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Objective: Postoperative limb infection is associated with a poor prognosis and a low amputation-free survival rate after surgical revascularization in patients with critical limb-threatening ischemia. The Global Vascular Guidelines 2019 recommend antibiotic therapy for patients with deep space foot infection or wet gangrene; however, no study is cited as evidence for this recommendation. The present study was performed to offer new evidence supporting the use of perioperative therapeutic antibiotics in patients with critical limb-threatening ischemia (CLTI) undergoing surgical revascularization., Methods: This single-center retrospective study was performed in Kyushu University Hospital and involved patients with CLTI who underwent surgical revascularization from 2003 to 2021. Ampicillin/sulbactam and cefazolin were defined as preventive antibiotics, and other types were defined as therapeutic antibiotics. Postoperative limb-associated infection was defined as an increased foot infection (fI) score in the Wound, Ischemia, and foot Infection (WIfI) classification system after surgical revascularization. The association between perioperative antibiotic therapy and postoperative limb-associated infection was assessed., Results: Among 286 limbs of 263 patients with CLTI, 27 (9%) limbs developed postoperative limb-associated infection after surgical revascularization. The fI scores were significantly higher in the patients with than without postoperative limb-associated infection (1.0 ± 0.2 vs 0.4 ± 0.1, respectively; p = 0.0033), indicating that an fI score of ≥1 was a risk factor for postoperative limb-associated infection. Perioperative therapeutic antibiotics significantly reduced the incidence of postoperative limb-associated infection compared with preventive antibiotics (0.0% vs. 44.8%, respectively; p = 0.0028) in the patients with CLTI who had an fI score of ≥1 after bypass surgery, although perioperative therapeutic antibiotics were not effective for patients with an fI score of 0., Conclusion: Perioperative therapeutic antibiotics for patients with an fI score of ≥1 are beneficial for reducing the incidence of postoperative limb-associated infection after surgical revascularization., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study aimed to evaluate three survival prediction models: the JAPAN Critical Limb Ischaemia Database (JCLIMB), Surgical Reconstruction Versus Peripheral Intervention in Patients With Critical Limb Ischaemia (SPINACH), and Vascular Quality Initiative (VQI) calculators., Methods: Multicentre data of patients who underwent infrainguinal revascularisation for chronic limb threatening ischaemia between 2018 and 2021 were analysed retrospectively. The prediction models were validated using a calibration plot analysis with the intercept and slope. The discrimination was evaluated using area under the curve (AUC) analysis. The observed two year overall survival (OS) was evaluated by the Kaplan - Meier method. The two year OS predicted by each model at < 50%, 50 - 70%, and > 70% was defined as high, medium, and low risk, respectively., Results: A total of 491 patients who underwent infra-inguinal revascularisation were analysed. The rates of surgical revascularisation, endovascular therapy, and hybrid therapy were 26.5%, 70.1%, and 5.5%, respectively. The average age was 75.6 years, and the percentages of patients with diabetes mellitus and dialysis dependent end stage renal disease were 66.6% and 44.6%, respectively. The tissue loss rate was 85.7%. The intercept and slope were -0.13 and 1.18 for the JCLIMB, 0.11 and 0.82 for the SPINACH, and -0.15 and 1.10 for the VQI. The AUC for the two year OS of JCLIMB, SPINACH, and VQI were 0.758, 0.756, and 0.740, respectively. The observed two year OS rates of low, medium, and high risk using the JCLIMB calculator were 80.1%, 61.1%, and 28.5%, respectively (p < .001), using the SPINACH calculator were 81.0%, 57.0%, and 38.1%, respectively (p < .001), and using the VQI calculator were 77.8%, 45.8%, and 49.6%, respectively (p < .001)., Conclusion: The JCLIMB, SPINACH, and VQI survival calculation models were useful, although the OS predicted by the VQI model appeared to be lower than the observed OS., (Copyright © 2023 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Recent advancements in systemic therapy for hepatocellular carcinoma (HCC) necessitate the establishment of resectability criteria for advanced HCC., Methods: A questionnaire survey sought to clarify the perspectives of Japanese expert hepatobiliary surgeons regarding surgical indications for HCC. Thirty-one questions were used to determine when surgery is strongly recommended (resectable: R) or not recommended (unresectable: UR)., Results: A total of 351 responses were obtained. While 64.7% of the respondents considered solitary tumors as being R, irrespective of size, opinions diverged on the upper limit of the number of tumors/tumor size for R: (1) up to three nodules with no size limit (27.9%), (2) up to three nodules ≤5 cm in diameter each (21.4%) and (3) up to three nodules ≤3 cm in diameter each (19.4%). Vp1, Vp2, Vp3, and Vp4 were considered as being R by 90.9%, 70.7%, 39.0%, and 8.0% of respondents, respectively. Half of the respondents indicated they would consider resection even for cases with extrahepatic spread under limited conditions., Conclusions: The current views of Japanese expert surgeons on the resectability criteria for HCC were clarified for the first time. The findings could serve as a basis for preparing expert consensus statements on the resectability criteria for HCC., (© 2024 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Purpose: To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria., Methods: The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging., Results: Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging., Conclusion: Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Prof. Setsuro Fujii achieved significant results in the field of drug discovery research in Japan. He developed nine well-known drugs: FT, UFT, S-1 and FTD/TPI are anticancer drugs, while cetraxate hydrochloride, camostat mesilate, nafamostat mesilate, gabexate mesilate and pravastatin sodium are therapeutic drugs for various other diseases. He delivered hope to patients with various diseases across the world to improve their condition. Even now, drug discovery research based on Dr. Fujii's ideas is continuing., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

BACKGROUND Regular physical activity (PA) is important for maintaining mental and physical health after liver transplantation (LT); however, the fluctuations in routine PA during COVID-19 and its putative impacts are currently unknown. This study examined the changes in PA during the COVID-19 pandemic and explored its association with fear and depression during the pandemic. MATERIAL AND METHODS This longitudinal study included 83 LT patients whose PA was measured using the short form of the International Physical Activity Questionnaire before and during COVID-19. Fear of COVID-19 was estimated based on previous studies, and depression was assessed using the Patient Health Questionnaire-9. Participants were also asked about important sources of information on COVID-19. PA was classified as inactive or active depending on the changes in PA, and logistic regression analyses with PA as a dependent variable were conducted to explore the associations among PA, depression, and fear of COVID-19. RESULTS Moderate and high PA exhibited decreasing trends before and during the COVID-19 pandemic, especially in males. Fear of being infected with SARS-CoV-2, the virus that causes COVID-19, while shopping was significantly higher in females and was significantly independent of inactivity during the COVID-19 pandemic. Only 1 patient reported that their transplant center was their main source of information about COVID-19. Only 4.9% of the LT participants were depressed. CONCLUSIONS Our study results indicate the need to support the provision of accurate information about COVID-19 by health care professionals in transplant centers, especially for patients with low PA, to prevent PA decline in LT patients.

