Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Itoh Shinji Last modified date:2019.06.23

Assistant Professor / Department of Surgery and Science / Liver Surgery / Kyushu University Hospital


Papers
1. shinji itoh, [Experience of 2013 Japan Exchange Fellow of the Japan Surgical Society and the American College of Surgeons]., Nihon Geka Gakkai zasshi, 115, 2, 113-115, 2014.01.
2. 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..
3. 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..
4. 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..
5. 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..
6. 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..
7. 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..
8. 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..
9. 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..
10. Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, N. Harimoto, Noboru Harada, shinji itoh, T. Toshima, T. Motomura, Yohei 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..
11. N. Harimoto, H. Nakagawara, K. Shirabe, Tomoharu Yoshizumi, shinji itoh, Toru Ikegami, Yuji 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..
12. 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, 2019.01, 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..
13. 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..
14. 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.
15. 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..
16. K. Kimura, K. Kudo, T. Kurihara, S. Yoshiya, Yohei Mano, kazuki takeishi, shinji itoh, Noboru Harada, Toru Ikegami, Tomoharu 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..
17. 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..
18. 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..
19. 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..
20. Kotoe Takayoshi, Goro Doi, Nobuhiro Tsuruta, Tomoyasu Yoshihiro, Kenta Nio, Kenji Tsuchihashi, hiroshi ariyama, Jun Odawara, Shinji Shimoda, Kenichi Kouhashi, Yoshinao Oda, shinji itoh, Norifumi Harimoto, Yoshihiko Maehara, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, Successful chemotherapeutic treatment for metastatic littoral cell angioma
A case report, Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries, 10.1097/MD.0000000000010378, 97, 15, 2018.04, Rationale:Metastatic littoral cell angioma (LCA) is extremely rare. No standard therapeutic strategy has been established, and the impact of chemotherapy has not yet been evaluated.Patient concerns:A 61-year-old woman was admitted because of bicytopenia. She had a splenectomy for LCA of the spleen 10 years earlier. Bone marrow aspiration was normal, and a computed tomography (CT) scan showed hepatomegaly with multiple liver tumors. Diagnoses:Liver biopsy samples showed macrophage-like cell infiltration in the hepatic sinusoids. Metastatic LCA was diagnosed based on immunohistochemistry, imaging tests, and the clinical course.Interventions:Immunosuppressive agents, such as prednisolone and cyclosporine, were ineffective. Next, cytotoxic agents, such as etoposide, paclitaxel, and vincristine, were administered.Outcomes:Cytotoxic agents showed a prominent effect against LCA. CT showed improvement of the hepatomegaly, and fluoro-deoxyglucose (FDG) uptake decreased markedly at a follow-up FDG- positron emission tomography (PET) scan.Lessons:Chemotherapeutic treatment based on hemophagocytic syndrome or angiosarcoma might have anti-tumor activity against metastatic LCA. Analysis of the molecular characteristics of this tumor is needed to develop better treatment options..
21. 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..
22. 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..
23. Norifumi Harimoto, K. Yugawa, Toru Ikegami, M. Ohira, Yohei Mano, T. Motomura, Takeo Toshima, shinji itoh, N. Harada, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Maehara, Yoshinao 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.
24. Norifumi Harimoto, Tomoharu Yoshizumi, Yukiko Fujimoto, Takashi Motomura, Yohei 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, 1-11, 2018.01, 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..
25. 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..
26. T. Motomura, Tomoharu Yoshizumi, M. Ohira, Yohei Mano, Takeo Toshima, shinji itoh, Noboru Harada, Norifumi Harimoto, Toru Ikegami, Yuji Soejima, Yoshihiko 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..
27. Norifumi Harimoto, Tomoharu Yoshizumi, T. Izumi, T. Motomura, Noboru Harada, shinji itoh, Toru Ikegami, H. Uchiyama, Yuji Soejima, Akihiro Nishie, T. Kamishima, R. Kusaba, K. Shirabe, Yoshihiko 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..
