the dissected surfaces. The transection line, including staples, was embedded in a polyester resin, and histological examination was performed for these polished sections of the resin. Pressure was significantly higher for BI (P < 0.01) than that for the other devices. In contrast, thermal denaturation of the pancreas parenchyma was observed at a depth of approximately 1 mm from the dissected portion for BS, while it extended beyond 15 mm for BI. The staple line was the first disruption point for all of ES cases. The pellicle of the pancreas is likely to be deficient after a surgical operation. If the pellicle is preserved, the strength of the pellicle may be insufficient for complete closure with high stapling mechanical pressure or the protein coagulation of usually used electrosurgical devices..
510. Shinji Okano, Haruhiko Kondoh, Takeo Toshima, Hidekazu Nakagawara, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Mamoru Harada, Yasunobu Yoshikai, Yoshihiko Maehara, Fas-deficient fully allogeneic dendritic cells administered via an intratumoral injection route show efficient antitumor effects in murine models., Unknown Journal, 104, 1, 15-26, 2013.01, Dendritic cell (DC)-based immunotherapy is a potent, active and specific cancer immunotherapy, as DCs are preferable professional APCs (pAPCs) that prime the tumor-associated antigen (TAA) -specific CD8+ T-cell response. In DC-based immunotherapy, allogeneic DCs may be an alternative source of DCs for patients in whom it is difficult to obtain a sufficient number of quality-guaranteed, autologous DCs. However, the usefulness of fully allogeneic DCs in DC-based immunotherapy is controversial, and many investigators have failed to demonstrate that fully allogeneic DCs can induce an efficient antitumor effect in various experimental settings. In this study, we found that the injection of Fas-deficient fully allogeneic DCs via an intratumoral injection route exerted efficient antitumor effects, as did syngeneic DCs, but wild-type fully allogeneic DCs did not. Intratumoral injection therapy using Fas-deficient syngeneic DCs does not show superior tumor growth suppression compared to that using wild-type syngeneic DCs, suggesting that the inhibition of functional Fas may be critical for overcoming the unfavorable factor related to allogeneic DCs, especially overcoming the rejection response to alloantigens, in therapy using fully allogeneic DCs. In addition, the intratumoral injection therapy using Fas-deficient fully allogeneic DCs induced the generation of a significant tumor-specific CD8+ T-cell response, which is restricted by a host-derived major histocompatibility antigen. Therefore, intratumoral injection therapy using fully allogeneic DCs of which functional Fas is inhibited may be an alternative in clinical DC-based immunotherapy, under circumstances that do not allow the use of autologous DCs..
511. Kazutoyo Morita, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Naotaka Hashimoto, Yohei Mano, Tatsunori Miyata, Yuji Soejima, Yoshihiko Maehara, Feasible isolated liver transplantation for a cirrhotic patient on chronic hemodialysis, Case Reports in Gastroenterology, 10.1159/000354140, 7, 2, 299-303, 2013.01, End-stage liver and kidney disease (ELKD) is an indication for deceased donor simultaneous liver-kidney transplantation. Although a few cases of living donor liver-kidney transplantation have been reported, the invasiveness remains to be discussed. Living donor liver transplantation (LDLT) is an alternative choice for ELKD, but has never been reported. Here, we report a case of successful LDLT for a patient with ELKD on hemodialysis. The patient was a 63-year-old male and had decompensated hepatitis C cirrhosis with seronegativity for hepatitis C virus. He had non-diabetic end-stage renal failure and had been on hemodialysis for 3 years. He was in good general condition except for hepatic and renal failure. The living donor was his 58-year-old healthy wife. A right lobe graft was transplanted to the recipient under continuous hemodiafiltration (CHDF) and extracorporeal veno-venous bypass. CHDF was continued until postoperative day 4, at which point CHDF was converted to hemodialysis. His posttransplant course was good and he was discharged on postoperative day 36. To the best of our knowledge, this is the first report of LDLT for a patient on chronic hemodialysis. Therefore, being on hemodialysis is not a contraindication for LDLT. LDLT is feasible for a patient with ELKD on hemodialysis..
512. Hiroto Kayashima, Ken Shirabe, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Liver regeneration and venous collateral formation in the right lobe living-donor remnant
Segmental volumetric analysis and three-dimensional visualization, Transplantation, 10.1097/TP.0b013e31827147d8, 95, 2, 353-360, 2013.01, BACKGROUND: In left lobe (LL) living-donor liver transplantation (LDLT), hepatic venous congestion (HVC) caused by ligation of the middle hepatic vein tributaries is unavoidable in the right lobe (RL) donor remnant. METHODS: To clarify the impact of HVC on liver regeneration and venous collateral formation (VCF), we used three-dimensional computed tomography to examine the volumes of total/segmental liver and HVC and the degree of VCF; preoperative data were compared with data obtained on postoperative day (POD) 35 in 13 LL LDLT donors. RESULTS: On POD 35, the congestion rate decreased from 32.5% to 1.6% and the total liver regeneration rate was 81.7%. Preoperatively, the anterior sector-to-RL volume ratio was significantly lower, and the posterior sector-to-RL volume ratio was significantly higher than postoperatively (56.7% vs. 52.9%, P<0.01, and 36.9% vs. 41.5%, P<0.01, respectively). There was no correlation between degree of HVC and liver regeneration. Obvious VCF was found in five (38.5%) cases. The RL and posterior sector volume per square meter of body surface area in the VCF group were significantly lower than that in the non-VCF group (412 cm/m vs. 492 cm/m, P<0.01, and 140 cm/m vs. 190 cm/m, P<0.01, respectively). The preoperative congestion rate and liver regeneration rate were not significantly different between the groups. CONCLUSIONS: Reconstruction of the middle hepatic vein tributaries in the RL donor remnant might not be necessary in LL LDLT, because the HVC improved dramatically by POD 35 regardless of the development of VCF..
513. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Mirror image hepatectomy in a patient with situs inversus totalis., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 430-434, 2013.01, Hepatectomy in a patient with situs inversus patient is technically challenging because of its complete mirror image anatomy, especially for a tumor located deep in the liver. Incorrectly identifying intrahepatic vessels and biliary system would lead to serious complications. We experienced a hepatectomy for a tumor in a patient with situs inversus totalis with referring to computer-generated mirror images. A 66-year-old female patient with situs inversus totalis was diagnosed with hepatocellular carcinoma, 5 cm in diameter, centrally located just above the hepatic hilum compressing the right and left hepatic duct. The liver infected with hepatitis C was cirrhotic with a moderate amount of ascites. We preoperatively created several diagrams of the mirror image anatomy and made plans for how to resect this tumor, presupposing the patient had an ordinary anatomy. The tumor was successfully enucleated with referring to these diagrams. The operation time was 454 minutes. Five units of fresh frozen plasma was transfused intraoperatively. Although she suffered refractory ascites which needed repeated paracentesis, she managed to leave the hospital two months after the operation. Creating a mirror image anatomy enables surgeons to safely perform a complex hepatectomy in a patient with situs inversus totalis..
514. Takashi Motomura, Ken Shirabe, Yohei Mano, Jun Muto, Takeo Toshima, Yuichiro Umemoto, Takasuke Fukuhara, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment, Journal of Hepatology, 10.1016/j.jhep.2012.08.017, 58, 1, 58-64, 2013.01, Background & Aims: Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Preoperative neutrophil-lymphocyte ratio (NLR) is a predictor of patient prognosis, but its mechanism has never been clarified. Methods: We assessed outcomes in 158 patients who had undergone living-donor liver transplantation (LDLT) for HCC. Recurrence-free survival (RFS) was determined in patients with high (≥4) and low (<4) NLR. Levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68, and CD163 were measured. Results: The 5-year RFS rate was significantly lower in patients with high (n = 26) than with low (n = 132) NLR (30.3% vs. 89.0%, p <0.0001), in patients with high (n = 15) than with low (n = 79) NLR who met the MC (73.6% vs. 100%, p = 0.0008) and in patients with high (n = 11) than with low (n = 53) NLR who exceeded the MC (0% vs. 76.1%, p = 0.0002). Tumor expression of VEGF, IL8, IL-17, CD68, and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 levels were significantly higher in the high-NLR group (p = 0.01 each). The density of peritumoral CD163 correlated with the density of peritumoral IL-17-producing cells (p = 0.04) and was significantly higher in the high-NLR group (p = 0.005). Conclusions: NLR predicts outcomes after LDLT for HCC via the inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC..
515. Keiji Yoshinaga, Hiroshi Saeki, Eiji Oki, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Prognostic markers for immunochemotherapy using tegafur -uracil (UFT) and protein-bound polysaccharide K (PSK)., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 549-558, 2013.01, We previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels. 98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years. There were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant. Serum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary..
