出版者・発行元：南江堂  

DOI： 10.15106/j_geka87_353

CiNii Research

記述言語：英語   出版者・発行元：Cancer Medicine  

Aim: With advances in systemic therapy, the number of patients with hepatocellular carcinoma (HCC) who can undergo hepatic resection has increased in recent years, but there are no reports evaluating the immune status in the peritumoral area. Methods: We enrolled 14 patients who underwent hepatic resection after lenvatinib (LEN, n = 7) or atezolizumab plus bevacizumab (ATZ/BEV, n = 5) therapy. Tumor-infiltrating lymphocytes (TILs), including CD3+ and CD8+ TILs, in the peritumoral area were evaluated by hematoxylin and eosin staining and immunohistochemistry. Results: The median TIL counts after LEN and ATZ/BEV therapy were 32 and 92 cells/0.237 mm², respectively (p = 0.0044). The median CD3+ TIL counts after LEN and ATZ/BEV therapy were 26 and 71 cells/0.237 mm², respectively (p = 0.0057). The median CD8+ TIL counts after LEN and ATZ/BEV therapy were 14 and 42 cells/0.237 mm², respectively (p = 0.0044). Conclusion: TIL counts, including those of CD3+ and CD8+ TILs, in the peritumoral area were significantly higher after ATZ/BEV than after LEN therapy.

DOI： 10.1002/cam4.70445

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

記述言語：英語   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   出版者・発行元：Transplantation Proceedings  

The Duct of Luschka represents a rare form of accessory biliary ducts. There are no reported cases of the Duct of Luschka in living donor hepatectomy. We report a 36-year-old man with the Duct of Luschka who underwent living-donor hepatectomy. Preoperative drip infusion cholangiography with computed tomography (DIC-CT) identified the Duct of Luschka originating from the right hepatic duct to the cystic duct. By choosing the left and caudate lobe hepatectomy, the Duct of Luschka was left intact during the procedure. The donor recovered uneventfully posthepatectomy, and the recipient also did not experience biliary complications. This case underscores the importance of preoperative DIC-CT and surgical planning, including graft selection, to prevent postoperative bile leaks.

DOI： 10.1016/j.transproceed.2025.02.010

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記述言語：英語   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 (mm Hg)=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). In addition, PVP at closure could be predicted using correlated operative factors, including measured PVP at laparotomy, as follows: predicted PVP at closure (mm Hg)=14.268 + 0.149 × (measured PVP at laparotomy [mm Hg]) - 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 patients with decompensated cirrhosis undergoing liver transplant. 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   出版者・発行元：シュプリンガー・ジャパン(株)  

記述言語：英語   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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記述言語：英語   出版者・発行元：Journal of Hepato Biliary Pancreatic Sciences  

Background: Few published reports have addressed the feasibility of living-donor liver transplantation (LDLT) using elderly donors. We aimed to examine LDLT outcomes in elderly donors and identify clinical factors impacting safely conducted LDLT. Methods: This study was conducted in collaboration with the Japanese Society of Hepatobiliary-Pancreatic Surgery. Data were collected from 140 patients who underwent LDLT using donors aged ≥50 years between 2013 and 2017 at nine collaborating hospitals. Results: The 1-, 3-, and 5-year graft survival rates in recipients after LDLT employing elderly donors were 84.3%, 78.5%, and 76.3%, respectively, with 6-month mortality of 12.1%. Specific recipient-donor age combinations did not emerge as adverse prognostic factors. A total of 32 recipients (22.9%) had major complications requiring reoperation after LDLT, and 15 donors (10.7%) had major complications of Clavien–Dindo grade ≥II. Multivariate analysis revealed that graft-to-recipient weight ratio (GRWR) <0.84% and neutrophil-to-lymphocyte ratio (NLR) >6.6 were independent predictors of 6-month graft loss after LDLT. Conclusion: LDLT using elderly donors aged ≥50 years has acceptable graft survival and morbidity rates, and donor age >50 years should not be an absolute contraindication for LDLT. In LDLT involving elderly donors, it is crucial to consider that GRWR <0.84% and NLR >6.6 are adverse prognostic factors. Addressing these factors is necessary to enhance the prognosis, aligning with the increasing public demand for this surgical procedure.