28. 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..
29. 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..
30. 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..
31. 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..
32. 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..
33. 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..
34. T. Motomura, Tomoharu Yoshizumi, H. Wang, A. Nagatsu, shinji itoh, Noboru Harada, Norifumi Harimoto, Toru Ikegami, H. Uchiyama, Yuji Soejima, Yoshihiko 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..
35. 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..
36. 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..
37. 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..
38. 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..
39. 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..
40. 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..
41. 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..
42. 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..
43. Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Norifumi Harimoto, shinji itoh, 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..
44. 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.
45. 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..
46. 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..
47. H. Okabe, Tomoharu Yoshizumi, Toru Ikegami, H. Uchiyama, Norifumi Harimoto, shinji itoh, K. Kimura, H. Baba, Yoshihiko 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..
48. 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..
49. 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..
50. 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..
51. 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..
52. 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..
53. 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 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..
54. 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..
55. 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 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..
56. 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..
57. 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..
58. 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.
59. 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..
60. 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.
61. 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..
62. 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..
63. 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..
64. 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..
65. Koichi Kimura, shinji itoh, Takeshi Kurihara, Yoshihiro Yoshida, Huanlin Wang, Norifumi Harimoto, Akihiro Nishie, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Predictors of Benign Status in Liver Tumors Under 3 cm in Diameter Misdiagnosed as Hepatocellular Carcinoma, Anticancer Research, 36, 2, 793-797, 2016.02, BACKGROUND: The clinical features of benign liver lesions misdiagnosed as hepatocellular carcinoma have not been fully described.
PATIENTS AND METHODS: This study included 187 patients who underwent hepatectomy at the Kyushu University Hospital following a diagnosis of solitary HCC of ≤3 cm in diameter.
RESULTS: Following hepatectomy, 9.6% patients were pathologically diagnosed with benign liver lesions. Univariate analysis showed that patient age ≤67 years, negativity for hepatitis C virus antigen, lesion size ≤1.5 cm, normal level of tumor markers, and absence of increase in tumor size were associated with benign lesions. Patient age ≤67 years and absence of tumor size increase were independent predictors of benign lesions.
CONCLUSION: Benign liver lesions misdiagnosed as HCC were not infrequent, accounting for approximately 10% of resected cases. Age ≤67 years and absence of tumor size increase were independent predictors of benign liver lesions, and may help in the correct diagnosis of HCC..
66. 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..
67. Koichi Kimura, shinji itoh, Takeshi Kurihara, Yoshihiro Yoshida, Huanlin Wang, Norifumi Harimoto, Akihiro Nishie, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Predictors of Benign Status in Liver Tumors Under 3 cm in Diameter Misdiagnosed as Hepatocellular Carcinoma, Anticancer Research, 36, 2, 793-797, 2016.02, BACKGROUND: The clinical features of benign liver lesions misdiagnosed as hepatocellular carcinoma have not been fully described.
PATIENTS AND METHODS: This study included 187 patients who underwent hepatectomy at the Kyushu University Hospital following a diagnosis of solitary HCC of ≤3 cm in diameter.
RESULTS: Following hepatectomy, 9.6% patients were pathologically diagnosed with benign liver lesions. Univariate analysis showed that patient age ≤67 years, negativity for hepatitis C virus antigen, lesion size ≤1.5 cm, normal level of tumor markers, and absence of increase in tumor size were associated with benign lesions. Patient age ≤67 years and absence of tumor size increase were independent predictors of benign lesions.
CONCLUSION: Benign liver lesions misdiagnosed as HCC were not infrequent, accounting for approximately 10% of resected cases. Age ≤67 years and absence of tumor size increase were independent predictors of benign liver lesions, and may help in the correct diagnosis of HCC..
68. 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..
69. 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..