516. Hiroshi Saeki, Eiji Oki, Yasuo Tsuda, Koji Ando, Yukiharu Hiyoshi, Shuhei Ito, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Relevance of totally laparoscopic gastrectomy for patients with advanced gastric cancer., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 405-412, 2013.01, Although the use of laparoscopic gastrectomy for gastric cancer has been widespread, it has remained controversial whether it can be applied for the patients with advanced gastric cancer. The aim of this study was to clarify the safety and usefulness of totally laparoscopic gastrectomy for patients with advanced gastric cancer. Totally laparoscopic gastrectomy was applied for a total of 38 patients with pStage IB-III advanced gastric cancer at our institute. The surgical and long-term results were analyzed in those patients. Twenty-seven patents underwent distal gastrectomy and 11 patients underwent total gastrectomy. The mean number of dissected lymph nodes was 41 (range, 16-87). The mean length of the operation and amount of blood loss was 324 min and 123 ml, respectively. Two cases of postoperative bleeding were noted, while neither anastomosis-related complications nor in-hospital death was observed. The follow-up period after surgery was 8-72 months. Postoperative recurrence was observed in 6 patients (peritoneal dissemination: 3 patients, pleural dissemination: 1 patient, liver metastasis: 1 patient, ovarian metastasis: 1 patient). The overall survival rates at 1, 3 and 5 years were 94.7%, 76.3% and 76.3%, respectively. Totally laparoscopic gastrectomy is safe and can lead to satisfactory long-term outcomes in cases of advanced gastric cancer. Prospective controlled studies are warranted to confirm our findings..
517. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo Ichi Yamashita, Tetsuo Ikeda, Hirofumi Kawanaka, Keishi Sugimachi, Koshi Mimori, Masayuki Watanabe, Masaru Morita, Eiji Oki, Hiroshi Saeki, Yoshihiko Maehara, Rex shunt for portal vein thrombosis after adult living donor liver transplantation., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 464-468, 2013.01, Portal vein thrombosis (PVT) after liver transplantation is a relatively common but serious complication which could lead to portal hypertension or a direct graft loss. A "Rex" shunt created between the superior mesenteric vein (SMV) and the umbilical portion of the left portal vein can be a useful option to treat PVT after pediatric liver transplantation, however, its application to adult patients has not been reported so far because appropriate vein grafts are hardly available. Herein we present a case of PVT after left lobe living donor liver transplantation (LDLT) who underwent the procedure using the own inferior jugular vein and the gonadal vein as a shunt graft. The shunt was patent immediately after the procedure but was thrombosed 2 days after probably due to the insufficient inflow from the SMV and the absence of anticoagulation therapy, for which emergent thrombectomy and ligation of the significant hepatofugal collateral veins followed by full anti-coagulation therapy were performed. The shunt remains open at 8 month after the procedure with a normal anmonia level and liver function. In conclusion, the Rex shunt using recipient's autologous vein grafts is a feasible and valuable option for adult patients to treat PVT after LDLT..
518. Masayuki Watanabe, Koki Matsuura, Hideo Baba, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Yoshihiko Maehara, Thoracoscopic pericardial drainage for gastric tube ulcer penetrated into the pericardium., Unknown Journal, 104, 10, 389-393, 2013.01, Peptic ulcer occurring in the gastric conduit for esophageal reconstruction sometimes penetrates into the mediastinal structures. We herein reported a case of pericardial penetration of gastric tube ulcer successfully treated with thoracoscopic pericardial drainage. A 66-year-old Japanese man, who had undergone esophagectomy for esophageal cancer 20 months before, visited our emergency room complaining severe back pain. Computed tomography revealed gastric tube ulcer penetrated into the pericardial space. Thoracoscopic pericardiotomy and drainage was performed and the patient made an uneventful recovery. Thoracoscopic pericardial drainage is useful to manage acute pyogenic pericarditis due to penetration of peptic ulcer which occurred in the gastric tube..
519. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Verification of our therapeutic criterion for acute cholecystitis
"perform a subemergency laparoscopic cholecystectomy when a patient is judged to be able to tolerate general anesthesia"--the experience in a single community hospital., Unknown Journal, 104, 10, 339-343, 2013.01, Our current therapeutic criterion for acute cholecystitis is: Perform a subemergency laparoscopic cholecystectomy (LC) when a patient is judged to be able to tolerate general anesthesia. The aim of the current study was to verify whether this criterion is justified. The outcomes of 21 cases of LC for acute cholecystitis performed between April 2011 and September 2013 were retrospectively analyzed. Subemergency LC was performed according to the aforementioned criterion (Subemergency group; n = 16). Patient who was judged to be unable to tolerate general anesthesia underwent percutaneous transhepatic gallbladder drainage (PTGBD) first, then LC after the patients' condition became stable (PTGBD group; n = 5). There is no conversion to open surgery throughout the study period. The mean of the total hospital stays in the Subemergency group was significantly shorter than that in the PTGBD group (11.5 +/- 5.3 vs. 30.4 +/- 8.5 days). Although two patients in the Subemergency group, who had already needed oxygen administration preoperatively, suffered postoperative respiratory failure, they completely recovered. On the other hand, there is no postoperative complication in the PTGBD group. Subemergency LC could be safely performed when surgeons as well as anesthesiologists judged a patient to be able to tolerate general anesthesia, which significantly shorten hospital stays compared to elective LC after PTGBD. However, elective LC after PTGBD is an absolutely safer therapeutic option in treating unstable patients..
520. Tetsuo Ikeda, Tomohiko Akahoshi, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Koshi Mimori, Masayuki Watanabe, Makoto Hashizume, Yoshihiko Maehara, [Optimum hepatic parenchymal dissection to prevent bile leak
a comparative study using electrosurgical and stapling devices in swine]., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 507-514, 2013.01, Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma..
521. Kazutoyo Morita, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Naotaka Hashimoto, Yohei Mano, Tatsunori Miyata, Yuji Soejima, Yoshihiko Maehara, Feasible isolated liver transplantation for a cirrhotic patient on chronic hemodialysis, Case Reports in Gastroenterology, 10.1159/000354140, 7, 2, 299-303, 2013.01, End-stage liver and kidney disease (ELKD) is an indication for deceased donor simultaneous liver-kidney transplantation. Although a few cases of living donor liver-kidney transplantation have been reported, the invasiveness remains to be discussed. Living donor liver transplantation (LDLT) is an alternative choice for ELKD, but has never been reported. Here, we report a case of successful LDLT for a patient with ELKD on hemodialysis. The patient was a 63-year-old male and had decompensated hepatitis C cirrhosis with seronegativity for hepatitis C virus. He had non-diabetic end-stage renal failure and had been on hemodialysis for 3 years. He was in good general condition except for hepatic and renal failure. The living donor was his 58-year-old healthy wife. A right lobe graft was transplanted to the recipient under continuous hemodiafiltration (CHDF) and extracorporeal veno-venous bypass. CHDF was continued until postoperative day 4, at which point CHDF was converted to hemodialysis. His posttransplant course was good and he was discharged on postoperative day 36. To the best of our knowledge, this is the first report of LDLT for a patient on chronic hemodialysis. Therefore, being on hemodialysis is not a contraindication for LDLT. LDLT is feasible for a patient with ELKD on hemodialysis..
522. Hiroto Kayashima, Ken Shirabe, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Liver regeneration and venous collateral formation in the right lobe living-donor remnant
Segmental volumetric analysis and three-dimensional visualization, Transplantation, 10.1097/TP.0b013e31827147d8, 95, 2, 353-360, 2013.01, BACKGROUND: In left lobe (LL) living-donor liver transplantation (LDLT), hepatic venous congestion (HVC) caused by ligation of the middle hepatic vein tributaries is unavoidable in the right lobe (RL) donor remnant. METHODS: To clarify the impact of HVC on liver regeneration and venous collateral formation (VCF), we used three-dimensional computed tomography to examine the volumes of total/segmental liver and HVC and the degree of VCF; preoperative data were compared with data obtained on postoperative day (POD) 35 in 13 LL LDLT donors. RESULTS: On POD 35, the congestion rate decreased from 32.5% to 1.6% and the total liver regeneration rate was 81.7%. Preoperatively, the anterior sector-to-RL volume ratio was significantly lower, and the posterior sector-to-RL volume ratio was significantly higher than postoperatively (56.7% vs. 52.9%, P<0.01, and 36.9% vs. 41.5%, P<0.01, respectively). There was no correlation between degree of HVC and liver regeneration. Obvious VCF was found in five (38.5%) cases. The RL and posterior sector volume per square meter of body surface area in the VCF group were significantly lower than that in the non-VCF group (412 cm/m vs. 492 cm/m, P<0.01, and 140 cm/m vs. 190 cm/m, P<0.01, respectively). The preoperative congestion rate and liver regeneration rate were not significantly different between the groups. CONCLUSIONS: Reconstruction of the middle hepatic vein tributaries in the RL donor remnant might not be necessary in LL LDLT, because the HVC improved dramatically by POD 35 regardless of the development of VCF..
523. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Mirror image hepatectomy in a patient with situs inversus totalis., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 430-434, 2013.01, Hepatectomy in a patient with situs inversus patient is technically challenging because of its complete mirror image anatomy, especially for a tumor located deep in the liver. Incorrectly identifying intrahepatic vessels and biliary system would lead to serious complications. We experienced a hepatectomy for a tumor in a patient with situs inversus totalis with referring to computer-generated mirror images. A 66-year-old female patient with situs inversus totalis was diagnosed with hepatocellular carcinoma, 5 cm in diameter, centrally located just above the hepatic hilum compressing the right and left hepatic duct. The liver infected with hepatitis C was cirrhotic with a moderate amount of ascites. We preoperatively created several diagrams of the mirror image anatomy and made plans for how to resect this tumor, presupposing the patient had an ordinary anatomy. The tumor was successfully enucleated with referring to these diagrams. The operation time was 454 minutes. Five units of fresh frozen plasma was transfused intraoperatively. Although she suffered refractory ascites which needed repeated paracentesis, she managed to leave the hospital two months after the operation. Creating a mirror image anatomy enables surgeons to safely perform a complex hepatectomy in a patient with situs inversus totalis..
524. Takashi Motomura, Ken Shirabe, Yohei Mano, Jun Muto, Takeo Toshima, Yuichiro Umemoto, Takasuke Fukuhara, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment, Journal of Hepatology, 10.1016/j.jhep.2012.08.017, 58, 1, 58-64, 2013.01, Background & Aims: Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Preoperative neutrophil-lymphocyte ratio (NLR) is a predictor of patient prognosis, but its mechanism has never been clarified. Methods: We assessed outcomes in 158 patients who had undergone living-donor liver transplantation (LDLT) for HCC. Recurrence-free survival (RFS) was determined in patients with high (≥4) and low (<4) NLR. Levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68, and CD163 were measured. Results: The 5-year RFS rate was significantly lower in patients with high (n = 26) than with low (n = 132) NLR (30.3% vs. 89.0%, p <0.0001), in patients with high (n = 15) than with low (n = 79) NLR who met the MC (73.6% vs. 100%, p = 0.0008) and in patients with high (n = 11) than with low (n = 53) NLR who exceeded the MC (0% vs. 76.1%, p = 0.0002). Tumor expression of VEGF, IL8, IL-17, CD68, and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 levels were significantly higher in the high-NLR group (p = 0.01 each). The density of peritumoral CD163 correlated with the density of peritumoral IL-17-producing cells (p = 0.04) and was significantly higher in the high-NLR group (p = 0.005). Conclusions: NLR predicts outcomes after LDLT for HCC via the inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC..
525. Keiji Yoshinaga, Hiroshi Saeki, Eiji Oki, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Prognostic markers for immunochemotherapy using tegafur -uracil (UFT) and protein-bound polysaccharide K (PSK)., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 549-558, 2013.01, We previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels. 98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years. There were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant. Serum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary..
526. Hiroshi Saeki, Eiji Oki, Yasuo Tsuda, Koji Ando, Yukiharu Hiyoshi, Shuhei Ito, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Relevance of totally laparoscopic gastrectomy for patients with advanced gastric cancer., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 405-412, 2013.01, Although the use of laparoscopic gastrectomy for gastric cancer has been widespread, it has remained controversial whether it can be applied for the patients with advanced gastric cancer. The aim of this study was to clarify the safety and usefulness of totally laparoscopic gastrectomy for patients with advanced gastric cancer. Totally laparoscopic gastrectomy was applied for a total of 38 patients with pStage IB-III advanced gastric cancer at our institute. The surgical and long-term results were analyzed in those patients. Twenty-seven patents underwent distal gastrectomy and 11 patients underwent total gastrectomy. The mean number of dissected lymph nodes was 41 (range, 16-87). The mean length of the operation and amount of blood loss was 324 min and 123 ml, respectively. Two cases of postoperative bleeding were noted, while neither anastomosis-related complications nor in-hospital death was observed. The follow-up period after surgery was 8-72 months. Postoperative recurrence was observed in 6 patients (peritoneal dissemination: 3 patients, pleural dissemination: 1 patient, liver metastasis: 1 patient, ovarian metastasis: 1 patient). The overall survival rates at 1, 3 and 5 years were 94.7%, 76.3% and 76.3%, respectively. Totally laparoscopic gastrectomy is safe and can lead to satisfactory long-term outcomes in cases of advanced gastric cancer. Prospective controlled studies are warranted to confirm our findings..
527. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo Ichi Yamashita, Tetsuo Ikeda, Hirofumi Kawanaka, Keishi Sugimachi, Koshi Mimori, Masayuki Watanabe, Masaru Morita, Eiji Oki, Hiroshi Saeki, Yoshihiko Maehara, Rex shunt for portal vein thrombosis after adult living donor liver transplantation., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 464-468, 2013.01, Portal vein thrombosis (PVT) after liver transplantation is a relatively common but serious complication which could lead to portal hypertension or a direct graft loss. A "Rex" shunt created between the superior mesenteric vein (SMV) and the umbilical portion of the left portal vein can be a useful option to treat PVT after pediatric liver transplantation, however, its application to adult patients has not been reported so far because appropriate vein grafts are hardly available. Herein we present a case of PVT after left lobe living donor liver transplantation (LDLT) who underwent the procedure using the own inferior jugular vein and the gonadal vein as a shunt graft. The shunt was patent immediately after the procedure but was thrombosed 2 days after probably due to the insufficient inflow from the SMV and the absence of anticoagulation therapy, for which emergent thrombectomy and ligation of the significant hepatofugal collateral veins followed by full anti-coagulation therapy were performed. The shunt remains open at 8 month after the procedure with a normal anmonia level and liver function. In conclusion, the Rex shunt using recipient's autologous vein grafts is a feasible and valuable option for adult patients to treat PVT after LDLT..
528. Masayuki Watanabe, Koki Matsuura, Hideo Baba, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Yoshihiko Maehara, Thoracoscopic pericardial drainage for gastric tube ulcer penetrated into the pericardium., Unknown Journal, 104, 10, 389-393, 2013.01, Peptic ulcer occurring in the gastric conduit for esophageal reconstruction sometimes penetrates into the mediastinal structures. We herein reported a case of pericardial penetration of gastric tube ulcer successfully treated with thoracoscopic pericardial drainage. A 66-year-old Japanese man, who had undergone esophagectomy for esophageal cancer 20 months before, visited our emergency room complaining severe back pain. Computed tomography revealed gastric tube ulcer penetrated into the pericardial space. Thoracoscopic pericardiotomy and drainage was performed and the patient made an uneventful recovery. Thoracoscopic pericardial drainage is useful to manage acute pyogenic pericarditis due to penetration of peptic ulcer which occurred in the gastric tube..
529. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Verification of our therapeutic criterion for acute cholecystitis
"perform a subemergency laparoscopic cholecystectomy when a patient is judged to be able to tolerate general anesthesia"--the experience in a single community hospital., Unknown Journal, 104, 10, 339-343, 2013.01, Our current therapeutic criterion for acute cholecystitis is: Perform a subemergency laparoscopic cholecystectomy (LC) when a patient is judged to be able to tolerate general anesthesia. The aim of the current study was to verify whether this criterion is justified. The outcomes of 21 cases of LC for acute cholecystitis performed between April 2011 and September 2013 were retrospectively analyzed. Subemergency LC was performed according to the aforementioned criterion (Subemergency group; n = 16). Patient who was judged to be unable to tolerate general anesthesia underwent percutaneous transhepatic gallbladder drainage (PTGBD) first, then LC after the patients' condition became stable (PTGBD group; n = 5). There is no conversion to open surgery throughout the study period. The mean of the total hospital stays in the Subemergency group was significantly shorter than that in the PTGBD group (11.5 +/- 5.3 vs. 30.4 +/- 8.5 days). Although two patients in the Subemergency group, who had already needed oxygen administration preoperatively, suffered postoperative respiratory failure, they completely recovered. On the other hand, there is no postoperative complication in the PTGBD group. Subemergency LC could be safely performed when surgeons as well as anesthesiologists judged a patient to be able to tolerate general anesthesia, which significantly shorten hospital stays compared to elective LC after PTGBD. However, elective LC after PTGBD is an absolutely safer therapeutic option in treating unstable patients..
530. Tetsuo Ikeda, Tomohiko Akahoshi, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Koshi Mimori, Masayuki Watanabe, Makoto Hashizume, Yoshihiko Maehara, [Optimum hepatic parenchymal dissection to prevent bile leak
a comparative study using electrosurgical and stapling devices in swine]., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 507-514, 2013.01, Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma..
