担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40792-024-02058-7

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出版者・発行元：南江堂  

DOI： 10.15106/j_geka86_1288

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：British Journal of Cancer  

Background: Identification of homologous recombination deficiency (HRD) remains a challenge in advanced pancreatic cancer (APC). We investigated the utility of circulating tumour DNA (ctDNA) profiling in the assessment of BRCA1/2 and ATM mutation status and treatment selection in APC. Methods: We analysed clinical and ctDNA data of 702 patients with APC enroled in GOZILA, a ctDNA profiling study using Guardant360. Results: Inactivating BRCA1/2 and ATM mutations were detected in 4.8% (putative germline, 3.7%) and 4.4% (putative germline, 0.9%) of patients, respectively. Objective response (63.2% vs. 16.2%) and PFS (HR 0.55, 95% CI 0.32–0.93) on platinum-containing chemotherapy were significantly better in patients with putative germline BRCA1/2 (gBRCA) mutation than those without. In contrast, putative gBRCA mutation had no impact on the efficacy of gemcitabine plus nab-paclitaxel. In 2 patients treated with platinum-containing therapy, putative BRCA2 reversion mutations were detected. Three of seven patients with somatic BRCA mutations responded to platinum-containing therapy, while only one of four with putative germline ATM mutations did. One-third of somatic ATM mutations were in genomic loci associated with clonal haematopoiesis. Conclusion: Comprehensive ctDNA profiling provides clinically relevant information regarding HRD status. It can be a practical, convenient option for HRD screening in APC.

DOI： 10.1038/s41416-024-02834-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40792-024-02033-2

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PubMed

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Surgery Today  

Purpose: To validate the reliability of fibrosis markers as predictors of graft survival in living donor liver transplantation (LDLT) recipients. Methods: We reviewed data retrospectively, from 163 patients who underwent adult LDLT with preoperative measurements of type IV collagen (CIV), Mac-2 binding protein glycosylation isomer (M2BPGi), and hyaluronic acid (HA). Patients were divided into high and low groups for each biomarker, based on optimal cutoff values, and graft loss within 6 months was evaluated in each group. Results: The high CIV level group showed significantly lower 6-month graft survival rates and significantly higher rates of postoperative sepsis and sepsis from pneumonia. However, the groups with high and low M2BPGi levels and those with high and low HA levels did not show significant differences in 6-month graft survival rates or rates of postoperative sepsis. Multivariate analysis revealed that a CIV level ≥ 590 was a significant predictor of graft loss within 6 months, postoperative sepsis, and sepsis from pneumonia. Conclusion: Unlike other fibrosis markers, preoperative CIV levels can predict graft survival, postoperative sepsis, and sepsis from pneumonia after LDLT.

DOI： 10.1007/s00595-024-02941-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

Aim: Reactivation of hepatitis B virus (HBV) after liver transplantation (LT) remains a problem; thus, development of more effective HBV reactivation prophylaxis is desirable. We evaluated the efficacy of a combination of a long-term nucleotide analog (NA), such as entecavir (ETV) or tenofovir alafenamide (TAF), and short-term hepatitis B immunoglobulin (HBIG) in preventing HBV reactivation and compared it with conventional HBV prophylaxis. Methods: Between February 1999 and August 2023, 135 patients underwent living-donor liver transplantation for liver cirrhosis or acute liver failure caused by HBV infection or received an LT from a hepatitis B core antibody-positive donor. Recipients who had undergone LT were classified as being in the first or second era (namely until September 2017 and from October 2017), respectively, and outcomes of prophylaxis against HBV reactivation were compared between the two eras. Results: In the second era, recipients with HBV-related disease or who had received hepatitis B core antibody-positive liver received combination therapy with short-term HBIG and an NA such as TAF and ETV long-term. The duration of HBIG treatment was markedly shorter than in the first era in both categories of patients and HBIG could be discontinued in all cases. Surprisingly, we observed HBV reactivation in the first era, but not in the second era, in both groups. Conclusions: We have established a protocol for prophylaxis against HBV reactivation using a combination of short-term HBIG and long-term NA. This protocol was found to be sufficient to prevent HBV reactivation after LT.

DOI： 10.1111/hepr.14110

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担当区分：責任著者   記述言語：日本語   出版者・発行元：一般財団法人 日本消化器病学会  

<p>肝細胞癌に対する肝移植の保険適用は5-5-500基準内もしくはミラノ基準内であり，肝細胞癌治療アルゴリズムではChild-Pugh分類C症例に推奨されている．肝移植は良好な治療成績をあげているが，一定数の再発を認める．術前因子や病理学的因子を用いた再発予測の検討や，ダウンステージの有用性が報告されている．肝移植後再発症例の予後不良因子として移植後早期再発，AFP高値，根治治療不能が報告されており，mTOR阻害剤を用いた免疫抑制剤の調節，可能な場合における積極的外科治療や局所療法の介入，マルチキナーゼ阻害剤を中心とした薬物療法のシークエンス治療が，肝移植後再発の治療において重要となる．</p>

DOI： 10.11405/nisshoshi.121.729

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40792-024-02014-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/jhbp.1345

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

Aim: Sarcopenia is reportedly associated with a poor prognosis in patients who undergo living-donor liver transplantation (LDLT), most of whom are not able to tolerate muscle strengthening exercise training. Myostatin is one of the myokines and a negative regulator of skeletal muscle growth. The clinical feasibility of an electrical muscle stimulation (EMS) system, which exercises muscle automatically by direct electrical stimulation, has been reported. In this study, we aimed to determine the effect of perioperative application of SIXPAD, which is a type of EMS system, with reference to the serum myostatin and sarcopenia in LDLT patients. Method: Thirty patients scheduled for LDLT were divided into a SIXPAD group (n = 16) and a control group (n = 14). In the SIXPAD group, EMS was applied to the thighs twice daily. The serum myostatin was measured in samples obtained before use of SIXPAD and immediately before LDLT. The psoas muscle index (PMI) at the level of the third lumbar vertebra and the quadriceps muscle area were compared on computed tomography images before use of SIXPAD and 1 month after LDLT. Results: The preoperative serum myostatin was found to be higher in LDLT patients than in healthy volunteers and EMS significantly reduced the serum myostatin. Electrical muscle stimulation prevented a postoperative reduction not only in the area of the quadriceps muscles but also in the PMI despite direct stimulation of the thigh muscles. Conclusion: Stimulation of muscles by EMS decreases the serum myostatin and helps to maintain skeletal muscle in patients who have undergone LDLT.

DOI： 10.1111/hepr.14027

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Surgery Today  

Background and purpose: In recent years, new systemic therapies have been developed for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the prognosis of patients with unresectable HCC treated with R0 hepatectomy after systemic therapy. Methods: Data from 27 patients who underwent hepatectomy for HCC after systemic therapy at six facilities were analyzed retrospectively. Cancer-specific survival (CSS) and recurrence-free survival (RFS) after hepatectomy were investigated using Kaplan–Meier curves. We examined the prognostic value of the oncological criteria of resectability for HCC reported by the Japanese Expert Consensus 2023. Results: R0 resection was performed in 24 of the 27 patients. Using the Response Evaluation Criteria in Solid Tumors, 0 patient had a complete response, 16 had a partial response, 6 had stable disease, and 2 had progressive disease. Median CSS was not evaluated, but the median RFS was 17.8 months. Patients with resectable and borderline resectable (BR) 1 cancers had a better prognosis than those with BR2 cancers. The group whose oncological criteria were improved by systemic therapy had a lower recurrence rate than the group whose oncological criteria were maintained, but no difference was observed in CSS. Conclusions: The findings of this study suggest that hepatectomy after systemic therapy may improve the prognosis of HCC patients.

DOI： 10.1007/s00595-024-02930-x

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Annals of Surgical Oncology  

Background: Ferroptosis is a cell death caused by iron-dependent accumulation of lipid peroxidation. Transferrin receptor (TFR) is a ferroptosis-related protein responsible for iron transport. The detailed biologic role of TFR in intrahepatic cholangiocarcinoma (ICC) is not fully elucidated. Methods: The study enrolled 92 ICC patients who had undergone hepatic resection. Immunohistochemistry (IHC) assays were performed for TFR protein expression. The regulation of malignant activity and the effect on sensitivity to the ferroptosis-inducer artesunate by TFR were investigated in vitro. Results: Using IHC staining, 23 patients were categorized as TFR-positive. The TFR-positive group had a significantly larger tumor size and more microscopic vascular invasion. In the multivariate analysis, TFR positivity was an independent poor prognostic factor. In vitro TFR-knockdown (KD) significantly decreased the intracellular iron levels and the cell proliferation, migration, and invasion rates. Artesunate treatment significantly decreased cell viability, whereas cisplatin promoted ferroptosis. When iron transport into cells was inhibited by TFR-KD, ferroptosis was significantly suppressed. Expression of PD-L1 was induced by cisplatin, with a further increase observed when artesunate and cisplatin were used in combination. Conclusions: Transferrin receptor is a poor prognostic factor for ICC and contributes to sensitivity to ferroptosis.

DOI： 10.1245/s10434-024-16065-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Surgery Today  

Purpose: We aimed to define borderline resectable colorectal liver metastases (CRLM) based on the analysis of risk factors for early surgical failure and investigate the efficacy of neoadjuvant chemotherapy in these patients. Methods: This was a retrospective analysis of a multi-institutional cohort of patients diagnosed with technically resectable CRLM. Early surgical failure within 6 months of liver surgery was defined as ESF6. We classified CRLM into three grades (A, B, and C) according to the definition of the Japanese Society for Cancer of the Colon and Rectum. Results: Among the 249 patients with technically resectable CRLM, 46 (18.5%) developed ESF6. The survival rate of these patients was significantly lower than that of the patients without ESF6. In the multivariate analysis of synchronous CRLM patients, no neoadjuvant chemotherapy, Grade B/C, and Charlson comorbidity index ≥ 3 were independent predictors of ESF6. Among patients with synchronous and Grade B/C CRLM, ESF6 rates, surgical failure-free survival, and overall survival in the neoadjuvant chemotherapy group were significantly better relative to the upfront surgery group. Conclusions: Patients with synchronous and Grade B/C CRLM are at a high risk of early surgical failure, have a poor long-term prognosis, and can be defined as borderline resectable and good candidates for neoadjuvant chemotherapy.

DOI： 10.1007/s00595-024-02920-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Surgery Today  

Purpose: Infectious complications, particularly post-transplant sepsis, have a critical impact on postoperative outcomes. This study examined the effects of perioperative synbiotic treatment on postoperative outcomes in patients receiving early enteral nutrition. Methods: We reviewed 210 living-donor liver transplantation procedures and retrospectively analyzed the postoperative outcomes with and without perioperative synbiotic treatment (live lactic acid bacteria, bifidobacteria, and oligosaccharides) 5 days before and after living-donor liver transplantation. Results: The synbiotic group (n = 34) had significantly fewer male donors (38.2% vs. 61.9%, p = 0.011) and a higher proportion of ABO-incompatible grafts (52.9% vs. 25.6%, p = 0.021) than the non-synbiotic group (n = 176). The incidence of sepsis was significantly lower in the synbiotic group than in the non-synbiotic group (0% vs. 7.4%, p = 0.029), with a lower incidence rate of sepsis due to bacteremia with intestinal bacteria (0% vs. 4.6%, p = 0.089). There were no significant differences in the proportions of acute rejection, small-for-size graft syndrome, or postoperative liver function between the two groups. Furthermore, there was no significant difference in the graft survival rates after LDLT between two groups. (p = 0.24). Conclusion: Perioperative synbiotic treatment prevents post-transplant sepsis, even with early enteral nutrition.

DOI： 10.1007/s00595-024-02918-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Radiology  

Purpose: Liver resection is currently considered the most effective treatment for patients with liver cancer. To the best of our knowledge, no study has investigated the association between gadoxetic acid-enhanced magnetic resonance imaging (MRI) findings and liver regeneration in patients who underwent hemihepatectomy. We aimed to clarify the relationship between the signal intensity (SI) of the liver parenchyma on gadoxetic acid-enhanced MRI and the degree of liver regeneration in patients who underwent hemihepatectomy. Materials and methods: Forty-one patients who underwent gadoxetic acid-enhanced MRI before hemihepatectomy were enrolled. We calculated the liver-to-erector spinae muscle SI ratio (LMR) in the hepatobiliary phase and the precontrast images. ΔLMR was calculated using the following equation: ΔLMR = (LMR in the hepatobiliary phase−LMR in the precontrast image)/LMR in the precontrast image. The preoperative and postoperative remnant liver volumes (LVs) were calculated using CT volumetry. We calculated the resection rate (RR) and liver regeneration index (LRI) using the following formulas: RR = Resected LV/Total LV × 100 and LRI = (postoperative remnant LV−preoperative remnant LV)/preoperative remnant LV × 100. The relationships among LRI, imaging, and clinicopathological factors were analyzed. Results: Univariate analysis showed RR and ΔLMR showed a positive correlation with LRI (ρ = 0.4133, p = 0.0072 and ρ = 0.7773, p < 0.001, respectively). Spleen volume showed a negative correlation with LRI (ρ = −0.3138, p = 0.0486). Stepwise multiple regression analysis showed ΔLMR and RR were independently correlated with LRI (β coefficient = 44.8771, p = 0.0198 and β coefficient = 1.9653, p < 0.001, respectively). Conclusion: ΔLMR may serve as a preoperative predictor of liver regeneration in patients undergoing hemihepatectomy.

DOI： 10.1007/s11604-024-01629-w

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担当区分：責任著者   記述言語：英語   出版者・発行元：Surgery Today  

Purpose: Treatment outcomes are predicted by analyzing peripheral blood markers such as serum lactate dehydrogenase (LDH). We conducted this study to investigate whether serum LDH levels can predict the prognosis of patients treated with atezolizumab plus bevacizumab (ATZ/BEV) therapy for hepatocellular carcinoma (HCC) and whether LDH levels correlate with metabolic changes. Methods: We enrolled 66 HCC patients treated with ATZ/BEV. Based on the change in serum LDH levels before and after treatment, the patients were divided into two groups, and the prognosis of each group was examined. Moreover, the association of LDH levels with tumor metabolism was analyzed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Results: There were 32 patients categorized as the LDH-decrease group. Kaplan–Meier survival analysis indicated worse progression-free survival (PFS) in the LDH-increase group than in the LDH-decrease group (p = 0.0029). Multivariate analysis showed that an increase in the LDH level was an independent risk factor for worse PFS (p = 0.0045). The baseline LDH level correlated significantly with a high maximum standardized uptake value of 18F-FDG, according to the PET/CT findings. Transcriptomic analyses of specimens resected after ATZ/BEV therapy showed downregulated mitochondria-related pathways. Conclusion: Serum LDH levels are a potential prognostic marker and an indicator of tumor metabolism.

DOI： 10.1007/s00595-024-02914-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Liver Transplantation  

Liver transplantation is the definitive treatment for advanced liver cirrhosis with portal hypertension. In Japan, the scarcity of deceased donors leads to reliance on living donors, often resulting in smaller grafts. Managing portal venous pressure (PVP) is critical to prevent fatal posttransplant complications. This study explored the possibility of predicting intraoperative PVP. We analyzed 475 living donor liver transplant cases from 2006 to 2023, excluding those with acute liver failure or prior splenectomy or splenic artery embolization. Patients were divided into a training group (n=425) and a test group (n=50). We evaluated the correlation between preoperative factors and PVP at laparotomy, to predict PVP at laparotomy and closure. The predictive model was validated with the test group data. PVP at laparotomy could be predicted using correlated preoperative factors: prothrombin time (p<0.001), predicted splenic volume (p<0.001), and presence of a portosystemic shunt (p=0.002), as follows: Predicted PVP at laparotomy (mmHg)=25.818 - 0.077×[prothrombin time (%)]+0.004×[predicted splenic volume (ml)] - 2.067×[1: with a portosystemic shunt] (p<0.001; R=0.346). Additionally, PVP at closure could be predicted using correlated operative factors, including measured PVP at laparotomy, as follows: predicted PVP at closure (mmHg)=14.268+0.149×[measured PVP at laparotomy (mmHg)] - 0.040×[GV/SLV (%)] - 0.862×[1: splenectomy (if yes)] - 3.511×[1: splenic artery ligation without splenectomy (if yes)] (p<0.001; R=0.339).This study demonstrated the feasibility of predicting intraoperative PVP using preoperative factors in liver transplant patients with decompensated cirrhosis. This predictive approach could refine surgical planning, potentially improving patient outcomes.

DOI： 10.1097/LVT.0000000000000433

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Transplantation  

Background. The consensus that portal venous pressure modulation, including splenectomy (Spx), prevents portal hypertension-related complications after living-donor liver transplantation (LDLT) has been established. However, little evidence about the risk factors for graft loss after simultaneous Spx during LDLT is available. This study aimed to identify the independent predictors of graft loss after simultaneous Spx during LDLT. Methods. Data of 655 recipients who underwent LDLT between 1997 and 2021 were collected and separated into the simultaneous Spx group (n=461) and no-Spx group (n=194). Results. The simultaneous Spx group had significantly lower serum total bilirubin levels, drained ascites volumes, and prothrombin time-international normalized ratios on postoperative day 14 than the no-Spx group (P<0.001 for each). Incidences of small-for-size graft syndrome (P<0.001), acute cellular rejection (P=0.002), and sepsis (P=0.007) were significantly lower in the Spx group. Graft survival of the Spx group was significantly better than that of the no-Spx group (P<0.001; hazard ratio [HR], 1.788; 95% confidence interval, 1.214-2.431). A multivariate analysis revealed that 3 variables, platelet count ≤4.0×104/mm3 (P=0.029; HR, 2.873), donor age ≥60 y old (P=0.013; HR, 6.693), and portal venous pressure at closure ≥20 mm Hg (P=0.010; HR, 3.891), were independent predictors of graft loss within 6 mo after simultaneous Spx during LDLT. Conclusions. Spx is a safe inflow modulation procedure with a positive impact on both postoperative complications and prognosis for most patients. However, patients with the 3 aforementioned independent factors could experience graft loss after LDLT.

DOI： 10.1097/TP.0000000000004952

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastrointestinal Surgery  

Purpose: Although the incidence of recipients and donors with overweight and obesity is increasing worldwide, few reports have focused on outcomes of preoperative weight reduction (WR) in living-donor liver transplantation (LDLT). Therefore, we examined the outcomes and the impact of WR on the postoperative course. Methods: We analyzed 217 consecutive LDLT procedures performed from 2017 to 2022. We divided the recipients and donors into a WR group and non-WR group. Results: Twenty-two recipients (10.1%) achieved WR (preoperative recipient WR [RWR] group), reducing their weight by 6.8% ± 6.0% within 2.2 ± 1.4 months with a significant decrease in body mass index (BMI) (P < .0001). The RWR group showed no significant differences in short-term postoperative outcomes (operative factors, postoperative liver function tests, amount of ascites, and morbidity) or in the graft survival rate as a long-term outcome (P = .24) compared with the non-RWR group. Forty-one donors (18.9%) achieved WR (preoperative donor WR [DWR] group), reducing their weight by 9.7% ± 6.3% within 3.2 ± 5.8 months with a significant decrease in BMI (P < .0001). Compared with the non-DWR group, the DWR group showed no significant differences in short-term postoperative outcomes between themselves and recipients or in the graft survival rate (P = .49). Furthermore, WR resulted in an increase to 32 donor-eligible and 6 recipient-eligible patients. Conclusion: WR in LDLT recipients and donors had no harmful effect on postoperative outcomes and should lead to increase recipients’ chance of undergoing LDLT and to expand the donor pool.

DOI： 10.1016/j.gassur.2024.04.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Annals of Gastroenterological Surgery  

Aim: There is limited evidence regarding the feasibility of living-donor liver transplantation (LDLT) for patients aged over 70. The aims of this study were to assess postoperative outcomes in elderly recipients and to ascertain the potential feasibility and acceptability of LDLT. Methods: Data were collected from 762 recipients, including 26 in the elderly group (aged ≥70) and 736 in the younger group (aged <70), and reviewed even by propensity score matching (PSM). Results: No significant differences were observed in the frequency of postoperative complications between the two groups. Additionally, both groups exhibited a comparable 30-day mortality rate after LDLT (3.9% in both) and similar hospital stays (36 days vs. 40 days). The 1-, 3-, and 5-year graft survival rates in the elderly group were 92.0%, which was comparable to those in the younger group (p = 0.517), as confirmed by PSM. Notably, all donors for elderly patients were the children of the recipients, with an average age of 41.6 years, and grafts from donors aged ≥50 years were not utilized, signifying the use of high-quality grafts. Our inclusion criterion for elderly recipients was strictly defined as an ECOG-PS score of 0–2, which played a pivotal role in achieving favorable postoperative outcomes. Conclusion: LDLT can be performed safely for elderly patients aged 70 years or older, provided they have a preserved PS and receive high-quality grafts from younger donors, inevitably all children of elderly recipients. This approach yields acceptable long-term outcomes. Consequently, age alone should not serve as an absolute contraindication for LDLT.

DOI： 10.1002/ags3.12769

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Surgery Today  

Purpose: To evaluate the short term-outcomes of venous reconstruction using a round ligament-covered prosthetic vascular graft and assess its effectiveness in the prevention of prosthetic vascular graft migration in right‑lobe living donor liver transplantation (LDLT). Methods and results: Thirty patients underwent reconstruction of the middle hepatic vein (MHV) tributaries during right lobe LDLT between January, 2021 and October, 2022. These patients were divided into the autologous vascular graft group (A group, n = 24) and the round ligament-covered prosthetic vascular graft group (RP group, n = 6). The computed tomography (CT) density ratio of the drainage area in the posterior segment of patent grafts was significantly higher in the RP group than in the A group (0.91 vs. 1.06, p = 0.0025). However, the patency rates of reconstructed MHV tributaries in the A and RP groups were 61% and 67%, respectively, with no significant difference between the groups (p = 0.72). Prosthetic vascular graft migration did not occur in the RP group. Conclusion: Venous reconstruction using round ligament-covered prosthetic vascular grafts is a feasible and simple method to prevent prosthetic vascular graft migration in right-lobe LDLT.

DOI： 10.1007/s00595-024-02793-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

Aim: The Japanese indication criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC) have been updated based on living donor LT data to include either the Milan criteria (MC) or the 5-5-500 rule, which requires a nodule size of ≤5 cm, ≤5 nodules, and an alpha-fetoprotein (AFP) level ≤500 ng/mL. We aimed to validate the 5-5-500 rule and the MC for deceased donor LT (DDLT). Methods: Using national registry data from the United States from 2010 to 2014, we separated DDLT patients into four groups based on the MC and the 5-5-500 rule. The AFP values were stratified into categories: ≤100, 101–300, 301–500, and >500 ng/mL. Results: The 5-year survival rate was significantly lower for patients in the groups within MC/beyond 5-5-500 (56.3%) or beyond MC/5-5-500 (60.7%) than for patients in the groups within MC/5-5-500 (76.2%) and beyond MC/within 5-5-500 (72.3%) (p < 0.01). Hepatocellular carcinoma recurrence at 5 years was highest for the within MC/beyond 5-5-500 (25.4%) group, followed by the beyond MC/within 5-5-500 (13.1%), beyond MC/5-5-500 (9.6%), and within MC/5-5-500 (7.4%) groups. The stratified 5-year survival rates after DDLT were 76.5%, 72.4%, 58.4%, and 55.6% in the AFP ≤100, 101–300, 301–500, and >500 categories, respectively (p < 0.01). Conclusion: The 5-5-500 rule guides the appropriate selection of patients with HCC for DDLT. Patients with AFP levels from 300 to 500 ng/mL had inferior outcomes even when they met the 5-5-500 rule, so further investigation is needed to guide their treatment.

