Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(株)アークメディア  

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：(一社)日本腹部救急医学会  

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Language：Japanese   Publisher：(一社)日本腹部救急医学会  

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The University of Wisconsin (UW) solution is the most effective preservation solution currently used; however, to safely use expanded-criteria donor grafts, a new cold storage solution that alleviates graft injury more effectively is required. We prepared a heavy water (D2O)-containing buffer, Dsol, and observed strong protective effects during extended cold storage of rat hearts and livers. In the current study, we modified Dsol (mDsol) and tested its efficacy. The aim of the present study was to determine whether mDsol could protect the rat liver more effectively than the UW solution and to clarify the roles of D2O and deferoxamine (DFX). Rat livers were subjected to cold storage for 48 hours in test solutions: UW, mDsol, mDsol without D2O or DFX (mDsol-D2O[-], mDsol-DFX[-]), and subsequently reperfused on an isolated perfused rat liver for 90 minutes at 37°C. In the UW group, the liver was dehydrated during cold storage and rapidly expanded during reperfusion. Accordingly, the cumulative weight change was the highest in the UW group, together with augmented portal veinous resistance and ALT leakage and decreased oxygen consumption rate and bile production. These changes were significantly suppressed in the mDsol-treated group. In the mDsol-D2O(-) and mDsol-DFX(-) groups offered partial protection. In conclusion, mDsol appeared to be superior to the UW solution for simple cold storage of the rat liver, presumably due to improved microcirculation in the early phase of reperfusion. Both heavy water and deferoxamine are essential for alleviating seamless organ swelling that occurs during cold storage and subsequent reperfusion.

DOI： 10.1016/j.transproceed.2023.10.005

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BACKGROUND: After implementation of the Acuity Circles (AC) allocation policy, use of DCD liver grafts has increased in the United States. METHODS: We evaluated the impact of AC on rates of DCD-liver transplants (LT), their outcomes, and medical costs in a single practice. Adult LT patients were classified into three eras: Era 1 (pre-AC, 1/01/2015-12/31/2017); Era 2 (late pre-AC era, 1/01/2018-02/03/2020); and Era 3 (AC era, 05/10/2020-09/30/2021). RESULTS: A total of 520 eligible LTs were performed; 87 were DCD, and 433 were DBD. With each successive era, the proportion of DCD increased (Era 1: 11%; Era 2: 20%; Era 3: 24%; p < .001). DCD recipients had longer ICU stays, higher re-admission/re-operation rates, and higher incidence of ischemic cholangiopathy compared to those with DBD. Direct, surgical, and ICU costs during first admission were higher with DCD than DBD (+8.0%, p < .001; +4.2%, p < .001; and +33.3%, p = .001). DCD-related costs increased after Era 1 (Direct: +4.9% [Era 2 vs. 1] and +12.4% [Era 3 vs. 1], p = .04; Surgical: +17.7% and +21.7%, p < .001). In the AC era, there was a significantly higher proportion of donors ≥50 years, and more national organ sharing. Compared to DCD from donors <50 years, DCD from donors ≥50 years was associated with significantly higher total direct, surgical, and ICU costs (+12.6%, p = .01; +9.5%, p = .01; +84.6%, p = .03). CONCLUSIONS: The proportion of DCD-LT, especially from older donors, has increased after the implementation of AC policies. These changes are likely to be associated with higher costs in the AC era.

DOI： 10.1111/ctr.15190

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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We previously reported the efficacy of cold storage (CS) using a heavy water-containing solution (Dsol) and post-reperfusion hydrogen gas treatment separately. This study aimed to clarify the combined effects of these treatments. Rat livers were subjected to 48-hour CS and a subsequent 90-minute reperfusion in an isolated perfused rat liver system. The experimental groups were the immediately reperfused control group (CT), the CS with University of Wisconsin solution (UW) group, the CS with Dsol group, the CS with UW and post-reperfusion H2 treatment group (UW-H2), and the CS with Dsol and post-reperfusion H2 group (Dsol-H2). We first compared the Dsol-H2, UW, and CT groups to evaluate this alternative method to conventional CS. The protective potential of the Dsol-H2 group was superior to that of the UW group, as evidenced by lower portal venous resistance and lactate dehydrogenase leakage, a higher oxygen consumption rate, and increased bile production. Multiple comparison tests among the UW, Dsol, UW-H2, and Dsol-H2 groups revealed that both treatments, during CS and after reperfusion, conferred a similar extent of protection and showed additive effects in combination therapy. Furthermore, the variance in all treatment groups appeared smaller than that in the no-treatment or no-stress groups, with excellent reproducibility. In conclusion, combination therapy with Dsol during CS and hydrogen gas after reperfusion additively protects against graft injury.

DOI： 10.1016/j.transproceed.2023.03.061

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UNLABELLED: It has been reported that patients hospitalized outside regular working hours have worse outcomes. This study aims to compare outcomes following liver transplantation (LT) performed during public holidays and nonholidays. METHODS: We analyzed the United Network for Organ Sharing registry data for 55 200 adult patients who underwent an LT between 2010 and 2019. Patients were grouped according to LT receipt during public holidays ±3 d (n = 7350) and nonholiday periods (n = 47 850). The overall post-LT mortality hazard was analyzed using multivariable Cox regression models. RESULTS: LT recipient characteristics were similar between public holidays and nonholidays. Compared with nonholidays, deceased donors during public holidays had a lower donor risk index (median [interquartile range]: holidays 1.52 [1.29-1.83] versus nonholidays 1.54 [1.31-1.85]; P = 0.001) and shorter cold ischemia time (median [interquartile range]: holidays 5.82 h [4.52-7.22] versus nonholidays 5.91 h [4.62-7.38]; P < 0.001). Propensity score matching 4-to-1 was done to adjust for donor and recipient confounders (n = 33 505); LT receipt during public holidays (n = 6701) was associated with a lower risk of overall mortality (hazard ratio 0.94 [95% confidence interval, 0.86-0.99]; P = 0.046). The number of livers that were not recovered for transplant was higher during public holidays compared with nonholidays (15.4% versus 14.5%, respectively; P = 0.03). CONCLUSIONS: Although LT performed during public holidays was associated with improved overall patient survival, liver discard rates were higher during public holidays compared with nonholidays.

DOI： 10.1097/TXD.0000000000001463

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BACKGROUND: Acuity circle (AC) policy implementation improved the waitlist outcomes for certain liver transplant (LT)-candidates. The impact of the policy implementation for liver retransplant (reLT) candidates is unknown. METHODS: Using Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from January, 2018 to September, 2021, we investigated the effect of the AC policy on waitlist and post-LT outcomes among patients who had previously received a LT. Patients were categorized by relisting date: Pre-AC (Era 1: January 1, 2018-February 3, 2020; n = 750); and Post-AC (Era 2: February 4, 2020-June 30, 2021; n = 556). Patient and donor characteristics, as well as on-waitlist and post-reLT outcomes were compared across eras. RESULTS: In Era 2, the probability of transplant within 90 days overall and among patients relisted > 14 days from initial transplant (late relisting) were significantly higher compared to Era 1 (subdistribution hazard ratio [sHR] 1.40, 95% CI 1.18-1.64, p < .001; sHR 1.52, 95% CI 1.23-1.88, p = .001, respectively). However, there was no difference by era among patients relisted ≤14 days from initial transplant (early relisting; sHR 1.21, 95% CI .93-1.57, p = .15). Likewise, among early relisting patients, risks for 180-day graft loss and mortality were significantly higher in Era 2 versus Era 1 (adjusted hazard ratio [aHR] 5.77, 95% CI 1.71-19.51, p = .004; and aHR 8.22, 95% CI 1.85-36.59, p = .005, respectively); for late relisting patients, risks for these outcomes were similar across eras. CONCLUSION: Our results show that the implementation of AC policy has improved transplant rates and reduced waiting time for reLT candidates listed > 14 days from initial transplant. However, the impact upon early relisting patients may be mixed.

DOI： 10.1111/ctr.14977

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BACKGROUND: We have previously reported the efficacy of post-reperfusion H2 gas treatment in cold storage (CS) and subsequent reperfusion of the rat liver. The present study aimed to evaluate the effect of H2 gas treatment during hypothermic machine perfusion (HMP) in rat livers retrieved from donation after circulatory death (DCD) and elucidate the mechanism of action of H2 gas. METHODS: Liver grafts were procured from rats after 30 min of cardiopulmonary arrest. The graft was subjected to HMP for 3 hours at 7°C using Belzer MPS with or without dissolved H2 gas. The graft was reperfused using an isolated perfused rat liver apparatus at 37°C for 90 minutes. Perfusion kinetics, liver damage, function, apoptosis, and ultrastructure were evaluated. RESULTS: Portal venous resistance, bile production, and oxygen consumption rates were identical in the CS, MP, and MP-H2 groups. Liver enzyme leakage was suppressed by MP (vs control), whereas H2 treatment did not show a combination effect. Histopathology revealed poorly stained areas with a structural deformity just below the liver surface in the CS and MP groups, whereas these findings disappeared in the MP-H2 group. The apoptotic index in the CS and MP groups was high but decreased in the MP-H2 group. Mitochondrial cristae were damaged in the CS group but preserved in the MP and MP-H2 groups. CONCLUSIONS: In conclusion, HMP and H2 gas treatment are partly effective in DCD rat livers but insufficient. Hypothermic machine perfusion can improve focal microcirculation and preserve mitochondrial ultrastructure.

DOI： 10.1016/j.transproceed.2023.02.036

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BACKGROUND: Liver transplant (LT) candidates with hepatocellular carcinoma (HCC) often receive cancer treatment before transplant. We investigated the impact of pre-transplant treatment for HCC on the risk of posttransplant recurrence. METHODS: Adult HCC patients with LT at our institution between 2013 and 2020 were included. The impact of pre-LT cancer treatments on the cumulative recurrence was evaluated, using the Gray and Fine-Gray methods adjusted for confounding factors. Outcomes were considered in two ways: 1) by pathologically complete response (pCR) status within patients received pre-LT treatment; and 2) within patients without pCR, grouped by pre-LT treatment as A) none; B) one treatment; C) multiple treatments. RESULTS: The sample included 179 patients, of whom 151 (84%) received pretreatment and 42 (28% of treated) demonstrated pCR. Overall, 22 (12%) patients experienced recurrence. The 5-year cumulative post-LT recurrence rate was significantly lower in patients with pCR than those without pCR (4.8% vs. 19.2%, P = 0.03). In bivariable analyses, pCR significantly decreased risk of recurrence. Among the 137 patients without pCR (viable HCC in the explant), 28 (20%) had no pretreatment (A), 70 (52%) had one treatment (B), and 39 (20%) had multiple treatments (C). Patients in Group C had higher 5-year recurrence rates than those in A or B (39.6% vs. 8.2%, 6.5%, P = 0.004 and P < 0.001, respectively). In bivariable analyses, multiple treatments was significantly associated with recurrence. CONCLUSIONS: pCR is a favorable prognostic factor after LT. When pCR was not achieved by pre-LT treatment, the number of treatments might be associated with post-LT oncological prognosis.

DOI： 10.1245/s10434-022-12789-2

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DOI： 10.1245/s10434-022-12964-5

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DOI： 10.1245/s10434-022-12913-2

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OBJECTIVE: To clarify the short- and long-term postoperative outcomes and surgical indications for patients accompanied by hepatocellular carcinoma (HCC) with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA). SUMMARY BACKGROUND DATA: These patients are known to have an extremely poor prognosis; however, the postoperative outcomes have not been fully verified because of the rarity of this disease. METHODS: We contacted 211 specialized centers in Japan and collected data on liver resection for HCC with TT in the IVC or RA from centers with experience performing surgery for such patients. The patient characteristics, operative procedures, and surgical outcomes were then analyzed. RESULTS: A total of 119 patients from 23 institutions were enrolled; 49 patients had TT in the IVC below the diaphragm (type I), 42 had TT in the IVC above the diaphragm (type II), and 28 had TT entering the RA (type III). The severity and frequency of postoperative complications did not differ among the three groups. There was one surgery-related death in the type III group. The median survival times were 2.47 years in the type I group, 1.77 years in the type II group, and 1.02 years in the type III group. A multivariate analysis identified an indocyanine green retention rate at 15 min >15% and ≥3 tumors as prognostic factors affecting survival, while the use of cardiopulmonary bypass and ≥3 tumors were risk factors for recurrence. CONCLUSION: As the postoperative prognosis of patients with type I or type II disease and of patients with no risk factors is relatively good, surgery should be considered for these patient populations.

DOI： 10.1097/SLA.0000000000005789

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UNLABELLED: Liver allocation in the United States was updated on February 4, 2020, by introducing the acuity circle (AC)-based model. This study evaluated the early effects of the AC-based allocation on waitlist outcomes. METHODS: Adult liver transplant (LT) candidates listed between January 1, 2019, and September 30, 2021, were assessed. Two periods were defined according to listing date (pre- and post-AC), and 90-d waitlist outcomes were compared. Median transplant Model for End-stage Liver Disease (MELD) score of each transplant center was calculated, with centers categorized as low- (<25 percentile), mid- (25-75 percentile), and high-MELD (>75 percentile) centers. RESULTS: A total of 12 421 and 17 078 LT candidates in the pre- and post-AC eras were identified. Overall, the post-AC era was associated with higher cause-specific 90-d hazards of transplant (csHR, 1.32; 95% confidence interval [CI], 1.27-1.38; P < 0.001) and waitlist mortality (cause-specific hazard ratio [csHR], 1.20; 95% CI, 1.09-1.32; P < 0.001). The latter effect was primarily driven by high-MELD centers. Low-MELD centers had a higher proportion of donations after circulatory death (DCDs) used. Compared with low-MELD centers, mid-MELD and high-MELD centers had significantly lower cause-specific hazards of DCD-LT in both eras (mid-MELD: csHR, 0.47; 95% CI, 0.38-0.59 in pre-AC and csHR, 0.56; 95% CI, 0.46-0.67 in post-AC and high-MELD: csHR, 0.11; 95% CI, 0.07-0.17 in pre-AC and csHR, 0.14; 95% CI, 0.10-0.20 in post-AC; all P < 0.001). Using a structural Bayesian time-series model, the AC policy was associated with an increase in the actual monthly DCD-LTs in low-, mid-, and high-MELD centers (actual/predicted: low-MELD: 19/16; mid-MELD: 21/14; high-MELD: 4/3), whereas the increase in monthly donation after brain death-LTs were only present in mid- and high-MELD centers. CONCLUSIONS: Although AC-based allocation may improve waitlist outcomes, regional variation exists in the drivers of such outcomes between centers.