531. Kazutoyo Morita, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Naotaka Hashimoto, Yohei Mano, Tatsunori Miyata, Yuji Soejima, Yoshihiko Maehara, Feasible isolated liver transplantation for a cirrhotic patient on chronic hemodialysis, Case Reports in Gastroenterology, 10.1159/000354140, 7, 2, 299-303, 2013.01, End-stage liver and kidney disease (ELKD) is an indication for deceased donor simultaneous liver-kidney transplantation. Although a few cases of living donor liver-kidney transplantation have been reported, the invasiveness remains to be discussed. Living donor liver transplantation (LDLT) is an alternative choice for ELKD, but has never been reported. Here, we report a case of successful LDLT for a patient with ELKD on hemodialysis. The patient was a 63-year-old male and had decompensated hepatitis C cirrhosis with seronegativity for hepatitis C virus. He had non-diabetic end-stage renal failure and had been on hemodialysis for 3 years. He was in good general condition except for hepatic and renal failure. The living donor was his 58-year-old healthy wife. A right lobe graft was transplanted to the recipient under continuous hemodiafiltration (CHDF) and extracorporeal veno-venous bypass. CHDF was continued until postoperative day 4, at which point CHDF was converted to hemodialysis. His posttransplant course was good and he was discharged on postoperative day 36. To the best of our knowledge, this is the first report of LDLT for a patient on chronic hemodialysis. Therefore, being on hemodialysis is not a contraindication for LDLT. LDLT is feasible for a patient with ELKD on hemodialysis..
532. Hiroto Kayashima, Ken Shirabe, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Liver regeneration and venous collateral formation in the right lobe living-donor remnant
Segmental volumetric analysis and three-dimensional visualization, Transplantation, 10.1097/TP.0b013e31827147d8, 95, 2, 353-360, 2013.01, BACKGROUND: In left lobe (LL) living-donor liver transplantation (LDLT), hepatic venous congestion (HVC) caused by ligation of the middle hepatic vein tributaries is unavoidable in the right lobe (RL) donor remnant. METHODS: To clarify the impact of HVC on liver regeneration and venous collateral formation (VCF), we used three-dimensional computed tomography to examine the volumes of total/segmental liver and HVC and the degree of VCF; preoperative data were compared with data obtained on postoperative day (POD) 35 in 13 LL LDLT donors. RESULTS: On POD 35, the congestion rate decreased from 32.5% to 1.6% and the total liver regeneration rate was 81.7%. Preoperatively, the anterior sector-to-RL volume ratio was significantly lower, and the posterior sector-to-RL volume ratio was significantly higher than postoperatively (56.7% vs. 52.9%, P<0.01, and 36.9% vs. 41.5%, P<0.01, respectively). There was no correlation between degree of HVC and liver regeneration. Obvious VCF was found in five (38.5%) cases. The RL and posterior sector volume per square meter of body surface area in the VCF group were significantly lower than that in the non-VCF group (412 cm/m vs. 492 cm/m, P<0.01, and 140 cm/m vs. 190 cm/m, P<0.01, respectively). The preoperative congestion rate and liver regeneration rate were not significantly different between the groups. CONCLUSIONS: Reconstruction of the middle hepatic vein tributaries in the RL donor remnant might not be necessary in LL LDLT, because the HVC improved dramatically by POD 35 regardless of the development of VCF..
533. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Mirror image hepatectomy in a patient with situs inversus totalis., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 430-434, 2013.01, Hepatectomy in a patient with situs inversus patient is technically challenging because of its complete mirror image anatomy, especially for a tumor located deep in the liver. Incorrectly identifying intrahepatic vessels and biliary system would lead to serious complications. We experienced a hepatectomy for a tumor in a patient with situs inversus totalis with referring to computer-generated mirror images. A 66-year-old female patient with situs inversus totalis was diagnosed with hepatocellular carcinoma, 5 cm in diameter, centrally located just above the hepatic hilum compressing the right and left hepatic duct. The liver infected with hepatitis C was cirrhotic with a moderate amount of ascites. We preoperatively created several diagrams of the mirror image anatomy and made plans for how to resect this tumor, presupposing the patient had an ordinary anatomy. The tumor was successfully enucleated with referring to these diagrams. The operation time was 454 minutes. Five units of fresh frozen plasma was transfused intraoperatively. Although she suffered refractory ascites which needed repeated paracentesis, she managed to leave the hospital two months after the operation. Creating a mirror image anatomy enables surgeons to safely perform a complex hepatectomy in a patient with situs inversus totalis..
534. Takashi Motomura, Ken Shirabe, Yohei Mano, Jun Muto, Takeo Toshima, Yuichiro Umemoto, Takasuke Fukuhara, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment, Journal of Hepatology, 10.1016/j.jhep.2012.08.017, 58, 1, 58-64, 2013.01, Background & Aims: Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Preoperative neutrophil-lymphocyte ratio (NLR) is a predictor of patient prognosis, but its mechanism has never been clarified. Methods: We assessed outcomes in 158 patients who had undergone living-donor liver transplantation (LDLT) for HCC. Recurrence-free survival (RFS) was determined in patients with high (≥4) and low (<4) NLR. Levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68, and CD163 were measured. Results: The 5-year RFS rate was significantly lower in patients with high (n = 26) than with low (n = 132) NLR (30.3% vs. 89.0%, p <0.0001), in patients with high (n = 15) than with low (n = 79) NLR who met the MC (73.6% vs. 100%, p = 0.0008) and in patients with high (n = 11) than with low (n = 53) NLR who exceeded the MC (0% vs. 76.1%, p = 0.0002). Tumor expression of VEGF, IL8, IL-17, CD68, and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 levels were significantly higher in the high-NLR group (p = 0.01 each). The density of peritumoral CD163 correlated with the density of peritumoral IL-17-producing cells (p = 0.04) and was significantly higher in the high-NLR group (p = 0.005). Conclusions: NLR predicts outcomes after LDLT for HCC via the inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC..
535. Keiji Yoshinaga, Hiroshi Saeki, Eiji Oki, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Prognostic markers for immunochemotherapy using tegafur -uracil (UFT) and protein-bound polysaccharide K (PSK)., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 549-558, 2013.01, We previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels. 98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years. There were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant. Serum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary..
536. Hiroshi Saeki, Eiji Oki, Yasuo Tsuda, Koji Ando, Yukiharu Hiyoshi, Shuhei Ito, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Relevance of totally laparoscopic gastrectomy for patients with advanced gastric cancer., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 405-412, 2013.01, Although the use of laparoscopic gastrectomy for gastric cancer has been widespread, it has remained controversial whether it can be applied for the patients with advanced gastric cancer. The aim of this study was to clarify the safety and usefulness of totally laparoscopic gastrectomy for patients with advanced gastric cancer. Totally laparoscopic gastrectomy was applied for a total of 38 patients with pStage IB-III advanced gastric cancer at our institute. The surgical and long-term results were analyzed in those patients. Twenty-seven patents underwent distal gastrectomy and 11 patients underwent total gastrectomy. The mean number of dissected lymph nodes was 41 (range, 16-87). The mean length of the operation and amount of blood loss was 324 min and 123 ml, respectively. Two cases of postoperative bleeding were noted, while neither anastomosis-related complications nor in-hospital death was observed. The follow-up period after surgery was 8-72 months. Postoperative recurrence was observed in 6 patients (peritoneal dissemination: 3 patients, pleural dissemination: 1 patient, liver metastasis: 1 patient, ovarian metastasis: 1 patient). The overall survival rates at 1, 3 and 5 years were 94.7%, 76.3% and 76.3%, respectively. Totally laparoscopic gastrectomy is safe and can lead to satisfactory long-term outcomes in cases of advanced gastric cancer. Prospective controlled studies are warranted to confirm our findings..
537. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo Ichi Yamashita, Tetsuo Ikeda, Hirofumi Kawanaka, Keishi Sugimachi, Koshi Mimori, Masayuki Watanabe, Masaru Morita, Eiji Oki, Hiroshi Saeki, Yoshihiko Maehara, Rex shunt for portal vein thrombosis after adult living donor liver transplantation., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 464-468, 2013.01, Portal vein thrombosis (PVT) after liver transplantation is a relatively common but serious complication which could lead to portal hypertension or a direct graft loss. A "Rex" shunt created between the superior mesenteric vein (SMV) and the umbilical portion of the left portal vein can be a useful option to treat PVT after pediatric liver transplantation, however, its application to adult patients has not been reported so far because appropriate vein grafts are hardly available. Herein we present a case of PVT after left lobe living donor liver transplantation (LDLT) who underwent the procedure using the own inferior jugular vein and the gonadal vein as a shunt graft. The shunt was patent immediately after the procedure but was thrombosed 2 days after probably due to the insufficient inflow from the SMV and the absence of anticoagulation therapy, for which emergent thrombectomy and ligation of the significant hepatofugal collateral veins followed by full anti-coagulation therapy were performed. The shunt remains open at 8 month after the procedure with a normal anmonia level and liver function. In conclusion, the Rex shunt using recipient's autologous vein grafts is a feasible and valuable option for adult patients to treat PVT after LDLT..