DOI： 10.1002/jhbp.12118

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

記述言語：英語   出版者・発行元：Liver Cancer  

Introduction: TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target protein that has critical roles in glycolysis and redox balance. The reports about the effect of TIGAR on prognosis and its biological role in hepatocellular carcinoma (HCC) are limited. Methods: A total of 386 patients with HCC who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. Additionally, the regulation of malignant activity and ferroptosis by TIGAR was investigated in vitro. Results: Patients were divided into TIGAR-positive (n = 80, 20.7%) and -negative (n = 306, 79.3%) groups. TIGAR positivity was significantly correlated with lower albumin, higher α-fetoprotein/ des-gamma-carboxyprothrombin, larger tumor size/ number of tumors, and greater proportions of BCLC staging C/single nodular type/poor differentiation/microscopic vascular invasion/microscopic intrahepatic metastasis. In multivariate analysis, TIGAR positivity was an independent prognostic factor (p < 0.0001). In addition, TIGAR positivity was significantly associated with a smaller number of cluster of differentiation (CD) 8-positive T cells (p = 0.0450), larger number of CD68-positive macrophages (p = 0.0058), larger number of programmed death-ligand 1-positive cases (p = 0.0002), and larger number of vessels that encapsulate tumor cluster-positive cases (p = 0.0004). In vitro, TIGAR knockdown decreased cell motility and induced ferroptosis. TIGAR knockdown inhibited the phosphorylation of adenosine monophosphate-activated protein kinase and acetyl-CoA carboxylase. Ferroptosis induced by TIGAR knockdown was inhibited by liproxstatin and baicalein treatment. The combination of TIGAR knockdown and lenvatinib further induced ferroptosis. Conclusion: High expression of TIGAR impacted the clinical outcome of HCC patients and TIGAR was associated not only with tumor microenvironment but also with resistance to ferroptosis.

DOI： 10.1159/000540180

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

記述言語：英語   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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出版者・発行元：南江堂  

DOI： 10.15106/j_geka87_182

CiNii Research

記述言語：英語   出版者・発行元：Transplantation  

Background. New diagnostic criteria have recently been established to classify small-for-size syndrome (SFSS) after living donor liver transplantation into 3 groups based on severity. This study aimed to evaluate the clinical impact of grade A SFSS and identify the mortality risk. Methods. We collected data from 406 patients diagnosed with grade A SFSS after living donor liver transplantation. Grade A SFSS is characterized by total bilirubin >5 mg/dL on postoperative day (POD) 7 or total bilirubin >5 mg/dL or ascites >1 L/d on POD 14. After propensity score matching, 193 patients were categorized into the up-trend group, down-trend group, and ascites group, with 43 patients (22.3%) in the up-trend group (total bilirubin on POD 7 < POD 14), 107 patients (55.4%) in the down-trend group (total bilirubin on POD 7 > POD 14), and 43 patients (22.3%) in the ascites group (only satisfying ascites criteria). Results. There was no significant difference in survival between patients with grade A SFSS and those without SFSS (P = 0.152). The up-trend group showed a higher 90-d mortality rate than the down-trend and ascites groups (P = 0.025). The 1-y survival rate differed significantly between the groups (87.6%, 91.9%, and 97.7%, respectively; P = 0.044). The independent risk factors for survival were up-trend of total bilirubin, recipient age (65 y and older), model for end-stage liver disease score (≥30), and ABO incompatibility. Patients with ≥2 risk factors had worse survival rates than those with none and only 1 risk factor (P < 0.001). Conclusions. Although the survival rate was comparable between the grade A SFSS and non-SFSS cohorts, the up-trend group showed worse survival. Aggressive interventions should be considered for up-trend patients with risk factors.

DOI： 10.1097/TP.0000000000005225

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

記述言語：英語   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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記述言語：英語   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   出版者・発行元：International Journal of Oncology  

Colorectal cancer (CRC) is widely prevalent and represents a significant contributor to global cancer‑related mortality. There remains a pressing demand for advance‑ ments in CRC treatment modalities. The E3 ubiquitin ligase is a critical enzyme involved in modulating protein expression levels via posttranslational ubiquitin‑mediated proteolysis, and it is reportedly involved in the progression of various cancers, making it a target of recent interest in anticancer therapy. In the present study, using comprehensive expression analysis involving spatial transcriptomic analysis with single‑cell RNA sequencing in clinical CRC datasets, the ubiquitin‑associated protein Shank‑associated RH domain interactor (SHARPIN) was identified, located on amplified chromosome 8q, which could promote CRC progression. SHARPIN was found to be upregulated in tumor cells, with elevated expression observed in tumor tissues. This heightened expression of SHARPIN was positively associated with lymphatic invasion and served as an independent predictor of a poor prognosis in patients with CRC. In vitro and in vivo analyses using SHARPIN‑overexpressing or ‑knockout CRC cells revealed that SHARPIN overexpression upregulated MDM2, resulting in the downregulation of p53, while SHARPIN silencing or knockout downregulated MDM2, leading to p53 upregulation, which affects cell cycle progression, tumor cell apoptosis and tumor growth in CRC. Furthermore, SHARPIN was found to be overexpressed in several cancer types, exerting significant effects on survival outcomes. In conclusion, SHARPIN represents a newly identified novel gene with the potential to promote tumor growth following apoptosis inhibition and cell cycle progression in part by inhibiting p53 expression via MDM2 upregulation; therefore, SHARPIN represents a potential therapeutic target for CRC.