DOI： 10.1097/TXD.0000000000001356

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BACKGROUND: Cold climate is known to affect the frequency and attributable mortality of various illnesses. This study aims to evaluate the effect of climate among regions on liver transplant (LT) outcomes. METHODS: We analyzed data from the United Network for Organ Sharing registry for 98,517 adult patients (aged ≥ 18 years) who were listed for LT between 2010 and 2019. During this period, 51,571 patients underwent single-organ, deceased LT. States were categorized based on their mean winter temperature: warm states (45°F-70°F), intermediate states (30°F-45°F), and cold states (0°F-30°F). Post-LT outcomes at 1 month, 1 year, and 3 years were compared using Cox proportional hazard models. Ninety-day and 1-year waitlist outcomes were compared among climate regions using Fine-Gray hazard regression model. RESULTS: After adjusting risks for recipient and donor characteristics, LT candidates in cold states had a significantly higher waitlist (90-day: subdistribution hazard ratio (HR) 1.46; 1-year: subdistribution HR 1.41; P < .001) and posttransplant mortality (30-day: subdistribution HR 1.23; P = .009, 1-year: subdistribution HR 1.16; P = .001; 3-year: subdistribution HR 1.08; P = .007). LT recipients in cold states had a higher proportion of deaths due to infections than warm states (cold states: 2.3%; intermediate states: 2.1%; and warm states: 1.7%; P < .001). CONCLUSIONS: Potential reasons include weather-related changes in the behavioral and physiological parameters of patients.

DOI： 10.1016/j.transproceed.2022.08.018

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Combined liver and lung transplantation (CLLT) is indicated in patients with both end-stage liver and lung disease. Ex-situ normothermic machine perfusion (NMP) has been previously used for extended normothermic lung preservation in CLLT. We aim to describe our single-center experience using ex-situ NMP for extended normothermic liver preservation in CLLT. Four CLLTs were performed from 2019 to 2020 with the lung transplanted first for all patients. Median ex-situ pump time for the liver was 413 min (IQR 400-424). Over a median follow-up of 15 months (IQR 14-19), all patients were alive and doing well. Normothermic extended liver preservation is a safe method to allow prolonged cold ischemia using normothermic perfusion of the liver during CLLT.

DOI： 10.1111/ajt.17053

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BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the number of patients with chronic kidney disease (CKD) is on the rise because of the increase in lifestyle-related diseases. AIM: To establish a tailored management strategy for HCC patients, we evaluated the impact of comorbid renal dysfunction (RD), as stratified by using the estimated glomerular filtration rate (EGFR), and assessed the oncologic validity of hepatectomy for HCC patients with RD. METHODS: We enrolled 800 HCC patients who underwent hepatectomy between 1997 and 2015 at our university hospital. We categorized patients into two (RD, EGFR < 60 mL/min/1.73 m2; non-RD, EGFR ≥ 60 mL/min/1.73 m2) and three groups (severe CKD, EGFR < 30 mL/min/1.73 m2; mild CKD, 30 ≤ EGFR < 60 mL/min/1.73 m2; control, EGFR ≥ 60 mL/min/1.73 m2) according to renal function as defined by the EGFR. Overall survival (OS) and recurrence-free survival (RFS) were compared among these groups with the log-rank test, and we also analyzed survival by using a propensity score matching (PSM) model to exclude the influence of patient characteristics. The mean postoperative observation period was 64.7 ± 53.0 mo. RESULTS: The RD patients were significantly older and had lower serum total bilirubin, aspartate aminotransferase, and aspartate aminotransferase levels than the non-RD patients (P < 0.0001, P < 0.001, P < 0.05, and P < 0.01, respectively). No patient received maintenance hemodialysis after surgery. Although the overall postoperative complication rates were similar between the RD and non-RD patients, the proportions of postoperative bleeding and surgical site infection were significantly higher in the RD patients (5.5% vs 1.8%; P < 0.05, 3.9% vs 1.8%; P < 0.05, respectively), and postoperative bleeding was the highest in the severe CKD group (P < 0.05). Regardless of the degree of comorbid RD, OS and RFS were comparable, even after PSM between the RD and non-RD groups to exclude the influence of patient characteristics, liver function, and other causes of death. CONCLUSION: Comorbid mild RD had a negligible impact on the prognosis of HCC patients who underwent curative hepatectomy with appropriate perioperative management, and close attention to severe CKD is necessary to prevent postoperative bleeding and surgical site infection.

DOI： 10.4240/wjgs.v14.i7.670

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BACKGROUND: In recipients with HCV/HIV coinfection, the impact that the wider use of direct-acting antivirals (DAAs) has had on post-liver transplant (LT) outcomes has not been evaluated. We investigated the impact of DAAs introduction on post-LT outcome in patients with HCV/HIV coinfection. METHODS: Using Organ Procurement and Transplant Network/United Network for Organ Sharing data, we compared post-LT outcomes in patients with HCV and/or HIV pre- and post-DAAs introduction. We categorized these patients into two eras: pre-DAA (2008-2012 [pre-DAA era]) and post-DAA (2014-2019 [post-DAA era]). To study the impact of DAAs introduction, inverse probability of treatment weighting was used to adjust patient characteristics. RESULTS: A total of 17 215 LT recipients were eligible for this study (HCV/HIV [n = 160]; HIV mono-infection [n = 188]; HCV mono-infection [n = 16 867]). HCV/HIV coinfection and HCV mono-infection had a significantly lower hazard of 1- and 3-year graft loss post-DAA, compared pre-DAA (1-year: adjusted hazard ratio [aHR] 0.29, 95% confidence interval (CI) 0.16-0.53 in HIV/HCV, aHR 0.58, 95% CI 0.54-0.63, respectively; 3-year: aHR 0.30, 95% CI 0.14-0.61, aHR 0.64, 95% CI 0.58-0.70, respectively). The hazards of 1- and 3-year graft loss post-DAA in HIV mono-infection were comparable to those in pre-DAA. HCV/HIV coinfection had significantly lower patient mortality post-DAA, compared to pre-DAA (1-year: aHR 0.30, 95% CI 0.17-0.55; 3-year: aHR 0.31, 95% CI 0.15-0.63). CONCLUSIONS: Post-LT outcomes in patients with coinfection significantly improved and became comparable to those with HCV mono-infection after introducing DAA therapy. The introduction of DAAs supports the use of LT in the setting of HCV/HIV coinfection.

DOI： 10.1111/tid.13808

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BACKGROUND The new simultaneous liver-kidney transplantation (SLK) listing criteria in the United States was implemented in 2017. We aimed to investigate the impact on waitlist and post-transplantation outcomes from changes in the medical eligibility of candidates for SLK after policy implementation in the United States. MATERIAL AND METHODS We analyzed adult primary SLK candidates between January 2015 and March 2019 using the Organ Procurement and Transplant Network/United Network for Organ Sharing (OPTN/UNOS) registry. We compared waitlist practice, post-transplantation outcomes, and final transplant graft type in SLK candidates before and after the policy. RESULTS A total of 4641 patients were eligible, with 2975 and 1666 registered before and after the 2017 policy, respectively. The daily number of SLK candidates was lower after the 2017 policy (3.25 vs 2.89, P=0.01); 1956 received SLK and 95 received liver transplant alone (LTA). The proportion of patients who eventually received LTA was higher after the 2017 policy (7.9% vs 3.0%; P<0.001). The 1-year graft survival rate was worse in patients with LTA than in those with SLK (80.5% vs 90.4%; P=0.003). The adjusted risk of 1-year graft failure in patients with LTA was 2.01 (95% confidence interval 1.13-3.58, P=0.01) compared with patients with SLK among the SLK candidates. CONCLUSIONS Although the number of registrations for SLK increased, the number of SLK transplants decreased, and the number of liver transplants increased. LTA in this patient cohort was associated with worse post-transplantation outcomes.

DOI： 10.12659/AOT.934850

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UNLABELLED: Use of higher-risk grafts in liver transplantation for patients with acute-on-chronic liver failure (ACLF) has been associated with poor outcomes. This study analyzes trends in liver transplantation outcomes for ACLF over time based on the donor risk index (DRI). METHODS: Using the Organ Procurement and Transplantation Network and the United Network for Organ Sharing registry, 17 300 ACLF patients who underwent liver transplantation between 2002 and 2019 were evaluated. Based on DRI, adjusted hazard ratios for 1-y patient death were analyzed in 3 eras: Era 1 (2002-2007, n = 4032), Era 2 (2008-2013, n = 6130), and Era 3 (2014-2019, n = 7138). DRI groups were defined by DRI <1.2, 1.2-1.6, 1.6-2.0, and >2.0. RESULTS: ACLF patients had significantly lower risks of patient death within 1 y in Era 2 (adjusted hazard ratio, 0.69; 95% confidence interval, 0.61-0.78; P < 0.001) and Era 3 (adjusted hazard ratio, 0.48; 95% confidence interval, 0.42-0.55; P < 0.001) than in Era 1. All DRI groups showed lower hazards in Era 3 than in Era 1. Improvement of posttransplant outcomes were found both in ACLF-1/2 and ACLF-3 patients. In ACLF-1/2, DRI 1.2 to 1.6 and >2.0 had lower adjusted risk in Era 3 than in Era 1. In ACLF-3, DRI 1.2 to 2.0 had lower risk in Era 3. In the overall ACLF cohort, the 2 categories with DRI >1.6 had significantly higher adjusted risks of 1-y patient death than DRI <1.2. When analyzing hazards in each era, DRI > 2.0 carried significantly higher adjusted risks in Eras 1 and 3' whereas DRI 1.2 to 2.0 had similar adjusted risks throughout eras. Similar tendency was found in ACLF-1/2. In the non-ACLF cohort, steady improvement of posttransplant outcomes was obtained in all DRI categories. Similar results were obtained when only hepatitis C virus-uninfected ACLF patients were evaluated. CONCLUSIONS: In ACLF patients, posttransplant outcomes have significantly improved, and outcomes with higher-risk organs have improved in all ACLF grades. These results might encourage the use of higher-risk donors in ACLF patients and provide improved access to transplant.

DOI： 10.1097/TXD.0000000000001283

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PURPOSE: Active hexose-correlated compound (AHCC), a standardized extract of cultured Lentinula edodes mycelia, exerts antitumor effects through anti-inflammatory and immune-modulatory functions. Adjuvant therapy for patients with hepatocellular carcinoma (HCC) who have undergone curative hepatectomy has not been established. The purpose of this study was to evaluate the efficacy and safety of AHCC as adjuvant therapy in patients with advanced HCC after curative hepatectomy. PATIENTS AND METHODS: The study design was single-armed, non-randomized, open (no one was blinded), and uncontrolled. Patients with HCC who underwent curative hepatectomy were treated with AHCC (1 g) 3 times daily orally for 2 years. The inclusion criteria were HCC diagnosed preoperatively as stages A and B of the Barcelona clinic liver cancer (BCLC) classification and alpha-fetoprotein × protein induced by vitamin K absence or antagonist II (PIVKA-II) ≥ 105 for stage A. RESULTS: A total of 29 patients were treated with AHCC, of which 25 (4 patients discontinued) were followed up. The 2-year recurrence-free survival rate after resection was 48% for those without discontinuations and 55.2% for all patients with a history of treatment. Serum albumin levels decreased to a minimum in the first postoperative month and gradually recovered to the preoperative level at 6 months. Almost no change in lymphocyte percentage was observed during follow-up. Inflammation-based prognostic scores were maintained at favorable levels after hepatectomy. Toxicity and adverse events were not observed in any patient. CONCLUSION: AHCC may be safe and effective in preventing HCC recurrence after curative hepatectomy, and further randomized trials of AHCC for its use in this setting are warranted.This clinical trial was registered in UMIN Clinical Trials Registry (ID UMIN000024396).

DOI： 10.1177/15347354211073066

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Advanced age of liver donor is a risk factor for graft loss after transplant. We sought to identify recipient characteristics associated with negative post-liver transplant (LT) outcomes in the context of elderly donors. Using 2014-2019 OPTN/UNOS data, LT recipients were classified by donor age: ≥70, 40-69, and <40 years. Recipient risk factors for one-year graft loss were identified and created a risk stratification system and validated it using 2020 OPTN/UNOS data set. At transplant, significant recipient risk factors for one-year graft loss were: previous liver transplant (adjusted hazard ratio [aHR] 4.37, 95%CI 1.98-9.65); mechanical ventilation (aHR 4.28, 95%CI 1.95-9.43); portal thrombus (aHR 1.87, 95%CI 1.26-2.77); serum sodium <125 mEq/L (aHR 2.88, 95%CI 1.34-6.20); and Karnofsky score 10-30% (aHR 2.03, 95%CI 1.13-3.65), 40-60% (aHR 1.65, 95%CI 1.08-2.51). Using those risk factors and multiplying HRs, recipients were divided into low-risk (n = 931) and high-risk (n = 294). Adjusted risk of one-year graft loss in the low-risk recipient group was similar to that of patients with younger donors; results were consistent using validation dataset. Our results show that a system of careful recipient selection can reduce the risks of graft loss associated with older donor age.

DOI： 10.3389/ti.2022.10489

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Intracholecystic papillary neoplasm of the gallbladder (ICPN) is a type of intraductal papillary neoplasm of the bile duct that occurs in the gallbladder, and is a relatively newer concept. Therefore, there are few reports regarding ICPN. Menetrier's disease is a rare disease characterized by giant hypertrophy of the gastric folds that causes protein-losing gastroenteropathy (PLG). Although Menetrier's disease is a known risk factor for gastric adenocarcinoma, the association between Menetrier's disease and malignancy other than a malignancy of the stomach is unclear. A 69-year-old man presented to the Hokkaido Social Work Association Obihiro Hospital with gallbladder tumours diagnosed by ultrasonography at a previous institution. In addition, he had previously been diagnosed with PLG due to Menetrier's disease. Abdominal contrast-enhanced computed tomography (CT) revealed an irregular mass with a contrast effect at the fundus of the gallbladder on the free abdominal cavity side. Positron emission tomography-CT showed a tumour with a standard uptake value (SUV) of 8.28 at the fundus of the gallbladder. Cholecystectomy and resection of the gallbladder bed were performed. Based on the microscopy findings, the patient was diagnosed with ICPN. Although he had postoperative ileus, he was discharged 14 days postoperatively due to improvement through conservative treatment. Such cases of ICPN complicated with Menetrier's disease are extremely rare. However, patients with Menetrier's disease may need to be screened for malignancies.