DOI： 10.1111/hepr.14017

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Surgery Today  

Some patients with refractory esophagogastric varices require surgery, such as gastric devascularization and splenectomy (Hassab’s procedure). However, these patients are at risk of perioperative morbidities when undergoing devascularization to develop collateral vessels. We performed a more simplified procedure, splenectomy, and en bloc gastropancreatic fold division (GPFD) with hand-assisted laparoscopic surgery. Four patients with refractory esophagogastric varices and portal hypertension underwent splenectomy and GPFD. We reviewed patients’ perioperative laboratory and morphological data, operative variables, and postoperative outcomes. Esophagogastric varices improved in 3 (75%) of the 4 patients. In one patient, esophageal varices (F1RC0) were observed 3 years after surgery, but they required no treatment and only received follow-up. Treatment with splenectomy and GPFD is not only less invasive than Hassab’s procedure but also provides effective outcomes for refractory esophagogastric varices.

DOI： 10.1007/s00595-023-02780-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Surgery Today  

Living-donor liver transplantation (LDLT) is an established treatment for patients with end-stage liver disease or acute liver failure, and outflow reconstruction is considered one of the most vital techniques in LDLT. To date, many strategies have been reported to prevent outflow obstruction, which can be refractory to liver dysfunction and can cause life-threatening graft loss or mortality. In addition, in this era of laparoscopic hepatectomy in donor surgery, especially LDLT using a left liver graft, it has been predicted that cutting the hepatic vein with automatic linear staplers will lead to more outflow-related problems than with conventional open hepatectomy because of the short neck of the anastomosis orifice. We herein review 10 cases of venoplasty performed with a novel venous cuff system using a donor’s round ligament around the hepatic vein in LDLT with a left lobe graft, which makes anastomosis of the hepatic vein sterically easy for postoperative venous patency.

DOI： 10.1007/s00595-023-02791-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Liver Transplantation  

DOI： 10.1097/LVT.0000000000000308

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出版者・発行元：日本メディカルセンター  

DOI： 10.19020/cg.0000003026

CiNii Research

出版者・発行元：金原出版  

DOI： 10.18888/op.0000003803

CiNii Research

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology and Hepatology (Australia)  

Aim: Pretreatment peripheral blood markers have value in predicting the treatment outcome of various cancers. In particular, the eosinophil count has recently gained attention. However, no study has reported the influence of the pretreatment eosinophil count on the outcomes of atezolizumab plus bevacizumab (ATZ/BEV), which is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (u-HCC). Methods: We enrolled 114 patients with u-HCC treated with ATZ/BEV (n = 48) or lenvatinib (n = 66). The patients receiving ATZ/BEV or lenvatinib were divided into two groups by calculating the cutoff value of the pretreatment eosinophil count. The groups were compared regarding the clinicopathological characteristics, outcomes, and incidence of adverse events (AEs). Results: Twenty-three of 48 patients (47.9%) who received ATZ/BEV therapy were categorized as the ATZ/BEV-eosinophil-high group, which had better responses than the ATZ/BEV-eosinophil-low group (P = 0.0090). Kaplan–Meier curves revealed a trend toward significantly better progression-free survival (PFS) in the ATZ/BEV-eosinophil-high group than the ATZ/BEV-eosinophil-low group (the median PFS: 4.7 months in the ATZ/BEV-eosinophil-low group vs 12.6 months in the ATZ/BEV-eosinophil-high group; P = 0.0064). Multivariate analysis showed that a low eosinophil count was an independent risk factor for worse PFS after ATZ/BEV therapy (P = 0.0424, hazard ratio: 2.24, 95% confidence interval: 1.02–4.89). AEs (≥ grade 3) were significantly more likely to occur in the ATZ/BEV-eosinophil-high group (P = 0.0285). The outcomes did not significantly differ between the LEN-eosinophil-high group and the LEN-eosinophil-low group. Conclusion: A high pretreatment eosinophil count predicted a better response to ATZ/BEV therapy for u-HCC and was associated with the incidence of AEs (≥ grade 3).

DOI： 10.1111/jgh.16441

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出版者・発行元：金原出版  

DOI： 10.18888/op.0000003667

CiNii Research

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40792-024-01807-y

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PubMed

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Annals of Gastroenterological Surgery  

Background: There is limited published information regarding the expression of mechanistic target of rapamycin (mTOR) in vessels that encapsulate tumor cluster (VETC)-positive hepatocellular carcinoma (HCC). The mTOR inhibitor, everolimus, has been approved as an immunosuppressant for use in HCC patients after living donor liver transplantation (LDLT). Methods: Using a database of 214 patients who underwent LDLT for HCC, we examined the mTOR protein and angiopoietin-2 (Ang-2) in VETC-positive HCC by immunohistochemical staining. The presence of VETC and mTOR expression were evaluated in both primary and recurrent HCC lesions. Results: Forty-three of the 214 patients (20.1%) were VETC-positive, and 29 of these 43 patients (67.4%) expressed mTOR. Relative Ang-2 expression was significantly higher in the mTOR-positive than in the mTOR-negative group (p = 0.037). Thirty-four of the 214 patients experienced HCC recurrence after LDLT; 20 of these were operable. The primary lesions of six of these 20 patients were VETC-positive; five of these six patients also had VETC-positive recurrent lesions (p < 0.001). The expression of mTOR was significantly higher in the VETC-positive lesions (p = 0.0018). Conclusions: We showed that mTOR expression was higher in the VETC-positive primary and recurrent lesions than in the VETC-negative ones.

DOI： 10.1002/ags3.12735

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記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

腫瘍クラスターを被包する血管(VETC)陽性の肝細胞癌(HCC)におけるmTOR発現に関する報告は少ない。mTOR阻害物質であるエベロリムスが、生体肝移植(LDLT)後のHCC患者に対する免疫抑制剤として認可された。HCCに対してLDLTを施行した214例のデータを用いて、VETC陽性HCCにおけるmTOR蛋白質およびアンギオポエチン-2(Ang-2)の発現を免疫組織化学的染色により検討した。VETCおよびmTOR発現の有無を原発性および再発性HCC病変の両方で評価した。214例中43例(20.1%)はVETC陽性で、この43例中29例(67.4%)はmTORを発現していた。相対的Ang-2発現は、mTOR発現例でmTOR陰性例よりも有意に多かった(P=0.037)。214例中34例でLDLT後にHCCの再発が認められ、うち20例は手術適応であった。これら20例のうち6例の原発巣はVETC陽性で、この6例中5例は再発巣でもVETC陽性であった(P<0.001)。以上より、mTORの発現はVETC陽性病変で有意に多かった。VETC陽性の原発および再発病変において、VETC陰性病変と比較してmTOR発現高いことが示された。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Surgery Today  

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

DOI： 10.1007/s00595-023-02710-z

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cancer Science  

TP53-induced glycolysis and apoptosis regulator (TIGAR) is an important gene that encodes a regulatory enzyme of glycolysis and reactive oxygen species (ROS) detoxification and is associated with worse prognosis in various cancers. Ferroptosis is a recently identified type of programmed cell death that is triggered by iron-dependent lipid peroxidation. There are no reports on the prognostic impact of TIGAR on intrahepatic cholangiocarcinoma (ICC), and its role in ferroptosis is unclear. Ninety ICC patients who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. The regulation of malignant activity by TIGAR and the association between ferroptosis and TIGAR were investigated in vitro. Twenty-two (24.4%) patients were categorized into TIGAR-high and -low groups by immunohistochemical staining. There were no noticeable differences in background factors between the two groups, but TIGAR positivity was an independent prognostic factor in disease-free survival (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.04–3.85, p = 0.0378) and overall survival (HR, 2.10; 95% CI, 1.03–4.30, p = 0.00422) in a multivariate analysis. In vitro, TIGAR knockdown (KD) decreased cell motility (cell proliferation/migration/invasion/colony-forming capabilities) and elevated ROS and lipid peroxidation. This indicated that TIGAR KD induced ferroptosis. TIGAR KD-induced ferroptosis was suppressed using liproxstatin. TIGAR KD decreased the expression of glutathione peroxidase 4, known as factor-suppressing ferroptosis. The combination of TIGAR KD with cisplatin significantly induced more ferroptosis. In conclusion, TIGAR is associated with poor outcomes in ICC patients and resistance to ferroptosis.

DOI： 10.1111/cas.15981

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

Aim: To investigate the prognostic value of the preoperative albumin–lymphocyte–platelet–C-reactive protein (ALPC) index in patients with hepatocellular carcinoma (HCC) undergoing curative hepatectomy. We also evaluated the relationship between the ALPC index and the phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) levels. Methods: Data were analyzed retrospectively from 256 patients who underwent resection for HCC. For cross-validation, patients were divided into the training and testing cohort. We assessed eight combinations of inflammatory markers for predictive value for recurrence. We examined the associations of the ALPC index with recurrence-free survival and overall survival in univariate and multivariate analyses (Cox proportional hazards model). Immunohistochemical staining of p-Nrf2 was performed on tumor samples of 317 patients who underwent hepatic resection for HCC. Results: A high preoperative ALPC index correlated with a high serum albumin concentration, small tumor size, low rate of poor differentiation, solitary tumor, early Barcelona Clinic Liver Cancer stage, and low rate of microscopic intrahepatic metastasis in the training dataset. A high preoperative ALPC index correlated with a high serum albumin concentration, high serum alpha-fetoprotein concentration, small tumor size, a low rate of poor differentiation and a low rate of microscopic intrahepatic metastasis in the testing dataset. A higher preoperative ALPC index was an independent predictor of longer recurrence-free survival and overall survival in the training and testing datasets. A high ALPC index was associated with negative p-Nrf2 expression in HCC tumor cells. Conclusions: We showed that a high ALPC index was an independent prognostic factor for patients with HCC undergoing curative hepatic resection.

DOI： 10.1111/hepr.13958

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/jgh3.13018

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s10147-023-02399-7

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Surgeon  

Background: Increasing evidence indicates that increased systemic inflammation is correlated with poorer cancer-specific survival in various cancer types. This study aimed to evaluate the prognostic value of various combinations of inflammatory factors in patients who underwent surgical resection for pancreatic cancer (PC). Methods: We retrospectively analyzed 97 consecutive patients with PC who underwent pancreatectomy. We assessed the predictive impact for recurrence using a combination of 5 inflammatory markers and focused on the lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for recurrence-free survival (RFS) and overall survival (OS) in univariate and multivariate analyses using the Cox proportional hazards model. Results: Low preoperative LCR was correlated with low serum hemoglobin, low serum albumin concentration, high frequency of microscopic vascular invasion, and high frequency of microscopic perineural invasion. The low LCR group had significantly worse RFS and OS. Lower preoperative LCR was an independent predictor of shorter RFS and OS in this cohort. Discussion: Preoperative LCR is a novel and convenient prognostic marker for patients with PC. Patients with low LCR may require more favorable intensive therapy.

DOI： 10.1177/00031348221117034

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：John Wiley & Sons Australia, Ltd  

腹腔鏡下胆嚢摘出術が施行された急性胆嚢炎患者189例を対象に、臨床転帰を評価する新たな複合指標であるtextbook outcome(TO)を検討した。TOは、開腹手術への移行、術中合併症、Clavien-Dindo分類でGrade II以上の術後合併症、10日以上の在院期間の延長、術後30日以内の再入院がない腹腔鏡下胆嚢摘出術と定義した。TOは154例で達成した。開腹手術への移行は10例、術中合併症は1例、術後合併症は5例で発生し、29例で在院期間が10日以上であった。患者をTO達成群154例(男性107例、女性47例、年齢中央値63歳)と非達成群35例(男性23例、女性12例、年齢中央値74歳)に分類した。医療費はTO達成群が有意に低かった。多変量解析の結果、70歳以上、ヘモグロビン濃度11.9g/dL未満、白血球数18000/μL以上がTOの非達成を予測する独立因子であった。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Transplantation Proceedings  

Autoimmune encephalitis after liver transplantation (LT) is a rare disorder. This is because patients are usually in an immunosuppressed state after LT. Here, we report a rare case of autoantibody-negative autoimmune-encephalitis-induced coma after living-donor (LD) LT. A 45-year-old woman who underwent LDLT for primary biliary cholangitis (PBC) was brought to our hospital with the chief complaint of cognitive deficiency and an episode of memory loss. Physical examination, laboratory tests, and cerebrospinal fluid analysis revealed no significant findings. However, diffusion-weighted magnetic resonance imaging showed hyperintensity in the bilateral hippocampus. No autoantibodies associated with autoimmune encephalitis were detected. The diagnosis of antibody-negative autoimmune encephalitis was made on the basis of low immunosuppressive drug levels in the blood (indicative of poor adherence) and the presence of PBC as the autoimmune disease. The patient regained consciousness after intravenous methylprednisolone pulse therapy and plasma exchange. This case highlights that when examining patients with impaired consciousness after LDLT, it is important to consider autoimmune encephalitis as a potential diagnosis.

DOI： 10.1016/j.transproceed.2023.07.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi:10.1016/j.transproceed.2023.07.029

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1245/s10434-023-14053-7

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Surgical Case Reports  

Surgical therapy following lenvatinib (LEN) plus transarterial chemoembolization (TACE) is a useful therapeutic option for intermediate-stage hepatocellular carcinoma (HCC). A 66-year-old man with a history of hepatitis C was detected four masses in the caudate lobe and segment 6/7 of the liver, with a maximum lesion diameter of 14 cm by computed tomography. The patient was diagnosed with intermediate-stage HCC and received LEN plus TACE. After resuming LEN for 8 weeks, computed tomography showed weakened stained areas of the tumors, and no new lesions. Thus, the patient was evaluated as having a partial response in the modified Response Evaluation Criteria in Solid Tumors. The patient underwent hepatic caudate lobectomy, partial hepatectomy of S6/7, and S6 microwave coagulation therapy for radical resection. The patient is currently alive and recurrence-free at 12 months postoperatively. In patients with multiple HCC lesions, hepatic resection combined with local therapy might be an effective treatment option.

DOI： 10.1093/jscr/rjad485

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s10147-023-02358-2

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41416-023-02189-y.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/hepr.13902

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Journal of Gastroenterology  

We herein describe three patients with Fontan-associated liver disease who developed hepatocellular carcinoma (HCC). The first patient was a 28-year-old woman who had undergone the Fontan operation (FO) at the age of 4 years. She was diagnosed with HCC (cT4aN0M0, Stage IVA, UICC 8th edition), for which she underwent extended posterior right sectionectomy and partial hepatectomy of S2. She developed recurrence of peritoneal dissemination after 12 months, and she was alive 18 months after surgery. The second patient was a 43-year-old man who had undergone the FO at the age of 3 years. He was diagnosed with HCC (cT2N0M0, Stage II), for which he underwent laparoscopic-assisted partial hepatectomy of S3. He remained free from recurrent HCC for 17 months. The third patient was a 21-year-old woman who had undergone the FO at the age of 3 years. She was diagnosed with HCC (cT3N0M0, Stage III), for which she underwent laparoscopic-assisted partial hepatectomy of S2 and S4. She remained free from recurrent HCC for 30 months. We reviewed 18 surgical cases of HCC arising from Fontan-associated liver disease, including our 3 cases, and found that a high preoperative alpha-fetoprotein concentration might be a predictor of HCC recurrence.

DOI： 10.1007/s12328-023-01795-w

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

Aim: We aimed to evaluate the association between the intraoperative indocyanine green (ICG) fluorescence imaging (FI) pattern, preoperative magnetic resonance imaging (MRI) findings using gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), preoperative diffusion-weighted imaging (DWI) of MRI, and histological differentiation of hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed the data for 80 tumors of 64 patients. Intraoperative ICG FI patterns were classified into cancerous or rim-positive type. We evaluated the signal intensity ratio of the tumor and the surrounding liver tissue in the portal phase (SIRPP) and intensity in the hepatobiliary phase (HBP) of Gd-EOB-DTPA-enhanced MRI, the apparent diffusion coefficient (ADC) in the DWI of MRI, and clinicopathologic factors. Results: In the rim-positive group, the rate of poorly differentiated HCC and hypointensity type in HBP were significantly higher, and SIRPP and ADC were significantly lower than the rim-negative group. In the cancerous group, the rate of well or moderately differentiated HCC and hyperintensity type in HBP, SIRPP, and ADC were significantly higher than the noncancerous group. Multivariate analysis identified low SIRPP, low ADC, and hypointensity type in HBP as the significant predictive factors for rim-positive HCC and high SIRPP, high ADC, and hyperintensity type in HBP as the significant predictive factors for cancerous HCC. The positive rate of programmed cell death 1-ligand 1 and vessels that encapsulate tumor clusters status of the rim-positive HCC and HCC with low SIRPP were significantly higher than the control group. Conclusions: The intraoperative ICG FI pattern of HCC closely correlated with histological differentiation, preoperative SIRPP and intensity type in the Gd-EOB-DTPA MRI, and preoperative ADC in the DWI of MRI.

DOI： 10.1111/hepr.13902

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出版者・発行元：南江堂  

DOI： 10.15106/j_geka85_863

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1245/s10434-022-13058-y

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/hepr.13885

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Surgeon  

Backgroud: The systemic inflammation score (SIS), which is based on the preoperative lymphocyte-to-monocyte ratio (LMR) and serum albumin (Alb) level, is a prognostic indicator for several cancer types. However, the prognostic significance of the SIS in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Methods: Seventy-eight patients who underwent radical surgery for PDAC were categorized as follows: SIS 0 (LMR ≥3.51 and Alb ≥4.0 g/dl), n = 26; SIS 1 (LMR <3.51 or Alb <4.0 g/dl), n = 29 and SIS 2 (LMR <3.51 and Alb <4.0 g/dl), n=23. Results: The tumour size sequentially increased in SIS 0, 1 and 2 groups. A higher SIS was associated with increased vascular invasion, perineural invasion and surgical margin positivity rate. Recurrence-free survival (RFS) rates between the SIS 1 and 2 groups showed no significant difference However, patients of the SIS 1 and 2 groups had poorer outcomes than those of the SIS 0 group for RFS. Overall survival (OS) rates between the SIS 1 and 2 groups also showed no significant difference. However, patients of the SIS 1 and 2 groups had poorer outcomes than those of the SIS 0 group for OS. The SIS was an independent prognostic factor for RFS and OS. Discussion: The SIS is a simplified prognostic factor for patients with PDAC.

DOI： 10.1177/00031348221086782

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3389/fcimb.2023.1197349

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/hepr.13875.

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

Aims: The fibroblast growth factor receptor 2 (FGFR2) fusion gene is frequently found as a genetic abnormality in the FGFR pathway in patients with intrahepatic cholangiocarcinoma (ICC). The FGFR fusion protein, produced from the FGFR fusion gene, is thought to cause tumor cell growth. To date, there have been few reports on the relationship between pathologic FGFR2 expression and prognosis in patients who have undergone hepatectomy for ICC, and on the relationship between FGFR2 and tumor-infiltrating lymphocytes (TILs). Methods and Results: We enrolled 92 patients who underwent hepatectomy for ICC and performed immunohistochemical staining for FGFR2 and cluster of differentiation 8, and hematoxylin and eosin staining for evaluating TILSs. The relationships between the FGFR2 and clinicopathological characteristics and outcomes were analyzed, and patients were classified into positive (n = 18) and negative (n = 74) FGFR2 groups. The FGFR2-positive group contained more men (p < 0.0001) and had lower serum albumin (p = 0.0355) and higher carcinoembryonic antigen (p = 0.0099). Furthermore, multivariable analyses revealed that the FGFR2-positive group had worse disease-free survival (DFS) (p = 0.0002). Multivariate analysis showed that the independent prognostic factors for DFS were maximum tumor size (≥5 cm) (p = 0.0011), tumor localization (perihilar type) (p = 0.0180), and FGFR2 positivity (p = 0.0029). There was no significant difference in TILs count between the two groups. Conclusion: We showed that FGFR2 high expression was an independent prognostic factor for recurrence of resected ICC.

DOI： 10.1111/hepr.13875

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出版者・発行元：南江堂  

DOI： 10.15106/j_geka85_489

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/ases.13238

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Journal of Gastroenterology  

A combined therapy of atezolizumab and bevacizumab (atezo/bev) is used as the first-line treatment for unresectable hepatocellular carcinoma (HCC). In this study, we report the case of curative hepatic resection in a 77-year-old man who initially had unresectable advanced-stage HCC with lung metastases. This rare hepatectomy conversion was owing to the administration of atezo/bev. Notwithstanding the side effects of immune-related adverse event hepatitis and intratumoral hemorrhage developed during atezo/bev treatment; after seven treatment cycles, the patient’s tumor markers normalized, the tumor shrank markedly, and the metastasis disappeared. Subsequently, conversion therapy with hepatic resection was performed, and pathology confirmed complete tumor necrosis. No cancer recurrence was observed at the 8-month postoperative follow-up, and the patient remained drug free.