DOI： 10.3892/ijo.2024.5701

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記述言語：英語  

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

出版者・発行元：American Journal of Transplantation  

The authors regret that the original corrected proofs contained incomplete authorship and funding information. Authors Nobuaki Nakayama, Satoshi Mochida, and Atsushi Tanaka were inadvertently missed from the author list and have now been added. The Authors have also made correction to Section 2.1. Study design and Table 4, as well as the Acknowledgments and Funding sections of the article. The online article has been updated accordingly. The authors would like to apologise for any inconvenience caused.

DOI： 10.1016/j.ajt.2024.08.001

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記述言語：英語   出版者・発行元：(一社)日本外科学会  

症例は82歳女性で、特に病歴はなかったが、外陰部に黒色の結節があった。臨床検査により、人差し指の先端ほどの大きさの腫瘤が陰核に認められ、悪性黒色腫が示唆された。結節を切除し、最終診断は陰核悪性黒色腫(pT4bN0M0、pStage IIC)であった。4年後のCTで右肺下葉に5mm大の腫瘤が認められため、右肺の部分切除を行った。切除標本の病理学的検査で悪性黒色腫の肺転移が明らかになったため、術後補助化学療法としてペムブロリズマブ単剤療法を1年間行った。原発巣の外科的切除から9年後の経過観察時に行ったCTで、肝臓のS2領域に18mm大の腫瘤が認められため、ロボット支援腹腔鏡下肝切除術を行った。病理学的検査では、メラニン色素沈着と楕円形から紡錘形の核を有する腫瘍細胞が、シート状および巣状に増殖しているのが認められた。免疫組織化学検査では、melanoma-associated antigen 45およびmelanin-A陽性であり、悪性黒色腫肝転移と診断した。ペムブロリズマブ単剤療法を術後補助化学療法として1年間行った。1年半後の経過観察では再発の徴候は認められなかった。

記述言語：英語   出版者・発行元：Transplantation Proceedings  

Introduction: Depression prevention is crucial for maintaining both physical and mental health and enhancing individuals’ quality of life (QOL) post-transplantation. Despite the heightened susceptibility of post-transplant patients to COVID-19 infection, the relationship between depression and QOL during the pandemic remains unclear. This study aimed to (1) identify depression and QOL during the pandemic in kidney and liver transplant patients, and (2) explore the relationship between QOL and depression. Design: This cross-sectional study involved patients aged 20 years or older who were at least 6 months post-transplantation. Depression and QOL were assessed using the Patient Health Questionnaire-9 and the 8-item Short-Form Health Survey, respectively. Logistic regression analysis was conducted to examine the relationship between QOL and depression. The study included 204 participants comprising 68 postkidney transplant and 136 postliver transplant patients. Results: Among all participants, depressive symptoms were present 30% of the time, with 8.3% experiencing moderate or severe depression. Logistic regression analysis revealed that depression (mental component summary; OR = 2.419, P < .001, 95% CI: 1.862–2.915) and postoperative period (physical component summary; OR = 1.397, P = .008, 95% CI: 1.094–1.733) significantly influenced QOL. Conclusion: This study suggests that the prevention of depression in emerging infectious disease pandemics may contribute to maintaining the mental QOL of transplant recipients.

DOI： 10.1016/j.transproceed.2024.08.034

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出版者・発行元：American Journal of Transplantation  

Liver transplantation is often the only lifesaving option for acute liver failure (ALF); however, the predictors of short-term mortality (death within one year) after living donor liver transplantation (LDLT) for ALF have yet to be defined. We retrospectively collected patients ≥18 years old who underwent LDLT for ALF between 2010 and 2020 at 35 centers in Asia. Univariate and multivariate logistic regression analyses were conducted to identify the clinical variables related to short-term mortality and establish a novel scoring system. The Kaplan-Meier method was performed to explore the association between the score and overall survival. Of the 339 recipients, 46 (13.6%) died within 1 year after LDLT. Multivariate analyses revealed 4 independent risk factors for death: use of vasopressors or mechanical ventilation, the higher model for end-stage liver disease score, and a lower graft-to-recipient weight ratio. The internally validated c-statistic of the short-term mortality after transplant (SMT) score derived from these 4 variables was 0.80 (95% confidence interval: 0.74-0.87). The SMT score successfully stratified recipients into low-, intermediate-, and high-risk groups with 1-year overall survival rates of 96%, 80%, and 50%, respectively. In conclusion, our novel SMT score based on 4 predictors will guide ALF recipient and living donor selection.