DOI： 10.3892/mco.2021.2396

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BACKGROUND: The prognosis of advanced hepatocellular carcinoma (HCC) that is not indicated for curative hepatectomy remains poor, despite advances in the treatment of HCC, including the development of tyrosine kinase inhibitors (TKIs). The outcomes of reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy, including those of recently treated cases, should be investigated. AIM: To examine the outcomes of combination treatment with reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy. METHODS: Thirty cases of advanced HCC that were not indicated for curative hepatectomy, in which reduction hepatectomy was performed between 2000 and 2018 at the Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, were divided into postoperative complete remission (POCR) (+) and POCR (-) groups, depending on whether POCR of all evaluable lesions was achieved through postoperative treatment. The cases in the POCR (-) group were subdivided into POCR (-) TKI (+) and POCR (-) TKI (-) groups, depending on whether TKIs were administered postoperatively. RESULTS: The 5-year overall survival rate and mean survival time (MST) after reduction hepatectomy were 15.7% and 28.40 mo, respectively, for all cases; 37.5% and 56.55 mo, respectively, in the POCR (+) group; and 6.3% and 14.84 mo, respectively, in the POCR (-) group (P = 0.0041). Tumor size, major vascular invasion, and the number of tumors in the remnant liver after the reduction hepatectomy were also found to be related to survival outcomes. The number of tumors in the remnant liver was the only factor that differed significantly between the POCR (+) and POCR (-) groups, and POCR was achieved significantly more frequently when ≤ 3 tumors remained in the remnant liver (P = 0.0025). The MST was 33.52 mo in the POCR (-) TKI (+) group, which was superior to the MST of 10.74 mo seen in the POCR (-) TKI (-) group (P = 0.0473). CONCLUSION: Reduction hepatectomy combined with multidisciplinary postoperative treatment for unresectable advanced HCC that was not indicated for curative hepatectomy was effective when POCR was achieved via multidisciplinary postoperative therapy. To achieve POCR, reduction hepatectomy should aim to ensure that ≤ 3 tumors remain in the remnant liver. Even in cases in which POCR is not achieved, combined treatment with reduction hepatectomy and multidisciplinary therapy can improve survival outcomes when TKIs are administered.

DOI： 10.4240/wjgs.v13.i10.1245

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The outcomes of hepatectomy alone for liver metastasis derived from non-cutaneous melanoma are insufficient, and the outcomes of systemic therapy alone are also insufficient, even since the development of immune checkpoint inhibitors (ICIs). We report the cases of three patients, in whom liver metastasis derived from non-cutaneous melanoma was treated with hepatectomy combined with ICI therapy, which was administered in various settings. One patient received ICI treatment for recurrent melanoma and survived 107 months after the first hepatectomy, one patient received both preoperative and adjuvant ICI treatment and has been disease-free for 27 months, and another patient received postoperative ICI treatment after reduction hepatectomy and has been alive with disease for 47 months. Since long-term survival is possible, hepatectomy combined with ICI therapy should be considered for the treatment of liver metastasis derived from non-cutaneous melanoma.

DOI： 10.1007/s13691-021-00495-x

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Background: Currently, the population with type 2 diabetes mellitus (DM) is increasing worldwide. However, the influence of DM or hyperglycemia on the outcome of resected hepatocellular carcinoma (HCC) is unclear. Methods: We analyzed 756 patients with HCC who underwent hepatectomy. These patients were assigned to an HbA1c ≥7.0% (H-A1c; n=100) or HbA1c <7.0% (L-A1c; n=656) group depending on their HbA1c level at admission. We investigated prognoses, clinicopathological characteristics and surgical outcomes including morbidities of HCC patients with high HbA1c, prognoses according to the treatment for DM were also investigated. Results: Among all patients and those with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, overall survival (OS) and relapse-free survival (RFS) did not differ significantly between the H-A1c and L-A1c groups. In contrast, the 5-year OS rate of the H-A1c group was 55% and that of the L-A1c group 71% among patients without HBV and HCV (NBNC patients) (P=0.03). Among NBNC patients, the median RFS of the H-A1c group was 13 months, and that of the L-A1c group was 26 months (P=0.02). In addition, metformin use was an independent favorable factor for both OS and RFS. The H-A1c group had significantly higher rates of hyperbilirubinemia, wound infection, and pneumonia. Conclusions: HCC patients with high HbA1c might have poor prognoses for both survival and recurrence in NBNC-HCC. High HbA1c may also be a risk factor for morbidities after hepatectomy. Metformin use may constitute a good option for NBNC patients with HCC.

DOI： 10.21037/hbsn.2020.01.03

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Neuroendocrine tumors (NETs) account for approximately 1-2% of all gastrointestinal tumors. In particular, primary hepatic NETs (PHNETs) are extremely rare. A 42-year-old female patient was given a diagnosis of liver tumor after a medical check-up with ultrasonography. An enhanced CT scan and MRI were suggestive for a hepatic hemangioma or adenoma, but the possibility of hepatocellular carcinoma could not be denied. Moreover, this tumor grew larger, so we performed a laparoscopic partial hepatectomy for the diagnosis and treatment of the patient. Pathological examination revealed that the tumor cells were spindle-shaped, forming glandular-tubular structures, and had less visible nucleoli and increased mitotic figures on H&E staining. Immunohistochemical findings indicated that CK19, MOC-31, CD56, synaptophysin, and chromogranin A were positive; CK7, AFP, and glypican-3 were negative; and the Ki-67 index was 3.6%, so the final diagnosis was a PHNET G2. PHNETs differ from other NETs, as they do not produce biologically active polypeptides or amines. As a result, there are no manifestations of carcinoid syndrome. In addition, PHNETs grow slowly, and most patients show no symptoms in the early stages. Laparoscopic hepatectomy is a very useful procedure for diagnosis and treatment in such cases and can be performed safely.

DOI： 10.1007/s12328-021-01403-9

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Background: Liver elastography with virtual touch quantification (VTQ) measures the velocity of the shear wave generated by a short-duration acoustic force impulse, with values expressed in units of velocity (m/s). VTQ can evaluate right or left hepatic lobes separately. VTQ might be appropriate for the evaluation of future remnant liver after hepatectomy. Methods: We analyzed 95 patients underwent liver elastography with VTQ and both future remnant liver and resected side before hepatectomy of more than two sections, except for central bisectionectomy. We divided the patients into a high VTQ group (≥1.52 m/s, n=37, 39%) and a low VTQ group (<1.52 m/s, n=58, 61%) according to the VTQ of future remnant liver. Transient elastography could not be performed in 22 cases due to tumor size. We defined the group with liver stiffness measurement (LSM) ≥7.9 kPa as the high LSM group (n=29, 40%) and those with LSM <7.9 kPa as the low LSM group (n=44, 60%). We investigated the outcome after hepatectomy and the correlations between the VTQ of future remnant liver and other indicators for hepatic fibrosis. Results: The high VTQ group showed significantly higher postoperative ascites (19% vs. 3%; P=0.01), pathological fibrosis (19% vs. 5%; P=0.03), and rates of patients with postoperative T-bil ≥2.0 mg/dL (70% vs. 40%; P<0.01). The high LSM group showed no significant postoperative outcomes compared to the low LSM group. The high VTQ group showed a higher frequency of male gender (78% vs. 57%; P=0.03), higher indocyanine green retention rate at 15 min (ICGR15) (10.5% vs. 6.3%; P<0.01), hyaluronic acid (100 vs. 67 ng/mL; P=0.02), type IV collagen 7S (7.6 vs. 5.1 ng/mL; P<0.01), Mac-2 binding protein glycan isomer (M2BPGi) (1.19 vs. 1.00; P=0.01), Fibrosis-4 (FIB-4) index (2.25 vs. 1.76; P=0.01), and aspartate aminotransferase to platelet ratio index (APRI) score (0.64 vs. 0.41; P<0.01). We also observed an especially strong positive correlation between the high VTQ and hyaluronic acid or type IV collagen 7S. Conclusions: Elastography with VTQ for future remnant liver before major hepatectomy is an accurate and useful method as a preoperative evaluation.

DOI： 10.21037/qims-20-1073

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The OPTN/UNOS policy regarding kidney allocation for liver transplant (LT) patients was implemented in August 2017. This study aimed to evaluate the effects of the simultaneous liver-kidney transplant policy on outcomes in LT alone (LTA) patients with kidney dysfunction. We analyzed adult primary LTA patients with kidney dysfunction at listing (estimated glomerular filtration rate [eGFR] less than 30mL/min or dialysis requirement) between January 2015 and March 2019 using the OPTN/UNOS registry. Waitlist practice and kidney transplant (KT) listing after LTA were compared between pre- and post-policy groups. 3,821 LTA listings with eGFR<30mL/min were included. The daily number of listings on dialysis was significantly higher in Era2 (post-policy group) than Era1 (pre-policy group) (1.21/day vs. 0.95/day, P<0.001). Of these LTA listings, 90-day LT waitlist mortality, LTA probability, and one-year post-LTA survival were similar between eras. LTA recipients in Era2 had a higher probability for KT listing post-LTA than those in Era1 (6.2% vs. 3.9%, odds ratio=3.30, P<0.001), especially those on dialysis (8.4% vs. 2.0%, odds ratio=4.38, P<0.001). Under the safety-net rule, there was a higher KT probability after LTA (26.7% and 53% at 6 months in Eras 1 and 2, respectively, P=0.017). Conclusion: After the implementation of the policy, the number of LTA listings among patients on dialysis significantly increased. While their post-transplant survival was not changed, KT listing after LTA increased. The safety-net rule led to high KT probability and low waitlist mortality rate in patients who were listed for KT after LTA. These results suggest that the policy successfully achieved the goals, which did not compromise LTA waitlist or post-transplant outcomes in patients with kidney dysfunction, and provided KT opportunities if they developed kidney failure after LTA.

DOI： 10.1002/lt.26107

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Cold preservation in University of Wisconsin (UW) solution is not enough to maintain the viability of the small intestine, due to the oxidative stress. The novel phenolic antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) has dual properties to reduce oxidative stress, radical scavenging, and antioxidant protein induction, in other cells. This study was designed to determine whether DHMBA reduces cold preservation injury of enterocytes, and to identify the effector site. Enterocytes were subjected to 48-h cold preservation under atmosphere in UW solution (±DHMBA), and then returned to normal culture to replicate reperfusion of the small intestine after cold preservation. At the end of cold preservation (ECP) and at 1, 3, 6, and 72 h after rewarming (R1h, R3h, R6h, and R72h), we evaluated cell function and the injury mechanism. The results showed that DHMBA protected mitochondrial function mainly during cold preservation, and suppressed cell death after rewarming, as shown by the MTT, ATP, mitochondrial membrane potential, LDH, and lipid peroxidation assays, together with enhanced survival signals (PI3K, Akt, p70S6K) and induction of antioxidant proteins (HO-1, NQO-1, TRX-1). We found that DHMBA mitigates the cold-induced injury of enterocytes by protecting the mitochondria through direct and indirect antioxidative activities.

DOI： 10.3390/jcm10091972

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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BACKGROUND: In terms of anatomical liver sectionectomy approaches, both a central hepatectomy (CH) and major hepatectomy (MH) are feasible options for a centrally located hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the surgical outcomes of central HCC patients who underwent CH or MH. MH includes hemihepatectomy or trisectionectomy, whereas CH involves a left medial sectionectomy, right anterior sectionectomy, or central bisectionectomy. The surgical outcomes were compared before and after propensity score matching (PSM). RESULTS: A total of 233 patients were enrolled, including 132 in the CH group and 101 in the MH group. The MH group cases were pathologically more advanced and had poorer overall survival rates than the CH group. After PSM, 68 patients were selected into each group, both of which showed similar overall and recurrence-free survival outcomes. The CH group showed a tendency for a longer operation time; however, other perioperative outcomes were similar between the two groups. Multivariate analyses of our matched HCC patients revealed that the type of surgery (CH or MH) was not an independent prognostic factor. More patients in the matched CH group experienced a repeat hepatectomy for recurrence and no patients in this group underwent a preoperative portal vein embolization. CONCLUSIONS: The short- and long-term surgical outcomes of CH and MH for a centrally located HCC are similar under a matched clinicopathological background. CH has the advantage of not requiring a preoperative portal vein embolization and increased chances of conducting a repeat hepatectomy for recurrence.

DOI： 10.1245/s10434-021-09751-z

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Language：English   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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BACKGROUND: Preoperative portal vein embolization (PVE) is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant. PVE induces hypertrophy of the future liver remnant (FLR) and a shift of the functional reserve to the FLR. However, whether the increase of the FLR volume (FLRV) corresponds to the functional transition after PVE remains unclear. AIM: To investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional (3D) computed tomography (CT) and 99mTc-galactosyl-human serum albumin (99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODS: Thirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I, Hokkaido University Hospital between October 2013 and March 2018 were enrolled. Three-phase dynamic multidetector CT and 99mTc-GSA SPECT scintigraphy were performed at pre-PVE, and at 1 and 2 wk after PVE; 3D 99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system. Functional FLRV (FFLRV) was defined as the total liver volume × (FLR volume counts/total liver volume counts) on the 3D 99mTc-GSA SPECT CT-fused images. The calculated FFLRV was compared with FLRV. RESULTS: FFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE (P < 0.01). The increase in FFLRV and FLRV was 55.1% ± 41.6% and 26.7% ± 17.8% (P < 0.001), respectively, at 1 wk after PVE, and 64.2% ± 33.3% and 36.8% ± 18.9% (P < 0.001), respectively, at 2 wk after PVE. In 3 of the 33 patients, FFLRV levels decreased below FLRV at 2 wk. One of the three patients showed rapidly progressive fatty changes in FLR. The biopsy at 4 wk after PVE showed macro- and micro-vesicular steatosis of more than 40%, which improved to 10%. Radical resection was performed at 13 wk after PVE. The patient recovered uneventfully without any symptoms of pos-toperative liver failure. CONCLUSION: The functional transition lagged behind the increase in FLRV after PVE in some cases. Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.

DOI： 10.4240/wjgs.v13.i2.153

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BACKGROUND: Hepatic angiomyolipoma (HAML) is a rare liver tumor, and hepatectomy is the only effective treatment. Due to the difficulty of correct diagnosis of HAML before surgery by image studies, more than 36.6% of reported HAMLs are misdiagnosed as other malignant liver tumors before surgery. As there are only few reported cases in which HAMLs were removed using laparoscopic hepatectomy, the effectiveness of laparoscopic hepatectomy for such HAMLs in which are diagnosed as other malignant liver tumor before surgery has not been reported. Case presentation Case 1: a 58-year-old female with a history of treatment for autoimmune hepatitis was preoperatively diagnosed with hepatocellular carcinoma (size: 20 mm) in segment 7 (S7) of the liver. The tumor was removed by laparoscopic partial resection and was diagnosed as a HAML through a pathological examination. The patient's postoperative course was good, and she was recurrence-free at 37 months after the hepatectomy. Case 2: a 29-year-old female with a history of surgery for a right mature cystic teratoma was referred to our department to receive treatment for a growing 20-mm liver tumor with some calcification, which arose in S3 of the liver. A metastatic liver tumor derived from the mature cystic teratoma was suspected, and laparoscopic left lateral sectionectomy was performed. The liver tumor was diagnosed as a HAML after a pathological examination. The patient's postoperative course was unremarkable, and more than 54 months have passed since the hepatectomy without any recurrence. CONCLUSIONS: Two cases in which HAMLs were preoperatively diagnosed as other malignant liver tumor were successfully removed by laparoscopic hepatectomy with a correct postoperative diagnosis. Laparoscopic hepatectomy for the present 2 cases of HAML seemed to be effective for providing a correct diagnosis after the curative removement of liver tumor with a smaller invasion compared to open hepatectomy, and for denying risk of dissemination of the malignant tumor by needle biopsy that had to be considered before ruling out malignant tumor.