DOI： 10.1007/s12328-022-01744-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/cas.15644

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：大道学館出版部  

食道癌手術症例における入院前周術期支援の介入の有無と術後合併症との関連について検討し、入院前周術期支援の有用性について検証した。2018年4月～2020年9月にかけて、食道癌手術症例120例を、入院前周術期支援を開始した2019年10月前後で入院時支援介入なし群75例と介入あり群45例に分類した。術後合併症は全体で51例(43%)に認められ、内容としては最多が肺炎で16例(13.9%)、嚥下障害・反回神経麻痺が14例(12.2%)、不整脈8例(7.0%)であった。介入なし群での合併症頻度は75例中37例(49%)であったのに対して、介入あり群で45例中14例(31%)と介入あり群の方が合併症の発生頻度が低かった。周術期支援による術後合併症の減少が示唆される結果が得られ、他癌腫への応用も視野に、周術期支援の充実を図ることが重要と考えられた。

出版者・発行元：金原出版  

DOI： 10.18888/op.0000003119

CiNii Research

担当区分：責任著者   記述言語：日本語   出版者・発行元：一般社団法人　日本肝臓学会  

<p>肝癌に対する肝切除における内科医と外科医の現状と肝切除に対する考え方を整理することを目的にアンケートを実施した．九州肝臓外科研究会世話人施設15施設の内科医および外科医を対象とした．切除のボーダーラインに関して内科医は個数とVpに関して制限を，外科医はVvに制限を感じていた．イメージ症例に対してBCLC-B・up to 7 outは内科医・外科医ともにICIを選択し，内科医は奏功しても切除の選択は少なかった．門脈近接症例に対して外科医はConversion企図の治療選択であったが，内科医は治療奏功後に結果として切除を選択していた．内科医としての切除前後での関わりに関してはConversionを企図した薬物療法・局所治療の選択を希望していた．今後さらに複雑化する肝癌治療において肝切除と薬物治療・局所治療をシームレスに行うためにより一層内科医と外科医の意識改革が必要であることが明らかとなった．</p>

DOI： 10.2957/kanzo.64.1

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CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.transproceed.2022.09.031

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/hepr.13834

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13691-022-00585-4

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Transplant International  

The recipient muscle status is closely associated with postoperative poor survival in recipients of living donor liver transplantation (LDLT). However, it is uncertain whether LDLT donor muscle quality and quantity affect graft quality. Hence, we analyzed the correlation between donor muscle status and graft function. We measured the skeletal muscle mass index (SMI) and intramuscular adipose tissue content (IMAC) of 380 LDLT donors. We examined the correlation between donor SMI or IMAC and graft mortality, the occurrence rates of small-for-size graft (SFSG) syndrome, and 6-month graft survival rates. The donor SMI had no effect on the occurrence of SFSG syndrome and graft survival, while a high IMAC in both male and female donors was significantly correlated with the rate of SFSG syndrome [high vs low: (male donors) 15.8% vs. 2.5%, p = 0.0003; (female donors) 12.8% vs. 3.1%, p = 0.0234] and 6-month graft survival rates [(male donors) 87.7% vs 95.9%, p = 0.02; (female donors) 83.0% vs. 99.0%, p < 0.0001]. Multivariate analysis revealed that a high donor IMAC (HR; 5.42, CI; 2.13–13.8, p = 0.0004) was an independent risk factor for 6-month graft survival, and the donor IMAC is useful for donor selection for high-risk recipients.

DOI： 10.3389/ti.2022.10723

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出版者・発行元：南江堂  

DOI： 10.15106/j_geka84_1362

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Transplantation Proceedings  

Although there have been a few liver transplantations (LTs) between identical twins, to our knowledge hepatic damage after LT in an immunosuppressant-free patient has not been reported. Autoimmune liver disease recurrence after LT is also a postoperative problem. In this follow-up to our previous report, we present the case of a 57-year-old man with acute liver failure who underwent living donor liver transplantation (LDLT) from an identical twin. Six months after LDLT, the patient was free from immunosuppressive medication and showed good liver function. However, 1 year after LDLT, he developed liver damage and was diagnosed with autoimmune hepatitis by liver biopsy. His liver function was improved with steroid pulse therapy and the resumption of immunosuppressive medications. Even after LDLT from an identical twin, careful management is required for patients to remain free of immunosuppressive medications, considering the background liver disease.

DOI： 10.1016/j.transproceed.2022.09.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40792-022-01533-3

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Surgical Case Reports  

The case is a 78-year-old female. A giant liver cyst was pointed out by abdominal echo from 7 years ago, but because the size of the cyst tended to increase, it was decided to operate taking into account the risk of the cyst rupturing. Laparoscopic surgery was started, and the cyst contents did not fluorescent when observed by the indocyanine green (ICG) fluorescence method. Laparoscopic liver cyst fenestration was performed using the ICG fluorescence method, paying attention to the damage to the bile duct excluded by the cyst. The opened cyst was filled with the greater omentum. In this report, we describe that the ICG fluorescence method can evaluate the presence or absence of bile leakage from the hepatic dissection and the running of the bile duct on the inner wall of the cyst, and is considered to contribute to safer laparoscopic liver cyst fenestration.

DOI： 10.1093/jscr/rjac479

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Springer Berlin Heidelberg  

症例は39歳女性で、生体移植のためにドナー肝切除を施行された。合併症はなく、術前MD-CTでは残肝容積は429mL(40.5%)を示し、先天性門脈体循環シャントの拡張が認められた。シャント径は9cmに及び、左胃静脈(LGV)から左腎静脈(LRV)への流入を認めたが、臨床検査所見に異常はなかった。術中所見では肝臓の外観は正常であり、手術時間は320分、推定出血量は245mLで術後経過は良好であった。しかし、術後9日目、活動量低下と記憶障害をきたし、軽度脳症と全身性血中アンモニア高値が検出された。MD-CTでは明らかな門脈血栓はみられなかったが、門脈幹の狭小化と門脈血流の低下を認め、先天性門脈体循環シャントへの盗血が疑われた。さらに、プロトロンビン時間-国際標準化比(PT-INR)とD-ダイマーの上昇が確認されたことから、門脈血流不良による門脈微小血栓の存在が示唆された。このため、右大腿静脈アプローチによるバルーン閉塞下逆行性経静脈的塞栓術(B-RTO)を行うこととし、門脈圧を13mmHgに設定してLGV-LRVシャントを閉塞した。術後、肝性脳症と高アンモニア血症の改善が得られ、PT-INRも正常化しB-RTO施行後9日目に退院となった。6ヵ月後のMD-CTでは門脈幹の拡大と残肝の再生促進が得られていた。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular and Clinical Oncology  

The association of Jumonji domain-containing 6 (JMJD6) with the prognosis of various types of cancer has been demonstrated, except in intrahepatic cholangiocarci-noma (ICC). The present study aimed to clarify the impact of JMJD6 on ICC. The liver specimens of 51 patients who underwent surgery for ICC were analyzed for JMJD6 expression using immunohistochemistry staining. The relationship between clinicopathological factors and JMJD6 expression was investigated. The cellular activity was also evaluated in JMJD6 knocked down cells with Transwell migration assay and viability assay. In the immunohistochemistry staining of clinical samples, high expression of JMJD6 was seen in 32 of 51 samples. High expression was also associated with improved overall survival (OS) and recurrence-free survival (RFS) (P=0.0033 and 0.048, respectively). Further analyses revealed that higher JMJD6 expression was one of the improved independent prognostic factors of OS and RFS. Expression of JMJD6 was knocked down in commercial culture cell lines of ICC, and RNA and protein were extracted to analyze the downstream gene expression using RNA-sequencing and western blotting. JMJD6 knockdown was associated with higher programmed death-ligand 1 (PD-L1) expression in RNA-sequencing and western blotting. In addition, PD-L1 expression was higher in JMJD6 low expression clinical samples when measured using immunohistochemistry staining. In conclusion, high expression of JMJD6 was an independent favorable prognostic factor of ICC. JMJD6 may influence the prognosis of ICC through the regulation of PD-L1 expression.

DOI： 10.3892/mco.2022.2564

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   出版者・発行元：一般財団法人 日本消化器病学会  

<p>肝細胞癌に対する肝移植の保険適用が新日本基準（5-5-500基準内あるいはミラノ基準内）に拡大された．本邦の肝細胞癌治療アルゴリズムでは，肝移植はChild-Pugh C症例で新基準内に留まっているものに推奨されている．このため肝予備能が許容される限り，肝切除，焼灼療法，塞栓療法，肝動注，薬物療法などが行われ，肝機能不良となった症例に肝移植が施行される．肝細胞癌に対してチロシンキナーゼ阻害剤や免疫チェックポイント阻害剤が使用可能となり，肝移植前のdown stageあるいは移植後の補助療法・再発後の治療に，これらの薬物療法を使用した報告が見られるようになった．これらの報告とわれわれの経験を概説する．</p>

DOI： 10.11405/nisshoshi.119.432

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PubMed

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pancreas  

DOI： 10.1097/MPA.0000000000001976

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

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

DOI： 10.1038/s41598-022-05444-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.pan.2021.08.003

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00595-021-02358-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10147-021-01985-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jgh3.12588

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10147-021-01962-4

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1245/s10434-020-09339-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/SLA.0000000000005001

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.transproceed.2021.02.020

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1245/s10434-021-10209-5

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00595-021-02305-6

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00423-021-02103-1

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ags3.12412

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/hepr.13667

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00595-021-02276-8

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/hep4.1659

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41379-020-00702-9

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/cam4.3519

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-021-85186-6

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/hep4.1643

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejso.2020.08.002

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jhep.2020.08.017

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1155/2021/8813410

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/hepr.13607

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ags3.12412

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00280-020-04178-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.pan.2020.07.011

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.6002/ect.2020.0041

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are reportedly predictive of the long-term outcomes of several cancers. We evaluated their correlations with the post-surgical long-term outcomes of patients with mass-forming (MF) intrahepatic cholangiocarcinoma (ICC). Methods: The subjects of this study were 52 patients who underwent hepatic resection for MF-ICC at our hospital. We measured the cutoff values of NLR, LMR and PLR, using receiver operating characteristic curves, and compared the survival rates of patients with high vs. those with low values. We also evaluated a prognostic scoring system based on significant inflammatory biomarkers. Results: The cutoff values for NLR, LMR, and PLR were 1.93, 4.78, and 98, respectively. The high-NLR and low-LMR groups had significantly worse prognoses than the low-NLR and high-LMR groups. We designed a scoring system using the inflammation score (IS) based on NLR and LMR values, stratifying patients into three groups with scores of 0, 1, or 2. The IS was significantly correlated with overall survival (OS), with 5-year survival rates by the IS score of 100% for 0, 61% for 1, and 32% for 2 (P = 0.011). The IS was found to be an independent predictor of OS in multivariate analysis. Conclusions: Our IS scoring system may predict long-term outcomes after surgery for MF-ICC.

DOI： 10.1007/s00595-019-01905-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.21037/hbsn.2019.09.14

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Metabolic syndrome (MS) is the most common long-term complication after liver transplantation, and it has been increasing in incidence. The aim of this study was to clarify the risk factors for each MS component -hypertension, diabetes mellitus, and dyslipidemia-after living-donor liver transplantation (LDLT), including characteristics of living-donors. Methods: Data related to clinicopathological parameters including MS components in 461 consecutive patients who underwent LDLT were analyzed retrospectively. Results: Prevalence of all MS components (hypertension, diabetes mellitus, and dyslipidemia) increased from 9.3%, 16.5%, and 7.2% before LDLT to 44.9%, 45.3%, and 50.8% after LDLT, respectively. By multivariate logistic regression analysis, the three factors, cyclosporine use (OR 2.086, P = 0.001), recipient age (OR 1.036, P = 0.001), and BMI (OR 1.072, P = 0.026) were independent predictors for post-LDLT hypertension. Next, the three factors, male recipient (OR 2.471, P < 0.001), recipient age (OR 1.039, P = 0.002), and donor BMI (OR 1.124, P = 0.012) were independent for post-LDLT diabetes mellitus. The four factors, cyclosporine use (OR 2.015, P = 0.001), prolonged prednisolone use (OR 1.928, P = 0.002), recipient age (OR 1.019, P = 0.037), and GRWR (OR 0.316, P = 0.037) were independent for post-LDLT dyslipidemia as well. Conclusions: Not only recipient-related factors but also donor-related factors were independently associated with each targeted post-LDLT MS component.

DOI： 10.1016/j.hpb.2019.08.008

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The processing of intracellular reactive oxygen species (ROS) by nuclear factor erythroid-derived 2-like 2 (Nrf2) and NADPH quinone oxidoreductase 1 (Nqo1) is important for tumor metastasis. However, the clinical and biological significance of Nrf2/Nqo1 expression in hepatocellular carcinoma (HCC) remains unclear. We aimed to clarify the clinical importance of Nrf2/Nqo1 expression in HCC and evaluate the association of Nrf2/Nqo1 expression with HCC metastasis. We also evaluated the impact of Nqo1 modulation on HCC metastatic potential. We used spheroids derived from HCC cell lines. In anchorage-independent culture, HCC cells showed increased ROS, leading to the upregulation of Nrf2/Nqo1. Futile stimulation of Nqo1 by β-lapachone induces excessive oxidative stress and dramatically increased anoikis sensitivity, finally diminishing the spheroid formation ability, which was far stronger than depletion of Nqo1. We analyzed 117 cases of primary HCC who underwent curative resection. Overexpression of Nrf2/Nqo1 in primary HCC was associated with tumor size, high α-fetoprotein, and des-γ-carboxy-prothrombin levels. Overexpression of Nrf2/Nqo1 was also associated with multiple intrahepatic recurrences (P =.0073) and was an independent risk factor for poor prognosis (P =.0031). NADPH quinone oxidoreductase 1 plays an important role in anchorage-independent survival, which is essential for survival for circulation and distant metastasis of HCC cells. These results suggest that targeting Nqo1 activity could be a potential strategy for HCC adjuvant therapy.

DOI： 10.1111/cas.14320

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Extrahepatic malignancy is a relative contraindication for liver transplant in many countries. Nevertheless, the indications for living-donor liver transplantation (LDLT) for such patients vary by institution. Our aim was to reevaluate the indications for LDLT in patients with extrahepatic malignancy. We retrospectively reviewed data for 609 patients who underwent adult LDLT from May 1997 to January 2018 and analyzed patients with a history of extrahepatic malignancies or concurrent malignancies. Fourteen patients had extrahepatic malignancies concurrent with or before LDLT. Malignancies in 9 patients were detected during their systematic screening for LDLT. The mean duration between surgeries was 70 days (range, 20-209 days). Five patients had a history of extrahepatic malignancies before considering LDLT. The estimated 5-year survival rate was 100%. Although the risk and long-term prognosis of patients with extrahepatic malignancy are not well known, such patients can be candidates for LDLT if they undergo curative surgery for the malignancy, and if the prognosis of the malignancy is the same or superior to that of LDLT.

DOI： 10.1016/j.transproceed.2019.12.041

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hepatocellular carcinoma (HCC) has a poor prognosis in the setting of chronic inflammation and fibrosis, both of which promote nuclear DNA oxidative damage. 8-hydroxy-deoxyguanosine (8-OHdG) DNA glycosylase (OGG1) enhances the repair of 8-OHdG, which is the primary oxidative stress-induced mutation that leads to malignant alterations. This study aims to clarify the relationships between oxidative stress-induced factors and HCC progression. The clinicopathological factors were compared with immunohistochemistry OGG1 and 8-OHdG expressions in 86 resected HCC specimens. High 8-OHdG expression was associated with high serum aspartate transaminase and total bilirubin levels, as well as a low platelet count, compared with low 8-OHdG expression. Histological liver cirrhosis and poor differentiation were more frequent in patients with high 8-OHdG expression than in those with low 8-OHdG expression. The 8-OHdG was negatively correlated with OGG1 expression in HCC patients. Therefore, we classified the patients into two groups, low OGG1/high 8-OHdG group and the other group. The patients with low OGG1/high 8-OHdG expressions had worse prognosis than those with the other expressions. Our results showed that low OGG1/high 8-OHdG expressions in nuclei influence HCC patient outcomes. Evaluating the patterns of OGG1 and 8-OHdG expressions might provide pivotal prognostic biomarkers in patients with HCC.

DOI： 10.1111/pin.12952

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Osteopenia, loss of bone mineral density (BMD), was recently identified to be independently associated with early marker of deconditioning that precedes sarcopenia in patients with hepatocellular carcinoma (HCC). The aim of this study was to clarify the impact of osteopenia as the risk factor for mortality after living donor liver transplantation (LDLT) compared with already-reported biological markers. Methods: Data were collected retrospectively for all consecutive patients who underwent LDLT for HCC at our institution between January 1998 and December 2015. BMD was evaluated with computed tomographic measurement of pixel density in the midvertebral core of the 11th thoracic vertebra. Data related to clinicopathological parameters and prognosis were analyzed. Results: The median value of BMD was 163.6 Hounsfield units and osteopenia was identified in 103 (53.4%) of the 193 recipients, according to the age-specific formula. In addition to the other tumor burdens, such as tumor numbers ≥5 (HR 2.521, P = 0.027), DCP levels >200 mAU/mL (HR 2.678, P = 0.006), and neutrophil-to-lymphocyte ratio ≥3.01 (HR 2.068, P = 0.025), osteopenia (HR 2.106, P = 0.024) was independent risk factor for mortality by multivariate analysis. Overall survival of the patients who met the two risk factors and more was significantly lower than the others (HR 5.382, P < 0.001). Besides, the calibration plot for the 5-year overall survival using nomogram was predicted very well (C-index 0.746). Conclusions: Preoperative osteopenia was independently associated with post-LDLT mortality among patients with HCC. Moreover, risk score and nomogram with calibration curve were developed to confirm the clinical usefulness of osteopenia for post-LDLT patients.

DOI： 10.1007/s00268-019-05206-5

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The Japan criteria (JC, maximum tumor size within 5 cm, within five tumor nodules, AFP within 500 ng/mL or within Milan criteria) have been applied to cadaveric liver transplantation (LT) for hepatocellular carcinoma (HCC) and will be used for living donor LT (LDLT) in Japan. The aim of this study was to verify the JC in LDLT and to clarify the risk factor of HCC recurrence and mortality after LDLT beyond the JC. Patients and methods: Adult patients who underwent LDLT for end-stage liver disease with HCC until October 2019 were reviewed retrospectively (n = 246). Patients were divided into two groups according to whether they were within JC (n = 203) or beyond JC (n = 43). Recurrence-free or overall survival rates after LDLT were compared. Univariate and multivariate analyses were performed to identify risk factors of HCC recurrence and HCC-related mortality after LDLT for patients beyond the JC. Results: Patients beyond the JC had significantly poorer 5-year recurrence-free (50.3% vs 95.9%, P <.001) or overall (61.7% vs 98.1%, P <.001) survival rates compared with patients within the JC. A multivariate analysis revealed that des-gamma-carboxy prothrombin (DCP) ≥ 300 mAU/mL (hazard ratio 9.36, 95% CI; 2.41-36.4, P =.001) was an independent risk factor for HCC recurrence and HCC-related mortality (hazard ratio 13.8, 95% CI; 1.92-98.6, P =.01) after LDLT in patients beyond the JC. Conclusion: The outcome of LDLT for patients within the JC was favorable. Patients beyond the JC with DCP ≥ 300 mAU/mL might be contraindicated for LDLT.

DOI： 10.1002/ags3.12335

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction: The aim of this study was to clarify the impact of middle hepatic artery reconstruction on the outcomes of duct-to-duct biliary anastomosis after living donor liver transplantation (LDLT) using the left lobe. Materials and Methods: Among 258 patients who underwent LDLT using the left lobe, 216 patients who underwent hepatic artery reconstruction and one hepatic duct reconstruction with duct-to-duct interrupted anastomosis were divided into three groups: Group A (n = 123), one arterial stump with left hepatic artery reconstruction; Group B (n = 32), two arterial stumps with only left hepatic artery reconstruction; and Group C (n = 61), two arterial stumps with reconstruction of the left and middle hepatic arteries. The outcomes after LDLT were compared among the three groups. Results: No hepatic artery complications occurred. Group B had a significantly greater incidence of anastomotic biliary stricture than Group C. A multivariate analysis with Cox regression revealed that being in Group B was the only significant independent risk factor for postoperative anastomotic biliary stricture after LDLT. Conclusions: Middle and left hepatic artery reconstruction is safe in LDLT and may prevent biliary stricture caused by dual hepatic artery reconstruction when the graft has left and middle hepatic artery stumps.

DOI： 10.1111/ctr.13850

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The surgical indication for non-hypervascular hypointense nodules (NHVN) detected incidentally on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) for classical hepatocellular carcinoma (HCC) is unknown. Our aim is to clarify the long-term outcomes in patients with this finding. Methods: We reviewed the cases of 290 HCC patients, including 66 patients with NHVN, who underwent Gd-EOB-MRI prior to hepatectomy, between October 2008 and December 2017 at our center. We divided the patients into three groups: a no-NHVN group, a treated NHVN group, and an untreated NHVN group. Results: There was no significant difference in (RFS) or overall survival (OS) between the no-NHVN and untreated NHVN groups (p = 0.103 and 0.103, respectively). There was no significant difference between these two groups after propensity score matching. Multivariate analyses showed that microscopic intrahepatic metastases and the size of the main classical HCC, the target tumor, were independent prognostic factors of overall survival, but the presence of non-hypervascular hypointense nodules was not. There was no significant difference in RFS or OS between the treated NHVN and untreated NHVN groups (p = 0.158 and 0.109, respectively). Conclusions: Non-hypervascular hypointense nodules detected incidentally on Gd-EOB-MRI associated with targeted hypervascular HCC did not reflect prognosis of HCC after hepatectomy. Surgical procedures for classical enhancing HCC may be performed even if non-hypervascular hypointense nodules adjacent to the targeted HCC cannot be removed completely.

DOI： 10.1245/s10434-020-08419-4

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: There is increasing evidence that inflammation-based prognostic scores are stage-independent predictors of poor outcome in patients with hepatocellular carcinoma (HCC). However, these findings were observed in a small-sized study comparing the prognostic value of these scores for patients after curative resection for HCC. Methods: We retrospectively analyzed 717 consecutive patients with HCC who underwent curative liver resection at Hiroshima Red Cross Hospital & Atomic Bomb Survivors Hospital. Clinicopathological variables including preoperative inflammation-based prognostic scores, such as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Controlling Nutritional Status score, prognostic nutritional index (PNI), and Glasgow Prognostic Score were analyzed. The prognostic value of these scores was compared by the time-dependent receiver operating characteristic curve analyses. Results: The integrate area under the curve of PNI, Controlling Nutritional Status score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and Glasgow Prognostic Score were 0.6751, 0.6435, 0.5845, 0.5276, and 0.5351 for overall survival (OS), respectively, and 0.5955, 0.5694, 0.4692, 0.4873, and 0.5272 for disease-free survival, respectively. Multivariate analyses for prognosis factor in HCC patients showed that PNI was an independent predictor of both OS (HR 0.91, P < 0.001) and disease-free survival (HR 0.94, P < 0.001). When the patients were divided into high and low PNI groups, the patients in the low PNI group had significant poorer OS (P < 0.001) and disease-free survival (P < 0.001), even after background factors were matched between these two groups. Conclusions: PNI is superior to Controlling Nutritional Status score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, or Glasgow Prognostic Score as a predictor of OS and recurrence-free survival in patients with HCC who underwent curative hepatic resection.

DOI： 10.1111/hepr.13431

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Management of portal vein thrombosis (PVT), especially advanced PVT involving the superior mesenteric vein (SMV), in living donor liver transplantation (LDLT) is challenging. There were 514 adults who underwent LDLT between 2005 and 2018 included in this retrospective study, and PVT was observed in 67 (13.0%) patients. The LDLT recipients with PVT were characterized by increased portal pressure at laparotomy (26.1 ± 6.0 versus 24.3 ± 5.9 mm Hg; P = 0.03) and at closure (16.8 ± 3.9 versus 15.6 ± 3.6 mm Hg; P = 0.02), increased operative blood loss (14.6 ± 29.7 versus 5.7 ± 6.3 L; P < 0.01), and decreased 1-year graft survival (83.5% versus 92.8%; P = 0.04). Among the 18 patients with atrophic or vanished portal vein on pre-LDLT computed tomography, significant portal atrophy was actually observed only in 1 (5.6%) patient during LDLT surgery. For advanced PVT (n = 7) involving SMV in era 1, we performed nonanatomical inflow reconstruction using interposition grafts, resulting in significant inflow problems in 4 (57.1%) patients. Thus, for the patients with advanced PVT (n = 4) in era 2, we abandoned nonanatomical reconstruction and applied extensive thrombectomy under ultrasound guidance with secure shunt ligation, resulting in no inflow problems and no graft loss. In conclusion, even for advanced PVT involving SMV, extensive thrombectomy under sonogram guidance followed by anatomical inflow reconstruction and shunt ligation is a legitimate strategy in adult LDLT with PVT.