70. 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..
71. 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..
72. 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..
73. 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..
74. 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..
75. 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..
76. 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..
77. 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..
78. 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..
79. 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..
80. 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..
81. Daisuke Yoshida, shinji itoh, Nao Kinjo, Norifumi Harimoto, Seiji Maruyama, Hirofumi Kawanaka, Ken Shirabe, Akito Matsukuma, Shunji Kohnoe, Yoshihiko Maehara, Laparoscopic intraperitoneal mesh repair of Spigelian hernia
A case report, Asian journal of endoscopic surgery, 10.1111/ases.12205, 8, 4, 477-479, 2015.11, Spigelian hernia is a rare congenital defect of the anterior abdominal wall located along the semilunar line through the aponeurosis fascia of the transversus abdominis muscle. It represents 1%-2% of all abdominal wall hernias. Few cases of laparoscopic treatment for Spigelian hernia have been reported, especially in Japan. However, several reports of laparoscopic surgery to repair Spigelian hernias have been published, and some have shown that the laparoscopic approach repair is feasible because it is associated with less morbidity and a shorter hospital stay than open surgery. We herein describe a 63-year-old Japanese woman who presented with painful bulging in the right lower abdominal quadrant. A preoperative diagnosis of Spigelian hernia was made, and we performed laparoscopic intraperitoneal repair. The patient was discharged 6 days after laparoscopic surgery with no perioperative complications. This report describes the first successful laparoscopic intraperitoneal mesh repair of Spigelian hernia in Japan..
82. 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.
83. Yuki Bekki, Yo Ichi Yamashita, shinji itoh, Norifumi Harimoto, Ken Shirabe, Yoshihiko Maehara, Predictors of the Effectiveness of Prophylactic Drains after Hepatic Resection, World Journal of Surgery, 10.1007/s00268-015-3116-3, 39, 10, 2543-2549, 2015.10, Background: Randomized clinical trials have demonstrated the limited efficacy of prophylactic drains following hepatic resection. However, many surgeons still insist on using prophylactic drains. This study was designed to identify patients who require prophylactic drains to manage or monitor postoperative complications after hepatic resection. Methods: Data were retrospectively collected from 316 patients who underwent hepatic resection and received a prophylactic drain. The patients were divided into two groups according to whether the drain was used to manage or monitor the following postoperative complications: bile leakage (prophylactic drains were used to monitor and treat bile leakage) and postoperative hemorrhage (the drainage fluid was macroscopically bloody and required drain fluid blood counts and monitoring to assess the need for transfusion or reoperation). The results were then validated in a separate cohort of 101 patients. Results: In 25/316 patients (7.9 %), the prophylactic drains were clinically effective, being used to manage bile leakage in 18 patients and hemorrhage in 8. Intraoperative bile leakage (P = 0.021) and long operation time (≥360 min) (P = 0.017) were independent predictors of bile leakage. Intraoperative blood loss (≥650 ml) (P = 0.0009) was an independent predictor of hemorrhage. In the subsequent 101 patients, prophylactic drains were clinically effective in patients with one of these predictors with sensitivity, specificity, and false-negative rates of 88.9, 62.0, and 1.7 %, respectively. Conclusion: A prophylactic drain should be considered following hepatic resection for patients with intraoperative bile leakage, operation time of ≥360 min, or blood loss of ≥650 ml..
84. 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.
85. 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..
86. 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.
87. 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..
88. 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..
89. Tomoharu Yoshizumi, shinji itoh, D. Imai, Toru Ikegami, M. Ninomiya, T. Iguchi, Norifumi Harimoto, K. Takeishi, Y. Kimura, H. Uchiyama, Yuji Soejima, Tetsuo Ikeda, H. Kawanaka, K. Shirabe, Yoshihiko 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..