Aim: Recently, new diagnostic criteria for acute-on-chronic liver failure (ACLF) were established in Japan. However, there is little evidence regarding the feasibility of classifying patients undergoing living-donor liver transplantation (LDLT). The aim was to re-evaluate the impact of these new diagnostic criteria on ACLF and the severity classification of patients undergoing LDLT., Methods: We collected data of 82 recipients who underwent LDLT for liver failure between 1997 and 2020 and reviewed it retrospectively., Results: Of the 82 patients with liver failure, 31 (37.8%) were diagnosed with ACLF; Grade 0 (n = 6), Grade 1 (n = 7), Grade 2 (n = 9), and Grade 3 (n = 9). There was no substantial difference in overall survival (OS) and the occurrence of postoperative complications between liver failure patients with and without ACLF. The OS after LDLT was significantly different among the four groups of ACLF patients (P = .036). Interestingly, ACLF Grade 3 patients had substantially lower OS compared to other ACLF groups even after LDLT (P = .006; 5-year OS rates, 33.3% vs. 85.9%)., Conclusion: Proper use of the new diagnostic criteria for ACLF in Japan demonstrated that the presence and severity of ACLF, especially the presence of multiple organ failures, leads to morbidity and mortality even in an LDLT setting. Considering that the patients with ACLF Grade 3 do not have the favorable outcomes of LDLT, deceased-donor liver transplantation usage, or LDLT before reaching the severity of Grade 3 may be suitable for further research., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In light of the present evidence, machine perfusion is opening up new horizons in the field of liver transplantation. Although many advances have been made in liver transplantation, organ preservation methods have so far changed very little. Static cold storage is universally used for graft preservation in liver transplantation; however, there is a need for better preservation methods, such as ex vivo machine perfusion, to improve the outcomes by decreasing warm ischemic damage. Based on the findings of basic and clinical trials, hypothermic and normothermic machine perfusion techniques are now commercially available and include the OrganOx metra, Liver Assist, Cleveland NMP device, Organ Care System, and LifePort Liver. Recent clinical trials have provided further evidence for the potential role of normothermic machine perfusion to resuscitate and subsequently improve utilization of marginal or currently discarded livers. Further studies are required to explore the longer-term outcomes, late biliary complications, outcomes in specific high-risk groups, viability biomarkers, optimum and maximum perfusion duration, perfusate composition, and liver-directed therapeutic interventions during normothermic machine perfusion. The use of organs from marginal donors after brain death, such as fatty livers and the livers from elderly donors with multiple comorbidities, may be accepted for machine perfusion in Japan in the near future., (© 2021. Springer Nature Singapore Pte Ltd.)

We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996-2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60-69 years, 70-79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease., (© 2022. The Author(s).)

Background: Intrahepatic cholangiocarcinoma had been considered a contraindication for liver transplantation because of poorer outcomes. However, incidental intrahepatic cholangiocarcinoma in the explanted liver has been reported because of the difficulty of obtaining an accurate diagnosis in cirrhotic livers on preoperative imaging., Methods: We conducted a nationwide survey to analyze the incidence of incidental intrahepatic cholangiocarcinoma and outcomes after liver transplantation, in Japan., Results: Forty-five of 64 institutions (70%) responded to our initial investigation. Between January 2001 and December 2015, 6627 liver transplantations were performed in these 45 institutions, with 19 cases (0.3%) of incidental intrahepatic cholangiocarcinoma reported from 12 transplant centers. Six cases were diagnosed as hepatocellular carcinoma preoperatively. The 1-, 3-, and 5-year recurrence-free survival rates were 79%, 45%, and 45%, respectively. Tumor recurrence after liver transplantation was found in 10 patients (53%). The 1-, 3-, and 5-year overall survival rates were 79%, 63%, and 46%, respectively., Conclusions: Intrahepatic cholangiocarcinoma at liver transplantation is associated with a high risk of recurrence and poor prognosis, even these tumors are detected incidentally in the explanted liver., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background & Aims: Small-for-size graft (SFSG) syndrome is a major cause of graft loss after living donor liver transplantation (LDLT). Splenectomy (Spx) is an option to prevent this catastrophic complication, but its effect remains controversial. Herein, we aimed to elucidate the effect of simultaneous Spx on graft function and long-term outcomes after LDLT., Methods: Three hundred and twenty patients were divided into 2 groups: those undergoing (n = 258) and those not undergoing (n = 62) simultaneous Spx. To overcome selection bias, propensity score matching (PSM) was performed (n = 50 in each group)., Results: Before PSM, recipients undergoing simultaneous Spx showed better graft function on post-operative day (POD) 7 and 14, as well as lower sepsis frequency within 6 months after LDLT and better graft survival rates compared to those not undergoing Spx. After PSM, compared to patients not undergoing Spx, those undergoing Spx had a lower frequency of early graft dysfunction on POD 7 (p = 0.04); a lower frequency of SFSG syndrome (p = 0.01), lower serum total bilirubin levels (p = 0.001), and lower international normalized ratio (p = 0.004) on POD 14; lower sepsis frequency within 6 months after LDLT (p = 0.02), and better graft survival rates (p = 0.04). Univariate analysis revealed that not undergoing Spx (hazard ratio 3.06; 95% CI 1.07-11.0; p = 0.037) was the only risk factor for graft loss after LDLT., Conclusions: Simultaneous Spx may prevent SFSG syndrome and is a predictive factor for graft survival after LDLT. Simultaneous Spx is recommended when a small graft (≤35% of standard liver weight) is predicted preoperatively, or for patients with portal hypertension or high portal pressure (above 20 mmHg) after reperfusion in LDLT., Lay Summary: Living donor liver transplantation (LDLT) for patients with acute or chronic liver failure is an alternative to overcome the deceased donor shortage. The potential mismatch between graft and body size is a problem that needs to be solved for LDLT recipients. Herein, we evaluated the impact of simultaneous splenectomy and showed that it was associated with favorable outcomes in patients undergoing LDLT., Competing Interests: Conflicts of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Liver transplantation is the most suitable treatment option available for end-stage liver disease. However, some patients require retransplantation, despite medical advances that have led to improved survival. We aimed to compile a definitive, nationwide resource of liver retransplantation data in Japan, seeking to identify the predictors of patient survival posttransplantation., Methods: Questionnaires were sent to 32 institutions that had conducted 281 retransplantations before 2015., Results: Among the 265 patients included in this study (142 pediatric cases), the average age at primary transplantation was 23 years, and retransplantation was performed after an average of 1468 days. The main indication for retransplantation was graft rejection (95 patients). Living-donor liver transplantation accounted for 94.7% of primary transplantations and 73.2% of retransplantations. Patient survival at 1, 3, or 5 years did not differ by type of transplantation but was better for pediatric (70.8%, 68.3%, and 60.1%, respectively) than for adult (57.2%, 50.4%, and 45.2%, respectively) recipients (P = 0.0003). Small-for-size syndrome, retransplantation within 365 days, and inpatient status at retransplantation were significant predictors of poor survival in pediatric cases. Retransplantation within 365 days and conditions warranting retransplantation were significant predictors of poor survival in adult patients., Conclusions: In Japan, where >70% of retransplantations are performed using living donors, the indications and timing are different from those in previous reports from other countries, while maintaining comparable survival rates. Considering technical challenges, graft failure within 365 days should be thoroughly restricted to justify the use of living donor.