DOI： 10.1002/lt.25623

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. Materials and methods, and results: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. Conclusion: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival.

DOI： 10.1007/s10147-019-01499-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum glycomarker used to assess liver fibrosis. However, it has been reported that M2BPGi is likely to reflect other factors not limited to liver fibrosis. Methods: We retrospectively analyzed 79 patients with liver tumors who underwent liver resection. M2BPGi was measured within 1 week before operation and almost 1 month after operation. We introduced a value termed the “ΔM2BPGi ratio” (=M2BPGi_{after operation}/M2BPGi_{before operation}), and analyzed factors that influenced the ΔM2BPGi ratio. Results: The median value of the ΔM2BPGi ratio was 1.28 (range, 0.36-5.68). In 64 patients (81.0%), the cutoff index values of M2BPGi were elevated approximately 1 month after operation, especially in patients who experienced post-hepatectomy liver failure (PHLF). Multiple linear regression showed total Pringle time, PHLF grade ≥B, and preoperative value of creatinine were significant predictors of the ΔM2BPGi ratio. The mean values of the ΔM2BPGi ratio were 1.37 ± 0.07, 1.52 ± 0.22, and 2.94 ± 0.30 for PHLF grade 0, grade A, and grade B, respectively, resulting in statistically significant differences by the Kruskal-Wallis test (P = 0.022). Conclusions: Total Pringle time, PHLF grade ≥B, and preoperative creatinine significantly influenced the elevation of M2BPGi almost 1 month after liver resection. This study strongly affirms the previous suggestion that M2BPGi is likely to reflect other factors not limited to liver fibrosis.

DOI： 10.1002/ags3.12271

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Tumor immune reactions not only provide host defense but also accelerate tumor immune escape and phenotype switching. Here, we examined the association of programmed cell death ligand 1 (PD-L1) expression with epithelial-mesenchymal transition (EMT)–associated markers in pancreatic ductal adenocarcinoma (PDA) within the context of the tumor microenvironment. Materials and methods: PDA samples from 36 patients were analyzed for PD-L1, vimentin, E-cadherin, and Snail expressions and for PDA cell and immune cell infiltration. PD-L1 expression and EMT in PDA cell lines under conditions of altering interferon gamma (IFN-γ) signals were also assessed. Results: Immunohistochemistry revealed a significant correlation between vimentin and PD-L1 expression, whereas double staining showed them to be simultaneously expressed by PDA cells. Positive vimentin expression was associated with the infiltration of a lower number of CD8 ⁺ T cells and a higher number of FoxP3 ⁺ cells and poor patient prognosis (P = 0.03). PDA tumor cells promoted PD-L1 expression and EMT under the presence of IFN-γ which was inhibited by the signal transducer and activator of transcription (STAT)1 small interfering RNA. Conclusions: Strong correlations were observed between PD-L1 expression, EMT, and the immunosuppressive tumor microenvironment. Targeting STAT1 combined with PD-1/PD-L1 immunotherapy may improve outcomes for patients with PDA.

DOI： 10.1016/j.jss.2019.02.038

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: We studied the prognostic impact of sarcopenia after hepatic resection for intrahepatic cholangiocarcinoma (ICC). Methods: Sixty-one patients who underwent surgery for ICC during 2000–2017 were analyzed retrospectively. Psoas muscle areas were measured on CT scans at the third lumbar vertebra. Areas less than the sex-specific median were deemed low skeletal muscle masses (SMMs). Results: Low-SMM patients were significantly more often older (p = 0.002) than high-SMM patients, had lower serum albumin (p = 0.004), higher serum C-reactive protein (CRP) (p = 0.002), and higher carbohydrate antigen 19-9 (p < 0.001). Five-year overall survival rates were 72.5% and 17.6% and 5-year recurrence-free survival rates were 58.6% and 21.1%, respectively, in high- and low-SMM patients. Multivariable analysis revealed that low SMM predicted unfavorable prognoses. SMM was associated with immune nutritional status (e.g., prognostic nutritional index, Glasgow prognostic score, CRP/albumin ratio). Conclusion: Low SMM was related to worse surgical outcomes in patients with ICC following hepatic resection.

DOI： 10.1016/j.amjsurg.2019.03.010

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction: The aim of this study was to evaluate the effect of hepatic artery (HA) size mismatch anastomosis on outcomes after living-donor liver transplantation (LDLT). Materials and methods: After excluding 128 patients with the exclusion criteria among 233 LDLTs using the right lobe, 104 LDLT patients were divided into two groups: donor HA diameter that was greater than or equal to the recipient HA diameter (D ≥ R group; n = 79), and donor HA diameter that was smaller than the recipient HA diameter (D < R group; n = 25). Results: Hepatic artery-related complications occurred in only one patient (HA thrombosis; 1.0%) who was in the D < R group. The reconstructed HA flow in the D ≥ R group was significantly greater than that in the D < R group (P = 0.015). There was a higher incidence of anastomotic biliary stricture in the D < R group (32.0%) compared with the D ≥ R group (13.9%, P = 0.022) after LDLT. A multivariate analysis with Cox regression revealed that the HA anastomosis of the D < R group and hepaticojejunostomy were significant independent risk factors for postoperative anastomotic biliary stenosis. Conclusions: Hepatic artery anastomosis with a donor HA diameter smaller than that of the recipient HA might be an independent risk factor for postoperative biliary stenosis after LDLT using the right lobe.

DOI： 10.1111/ctr.13444

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/lt.25339

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Autophagy has a critical role in liver regeneration. However, no studies have demonstrated autophagic flux in the regenerating fatty liver. The aim of this study was to clarify the dynamics of autophagy in the regeneration of the fatty liver. Following 70% partial hepatectomy (PH) in db/db fatty mice, which is a non-alcoholic fatty liver disease (NAFLD) model, we investigated the survival rate and recovery of liver volume. Histological examination of the regenerating liver was examined using electron microscopy. The 7-day survival rate after PH in db/db mice was 20%, which was significantly lower than that in control mice (P<.01). Liver regeneration within 48 h after PH was significantly impaired in db/db mice (P<.05). The number of proliferating cell nuclear antigen (PCNA) positive cells and the expression levels of cell-cycle markers cyclins D, E, and A were lower in db/db mice compared with controls. In the regenerating liver, LC3-II level was higher in db/db mice, but p62 expression was increased and cathepsin D expression, a marker of autophagolysosome proteolysis, was decreased compared with controls. Additionally, electronic microscopy revealed that autophagosomes during liver regeneration in db/db mice were mainly located in lipid droplets. Our findings indicate that the different localization of autophagosomes in db/db mice compared with controls led to impairment of liver regeneration in the fatty liver.

DOI： 10.1080/15476278.2019.1633872

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aim: The effects of oxidative stress on various carcinomas were reported in previous studies, but those in intrahepatic cholangiocarcinoma (ICC) have not been fully elucidated. The purpose of this study was, thus, to reveal the effects of oxidative DNA damage and repair enzymes on ICC. Materials and Methods: The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-OHdG DNA glycosylase (OGG1) were immunohistochemically evaluated in specimens resected from 63 patients with ICC. Results: Low OGG1 expression was related to tumour depth T4 (p=0.04), venous invasion (p=0.0005), lymphatic vessel invasion (p=0.03), and perineural invasion (p=0.03). Compared to the high-OGG1-expression group, patients with low OGG1 expression had a significantly poorer prognosis (overall survival: p=0.04, recurrence-free survival: p=0.02). Unlike for OGG1, the expression levels of 8-OHdG showed no association with prognosis. Conclusion: Oxidative DNA damage and DNA repair enzymes may be closely related to ICC progression.

DOI： 10.21873/anticanres.13465

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Backgrounds: Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is an extended surgical procedure for patients with locally advanced cancer of the pancreatic body and tail. Recently, the usability of neoadjuvant chemotherapy (NAC) in pancreatic cancer was reported. The purpose of this study was to clarify the impact of NAC on surgical outcomes and prognosis in DP-CAR patients. Methods: This study retrospectively reviewed 20 consecutive patients who underwent DP-CAR at a single institution. Results: Eleven of 20 patients (55.0%) received NAC. Their first regimens were gemcitabine (GEM) plus nab-PTX (n = 7, 63.6%), GEM plus S-1 (n = 3, 27.3%), and GEM (n = 1, 9.1%). Although two patients converted to a second regimen, none abandoned NAC due to adverse effects or could not undergo a planned procedure for disease progression. There were no significant differences in intraoperative variables, morbidity, including pancreatic fistula and delayed gastric emptying, and mortality between patients with and without NAC; however, patients with NAC had a significantly lower proportion of arterial invasion (p = 0.025), lymphatic invasion (p < 0.0001), and vascular invasion (p = 0.035). There were no significant differences in the induction rate of adjuvant chemotherapy (p = 0.201). The recurrence-free survival and overall survival rates in patients with NAC were significantly higher than in patients without NAC (p = 0.041 and p = 0.018, respectively). Conclusion: DP-CAR following NAC was associated with a preferable prognosis and had no negative effect on surgical outcomes. Therefore, NAC in DP-CAR patients might be a beneficial and safe therapeutic strategy.

DOI： 10.1007/s11605-019-04324-8

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Chimeric mice with humanized liver were first established by transplanting primary human hepatocytes (PHHs) isolated from a Japanese 27-year-old donor into complementary DNA-urokinase-type plasminogen activator/severe combined immunodeficiency mice. The PHHs from the Japanese donor increased more than 100-fold in the mouse liver, and human hepatocytes purified from the chimeric mouse liver (hcPHs) were successfully transplanted into second-passaged mice. These PHHs and hcPHs can produce human albumin and preserve many liver-specific enzyme genes, which are important for liver function. Interestingly, hepatitis B virus can be infected with these chimeric mice; hepatitis B viral DNA and hepatitis B surface antigen levels were detectable. In conclusion, hcPHs can be an ideal cell source for analysis of human hepatocytes.

DOI： 10.1016/j.transproceed.2018.06.035

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aim: Computed tomography (CT) has recently been applied to measure bone mineral density (BMD). However, the definition of osteopenia, which means depletion of BMD, using CT remains controversial. The aim of this study was to establish formulae to calculate standard BMD. Patients and Methods: Fifty healthy donors for liver transplantation underwent CT. BMD was measured as crosssectional average pixel density (Hounsfield units) only in trabecular-bone at Th11 bottom. Validation was performed on another 50 healthy donors to check the accuracy of formulae for standard BMD. Results: Measured BMD was significantly correlated with age in both males and females (p<0.0001). The formulae to calculate standard BMD were 308.82-2.49 × Age in males and 311.84-2.41 × Age in females. Estimated BMD was significantly correlated with measured BMD in males and females (p<0.0001). Conclusion: Osteopenia can be defined by the difference between measured data and calculated data using our new formula based on each age.

DOI： 10.21873/anticanres.13009

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recent studies revealed that systemic inflammation was correlated with poorer prognosis in various cancers. We investigated the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients who underwent living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). We retrospectively analyzed the records of 216 patients who underwent LDLT for HCC. Patients were divided into high (n = 126) and low (n = 90) LMR groups. Their clinicopathological parameters and survival times were compared. To determine the mechanisms of the change in the LMR, we performed immunohistochemical analyses of CD3 and CD68 expression. A low LMR was significantly associated with a high Model for End-Stage Liver Disease score; a high Child-Pugh score; elevation of alpha-fetoprotein, des-gamma-carboxyprothrombin, and neutrophil-to-lymphocyte ratio; larger tumor size; more tumors; and poorer prognosis. A low LMR was associated with poor prognosis and represented an independent prognostic factor, particularly among patients beyond the Milan criteria. The ratio of CD3-positive to CD68-positive cells was significantly lower in the low-LMR group. In conclusion, our results show that the LMR was an independent predictor of survival of patients with HCC beyond the Milan criteria who underwent LDLT. The LMR reflected the immune status of the tumor microenvironment.

DOI： 10.1002/lt.25204

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The Controlling Nutritional Status (CONUT) score is an objective tool that is widely used to assess the nutritional status in patients, including those with cancer. The relationship between the CONUT score and prognosis in patients who have undergone hepatic resection has not been evaluated in a multi-institutional study. Methods: Data were retrospectively collected for 2461 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent at 13 institutions between January 2004 and December 2015. Patients were assigned to two groups: preoperative CONUT scores ≤ 3 (low CONUT score) and ≥ 4 (high CONUT score). Clinicopathological characteristics, surgical outcomes, and long-term survival were compared using propensity score matching analysis. Results: Of the 2461 patients, 540 (21.9%) had high (≥ 4) and 1921 (78.1%) had low (≤ 3) preoperative CONUT scores. Overall, a high CONUT score was significantly associated with older age, female sex, low body mass index, low serum albumin, high serum total bilirubin, low lymphocyte count, low serum cholesterol, shorter prothrombin time, higher indocyanine green retention test at 15 min, Child–Pugh B (vs. A), liver cirrhosis, minor resection, shorter operation time, massive blood loss, blood transfusion, and postoperative complications. After propensity score matching, a higher CONUT score was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS) using multivariate analysis. Conclusions: This retrospective, multi-institutional analysis showed that, in patients who undergo curative hepatectomy for HCC, the preoperative CONUT score is predictive of worse OS and RFS, even after propensity score matching analysis.

DOI： 10.1245/s10434-018-6672-6

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim The clinical impact of pathological classification based on architectural pattern in hepatocellular carcinoma (HCC) remains elusive in spite of its well-known and common feature. Methods The prognostic impact of pathological classification was examined with prospective database. Three hundred and eighty HCC patients who underwent curative hepatectomy as an initial treatment in Kumamoto University were enrolled as a test cohort. The outcome was confirmed with a validation cohort in Kyushu University. Results Macrotrabecular (macro-T) subtype (n = 38) and compact subtype (n = 43) showed similar biological and prognostic features. Both showed higher AFP level and worse overall survival than microrabecular (micro-T) subtype (n = 266). Multivariate analysis for overall survival revealed that DCP 40, multiple tumor and macro-T/compact subtype were associated with poor overall survival (risk ratio = 2.2, 1.6 and 1.6; p = 0.002, 0.020, and 0.047, respectively). Of note, 32% of macro-T/compact subtype showed early recurrence within 1 year, which showed substantially low (5%) 5 year overall survival, whereas 16% of micro-T/PG subtype did. Twenty-one percent of macro-T/compact subtype showed multiple intrahepatic metastases ( 4) or distant metastases, which resulted in non-curative treatment, whereas 5% of micro-T/PG subtype did. In validation cohort, macro-T/compact subtype was an independent predictor of worse overall survival. Conclusion Macro-T/compact subtype is biologically discriminated from micro-T and PG subtypes due to its aggressive features and poor prognosis after curative treatment. Additional treatment with curative hepatectomy on Macro-T/compact subtype should be discussed because of high possibility of systemic residual cancer cell.

DOI： 10.1371/journal.pone.0203856

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aim: This study’s aim was to investigate the safety and effectiveness of asunaprevir and daclatasvir treatment for recurrent hepatitis C virus (HCV) infection in transplant recipients. The study cohort comprised 14 transplant recipients with recurrent hepatitis C who were receiving asunaprevir and daclatasvir. Patients and Methods: Serum concentrations of asunaprevir and daclatasvir, their therapeutic effects, trough concentrations/dose ratios of tacrolimus, and adverse effects were evaluated. Results: Hepatitis C virus was still undetectable in 12 (85.7%) out of 14 patients 12 weeks after completing treatment. One week after starting treatment, asunaprevir concentrations were significantly higher in patients with baseline albumin concentrations ≤3.6 g/dl than in those with baseline albumin concentrations >3.6 g/dl. No marked fluctuations were identified in tacrolimus trough concentrations/dose ratios during the 24 weeks of therapy. Conclusion: Full doses of asunaprevir and daclatasvir-based treatment can be safely and effectively administered to liver transplant recipients for recurrent HCV genotype 1b after living donor liver transplantation (LDLT) with little effect on blood concentrations of tacrolimus.

DOI： 10.21873/anticanres.12885

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Although risk factors for the long-term mortality of liver transplantation are well described, there is a lack of detailed study regarding these factors for adult living donor liver transplantation (LDLT). Methods We retrospectively analyzed 528 adult LDLT recipients in our hospital. The risk factors were analyzed for overall deaths more than 5 years post-LDLT. Results Over the 20-year follow-up, 137 patients died. Patient survival at 1, 3, 5, and 10 years post-LDLT was 87.8%, 81.8%, 79.4%, and 72.8%, respectively. The independent risk factors for more than 5 years post-LDLT overall death were hepatocellular carcinoma recurrence (hazard ratio [HR], 38.9; P < 0.001), lymphoid de novo malignancy (HR, 47.2; P = 0.001), primary sclerosing cholangitis as primary diagnosis (HR, 11.5; P < 0.001), chronic rejection (HR, 6.93; P = 0.006), acute rejection (HR, 2.96; P = 0.017), and bile duct stenosis (HR, 2.30; P = 0.045). Conclusions Not only malignancies and rejection but also bile duct stenosis and primary sclerosing cholangitis had significant impacts on late period post-LDLT mortality.

DOI： 10.1097/TP.0000000000002324

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The prognosis of hepatocellular carcinoma (HCC) with portal hypertension (PH) is very poor. Splenomegaly is considered important evidence of PH. Our aim was to clarify the prognostic value of splenic volume (SV) and the effect of splenectomy on the prognosis of HCC within the Milan criteria after curative hepatectomy. Methods: In this single-center retrospective study, we reviewed 160 patients with HCC that met the Milan criteria, including 138 who had undergone hepatectomy and 22 who had undergone hepatectomy and splenectomy between July 2004 and December 2010. SV was measured by three-dimensional computed tomography and patients allocated to three groups (high SV ≥300 mL; low OpenSPiltSPi300 mL; and splenectomy) to compare post-hepatectomy survival rates. Results: Multivariate analyses showed that SV is an independent prognostic factor for overall and disease-free survival. The overall survival rates at 5 years in the high SV, low SV, and splenectomy groups were 39, 75, and 88%, respectively. The overall survival rate in the high SV group was significantly worse than in the low SV and splenectomy groups (P OpenSPiltSPi 0.001). There was no significant difference between the low SV and splenectomy groups (P = 0.831). Conclusions: High SV is an independent predictor of post-hepatectomy HCC recurrence and overall survival. There is no significant difference in prognosis between low SV and splenectomy groups, even though the latter had high SV. Combined splenectomy with hepatectomy for HCC and PH may improve prognosis and be an appropriate alternative when liver transplantation cannot be performed.

DOI： 10.1007/s00268-017-4232-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: Liver ischemia–reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High-mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage-associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury. Methods: Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1. Results: In rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(−) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(−) group after surgery (P < 0.001). The levels of tumor necrosis factor-α and interleukin-6 in the liver tissue 24 h after surgery were significantly lower in the rTM(+) group than the rTM(−) group (P < 0.001). The plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(−) group (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(−) group (P < 0.001). Conclusions: Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1.

DOI： 10.1111/hepr.13005

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: We aimed to evaluate the effect of antibody to hepatitis B core antigen (HBcAb) positivity on clinical outcomes after hepatic resection in hepatocellular carcinoma (HCC) patients with negative hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb), termed non-B, non-C HCC (NBNC-HCC), or with HCV-related HCC. Methods: Two hundred and sixty-three patients who underwent hepatic resection for HCC and measurements of HBsAg, HCVAb, and HBcAb were enrolled in this study. Results: The percentages of HBcAb positivity were 52.3% (n = 57) and 56.9% (n = 66) in patients with NBNC- and HCV-related HCC, respectively. The proportion of multiple NBNC-HCCs was significantly greater in patients with HBcAb positivity compared to HBcAb negativity (P = 0.028). There were no significant differences in the recurrence-free and overall survival rates between NBNC-HCC patients with HBcAb positivity versus negativity (P = 0.461 and P = 0.190, respectively). Furthermore, for HCV-related HCC patients, there were no significant differences in the baseline factors between patients with positive versus negative HBcAb. The proportion of patients with HBcAb-positive HCV-related HCC who underwent anatomical resection of the liver was significantly greater than that of HBcAb-negative patients, whereas the recurrence-free and overall survival rates were not significantly different (P = 0.158 and P = 0.191, respectively). Conclusion: In our study, the presence of HBcAb had no impact on surgical outcomes after hepatic resection in patients with NBNB- and HCV-related HCC. Occult HBV infection might be associated with hepatocarcinogenesis in patients with NBNC-related HCC.

DOI： 10.1111/hepr.12939

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Laparoscopic gastric devascularization(Lap GDS) and splenectomy (SPL) for gastric varices is technically challenging because of highly developed collateral vessels and bleeding tendency. We investigated the feasibility of customization of Lap GDS and SPL based on CT vascular anatomy. Methods: We analyzed 61 cirrhotic patients with gastric varices who underwent Lap GDS and SPL between 2006 and 2014. Lap GDS was customized according to the afferent feeding veins (left gastric vein (LGV) and/or posterior gastric vein (PGV)/short gastric vein (SGV)) and efferent drainage veins (gastrorenal shunt and/or gastrophrenic shunt, or numerous retroperitoneal veins) based on CT imaging. Results: Thirty-four patients with efferent drainage veins suitable for balloon-occluded retrograde transvenous obliteration (B-RTO) underwent B-RTO instead of surgical GDS, with subsequent Lap SPL. Among 27 patients with gastric varices unsuitable for B-RTO, 15 patients with PGV/SGV underwent Lap GDS of the greater curvature and SPL, and 12 patients with LGV or LGV/PGV/SGV underwent Lap GDS of the greater and lesser curvature and SPL. The mean operation time was 294 min and mean blood loss was 198 g. There was no mortality or severe morbidity. Gastric varices were eradicated in all 61 patients, with no bleeding or recurrence during a mean follow-up of 55.9 months. The cumulative 3-, 5-, and 7-year survival rates were 92, 82, and 64%, respectively. Conclusions: Lap GDS and SPL customized based on CT vascular anatomy is a safe and effective procedure for treating gastric varices.