538. Masayuki Watanabe, Koki Matsuura, Hideo Baba, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Yoshihiko Maehara, Thoracoscopic pericardial drainage for gastric tube ulcer penetrated into the pericardium., Unknown Journal, 104, 10, 389-393, 2013.01, Peptic ulcer occurring in the gastric conduit for esophageal reconstruction sometimes penetrates into the mediastinal structures. We herein reported a case of pericardial penetration of gastric tube ulcer successfully treated with thoracoscopic pericardial drainage. A 66-year-old Japanese man, who had undergone esophagectomy for esophageal cancer 20 months before, visited our emergency room complaining severe back pain. Computed tomography revealed gastric tube ulcer penetrated into the pericardial space. Thoracoscopic pericardiotomy and drainage was performed and the patient made an uneventful recovery. Thoracoscopic pericardial drainage is useful to manage acute pyogenic pericarditis due to penetration of peptic ulcer which occurred in the gastric tube..
539. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Verification of our therapeutic criterion for acute cholecystitis
"perform a subemergency laparoscopic cholecystectomy when a patient is judged to be able to tolerate general anesthesia"--the experience in a single community hospital., Unknown Journal, 104, 10, 339-343, 2013.01, Our current therapeutic criterion for acute cholecystitis is: Perform a subemergency laparoscopic cholecystectomy (LC) when a patient is judged to be able to tolerate general anesthesia. The aim of the current study was to verify whether this criterion is justified. The outcomes of 21 cases of LC for acute cholecystitis performed between April 2011 and September 2013 were retrospectively analyzed. Subemergency LC was performed according to the aforementioned criterion (Subemergency group; n = 16). Patient who was judged to be unable to tolerate general anesthesia underwent percutaneous transhepatic gallbladder drainage (PTGBD) first, then LC after the patients' condition became stable (PTGBD group; n = 5). There is no conversion to open surgery throughout the study period. The mean of the total hospital stays in the Subemergency group was significantly shorter than that in the PTGBD group (11.5 +/- 5.3 vs. 30.4 +/- 8.5 days). Although two patients in the Subemergency group, who had already needed oxygen administration preoperatively, suffered postoperative respiratory failure, they completely recovered. On the other hand, there is no postoperative complication in the PTGBD group. Subemergency LC could be safely performed when surgeons as well as anesthesiologists judged a patient to be able to tolerate general anesthesia, which significantly shorten hospital stays compared to elective LC after PTGBD. However, elective LC after PTGBD is an absolutely safer therapeutic option in treating unstable patients..
540. Tetsuo Ikeda, Tomohiko Akahoshi, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Koshi Mimori, Masayuki Watanabe, Makoto Hashizume, Yoshihiko Maehara, [Optimum hepatic parenchymal dissection to prevent bile leak
a comparative study using electrosurgical and stapling devices in swine]., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 507-514, 2013.01, Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma..
541. Kazutoyo Morita, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Naotaka Hashimoto, Yohei Mano, Tatsunori Miyata, Yuji Soejima, Yoshihiko Maehara, Feasible isolated liver transplantation for a cirrhotic patient on chronic hemodialysis, Case Reports in Gastroenterology, 10.1159/000354140, 7, 2, 299-303, 2013.01, End-stage liver and kidney disease (ELKD) is an indication for deceased donor simultaneous liver-kidney transplantation. Although a few cases of living donor liver-kidney transplantation have been reported, the invasiveness remains to be discussed. Living donor liver transplantation (LDLT) is an alternative choice for ELKD, but has never been reported. Here, we report a case of successful LDLT for a patient with ELKD on hemodialysis. The patient was a 63-year-old male and had decompensated hepatitis C cirrhosis with seronegativity for hepatitis C virus. He had non-diabetic end-stage renal failure and had been on hemodialysis for 3 years. He was in good general condition except for hepatic and renal failure. The living donor was his 58-year-old healthy wife. A right lobe graft was transplanted to the recipient under continuous hemodiafiltration (CHDF) and extracorporeal veno-venous bypass. CHDF was continued until postoperative day 4, at which point CHDF was converted to hemodialysis. His posttransplant course was good and he was discharged on postoperative day 36. To the best of our knowledge, this is the first report of LDLT for a patient on chronic hemodialysis. Therefore, being on hemodialysis is not a contraindication for LDLT. LDLT is feasible for a patient with ELKD on hemodialysis..
542. Hiroto Kayashima, Ken Shirabe, Kazutoyo Morita, Naotaka Hashimoto, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Liver regeneration and venous collateral formation in the right lobe living-donor remnant
Segmental volumetric analysis and three-dimensional visualization, Transplantation, 10.1097/TP.0b013e31827147d8, 95, 2, 353-360, 2013.01, BACKGROUND: In left lobe (LL) living-donor liver transplantation (LDLT), hepatic venous congestion (HVC) caused by ligation of the middle hepatic vein tributaries is unavoidable in the right lobe (RL) donor remnant. METHODS: To clarify the impact of HVC on liver regeneration and venous collateral formation (VCF), we used three-dimensional computed tomography to examine the volumes of total/segmental liver and HVC and the degree of VCF; preoperative data were compared with data obtained on postoperative day (POD) 35 in 13 LL LDLT donors. RESULTS: On POD 35, the congestion rate decreased from 32.5% to 1.6% and the total liver regeneration rate was 81.7%. Preoperatively, the anterior sector-to-RL volume ratio was significantly lower, and the posterior sector-to-RL volume ratio was significantly higher than postoperatively (56.7% vs. 52.9%, P<0.01, and 36.9% vs. 41.5%, P<0.01, respectively). There was no correlation between degree of HVC and liver regeneration. Obvious VCF was found in five (38.5%) cases. The RL and posterior sector volume per square meter of body surface area in the VCF group were significantly lower than that in the non-VCF group (412 cm/m vs. 492 cm/m, P<0.01, and 140 cm/m vs. 190 cm/m, P<0.01, respectively). The preoperative congestion rate and liver regeneration rate were not significantly different between the groups. CONCLUSIONS: Reconstruction of the middle hepatic vein tributaries in the RL donor remnant might not be necessary in LL LDLT, because the HVC improved dramatically by POD 35 regardless of the development of VCF..
543. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Mirror image hepatectomy in a patient with situs inversus totalis., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 430-434, 2013.01, Hepatectomy in a patient with situs inversus patient is technically challenging because of its complete mirror image anatomy, especially for a tumor located deep in the liver. Incorrectly identifying intrahepatic vessels and biliary system would lead to serious complications. We experienced a hepatectomy for a tumor in a patient with situs inversus totalis with referring to computer-generated mirror images. A 66-year-old female patient with situs inversus totalis was diagnosed with hepatocellular carcinoma, 5 cm in diameter, centrally located just above the hepatic hilum compressing the right and left hepatic duct. The liver infected with hepatitis C was cirrhotic with a moderate amount of ascites. We preoperatively created several diagrams of the mirror image anatomy and made plans for how to resect this tumor, presupposing the patient had an ordinary anatomy. The tumor was successfully enucleated with referring to these diagrams. The operation time was 454 minutes. Five units of fresh frozen plasma was transfused intraoperatively. Although she suffered refractory ascites which needed repeated paracentesis, she managed to leave the hospital two months after the operation. Creating a mirror image anatomy enables surgeons to safely perform a complex hepatectomy in a patient with situs inversus totalis..
544. Takashi Motomura, Ken Shirabe, Yohei Mano, Jun Muto, Takeo Toshima, Yuichiro Umemoto, Takasuke Fukuhara, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment, Journal of Hepatology, 10.1016/j.jhep.2012.08.017, 58, 1, 58-64, 2013.01, Background & Aims: Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Preoperative neutrophil-lymphocyte ratio (NLR) is a predictor of patient prognosis, but its mechanism has never been clarified. Methods: We assessed outcomes in 158 patients who had undergone living-donor liver transplantation (LDLT) for HCC. Recurrence-free survival (RFS) was determined in patients with high (≥4) and low (<4) NLR. Levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68, and CD163 were measured. Results: The 5-year RFS rate was significantly lower in patients with high (n = 26) than with low (n = 132) NLR (30.3% vs. 89.0%, p <0.0001), in patients with high (n = 15) than with low (n = 79) NLR who met the MC (73.6% vs. 100%, p = 0.0008) and in patients with high (n = 11) than with low (n = 53) NLR who exceeded the MC (0% vs. 76.1%, p = 0.0002). Tumor expression of VEGF, IL8, IL-17, CD68, and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 levels were significantly higher in the high-NLR group (p = 0.01 each). The density of peritumoral CD163 correlated with the density of peritumoral IL-17-producing cells (p = 0.04) and was significantly higher in the high-NLR group (p = 0.005). Conclusions: NLR predicts outcomes after LDLT for HCC via the inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC..