DOI： 10.1186/s40792-021-01125-7

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Language：English   Publisher：(一社)日本肝胆膵外科学会  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Background and Aim: Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (EOB-MRI) has been recognized as a useful imaging technique to distinguish the biological behavior of hepatocellular carcinoma (HCC). Methods: We analyzed 217 hepatectomy recipients with HCCs measuring 10 cm or less. We divided the patients into a decreased intensity (DI) group (n = 189, 87%) and an increased or neutral intensity (INI) group (n = 28, 13%) according to the ratio of tumor intensity to liver intensity during the hepatobiliary phase (HBP). According to the ratio of the maximum tumor diameter (including peritumoral hypointensity) between HBP images and precontrast T1-weighted images (RHBPP), we divided the patients as follows: The group whose RHBPP was ≥1.036 was the high RHBPP group (n = 60, 28%), and the group whose RHBPP was <1.036 was the low RHBPP group (n = 157, 72%). We investigated the prognoses and clinicopathological characteristics of these patients. Results: DI versus INI was not a prognostic factor for either survival or recurrence; however, a high RHBPP was an independent predictor of unfavorable survival and recurrence in patients. In addition, the INI group showed significantly lower α-fetoprotein (AFP) levels and higher rates of well-differentiated HCC and ICGR15 ≥15% than the DI group. The high RHBPP group showed significantly higher rates of vascular invasion and poorly differentiated HCC than the low RHBPP group. Conclusions: A high RHBPP by EOB-MRI is a preoperative predictor of vascular invasion and an unfavorable prognostic factor for survival and recurrence. These patients might be considered for highly curative operations such as anatomical liver resection.

DOI： 10.1002/jgh3.12444

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Gastroenterological Surgery  

The patient was an 18-year-old man with a high γ-GTP level and a huge tumor found in the lateral segment of the liver on abdominal US. He was admitted to our hospital. Dynamic CT showed a tumor of 18 cm in diameter in the left lateral segment. The tumor was strongly enhanced in the arterial phase and showed prolonged enhancement in the delayed phase. In addition, PIVKA-II was elevated to 481 mAU/ml. The diagnosis was suspected hepatocellular adenoma (HCA), but the possibility of hepatocellular carcinoma could not be ruled out. Given the risk of rupture, we decided to perform hepatectomy and we ultimately performed left hemihepatectomy. The tumor was finally diagnosed as inflammatory type of HCA (CD34 (+), serum-amyloid-A (+), β-catenin (−), liver fatty acid-binding protein (−)) by immunohistochemistry examination. The postoperative course was uneventful and the patient was discharged 7 days after surgery. HCA may be an appropriate differential diagnosis for a huge liver mass in a young patient, and surgical resection should be considered for diagnosis and treatment.

DOI： 10.5833/jjgs.2020.0055

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Gastroenterological Surgery  

A 61-year-old man underwent right trisegmentectomy combined with diaphragmatic resection for hepatocellular carcinoma (HCC) at age 52, and thoracoscopic left upper and lower lobe partial resection for lung metastases at age 56. At age 59, PIVKA-II was elevated, transcatheter arterial chemoembolization was performed for diagnosis of intrahepatic recurrence, and PIVKA-II also decreased. In the next year, PIVKA-II re-elevated and a tumor of 5 cm was found in the right gastrocnemius muscle. Needle biopsy was performed for diagnosis of skeletal muscle metastasis. Extended tumor resection and latissimus dorsi musculocutaneous flap and skin graft were performed. The histopathological diagnosis was metastasis of HCC, moderately to poorly differentiated, and venous invasion was observed. The patient is alive without recurrence 16 months after the last surgery. While skeletal muscle metastasis of HCC is rare, this case shows that a favorable prognosis is possible after tumor resection.

DOI： 10.5833/JJGS.2019.0162

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

症例は生来健康な17歳の男性.腹部膨満を契機に,肝右葉に径25cmの肝腫瘍が発見された.肝炎ウイルスマーカーは陰性,AFPは正常値でPIVKA-IIが12,738mAU/mlと異常高値を認めた.造影CTおよびMRIで腫瘍は漸増性の造影効果を伴っており,一部造影効果の乏しい不整形領域を認めた.腫瘍の大部分はEOB-MRIの肝細胞相で取り込み低下は軽度であり,肝細胞癌としては非典型的であったが悪性の可能性が否定できないことと破裂の危険性があることから手術適応と考え,肝右3区域切除を施行した.術後経過は良好で,術後13日目に退院となった.病理診断はβ-catenin活性化型肝細胞腺腫であり,悪性所見は認めなかった.PIVKA-IIは切除後速やかに低下した.今回,若年男性に発生した稀な巨大肝細胞腺腫の1切除例を経験したため,文献的考察を加えて報告する.(著者抄録)

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The N‑glycoforms of glycoproteins modify protein function and control a number of biological pathways. The aim of the present study was to investigate the correlation between alterations in N‑glycans and cancer aggressiveness in terms of cancer cell invasion ability. The expression of urokinase‑type plasminogen activator (uPA) and N‑acetylglucosaminyltransferase V (GnT‑V) in liver cancer cell lines was analyzed by western blotting. Cell invasiveness was analyzed by Matrigel invasion assays. uPA and GnT‑V expression in liver cancer cell lines was knocked down by RNA interference. Furthermore, uPA was overexpressed in liver cancer cells using lentiviral vectors, and a mutant strain of HepG2 cells overexpressing uPA deficient in N‑glycans was established. A glycoblotting‑assisted matrix‑assisted laser desorption/ionization‑time‑of‑flight/mass spectrometry‑based quantitative analysis of liver cancer cell lines was performed, in which invasiveness was altered by modifying the expression of uPA and GnT‑V. N‑glycan profiles were found to differ between the highly invasive liver cancer cell line HLE and the less invasive cell line HepG2. The expression of several N‑glycans, including a form with m/z=1892, was changed according to invasiveness controlled by knockdown and overexpression of uPA. The invasiveness of HepG2 cells with mutant uPA did not increase regardless of the level of expression of uPA. Following GnT‑V knockdown and N‑glycan alteration, uPA expression did not change, whereas cell invasiveness decreased. One N‑glycan (m/z=1892) was common among N‑glycans in the comparative analysis between HLE and HepG2, HLE and uPA knockdown HLE, HepG2 and uPA‑overexpressing HepG2, and HLE and GnT‑V knockdown HLE cells and among N‑glycan profiles in human uPA. Therefore, N‑glycosylation is an important factor controlling invasiveness of liver cancer cells, and a specific N‑glycan (m/z=1892) associated with the invasion of liver cancer cells via uPA was identified in the present study.

DOI： 10.3892/or.2020.7795

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Inappropriate activation of the canonical Wnt signaling pathway is associated with progression of hepatocellular carcinoma (HCC). However, the association between the non-canonical pathway activated by Wnt5a and HCC is not well known. The present study investigated the significance of Wnt5a expression in HCC. Immunohistochemical staining of Wnt5a was performed on specimens from 243 patients who underwent hepatic resection for HCC. The present study investigated whether Wnt5a expression was associated with clinical and pathological factors and prognosis. Wnt5a expression in human HCC cell lines was investigated using western blotting. The effects of overexpression or knockdown of Wnt5a were evaluated using proliferation and invasion assays. Changes in epithelial-mesenchymal transition (EMT)-related molecules were investigated using western blotting. Wnt5a negativity was significantly associated with poor tumor differentiation and positive vascular invasion. In univariate analysis, Wnt5a negativity was identified as a significant prognostic factor for overall survival (OS). Multivariate analysis of OS demonstrated that Wnt5a negativity was an independent prognostic factor. Wnt5a expression was lower in HLE and HLF cells than in HepG2 and Huh7 cells. Knockdown of Wnt5a by short hairpin RNA transfection increased the proliferation and invasiveness of Huh7 cells, and decreased the expression levels of E-cadherin. In HLF cells, overexpression of Wnt5a inhibited invasiveness and decreased the expression levels of vimentin. Wnt5a negativity was associated with poor tumor differentiation and positive vascular invasion, and was an independent poor prognostic factor in patients with HCC. Wnt5a may be a tumor suppressor involved in EMT-mediated changes in invasiveness.

DOI： 10.3892/ol.2020.12131

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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PURPOSE: We evaluated the short- and long-term surgical outcomes of hepatectomy combined with diaphragmatic resection for hepatocellular carcinoma (HCC) with diaphragmatic involvement. METHODS: We retrospectively reviewed the surgical outcomes of HCC patients with diaphragmatic resection (DR group) and HCC patients without diaphragmatic resection (non-DR group). We applied 1:1 propensity score matching (PSM) to these subjects. RESULTS: The study included 46 patients in DR group and 828 patients in non-DR group. The DR group cases were pathologically more advanced, and both overall and relapse-free survival among the patients in this group with pathological diaphragmatic invasion were similar to cases with pathological diaphragmatic fibrous adhesion. There were 40 patients from each group subjected to PSM. In these matched cohorts, there was no statistically significant difference between the two groups regarding perioperative outcomes, overall survival, and relapse-free survival. Multivariate analyses of our matched HCC patients revealed that alpha-fetoprotein expression and tumor size were independent prognostic factors for overall survival and poor differentiation for relapse-free survival, whereas neither diaphragmatic invasion nor diaphragmatic resection were prognostic indicators. The most frequent site of recurrence in non-DR group was the liver, whereas the most frequent site of recurrence in DR group was the lung before and after PSM. CONCLUSIONS: The short- and long-term surgical outcomes of DR HCC cases are equivalent to their non-DR counterparts under a matched clinicopathological background. Hepatectomy combined with DR is an acceptable treatment for HCC with either diaphragmatic fibrous adhesion or diaphragmatic invasion.

DOI： 10.1245/s10434-020-08754-6

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌学会  

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Background: Treatment for acute abdomen during chemotherapy is frequently difficult because of the complicated status of the patients, and there have been only a few case series summarizing the outcomes of emergent surgery during chemotherapy. The aim of this study was to clarify the clinical outcomes of emergency surgery for acute abdomen during chemotherapy and identify predictive factors associated with mortality. Methods: We retrospectively analyzed the records of patients who underwent emergency surgery for acute abdomen within 30-days after anti-cancer drugs administration between 2009 and 2020. Results: Thirty patients were identified. The primary malignancies were hematological (n = 7), colorectal (n = 4), lung (n = 4), stomach (n = 2), breast (n = 2), prostate (n = 2) and others (n = 5). Fifteen patients were treated with the regimen, including molecular-targeted anti-cancer drugs (Bevacizumab: 8 cases, Rituximab: 4, Ramucirumab: 2, and Gefitinib: 1). Indications for emergency surgery were perforation of the gastrointestinal tract (n = 24), appendicitis (n = 3), bowel obstruction (n = 2), and gallbladder perforation (n = 1). Severe morbidity (Clavien-Dindo IIIa or more) occurred in 8 cases (27%), and there were 6 in-hospital deaths (20%). Significant factors related to in-hospital death were age >70 years old (P = 0.029), poor performance status (ECOG score 1 or 2) (P = 0.0088), and serum albumin level <2.6 g/dl (P = 0.026). The incidence of acute abdomen (odds ratio 5.31, P = 0.00017) was significantly higher in the patients receiving anti-VEGF drugs than in those without anti-VEGF drugs. Conclusion: This study identified three predictive factors associated with in-hospital death after emergency surgery during chemotherapy: an older age, poor performance status, and low serum albumin level.

DOI： 10.1016/j.amsu.2020.07.038

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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PURPOSE: A lack of effective systemic therapy is one reason for the poor prognosis of intrahepatic cholangiocarcinoma. Newly developed immune checkpoint inhibitors function by minimizing CD8+ T cell suppression to improve tumor-specific responses. This study aimed to examine the characteristics of CD8+ T cells in intrahepatic cholangiocarcinoma. METHODS: Clinicopathological data, including the overall survival, of 69 cases of postoperative intrahepatic cholangiocarcinoma were prospectively investigated. We then immunohistochemically stained for CD8, Foxp3, CD163, PD-L1, and human leukocyte antigen (HLA) class I and counted the number of CD8+ T cells, Foxp3+ T cells, and CD163+ macrophages in different areas (outer border, interborder, and intratumor). RESULTS: A significant difference was found in the 5-year overall survival between the CD8+ T cell high group (45.5%) and low group (24.7%) in the outer border area (p = 0.0103). Furthermore, the number of CD8+ T cells and the high expression of HLA class I were positively correlated (p = 0.0341). CONCLUSION: The number of CD8+ T cells in the outer border area of the tumor correlated with the HLA class I expression of intrahepatic cholangiocarcinoma and may therefore be a prognostic factor for patients with postoperative intrahepatic cholangiocarcinoma.

DOI： 10.1007/s00595-020-01967-y

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BACKGROUND: We assessed the usefulness of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging for the prediction of posthepatectomy liver failure (PHLF) after a major hepatectomy. METHODS: We reviewed 140 cases involving a hepatectomy of two or more sections between 2010 and 2016 (study cohort). We used the standardized remnant hepatocellular uptake index (SrHUI) which was calculated by: SrHUI = future remnant liver volume × [(signal intensity of remnant liver on hepatobiliary phase images/signal intensity of spleen on hepatobiliary phase images) - 1]/body surface area. Validation of the SrHUI was performed in another cohort of 52 major hepatectomy cases between 2017 and 2018 (validation cohort). RESULTS: The SrHUI of patients with PHLF was significantly lower than that of non-PHLF cases. Receiver operating characteristic analysis and the Youden index revealed that the SrHUI cutoff value for the prediction of PHLF and PHLF grade ≥ B were 0.313 L/m2 and 0.257 L/m2 , respectively. In the validation cohort, the cutoff value of SrHUI for the prediction of PHLF or PHLF grade ≥ B had a sensitivity of 75.0% or 88.8%, and specificity of 78.1% or 91.6%, respectively. CONCLUSIONS: The SrHUI value is a predictor for PHLF after a major hepatectomy.