90. K. Takeishi, Toru Ikegami, Tomoharu Yoshizumi, shinji itoh, Norifumi Harimoto, Noboru Harada, E. Tsujita, Y. Kimura, Y. Yamashita, K. Saeki, Eiji Oki, K. Shirabe, Yoshihiko 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..
91. Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Norifumi Harimoto, shinji itoh, K. Takeishi, H. Uchiyama, H. Kawanaka, Y. I. Yamashita, E. Tsujita, Noboru Harada, Eiji Oki, Hiroshi Saeki, Y. Kimura, K. Shirabe, Yoshihiko 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..
92. Takahiro Tomino, shinji itoh, Daisuke Yoshida, Takahiro Nishida, Hirofumi Kawanaka, Tetsuo Ikeda, Shunji Kohnoe, Ken Shirabe, Yoshihiko Maehara, Right paraduodenal hernia successfully treated with laparoscopic surgery, Asian journal of endoscopic surgery, 10.1111/ases.12139, 8, 1, 87-90, 2015.02, A 23-year-old Japanese man presented with a history of sudden-onset right abdominal pain accompanied by nausea and vomiting. Contrast-enhanced CT showed a large cluster on the right side of the retroperitoneum, with most of the small bowel incarcerated. The patient was diagnosed with small bowel obstruction caused by a right paraduodenal hernia, and emergency laparoscopic surgery was performed. The large retroperitoneal cluster on the right side contained almost all segments of the small bowel, although the incarcerated bowel showed no evidence of volvulus or ischemia. The bowel was reduced, and the hernia orifice was closed. The patient made good progress and was discharged 7 days after surgery. We herein report an acute case of right paraduodenal hernia with small bowel obstruction that was successfully treated with emergency laparoscopic surgery. With an early preoperative diagnosis, laparoscopic surgery is appropriate for the treatment of right paraduodenal hernia..
93. Hideaki Uchiyama, Kazutoyo Morita, shinji itoh, Kenji Takenaka, Yoshihiko Maehara, BiClamp-Fracture Method in Pure Laparoscopic Hepatectomy
Verifying its Efficacy Irrespective of Liver Stiffness, Surgical Laparoscopy, Endoscopy and Percutaneous Techniques, 10.1097/SLE.0000000000000172, 25, 4, e113-e116, 2015.01, Background: Transecting cirrhotic liver in pure laparoscopic hepatectomy (PLH) is generally considered technically demanding. We have preferentially used BiClamp in PLH by fracturing liver parenchyma using this device. The aim of the current study was to retrospectively verify the efficacy of BiClamp-fracture method in transecting cirrhotic parenchyma. Methods: The medical records of 21 patients who underwent PLH using BiClamp-fracture method between April 2011 and September 2014 were examined. The patients were divided into the Nonstiff group (F0-F2, n=11) and the Stiff group (F3 and F4, n=10) and various surgical factors were compared between the groups. Results: The mean operation time, the mean intraoperative blood loss, and the mean postoperative hospital stay in the Stiff group were comparable with those in the Nonstiff group. There were no postoperative complications in both groups. Conclusion: BiClamp-fracture method was effective in transecting liver parenchyma irrespective of liver stiffness in PLH..
94. K. Takeishi, K. Shirabe, Y. Yoshida, Y. Tsutsui, T. Kurihara, K. Kimura, shinji itoh, Norifumi Harimoto, Y. I. Yamashita, Toru Ikegami, Tomoharu Yoshizumi, Akihiro Nishie, Yoshihiko 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..
95. Norifumi Harimoto, H. Wang, Toru Ikegami, K. Takeishi, shinji itoh, Y. I. Yamashita, Tomoharu Yoshizumi, S. Aishima, K. Shirabe, Yoshinao Oda, Yoshihiko 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, 2015.01.
96. 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, 2015.01, 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..
97. 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, 2015.01, 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..
98. 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, 2015.01, 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..
99. 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, 2015.01, 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..
100. 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, 2015.01, 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..