DOI： 10.1016/j.ajt.2024.04.016

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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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記述言語：英語  

DOI： 10.1186/s40792-024-02014-5

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DOI： 10.1097/01.tp.0001065652.38684.34

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DOI： 10.1097/01.tp.0001068216.93552.f1

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記述言語：英語   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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記述言語：英語   出版者・発行元：(一社)日本外科学会  

DOI： 10.1097/01.tp.0001066360.15680.df

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

単一施設の生体肝移植(LDLT)患者30例(男性11例、女性19例、中央値60歳)を対象に、血清ミオスタチン値およびサルコペニアに対する周術期筋電気刺激(EMS)の効果を評価した。16例をEMSシステムSIXPAD群、14例を対照群に無作為に割り付けた。SIXPAD群では、割付け時から術後の退院時まで大腿筋に20分のEMSを1日2回行った。SIXPAD使用前とLDLT直前の血清を用いて、ミオスタチンを評価した。SIXPAD使用前とLDLT後1ヵ月時にCT検査を行い、第3腰椎レベルの腸腰筋指数(PMI)および大腿四頭筋面積を評価した。LDLT患者におけるLDLT直前の血清ミオスタチンは、健常者に比べて有意に高値であった。SIXPAD群では血清ミオスタチンが有意に低下したが、対照群では有意な低下を認めなかった。SIXPAD群では対照群に比べてLDLT後の大腿四頭筋面積の減少が有意に小さく、LDLT後のPMI低下も抑制された。LDLTを行う患者において、EMSプロトコルは実行可能であることが示された。

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   出版者・発行元：Bjs Open  

Background: Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set. Methods: The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model. Results: Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors. Conclusion: This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy.

DOI： 10.1093/bjsopen/zrae079

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

70歳以上のレシピエントにおける生体肝移植(LDLT)の成績を調べるとともに、LDLTの実施可能性を評価した。1997年5月～2022年4月に当院でLDLTを施行された762例を対象とした。LDLTの適応疾患は、C型肝炎による肝硬変が240例、胆汁うっ滞性肝硬変が152例、急性肝不全が86例、アルコール中毒が81例、B型肝炎が63例、非アルコール性脂肪肝炎が53例、自己免疫性肝炎が21例、その他が66例であった。患者を70歳以上の高齢群26例(男性30.8%、平均71.2±1.6歳)と70歳未満の736例(男性45.8%、平均53.2±11.3歳)に分けて比較した。その結果、両群ともLDLT後の30日死亡率および入院期間は同程度であった。高齢群の1年、3年、5年目の移植肝生着率は92.0%であり、これは若年者群の生着率と同程度であった。高齢群のドナーはいずれもレシピエントの子供(平均41.6歳)であり、50歳以上のドナーからの移植例はなかった。

記述言語：英語   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   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   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  

DOI： 10.26508/lsa.202302423

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記述言語：英語   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   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   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   出版者・発行元：シュプリンガー・ジャパン(株)  

右葉生体肝移植(LDLT)にてround ligament-covered prosthetic vascular graft(RP)を用いた静脈再建の短期成績を評価し、人工血管グラフトの移動防止として有効か検討した。当院で2021年1月～2022年10月に右葉LDLTで中肝静脈(MHV)分枝の再建を行った30例を、自家血管グラフト群(A群、24例)とRP群(6例)に分けた。開存グラフトにおける後区域ドレナージ領域のCT density ratioはRP群がA群よりも有意に高かった。しかし、MHV分枝再建の開存率はA群61%、RP群67%で有意差はなかった。RP群に人工血管グラフトの移動は認めなかった。以上より、RPを用いた静脈再建は、右葉LDLTでの人工血管グラフトの移動防止に実行可能かつ簡便な方法であることが示された。