DOI： 10.1002/jhbp.769

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：English   Publisher：(資)医薬出版  

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Warm ischemia and reperfusion injury (IRI) is a prognostic factor in donation after cardiac death donor transplantation. However, a reliable method to predict IRI before transplantation has not been established. The aim of this study was to identify predictive markers of hepatic IRI by simultaneous measurement of endogenous molecules using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Rats were subjected to hepatic warm ischemia (70%) for 30 or 90 minutes and subsequent reperfusion. The livers were collected at the end of ischemia and 1 hour, 6 hours, and 24 hours after reperfusion. The liver tissue sections were applied to IMS (m/z 200-2000). Candidate molecules were identified by tandem mass spectrometry. Imaging mass spectrometry (IMS) revealed a significant increase in the taurine conjugates of dihydroxycholanoic acid (TDHCA) during ischemia and a tendency to return to the basal level after reperfusion. Notably, high-resolution measurements revealed focal accumulation of TDHCA in the intrahepatic bile duct with ischemic time. In conclusion, IMS is a useful method to detect minute changes provoked by ischemia, which are barely detectable in assays involving homogenization. Accordingly, focal accumulation of TDHCA during ischemia may be a candidate marker for predicting later IRI.

DOI： 10.1016/j.transproceed.2020.01.169

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OBJECTIVES: The aim was to evaluate the prognostic factors, clinicopathological characteristics, and surgical outcomes after hepatectomy in very elderly patients with hepatocellular carcinoma (HCC). METHODS: We analyzed 796 patients with HCC from 2000 to 2017. Patients aged 80 years or older were classified into the very elderly group (group VE; n = 49); patients younger than 80 years old and aged 65 years or older were classified into the elderly group (group E; n = 363), and patients younger than 65 years old were classified into the young group (group Y; n = 384). We investigated the prognoses, clinicopathological characteristics, and surgical outcomes after hepatectomy. RESULTS: The number of surgical procedures and outcomes, including morbidities, was not significantly different. Groups VE, E, and Y showed similar prognoses in terms of both survival and recurrence. In group VE, prothrombin activity (PA) < 80% and PIVKA-II ≥ 400 mAU/ml were unfavorable factors for survival, and PIVKA-II ≥ 400 mAU/ml and the presence of portal venous invasion (PVI), hepatic venous invasion, and fibrosis were unfavorable factors for recurrence. In group E, ChE < 180 IU/l, AFP ≥ 20 ng/ml, tumor size ≥ 10 cm, and the presence of multiple tumors, PVI, and hepatic venous invasion (HVI) were unfavorable factors for survival, and ChE < 180 IU/l, tumor size ≥ 10 cm, and the presence of multiple tumors, PVI, and HVI were unfavorable factors for recurrence. In group Y, AFP ≥ 20 ng/ml, the presence of multiple tumors, poor differentiation, PVI, HVI, and blood loss ≥ 400 ml were unfavorable factors for survival, and PA < 80%, albumin < 3.5 g/dl, AFP ≥ 20 ng/ml, tumor size ≥ 10 cm, and the presence of multiple tumors, poor differentiation, and PVI were unfavorable factors for recurrence. CONCLUSIONS: Tumor factors might have limited influence on the prognosis of very elderly patients, and liver function reserve might be important for the long-term survival of very elderly patients. Hepatectomy can be performed safely, even in very elderly patients. Hepatectomy should not be avoided in very elderly patients with HCC if patients have a good general status because these patients have the same prognoses as nonelderly individuals.

DOI： 10.1186/s12957-020-01899-4

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BACKGROUND AND OBJECTIVES: The aim was to evaluate long-term prognostic factors in hepatocellular carcinoma (HCC) patients who survived over 10 years after hepatectomy and compare prognostic factors between patients with recurrence who died and survived 10 years after initial hepatectomy. METHODS: We analyzed the HCC patients without recurrence over 10 years after hepatectomy (n = 35), those with recurrence who survived over 10 years (n = 48), and those who died within 10 years (n = 132). RESULTS: The rate of recurrence was 16.3%, 10-year overall survival rate was 38.6%, and the 10-year recurrence-free survival (RFS) rate was 16.7%. Nonviral, solitary tumor, well differentiation, and without severe fibrosis were independent favorable factors for long-term RFS. High cholinesterase levels, small tumors and without portal vein invasion were independent favorable factors for long-term survival among patients with recurrence. Long-term survivors with recurrence showed significantly low early recurrence, extrahepatic recurrence, multiple intrahepatic recurrences. CONCLUSION: Important factors for long-term prognoses in HCC patients were a solitary tumor, small tumors, and no advanced fibrosis. A treatment for nonviral hepatitis is needed to achieve long-term RFS. Even patients who relapse might survive long term if they have a late or solitary intrahepatic recurrence, nonsevere cirrhosis, and curative treatment at recurrence.

DOI： 10.1002/jso.25910

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Language：Japanese   Publisher：(一社)日本インターベンショナルラジオロジー学会  

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Background: Although hepatectomy is the standard and only curative treatment for colorectal liver metastases, recurrence occurs in various organs, including the remnant liver, lung, peritoneum, and others. The outcomes and predictive factors of repeat metastasectomy for recurrence after initial hepatectomy remains controversial. Methods: We retrospectively assessed a consecutive series of 132 patients who underwent hepatectomy for colorectal liver metastases in a single institute. Results: There were 99 recurrence cases after initial hepatectomy, and 42 patients underwent metastasectomy (first repeat metastasectomy) to achieve R0 (17 liver cases, 16 lung cases, and 9 multiple or other cases), while 19 patients underwent subsequent second repeat metastasectomy (4 liver cases, 7 lung cases, and 8 multiple or other cases). Among the 99 recurrent cases after initial hepatectomy, the 5-year overall survival rate of the patients who underwent first repeat metastasectomy was significantly higher than that of chemotherapy/BSC (best supportive care) patients (60% vs. 14%, P < 0.0001). Furthermore, among the 26 recurrent cases after first repeat metastasectomy, the 5-year overall survival rate of the patients who underwent second repeat metastasectomy was significantly higher than that of chemotherapy/BSC patients (P = 0.024). A multivariate analysis revealed that lack of adjuvant chemotherapy, a short (<12 months) disease-free interval, and right-side colon primary were the independent poor prognostic factors for the overall survival after first repeat metastasectomy. Conclusion: The current study indicated that repeat metastasectomy for recurrence after initial hepatectomy for colorectal liver metastases could achieve a longer survival time, especially for patients with favorable predictive factors.

DOI： 10.1016/j.amsu.2020.01.006

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Language：Japanese   Publisher：日本臨床外科学会  

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AIM: A new classification of combined hepatocellular cholangiocarcinoma (CHC) was recently reported. Cancer stem cells have been associated with CHC carcinogenesis. This study examined the association of cancer stem cell marker expression and prognosis in CHC classified using the new classification. METHODS: We enrolled 26 CHC patients and classified them according to the new classification. We evaluated the expression of cancer stem cell markers (CD56, CD133, and epithelial cell adhesion molecule [EpCAM]) by immunohistochemical staining in each component. We analyzed the association between expressions and prognosis. RESULTS: Seven cases were hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC-CCA), 12 were HCC and intermediate cell carcinoma (HCC-INT), and seven were intermediate cell carcinoma (INT). The CD133-positive rate tended to be higher in the CCA (42.9%) and INT component (50.0%) than the HCC component (14.3%) in cHCC-CCA. In HCC-INT, the CD133-positive rate in the INT component (83.3%) was significantly higher than the HCC component (8.3%; P = 0.001). For EpCAM, the positive rate in the CCA component (71.4%) and INT component (50.0%) tended to be higher than the HCC component (14.3%) in cHCC-CCA. Overall survival and disease-free survival were significantly worse in cases with CD133-positive (P = 0.048 and P = 0.048, respectively) or EpCAM-positive (P = 0.041 and P = 0.041, respectively) CCA component in cHCC-CCA. CONCLUSIONS: INT and CCA components showed higher expression rates of cancer stem cell markers than the HCC component. CD133 or EpCAM expression in the CCA component was associated with poor prognosis in cHCC-CCA.

DOI： 10.1111/hepr.13443

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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BACKGROUND: Heavy water (D2O) has many biological effects due to the isotope effect of deuterium. We previously reported the efficacy of D2O containing solution (Dsol) in the cold preservation of rat hearts. Here, we evaluated whether Dsol reduced hepatic cold preservation and reperfusion injury. METHODS: Rat livers were subjected to 48-hour cold storage in University of Wisconsin (UW) solution or Dsol, and subsequently reperfused on an isolated perfused rat liver. Graft function, injury, perfusion kinetics, oxidative stress, and cytoskeletal integrity were assessed. RESULTS: In the UW group, severe ischemia and reperfusion injury (IRI) was shown by histopathology, higher liver enzymes leakage, portal resistance, and apoptotic index, oxygen consumption, less bile production, energy charge, and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio (versus control). The Dsol group showed that these injuries were significantly ameliorated (versus the UW group). Furthermore, cytoskeletal derangement was progressed in the UW group, as shown by less degradation of α-Fodrin and by the inactivation of the actin depolymerization pathway, whereas these changes were significantly suppressed in the Dsol group. CONCLUSION: Dsol reduced hepatic IRI after extended cold preservation and subsequent reperfusion. The protection was primarily due to the maintenance of mitochondrial function, cytoskeletal integrity, leading to limiting oxidative stress, apoptosis, and necrosis pathways.

DOI： 10.3390/jcm8111818

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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BACKGROUND AND AIM: Combined hepatocellular-cholangiocarcinoma (CHC) is a primary liver cancer containing both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) elements. Its reported clinicopathological features and prognoses have varied because of its low prevalence. This study aimed to clarify these aspects of CHC. METHODS: We enrolled 28 patients with CHC, 1050 with HCC, and 100 with ICC and compared the clinicopathological characteristics and prognosis of CHC with HCC and ICC. We also analyzed prognostic factors, recurrence patterns, and management in CHC patients. RESULTS: The incidences of hepatitis B virus and high α-fetoprotein and protein induced by vitamin K absence or antagonists-II levels were significantly higher among CHC compared with ICC patients. Multiple tumors were more frequent in CHC compared with the other groups, while vascular invasion and lymph node metastasis were more frequent in the CHC than the HCC group. The 5-year overall survival and disease-free survival rates for CHC were 25.1% and 22.6%, respectively. Overall survival was significantly lower than for HCC (P < 0.001) but not ICC (P = 0.152), while disease-free survival was significantly lower than for HCC and ICC (P = 0.008 and P = 0.005, respectively). Multivariate analysis identified carcinoembryonic antigen levels and tumor size as independent predictors in patients with CHC. CONCLUSIONS: The clinical features of CHC, including sex, hepatitis B virus infection, α-fetoprotein, and protein induced by vitamin K absence or antagonists-II levels, were similar to HCC, while its prognosis and pathological features, including vascular invasion and lymph node metastasis, were similar to ICC. Carcinoembryonic antigen levels and tumor size were independent prognostic factors in patients with CHC.

DOI： 10.1111/jgh.14547

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BACKGROUND: The aim was to evaluate the prognoses and clinicopathological characteristics of solitary hepatocellular carcinoma (HCC) originating from the caudate lobe (HCC-CL). METHODS: We analyzed 584 patients with a solitary tumor <10 cm from January 1990 to November 2014. Patients were classified into a caudate lobe group (CL; n = 39) and a non-caudate lobe group (NCL; n = 545). We investigated the prognoses and clinicopathological characteristics of solitary HCC-CL. We compared the surgical procedures performed in these cases. RESULTS: HCC-CL had a similar rate of portal venous invasion (PVI) as HCC-NCL (21% vs. 19%); however, the frequency of tumor thrombus at the first branch of the portal vein (PV) or extension to the trunk or the opposite side of the PV was significantly higher in HCC-CL (8% vs. 2%). HCC-CL had similar OS rates compared to HCC-NCL; however, HCC-CL showed significantly poorer RFS. Although there were no significant differences among the three surgical procedures, blood loss and complication rates tended to be higher in cases who underwent an isolated caudate lobectomy. Tumor size ≥5 cm, PVI, and liver fibrosis or cirrhosis (LF or LC) were independent unfavorable factors for both OS and RFS. PIVKA-II ≥120 mAU/ml was an independent unfavorable factor for RFS. CONCLUSION: HCC-CL presented a poorer RFS rate. Patients with a tumor size ≥5 cm, PIVKA-II ≥120 mAU/ml, portal venous invasion, and LF or LC should be diligently followed up as these cases have a high risk of recurrence.

DOI： 10.1007/s00268-018-4869-2

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BACKGROUND: Percutaneous transhepatic portal embolization (PTPE) is useful for safe major hepatectomy. This study investigated the correlation between hepatic hypertrophy and hemodynamics of portal venous flow by ultrasound sonography after PTPE. METHODS: We analyzed 58 patients with PTPE, excluding those who underwent recanalization (n = 10). Using CT volumetry results 2 weeks after PTPE, the patients were stratified into a considerable hypertrophy group (CH; n = 15) with an increase rate of remnant liver volume (IR-RLV) ≥ 40% and a minimal hypertrophy group (MH; n = 33) with an IR-RLV < 40%. We investigated the hemodynamics of portal venous flow after PTPE and the favorable factors for hepatic hypertrophy. RESULTS: Univariate and multivariate analysis identified the indocyanine green retention rate at 15 min (ICGR15) and increase rate of portal venous flow volume (IR-pFV) at the non-embolized lobe on day 3 after PTPE as independent favorable factors of IR-RLV. Patients with IR-pFV on day 3 after PTPE ≥100% and ICGR15 ≤ 15% (n = 13) exhibited significantly increased IR-RLV compared with others (n = 35). CONCLUSIONS: Cases with high IR-pFV on day 3 after PTPE exhibited better hepatic hypertrophy. Preserved liver function and increased portal venous flow on day 3 were important.

DOI： 10.1186/s12893-019-0486-8

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Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycoprotein that is synthesized by stromal cells in bone marrow. Several cases of G-CSF-producing malignant tumors in various organs have been reported, but it is extremely rare in hepatocellular carcinoma (HCC). Here, we report a rare case of HCC producing G-CSF. The patient presented with a continuous fever and had a huge liver mass in the right lobe with portal vein tumor thrombus (PVTT) in the right first branch. He had marked granulocytosis, and his serum level of G-CSF was elevated. A complete curative liver resection was performed after preoperative radiotherapy to PVTT. The pathological findings of the resected specimen revealed poorly/moderately differentiated HCC, and immunohistochemical staining of G-CSF was negative the first time it was tested, but the second time, it was positive in the cytoplasm of other tumor cells of HCC. Only a few cases of G-CSF-producing HCC have been reported, and they resulted in rapid tumor growth, metastases, and poor prognosis. In our case with PVTT, there was no liver recurrence, although multiple lung metastases occurred at 8 months after curative resection. We should consider G-CSF-producing HCC and diagnose promptly when encountering liver tumor patients with leukocytosis, and we should perform multimodal treatment including radiation, radical surgery, and chemotherapy.