545. Keiji Yoshinaga, Hiroshi Saeki, Eiji Oki, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Prognostic markers for immunochemotherapy using tegafur -uracil (UFT) and protein-bound polysaccharide K (PSK)., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 549-558, 2013.01, We previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels. 98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years. There were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant. Serum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary..
546. Hiroshi Saeki, Eiji Oki, Yasuo Tsuda, Koji Ando, Yukiharu Hiyoshi, Shuhei Ito, Masaru Morita, Tetsuo Ikeda, Keishi Sugimachi, Yo Ichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Hirofumi Kawanaka, Koshi Mimori, Masayuki Watanabe, Yoshihiko Maehara, Relevance of totally laparoscopic gastrectomy for patients with advanced gastric cancer., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 405-412, 2013.01, Although the use of laparoscopic gastrectomy for gastric cancer has been widespread, it has remained controversial whether it can be applied for the patients with advanced gastric cancer. The aim of this study was to clarify the safety and usefulness of totally laparoscopic gastrectomy for patients with advanced gastric cancer. Totally laparoscopic gastrectomy was applied for a total of 38 patients with pStage IB-III advanced gastric cancer at our institute. The surgical and long-term results were analyzed in those patients. Twenty-seven patents underwent distal gastrectomy and 11 patients underwent total gastrectomy. The mean number of dissected lymph nodes was 41 (range, 16-87). The mean length of the operation and amount of blood loss was 324 min and 123 ml, respectively. Two cases of postoperative bleeding were noted, while neither anastomosis-related complications nor in-hospital death was observed. The follow-up period after surgery was 8-72 months. Postoperative recurrence was observed in 6 patients (peritoneal dissemination: 3 patients, pleural dissemination: 1 patient, liver metastasis: 1 patient, ovarian metastasis: 1 patient). The overall survival rates at 1, 3 and 5 years were 94.7%, 76.3% and 76.3%, respectively. Totally laparoscopic gastrectomy is safe and can lead to satisfactory long-term outcomes in cases of advanced gastric cancer. Prospective controlled studies are warranted to confirm our findings..
547. Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo Ichi Yamashita, Tetsuo Ikeda, Hirofumi Kawanaka, Keishi Sugimachi, Koshi Mimori, Masayuki Watanabe, Masaru Morita, Eiji Oki, Hiroshi Saeki, Yoshihiko Maehara, Rex shunt for portal vein thrombosis after adult living donor liver transplantation., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 11, 464-468, 2013.01, Portal vein thrombosis (PVT) after liver transplantation is a relatively common but serious complication which could lead to portal hypertension or a direct graft loss. A "Rex" shunt created between the superior mesenteric vein (SMV) and the umbilical portion of the left portal vein can be a useful option to treat PVT after pediatric liver transplantation, however, its application to adult patients has not been reported so far because appropriate vein grafts are hardly available. Herein we present a case of PVT after left lobe living donor liver transplantation (LDLT) who underwent the procedure using the own inferior jugular vein and the gonadal vein as a shunt graft. The shunt was patent immediately after the procedure but was thrombosed 2 days after probably due to the insufficient inflow from the SMV and the absence of anticoagulation therapy, for which emergent thrombectomy and ligation of the significant hepatofugal collateral veins followed by full anti-coagulation therapy were performed. The shunt remains open at 8 month after the procedure with a normal anmonia level and liver function. In conclusion, the Rex shunt using recipient's autologous vein grafts is a feasible and valuable option for adult patients to treat PVT after LDLT..
548. Masayuki Watanabe, Koki Matsuura, Hideo Baba, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Koshi Mimori, Keishi Sugimachi, Hiroshi Saeki, Yoshihiko Maehara, Thoracoscopic pericardial drainage for gastric tube ulcer penetrated into the pericardium., Unknown Journal, 104, 10, 389-393, 2013.01, Peptic ulcer occurring in the gastric conduit for esophageal reconstruction sometimes penetrates into the mediastinal structures. We herein reported a case of pericardial penetration of gastric tube ulcer successfully treated with thoracoscopic pericardial drainage. A 66-year-old Japanese man, who had undergone esophagectomy for esophageal cancer 20 months before, visited our emergency room complaining severe back pain. Computed tomography revealed gastric tube ulcer penetrated into the pericardial space. Thoracoscopic pericardiotomy and drainage was performed and the patient made an uneventful recovery. Thoracoscopic pericardial drainage is useful to manage acute pyogenic pericarditis due to penetration of peptic ulcer which occurred in the gastric tube..
549. Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tetsuo Ikeda, Hirofumi Kawanaka, Yo Ichi Yamashita, Masaru Morita, Eiji Oki, Koushi Mimori, Keishi Sugimachi, Hiroshi Saeki, Masayuki Watanabe, Kenji Takenaka, Yoshihiko Maehara, Verification of our therapeutic criterion for acute cholecystitis
"perform a subemergency laparoscopic cholecystectomy when a patient is judged to be able to tolerate general anesthesia"--the experience in a single community hospital., Unknown Journal, 104, 10, 339-343, 2013.01, Our current therapeutic criterion for acute cholecystitis is: Perform a subemergency laparoscopic cholecystectomy (LC) when a patient is judged to be able to tolerate general anesthesia. The aim of the current study was to verify whether this criterion is justified. The outcomes of 21 cases of LC for acute cholecystitis performed between April 2011 and September 2013 were retrospectively analyzed. Subemergency LC was performed according to the aforementioned criterion (Subemergency group; n = 16). Patient who was judged to be unable to tolerate general anesthesia underwent percutaneous transhepatic gallbladder drainage (PTGBD) first, then LC after the patients' condition became stable (PTGBD group; n = 5). There is no conversion to open surgery throughout the study period. The mean of the total hospital stays in the Subemergency group was significantly shorter than that in the PTGBD group (11.5 +/- 5.3 vs. 30.4 +/- 8.5 days). Although two patients in the Subemergency group, who had already needed oxygen administration preoperatively, suffered postoperative respiratory failure, they completely recovered. On the other hand, there is no postoperative complication in the PTGBD group. Subemergency LC could be safely performed when surgeons as well as anesthesiologists judged a patient to be able to tolerate general anesthesia, which significantly shorten hospital stays compared to elective LC after PTGBD. However, elective LC after PTGBD is an absolutely safer therapeutic option in treating unstable patients..
550. Tetsuo Ikeda, Tomohiko Akahoshi, Hirofumi Kawanaka, Hideaki Uchiyama, Yo ichi Yamashita, Masaru Morita, Eiji Oki, Hiroshi Saeki, Keishi Sugimachi, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Koshi Mimori, Masayuki Watanabe, Makoto Hashizume, Yoshihiko Maehara, [Optimum hepatic parenchymal dissection to prevent bile leak
a comparative study using electrosurgical and stapling devices in swine]., Fukuoka igaku zasshi = Hukuoka acta medica, 104, 12, 507-514, 2013.01, Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma..
551. Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara, Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma
Report of a case, Surgery today, 10.1007/s00595-012-0332-4, 42, 12, 1210-1214, 2012.12, The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection..
552. Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara, Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma
Report of a case, Surgery today, 10.1007/s00595-012-0332-4, 42, 12, 1210-1214, 2012.12, The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection..
553. Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara, Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma
Report of a case, Surgery today, 10.1007/s00595-012-0332-4, 42, 12, 1210-1214, 2012.12, The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection..
554. Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara, Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma
Report of a case, Surgery today, 10.1007/s00595-012-0332-4, 42, 12, 1210-1214, 2012.12, The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection..
555. Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara, Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma: report of a case., Surgery today, 10.1007/s00595-012-0332-4, 42, 12, 1210-4, 2012.12, The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection..
556. Takashi Motomura, Ken Shirabe, Norihiro Furusyo, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tomohiko Akahoshi, Morimasa Tomikawa, Takasuke Fukuhara, Jun Hayashi, Yoshihiko Maehara, Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype, BMC Gastroenterology, 10.1186/1471-230X-12-158, 12, 2012.11, Background: IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.Methods: Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.Results: Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.Conclusions: IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype..
557. Takashi Motomura, Yuki Ono, Ken Shirabe, Takasuke Fukuhara, Hideyuki Konishi, Yohei Mano, Takeo Toshima, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Neither MICA nor DEPDC5 genetic polymorphisms correlate with hepatocellular carcinoma recurrence following hepatectomy, HPB Surgery, 10.1155/2012/185496, 2012, 2012.11, Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7 in MICA GG allele carriers, 38.7 in GA, and 20.8 in AA, respectively (P = 0.72). The five-year RFS rate was 23.8 in DEPDC5 TT allele carriers and 31.8 in TG/GG, respectively (P = 0.47). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers (P 0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages..