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.

Aims: This study examined the long-term quality of life (QOL) of living liver donors (LLDs) in Japan using both generic and LLD-specific instruments., Methods: The sample comprised 374 LLDs from five university hospitals in Japan who underwent surgery more than a year previously. QOL was evaluated using the Short Form-36 health survey (SF-36) and LLD-QOL scale., Results: SF-36 results indicated that the overall long-term QOL of LLDs was significantly better than the Japanese standard. When comparing by donor factors, LLDs whose recipients were children scored higher for "satisfaction" than those whose recipients were adults on the LLD-QOL scale. LLDs with complications had lower QOL for "scars" and "burden" on the LLD-QOL scale but no differences in SF-36 scores. LLDs with longer hospital stay had lower physical QOL on SF-36 and lower QOL for "scars" and "after-effects" on the LLD-QOL scale. LLDs whose recipients have died showed lower mental QOL on SF-36 and lower "satisfaction" and greater "lack of understanding of donor health" on the LLD-QOL scale., Conclusions: Our multicenter study clarified the long-term QOL of LLDs and suggested that donors' QOL was related to the donors' and recipients' ages, donor's complications and hospital stay length, and recipient's prognosis., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors have declared that no competing interests exist.

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.

Introduction and Aim: Occult hepatitis B virus (HBV) infection (OBI) represents a state without detectable hepatitis B surface antigen, but positive for HBV DNA. The correlation between OBI and hepatocellular carcinoma (HCC) carcinogenesis is controversial. We studied the frequency and characteristics of OBI among HCC patients and metastatic liver cancer patients., Material and Methods: DNA was obtained from tumor and non-tumor tissues from 75 HCC patients (15 chronic hepatitis B (CHB), 39 chronic hepatitis C (CHC), 21 cryptogenic) and 15 metastatic liver cancer patients who underwent liver resection. HBV DNA and covalentlyclosed circular (ccc) DNA were detected using real-time polymerase chain reaction (PCR), and four HBV DNA regions were detected by nested PCR. Clinicopathological factors were compared between patients with and without OBI., Results: HBV DNA was detected in 14 (93.3%) CHB, five (22.7%) cryptogenic and four (10.3%) CHC patients. cccDNA was detected in 12 (80.0%) CHB, three (14.3%) cryptogenic and two (5.1%) CHC patients. All CHB, eight (38.1%) cryptogenic and ten (25.6%) CHC patients tested positive with nested PCR. No metastatic liver cancer patients were positive for any HBV DNA regions. OBI patients had shorter prothrombin times (P = 0.0055), and lower inflammation activity score in non-tumor liver (P = 0.0274). There were no differences in anti-HBV antibodies., Conclusions: OBI was detected in 38% of cryptogenic and 25.6% of CHC patients. There was no correlation between OBI and anti-HBV antibodies, but fewer patients with OBI had high inflammatory activity, suggesting that factors other than inflammation may be involved in HCC carcinogenesis in patients with OBI.

Approximately 10-20% of patients with primary biliary cholangitis (PBC) progress to jaundice stage regardless of treatment with ursodeoxycholic acid and bezafibrate. In this study, we performed a GWAS and a replication study to identify genetic variants associated with jaundice-stage progression in PBC using a total of 1,375 patients (1,202 early-stage and 173 jaundice-stage) in a Japanese population. SNP rs13720, which is located in the 3'UTR of cathepsin Z (CTSZ), showed the strongest association (odds ratio [OR] = 2.15, P = 7.62 × 10 -7 ) with progression to jaundice stage in GWAS. High-density association mapping at the CTSZ and negative elongation factor complex member C/D (NELFCD) loci, which are located within a strong linkage disequilibrium (LD) block, revealed that an intronic SNP of CTSZ, rs163800, was significantly associated with jaundice-stage progression (OR = 2.16, P = 8.57 × 10 -8 ). In addition, eQTL analysis and in silico functional analysis indicated that genotypes of rs163800 or variants in strong LD with rs163800 influence expression levels of both NELFCD and CTSZ mRNA. The present novel findings will contribute to dissect the mechanism of PBC progression and also to facilitate the development of therapies for PBC patients who are resistant to current therapies.