DOI： 10.1007/s00464-017-5646-2

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: The aims of this study were to clarify the relationship of gait speed, hand grip strength, and skeletal muscle mass with complications after hepatic resection and to identify risk factors for complications in patients who underwent hepatic resection. Methods: We evaluated the risk factors for complications after hepatic resection in 154 consecutive patients. Preoperative factors included gait speed, hand grip strength, and skeletal muscle mass. The gait speed and hand grip strength of patients were measured by physical therapists, and skeletal muscle mass was measured by computed tomography. Multivariate logistic regression analyses using preoperative factors were performed to assess predictors of the development of complications after hepatic resection. Results: Thirty-three patients (21.4%) developed complications after hepatic resection. These patients had a significantly lower serum albumin level (p = 0.015), slower gait speed (p = 0.007), higher rate of hepatic resection ≥ 2 Couinaud segments (p = 0.014), and lower rate of laparoscopic hepatic resection (p = 0.017) than patients without complications. Multivariate analysis revealed that a gait speed ≤ 1.10 m/s and a serum albumin level of ≤ 4.0 g/dl were independent risk factors for complications after hepatic resection. Conclusions: Slow gait speed and low serum albumin level are significant risk factors for complications after hepatic resection. These data will be helpful for perioperative patient management.

DOI： 10.1007/s11605-018-3993-5

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Liver transplantation has been established as the optimal treatment for hepatocellular carcinoma in cirrhotic patients, but hepatic resection is also effective in patients with well-preserved liver function. Determining the suitable surgical treatment for patients with Child–Pugh class B cirrhosis is a more difficult challenge.Methods: We retrospectively compared the results of hepatic resection and living donor liver transplantation for hepatocellular carcinoma in 137 patients with Child–Pugh class B cirrhosis. The procedures were performed at Kyushu University Hospital from April 2014 through October 2016. Results: Patients who underwent hepatic resection were significantly older and had better liver function, larger tumor size, smaller number of tumors, and less surgical stress compared with patients who underwent living donor liver transplantation. The overall survival rate and the recurrence-free survival rate in patients with transplantation were significantly better than that in patients with resection. The multivariate analysis showed that recurrent hepatocellular carcinoma and microvascular invasion were significant prognostic factors for both overall and recurrence-free survival in the hepatic resection group. In the group with protein induced by vitamin K absence or antagonist-II ≥300 mAU/mL, both the overall survival curve and the recurrence-free survival curve in patients with living donor liver transplantation were not significantly different from those in patients with hepatic resection. Conclusions: Living donor liver transplantation for hepatocellular carcinoma in patients with Child–Pugh class B cirrhosis was favorable under the condition of protein induced by vitamin K absence or antagonist-II <300 mAU/mL in selected recipients and donors. Hepatic resection for recurrent hepatocellular carcinoma and excessive blood loss should be avoided in patients with Child–Pugh class B cirrhosis.

DOI： 10.1007/s00268-018-4493-1

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jgh.13975

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Expanding patient selection beyond the Milan criteria in living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) has long been a matter for debate. We have used the Kyushu University Criteria – maximum tumor diameter <5 cm or des-γ-carboxy prothrombin <300 mAU/ml – in LDLT for HCC since June 2007. The aim of the present study was to present the results of our prospective patient selection by Kyushu University Criteria and to confirm whether or not our criteria were justified. Methods The entire study period was divided into the pre-Kyushu era (July 1999–May 2007) and the Kyushu era (June 2007–November 2014). Eighty-nine and 90 patients underwent LDLT for HCC in the pre-Kyushu era and the Kyushu era, respectively. Results In the pre-Kyushu era, there were significant differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients. In the Kyushu era, however, the differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients disappeared. The 5-year overall patient survival in the Kyushu era was 89.4%. Conclusion Our selection criteria enabled a considerable number of beyond-Milan patients to undergo LDLT without jeopardizing the recurrence-free, and disease-specific, and overall patient survival.

DOI： 10.1016/j.hpb.2017.08.004

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Sarcopenia is an independent predictor of death after living-donor liver transplantation (LDLT). However, the ability of the Asian Working Group for Sarcopenia criteria for sarcopenia (defined as reduced skeletal muscle mass plus low muscle strength) to predict surgical outcomes in patients who have undergone LDLT has not been determined. Methods This study prospectively enrolled 366 patients who underwent LDLT at Kyushu University Hospital. Skeletal muscle area (determined by computed tomography), hand-grip strength, and gait speed were measured in 102 patients before LDLT. We investigated the relationship between sarcopenia and surgical outcomes after LDLT performed in three time periods. Results The number of patients with lower skeletal muscle area has increased to 52.9% in recent years. The incidence of sarcopenia according to the Asian Working Group for Sarcopenia criteria was 23.5% (24/102). Patients with sarcopenia (defined by skeletal muscle area and functional parameters) had significantly lower skeletal muscle area and weaker hand-grip strength than did those without sarcopenia. Compared with non-sarcopenic patients, patients with sarcopenia also had significantly worse liver function, greater estimated blood loss, greater incidence of postoperative complications of Clavien-Dindo grade IV or greater (including amount of ascites on postoperative day 14, total bilirubin on postoperative day 14, and postoperative sepsis), and longer postoperative hospital stay. Multiple logistic regression analysis revealed sarcopenia as a significant predictor of 6-month mortality. Conclusions The combination of skeletal muscle mass and function can predict surgical outcomes in LDLT patients.

DOI： 10.1016/j.transproceed.2017.09.017

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: In recent years, the establishment of new staging systems for hepatocellular carcinoma (HCC) has been reported worldwide. The system combining albumin–bilirubin (ALBI) with tumor–node–metastasis stage, developed by the Liver Cancer Study Group of Japan, was called the ALBI-T score. Methods: Patient data were retrospectively collected for 357 consecutive patients who had undergone hepatic resection for HCC with curative intent between January 2004 and December 2015. The overall survival and recurrence-free survival were compared by the Kaplan–Meier method, using different staging systems: the Japan integrated staging (JIS), modified JIS, and ALBI-T. Results: Multivariate analysis identified five poor prognostic factors (higher age, poor differentiation, the presence of microvascular invasion, the presence of intrahepatic metastasis, and blood transfusion) that influenced overall survival, and four poor prognostic factors (the presence of intrahepatic metastasis, serum α-fetoprotein level, blood transfusion, and each staging system (JIS, modified JIS, and ALBI-T score)) that influenced recurrence-free survival. Patients for each these three staging system had a significantly worse prognosis regarding recurrence-free survival, but not with overall survival. The modified JIS score showed the lowest Akaike information criteria statistic value, indicating it had the best ability to predict overall survival compared with the other staging systems. Conclusions: This retrospective analysis showed that, in post-hepatectomy patients with HCC, the ALBI-T score is predictive of worse recurrence-free survival, even when adjustments are made for other known predictors. However, modified JIS is better than ALBI-T in predicting overall survival.

DOI： 10.1111/hepr.12868

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The Controlling Nutritional Status (CONUT) score is an objective tool widely used to assess nutritional status in patients with inflammatory disease, chronic heart failure, and chronic liver disease. The relationship between CONUT score and prognosis in patients who have undergone hepatic resection, however, has not been evaluated. Methods: Data were retrospectively collected for 357 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent between January 2004 and December 2015. The patients were assigned to two groups, those with preoperative CONUT scores ≤3 (low CONUT score) and >3 (high CONUT score), and their clinicopathological characteristics, surgical outcomes, and long-term survival were compared. Results: Of the 357 patients, 69 (19.3%) had high (>3) and 288 (80.7%) had low (≤3) preoperative CONUT scores. High CONUT score was significantly associated with HCV infection, low serum albumin and cholesterol concentrations, low lymphocyte count, shorter prothrombin time, Child–Pugh B and liver damage B scores, and blood transfusion. Multivariate analysis identified six factors prognostic of poor overall survival (older age, liver damage B score, high CONUT score, poor tumor differentiation, the presence of intrahepatic metastases, and blood transfusion) and five factors prognostic of reduced recurrence-free survival (older age, higher ICGR15, larger tumor size, presence of intrahepatic metastasis, and blood transfusion). Conclusions: In patients with HCC, preoperative CONUT scores are predictive of poorer overall survival, even after adjustments for other known predictors.

DOI： 10.1007/s00268-017-4097-1

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Autophagy is a homeostatic process regulating turnover of impaired proteins and organelles, and p62 (sequestosome-1, SQSTM1) functions as the autophagic receptor in this process. p62 also functions as a hub for intracellular signaling such as that in the mammalian target of rapamycin (mTOR) pathway. Liver stem/progenitor cells have the potential to differentiate to form hepatocytes or cholangiocytes. In this study, we examined effects of autophagy, p62, and associated signaling on hepatic differentiation. Adult stem/progenitor cells were isolated from the liver of mice with chemically induced liver injury. Effects of autophagy, p62, and related signaling pathways on hepatic differentiation were investigated by silencing the genes for autophagy protein 5 (ATG5) and/or SQSTM1/p62 using small interfering RNAs. Hepatic differentiation was assessed based on increased albumin and hepatocyte nuclear factor 4α, as hepatocyte markers, and decreased cytokeratin 19 and SOX9, as stem/progenitor cell markers. These markers were measured using quantitative RT-PCR, immunofluorescence, and Western blotting. ATG5 silencing decreased active LC3 and increased p62, indicating inhibition of autophagy. Inhibition of autophagy promoted hepatic differentiation in the stem/progenitor cells. Conversely, SQSTM1/p62 silencing impaired hepatic differentiation. A suggested mechanism for p62-dependent hepatic differentiation in our study was activation of the mTOR pathway by amino acids. Amino acid activation of mTOR signaling was enhanced by ATG5 silencing and suppressed by SQSTM1/p62 silencing. Our findings indicated that promoting amino acid sensitivity of the mTOR pathway is dependent on p62 accumulated by inhibition of autophagy and that this process plays an important role in the hepatic differentiation of stem/progenitor cells. J. Cell. Physiol. 232: 2112–2124, 2017.

DOI： 10.1002/jcp.25653

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Aim: Hepatic stellate cells (HSCs) play a central role in hepatic fibrosis and are regulated by Kupffer cells (KCs). Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA⁺-M2BP) was recently identified as a serum marker for hepatic fibrosis. Although WFA⁺-M2BP was identified as a ligand of Mac-2, the function of WFA⁺-M2BP in hepatic fibrosis remains unclear. Methods: Liver specimens were obtained from five patients with cirrhosis, five with chronic hepatitis, and five without hepatic fibrosis. WFA⁺-M2BP kinetics were evaluated histologically and in subpopulations of liver cells such as HSCs, KCs, endothelial cells, biliary epithelial cells, and hepatocytes in in vitro culture. The function of WFA⁺-M2BP in activated HSCs was evaluated using immunoblot analysis. Results: Numbers of WFA⁺-M2BP-positive cells in liver tissues increased with fibrosis stage. There were significant differences in WFA⁺-M2BP levels between fibrosis stages F0 and F1–2 (P = 0.012) and between fibrosis stages F1–2 and F3–4 (P < 0.001). HSCs were the source of WFA⁺-M2BP secretion in in vitro cultures of liver cells, as determined by sandwich immunoassay. Cells of the human HSC line LX-2 also secreted WFA⁺-M2BP. Histologically, tissue sections showed that WFA⁺-M2BP was located in Mac-2-expressing KCs. In vitro assays showed that exogenous WFA⁺-M2BP stimulation enhanced Mac-2 expression in KCs and that HSCs co-cultured with KCs increased α-smooth muscle actin expression. Finally, Mac-2-depleted KCs with short interfering RNA had reduced α-smooth muscle actin expression following co-culturing with HSCs. Conclusions: WFA⁺-M2BP from HSCs induces Mac-2 expression in KCs, which in turn activates HSCs to be fibrogenic.

DOI： 10.1111/jgh.13708

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive tumor-microenvironment (TME) that supports the growth of tumors and mediates tumors enabling evasion of the immune system. Expression of programmed cell death ligand 1 (PD-L1) and loss of human leukocyte antigen (HLA) class I on tumor cells are methods by which tumors escape immunosurveillance. We examined immune cell infiltration, the expression of PD-L1 and HLA class I by PDA cells, and the correlation between these immunological factors and clinical prognosis. PDA samples from 36 patients were analyzed for HLA class I, HLA-DR, PD-L1, PD-1, CD4, CD8, CD56, CD68, and FoxP3 expression by immunohistochemistry. The correlations between the expression of HLA class I, HLA-DR, PD-L1 or PD-1 and the pattern of tumor infiltrating immune cells or the patients’ prognosis were assessed. PD-L1 expression correlated with tumor infiltration by CD68⁺ and FoxP3⁺ cells. Low HLA class I expression was an only risk factor for poor survival. PD-L1 negative and HLA class I high-expressing PDA was significantly associated with higher numbers of infiltrating CD8⁺ T cells in the TME, and a better prognosis. Evaluation of both PD-L1 and HLA class I expression by PDA may be a good predictor of prognosis for patients. HLA class I expression by tumor cells should be evaluated when selecting PDA patients who may be eligible for treatment with PD-1/PD-L1 immune checkpoint blockade therapies.

DOI： 10.1002/cam4.1087

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The aim of this study was to identify the preoperative predictors of prognosis in patients with intrahepatic cholangiocarcinoma (ICC) undergoing resection. Patients and Methods: We enrolled 90 patients with ICC who underwent surgical resection, including 59 in whom surgery was considered curative, and measured the overall survival (OS), recurrence-free survival (RFS), and other outcomes and potential prognostic factorS. Results: Multivariate Cox proportional hazards analysis showed that tumor in the resection margins (R>0) independently predicted long-term OS in the whole cohort. In the curatively-resected group (R0), lymph node involvement was the only independent predictor of long-term OS. Multiple tumors, perihilar tumor location and serum carcinoembryonic antigen (CEA) concentration >2.2 ng/ml were independent predictors of lymph node involvement before curative resection. Conclusion: Patients with ICC with multiple tumors, perihilar tumors and serum CEA concentration >2.2 ng/ml in association with lymph node involvement may need additional preoperative chemotherapy.

DOI： 10.21873/anticanreS.11751

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Prognostic indicators of the malignant potential of pancreatic neuroendocrine tumors (PNET) are limited. We assessed tumor shape and enhancement pattern on contrast-enhanced computed tomography as predictors of malignant potential. Methods: Sixty cases of PNET patients undergoing curative surgery from 2001 to 2014 were enrolled onto our retrospective study. Preoperative enhanced CTs were assessed, and criteria defined for regularly shaped and enhancing tumors (group 1), and irregularly shaped and/or enhancing tumors (group 2). The relation of tumor shape and enhancement pattern to outcome was assessed. Results: Interobserver agreement was substantial (kappa = 0.74). Group 2 (n = 24) was significantly correlated with synchronous liver metastasis (23 vs. 0 %), lymph node metastasis (36 vs. 3 %), pathologic capsular invasion (68 vs. 8 %), larger tumor size (30 vs. 12 mm), tumor, node, metastasis classification system (TNM) stage III/IV disease (46 vs. 3 %), and histologic grade 2/3 (41 vs. 0 %). Multivariate analysis revealed that tumor grade 2/3 and group 2 criteria correlated with tumor relapse (hazard ratio 6.5 and 13.6, P = 0.0071 and 0.039, respectively), and that only group 2 criteria were independently correlated with poor overall survival (hazard ratio 5.56e + 9, P = 0.0041). Conclusions: Irregular tumor shape/enhancement on preoperative computed tomography is a negative prognostic factor after curative surgery for PNET.

DOI： 10.1245/s10434-016-5630-4

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: De novo malignancy, including primary lung cancer, is one of the limitations to long-term survival after liver transplantation. The purpose of this study was to describe patients who developed de novo lung cancer after living-donor liver transplantation (LDLT) and investigate their clinicopathological features as well as the feasibility of surgical resection. Patients and Methods: We investigated 554 patients who underwent LDLT. Results: De novo lung cancer after LDLT was observed in five (0.9%) out of 554 studied patients: four men and one woman, aged 61-78 years (mean=67 years). All four men had a smoking history. Clinical stages of de novo lung cancer were stage IA in three patients, and stage IB and IV in one patient each. Three out of five patients underwent pulmonary lobectomy and pathological stage was IA in two patients and IIA in one. All patients who underwent surgery stopped immunosuppressive therapy 1 day preoperatively and restarted on postoperative day 1. There were no serious postoperative complications. All three patients are still alive without any recurrence, with survival ranging from 8 to 29 months, with an average of 16.3 months after diagnosis of lung cancer. Conclusion: Although the study population was small, these results suggest that pulmonary lobectomy of de novo lung cancer after LDLT, even under immunosuppressive conditions, is a feasible procedure and may yield a survival benefit.

DOI： 10.21873/anticanres.11608

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Although posthepatectomy pleural effusion (PHPE) is a commonly observed phenomenon, its precise etiology and the impact of its emergence on oncological outcomes have still unknown. The aim of the current study was to retrospectively investigate risk factors for PHPE and its impact on oncological outcomes of hepatocellular carcinoma (HCC). Methods: Medical records of 330 patients who underwent primary curative hepatectomy for HCC were reviewed. All 330 patients had CT around day 7 after hepatectomy, and the emergence of PHPE on CT was examined. Presumed 38 risk factors for the emergence of PHPE and already-known 9 risk factors together with PHPE for HCC recurrence and patient death after hepatectomy were analyzed. Results: The overall incidence of PHPE was 54.5% (180/330). One hundred seventy-nine and 38 out of the 180 patients had right-sided PHPE and left-sided PHPE, respectively. The independent risk factors for right-sided PHPE were hepatitis B or C back ground, lower preoperative white blood cell count, larger intraoperative blood loss, longer operation time, subcostal incision, and longer total inflow occlusion time, while the only independent risk factor for left-sided PHPE was longer operation time. Left-sided PHPE was testified to be one of the independent risk factors not only for HCC recurrence but also for patient death. Conclusions: Although the cause of PHPE after hepatectomy might be multifactorial, the emergence of left-sided PHPE is a portent of worse oncological outcomes after curative hepatectomy for HCC and patients with left-sided PHPE need close follow-ups.

DOI： 10.1007/s00268-016-3826-1

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: We aimed to evaluate whether functional assessment of the future remnant liver is a predictor of postoperative morbidity after hepatic resection in patients with hepatocellular carcinoma (HCC). Methods: One hundred forty-six patients who underwent hepatic resection for HCC were enrolled in this study. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI (EOB-MRI) analysis for functional liver assessment was carried out before hepatic resection. The signal intensity in the remnant liver was measured and divided by the signal intensity of the major psoas muscle (the liver to major psoas muscle ratio, LMR) for standardization. The remnant liver function was calculated using the formula (LMR on the hepatobiliary phase/LMR on the precontrast image). Computed tomography liver volumetry was also carried out. The remnant functional liver was calculated as the remnant liver volume or volumetric rate × remnant liver function by EOB-MRI. Results: Morbidities developed in 19 (13.0%) patients. Morbidities associated with the liver occurred in 7 patients (4.7%). There was no mortality during surgery. Median remnant liver function scores using EOB-MRI and remnant functional liver using volumetric rate or volumetry were 1.82 (range, 1.25–2.96), 155.9 (range, 64.7–285.3), and 1027 (range, 369–2148), respectively. Logistic regression analysis identified the remnant functional liver volume as the only independent predictor for liver-related morbidity. Conclusion: Remnant functional liver volume using computed tomography liver volumetry and EOB-MRI was a significantly useful predictor for liver-related morbidity after hepatic resection in patients with HCC.

DOI： 10.1111/hepr.12761

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: To assess the correlations among pancreatic fibrosis, pancreatic stiffness, and postoperative pancreatic fistula (PF). Patients and Methods: The study population consisted of 17 consecutively enrolled patients who underwent subtotal stomach-preserving pancreaticoduodenectomy (SSPPD). The liver fibrosis (LF) index as pancreatic stiffness was measured by real- time tissue elastography (RTE) before SSPPD. We also obtained the pathological fibrosis assessment of the pancreatic stump after SSPPD. Results: The LF index was significantly correlated with pathological pancreatic stump fibrosis. The LF index of patients without PF was significantly higher than that of patients with PF. The optimal cut-off value of the LF index to predict postoperative PF was defined as an LF index ≤1.91. Multivariate analysis revealed that a preoperative LF index ≤1.91 was an independent predictive factor of postoperative PF. Conclusion: Evaluation of pancreatic stiffness using RTE might be an objective index to estimate pancreatic fibrosis and predict postoperative PF.

DOI： 10.21873/anticanres.11529

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Refractory ascites is a serious posthepatectomy complication in cirrhotic patients with hepatocellular carcinoma (HCC). In order to avoid this complication, surgeons should preserve as much liver parenchyma as possible in performing hepatectomy in such patients. However, we still occasionally encounter refractory ascites even after limited or small hepatectomy. The aim of this study was to identify risk factors for post-hepatectomy refractory ascites in cirrhotic patients, focusing on limited or small hepatectomy. Patients and Methods: The data of 73 cirrhotic patients with HCC who underwent limited or small hepatectomy were analyzed. Limited or small hepatectomy was defined as hepatectomy equal to or of less than subsegmentectomy. We compared the clinicopathological factors between patients with and without postoperative refractory ascites. Results: Fourteen cirrhotic patients suffered postoperative refractory ascites. Total cholesterol, duration of operation, duration of Pringle maneuver, resection of segment VII, intraoperative blood loss, and intraoperative blood transfusion were found to be significant risk factors for postoperative refractory ascites in univariate analyses. Multivariate analysis revealed that resection of segment VII was an independent risk factor. Conclusion: Resection of segment VII necessitates extensive dissection of the right triangular or coronary ligaments, which could explain that it was an independent risk factor for posthepatectomy refractory ascites. Surgeons should avoid extensive dissection of these ligaments in order to avoid this detrimental complication.

DOI： 10.21873/anticanres.11459

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background. Biliary anastomosis stricture (BAS) is still among the major concerns after living donor liver transplantation (LDLT), even after the technical refinements including the universal use of the blood flow-preserving hilar dissection technique. The aim of this study is to investigate what are still the factors for BAS after LDLT. Methods. An analysis of 279 adult-to-adult LDLT grafts (left lobe, n = 161; right lobe, n = 118) with duct-to-duct biliary reconstruction, since the universal application of minimal hilar dissection technique and gradual introduction of eversion technique, was performed. Results. There were 39 patients with BAS. Univariate analysis showed that a right lobe graft (P = 0.008), multiple bile ducts (P < 0.001), ductoplasty (P < 0.001), not using the eversion technique (P = 0.004) and fewer biliary stents than bile duct orifices (P = 0.002) were among the factors associated with BAS. The 1-year and 5-year BAS survival rates were 17.7% and 21.2% in the noneversion group (n = 134), and 6.2% and 7.9% in the eversion group (n = 145), respectively (P = 0.002). The perioperative factors including graft biliary anatomy were not different between everted (n = 134) and noneverted (n = 145) patients. Conclusions. The application of eversion technique under minimal hilar dissection technique could be a key for preventing BAS in duct-to-duct biliary reconstruction in LDLT.