558. Yuji Soejima, Toru Ikegami, Hideki Ijichi, Tetsuo Ikeda, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hiroshi Matsuura, Kenichiro Okadome, Yoshihiko Maehara, Technical evolution of laparoscopic hepatic resection
a single institutional experience., Unknown Journal, 103, 11, 226-232, 2012.11, Laparoscopic hepatic resection (LHR) is still a challenging and developing surgical modality because of technical difficulty and a lack of training opportunities and experience. In this study, we present the results of our initial experiences of LHR, focusing on technical evolution in the management of LHR. Between April 2011 and March 2012, a total of 12 LHRs were performed. The first 5 of these LHRs were performed under laparoscopic assistance (hybrid-LHR), while the last 7 LHRs were performed totally laparoscopically (pure-LHR). Indications for LHR were hepatocellular carcinoma (n = 9) and metastatic liver cancer (n = 3). LHR procedures consisted of partial resection (n = 2), left lateral segmentectomy (n = 2), and left lobectomy (n = 1) in the hybrid-LHR group, and partial resection (n = 4), left lateral segmentectomy (n = 2), and right lobectomy (n = 1) in the pure-LHR group. Operative outcomes were compared between the groups and technical modifications were evaluated. The mean operative time, blood loss, and length of hospital stay in the hybrid- and pure-LHR groups were 3.8 and 6.1 hours, 220 and 611 ml, and 9.4 and 7.4 days, respectively. There were no postoperative complications in both groups. Tumor margins were negative in all cases. LHR is a feasible and effective procedure for patients with various types of liver tumors, although technical challenges still need to be overcome..
559. Shohei Yoshiya, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31826969e6, 94, 9, 947-952, 2012.11, BACKGROUND: Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. METHODS: A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. RESULTS: The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). CONCLUSIONS: Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group..
560. Takashi Motomura, Ken Shirabe, Norihiro Furusyo, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tomohiko Akahoshi, Morimasa Tomikawa, Takasuke Fukuhara, Jun Hayashi, Yoshihiko Maehara, Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype, BMC Gastroenterology, 10.1186/1471-230X-12-158, 12, 2012.11, Background: IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.Methods: Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.Results: Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.Conclusions: IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype..
561. Takashi Motomura, Yuki Ono, Ken Shirabe, Takasuke Fukuhara, Hideyuki Konishi, Yohei Mano, Takeo Toshima, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Neither MICA nor DEPDC5 genetic polymorphisms correlate with hepatocellular carcinoma recurrence following hepatectomy, HPB Surgery, 10.1155/2012/185496, 2012, 2012.11, Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7 in MICA GG allele carriers, 38.7 in GA, and 20.8 in AA, respectively (P = 0.72). The five-year RFS rate was 23.8 in DEPDC5 TT allele carriers and 31.8 in TG/GG, respectively (P = 0.47). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers (P 0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages..
562. Yuji Soejima, Toru Ikegami, Hideki Ijichi, Tetsuo Ikeda, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hiroshi Matsuura, Kenichiro Okadome, Yoshihiko Maehara, Technical evolution of laparoscopic hepatic resection
a single institutional experience., Unknown Journal, 103, 11, 226-232, 2012.11, Laparoscopic hepatic resection (LHR) is still a challenging and developing surgical modality because of technical difficulty and a lack of training opportunities and experience. In this study, we present the results of our initial experiences of LHR, focusing on technical evolution in the management of LHR. Between April 2011 and March 2012, a total of 12 LHRs were performed. The first 5 of these LHRs were performed under laparoscopic assistance (hybrid-LHR), while the last 7 LHRs were performed totally laparoscopically (pure-LHR). Indications for LHR were hepatocellular carcinoma (n = 9) and metastatic liver cancer (n = 3). LHR procedures consisted of partial resection (n = 2), left lateral segmentectomy (n = 2), and left lobectomy (n = 1) in the hybrid-LHR group, and partial resection (n = 4), left lateral segmentectomy (n = 2), and right lobectomy (n = 1) in the pure-LHR group. Operative outcomes were compared between the groups and technical modifications were evaluated. The mean operative time, blood loss, and length of hospital stay in the hybrid- and pure-LHR groups were 3.8 and 6.1 hours, 220 and 611 ml, and 9.4 and 7.4 days, respectively. There were no postoperative complications in both groups. Tumor margins were negative in all cases. LHR is a feasible and effective procedure for patients with various types of liver tumors, although technical challenges still need to be overcome..
563. Shohei Yoshiya, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31826969e6, 94, 9, 947-952, 2012.11, BACKGROUND: Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. METHODS: A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. RESULTS: The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). CONCLUSIONS: Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group..
564. Takashi Motomura, Ken Shirabe, Norihiro Furusyo, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tomohiko Akahoshi, Morimasa Tomikawa, Takasuke Fukuhara, Jun Hayashi, Yoshihiko Maehara, Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype, BMC Gastroenterology, 10.1186/1471-230X-12-158, 12, 2012.11, Background: IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.Methods: Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.Results: Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.Conclusions: IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype..
565. Takashi Motomura, Yuki Ono, Ken Shirabe, Takasuke Fukuhara, Hideyuki Konishi, Yohei Mano, Takeo Toshima, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Neither MICA nor DEPDC5 genetic polymorphisms correlate with hepatocellular carcinoma recurrence following hepatectomy, HPB Surgery, 10.1155/2012/185496, 2012, 2012.11, Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7 in MICA GG allele carriers, 38.7 in GA, and 20.8 in AA, respectively (P = 0.72). The five-year RFS rate was 23.8 in DEPDC5 TT allele carriers and 31.8 in TG/GG, respectively (P = 0.47). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers (P 0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages..
566. Yuji Soejima, Toru Ikegami, Hideki Ijichi, Tetsuo Ikeda, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hiroshi Matsuura, Kenichiro Okadome, Yoshihiko Maehara, Technical evolution of laparoscopic hepatic resection
a single institutional experience., Unknown Journal, 103, 11, 226-232, 2012.11, Laparoscopic hepatic resection (LHR) is still a challenging and developing surgical modality because of technical difficulty and a lack of training opportunities and experience. In this study, we present the results of our initial experiences of LHR, focusing on technical evolution in the management of LHR. Between April 2011 and March 2012, a total of 12 LHRs were performed. The first 5 of these LHRs were performed under laparoscopic assistance (hybrid-LHR), while the last 7 LHRs were performed totally laparoscopically (pure-LHR). Indications for LHR were hepatocellular carcinoma (n = 9) and metastatic liver cancer (n = 3). LHR procedures consisted of partial resection (n = 2), left lateral segmentectomy (n = 2), and left lobectomy (n = 1) in the hybrid-LHR group, and partial resection (n = 4), left lateral segmentectomy (n = 2), and right lobectomy (n = 1) in the pure-LHR group. Operative outcomes were compared between the groups and technical modifications were evaluated. The mean operative time, blood loss, and length of hospital stay in the hybrid- and pure-LHR groups were 3.8 and 6.1 hours, 220 and 611 ml, and 9.4 and 7.4 days, respectively. There were no postoperative complications in both groups. Tumor margins were negative in all cases. LHR is a feasible and effective procedure for patients with various types of liver tumors, although technical challenges still need to be overcome..
567. Shohei Yoshiya, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31826969e6, 94, 9, 947-952, 2012.11, BACKGROUND: Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. METHODS: A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. RESULTS: The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). CONCLUSIONS: Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group..
568. Takashi Motomura, Ken Shirabe, Norihiro Furusyo, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tomohiko Akahoshi, Morimasa Tomikawa, Takasuke Fukuhara, Jun Hayashi, Yoshihiko Maehara, Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype, BMC Gastroenterology, 10.1186/1471-230X-12-158, 12, 2012.11, Background: IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.Methods: Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.Results: Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.Conclusions: IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype..
569. Takashi Motomura, Yuki Ono, Ken Shirabe, Takasuke Fukuhara, Hideyuki Konishi, Yohei Mano, Takeo Toshima, Shohei Yoshiya, Jun Muto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara, Neither MICA nor DEPDC5 genetic polymorphisms correlate with hepatocellular carcinoma recurrence following hepatectomy, HPB Surgery, 10.1155/2012/185496, 2012, 2012.11, Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7 in MICA GG allele carriers, 38.7 in GA, and 20.8 in AA, respectively (P = 0.72). The five-year RFS rate was 23.8 in DEPDC5 TT allele carriers and 31.8 in TG/GG, respectively (P = 0.47). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers (P 0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages..