DOI： 10.1007/s13691-018-0346-x

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BACKGROUND AND PURPOSE: We reported previously that hydrogen gas (H2) reduced hepatic ischemia and reperfusion injury (IRI) after prolonged cold storage (CS) of livers retrieved from heart-beating donors. The present study was designed to assess whether H2 reduced hepatic IRI during donation of a cardiac death (DCD) graft with subsequent CS. METHODS: Rat livers were harvested after 30-min cardiac arrest and stored for 4 h in University of Wisconsin solution. The graft was reperfused with oxygenated buffer, with or without H2 (H2 or NT groups, respectively), at 37° for 90 min on isolated perfused rat liver apparatus. RESULTS: In the NT group, liver enzyme leakage, apoptosis, necrosis, energy depletion, redox status, impaired microcirculation, and bile production were indicative of severe IRI, whereas in the H2 group these impairments were significantly suppressed. The phosphorylation of cytoplasmic MKK4 and JNK were enhanced in the NT group and suppressed in the H2 group. NFkB-p65 and c-Fos in the nucleus were unexpectedly unchanged by IRI regardless of H2 treatment, indicating the absence of inflammation in this model. CONCLUSION: H2 was observed to ameliorate IRI in the DCD liver by maintaining microcirculation, mitochondrial functions, and redox status, as well as suppressing the cytoplasmic MKK4-JNK-mediated cellular death pathway.

DOI： 10.1007/s00595-018-1693-0

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BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) shows differing clinical outcomes depending on its localization. METHODS: We reviewed the surgical outcomes of 104 ICC patients who underwent liver resection at our institution. We divided ICC into hilar type (HICC) and peripheral type (PICC) depending on positive contact with the hepatic hilum on preoperative computed tomography (CT). RESULTS: The survival outcomes were significantly poorer in HICC patients. HICCs showed a larger tumor size and more frequent bile duct invasion, lymph node metastasis, and non-curative resection than PICC. Resections for HICC had greater blood loss and required a longer operation time, larger hepatectomy, and more frequent extrahepatic bile duct resection. HICCs, even if small in size, also showed a greater tendency to metastasize to the lymph nodes of the hepatoduodenal ligament. Univariate analysis of the ICCs in our current cohort revealed that tumor size, multiple tumors, bile duct invasion, lymph node metastasis, non-curative resection, and HICC are associated with a poorer overall survival outcome. Multivariate analysis indicated that multiple tumors and non-curative resection were independent prognostic factors for survival. Among the curative resection cases, however, survival did not differ significantly between HICC and PICC. The accuracy rate of our CT-based classification for the pathological classification was 81.7%. CONCLUSIONS: HICC shows more frequent bile duct invasion and lymph node metastasis, requires more extensive surgery, and has a higher rate of non-curative resection than PICC. However, if curative resection is achieved, the survival outcomes are expected to be equivalent between HICC and PICC.

DOI： 10.1007/s00535-018-1469-8

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BACKGROUND: Local antitumor efficacy and the outcome of neoadjuvant chemoradiotherapy (NACRT) with low-dose gemcitabine and wide irradiation area for borderline resectable and unresectable pancreatic cancer were evaluated. PATIENTS AND METHODS: Thirty-four cases of borderline resectable and unresectable pancreatic cancer were recruited. Three-dimensional conformal radiotherapy to the pancreatic bed and the region scheduled for lymph node dissection was performed to a total dose of 50.4 Gy28 fractions with gemcitabine at a dose of 150 mg/m2 weekly. Clinical and pathological results were examined. RESULTS: Twenty-seven patients (79.4%) completed the protocol. Grade 3/4 leucopenia (n=10), and grade 3 anorexia (n=1) occurred. Seven cases were excluded (two refused treatment; five had progressive disease), 20 underwent laparotomy, and 16 resected (47.1%) cases achieved R0 resection. Median survival time, and 3-year and 5-year survival rates were 39.0 months, and 56.3% and 28.1% in resected cases, respectively. CONCLUSION: NACRT with low-dose gemcitabine and wide irradiation area achieved 100% R0 resection and acceptable prognosis.

DOI： 10.21873/invivo.11362

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Recently, several reports demonstrated the efficacy of neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT) for patients with borderline resectable (BRPC) and locally advanced unresectable pancreatic carcinoma (LAPC). The aim of this study was to evaluate the treatment response after NACRT, especially for nerve plexuses, and the optimal resection area for superior mesenteric artery nerve plexuses in BRPC and LAPC patients after NACRT.A total of 17 patients with BRPC and LAPC received preoperative gemcitabine-based NACRT. The numbers of BRPC and LAPC patients were 13 and 4, respectively. We evaluated nerve plexus invasion by CT before and after NACRT, decided on the resection area of plexus invasion in SMA before NACRT, and compared the preoperative evaluation and clinicopathological findings.In the plexus of the supra-mesenteric artery (pl-SMA), arterial nerve plexus invasion, in cases <90°, all patients showed the absence of residual cancer in the resected specimen after NACRT. In cases between 90° and 180°, 1 of 2 patients (50%) showed nerve plexus invasion. In cases over 180°, all patients showed nerve plexus invasion. We could perform R0 resection in all 10 cases, and pl-SMA invasion disappeared in 6 of 7 BRPC patients.We demonstrated the relationship between the angle of nerve plexus tumor invasion and treatment effect after NACRT. We could perform R0 resection in all pl-SMA invasion cases, deciding on the resection area of pl-SMA based on CT before NACRT.

DOI： 10.1097/MD.0000000000011309

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Verlag  

PURPOSE: To increase the surgical opportunities for locally advanced perihilar bile duct cancers that require left-sided hepatectomies, we developed the transparenchymal glissonean approach (TGA); it comprises intra-hepatic exposure and dissection of the Glisson's sheath to gain access to the hepatic artery and portal vein for reconstruction. METHODS: Following skeletonization of the hepatoduodenal ligament, the proximal portions of invaded vessels are exposed. If extra-hepatic attempts to access the distal portions of the invaded vessels fail, TGA can be used. The distal portion of the invaded right or right posterior Glisson's sheath is exposed following liver transection. The anterior portion of the wall of bile duct is cut and transected circumferentially including the fibrous plate tissue. The non-invaded portal vein and hepatic artery are isolated and dissected towards the hepatic hilum until the invaded distal portion of the vessels, and vascular reconstructions are performed. RESULTS: TGA was performed in 9 patients; 5 patients underwent left hemihepatectomy and 4 underwent left tri-sectionectomy. Eight patients needed vascular reconstruction. Clavien-Dindo classification (CDC) grades IIIa and IIIb were recorded in 6 and 1 patients, respectively. No patients had CDC grades IV and V disease. Pathologically, all cases were pT4; 3 cases were R0, 5 were R1 with microscopic positive margin, and 2 were R1 with microscopic metastasis. The overall median survival time was 25.0 months. CONCLUSIONS: TGA is feasible with acceptable prognosis and expands the surgical opportunities.

DOI： 10.1007/s00423-017-1633-2

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BACKGROUND In cases of celiac axis occlusion requiring pancreaticoduodenectomy for malignancy, both oncologic curability and control of hepatic arterial flow must be considered, but the operative strategy is undeveloped. CASE REPORT Case 1: A 74-year-old man was diagnosed with hilar cholangiocarcinoma with celiac axis stenosis. The collateral from the superior mesenteric artery ran through the pancreas head but no invasion was observed in preoperative imaging. Hepatopancreatoduodenectomy with preservation of a collateral was performed. Case 2: A 69-year-old woman was diagnosed with pancreas head cancer with celiac axis occlusion. The collateral from the superior mesenteric artery ran through pancreas head and tumor invasion was observed. Pancreaticoduodenectomy with bypass revascularization using a vein graft was performed. Both operations were performed safely oncologically under preoperative planning that was based on computed tomographic angiography. The operative procedure was ultimately determined by evaluation of perioperative blood flow under Doppler ultrasonography after clamping the gastroduodenal artery. CONCLUSIONS Preoperative simulations of arterial revascularization and perioperative evaluation of blood flow are necessary for the success of this procedure.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

The patient was a 63-year-old man. Computed tomography(CT)showed a 99mm in diameter low-density mass in hepatic segments 4 and 8 as the main locus. This tumor was diagnosed as intrahepatic cholangiocarcinoma and was suspected to invade to left and right Gleason's sheath, and radical cure was judged impossible. After hepatic arterial chemotherapy and radiotherapy were performed, tumor shrinkage was confirmed, and tumor markers also became negative. So he was referred to our hospital for surgical indication. CT revealed that the tumor did not invade to the left Gleason's sheath. After percutaneous transhepatic portal embolization, hepatic right trisectionectomy was performed. He was administered gemcitabine as an adjuvant chemotherapy for 1 year. One year 5 months after surgery, the patient is alive without relapse. Preoperative hepatic arterial chemotherapy and radiotherapy could be an effective treatment for unresectable locally advanced intrahepatic cholangiocarcinoma.

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Intraductal papillary mucinous neoplasms (IPMNs) are characterized by the papillary proliferation of atypical mucinous epithelial cells in the pancreatic ductal system. There are two recurrence patterns following resection of IPMNs: Metachronous multifocal occurrence of IPMNs, and distinct pancreatic ductal adenocarcinoma (PDAC) in the remnant pancreas. Several recent studies investigated the development of distinct PDAC during follow-up evaluation of IPMNs and the incidence rate ranged from 4.5 to 8%. Thus, IMPNs may be a good predictor for the early detection of PDAC during observation or after the resection of IPMNs. We herein report the rare case of a patient who underwent resection of PDAC that developed in the remnant pancreas 13 years after distal pancreatectomy with splenectomy for IPMNs. PDAC may develop in the remnant pancreas after pancreatectomy for IPMNs; thus, careful long-term follow-up with periodic surveillance, at least every 6 months, is warranted.

DOI： 10.3892/mco.2018.1556

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AIM: We aimed to evaluate the short- and long-term surgical outcomes of salvage hepatectomy for recurrent hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) and/or transcatheter arterial chemoembolization (TACE). METHODS: We reviewed the surgical outcomes of 90 recurrent HCC patients after RFA and/or TACE (salvage group) and 490 HCC patients without preoperative treatment (primary group). We performed 1:1 propensity score matching (PSM) between the 2 groups and matched 87 patients in each group. RESULTS: Before PSM, the salvage group was pathologically more advanced than the primary group. After PSM, there were no significant differences in the clinicopathological features between the groups. The outcomes of propensity score-matched groups were compared and there was no statistically significant difference between the 2 groups regarding perioperative outcomes and survival. Univariate and multivariate analyses of propensity score-matched HCC patients revealed that stage, tumor size, differentiation, and portal vein invasion were independent prognostic factors for survival. Preoperative RFA and/or TACE was not a prognostic factor in a propensity score-matched cohort. CONCLUSIONS: The short- and long-term surgical outcomes of the primary and salvage groups were similar under the matched clinicopathological background. Salvage hepatectomy might be an acceptable treatment for recurrent HCC patients after RFA and/or TACE.

DOI： 10.1159/000480521

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

BACKGROUND: Because hepatectomy is not recommended in patients with stage B hepatocellular carcinoma (HCC) of the Barcelona Clinic Liver Cancer (BCLC) staging, we evaluated the survival outcomes of hepatectomy for stage B in the BCLC system. METHODS: Data were collected from 297 consecutive adult stage B patients who underwent curative hepatectomy for HCC between 1996 and 2014 in Hokkaido University Hospital. Overall survival (OS), disease-free survival (DFS), and risk factors were analyzed using the Kaplan-Meier method. Independent prognostic factors were evaluated using a Cox proportional hazards regression model. AP-factor (alpha-fetoprotein [AFP] × protein induced by vitamin K absence or antagonism factor II [PIVKA-II]) was categorized according to the serum concentrations of AFP and PIVKA-II: AP1 (AFP < 200 ng/ml and PIVKA-II < 100 mAU/ml), AP2 (AFP × PIVKA-II < 105), and AP3 (AFP × PIVKA-II ≥ 105). RESULTS: There were 130 deaths among our 297 stage B patients (43.8%). The causes of death in these cases were HCC recurrence (n = 106; 81.5%), liver failure (n = 7; 5.4%), and other causes (n = 17; 16.1%). The operative mortality rate was 0.34% (1/297). The 5-year OS and DFS rates for the stage B cases were 54.3 and 21.9%, respectively. By multivariate analysis, tumor number and AP-factor were risk factors for both survival and recurrence that were tumor related and could be evaluated preoperatively. The study patients with stage B HCC were classified into three groups by tumor number (B1, 1; B23, 2 or 3; B4over: ≥4) and into three groups stratified by AP-factor (AP1, AP2, and AP3). The 5-year OS rates of B1, B23, and B4over were 63.6, 52.3, and 29.0%. The 5-year OS rates of AP1, AP2, and AP3 were 67.6, 65.2, and 39.1%. Stratified by the 5-year OS rate, stage B HCC patients were classified into three subgroups (A-C).The 5-year OS rates of groups A (B1 or B23 and AP-1 or AP-2), B (B1 or B23 and AP-3, or B4over and AP-1 or AP-2), and C (B4over and AP-3) were 69.5, 43.7, and 21.3%. CONCLUSION: Stage B HCC patients with a tumor number ≤ 3 and/or AP-factor < 1 × 105 show acceptable 5-year OS rates and could be treated by hepatectomy.

DOI： 10.1186/s12957-017-1229-x

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

BACKGROUND: The aims of this study were to investigate predictive factors for microscopic portal venous invasion (mPVI) in hepatocellular carcinoma (HCC) and whether anatomical liver resection (ALR) was useful in such cases. METHODS: We analyzed 852 patients with HCC without macroscopic portal venous invasion who were treated at our hospital between January 1990 and May 2014. These patients were stratified into a microscopic portal venous invasion group (mPVI group; n = 153) and non-microscopic portal venous invasion group (NmPVI group; n = 699). RESULTS: PIVKA-II ≥100 mAU/ml, a tumor size ≥5 cm, a confluent lesion, and poor differentiation were found to be independent risk factors for mPVI. Among the mPVI group who had single HCC under 5 cm, serum albumin level <4.0 g/dl, PIVKA-II ≥100 mAU/ml, a positive surgical margin, and non-ALR (NALR) were independent unfavorable prognostic factors for overall survival (OS). PIVKA-II ≥100 mAU/ml, a positive surgical margin and NALR were independent unfavorable prognostic factors for relapse-free survival (RFS). ALR was significantly favorable factor for both OS and RFS of the mPVI group who had single HCC under 5 cm. CONCLUSIONS: Even if no portal venous invasion is detectable in HCC patients preoperatively, a PIVKA-II ≥100 mAU/ml, tumor size ≥5 cm, and a confluent lesion indicate a high risk of mPVI. ALR should be considered for the patients with these characteristics because it is a favorable prognostic factor in these cases with mPVI.