DOI： 10.1097/TP.0000000000001533

記述言語：英語  

Autophagy regulates protein and organelle turnover and produces adenosine 5'-triphosphate (ATP) by using the amino acids from degraded proteins. We generated liver-specific autophagy-related gene 5 (Atg5)-knockout (KO) mice to investigate the activity of autophagy-associated pathways in liver regeneration after partial hepatectomy (PHx). The proliferation of remnant liver in Atg5 KO mice was severely impaired by 70% PHx with a reduction in postoperative mitosis, but a compensating increase in hepatocyte size. PHx injured cellular mitochondria and induced the intracellular ATP and β-oxidation reduction. Besides, hepatic accumulation of p62 and ubiquitinated proteins were enhanced. These results indicated that the reorganization of intracellular proteins and organelles during autophagy was impaired in the regenerating liver in this setting. Upregulation of p21 was associated with hepatocyte senescence and irreversible growth arrest. In the results, autophagy plays a critical role in regenerating liver and in the preservation of cellular quality by preventing hepatocytes from becoming fully senescent and hypertrophic in liver regeneration.

DOI： 10.1016/B978-0-12-812146-7.00023-8

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/lt.24644

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Surgical resection of retrocaval giant pheochromocytomas (PCs) and of extra-adrenal paragangliomas (EAPs) is a technically challenging procedure but data on these procedures are scarce. The purpose of this study was to present and evaluate our surgical results for such tumors. Patients and Methods: We retrospectively analyzed four consecutive patients who had surgery for giant retro-caval PCs and EAPs in terms of surgical technique, resectability of the tumor, requirement for bypass, and postoperative complications. A laparoscopic approach was not feasible in all cases because of the undesirable location of the tumors. Results: In all cases, the liver was completely mobilized from the right side to expose and control the supra- and infra-hepatic inferior vena cava. Resection of the tumors was feasible for all patients with a minimum titration of blood pressure during surgery. None of the cases required venous bypass. In the patient who had the largest tumor, the infra-hepatic inferior vena cava was transected temporally to obtain direct and maximum exposure of the tumor. None of the patients have had any postoperative complications and all are currently alive without recurrence and use of antihypertensive drugs. Conclusion: Resection of retrocaval giant PCs and EAPs is a safe procedure. Temporal transection of the infra-hepatic inferior vena cava can offer excellent exposure, especially for an extremely large tumor, without compromising hepatic and systemic hemodynamics.

DOI： 10.21873/anticanres.11318

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Treatment strategies for lymph node (LN) metastasis after liver transplantation (LT) for hepatocellular carcinoma (HCC) have not been studied. Patients and Methods: The treatment modes and outcomes in patients with LN metastasis after LT (n=6) for HCC were reviewed. Results: The mean time from LT to LN recurrence was 2.0±1.3 years, and the locations of the LNs recurrences included the phrenic (n=2), common hepatic artery (n=2), inferior vena cava (n=1) and gastric (n=1) regions. Treatments included surgery alone (n=3), surgery followed by chemoradiation (n=1), radiation followed by chemotherapy (n=1), and chemotherapy, radiation and sorafenib (n=1). Although the patients receiving nonsurgical treatments (n=3) died within 1.2 years, those who underwent surgical removal of the metastatic LNs survived 11.2 years, 4.5 years and 0.8 years, respectively, without any signs of re-recurrence. Conclusion: Surgical resection is the only feasible and potentially curative treatment for LN metastasis after LT for HCC.

DOI： 10.21873/anticanres.11395

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Small-for-size syndrome (SFSS) is the most significant cause of graft loss after living donor liver transplantation (LDLT), especially after left lobe (LL) LDLT in adults. The safety limit of applying LL-LDLT in adults without severe SFSS with a high rate of lethality needs to be determined. A total of 207 LL-LDLTs in adults since September 2005 were evaluated to analyze the risk factors for severe SFSS, defined as a serum total bilirubin concentration of ≥20.0 mg/dL after LDLT. Although there were no significant differences in cumulative graft survival after LDLT between medium grafts (graft volume [GV] to standard liver volume [SLV] ratio ≥ 40.0%), small grafts (35.0% ≤ GV/SLV < 40.0%), and extra small grafts (GV/SLV < 35.0%), patients with severe SFSS showed a significantly lower 5-year graft survival rate than those without (42.9% versus 94.3%, respectively; P < 0.001). Multivariate analysis for severe SFSS after LL-LDLT showed that donor age of ≥48 years (P = 0.01), Model for End-Stage Liver Disease (MELD) score of ≥ 19 (P < 0.01), and end portal venous pressure of ≥19 mm Hg (P = 0.04) were the significant and independent factors for severe SFSS after LL-LDLT. Within such high-risk subgroups of patients with a donor age of ≥48 years or MELD score of ≥ 19 before LDLT, operative blood loss volume of ≥8.0 L was a risk factor for severe SFSS. LL-LDLT in adults could be indicated and provide acceptable outcomes for the combinations of donors aged < 48 years and recipients with a MELD score of <19. Smaller grafts might yield acceptable outcomes in appropriately selected donor-recipient combinations. Liver Transplantation 22 1666–1675 2016 AASLD.

DOI： 10.1002/lt.24611

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The learning curve for performing living donor hemiliver procurement (LDHP) via small upper midline incision (UMI) has not been determined. Living donors (n=101) who underwent LDHP via UMI were included to investigate the learning curve using cumulative sum analysis. The cumulative sum analysis showed that nine cases for right lobe (case #23) and 19 cases for left lobe (case #32 in the whole series) are needed for stable and acceptable surgical outcomes in LDHP via UMI. The established phase (n=69, since case #33) had a significantly shorter operative time, a smaller incision size, and less blood loss than the previous learning phase (n=32, serial case number up to the last 19th left lobe case). Multivariate analysis showed that the learning phase, high body mass index ≥25 kg/m², and left lobe graft procurement are the factors associated with surgical events including operative blood loss ≥400 mL, operative time ≥300 minutes, or surgical complications ≥Clavien-Dindo grade II. There is an obvious learning curve in performing LDHP via UMI, and 32 cases including both 19 cases for left lobe and nine cases for right lobe are needed for having stable and acceptable surgical outcomes.

DOI： 10.1111/ctr.12850

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: The present study investigated the effect of sarcopenia on short- and long-term surgical outcomes and identified potential prognostic factors for hepatocellular carcinoma (HCC) following hepatectomy among patients 70 years of age and older. Methods: Patient data were retrospectively collected for 296 consecutive patients who underwent hepatectomy for HCC with curative intent. Patients were assigned to two groups according to age (younger than 70 years, and 70 years and older), and the presence of sarcopenia. The clinicopathological, surgical outcome, and long-term survival data were analyzed. Results: Sarcopenia was present in 112 of 296 (37.8%) patients with HCC, and 35% of patients aged 70 years and older. Elderly patients had significantly lower serum albumin levels, prognostic nutrition index, percentage of liver cirrhosis, and histological intrahepatic metastasis compared with patients younger than 70 years. Overall survival and disease-free survival rates in patients with sarcopenia correlated with significantly poor prognosis in the group aged 70 years and older. Multivariate analysis revealed that sarcopenia was predictive of an unfavorable prognosis. Conclusion: This retrospective analysis revealed that sarcopenia was predictive of worse overall survival and recurrence-free survival after hepatectomy in patients 70 years of age and older with HCC.

DOI： 10.1111/hepr.12674

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Inflammation-besed prognostic score including neutrophil/lymphocyte ratio (NLR), platelet/ lymphocyte ratio (PLR), modified Glasgow prognostic score (mGPS) and prognostic nutritional index (PNI) have prognostic value in various malignancies. Patients and Methods: We retrospectively investigated their prognostic value in 213 patients with living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). Disease-free survival (DFS) following LDLT was calculated; NLR, PLR, PNI and mGPS values in patients with and without recurrence were compared. Risk factors for HCC recurrence were identified by univariate and multivariate analyses. Results: Both NLR and PLR were significantly increased in patients with recurrence. Multivariate analysis showed that desgamma-carboxy prothrombin (DCP) 300 mAU/ml, NLR 2.66, <3 months between last HCC treatment to LDLT were independent predictors of DFS. Conclusion: Preoperative NLR was an independent, inflammation-based prognostic marker of DFS and was predictive of recurrence following LDLT.

DOI： 10.21873/anticanres.11137

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In living donor liver transplantation (LDLT), a left hepatic graft occasionally includes a replaced or accessory left hepatic artery (LHA). The procuring of such grafts requires extensive dissection along the lesser curvature of the stomach to elongate the replaced or accessory LHA on the donor side. On the recipient side, complicated arterial reconstruction is often necessary to use such grafts. We retrospectively reviewed the medical records of 206 adult recipients who underwent LDLT and their respective donors. The recipients and donors were divided into two groups according to the presence of the replaced or accessory LHA. Twenty-five grafts included a replaced or accessory LHA. Only one hepatic artery-related complication was observed in the current series, in which a pseudoaneurysm arose at the site of anastomosis between the donor accessory LHA and the recipient LHA. There was no increase in the incidence of postoperative complications in the donors with a replaced or accessory LHA in comparison with the donors without these arteries. The use of left hepatic grafts that included a replaced LHA or accessory LHA did not have any negative impact on the outcomes on either the donor or the recipient side.

DOI： 10.1111/ctr.12783

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: To evaluate the efficacy of age on the surgical outcomes in hepatic or pancreatic resection. Patients and Methods: We performed 50 hepatic or pancreatic resections in our community hospital and divided them into 2 groups based on age: patients aged 85 years old and patients aged <85 years old. We calculated the Estimation of Physiologic Ability and Surgical Stress (EPASS) score and the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) system and compared the surgical outcome between the two groups. Results: There was no significant difference between the two groups with regard to E-PASS and POSSUM scores. Patients aged 85 years had a significantly higher frequency of anti-platelet agents. The incidence of postoperative complications and mortality in patients 85 years old were comparable to those in patients aged <85 years old. Conclusion: Hepatic or pancreatic resection for elderly patients aged 85 years or older can be safely performed under a given careful patient selection.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

To ensure donor safety in living donor liver transplantation (LDLT), the left and caudate lobe (LL) is the preferred graft choice. However, patient prognosis may still be poor even if graft volume (GV) selection criteria are met. Our aim was to evaluate the effects of right lobe (RL) donation when the LL graft selection criteria are met. Consecutive donors (n = 135) with preoperative LL graft volumetric GV/standard liver volume (SLV) of ≥35% and RL remnant of ≥35% were retrospectively studied. Patients were divided into 2 groups: LL graft and RL graft. Recipient's body surface area (BSA), Model for End-Stage Liver Disease (MELD) score, and the donor's age were higher in the RL group. The donor's BSA and preoperative volumetric GV/SLV of the LL graft were smaller in the RL group. The predicted score (calculated using data for graft size, donor age, MELD score, and the presence of portosystemic shunt, which correlated well with graft function and with 6-month graft survival) of the RL group, was significantly lower if the LL graft were used, but using the actual RL graft improved the score equal to that of the LL group. Six-month and 12-month graft survival rates did not differ between the 2 groups. In patients with a poor prognosis, a larger RL graft improved the predicted score and survival was equal to that of patients who received LL grafts. In conclusion, graft selection by GV, donor age, and recipient MELD score improves outcomes in LDLT. Liver Transplantation 22 914–922 2016 AASLD.

DOI： 10.1002/lt.24431

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The causative agent of hepatic encephalopathy (HE) has not been identified with certainty. The recovery of consciousness in patients with acute liver failure (ALF) who underwent liver transplantation (LT) is sometimes drastic ; therefore, we thought that the causative agents of HE would change markedly peri-operatively in these patients. We examined the biomarkers including new agents in the serum of patients using the ProteinChip® System 4000 (Ciphergen Biosystems, Yokohama, JAPAN). Sixteen samples were obtained from four patients with ALF who underwent living donor LT (LDLT) at four time points ; pre-operative, one post-operative day (1POD), 3POD, and 7POD. We used three chips made by the Biomek2000 robot. All duplicated samples were assayed and analyzed using the CiphergenExpressTM data manager. We divided the peri-operative changes in the intensity of identified peaks into seven patterns. The number of peaks whose intensity shows significant changes peri-operatively reached 755. Of course, it is difficult to determine each structure in all 755 peaks ; therefore, we should narrow down the candidates for causative agents of HE in further studies. Our own results suggest that many difficulties lie ahead in determining the causative agent of HE.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aim: We aimed to evaluate the effect of body composition on the outcome of living-donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC). Patients and Methods: We performed LDLT in 153 patients with HCC and divided the patients into two groups based on skeletal muscle mass-to-visceral fat area ratio (SVR), as assessed by computed tomography (CT) measurement, namely a low-SVR group (n=38) and a notlow SVR group (n=112). We compared surgical outcomes between the two groups. Results: A low SVR was significantly correlated with a higher body mass index and male sex. No differences were found between the two groups in terms of other factors. The patients in the low-SVR group had a significantly poorer prognosis than those in the notlow SVR group in terms of recurrence-free (p=0.01) and overall (p=0.03) survival. The results of the multivariate analysis showed low SVR to be an independent and prognostic indicator for patients with HCC who had undergone LDLT. Conclusion: Pre-transplant body composition measured by CT is a major determinant of prognosis in LDLT for HCC in Japan.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. First, we performed microarray analyses of samples from a liver with primary HCC, a liver that was noncancerous, and a liver that had recurrence-metastasis from 3 patients with posttransplant recurrence. Then we selected miRNAs with consistently altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous livers was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. MicroRNA-18a (miR-18a) expression was increased, and microRNA-199a-5p (miR-199a-5p) expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor, and insulin-like growth factor 2. In conclusion, increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT.

DOI： 10.1002/lt.24400

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aging of Japan’s population is becoming pronounced, and hepatobiliary pancreatic surgery for elderly patients is increasingly performed. Elderly patients generally have extensive comorbidities, the risk of malnutrition, and diminished renal, liver, and cardiopulmonary function. Therefore, the indications of surgery should be individually evaluated considering surgical risk, impaired quality of life, and prognosis after surgery. Japanese insurance allows left lateral segmentectomy and partial resection for liver malignancy to be performed by laparoscopic surgery. Laparoscopic surgery may prevent sarcopenia, which is a predictor of survival in patients with various malignancies or those with liver cirrhosis. Elderly patients often develop delirium or severe aspiration pneumonia postoperatively. Interprofessional collaboration for pain control and early mobilization is the key to prevent severe complications in elderly patients. Thirty percent of patients with hepatocellular carcinoma are older than 75 years of age. Morbidity and mortality rates after hepatic resection in the elderly with acceptable cardiopulmonary function are comparable to those in younger individuals with adequate patient selection. Recipient age does not affect the outcome after living-donor liver transplantation (LDLT), as long as patient status is relatively good. Therefore, age alone should not be considered a contraindication for LDLT.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ϵ (CK1ϵ) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of β-catenin activation in human HCC. Methods: Gene alteration in exon3 of CTNNB1, gene expression of β-catenin targets such as glutamate synthetase (GS), axin2, lect2 and regucalcin (RGN), and protein expression of β-catenin were examined in 125 human HCC tissues. Results: Sixteen patients (12.8%) showed conventional missense mutations affecting codons 33, 37, 41, and 45. Fifteen additional patients (12.0%) had other missense mutations in codon 32, 34, and 35. Induction of exon3 mutation caused described β-catenin target gene upregulation in HCC cell line. Interestingly, conventional and non-phosphorylation site mutations were equally associated with upregulation of β-catenin target genes. Nuclear localization of β-catenin was associated with poor overall survival (p = 0.0461). Of these patients with nuclear β-catenin localization, loss of described β-catenin target gene upregulation showed significant poorer overall survival than others (p = 0.0001). Conclusion: This study suggests that both conventional and other missense mutations in exon 3 of CTNNB1 lead to β-catenin activation in human HCC. Additionally, the mechanism of nuclear β-catenin localization without upregulation of described β-catenin target genes might be of clinical importance depending on distinct mechanism.

DOI： 10.1371/journal.pone.0152695

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: We aimed to evaluate whether skeletal muscle mass measured by computed tomography (CT) or bioelectrical impedance analysis (BIA) correlated to muscle strength and physical performance in liver-related hospital cases. Methods: We prospectively conducted this study in 120 liver-related hospital cases. Skeletal muscle mass was measured by CT scan and BIA. Muscle strength was determined by hand grip strength and physical performance by usual gait speed. Results: Skeletal muscle mass measured using CT significantly correlated to usual gait speed (r²=0.17, P<0.0001) and hand grip strength (r²=0.66, P<0.0001), but the correlations were lower using BIA (r²=0.1, P=0.0005; r²=0.54, P<0.0001). With regard to liver function, the relationship between skeletal muscle mass measured by CT and BIA and two muscle function parameters in the Child-Pugh A group were significant. In contrast, skeletal muscle mass measured by BIA in the Child-Pugh B or C group was not significantly related to usual gait speed. Conclusion: Skeletal muscle mass measured by CT was significantly correlated to hand grip strength and usual gait speed, with higher correlations compared with BIA. Moreover, skeletal muscle mass measured by CT significantly correlated with two muscle functions, even in patients with Child-Pugh B or C.

DOI： 10.1111/hepr.12537

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/lt.24377

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: Our aim was to evaluate the clinical outcomes of telaprevir (TVR)- or simeprevir (SMV)-based triple therapy for recurrent hepatitis C after living donor liver transplantation. Methods: Twenty-six patients received antiviral therapy, consisting of either TVR (n=12) or SMV (n=14) in combination with pegylated interferon and ribavirin, plus cyclosporin. Results: More patients had a dose reduction of the direct-acting agent (36.3% vs 0.0%, P=0.02) or required blood transfusion for anemia (58.3% vs 7.1%, P<0.01) in the TVR group. The cyclosporin trough/dose ratio increased significantly from week 0 to week 4 in the TVR group (1.6±0.4 to 5.1±2.0, P<0.01), but not in the SMV group (1.2±0.3 to 1.3±0.2, P=0.68). The 24-week cumulative viral clearance rate was 91.7% and 85.7% in the TVR and in SMV groups, respectively. The early viral response and sustained viral response rates were 91.7% and 83.3%, respectively, in the TVR group, compared with 85.7% and 64.3%, respectively, in the SMV group. Interferon-mediated graft dysfunction occurred in four and five patients in the TVR and SMV groups, respectively; two patients were treated by oral steroids, five by steroid pulse and two by thymoglobulin, resulting in viral breakthrough in one case. Conclusion: SMV-based triple therapy was associated with fewer adverse events and drug interactions with cyclosporin, and possibly less antiviral properties to TVR. Interferon-mediated graft dysfunction is a significant clinical problem that warrants particular caution following living donor liver transplantation.

DOI： 10.1111/hepr.12546

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Pancreatic fistula (PF) remains the most important morbidity after pancreaticoduodenectomy (PD). Early drain removal was recently recommended. However, this is not applicable to all cases because the development of severe PF may not be obvious until a later postoperative day (POD). This study aimed to discover ways to detect clinically relevant PF early during the postoperative stage after PD. Methods: We studied 120 patients who underwent PD. Grades B/C PF classified according to the International Study Group of Pancreatic Surgery guidelines were defined as clinically relevant PF. Logistic regression was used to identify detection factors for clinically relevant PF. Receiver operating characteristic curves were used to identify the optimal cutoff value for clinically relevant PF, and the k-fold cross-validation model to validate the cutoff value. Results: Drain amylase on POD 1 and C-reactive protein (CPR) on POD 2 were independent factors for clinically relevant PF. Drain amylase >1300 IU/l on POD 1 and CRP >12.8 g/dl on POD 2 were the best cutoff values for clinically relevant PF detection and were confirmed by k-fold cross-validation. The sensitivity and specificity values were 79 and 81 %, respectively. Conclusions: Values of drain amylase and CRP combined were useful to distinguish clinically relevant PF.

DOI： 10.1007/s11605-015-3030-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The clinical features of benign liver lesions misdiagnosed as hepatocellular carcinoma have not been fully described.
PATIENTS AND METHODS: This study included 187 patients who underwent hepatectomy at the Kyushu University Hospital following a diagnosis of solitary HCC of ≤3 cm in diameter.
RESULTS: Following hepatectomy, 9.6% patients were pathologically diagnosed with benign liver lesions. Univariate analysis showed that patient age ≤67 years, negativity for hepatitis C virus antigen, lesion size ≤1.5 cm, normal level of tumor markers, and absence of increase in tumor size were associated with benign lesions. Patient age ≤67 years and absence of tumor size increase were independent predictors of benign lesions.
CONCLUSION: Benign liver lesions misdiagnosed as HCC were not infrequent, accounting for approximately 10% of resected cases. Age ≤67 years and absence of tumor size increase were independent predictors of benign liver lesions, and may help in the correct diagnosis of HCC.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Early treatment of disseminated intravascular coagulation (DIC) can be associated with improved early outcomes. We aimed to evaluate the effectiveness of recombinant human soluble thrombomodulin (rTM) administration in patients with peritonitis-induced DIC. Patients and Methods: We treated 39 patients with DIC or pre-DIC caused by peritonitis at the Department of Surgery and Science, Kyushu University, and related facilities between January and December 2013. Results: Patients surviving to 28 days after DIC treatment had significantly better platelet counts, DIC scores, and sequential organ failure assessment scores at 7 days than did those who died earlier than 28 days. Patients receiving rTM had significantly better overall survival rates at 28 days and the results of multivariate analysis showed that rTM administration for DIC treatment was a prognostic indicator of 28-day survival in patients with peritonitis. Conclusion: rTM administration for the treatment of DIC or pre-DIC complicated by peritonitis had acceptable early outcomes.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Postoperative pancreatic fistula (POPF) remains a major complication after pancreaticoduo-denectomy (PD), and the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) after PD is poor. Patients and Methods: A multi-institutional retrospective study was performed in 174 patients who underwent PD for PDAC from 2007 to 2012. The details of clinical data were examined, and risk factors for POPF and poor prognostic factors after PD were identified. Results: POPF occured in 26 patients (15%), and 18 patients (10%) were diagnosed as Grade B/C POPF. The independent risk factors for Grade B/C POPF were body mass index (BMI) ≥25 (Odds Ratio [OR]=21.1, p=0.006) and absence of post-operative enteral nutrition (EN) (OR=10.2, p=0.04). The 1-, 3-, and 5-year overall survivals of patients with PDAC after PD were 76%, 35%, and 18%, respectively. R1/2 operation was identified as the only independent poor prognostic factor (Hazard Ratio=3.66; p=0.0002). Conclusion: Patients with BMI ≥25 should be closely monitored for POPF after PD. Post-operative EN might help prevent POPF. Performing R0 resection is an important goal for ensuring patient survival after PD for PDAC.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aim of the present study was to clarify the outcome of living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.
PATIENTS AND METHODS: The study comprised of 197 adult patients. One hundred twenty-nine patients were within Milan criteria. The overall and recurrence-free survival rates after the LDLT were calculated.
RESULTS: The 1-, 5- and 10-year overall survival rates were 94.5%, 89.9% and 88.6%, respectively. The 1-, 5- and 10-year recurrence-free survival rates were 100%, 97.0% and 94.0%, respectively. Four patients had HCC recurrence. The mean neutrophil to lymphocyte ratio (NLR) (6.75 vs. 2.75, p=0.002) or alpha-fetoprotein (AFP) (3,239 vs. 197, p<0.001) of these four recipients was significantly higher compared to that of 125 recipients without HCC recurrence.
CONCLUSION: The outcome of LDLT for patients with HCC within Milan criteria was outstanding. Careful follow-up after LDLT is necessary for patients with high NLR or AFP.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background. Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery, and steatosis is a risk factor for liver damage. Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) contribute to liver dysfunction. Here we examined the role of NOX in I/R injury of fatty livers. Methods. Rats were fed a methionine and cholinedeficient diet to induce a fatty liver. Rats then underwent surgically induced partial hepatic ischemia followed by reperfusion. Results. The overall survival rate after I/R was lower in rats with fatty livers than with normal livers (P < 0.01). Necrotic area and the concentrations of 8-hydroxy-2α-deoxyguanosine (8-OHdG), TNFÁ, and IL-6 were higher in fatty liver tissue than in normal liver tissue (P < 0.01). The number of p47phox-positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 24 hours after reperfusion. The number of TLR-4 positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 4 and 24 hours after reperfusion coupled with a decreased number of high-mobility group box 1-positive hepatocytes. Apocynin significantly improved the survival rate, necrotic area, and concentrations of 8-hydroxy-2α-deoxyguanosine, TNFα, and IL-6 (P < 0.01). The protective effect of apocynin on fatty livers was greater than on normal livers. Conclusions. Ischemia-reperfusion injury was associated with increased high-mobility group box 1, TLR4, and NOX2. Inhibition of NOX activity improved oxidative stress and may prevent I/R injury in fatty liver.