The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n = 1) in the NS3, and at L31 (n = 4), Y93 (n = 4), and L31/Y93 (n = 1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n = 12). Univariate analysis showed that a history of SMV (P < .01) and the presence of mutations in NS5A (P = .02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The optimal therapy for recurrent hepatitis C virus (HCV) infection after liver transplantation has not yet been established. This study aimed to clarify the efficacy and safety of interferon-free therapy with sofosbuvir and ledipasvir without ribavirin for 12 weeks in Japanese patients with HCV genotype 1b infection after living donor liver transplantation., Methods: A cohort study of living donor liver transplant recipients with recurrent HCV genotype 1b infection treated with sofosbuvir (400 mg/day) and ledipasvir (90 mg/day) was performed at six liver transplant centers in Japan., Results: Fifty-four patients were treated with sofosbuvir and ledipasvir. Thirty-eight patients (70%) were treatment experienced, including 17 patients who had undergone prior direct-acting-antiviral-based triple therapy. Ten patients had resistance-associated substitutions at L31 or Y93 in the NS5A region of the HCV genome. Fifty-three patients completed the 12-week treatment protocol; treatment was discontinued in one patient who developed pneumonia at 4 weeks and died thereafter. All 53 patients who completed the treatment regimen achieved a sustained virological response 12 weeks after completion of treatment. Treatment was well tolerated in most patients, but seven patients developed serious adverse events, including hemorrhagic duodenal ulcers (n = 3), infection (n = 2), pleural effusion (n = 1), and alveolar hemorrhage (n = 1)., Conclusions: Sofosbuvir and ledipasvir treatment without ribavirin for 12 weeks was highly effective in achieving a sustained virological response in Japanese patients who developed recurrent HCV genotype 1b infection after living donor liver transplantation.

Background: A retrospective study was performed at some high-volume institutions to clarify the prognostic significance of postoperative complications in patients who had undergone hepatectomy for hepatocellular carcinoma (HCC). No published studies have investigated the relationship between postoperative complications of Clavien-Dindo grade III or more and prognosis in patients who have undergone hepatic resection., Methods: Patient data were retrospectively collected for 966 consecutive patients who had undergone hepatectomy for HCC with curative intent between January 2004 and December 2012. The patients were assigned to two groups according to the presence of postoperative complications. Clinicopathologic, surgical outcome, and long-term survival data were analyzed., Results: Hospital deaths occurred in nine patients (0.9%). Postoperative complications were identified in 165 patients (17.1%). Compared with patients without complications, patients with complications had significantly larger tumors, more advanced-stage tumors, more poorly differentiated tumors, more intrahepatic metastasis, longer operation time, greater blood loss, more blood transfusion, and more anatomic resection and combined resection. The overall 5-y survival rates were 48.6% in patients with postoperative complications and 73.2% in patients without them. The 5-y recurrence-free survival rates were 23.7% in patients with postoperative complications and 36.7% in patients without them. Multivariate analysis revealed that longer operation time and lower serum albumin level of albumin were independent predictive factors for occurrence of postoperative complications., Conclusions: In patients with HCC, posthepatectomy complications are predictive of a worse overall survival, even when adjustments have been made for other known predictors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: The feasibility of telaprevir-based triple therapy for recurrent hepatitis C after liver transplantation (LT) has not been evaluated in Asian patients., Methods: Eleven Japanese patients received reduced-dose telaprevir (1500 mg) and adjusted-dose cyclosporine after LT. Six patients were nonresponders and three were transient responders to dual therapy., Results: Rapid viral response, early viral response, end of treatment response, and sustained viral response were achieved in 27.3%, 90.9%, 90.9%, and 81.8% of patients, respectively. One patient had viral breakthrough at week 8 with a T54A mutation in NS3. Deep sequence analysis showed that the T54A mutation reverted to wild-type after stopping telaprevir administration. Seven patients developed severe anemia, and six received blood transfusions (4-20 U). Their hemoglobin and estimated glomerular filtration rate remained significantly lower than pretreatment values at 36 weeks after treatment. Four patients developed plasma cell hepatitis after completing telaprevir treatment, and it was treated by increasing the immunosuppressants. Although the cyclosporine level/dose ratio was 2.7 times higher at week 4 than before treatment, it was 0.7 times lower at week 36., Conclusions: Reduced-dosed telaprevir-based triple antiviral therapy achieved a high viral clearance rate in Japanese patients after LT. Major adverse events included severe anemia, renal dysfunction, and plasma cell hepatitis.

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.

Background: We sought to evaluate the surgical results of third or more repeat hepatectomy for recurrent hepatocellular carcinoma (HCC). The role of repeat hepatectomy for recurrent HCC, especially in cases with third or more repeat hepatectomy, is controversial., Methods: We performed A retrospective, cohort study to analyze the surgical results of repeat hepatectomy performed at a single medical center from 1989 to 2011. A total of 1,000 hepatectomies for HCC were divided into 3 groups: A first hepatectomy group (n = 791), second hepatectomy group (n = 163), and third or more hepatectomy group (n = 46). Operative results and patient prognoses were compared among the 3 groups., Results: There were no differences in early surgical results such as mortality and morbidity among the 3 groups. The 5-year survival rates after the first, second, and third or more hepatectomy were 67%, 60%, and 43%, respectively (P = .1913). There was a significant difference in disease-free survival among the 3 groups, and the 5-year disease-free survival rates after first, second, and third or more hepatectomy were 37%, 29%, and 18%, respectively (P = .0169)., Conclusion: Third or more repeat hepatectomy for recurrent HCC was performed safely and associated with relatively long-term survival. Third or more repeat hepatectomy for recurrent HCC seems justified, but high rate of HCC recurrence remains a problem., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Our current therapeutic criterion for acute cholecystitis is: Perform a subemergency laparoscopic cholecystectomy (LC) when a patient is judged to be able to tolerate general anesthesia. The aim of the current study was to verify whether this criterion is justified., Methods: The outcomes of 21 cases of LC for acute cholecystitis performed between April 2011 and September 2013 were retrospectively analyzed. Subemergency LC was performed according to the aforementioned criterion (Subemergency group; n = 16). Patient who was judged to be unable to tolerate general anesthesia underwent percutaneous transhepatic gallbladder drainage (PTGBD) first, then LC after the patients' condition became stable (PTGBD group; n = 5)., Results: There is no conversion to open surgery throughout the study period. The mean of the total hospital stays in the Subemergency group was significantly shorter than that in the PTGBD group (11.5 +/- 5.3 vs. 30.4 +/- 8.5 days). Although two patients in the Subemergency group, who had already needed oxygen administration preoperatively, suffered postoperative respiratory failure, they completely recovered. On the other hand, there is no postoperative complication in the PTGBD group., Discussion: Subemergency LC could be safely performed when surgeons as well as anesthesiologists judged a patient to be able to tolerate general anesthesia, which significantly shorten hospital stays compared to elective LC after PTGBD. However, elective LC after PTGBD is an absolutely safer therapeutic option in treating unstable patients.