101. 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, 2015.01, 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..
102. Norifumi Harimoto, Y. Yoshida, T. Kurihara, K. Takeishi, shinji itoh, Noboru Harada, E. Tsujita, Y. I. Yamashita, H. Uchiyama, Yuji Soejima, Toru Ikegami, Tomoharu Yoshizumi, H. Kawanaka, Tetsuo Ikeda, K. Shirabe, Hiroshi Saeki, Eiji Oki, Y. Kimura, Yoshihiko 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, 2015.01, 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..
103. Tomoyuki Uchihara, Yo Ichi Yamashita, Wang Hualin, Kazuki Takeishi, shinji itoh, Norifumi 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, 2015.01, 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..
104. 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..
105. shinji itoh, Hideaki Uchiyama, Hirofumi Kawanaka, Takahiro Higashi, Akinori Egashira, Daihiko Eguchi, Toshiro Okuyama, Masahiro Tateishi, Daisuke Korenaga, Kenji Takenaka, Characteristic risk factors in cirrhotic patients for posthepatectomy complications
Comparison with noncirrhotic patients, American Surgeon, 80, 2, 166-170, 2014.02, There seemed to be characteristic risk factors in cirrhotic patients for posthepatectomy complications because these patients have less hepatic reserve as compared with noncirrhotic patients. The aim of the current study was to identify these characteristic risk factors in cirrhotic patients. We performed 419 primary hepatectomies for hepatocellular carcinoma. The patients were divided into the cirrhotic group (n 5 198) and the noncirrhotic group (n 5 221), and the risk factors for posthepatectomy complications were compared between the groups. Thirty-six cirrhotic patients (18.2%) experienced Clavien's Grade III or more complications. Tumor size, intraoperative blood loss, duration of operation, major hepatectomy (two or more segments), and necessity of blood transfusion were found to be significant risk factors in univariate analyses. Multivariate analysis revealed that major hepatectomy and intraoperative blood loss were independent risk factors for posthepatectomy complications in patients with cirrhosis. On the other hand, the duration of operation was only an independent risk factor for posthepatectomy complication in noncirrhotic patients. Cirrhotic patients should avoid a major hepatectomy and undergo a limited resection preserving as much liver tissue as possible and meticulous surgical procedures to lessen intraoperative blood loss are mandatory to prevent major posthepatectomy complications..
106. 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, 2014.01, 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..
107. Mizuki Ninomiya, Shinichi Aishima, Tomoharu Yoshizumi, Toru Ikegami, Huanlin Wang, Norifumi Harimoto, shinji itoh, 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, 2014.01.
108. 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, 2014.01, 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..
109. Yo Ichi Yamashita, Tetsuo Ikeda, Takeshi Kurihara, Yoshihiro Yoshida, Kazuki Takeishi, shinji itoh, Norifumi Harimoto, Hirofumi Kawanaka, Ken Shirabe, Yoshihiko Maehara, Long-term favorable surgical results of laparoscopic hepatic resection for hepatocellular carcinoma in patients with cirrhosis
A single-center experience over a 10-year periods, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.09.003, 219, 6, 1117-1123, 2014.01, Background: We first performed laparoscopic hepatic resection (Lap-Hx) for hepatocellular carcinoma (HCC) in 1994. Here we review the long-term surgical results of Lap-Hx for HCC in patients with cirrhosis over a 10-year period at a single institution. Study Design: Between January 2000 and December 2013, 99 patients with cirrhosis underwent open hepatic resection (Open-Hx) and 63 underwent Lap-Hx for primary HCC within the Milan criteria. We compared the operative outcomes and patient survival between the 2 groups. RESULTS: There were no significant differences regarding patient background characteristics or tumorrelated factors between the 2 groups. The morbidity rate of the Lap-Hx group was significantly lower than that of the Open-Hx group (26% vs 10%; p = 0.0459), and the complication rate of ascites was significantly lower (7% vs 0%; p = 0.0077). The mean duration of hospital stay of the Lap-Hx group was significantly shorter than that of the Open-Hx group (16 vs 10 days; p = 0.0008). There were no significant between-group differences regarding overall or disease-free survival. Conclusions: Laparoscopic-Hx for HCC in patients with cirrhosis is associated with less morbidity and shorter hospital stays, with no compromise in patient survival. It may be time to consider changing the standard operation for primary HCC within the Milan criteria to Lap-Hx in patients with cirrhosis..