DOI： 10.1097/TP.0000000000001130

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Early treatment of disseminated intravascular coagulation (DIC) can be associated with improved early outcomes. We aimed to evaluate the effectiveness of recombinant human soluble thrombomodulin (rTM) administration in patients with peritonitis-induced DIC. Patients and Methods: We treated 39 patients with DIC or pre-DIC caused by peritonitis at the Department of Surgery and Science, Kyushu University, and related facilities between January and December 2013. Results: Patients surviving to 28 days after DIC treatment had significantly better platelet counts, DIC scores, and sequential organ failure assessment scores at 7 days than did those who died earlier than 28 days. Patients receiving rTM had significantly better overall survival rates at 28 days and the results of multivariate analysis showed that rTM administration for DIC treatment was a prognostic indicator of 28-day survival in patients with peritonitis. Conclusion: rTM administration for the treatment of DIC or pre-DIC complicated by peritonitis had acceptable early outcomes.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: The rupture of hepatocellular carcinoma (HCC) is defined as a detrimental staging factor. The aim of the present study was to elucidate whether the prognosis of surgical patients with ruptured HCC was truly appalling.
PATIENTS AND METHODS: The data obtained from the medical records of 1,031 patients who underwent primary R0 hepatecomy for HCC between August 2003 and November 2014 at the Department of Surgery and Science, Kyushu University Hospital and its two affiliated hospitals, were retrospectively analyzed. Twenty-seven patients had ruptured HCC.
RESULTS: The recurrence-free and overall survival for patients with ruptured HCC were favorable. All 19 patients with ruptured HCC who experienced recurrence had intrahepatic recurrence, while only three had peritoneal recurrence. The multivariate risk factor analyses showed that rupture itself was not relevant to recurrence-free survival nor to overall patient survival.
CONCLUSION: Rupture itself does not have much relevance to the outcome for patients who undergo hepatectomy.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Postoperative pancreatic fistula (POPF) remains a major complication after pancreaticoduo-denectomy (PD), and the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) after PD is poor. Patients and Methods: A multi-institutional retrospective study was performed in 174 patients who underwent PD for PDAC from 2007 to 2012. The details of clinical data were examined, and risk factors for POPF and poor prognostic factors after PD were identified. Results: POPF occured in 26 patients (15%), and 18 patients (10%) were diagnosed as Grade B/C POPF. The independent risk factors for Grade B/C POPF were body mass index (BMI) ≥25 (Odds Ratio [OR]=21.1, p=0.006) and absence of post-operative enteral nutrition (EN) (OR=10.2, p=0.04). The 1-, 3-, and 5-year overall survivals of patients with PDAC after PD were 76%, 35%, and 18%, respectively. R1/2 operation was identified as the only independent poor prognostic factor (Hazard Ratio=3.66; p=0.0002). Conclusion: Patients with BMI ≥25 should be closely monitored for POPF after PD. Post-operative EN might help prevent POPF. Performing R0 resection is an important goal for ensuring patient survival after PD for PDAC.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aim of the present study was to clarify the outcome of living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.
PATIENTS AND METHODS: The study comprised of 197 adult patients. One hundred twenty-nine patients were within Milan criteria. The overall and recurrence-free survival rates after the LDLT were calculated.
RESULTS: The 1-, 5- and 10-year overall survival rates were 94.5%, 89.9% and 88.6%, respectively. The 1-, 5- and 10-year recurrence-free survival rates were 100%, 97.0% and 94.0%, respectively. Four patients had HCC recurrence. The mean neutrophil to lymphocyte ratio (NLR) (6.75 vs. 2.75, p=0.002) or alpha-fetoprotein (AFP) (3,239 vs. 197, p<0.001) of these four recipients was significantly higher compared to that of 125 recipients without HCC recurrence.
CONCLUSION: The outcome of LDLT for patients with HCC within Milan criteria was outstanding. Careful follow-up after LDLT is necessary for patients with high NLR or AFP.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background. Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery, and steatosis is a risk factor for liver damage. Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) contribute to liver dysfunction. Here we examined the role of NOX in I/R injury of fatty livers. Methods. Rats were fed a methionine and cholinedeficient diet to induce a fatty liver. Rats then underwent surgically induced partial hepatic ischemia followed by reperfusion. Results. The overall survival rate after I/R was lower in rats with fatty livers than with normal livers (P < 0.01). Necrotic area and the concentrations of 8-hydroxy-2α-deoxyguanosine (8-OHdG), TNFÁ, and IL-6 were higher in fatty liver tissue than in normal liver tissue (P < 0.01). The number of p47phox-positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 24 hours after reperfusion. The number of TLR-4 positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 4 and 24 hours after reperfusion coupled with a decreased number of high-mobility group box 1-positive hepatocytes. Apocynin significantly improved the survival rate, necrotic area, and concentrations of 8-hydroxy-2α-deoxyguanosine, TNFα, and IL-6 (P < 0.01). The protective effect of apocynin on fatty livers was greater than on normal livers. Conclusions. Ischemia-reperfusion injury was associated with increased high-mobility group box 1, TLR4, and NOX2. Inhibition of NOX activity improved oxidative stress and may prevent I/R injury in fatty liver.

DOI： 10.1097/TP.0000000000001130

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: This retrospective study aimed to investigate the clinical characteristics and long-term outcomes after hepatectomy in patients with non-B, non-C (NBNC) hepatocellular carcinoma (HCC) who were negative for hepatitis B virus surface antigen and anti–hepatitis C virus antibody. Methods: We retrospectively reviewed 666 patients with HCC who underwent hepatectomy. The patients were divided into NBNC-HCC patients [n = 117 (17.6 %)] and hepatitis virus (HV)-HCC patients [n = 547 (82.4 %)]. We compared the clinicopathologic characteristics and long-term outcomes between the 2 groups. Two patients with incomplete virus-marker data were not analyzed. Results: NBNC-HCC patients had better liver function but more advanced and larger HCCs and a high incidence of intrahepatic metastasis compared to HV-HCC patients. Recurrence-free and overall survival were similar in both groups. Multivariate analysis showed that aspartate aminotransferase (AST) and α-fetoprotein were independently associated with disease-free and overall survival in NBNC-HCC patients after hepatectomy. High AST was significantly associated with tumor size and rate of capsule formation with cancer cell infiltration in NBNC-HCC patients, but not with other liver function tests, fibrosis, or necrosis of noncancerous lesions. Conclusions: NBNC-HCC patients have better liver function than HV-HCC patients, despite having more advanced HCC at diagnosis. There were no differences in long-term outcomes after hepatectomy between NBNC-HCC and HV-HCC patients. Preoperative AST and α-fetoprotein were independently associated with the prognosis of NBNC-HCC after hepatectomy. Serum AST levels might be associated with tumor malignancy in NBNC-HCC patients.

DOI： 10.1245/s10434-015-4728-4

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: The incidence of hepatitis B virus (HBV) recurrence after liver transplantation (LT) has been reduced by prophylaxis with hepatitis B immunoglobulin (HBIG) and nucleoside analogs, but the factors associated with HBV recurrence are unclear. The aim of this study was to determine the risk factors associated with HBV recurrence after living donor LT (LDLT). Methods: A retrospective review was performed for 45 patients (28 male and 17 female; median age, 54years) who underwent LDLT for HBV-related liver disease and were followed up for at least 6months between October 1996 and June 2013. The virological data, tumor burden, antiviral therapy and immunosuppressive therapy were evaluated and compared between the HBV recurrence ad non-recurrence groups. Results: Seven of the 45 patients (15.6%) developed post-LT HBV recurrence. The median interval between LDLT and HBV recurrence was 23.7months (range, 0.8-35.9). Three of the seven patients (42.9%) developed recurrence after cessation of HBIG, and three (42.9%) were cases with hepatocellular carcinoma (HCC) recurrence after LDLT. The remaining case underwent transplantation from a donor with positive hepatitis B surface antigen. Based on the univariate and multivariate analyses, HBIG cessation (hazard ratio [HR], 20.17; 95% confidence interval [95% CI], 2.091-194.593; P=0.009) and HCC recurrence (HR, 30.835; 95% CI, 3.132-303.593; P=0.003) were independent risk factors for HBV recurrence after LDLT. Conclusion: In LDLT patients, cessation of HBIG and HCC recurrence were risk factors associated with HBV recurrence, so careful monitoring for serological HBV markers is needed in patients with these factors.

DOI： 10.1111/hepr.12489

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: Sarcopenia is an independent predictor of mortality and sepsis after living donor liver transplantation (LDLT). However, the exact mechanisms by which sarcopenia affects poor prognosis or worse immunity against postoperative sepsis are unclear, particularly regarding muscular amino acid metabolism, and the authors aimed to identify the role of plasma amino acids in sarcopenia by retrospective study. Methods: The area of the psoas muscle in 228 recipients of LDLT was retrospectively measured by dynamic computed tomography. Additionally, plasma amino acid levels were measured both pre- and postoperatively. The impact of plasma amino acids for postoperative sepsis and the relationship between sarcopenia and early nutrition after LDLT were analyzed. Results: Among the plasma amino acids, only leucine, isoleucine and glutamine in patients with sarcopenia were significantly lower than those without sarcopenia (each, P<0.05). Multivariate analysis identified the lower plasma glutamine levels as a risk factor of postoperative sepsis after LDLT (odds ratio 5.371, P=0.002). In sarcopenia patients, plasma glutamine levels after LDLT were significantly decreased compared with before LDLT in patients both with and without postoperative early nutrition. However, in non-sarcopenia patients with early nutrition, plasma glutamine levels after LDLT were comparable with those before LDLT. Conclusion: This is the first report to study the profile of plasma amino acid change before and after LDLT. Low preoperative glutamine values were an independent risk factor for predicting postoperative sepsis. The efficacy of postoperative early nutrition may prevent postoperative sepsis by improving glutamine levels.

DOI： 10.1111/hepr.12484

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jamcollsurg.2015.08.005

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Randomized clinical trials have demonstrated the limited efficacy of prophylactic drains following hepatic resection. However, many surgeons still insist on using prophylactic drains. This study was designed to identify patients who require prophylactic drains to manage or monitor postoperative complications after hepatic resection. Methods: Data were retrospectively collected from 316 patients who underwent hepatic resection and received a prophylactic drain. The patients were divided into two groups according to whether the drain was used to manage or monitor the following postoperative complications: bile leakage (prophylactic drains were used to monitor and treat bile leakage) and postoperative hemorrhage (the drainage fluid was macroscopically bloody and required drain fluid blood counts and monitoring to assess the need for transfusion or reoperation). The results were then validated in a separate cohort of 101 patients. Results: In 25/316 patients (7.9 %), the prophylactic drains were clinically effective, being used to manage bile leakage in 18 patients and hemorrhage in 8. Intraoperative bile leakage (P = 0.021) and long operation time (≥360 min) (P = 0.017) were independent predictors of bile leakage. Intraoperative blood loss (≥650 ml) (P = 0.0009) was an independent predictor of hemorrhage. In the subsequent 101 patients, prophylactic drains were clinically effective in patients with one of these predictors with sensitivity, specificity, and false-negative rates of 88.9, 62.0, and 1.7 %, respectively. Conclusion: A prophylactic drain should be considered following hepatic resection for patients with intraoperative bile leakage, operation time of ≥360 min, or blood loss of ≥650 ml.

DOI： 10.1007/s00268-015-3116-3

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jamcollsurg.2015.05.009

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction. Living donor liver transplantation (LDLT) using ABO-incompatible (ABOi) graft for acute liver failure (ALF) is a developing treatment modality. Methods. We reviewed the changes in our treatment strategies in applying ABOi LDLT for FH over our fourteen years of experience. Results. Five patients with ALF received LDLT in adults using ABOi grafts, with different but gradually renewed protocols. The etiologies for acute liver failure included autoimmune hepatitis (n=3) and unknown (n=2). The desensitization protocol for ABOi barrier included Case #1; local infusion (portal vein)+plasma exchange (PE), Case #2; local infusion (hepatic artery)+rituximab+PE, Case #3 and #4; rituximab+PE, and Case #5; rituximab+PE under high-flow continuous hemodiafiltration. Local infusion was abandoned since Case #3, because Case #1 had portal vein thrombosis resulting in graft necrosis and Case #2 had hepatic artery dissection. The patients (Case #2 and #3), who received rituximab within 7 days before LDLT, experienced antibody-mediated rejection. Thus, the most recent protocol for ABOi-LDLT is that rituximab is given 2 weeks before LDLT, followed by high-flow continuous hemodiafiltration to obstacle hepatic encephalopathy until LDLT. The four patients except Case #1 are doing well with good graft function over 3.8±3.7 years. Conclusion. Rituximab-based ABOi-LDLT, most-recently under high-flow hemodiafiltration for treating encephalopathy, is a feasible option for applying LDLT for ALF.

DOI： 10.2152/jmi.62.184

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purposes: The purpose of this study was to evaluate the impact of splenectomy in adult-to-adult living donor liver transplantation (LDLT). Methods: Adult-to-adult LDLTs (n = 276) were divided into those with simultaneous splenectomy during LDLT (Splenectomy group, n = 154) and those without (Non-Splenectomy group, n = 122). Results: In the Splenectomy group, splenectomy decreased the portal venous pressure from 24.0 to 19.1 mmHg (p < 0.001). At the end of surgery, the portal venous pressure was significantly lower and the graft compliance was significantly higher in the Splenectomy group compared with the Non-Splenectomy group. The graft portal venous flow was also better in the Splenectomy group (y = 625–5.1x; r² = 0.08, p < 0.01) than in the Non-Splenectomy group (y = 470–2.9x; r² = 0.04, p = 0.03). Fourteen days after LDLT, the total bilirubin and ascites output were lower in the Splenectomy group than in the Non-Splenectomy group. Among the patients with hepatitis C, splenectomy was associated with a significantly higher rate of a sustained viral response (59.4 vs. 35.9 %, p = 0.020) than was noted in those without splenectomy (n = 39). There were no patients with post-splenectomy sepsis under vaccination. Conclusions: By decreasing the portal pressure and increasing the graft vascular compliance, splenectomy conferred better graft outcomes in adult-to-adult LDLT

DOI： 10.1007/s00595-014-0999-9

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aims of this study were to evaluate the efficacy of repeat hepatectomy (Hx) and salvage living donor liver transplantation (LDLT) for recurrent hepatocellular carcinoma (HCC). A retrospective cohort study was performed to analyze the surgical results of repeat Hx and salvage LDLT for patients with recurrent HCC within the Milan criteria from 1989 to 2012. A total of 159 patients were divided into 2 groups: a repeat Hx group (n = 146) and a salvage LDLT group (n = 13). Operative results and patient prognoses were compared between the 2 groups. The operative invasiveness, including the operation time (229.1 ±â€‰97.7 versus 862.9 ±â€‰194.4 minutes; P < 0.0001) and blood loss (596.3 ±â€‰764.9 versus 24,690 ±â€‰59,014.4 g; P < 0.0001), were significantly higher in the salvage LDLT group. The early surgical results, such as morbidity (31% versus 62%; P = 0.0111) and the duration of hospital stay (20 ±â€‰22 versus 35 ±â€‰21 days; P = 0.0180), were significantly worse in the salvage LDLT group. There was no significant difference in the overall survival (OS) rate, but the disease-free survival rate of the salvage LDLT group was significantly better (P = 0.0002). The OS rate of patients with grade B liver damage in the repeat Hx group was significantly worse (P < 0.0001), and the 5-year OS rate was quite low, that is, 20% (liver damage A, 77% for the repeat Hx group and 75% for the salvage LDLT group). The prognosis of patients with grade B liver damage after repeat Hx for recurrent HCC is poor, and salvage LDLT would be a potent option for such patients.

DOI： 10.1002/lt.24111

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Several animal models have revealed that platelet-derived serotonin initiates liver regeneration after hepatectomy. However, there are few reports regarding the effects of serotonin in the clinical setting. The aim of this study was to explore the impact of serotonin and platelets in the early phase after healthy living donor hepatectomy. Study Design Stored samples from 34 living donors who received left lobectomy with caudate lobectomy (LL+C) or right lobectomy (RL) were available in the study. Serum serotonin levels and platelet counts associated with liver regeneration such as whole liver volume and hepatic graft weight (GW) were retrospectively collected from the database and analyzed. Results The remnant liver volume rate of RL grafts was smaller than that of LL+C grafts (45.4% vs 64.7%; P <.001). The regeneration rate at 7 days after surgery did not differ between the 2 groups (123% vs 122%). The serotonin levels and platelet counts decreased after surgery until postoperative day 3, then increased thereafter. The platelet counts and serotonin levels of LL+C donors were significantly higher than those of RL donors. Conclusions Our findings suggest that platelets and serotonin play a pivotal role in initiating liver regeneration in the remnant liver.

DOI： 10.1016/j.transproceed.2014.11.050

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Hepatitis C viral graft reinfection is almost a universal event after liver transplantation with consequent disease progression. Methods We applied triple therapy (n = 21) with the use of telaprevir (TVR; n = 12) or simeprevir (SVR; n = 9). Results TVR was given at the dose 1,500 mg daily (n = 11) with reduced dose of cyclosporine at 25% to 50%, and SVR was given at the dose 100 mg daily with unadjusted cyclosporine, followed by 12 weeks of dual therapy. The early viral response was achieved in 91.7% (n = 11), end of treatment response rate was 91.7% (n = 11), and sustained viral response rate was 83.3% (n = 10) in the TVR group, and respective rates were 88.9% (n = 8), 77.8% (n = 7), and 77.8% (n = 7) in the SVR group. Although granulocyte colony-stimulating factor was not given in the patients with triple therapy, blood transfusion was performed in 7 cases (58.3%) in the TVR group and 1 case (11.1%) in the SVR group. Interferon-mediated graft dysfunction was observed in 4 cases (33.3%) in the TVR group and 3 cases (33.3%) in the SVR group, respectively. The cumulative viral clearance rates in triple (n = 21) and dual (n = 105) therapy were 95.0% and 18.1% at 12 weeks, and 95.0% and 40.0%, respectively, at 24 weeks (P <.01). Conclusions Although careful monitoring for possible adverse events is required during treatment, triple therapy with the use of direct-acting agents are very effective in treating hepatitis C after liver transplantation.

DOI： 10.1016/j.transproceed.2014.10.058

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 23-year-old Japanese man presented with a history of sudden-onset right abdominal pain accompanied by nausea and vomiting. Contrast-enhanced CT showed a large cluster on the right side of the retroperitoneum, with most of the small bowel incarcerated. The patient was diagnosed with small bowel obstruction caused by a right paraduodenal hernia, and emergency laparoscopic surgery was performed. The large retroperitoneal cluster on the right side contained almost all segments of the small bowel, although the incarcerated bowel showed no evidence of volvulus or ischemia. The bowel was reduced, and the hernia orifice was closed. The patient made good progress and was discharged 7 days after surgery. We herein report an acute case of right paraduodenal hernia with small bowel obstruction that was successfully treated with emergency laparoscopic surgery. With an early preoperative diagnosis, laparoscopic surgery is appropriate for the treatment of right paraduodenal hernia.

DOI： 10.1111/ases.12139

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Transecting cirrhotic liver in pure laparoscopic hepatectomy (PLH) is generally considered technically demanding. We have preferentially used BiClamp in PLH by fracturing liver parenchyma using this device. The aim of the current study was to retrospectively verify the efficacy of BiClamp-fracture method in transecting cirrhotic parenchyma. Methods: The medical records of 21 patients who underwent PLH using BiClamp-fracture method between April 2011 and September 2014 were examined. The patients were divided into the Nonstiff group (F0-F2, n=11) and the Stiff group (F3 and F4, n=10) and various surgical factors were compared between the groups. Results: The mean operation time, the mean intraoperative blood loss, and the mean postoperative hospital stay in the Stiff group were comparable with those in the Nonstiff group. There were no postoperative complications in both groups. Conclusion: BiClamp-fracture method was effective in transecting liver parenchyma irrespective of liver stiffness in PLH.

DOI： 10.1097/SLE.0000000000000172

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Although the Milan criteria are widely accepted for liver transplantation (LT) in patients for hepatocellular carcinoma (HCC), they have not been fully evaluated for salvage LT in patients with recurrent HCC. We have previously reported outcomes of living-donor LT (LDLT) for HCC and identified 2 risk factors affecting recurrence-free survival (RFS): tumor size >5 cm and des-γ-carboxyl prothrombin (DCP) concentration >300 mAU/mL (Kyushu University criteria). This study was designed to clarify risk factors for tumor recurrence after LDLT in patients with recurrent HCC. Methods Outcomes in 114 patients who underwent LDLT for recurrent HCC were analyzed retrospectively. RFS rates after LDLT were calculated, and risk factors for tumor recurrence were identified. Results The 1-, 3-, and 5-year RFS rates after LDLT were 90.6%, 80.4%, and 78.8%, respectively. Univariate analysis showed that tumor recurrence was associated with alpha-fetoprotein concentration ≥300 ng/mL, DCP concentration ≥300 mAU/mL, tumor number ≥4, tumor size ≥5 cm, transarterial chemotherapy before LDLT, duration of last treatment of HCC to LDLT <3 months, bilobar distribution, exceeding Milan criteria, exceeding Kyushu University criteria, poor differentiation, and histologic vascular invasion. Multivariate analysis showed that DCP ≥300 mAU/mL (P =.03) and duration from last treatment to LDLT <3 months (P =.01) were independent predictors of RFS. Conclusions DCP concentration and time between last treatment and LDLT are prognostic of RFS in patients undergoing LDLT for HCC.