Backgrounds: Pancreaticoduodenectomy (PD) is an aggressive surgery with considerable operative risks, but offers the only chance for cure in patients with periampullary tumors. A growing number of elderly patients are being offered PD because of the aging of populations in developed countries. We examined surgical outcomes of PD in patients aged 75 years and older (≥75 years)., Methods: A retrospective cohort study was performed in 65 consecutive patients who underwent PD for periampullary tumors at a single medical center during the 5 years from 2006 to 2010. We analyzed surgical outcomes such as mortality and morbidity after PD in patients aged ≥75 years (n = 21) compared to those in patients aged <75 years (n = 44)., Results: The positive rate of comorbidities such as hypertension was significantly higher in patients aged ≥75 years than in patients aged <75 years (76 vs. 48 %; p = 0.03). The incidence of wound infection was significantly higher in patients aged ≥75 years than in patients aged <75 years (19 vs. 0 %; p < 0.01). However, there was no significant difference in the mortality rate (0 vs. 2 %; p = 0.49) or the overall morbidity rate (33 vs. 32 %; p = 0.90). There was no significant difference in changes in body weight or serum albumin levels during the 3 months after PD between the two groups, but the recovery of serum prealbumin levels from 1 to 3 months after PD in patients aged ≥75 years was significantly delayed compared to that in patients aged <75 years (p = 0.04). There was no statistically significant difference in long-term survival between the two groups., Conclusions: Advanced age alone should not discourage surgeons from offering PD, although nutritional supports after PD for elderly patients aged ≥75 years are needed.

The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short-term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram-negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P = 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post-LDLT pneumonia was associated with the following post-LDLT events: the prolonged use of mechanical ventilation (≥3 days), a prolonged stay in the intensive care unit (≥7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed-onset pneumonia, which occurred at least 10 days after transplantation (n = 15), and it was significantly associated with graft dysfunction. A combination of broad-spectrum antibiotics and aminoglycosides provided cover for most gram-negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad-spectrum antibiotics. Delayed-onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Objectives: There are few reports on the efficacy of hepatectomy for hepatocellular carcinoma (HCC) in patients with renal dysfunction (RD). This study aimed to clarify the validity of hepatectomy for treating HCC in RD patients, and to compare postoperative courses in RD and non-RD patients., Methods: The clinical features of 722 HCC patients who underwent curative hepatectomy between 1986 and 2009 were retrospectively reviewed. Seventeen patients (2.4%) with preoperative serum creatinine levels of >2.0 mg/dl were defined as the RD group, and, of these, seven who did not receive preoperative haemodialysis were defined as borderline patients. Clinicopathological characteristics and postoperative outcomes were compared between the RD group (n= 17) and the non-RD group (n= 705). The postoperative courses of borderline patients were reviewed in detail., Results: Overall survival (P= 0.177) and disease-free survival (P= 0.942) after hepatectomy did not differ significantly between the groups. Incidences of massive ascites (35.3% vs. 14.3%; P= 0.034) and pleural effusion (52.9% vs. 17.6%; P= 0.001), defined as massive effusion (ME), were significantly higher in the RD group than in the non-RD group. Hypoalbuminaemia (≤2.8 g/dl; P= 0.031), heavy blood loss (≥1000 ml; P= 0.012) and intraoperative blood transfusion (P= 0.007) were risk factors for ME. Among the borderline patients, serum creatinine values were not increased immediately after surgery and four patients underwent haemodialysis., Conclusions: Preoperative hypoalbuminaemia, heavy blood loss and blood transfusion are independent risk factors for ME in RD patients. Preoperative improvement of anaemia and reduction of blood loss by meticulous surgical techniques may prevent ME in RD patients who require hepatectomy for HCC., (© 2012 International Hepato-Pancreato-Biliary Association.)

Objectives: The prognosis in patients with hepatocellular carcinoma (HCC) accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this study was to clarify the factors linked to survival of >5 years after hepatectomy in HCC patients with MPVTT., Methods: Twenty-nine HCC patients with MPVTT were divided into two groups comprising, respectively, patients who survived >5 years after hepatectomy (survivors, n= 5) and those who did not (non-survivors, n= 24). The two groups were compared., Results: Overall survival rates at 1, 3 and 5 years were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had recurrences of HCC in which the number of recurrent nodules was under four. Three (21.4%) of the 14 non-survivors who underwent curative resection experienced recurrences of HCC and all of them demonstrated fewer than four recurrent nodules (P= 0.0114). Local therapy, such as radiofrequency ablation and resection of recurrence, had more often been used in survivors than in non-survivors (P= 0.0364)., Conclusions: Although surgical outcomes in patients with HCC accompanied by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the number of recurrent nodules is less than four, local therapy should be selected with the aim of achieving 5-year survival., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background: The management of cardiovascular risk factors is important for prevention of atherosclerotic cardiovascular diseases (ACVD). Visceral fat accumulation plays an important role in the clustering of cardiovascular risk factors, leading to ACVD. The present study investigated the gender- and age-specific relationship between obesity-related cardiovascular risk factor accumulation and computed tomography (CT)-measured fat distribution in a large-scale Japanese general population., Methods and Results: Fat distribution was measured on CT scans in 12,443 subjects (males/females = 10,080/2,363), who underwent medical health check-up at 9 centers in Japan. The investigated obesity-related cardiovascular risk factors were hyperglycemia, dyslipidemia, and elevated blood pressure. Visceral fat area (VFA) for all males and old females showed almost symmetric distribution, while that of young females showed skewed distribution with a marked left shift. Only a small proportion of young females had large visceral fat and cardiovascular risk accumulation. The mean number of risk factors exceeded 1.0 at around 100 cm(2) for VFA in all groups, irrespective of gender, age (cut-off age 55), and BMI (cut-off BMI 25 kg/m(2))., Conclusions: In this large-scale Japan-wide general population study, an absolute VFA value of about 100 cm(2) equated with obesity-related cardiovascular risk factor accumulation, irrespective of gender, age, and BMI.