110. 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, 2014.01, 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..
111. 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..
112. 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, 2014.01.
113. 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..
114. Hideaki Uchiyama, Kazutoyo Morita, shinji itoh, Kenji Takenaka, Tape-guided pure laparoscopic hepatectomy for laterally located tumors
A technique to yield an appropriate tumor-free surgical margin and to make parenchymal transection easier, Journal of the American College of Surgeons, 10.1016/j.jamcollsurg.2014.03.059, 219, 3, 2014.01.
115. Takahiro Tomino, Hideaki Uchiyama, shinji itoh, Takahiro Higashi, Ai Edagawa, Akinori Egashira, Daihiko Eguchi, Hirofumi Kawanaka, Toshiroh Okuyama, Masahiro Tateishi, Daisuke Korenaga, Kenji Takenaka, Outcomes of emergency surgery for acute abdomen in dialysis patients
Experience of a single community hospital, Surgery Today, 10.1007/s00595-013-0673-7, 44, 4, 690-695, 2014, Purpose: Long-term dialysis often causes physiological and metabolic problems that may affect the outcomes of surgery. The aim of this study was to elucidate whether emergency surgery for acute abdomen yields similar outcomes in dialysis patients versus non-dialysis patients. Methods: The subjects were 126 patients who underwent emergency surgery for acute abdomen between January, 2007 and November, 2011 in our hospital. They were divided into a dialysis group (HD group; n = 9) and a non-dialysis group (non-HD group; n = 117) and their postoperative morbidity and mortality were compared. Results: Postoperative morbidity and mortality were significantly worse in the HD group. All 9 of these patients succumbed to postoperative complications versus only 5 of the 117 patients in the non-HD group. Conclusion: The outcomes of emergency surgery for acute abdomen were significantly worse for dialysis patients than for non-dialysis patients. Prompt diagnosis, initiation of the most suitable surgical procedure, and meticulous postoperative cares are imperative to improving the surgical outcomes of dialysis patients..
116. 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, 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..
117. Hideaki Uchiyama, shinji itoh, Takahiro Higashi, Daisuke Korenaga, Kenji Takenaka, Pure laparoscopic partial hepatectomy using a newly developed vessel sealing device, BiClamp, Surgical Laparoscopy, Endoscopy and Percutaneous Techniques, 10.1097/SLE.0b013e3182806535, 23, 3, 2013.06, PURPOSE: The aim of the current study was to investigate whether pure laparoscopic partial hepatectomy can be safely performed using a newly developed vessel sealing device, BiClamp. METHODS: Nine cases of pure laparoscopic partial hepatectomy were performed by simply transecting liver parenchyma using the BiClamp. Four patients had a cirrhotic liver. The median tumor diameter was 1.5 cm (range, 1.0 to 2.7 cm). The tumors were located in segment (S) 3 in 3 cases, S4 in 1 case, S5 in 2 cases, S6 in 1 case, and S8 in 2 cases. Simultaneous cholecystectomy was performed in 4 cases. RESULTS: The median operation time was 187 minutes (range, 83 to 423 min) and the median estimated blood loss was little (range, little to 417 mL). All patients were discharged from the hospital without any adverse postoperative consequences. CONCLUSIONS: BiClamp is an effective device for transecting liver parenchyma during pure laparoscopic partial hepatectomy, even in cirrhotic livers..