DOI： 10.1007/s00268-017-3964-0

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

症例は67歳の男性で,慢性B型肝炎,アルコール性肝障害にて近医通院中,血液検査にてAFP 9,133ng/mlと高値であり,腹部超音波検査とCTから肝S1/8の48mm大の肝細胞癌と診断され,当科紹介となった.診断より2ヵ月後の入院時のCTでは腫瘍は造影効果に乏しく,中肝静脈腫瘍栓を伴っており,AFPは54.7ng/mlと著明に低下していた.低分化型肝細胞癌の診断にて尾状葉・中肝静脈合併左肝切除を施行した.切除標本の病理組織学的検査所見では,病変および肝静脈腫瘍栓は線維芽細胞の増生や組織球・リンパ球を主体とする炎症性細胞の浸潤を認める壊死組織であり,viableな癌細胞は認めず,肝細胞癌が自然消退したものと考えられた.肝細胞癌の完全自然退縮は極めてまれであり,腫瘍が残存していることが多いため,壊死を疑う症例でも外科的治療介入を考慮するべきである.(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01117&link_issn=&doc_id=20170829330005&doc_link_id=10.5833%2Fjjgs.2016.0167&url=https%3A%2F%2Fdoi.org%2F10.5833%2Fjjgs.2016.0167&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the impact of huge (≥10 cm) hepatocellular carcinoma (HCC) to the recurrence pattern and the prognosis after hepatectomy. METHODS: 574 patients who underwent hepatectomy by 17 surgeons (Open 536 and Laparoscopic 38) for HCC without major vascular invasion from 1990 to 2013 at single institute were retrospectively analyzed. RESULTS: Huge tumor, age, HCV, multiple tumors and microscopic portal invasion are independent risk factors for overall survival (OS), and huge tumor, ICGR15 ≥16%, multiple tumors, moderate/poor histology, microscopic portal invasion and a positive pathological margin are risk factors for relapse-free survival (RFS). The 5-year OS and RFS of patients with huge HCC (n = 53) (42.9 and 14.2%) were significantly worse than those of patients with HCC <10 cm (n = 521) (71.3 and 33.1%). Huge tumor is an independent risk factor for initial extra-hepatic recurrence (Hazard ratio 7.86, P < 0.0001). The 5-year OS of patients with initial extra-hepatic recurrence (n = 55) was significantly worse than patients with intra-hepatic recurrence (n = 338) (16.8 vs. 50.5%). CONCLUSIONS: Huge HCC (≥10 cm) is an independent risk factor due to a high risk for initial extra-hepatic recurrence. Future systemic adjuvant therapy is needed for these patients. J. Surg. Oncol. 2017;115:324-329. © 2016 Wiley Periodicals, Inc.

DOI： 10.1002/jso.24501

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Language：Japanese   Publisher：The Japan Society for Organ Preservation and Biology  

Extensive efforts to repair the extended criteria donor (ECD) grafts by machine perfusion has been reported. Although the optimal conditions, such as the perfusate, temperature, time, and the device, has not yet been established, organ perfusion is generally accepted as a promising concept. Here, we review current progress of antioxidant and anti-inflammatory treatment by induction of protective transcription factors (TFs), Nrf2 in relation to the other TFs (AP-1 and NF-kB). These TFs are mainly regulated by the redox status of intracellular thiols. Possible interactions of the TFs and the methods to regulate their activity have been described.

DOI： 10.11378/organbio.24.169

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Hydrogen gas reduces ischemia and reperfusion injury (IRI) in the liver and other organs. However, the precise mechanism remains elusive. We investigated whether hydrogen gas ameliorated hepatic I/R injury after cold preservation. Rat liver was subjected to 48-h cold storage in University of Wisconsin solution. The graft was reperfused with oxygenated buffer with or without hydrogen at 37° for 90 min on an isolated perfusion apparatus, comprising the H2 (+) and H2 (-) groups, respectively. In the control group (CT), grafts were reperfused immediately without preservation. Graft function, injury, and circulatory status were assessed throughout the perfusion. Tissue samples at the end of perfusion were collected to determine histopathology, oxidative stress, and apoptosis. In the H2 (-) group, IRI was indicated by a higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) leakage, portal resistance, 8-hydroxy-2-deoxyguanosine-positive cell rate, apoptotic index, and endothelial endothelin-1 expression, together with reduced bile production, oxygen consumption, and GSH/GSSG ratio (vs. CT). In the H2 (+) group, these harmful changes were significantly suppressed [vs. H2 (-)]. Hydrogen gas reduced hepatic reperfusion injury after prolonged cold preservation via the maintenance of portal flow, by protecting mitochondrial function during the early phase of reperfusion, and via the suppression of oxidative stress and inflammatory cascades thereafter.

DOI： 10.1111/aor.12710

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

We describe and assess our technique of preceding diaphragm resection and partial mobilization of the hepatic right lobe to treat a huge hepatic tumor with diaphragm invasion. The right hepatic artery and portal vein were divided at the hepatic hilum, and the mesenteries were then dissected with a vessel sealing device (LigaSure Impact™). The invaded diaphragm was dissected roundly using a vessel sealing device and the right lobe was partially mobilized. A soft catheter was then passed along the anterior aspect of the retrohepatic inferior vena cava and the liver parenchyma was dissected via a liver hanging maneuver. We performed eight hepatectomies using this technique. The median blood loss was 532.5 ml and the mean excised liver weight was 1859 g. Our results demonstrate the safety and efficiency of the preceding diaphragm resection and partial mobilization technique using a vessel sealing device for right hepatectomy to resect a very large tumor with diaphragm invasion.

DOI： 10.1007/s00595-016-1306-8

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BACKGROUND: This study aimed to evaluate the short- and long-term outcomes of hepatectomy for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT), including cases with obstructive jaundice. METHODS: The study reviewed 42 HCC patients with BDTT, including six patients who needed preoperative biliary drainage due to obstructive jaundice, and 732 HCC patients without BDTT. The authors analyzed the impact of BDTT on the surgical outcomes and assessed the outcomes of hepatectomy for patients presenting with obstructive jaundice. RESULTS: The HCC patients with BDTT, almost all with stage 3 or 4 disease, had increased alpha-fetoprotein expression, larger tumors, and more portal vein invasion status. The survival of the HCC patients with BDTT was significantly inferior to that of the patients without BDTT (p = 0.0003). Survival did not differ significantly between the HCC patients with BDTT and those without BDTT when the two groups were matched by stage (p = 0.3366). The HCC patients with BDTT who presented with obstructive jaundice demonstrated outcomes similar to those for the HCC patients with BDTT who did not present with obstructive jaundice in terms of the overall survival rate (p = 0.5469). The perioperative outcomes for the HCC patients with BDTT did not depend on the presence or absence of preoperative jaundice. No patients in either BDTT group demonstrated 90-day mortality in this study. CONCLUSIONS: Hepatectomy should be considered for HCC patients with BDTT, even for patients with obstructive jaundice, because the surgical outcomes equivalent to those for HCC without BDTT can be achieved.

DOI： 10.1245/s10434-016-5174-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BAISHIDENG PUBLISHING GROUP INC  

AIM: To evaluate the usefulness of the functional hepatic resection rate (FHRR) calculated using 3D computed tomography (CT)/(99m)Tc-galactosyl-human serum albumin (GSA) single-photon emission computed tomography (SPECT) fusion imaging for surgical decision making. METHODS: We enrolled 57 patients who underwent bi- or trisectionectomy at our institution between October 2013 and March 2015. Of these, 26 patients presented with hepatocellular carcinoma, 12 with hilar cholangiocarcinoma, six with intrahepatic cholangiocarcinoma, four with liver metastasis, and nine with other diseases. All patients preoperatively underwent three-phase dynamic multidetector CT and (99m)Tc-GSA scintigraphy. We compared the parenchymal hepatic resection rate (PHRR) with the FHRR, which was defined as the resection volume counts per total liver volume counts on 3D CT/(99m)Tc-GSA SPECT fusion images. RESULTS: In total, 50 patients underwent bisectionectomy and seven underwent trisectionectomy. Biliary reconstruction was performed in 15 patients, including hepatopancreatoduodenectomy in two. FHRR and PHRR were 38.6 ± 19.9 and 44.5 ± 16.0, respectively; FHRR was strongly correlated with PHRR. The regression coefficient for FHRR on PHRR was 1.16 (P < 0.0001). The ratio of FHRR to PHRR for patients with preoperative therapies (transcatheter arterial chemoembolization, radiation, radiofrequency ablation, etc.), large tumors with a volume of > 1000 mL, and/or macroscopic vascular invasion was significantly smaller than that for patients without these factors (0.73 ± 0.19 vs 0.82 ± 0.18, P < 0.05). Postoperative hyperbilirubinemia was observed in six patients. Major morbidities (Clavien-Dindo grade ≥ 3) occurred in 17 patients (29.8%). There was no case of surgery-related death. CONCLUSION: Our results suggest that FHRR is an important deciding factor for major hepatectomy, because FHRR and PHRR may be discrepant owing to insufficient hepatic inflow and congestion in patients with preoperative therapies, macroscopic vascular invasion, and/or a tumor volume of > 1000 mL.

DOI： 10.3748/wjg.v22.i17.4373

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Elsevier USA  

Cellular survival and death are at least partially regulated by the phosphorylation of proteins. A chaperon protein, 14-3-3ζ, regulates the activity of many proteins by covering the phosphorylation site within a 14-3-3 binding motif. Therefore, regulation of 14-3-3ζ activity may affect the fate of cells subjected to cold preservation and/or hypothermic oxygenated conditions. The present study assessed whether 14-3-3ζ protects cells from hypothermic oxygenation-induced injury and clarified its role in mitochondrial functions. Human renal tubular cell line HK-2 or 14-3-3ζ-overexpressed HK-2 (ζHK-2) cells were subjected to 72 hours of normoxic cold preservation in UW solution with or without antioxidants and hydroperoxides. Cellular death, adenosine triphosphate (ATP) content, and MTT catabolism were evaluated. Deferoxamine treatment reduced cellular death and augmented ATP content in both cell types. These indices were higher in ζHK-2, regardless of deferoxamine treatment. Exposure to hydroperoxides did not affect cellular death in either cell type, whereas hydroperoxide supplementation significantly reduced ATP content, except for low-dose hydrogen peroxide in HK-2 cells. MTT assay at normal state showed higher values in ζHK-2 cells, whereas it was impaired by hydroperoxides in both cell types. These results suggest that accumulation of hydroperoxides as a byproduct of the augmented oxidative phosphorylation by 14-3-3ζ overexpression causes mitochondrial dysfunction. In conclusion, despite possessing many potentially protective functions, 14-3-3ζ exacerbates cellular injury under hypothermic oxygenated conditions. 14-3-3ζ accelerates mitochondrial functions together with iron-dependent oxidative damage. Although further investigations are necessary, upregulation of 14-3-3ζ could be a method to maintain mitochondrial function under hypothermic oxygenated conditions, as shown in hypothermic machine preservation of renal grafts, when appropriate antioxidant treatment is administered.

DOI： 10.1016/j.transproceed.2015.09.066

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：E-MED  

BACKGROUND: We hypothesized that indocyanine green (ICG) fluorescence patterns using Clairvivo OPT in resected liver specimens could confirm hepatocellular carcinoma (HCC) better than earlier commercial imaging systems. This preclinical trial evaluated the effectiveness of fluorescence imaging as an intraoperative cancer navigation tool. METHODS: ICG fluorescence images of resected specimens from 190 patients with HCC were classified into two groups according to whether high fluorescence was seen in the HCC (high cancerous [HC] group) or in the surrounding liver tissue (high surrounding [HS] group). The HC and HS groups were sub-classified into whole and partial types and whole and ring types, respectively. RESULTS: The HC group had significantly higher prevalence of esophageal or gastric varices, and worse liver function than patients in the HS group. The HC group also had a higher percentage of limited resection cases than did the HS group. Cirrhotic liver histology was significantly more common in the HC group than in the HS group. Multivariate analysis revealed that the HC group was a predictive factor for cirrhosis in HCC patients. Among the HC patients, a higher percentage of well-differentiated HCC cases were seen in the partial-type subgroup than in the whole-type subgroup (23/48 (48 %) vs. 7/68 (10 %)). In the HS group, the ring-type subgroup had a higher percentage of poorly differentiated HCC cases than did the whole-type subgroup (6/37 (16 %) vs. 0/37 (0 %)). CONCLUSION: Tumor differentiation and fibrosis in the non-cancerous liver parenchyma could affect ICG fluorescence imaging in HCC. ICG fluorescence imaging may be a good indication for fibrosis stage. In future, we will try to evaluate fluorescence imaging with ICG for intraoperative cancer navigation in HCC, using a portable near-infrared fluorescence imaging system.

DOI： 10.1186/s40644-016-0064-6

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Sorafenib is the first molecularly targeted drug recommended as a treatment for advanced hepatocellular carcinoma (HCC). Herein, we report the efficacy of sorafenib for extrahepatic recurrence of HCC. From September 2004 to March 2015, 47 patients who were diagnosed with recurrent HCC after liver resection were treated with sorafenib. The overall response rate was 17.5% (complete response: CR 1, partial response: PR 6, stable disease: SD 17, progressive disease: PD 13, SD beyond PD 3), and the disease control rate was 67.5%. The median time to disease progression, including extrahepatic recurrence, was significantly better than in the group with only intrahepatic metastasis (p=0.034). Therefore, sorafenib might be an effective treatment for extrahepatic recurrence of HCC.

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

BACKGROUND AND PURPOSE: Hydrogen sulfide (H2S) ameliorates hepatic ischemia and reperfusion injury (IRI), but the precise mechanism remains elusive. We investigated whether sodium hydrogen sulfide (NaHS), a soluble derivative of H2S, would ameliorate hepatic IRI, and if so, via what mechanism. METHODS: Mice were subjected to partial warm ischemia for 75 min followed by reperfusion. Either NaHS or saline was administered intravenously 10 min before reperfusion. The liver and serum were collected 3, 6, and 24 h after reperfusion. RESULTS: In the NaHS(-) group, severe IRI was apparent by the ALT leakage, tissue injury score, apoptosis, lipid peroxidation, and inflammation (higher plasma TNF-α, IL-6, IL-1β, IFN-γ, IL-23, IL-17, and CD40L), whereas IRI was significantly ameliorated in the NaHS(+) group. These effects could be explained by the augmented nuclear translocation of Nrf2, and the resulting up-regulation of HO-1 and thioredoxin-1. Phosphorylation of the PDK-1/Akt/mTOR/p70S6k axis, which is known to mediate pro-survival and anti-apoptotic signals, was significantly augmented in the NaHS(+) group, with a higher rate of PCNA-positive cells thereafter. CONCLUSION: NaHS ameliorated hepatic IRI by direct and indirect anti-oxidant activities by augmenting pro-survival, anti-apoptotic, and anti-inflammatory signals via mechanisms involving Nrf-2, and by accelerating hepatic regeneration via mechanisms involving Akt-p70S6k.