Aim: Visceral fat accumulation is associated with obesity-related cardiovascular risk factor accumulation and atherosclerosis. The present study investigated whether one-year reduction of the visceral fat area (VFA) correlates with a decrease in the number of such factors in Japanese with or without visceral fat accumulation., Methods: The study subjects comprised 5,347 Japanese, who underwent health check-ups in 2007 and 2008, including measurements of VFA and subcutaneous fat area (SFA) by computed tomography at 9 centers in Japan. Subjects with one or more such factor(s) were categorized into tertiles based on the one-year change in VFA. We investigated the multivariate age, sex, and one-year change in SFA-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for reductions in the number of risk factors in each of the three categories based on the one-year change in VFA, in subjects with one or more such factors (n= 3,648)., Results: In the entire group (n=3,648), the OR and 95%CI for reductions in the number of risk factors in the first tertile were 0.804 (0.673-0.962, p=0.0172), compared with the second tertile set at 1.0. Subjects with VFA <100cm(2) showed no reduction in the number of risk factors. In subjects with VFA≥100 cm(2), OR in the first tertile was 0.788 (0.639-0.972, p=0.0257) relative to the second tertile set at 1.0., Conclusions: In subjects with multiple cardiovascular risk factors, visceral fat reduction correlated with a decrease in the number of such factors in subjects with VFA≥100cm(2), but not in those with VFA<100cm(2).

Background & Aims: Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC., Methods: Hepatocyte AFB1-DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non-B non-C hepatocellular carcinoma (NBNC HCC)., Results: AFB1-DNA adducts were detected in hepatocyte nuclei in 18/279 patients (6%), including 13/83 patients (16%) with NBNC HCC and 5/51 patients (10%) expressing hepatitis B surface antigen. None of the patients with HCV Ab (n=136) were positive for AFB1-DNA. The incidence of the G-T transversion and mutations in exon 7 of TP53 in patients with AFB1-DNA adducts were significantly higher in patients with than in patients without AFB1-DNA adducts. All three patients with the codon 249 AGG-AGT mutation had AFB1-DNA adducts., Conclusion: Although exposure to AFB1 is thought to be low in Japan, it is still associated with hepatocarcinogenesis, particularly in NBNC HCC and hepatitis B individuals., (© 2011 John Wiley & Sons A/S.)

Introduction: The optimal surgical technique has not been elucidated that reduces the occurrence of biliary strictures after living donor liver transplantation (LDLT)., Method: We performed retrospective analysis of 193 consecutive LDLTs, including 78 right and 115 left lobe grafts. An external biliary stent was used for all of the cases., Results: The overall 1-, 3-, and 5-year biliary stricture-free survival rates were 87.5%, 85.3%, and 85.3%, respectively. The 1- and 3-year biliary stricture-free survival rates for duct-to-duct reconstruction were 86.9% and 84.9%, and those for hepaticojejunostomy were 90.1% and 80.8%, respectively. A multivariate analysis revealed that the original number of graft bile ducts greater than the number of external stents, right lobe grafts, bile leaks, and recipient age older than 60 years represented the significant risk factors (P < .05) to develop a biliary stricture after LDLT. All cases with biliary strictures (n = 61) were initially managed nonsurgically, but 4 patients ultimately required interventions., Conclusions: Biliary reconstruction in LDLT using an appropriate number of external stents resulted in fairly acceptable outcomes. However, not only the proper use of stents or graft selection, but also nonsurgical factors, are important factors that determine the incidence of biliary strictures after LDLT., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background and Aims: The importance of hyponatremia in deceased donor liver transplantation (DDLT) has been recently discussed frequently. However, its impact on the outcomes in living donor liver transplantation (LDLT) has not yet been elucidated. The current study was designed to demonstrate the impact of pre-transplant sodium concentration on postoperative clinical outcomes., Methods: One hundred and thirty-four patients who underwent LDLT for end-stage liver diseases were examined to evaluate the significance of pre-transplant hyponatremia (Na < or = 130 mEq/L) on the short-term clinical outcomes and the efficacy of the Model for End-Stage Liver Disease and serum sodium (MELD-Na) score using the sodium concentration and original MELD score., Results: The preoperative sodium and MELD score for all patients were 133.9 mEq/L (range: 109-142) and 16.2 (range: 6-38), respectively. According to a multivariate analysis, not only the MELD score (P = 0.030) but also the sodium concentration (P = 0.005) were found to be significant predictive factors for short-term graft survival. Preoperative hyponatremia was a significant risk factor for the occurrence of sepsis (P < 0.001), renal dysfunction (P < 0.001) and encephalopathy (P = 0.026). The MELD-Na score was 19.6 (range: 6-51) and the area under the receiver-operator curve of that (c-statistics: 0.867) was higher than MELD score and sodium concentration (c-statistics: 0.820 and 0.842, respectively)., Conclusion: Preoperative hyponatremia was a significant risk for postoperative complications and short-term graft loss. The addition of sodium concentration to MELD score might therefore be an effective predictor for post-transplant short-term mortality in LDLT.

The purpose of this study was to examine the psychometric properties of the Adolescent Dissociative Experiences Scale (A-DES) applied to Japanese adolescents in school. A large sample of normal adolescents (N = 2,272) aged 11 to 18 years completed the A-DES, and the factor structure, frequency, and differences by gender and age were examined. The scores of Japanese adolescents were comparable to the results of similarly aged adolescents in the United States, England, and Turkey but much higher than those recorded in The Netherlands, Finland, and Sweden. In particular, adolescents aged 11 to 12 seemed to have more dissociative experiences than older adolescents. Out of 1-, 2-, 3-, and 4-factor structures that exploratory factor analyses regarded as competing models, confirmatory factor analyses seemed to support a 3-factor structure: depersonalization, disintegration of conscious control, and amnesia. The future implications of these results for clinicians and professionals who assess dissociative tendency in adolescents are described.