DOI： 10.1016/j.transproceed.2014.09.178

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aim: Survival of patients with multiple recurrences (MR) of hepatocellular carcinoma (HCC) is very poor as recurrent tumors are usually aggressive and not amenable to curative resection. The present study aimed to investigate retrospectively predictors of intrahepatic MR of HCC after hepatectomy. Patients and Methods: We reviewed 416 patients who underwent hepatectomy and developed intrahepatic recurrence during the follow-up period. According to the recurrence pattern, the patients were divided into two groups: 83 who had four or more recurrent lesions in the remnant liver were defined as the MR group and the others who constituted the control group. Results: Multivariate analysis showed that micro-intrahepatic metastasis, α-fetoprotein and tumor size were independent risk factors for MR after hepatectomy. The combination of these three independent factors was significantly associated with MR. The recurrence rates within 1 year after hepatectomy of MR and control groups were 53.0% and 27.6%, respectively (p=0.0001). The 5-year overall survival rate of the MR group was 39%, which was significantly less than that of the control group (68%, p<0.0001). Conclusions: MR of HCC was associated with an earlier recurrence and poorer survival after hepatectomy. The combination of three independent factors for MR might help predict MR occurrence during the follow-up period.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: This retrospective study investigated outcomes after laparoscopic hepatectomy in the semi-prone position compared to open hepatectomy in the conventional supine position, for HCC (hepatocellular carcinoma) located in segment 6, 7, or 8. Patients and Methods: Patients were divided into two groups according to the surgical approach. The clinicopathological and surgical outcomes were analyzed. Results: There were no significant differences in patient-related or tumor-related factors between the two groups. The laparoscopic-hepatectomy group had significantly less blood loss, fewer postoperative complications, and a shorter hospital stay than the open-hepatectomy group. There were no in-hospital deaths. The postoperative change in the serum C-reactive protein was a significantly larger decrease in the group treated with laparoscopic hepatectomy than that in the open-hepatectomy group. Conclusion: Laparoscopic hepatectomy in the semi-prone position for HCC is safe and minimally invasive, and can reduce intraoperative bleeding, postoperative complications, and hospital stay compared to open hepatectomy.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aim: Combined hepatocellular-cholangio carcinoma (cHC-CC) is found unexpectedly in explanted or resected liver specimens. The current study evaluated the longterm outcomes of living-donor liver transplantation (LDLT) between patients with cHC-CC and hepatocellular carcinoma (HCC). Patients and Methods: We performed 178 LDLT including 8 patients of pathologically and immunohistochemically diagnosed cHC-CC who all under went LDLT with a preoperative diagnosis of HCC by ima ging study. Results: Out of the 8 patients, 6 were within the Milan criteria and all were within the Kyushu University criteria. The 1-, 5- and 10-year overall survival (OS) and disease-free survival (DFS) rates after LDLT for patients with cHC-CC were 87.5, 72.9 and 48.6% and 85.7, 85.7 and 85.7%, respectively. The OS and DFS between patients with cHC-CC and HCC were not statistically different. Conclusion: LDLT for patients with cHC-CC using the Milan criteria or the Kyushu University criteria, as well as HCC, could have an acceptable long-term outcome.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Laparoscopic splenectomy (LS) is still challenging in patients with liver cirrhosis and portal hypertension. This study was designed to establish safe and less invasive LS in patients with liver cirrhosis and portal hypertension. Study Design We analyzed 390 patients with liver cirrhosis and portal hypertension, who underwent LS between 1993 and 2013. Patients were divided into 3 time periods; early (1993 to 2004, n = 106); middle (2005 to 2008, n = 159); and late (2008 to 2013, n = 125). During the middle time period, standardized technique for LS and selection criteria for hand-assisted LS were adopted. Patients with spleen volume ≥ 1,000 mL by CT volumetry, large perisplenic collateral vessels, and/or Child-Pugh score ≥ 9, underwent hand-assisted LS. During the late time period, the selection criteria were refined and patients with spleen volume ≥ 600 mL underwent hand-assisted LS. Results Conversion to open splenectomy decreased (10.4% in the early time period, 1.9% in the middle time period, and 3.2% in the late time period, p = 0.004), median blood loss decreased (300g, 87g, and 98g, respectively, p < 0.001), and the success rate of pure LS tended to improve (87.2%, 89.5%, and 98.0%, respectively, p = 0.110). Mortality was 0% in each time period, Clavien-Dindo grade IIIb or more complications tended to decrease (5.7%, 2.5%, and 0.8%, respectively, p = 0.081), and technique-related complications decreased significantly (10.4%, 3.8%, and 2.4%, respectively, p = 0.014). Conclusions Laparoscopic splenectomy is now a safe and less invasive approach, even in patients with liver cirrhosis and portal hypertension, because of its technical standardization with the refined selection criteria for pure or hand-assisted LS.

DOI： 10.1016/j.jamcollsurg.2015.04.011

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Our aim was to determine whether variant bile duct (BD) anatomy is associated with portal vein (PV) and/or hepatic artery (HA) anatomy. We examined the associations between BD anatomy and PV and/or HA anatomy in 407 living donor transplantation donors. We also examined whether the right posterior BD (RPBD) course was associated with the PV and/or HA anatomy. Variant PV, HA and BD anatomies were found in 11%, 25% and 25%, respectively, of 407 donors enrolled in this study. The presence of a variant BD was more frequently associated with a variant PV than with a normal PV (61% vs. 20%, p<0.0001). By contrast, the presence of a variant HA was not associated with a variant BD. A supraportal RPBD was found in 357 donors (88%) and an infraportal RPBD was found in 50 donors (12%). An infraportal RPBD was significantly more common in donors with a variant PV than in donors with a normal PV (30% vs. 10%, p=0.0004). Variant PV, but not variant HA, anatomies were frequently associated with variant BD anatomy. Additionally, an infraportal RPBD was more common in donors with a variant PV than in donors with a normal PV. This study investigating the anatomy of 407 living liver donors indicates that variant portal vein, but not variant hepatic artery, anatomies are frequently associated with variant bile duct anatomy.

DOI： 10.1111/ajt.12965

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recently, many studies of the patients with chronic liver disease have focused on sarcopenia. In the patients with chronic liver disease, sarcopenia occurs, because of advanced liver failure and hepatocellular carcinoma (HCC) . In both diseases, sarcopenia is an important prognostic factor. Thus, sarcopenia has been reported to be a predictor for recurrence of HCC and early mortality after liver transplantation. In the patients with HCC, the mechanism of sarcopenia is unknown. In the patients with endostea liver failure, muscle compensates energy breakdown of the liver and muscle atrophy occurs. Further research is necessary to clarify whether nutritional support and muscle training prevent from sarcopenia and as a result, improve survival of the patients with chronic liver disease.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

There seemed to be characteristic risk factors in cirrhotic patients for posthepatectomy complications because these patients have less hepatic reserve as compared with noncirrhotic patients. The aim of the current study was to identify these characteristic risk factors in cirrhotic patients. We performed 419 primary hepatectomies for hepatocellular carcinoma. The patients were divided into the cirrhotic group (n 5 198) and the noncirrhotic group (n 5 221), and the risk factors for posthepatectomy complications were compared between the groups. Thirty-six cirrhotic patients (18.2%) experienced Clavien's Grade III or more complications. Tumor size, intraoperative blood loss, duration of operation, major hepatectomy (two or more segments), and necessity of blood transfusion were found to be significant risk factors in univariate analyses. Multivariate analysis revealed that major hepatectomy and intraoperative blood loss were independent risk factors for posthepatectomy complications in patients with cirrhosis. On the other hand, the duration of operation was only an independent risk factor for posthepatectomy complication in noncirrhotic patients. Cirrhotic patients should avoid a major hepatectomy and undergo a limited resection preserving as much liver tissue as possible and meticulous surgical procedures to lessen intraoperative blood loss are mandatory to prevent major posthepatectomy complications.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose. To evaluate the effect of body composition on outcomes after hepatic resection for patients with hepatocellular carcinoma (HCC). Methods. We performed 190 hepatic resections for HCC and divided the patients into 2 groups on the basis of visceral fat area (VFA), assessed by computed tomographic measurement at the level of the umbilicus, into high VFA (H-VFA) (n = 106) and low VFA (L-VFA) (n = 84) groups. We compared the surgical outcomes between the two groups. Results. L-VFA was significantly correlated with a lower body mass index, sarcopenia, lower serum albumin, and liver cirrhosis. There was no difference in the incidence of postoperative complications and mortality between the 2 groups. Patients in the L-VFA group had a significantly poorer prognosis than those in the H-VFA group in terms of both overall (P = 0.043) and recurrence-free (P = 0.001) survival. The results of multivariate analysis showed that sarcopenia rather than L-VFA was an independent and prognostic indicator after hepatic resection with HCC. Conclusions. Body composition is an important factor affecting cancer outcomes after hepatic resection for HCC in Japan.

DOI： 10.1245/s10434-014-3686-6

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jamcollsurg.2014.03.059

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jamcollsurg.2014.04.021

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Thoracic fluid retention after living donor liver transplantation (LDLT) has various negative consequences, including atelectasis, pneumonia, and respiratory distress or failure. Study Design: We analyzed the clinical impact of preemptive thoracic drainage in 177 patients undergoing adult-to-adult LDLT for chronic liver diseases at a single center. Recipients were divided into 2 time periods. The earlier cohort (n = 120) was analyzed for risk factors for postoperative atelectasis retrospectively; the later cohort (n = 57), with a risk factor for postoperative atelectasis, underwent preemptive thoracic drainage prospectively. The incidence of postoperative pulmonary complications was compared between these 2 cohorts. Results: Independent risk factors for atelectasis in earlier cohort were body mass index ≥27 kg/m₂ (p < 0.001), performance status ≥3 (p = 0.003) and model for end-stage liver disease score ≥23 (p = 0.005). The rates of atelectasis (21.1% vs 42.5%, p = 0.005) and pneumonia (1.8% vs 10.0%, p = 0.049) were significantly lower in later than in earlier cohort. Moreover, the mean durations of ICU stay (3.6 ± 0.2 days vs 5.7 ± 0.6 days, p = 0.038) and postoperative oxygen support (5.1 ± 0.8 days vs 7.1 ± 0.5 days, p = 0.037) were significantly shorter in the later than in the earlier cohort. There were no significant differences in the incidence of adverse events associated with thoracic drainages between these 2 cohorts. Conclusions: Preemptive thoracic drainage for transplant recipients at high risk of postoperative atelectasis could decrease morbidities after LDLT.

DOI： 10.1016/j.jamcollsurg.2014.09.006

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Decreased antithrombin III (ATIII) activity and large splenic vein diameter (SVD) are risk factors for portal vein thrombosis (PVT) after splenectomy in liver cirrhosis with portal hypertension. Antithrombin III concentrates can prevent PVT. This study was designed to stratify risks for PVT after splenectomy in cirrhotic patients and to develop prophylactic protocols for PVT.
Study Design In 53 patients (testing cohort), the cutoff level of preoperative ATIII activity (≤60%) was evaluated for administration of ATIII concentrates. Antithrombin III activity and SVD were re-evaluated as criteria for prophylaxis of PVT. In 57 patients (validation cohort), the risk stratification of PVT and prophylactic protocols were validated.
Results In the testing cohort, 10 (19%) of 53 patients had PVT. Risk level of PVT was stratified and prophylactic protocols were developed. Patients at low risk (ATIII activity ≥70% and SVD <10 mm) were not treated; those at high risk (ATIII activity <70% or SVD ≥10 mm) received ATIII concentrates (1,500 U/day) for 3 days; and those at highest risk (SVD ≥15 mm) received ATIII concentrates for 3 days, followed by danaparoid sodium (2,500 U/day) for 14 days and warfarin. In the validation cohort, 0 of 14 low-risk and 2 of 32 high-risk patients had PVT. Although 8 of 11 patients at highest risk had temporary PVT, it disappeared within 3 months postoperatively. Finally, only 2 (3.5%) of 57 patients had PVT.
Conclusions Risk stratification of PVT after splenectomy and prophylaxis with ATIII concentrates and danaparoid sodium dramatically reduced the incidence of PVT.

DOI： 10.1016/j.jamcollsurg.2014.07.939

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: We first performed laparoscopic hepatic resection (Lap-Hx) for hepatocellular carcinoma (HCC) in 1994. Here we review the long-term surgical results of Lap-Hx for HCC in patients with cirrhosis over a 10-year period at a single institution. Study Design: Between January 2000 and December 2013, 99 patients with cirrhosis underwent open hepatic resection (Open-Hx) and 63 underwent Lap-Hx for primary HCC within the Milan criteria. We compared the operative outcomes and patient survival between the 2 groups. RESULTS: There were no significant differences regarding patient background characteristics or tumorrelated factors between the 2 groups. The morbidity rate of the Lap-Hx group was significantly lower than that of the Open-Hx group (26% vs 10%; p = 0.0459), and the complication rate of ascites was significantly lower (7% vs 0%; p = 0.0077). The mean duration of hospital stay of the Lap-Hx group was significantly shorter than that of the Open-Hx group (16 vs 10 days; p = 0.0008). There were no significant between-group differences regarding overall or disease-free survival. Conclusions: Laparoscopic-Hx for HCC in patients with cirrhosis is associated with less morbidity and shorter hospital stays, with no compromise in patient survival. It may be time to consider changing the standard operation for primary HCC within the Milan criteria to Lap-Hx in patients with cirrhosis.

DOI： 10.1016/j.jamcollsurg.2014.09.003

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Long-term dialysis often causes physiological and metabolic problems that may affect the outcomes of surgery. The aim of this study was to elucidate whether emergency surgery for acute abdomen yields similar outcomes in dialysis patients versus non-dialysis patients. Methods: The subjects were 126 patients who underwent emergency surgery for acute abdomen between January, 2007 and November, 2011 in our hospital. They were divided into a dialysis group (HD group; n = 9) and a non-dialysis group (non-HD group; n = 117) and their postoperative morbidity and mortality were compared. Results: Postoperative morbidity and mortality were significantly worse in the HD group. All 9 of these patients succumbed to postoperative complications versus only 5 of the 117 patients in the non-HD group. Conclusion: The outcomes of emergency surgery for acute abdomen were significantly worse for dialysis patients than for non-dialysis patients. Prompt diagnosis, initiation of the most suitable surgical procedure, and meticulous postoperative cares are imperative to improving the surgical outcomes of dialysis patients.

DOI： 10.1007/s00595-013-0673-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction. The feasibility of telaprevir-based triple therapy for recurrent hepatitis C after liver transplantation (LT) has not been evaluated in Asian patients. Methods. Eleven Japanese patients received reduced-dose telaprevir (1500 mg) and adjusted-dose cyclosporine after LT. Six patients were nonresponders and three were transient responders to dual therapy. Results. Rapid viral response, early viral response, end of treatment response, and sustained viral response were achieved in 27.3%, 90.9%, 90.9%, and 81.8% of patients, respectively. One patient had viral breakthrough at week 8 with a T54A mutation in NS3. Deep sequence analysis showed that the T54A mutation reverted to wild-type after stopping telaprevir administration. Seven patients developed severe anemia, and six received blood transfusions (4Y20U). Their hemoglobin and estimated glomerular filtration rate remained significantly lower than pretreatment values at 36 weeks after treatment. Four patients developed plasma cell hepatitis after completing telaprevir treatment, and it was treated by increasing the immunosuppressants. Although the cyclosporine level/dose ratio was 2.7 times higher at week 4 than before treatment, it was 0.7 times lower at week 36. Conclusions. Reduced-dosed telaprevir-based triple antiviral therapy achieved a high viral clearance rate in Japanese patients after LT. Major adverse events included severe anemia, renal dysfunction, and plasma cell hepatitis.

DOI： 10.1097/TP.0000000000000166

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The aim of the current study was to investigate whether pure laparoscopic partial hepatectomy can be safely performed using a newly developed vessel sealing device, BiClamp. METHODS: Nine cases of pure laparoscopic partial hepatectomy were performed by simply transecting liver parenchyma using the BiClamp. Four patients had a cirrhotic liver. The median tumor diameter was 1.5 cm (range, 1.0 to 2.7 cm). The tumors were located in segment (S) 3 in 3 cases, S4 in 1 case, S5 in 2 cases, S6 in 1 case, and S8 in 2 cases. Simultaneous cholecystectomy was performed in 4 cases. RESULTS: The median operation time was 187 minutes (range, 83 to 423 min) and the median estimated blood loss was little (range, little to 417 mL). All patients were discharged from the hospital without any adverse postoperative consequences. CONCLUSIONS: BiClamp is an effective device for transecting liver parenchyma during pure laparoscopic partial hepatectomy, even in cirrhotic livers.

DOI： 10.1097/SLE.0b013e3182806535

開催年月日： 2023年4月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2023年4月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：長崎市   国名：日本国  

開催年月日： 2022年12月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：名古屋市   国名：日本国  

開催年月日： 2022年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福岡市   国名：日本国  

開催年月日： 2022年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福岡市   国名：日本国  

開催年月日： 2022年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福岡市   国名：日本国  

開催年月日： 2022年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：神戸市   国名：日本国  

開催年月日： 2022年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：横浜市   国名：日本国  

開催年月日： 2022年6月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：横浜市   国名：日本国  

開催年月日： 2022年6月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：松山市   国名：日本国  

開催年月日： 2022年4月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2021年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2021年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2021年10月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2021年9月

記述言語：日本語  

国名：日本国  

開催年月日： 2021年7月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2021年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2021年6月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2021年6月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2021年4月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2021年4月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2021年1月

記述言語：日本語  

国名：日本国  

開催年月日： 2020年12月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：紙面発表   国名：日本国  

開催年月日： 2020年12月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2020年12月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：Web   国名：日本国  

開催年月日： 2020年11月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2020年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：Web   国名：日本国  

開催年月日： 2020年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：Web   国名：日本国  

開催年月日： 2020年8月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：Web   国名：日本国  

開催年月日： 2020年8月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：Web   国名：日本国  

開催年月日： 2019年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：高知市   国名：日本国  

開催年月日： 2019年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：横浜市   国名：日本国  

開催年月日： 2019年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：広島市   国名：日本国  

開催年月日： 2019年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2019年6月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：香川市   国名：日本国  

開催年月日： 2019年5月 - 2020年5月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2018年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2018年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2018年6月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：大阪市   国名：日本国  

開催年月日： 2018年5月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2018年5月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2018年4月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2017年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2017年11月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：熊本市   国名：日本国  

開催年月日： 2016年10月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：Kyoto   国名：日本国  

開催年月日： 2016年7月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：徳島市   国名：日本国  

開催年月日： 2015年12月

記述言語：英語  

開催地：Singapore   国名：シンガポール共和国  

開催年月日： 2015年4月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：仙台市   国名：日本国  

開催年月日： 2023年9月

記述言語：日本語  

開催地：横浜市   国名：日本国  

開催年月日： 2023年9月

記述言語：日本語  

開催地：札幌市   国名：日本国  

開催年月日： 2023年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：大阪市   国名：日本国  

開催年月日： 2023年7月

記述言語：日本語  

開催地：Seoul   国名：大韓民国  

開催年月日： 2023年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：大阪市   国名：日本国  

開催年月日： 2023年6月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2023年6月

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：佐賀市   国名：日本国  

開催年月日： 2023年6月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：横浜市   国名：日本国  

開催年月日： 2023年6月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：奈良市   国名：日本国  

開催年月日： 2023年2月

記述言語：日本語  

国名：日本国  

開催年月日： 2023年1月

記述言語：日本語  

国名：日本国  

開催年月日： 2022年12月

記述言語：日本語  

開催地：名古屋市   国名：日本国  

開催年月日： 2022年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福岡市   国名：日本国  

開催年月日： 2022年9月

記述言語：日本語  

開催地：大分市   国名：日本国  

開催年月日： 2022年7月

記述言語：日本語  

開催地：東京   国名：日本国  

開催年月日： 2022年6月

記述言語：日本語  

開催地：軽井沢市   国名：日本国  

開催年月日： 2022年6月

記述言語：日本語  

開催地：軽井沢市   国名：日本国  

開催年月日： 2022年5月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2022年4月

記述言語：日本語  

開催地：熊本市   国名：日本国  

開催年月日： 2022年3月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2021年10月

記述言語：日本語  

国名：日本国  

開催年月日： 2021年9月

記述言語：日本語  

国名：日本国  

開催年月日： 2021年8月

記述言語：日本語  

国名：日本国  

開催年月日： 2021年7月

記述言語：日本語  

国名：日本国  

開催年月日： 2021年7月

記述言語：日本語  

国名：日本国  

開催年月日： 2021年6月

記述言語：英語  

国名：日本国  

開催年月日： 2021年5月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2021年2月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：Web   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語  

開催地：紙面開催   国名：日本国  

開催年月日： 2020年8月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：Web   国名：日本国  

開催年月日： 2020年1月

記述言語：日本語  

開催地：東京   国名：日本国  

開催年月日： 2019年12月

記述言語：日本語  

国名：日本国  

開催年月日： 2019年10月

記述言語：日本語  

開催地：広島市   国名：日本国  

開催年月日： 2019年10月 - 2020年10月

記述言語：日本語  

開催地：名古屋市   国名：日本国  

開催年月日： 2019年9月

記述言語：日本語  

開催地：東京   国名：日本国  

開催年月日： 2019年7月

記述言語：日本語  

開催地：東京   国名：日本国  

開催年月日： 2019年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2019年4月

記述言語：日本語  

国名：日本国  

開催年月日： 2019年2月

記述言語：日本語  

開催地：福岡市   国名：日本国  

開催年月日： 2019年1月

記述言語：日本語  

開催地：福岡市   国名：日本国  

開催年月日： 2018年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2018年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2017年10月

記述言語：日本語  

開催地：福岡市   国名：日本国  

開催年月日： 2017年9月

記述言語：日本語  

開催地：横浜市   国名：日本国  

開催年月日： 2017年9月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2017年5月

記述言語：日本語  

開催地：名古屋市   国名：日本国  

開催年月日： 2017年4月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：横浜市   国名：日本国  

開催年月日： 2017年4月

記述言語：日本語  

開催地：東京   国名：日本国  

開催年月日： 2016年12月

記述言語：日本語  

開催地：横浜市   国名：日本国  

開催年月日： 2016年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2016年9月 - 2016年10月

記述言語：日本語  

開催地：東京   国名：日本国  

開催年月日： 2016年9月

記述言語：日本語  

開催地：鹿児島市   国名：日本国  

開催年月日： 2016年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：旭川市   国名：日本国  

開催年月日： 2016年6月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：大阪市   国名：日本国  

開催年月日： 2016年4月

記述言語：日本語  

開催地：東京   国名：日本国