570. Yuji Soejima, Toru Ikegami, Hideki Ijichi, Tetsuo Ikeda, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoichi Yamashita, Norifumi Harimoto, Takeo Toshima, Hiroshi Matsuura, Kenichiro Okadome, Yoshihiko Maehara, Technical evolution of laparoscopic hepatic resection
a single institutional experience., Unknown Journal, 103, 11, 226-232, 2012.11, Laparoscopic hepatic resection (LHR) is still a challenging and developing surgical modality because of technical difficulty and a lack of training opportunities and experience. In this study, we present the results of our initial experiences of LHR, focusing on technical evolution in the management of LHR. Between April 2011 and March 2012, a total of 12 LHRs were performed. The first 5 of these LHRs were performed under laparoscopic assistance (hybrid-LHR), while the last 7 LHRs were performed totally laparoscopically (pure-LHR). Indications for LHR were hepatocellular carcinoma (n = 9) and metastatic liver cancer (n = 3). LHR procedures consisted of partial resection (n = 2), left lateral segmentectomy (n = 2), and left lobectomy (n = 1) in the hybrid-LHR group, and partial resection (n = 4), left lateral segmentectomy (n = 2), and right lobectomy (n = 1) in the pure-LHR group. Operative outcomes were compared between the groups and technical modifications were evaluated. The mean operative time, blood loss, and length of hospital stay in the hybrid- and pure-LHR groups were 3.8 and 6.1 hours, 220 and 611 ml, and 9.4 and 7.4 days, respectively. There were no postoperative complications in both groups. Tumor margins were negative in all cases. LHR is a feasible and effective procedure for patients with various types of liver tumors, although technical challenges still need to be overcome..
571. Shohei Yoshiya, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation, Transplantation, 10.1097/TP.0b013e31826969e6, 94, 9, 947-952, 2012.11, BACKGROUND: Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. METHODS: A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. RESULTS: The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). CONCLUSIONS: Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group..
572. Takashi Motomura, Ken Shirabe, Norihiro Furusyo, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Tomohiko Akahoshi, Morimasa Tomikawa, Takasuke Fukuhara, Jun Hayashi, Yoshihiko Maehara, Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype., BMC gastroenterology, 10.1186/1471-230X-12-158, 12, 158-158, 2012.11, BACKGROUND: IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined. METHODS: Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen. RESULTS: Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy. CONCLUSIONS: IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype..
573. Shohei Yoshiya, Ken Shirabe, Koichi Kimura, Tomoharu Yoshizumi, Toru Ikegami, Hiroto Kayashima, Takeo Toshima, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara, The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation., Transplantation, 10.1097/TP.0b013e31826969e6, 94, 9, 947-52, 2012.11, BACKGROUND: Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. METHODS: A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. RESULTS: The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). CONCLUSIONS: Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group..
574. Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Authors' reply to "female-to-male match predicted poor survival following living donor liver transplantation-some issues needed to be clarified", Transplantation, 10.1097/TP.0b013e3182654d56, 94, 6, e36, 2012.09.
575. Toru Ikegami, Ken Shirabe, Rumi Matono, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Etiologies, risk factors, and outcomes of bacterial pneumonia after living donor liver transplantation, Liver Transplantation, 10.1002/lt.23483, 18, 9, 1060-1068, 2012.09, The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short-term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram-negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P = 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post-LDLT pneumonia was associated with the following post-LDLT events: the prolonged use of mechanical ventilation (≥3 days), a prolonged stay in the intensive care unit (≥7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed-onset pneumonia, which occurred at least 10 days after transplantation (n = 15), and it was significantly associated with graft dysfunction. A combination of broad-spectrum antibiotics and aminoglycosides provided cover for most gram-negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad-spectrum antibiotics. Delayed-onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed..
576. Hideaki Uchiyama, Hiroto Kayashima, Rumi Matono, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Toshiharu Matsuura, Tomoaki Taguchi, Yoshihiko Maehara, Relevance of HLA compatibility in living donor liver transplantation
The double-edged sword associated with the patient outcome, Clinical Transplantation, 10.1111/ctr.12019, 26, 5, E522-E529, 2012.09, HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA-A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host-versus-graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft-versus-host disease (GVHD) was also analyzed. No recipients with recipient-against-donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with "R→D MM 0" together with "donor-against-recipient MM 3" died of fatal GVHD. HLA compatibility in LDLT not only affected the long-term acceptance of graft livers but also the risk of fatal GVHD..
577. Mizue Matsuo, Toru Ikegami, Kazutoyo Morita, Hiroko Yano, Naotaka Hashimoto, Hiroto Kayashima, Toshirou Masuda, Naoko Kondou, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, [A case of successful multi-venous reconstruction using recipient's jugular vein in right lobe-living donor liver transplantation]., Unknown Journal, 103, 9, 186-190, 2012.09, In right lobe-living donor liver transplantation (RT-LDLT), hepatic venous reconstruction of the graft is essential to prevent posttansplant graft congestion and have a good outcome. The patient was a 56-year-old man who had decompensated liver cirrhosis secondary hepatitis C with massive ascites, jaundice and hepatic encephalopathy. He underwent LDLT using his son's right lobe graft. Preoperative simulation by 3D-CT volumetry revealed that the right lobe graft needed multi-venous reconstruction for right inferior hepatic vein (RIHV) and middle hepatic venous tributaries. Preoperative CT scan revealed that the recipient had portal venous thrombus and stenosis, which meant that the recipient's explanted portal vein (EPV) was not suitable for the venous reconstruction of the right lobe graft. Therefore, the recipient's internal and external jugular veins (IJV and EJV) were procured for venous reconstruction. The multiple veins of the right lobe graft were reconstructed to have single co-orifice at the backtable, and the co-orifice was anastomosed to inferior vena cava in short time. The recipient discharged on postoperative day 22 with good venous patency. In RT-LDLT unavailable for recipient's EPV, recipient's IJV and EJV grafts are very useful for multi-venous reconstruction..
578. Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Authors' reply to "female-to-male match predicted poor survival following living donor liver transplantation-some issues needed to be clarified", Transplantation, 10.1097/TP.0b013e3182654d56, 94, 6, e36, 2012.09.
579. Toru Ikegami, Ken Shirabe, Rumi Matono, Tomoharu Yoshizumi, Yuji Soejima, Hideaki Uchiyama, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara, Etiologies, risk factors, and outcomes of bacterial pneumonia after living donor liver transplantation, Liver Transplantation, 10.1002/lt.23483, 18, 9, 1060-1068, 2012.09, The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short-term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram-negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P = 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post-LDLT pneumonia was associated with the following post-LDLT events: the prolonged use of mechanical ventilation (≥3 days), a prolonged stay in the intensive care unit (≥7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed-onset pneumonia, which occurred at least 10 days after transplantation (n = 15), and it was significantly associated with graft dysfunction. A combination of broad-spectrum antibiotics and aminoglycosides provided cover for most gram-negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad-spectrum antibiotics. Delayed-onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed..
580. Hideaki Uchiyama, Hiroto Kayashima, Rumi Matono, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Toshiharu Matsuura, Tomoaki Taguchi, Yoshihiko Maehara, Relevance of HLA compatibility in living donor liver transplantation
The double-edged sword associated with the patient outcome, Clinical Transplantation, 10.1111/ctr.12019, 26, 5, E522-E529, 2012.09, HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA-A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host-versus-graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft-versus-host disease (GVHD) was also analyzed. No recipients with recipient-against-donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with "R→D MM 0" together with "donor-against-recipient MM 3" died of fatal GVHD. HLA compatibility in LDLT not only affected the long-term acceptance of graft livers but also the risk of fatal GVHD..
581. Mizue Matsuo, Toru Ikegami, Kazutoyo Morita, Hiroko Yano, Naotaka Hashimoto, Hiroto Kayashima, Toshirou Masuda, Naoko Kondou, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, [A case of successful multi-venous reconstruction using recipient's jugular vein in right lobe-living donor liver transplantation]., Unknown Journal, 103, 9, 186-190, 2012.09, In right lobe-living donor liver transplantation (RT-LDLT), hepatic venous reconstruction of the graft is essential to prevent posttansplant graft congestion and have a good outcome. The patient was a 56-year-old man who had decompensated liver cirrhosis secondary hepatitis C with massive ascites, jaundice and hepatic encephalopathy. He underwent LDLT using his son's right lobe graft. Preoperative simulation by 3D-CT volumetry revealed that the right lobe graft needed multi-venous reconstruction for right inferior hepatic vein (RIHV) and middle hepatic venous tributaries. Preoperative CT scan revealed that the recipient had portal venous thrombus and stenosis, which meant that the recipient's explanted portal vein (EPV) was not suitable for the venous reconstruction of the right lobe graft. Therefore, the recipient's internal and external jugular veins (IJV and EJV) were procured for venous reconstruction. The multiple veins of the right lobe graft were reconstructed to have single co-orifice at the backtable, and the co-orifice was anastomosed to inferior vena cava in short time. The recipient discharged on postoperative day 22 with good venous patency. In RT-LDLT unavailable for recipient's EPV, recipient's IJV and EJV grafts are very useful for multi-venous reconstruction..
582. Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Authors' reply to "female-to-male match predicted poor survival following living donor liver transplantation-some i