Background: To ensure donor safety in adult-to-adult living donor liver transplantation, we established a selection criterion for donors in which left lobe (LL) was the first choice of graft., Methods: Two hundred six consecutive donors were retrospectively studied. Donors were divided into two groups according to graft type: LL graft (n=137) and right lobe (RL) graft (n=69)., Results: Although mean intraoperative blood loss of LL was significantly increased compared with RL, mean peak postoperative total bilirubin levels and duration of hospital stay after surgery were significantly less for LL than RL (P<0.05). No donor died or suffered a life-threatening complication during the study period. The overall complication rate was 34.0%, including biliary complications in 5.3%. The number of biliary complications was four (2.9%) in LL and seven (10.1%) in RL (P<0.05). Logistic regression analysis revealed that only graft type (LL vs. RL) is significantly related to the occurrence of biliary complications (odds ratio 0.11; P=0.0012). The cumulative overall graft survival rates in the recipients with LL were not significantly different from that in the recipients with RL., Conclusions: LL grafting should be considered favorably when selecting donors for adult-to-adult living donor liver transplantation.

Background: Living donor liver transplantation has become an accepted treatment for various terminal liver diseases., Study Design: Forty-two living donor liver transplantations performed for acute liver failure during a 10-year period at Kyushu University Hospital were reviewed., Results: Causes of liver failure included hepatitis B (n=12), hepatitis C (n=1), autoimmune hepatitis (n=2), Wilson's disease (n=3), and unknown causes (n=24). The graft types were: left lobe (n=33), right lobe (n=8), and lateral segment (n=1). The mean graft volume to standard liver volume ratios were 42.2+/-9.2% in left lobe grafts and 50.5+/-3.9% in right lobe grafts (p < 0.05). Extubation was significantly delayed in grade IV encephalopathy patients (73.7 +/-18.2 hours) compared with patients with other grades (p < 0.01 to grades I and II, p < 0.05 to grade III). All other patients, except one with a subarachnoid hemorrhage, had complete neurologic recovery after transplantation. The 1- and 10-year survival rates were 77.6% and 65.5%, respectively, for grafts, and 80.0% and 68.2%, respectively, for patients., Conclusions: Outcomes of living donor liver transplantation for acute liver failure are fairly acceptable despite severe general conditions and emergent transplant settings. Living donor liver transplantation is now among the currently accepted life-saving treatments of choice for acute liver failure, although innovative medical treatments for this disease entity are still anticipated.

Donor safety is the priority when performing a living donor adult liver transplantation (LDALT). We herein present our findings using left-lobe graft in LDALT. Data on 119 recipients who underwent the LDALT, and on 119 donors who underwent extended left lobectomy were reviewed. The recipients were divided into groups above (n = 19) and below (n = 100) 50 years of donor age, into groups above (n = 63) and below (n = 56) 40% of graft size (graft volume/standard liver volume, GV/SLV), and above (n = 25) and below (n = 94) 20 of pre-operative model for end-stage liver disease (MELD). Total bilirubin (TB), volume of ascites, prothrombin time international normalized ratio on postoperative day 14 or survival rates were compared. TB (mg/dl) or volume of ascites (ml) of the group in donor age < 50 years was better than that of the group in donor age > or = 50 years (7.4 vs. 14.7 or 788 vs. 1379, P < 0.001 or P < 0.005, respectively). The graft and patient survival rates of the lower MELD group tended to be better than that of the higher MELD group. LDALT can be safely performed using a left-lobe graft. However, when using the graft from the donor > or = 50 years, especially for the recipients with the MELD > or = 20, the indications should be carefully discussed.

Background: Thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD) are important enzymes related to the metabolism of 5-fluorouracil and its derivatives. In this study, we analyzed the expression of these enzymes and evaluated the association between the expression of these enzymes and clinicopathological features and prognosis in patients with pancreatic cancer., Methods: TP, OPRT, and DPD mRNA expressions were detected using a real-time reverse transcriptional-polymerase chain reaction method or by immunohistochemistry, using surgical specimens obtained from 25 patients with pancreatic cancer., Results: TP mRNA expression was lower in cases with an alpha infiltration growth pattern than in cases with other infiltration growth patterns (P < 0.05). OPRT mRNA expression was higher in poorly differentiated-type cases than in differentiated type cases (P < 0.05). TP-, OPRT-, and DPD-positive stainings were found in 15 of 24 cases (63%), 10 of 19 cases (53%), and 14 of 21 cases (67%), respectively. There were significant correlations or trends between the mRNA and protein expressions of TP, OPRT, and DPD. Patients with a low TP/DPD ratio survived significantly longer than those with a high ratio (P < 0.05). Multivariate analysis demonstrated a significantly poorer outcome in patients with a high TP/DPD ratio compared with in patients with a low ratio (P < 0.05)., Conclusion: The TP/DPD ratio might be useful as a prognostic factor in patients with pancreatic cancer.

There is a growing consensus in terms of the need for effective use of magnetic resonance imaging (MRI) diagnostic devices in emergency medical care. However, a thorough assessment of risk management in emergency medical care is required because of the high magnetic field in the MRI room. To understand the conditions required for the execution of emergency MRI examinations in individual medical facilities, and to prepare guidelines for emergency MRI examinations, we carried out a questionnaire survey concerning emergency MRI examinations. We obtained responses from 71% of 230 medical facilities and used this information in considering a system of emergency MRI examinations. Moreover, some difficulties were experienced in half of the facilities where emergency MRI examinations had been enacted, the main cause of which was the medics. Based on the results of the questionnaire, guidelines are necessary to maintain an urgent system for MRI examinations. Moreover, we were able to comprehend the current state of emergency MRI examinations in other medical facilities through this investigation, and we are preparing a system for the implementation of emergency MRI examinations.