DOI： 10.1007/s00595-014-1064-4

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

BACKGROUND: Reports detailing microscopic observations of indocyanine green (ICG) fluorescence imaging (IFI) in hepatocellular carcinoma (HCC) and metastatic liver cancer are rare. We were able to perform macro- and microscopic IFI results in postoperative paraffin-embedded tissue samples and formalin-fixed specimens from liver tumors. METHODS: Between April 2010 and March 2014, 19 patients with HCC or liver metastases of colorectal tumors underwent liver resection. ICG solution was injected into the peripheral vein from 14 to 2 days prior to operation. We observed liver tumor IFI during the laparotomy and IFI in resected liver sections using a photo dynamic emission (PDE) camera. The IFI of paraffin-embedded tissue samples was observed using a charge-coupled device (CCD) camera. Moreover, we microscopically performed tissue section IFI using a fluorescence microscope with an ICG-B-NQF. RESULTS: We performed that IFI characteristics depended on tumor type macroscopically and microscopically. In normal liver tissue, fluorescence consistent with the bile canaliculus was observed. HCC had heterogeneous IFI, forming a total or partial tumor and rim pattern. In metastatic carcinoma, we performed that non-tumor cells in the marginal region showed fluorescence and tumor cells in the central region did not fluoresce. CONCLUSIONS: We confirmed that the variations of ICG fluorescence imaging patterns reflect different tumor characteristics in not only macroscopic imaging as previous reports but also microscopic imaging. Moreover, the ICG fluorescence method is useful for postoperative pathological detection of microscopic lesions in histopathological specimens. ICG fluorescence in paraffin-embedded tissue samples and formalin-fixed specimens is preserved in the long term.

DOI： 10.1186/s12957-015-0615-5

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

BACKGROUND: The aim of this study was to analyze the clinicopathological characteristics and the prognostic factors for survival and recurrence of young patients who had undergone hepatectomy for hepatocellular carcinoma. METHODS: Between 1990 and 2010, 31 patients aged 40 years or younger (younger patient group) among 811 consecutive patients with hepatocellular carcinoma who had undergone primary hepatectomy were analyzed with regard to patient factors, including liver function, tumor factors and operative factors. The clinicopathological characteristics of the younger patients were compared with those of patients over the age of 40 (older patient group). Then the prognostic factors of the younger patients were analyzed. Continuous variables were expressed as the means ± standard deviation and compared using the χ2 test for categorical variables. Overall survival and recurrence-free survival rates were determined by the Kaplan-Meier method and analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis. RESULTS: In the younger patients, the rates of HBs-antigen-positivity, high alpha-fetoprotein, portal invasion, intrahepatic metastasis, large tumors, low indocyanin green retention rate at 15 minutes, and anatomical resection were significantly higher than the same measures in the older patients. The five-year overall survival rate of the young patients was 49.6%. The prognostic factors of survival were HCV-antibody-positivity and low albumin status. Prognostic factors of recurrence were multiple tumors and the presence of portal invasion. CONCLUSIONS: In younger patients, survival appeared to be primarily affected by liver function, while recurrence was affected by tumor factors. Young patients with hepatocellular carcinoma should be aggressively treated with hepatectomy due to their good pre-surgical liver function.

DOI： 10.1186/1477-7819-11-52

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：北海道外科学会  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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OBJECTIVE: Treatment results of pancreatic head carcinoma are not good and long-term survival, especially in nonresectable cases is extremely difficult to obtain. The case reported here is of nonresectable pancreatic head carcinoma in which S-1+gemcitabine (GEM) proved to be effective. CASE: A 70-year-old male. The patient initially complained of epigastralgia. Jaundice was also noted and upon further study, pancreatic head carcinoma, portal vein and common hepatic artery infiltration along with duodenal infiltration were diagnosed. Gastrojejunostomy and cholecystectomy were performed with a preoperative diagnosis of Phb, TS2 infiltrative type T4, CH (+), DU (+), S (+), RP (-), PV (+), Ach (+), PLX, OO (-), N0, M0, and Stage IVa. Perioperative findings showed no hepatic or peritoneal metastases. Following surgery, S-1+ GEM (S-1 100 mg/day, day 1-14; GEM 1,000 mg/m(2) was administered on day 8 and day 15 for 2 weeks followed by one week of no administration) was started. After completing 2 courses, there was no change in the tumor, but after finishing the sixth course, there was a notable reduction in tumor size, and after finishing the 10th course, a further reduction was noted. Currently at the end of the 14th course, the tumors are unidentifiable upon imaging. At 1 year and 5 months from the initial diagnosis, there has been no recurrence and chemotherapy is being continued. In the case reported here, there have been no adverse side-effects from the S-1+GEM therapy, it is a safe method which does not lower QOL in patients with unresectable pancreatic carcinoma, and we can look forward to the possibility of extended survival times. CONCLUSION: In the case of unresectable pancreatic carcinoma, S-1+GEM therapy may be able to provide an improved long-term prognosis.

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：日本外科代謝栄養学会  

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Language：Japanese   Publisher：北海道外科学会  

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Language：Japanese   Publisher：北海道外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本ストーマ・排泄リハビリテーション学会  

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Language：Japanese   Publisher：北海道外科学会  

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Language：Japanese   Publisher：(一社)日本農村医学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：(一社)日本旅行医学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Authorship：Lead author   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Authorship：Corresponding author   Language：Japanese   Publisher：(一社)日本消化器外科学会  

症例は18歳の男性で,健診でのγ-GTP高値と近医での腹部超音波検査で肝外側区に巨大腫瘤を認め,当院を紹介受診した.Dynamic CTで肝外側区に動脈相で濃染され,平衡相で造影効果が遷延する最大径18cmの腫瘤を認めた.PIVKA-IIは481mAU/mlと高値であった.肝細胞腺腫(hepatocellular adenoma;以下,HCAと略記)を第一に考えたが,肝細胞癌の可能性も除外できず,破裂の危険性も鑑みて切除の方針とし,肝左葉切除を施行した.病理組織検査では,HCAと診断された.免疫染色検査では,CD34(+),SAA(+),β-catenin(-),L-FABP(-)でinflammatory typeと分類された.術後経過は良好であり,第7病日に退院した.若年男性の巨大肝腫瘤の鑑別診断としてHCAも念頭に置く必要があり,外科的切除は診断および治療に寄与すると考えられた.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J01117&link_issn=&doc_id=20210519510004&doc_link_id=10.5833%2Fjjgs.2020.0055&url=https%3A%2F%2Fdoi.org%2F10.5833%2Fjjgs.2020.0055&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Authorship：Corresponding author   Language：Japanese   Publisher：(一社)日本消化器外科学会  

症例は61歳の男性で,52歳時に肝細胞癌(hepatocellular carcinoma;以下,HCCと略記)に対して右三区域切除+横隔膜合併切除術,56歳時に肺転移に対して胸腔鏡下左上葉・下葉部分切除術を施行した.59歳時にPIVKA-IIの上昇を認め,残肝再発の診断で肝動脈化学塞栓術を施行した.術後の治療効果判定ではTE4となり,PIVKA-IIも低下した.しかし,翌年にPIVKA-IIの再上昇を認め,精査にて右下腿部腓腹筋に5cmの腫瘤を認めた.経皮的針生検を施行し,HCC腓腹筋転移の診断で拡大腫瘍切除術+広背筋遊離皮弁+植皮術を施行した.病理組織診断ではHCC,mod to porであり静脈侵襲を認めた.術後経過は良好で,術後16ヵ月現在無再発生存中である.HCCの骨格筋転移はまれではあるが,自験例のように切除により予後の改善が期待できる可能性がある.(著者抄録)

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Authorship：Corresponding author   Language：Japanese   Publisher：日本臨床外科学会  

症例は生来健康な17歳の男性.腹部膨満を契機に,肝右葉に径25cmの肝腫瘍が発見された.肝炎ウイルスマーカーは陰性,AFPは正常値でPIVKA-IIが12,738mAU/mlと異常高値を認めた.造影CTおよびMRIで腫瘍は漸増性の造影効果を伴っており,一部造影効果の乏しい不整形領域を認めた.腫瘍の大部分はEOB-MRIの肝細胞相で取り込み低下は軽度であり,肝細胞癌としては非典型的であったが悪性の可能性が否定できないことと破裂の危険性があることから手術適応と考え,肝右3区域切除を施行した.術後経過は良好で,術後13日目に退院となった.病理診断はβ-catenin活性化型肝細胞腺腫であり,悪性所見は認めなかった.PIVKA-IIは切除後速やかに低下した.今回,若年男性に発生した稀な巨大肝細胞腺腫の1切除例を経験したため,文献的考察を加えて報告する.(著者抄録)

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：北海道外科学会  

肝胆道悪性腫瘍に対する大量肝切除を安全に施行するために門脈塞栓術(PVE)は有用な方法である。PVEはMakuuchiらやKinoshitaらが臨床応用し、今や広く普及している。肝切除においては肝予備能で決まる切除量の安全限界内での過不足ない肝切除が求められる。しかしながら、PVEを施行しても十分に予定残肝の肥大が得られない症例も存在する。また、PVE後に肝体積の変化のみならず肝臓の「機能」が非塞栓葉にシフトすることも注目されている。当科では安全な肝切除を行うために、大量肝切除の際には積極的にPVEを用いている。また、これまでPVEにおける門脈血流変化と非塞栓葉の体積変化について評価を行ってきた。当科における肝予備能評価とPVEを用いた肝切除戦略、PVE後の変化および非塞栓葉増大に関わる因子について述べる。(著者抄録)

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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AMPK(AMP-activated protein kinase)はエネルギー代謝における主要な調節分子であるが、近年では、脂質代謝における重要な制御分子であることや虚血再灌流障害における抗酸化、抗炎症、抗アポトーシス、オートファジー調節作用に加えて、腫瘍細胞の増殖抑制作用も報告されている。多様な働きを有するAMPKについて、主に脂肪代謝、虚血再灌流障害、腫瘍との関連を中心に概説した。

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Authorship：Lead author   Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

AMPK(AMP-activated protein kinase)はエネルギー代謝における主要な調節分子であるが、近年では、脂質代謝における重要な制御分子であることや虚血再灌流障害における抗酸化、抗炎症、抗アポトーシス、オートファジー調節作用に加えて、腫瘍細胞の増殖抑制作用も報告されている。多様な働きを有するAMPKについて、主に脂肪代謝、虚血再灌流障害、腫瘍との関連を中心に概説した。

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Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞肝切除後腹水は,残肝が小さい場合や肝硬変など術後肝不全の病態と密接な関連性があるが,それに加えて腹腔内操作に伴うリンパ漏,胆汁漏などによる炎症,門脈血栓による門脈圧亢進などさまざまな原因により発生しうる複合的な病態である.腹水の治療の原則は利尿薬およびアルブミン製剤などの投与であるが,難治性の場合は腹腔ドレナージを考慮する必要がある.術前の綿密な肝予備能評価に加え,腹腔内操作に伴うリンパ漏に対しては手術手技の工夫,胆汁漏に伴う炎症や門脈血栓に対してはその原因の治療など,その病態の正確な理解と対処が肝切除後の腹水の治療には重要である.

DOI： 10.15106/j_geka80_609

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は63歳、男性。肝機能異常を認め、腹部造影CTで肝S4、S8を主座とする99mm大の乏血性腫瘍を認め、肝内胆管癌の診断となった。左右のグリソン鞘に浸潤を認め、根治切除不能と判断された。放射線療法併用肝動注化学療法を施行したところ、PR相当の腫瘍縮小を認め腫瘍マーカー陰性化も認めたため、手術適応に関して当科に紹介された。左グリソン鞘との距離を認め、門脈塞栓術後に肝右三区域切除術を施行した。病理結果は肝内胆管癌、pT3N0M0、pStage IIIであった。腫瘍断端が露出していたため、術後7週目より術後補助化学療法としてgemcitabineを静注で1年間投与した。術後1年5ヵ月経過し、無再発生存中である。局所過伸展による切除不能肝内胆管癌に対して、術前放射線療法併用肝動注化学療法が有効な手段となり得ると考えられた。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00296&link_issn=&doc_id=20180424490019&doc_link_id=%2Fab8gtkrc%2F2018%2F004504%2F020%2F0664-0666%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2018%2F004504%2F020%2F0664-0666%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(株)日本臨床社  

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DOI： 10.3919/jjsa.78.494

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DOI： 10.3919/jjsa.78.578

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

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症例は67歳の男性で,慢性B型肝炎,アルコール性肝障害にて近医通院中,血液検査にてAFP 9,133ng/mlと高値であり,腹部超音波検査とCTから肝S1/8の48mm大の肝細胞癌と診断され,当科紹介となった.診断より2ヵ月後の入院時のCTでは腫瘍は造影効果に乏しく,中肝静脈腫瘍栓を伴っており,AFPは54.7ng/mlと著明に低下していた.低分化型肝細胞癌の診断にて尾状葉・中肝静脈合併左肝切除を施行した.切除標本の病理組織学的検査所見では,病変および肝静脈腫瘍栓は線維芽細胞の増生や組織球・リンパ球を主体とする炎症性細胞の浸潤を認める壊死組織であり,viableな癌細胞は認めず,肝細胞癌が自然消退したものと考えられた.肝細胞癌の完全自然退縮は極めてまれであり,腫瘍が残存していることが多いため,壊死を疑う症例でも外科的治療介入を考慮するべきである.(著者抄録)

DOI： 10.5833/jjgs.2016.0167

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DOI： 10.3919/jjsa.77.2799

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Cellular survival and death during cold storage and hypothermic perfusion are regulated by intracellular signal, however, precise mechanisms remain elusive. Although the effector proteins of cellular fate work actually during 6 to 24 hours after rewarming and reoxygenation, the triggering events have already been regulated during organ procurement, transportation, and implantation before reperfusion. In this review, we summarize some potential mechanisms of regulating intracellular signals, mainly focused on the energy production and post-translational regulation under hypothermic conditions.<br>A chaperon protein, 14-3-3&zeta;, regulates over 200 of the protein activity by covering the phosphorylation site within a 14-3-3 binding motif. Sirtuins also regulates many proteins directly and indirectly relates to the cell survival and death under some difficult conditions including cold and/or hypoxic insults. Sirtuins regulate many mitochondrial proteins primarily by deacetylation instead of ATP consuming processes. Further, sirtuins and 14-3-3s interact each other and sharing some target proteins, especially relating energy production and mitochondrial functions. Although these facts have been reported in ectotherms, hibernators, to human, little is known about its role in organ preservation, perfusion, and transplantation. Here, we reviewed its potential significance for the future research in the field of organ repair.

DOI： 10.11378/organbio.23.173

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