Objective: Hallucinatory experiences in children are often thought to indicate serious psychopathology. However, they have also been reported in normally developing children and in association with temporary psychological reactions to acute stress. The aim of this study was to investigate the prevalence of hallucinatory experiences in a nonclinical population of children and to examine the relationship between the modality and content of hallucinations and psychopathology., Method: Seven hundred sixty-one Japanese children, 11 to 12 years old, completed a battery of four measures: (1) a questionnaire about the type of hallucinatory experience, (2) the Children's Depression Inventory, (3) the State-Trait Anxiety Inventory for Children, and (4) the Adolescent Dissociative Experiences Scale., Results: Approximately 21% of the subjects had experienced hallucinations. Subjects who had experienced hallucinations, in particular, hallucinations characterized by combined modalities, closely self-related auditory content, or concrete visual content, had more significant psychopathology than did those who had never experienced hallucinations., Conclusions: Therapeutic intervention should be considered for children who experience hallucinations in association with depression, anxiety, or dissociation.

Liver transplantation has been recognized as an effective therapeutic method for end-stage liver disease in Japan. Fulminant hepatic failure is also an indication for liver transplantation, and the number of patients undergoing liver transplantation has been increasing. Reversibility and urgency are characteristics of fulminant hepatitis. If given appropriate critical support, many patients recover spontaneously. However, many patients develop cerebral edema or multiorgan failure before the liver can regenerate. From October 1996 to July 2002, living donor liver transplantation (LDLT) was performed to 84 end stage liver disease patients in Kyushu University. Twenty-four (28.6%) of 84 LDLTs were for fulminant hepatic failure. In Kyushu University, LDLT candidates including urgent cases were discussed with indication in the liver transplantation committee (the medical professions division and an outside-the-university committee are included) and then the coordinator committee performs informed consent. LDLT can be performed only by cooperation of each section concerned such as Transfusion part, Medicine part, Radiation part, Operation part, Intensive Care Unit and so on. In this paper, we outline about fulminant hepatic failure and living donor liver transplantation, and describe the fulminant hepatitis medical treatment organization in Kyushu University.

Background: The significance of the small distal tubular adenoma detected by sigmoidoscopy as a predictor of proximal neoplasm remains controversial. The aim of this study was to examine the prevalence of proximal neoplasms in patients with and without distal neoplasms., Methods: This is a retrospective study of 3131 asymptomatic middle-aged men who underwent total colonoscopy. For 812 men with colorectal neoplasms characteristics of the identified neoplasms were determined., Results: The prevalence of proximal neoplasms in patients with small distal tubular adenoma was 20% (92 of 461), whereas the prevalence of proximal neoplasms in patients without distal neoplasms was 11.5% (301 of 2620). The prevalence of advanced proximal neoplasms in patients with small distal tubular adenoma and without distal neoplasm was 1.3% and 0.8%, respectively. In the 29 patients with advanced proximal neoplasms, only 6 (21%) had a small distal tubular adenoma., Conclusions: The presence of small distal tubular adenomas may provide a clue to the presence of small proximal tubular adenomas. However, the majority of advanced proximal neoplasms (79%) do not have a synchronous small distal tubular adenoma. (Gastrointest Endosc 2000;52:358-61).

The incidence of hepatitis C virus (HCV) antibody positivity is unknown. The purpose of this study was to clarify the prevalence of HCV infection among surgical patients and to identify high risk surgical patients. HCV antibody tests were performed in 789 surgical patients between April 1991 and March 1992. Of these patients, 129 (16.3%) tested positive, which was much higher than the positivity of the ordinary Japanese. Hepatobiliary diseases and portal hypertension were associated with a higher positivity than other disease categories (94 of 206, 45.6% versus 35 of 583, 6%; p < 0.0001). Patients above 50 years of age had a higher positivity than their younger counterparts (118 of 578, 20.4% versus 11 of 211, 5.3%; p < 0.0001). The HCV positivity was as high as 54.1% (119 of 220) among surgical patients with known risk factors for hepatitis, in contrast to only 1.9% (10 of 569) among those without such risk factors. We conclude that surgical patients have a high incidence of HCV infection, for whom medical professionals should pay special attention to avoid disease transmission.

We treated 154 patients with T1 glottic carcinoma with 6 MeV X rays through 16 cm2 parallel-opposing open fields on a free set-up delivering a median dose of 67 Gy in 6 2/3 weeks. Observed and relative 5-year survival rates for all patients were 87% and 100%, respectively. The local control rate at 5 years was 89%. Of 18 patients who clinically had local recurrence, 17 were salvaged by a secondary treatment. There were no complications requiring medical or surgical attention. A tendency toward increasing local control rates with increasing total doses was observed in the range between 57.5 Gy and 72.5. No significant correlation was found between local control rates and field size, daily dose, or the technique used. A tendency toward a lower local control rate was noted for patients whose anterior commissures were grossly involved; however, it is not known if this could be attributed to the use of 6 MeV X rays. The results are comparable to those obtained with 60Co as reported in the literature. It is concluded that 6 MeV X rays on a free set-up delivering 65-70 Gy in 6 1/2-7 weeks can be used satisfactorily for the treatment of early glottic carcinoma.

Treatment results of 244 patients with stage I-II cancer of the mobile tongue were analyzed according to the modalities employed (implantation, surgery, cryosurgery and intraoral irradiation). Overall local control rates at three years were 90 +/- 3% for implant, 89 +/- 7% for cryosurgery, and 84 +/- 9% for surgery. Local control rates in stage II patients treated with intraoral electron irradiation, however, were only 50 +/- 13%. Five-year survival rates were 72 +/- 3% with no significant differences observed in patients with either stage I or stage II regardless of treatment modality. Sixty percent (29/48) of the patients with local recurrences were salvaged by the second treatment. Since the local control and survival achieved by these modalities were similar, with the exception of patients with stage II treated by intraoral electron irradiation, we recommend interstitial implantation with iridium, intraoral electron irradiation or surgery for patients with T1 tumors, and iridium implantation or surgery for patients with T2 tumors. For those with superficial lesions measuring 5 mm or less in thickness, cryosurgery is being offered as an alternative. The patient can choose the treatment modality taking into account his/her age, sex and profession.