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

肝細胞癌患者の予後に関する米国全国登録のデータを用いて、脳死肝移植(DDLT)に対する5-5-500基準(腫瘍径5cm以内、かつ腫瘍個数5個以内、かつα-フェトプロテイン(AFP)500ng/mL以下)を評価した。2010年1月から2014年12月までに肝細胞癌に対して初回LTを受けた成人DDLTレシピエント5038例を対象とした。その結果、ミラノ基準(MC)内/5-5-500内群4668例(年齢中央値59歳)(76.2%)とMC外/5-5-500内群147例(年齢中央値60歳)(72.3%)よりも、MC内/5-5-500外群142例(年齢中央値58歳)(56.3%)またはMC外/5-5-500外群81例(年齢中央値59.5歳)(60.7%)の方が、5年生存率が有意に低かった(p<0.01)。5年目の肝細胞癌再発率は、MC内/5-5-500外群(25.4%)が最も高く、MC外/5-5-500内群(13.1%)、MC外/5-5-500外群(9.6%)、MC内/5-5-500内群(7.4%)と続いた。DDLT後の層別化5年生存率は、AFP値(ng/mL)がそれぞれ、≦100では76.5%、101～300では72.4%、301～500では58.4%、>500では55.6%であった(p<0.01)。以上より、5-5-500基準はDDLTに適した肝細胞癌患者の選択をもたらした。

記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

胃血行遮断術および脾臓摘出術(Hassab手術)のより簡便な手技として、用手補助腹腔鏡下での脾臓摘出術および胃膵ヒダ分離(GPFD)を行い、術後転帰を検討した。2018年1月から2022年5月までに当院で脾臓摘出術を施行した11例のうち、脾臓摘出術とGPFDを施行した4例を対象とした。4例中3例(75%)で食道胃静脈瘤の改善を得た。1例で術後3年目に食道静脈瘤(F1RC0)を認めたが、治療を要さず追跡調査のみ行った。以上より、難治性食道胃静脈瘤に対する脾臓摘出術とGPFDは、Hassab手術よりも低侵襲であるだけでなく、有効な治療成績をもたらすことが示唆された。

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

2001年8月～2022年1月に生体肝移植(LDLT)を受け生存期間が30日以上の成人レシピエント261人を対象に、遷延性難治性腹水の危険因子として術前三尖弁圧較差(TRPG)の価値を評価した。LDLT前のTRPG値25mmHgをカットオフ値とすると、低TRPG群163人・高TRPG群98人となり、難治性腹水の発生率は高TRPG群10.2%・低TRPG群3.1%と高TRPG群で有意に高かった。多変量解析ではTRPG群高値と開腹時腹水5000mL以上がいずれも難治性腹水の独立した危険因子として抽出された。術前心エコーによって測定されたTRPGはLDLT後に遷延する腹水のリスク因子のひとつとなる可能性がある。

記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

左葉グラフトを用いた生体肝移植(LDLT)においては、現在のドナー手術における腔鏡下肝切除術では、自動リニアステープラーを用いた肝静脈切断によって吻合口頸部が短くなるため、従来の開腹肝切除術に比べて流出路障害の発生が多くなることが予想されている。本稿では、左葉グラフトを用いたLDLTにおいて、肝静脈の周囲にドナー肝円索を用いた新規静脈カフシステムを使って静脈形成術を行い、立体的に容易な肝静脈吻合と術後の静脈開存を確保した10例についてレビューした。その結果、静脈カフに実現可能性があること、また術後の静脈開存に効果的であることが示唆された。

記述言語：英語   出版者・発行元：Cancer Science  

Considering the cost and invasiveness of monitoring postoperative minimal residual disease (MRD) of colorectal cancer (CRC) after adjuvant chemoradiotherapy (ACT), we developed a favorable approach based on methylated circulating tumor DNA to detect MRD after radical resection. Analyzing the public database, we identified the methylated promoter regions of the genes FGD5, GPC6, and MSC. Using digital polymerase chain reaction (dPCR), we termed the “amplicon of methylated sites using a specific enzyme” assay as “AMUSE.” We examined 180 and 114 pre- and postoperative serial plasma samples from 28 recurrent and 19 recurrence-free pathological stage III CRC patients, respectively. The results showed 22 AMUSE-positive of 28 recurrent patients (sensitivity, 78.6%) and 17 AMUSE-negative of 19 recurrence-free patients (specificity, 89.5%). AMUSE predicted recurrence 208 days before conventional diagnosis using radiological imaging. Regarding ACT evaluation by the reactive response, 19 AMUSE-positive patients during their second or third blood samples showed a significantly poorer prognosis than the other patients (p = 9E-04). The AMUSE assay stratified four groups by the altered patterns of tumor burden postoperatively. Interestingly, only 34.8% of cases tested AMUSE-negative during ACT treatment, indicating eligibility for ACT. The AMUSE assay addresses the clinical need for accurate MRD monitoring with universal applicability, minimal invasiveness, and cost-effectiveness, thereby enabling the timely detection of recurrences. This assay can effectively evaluate the efficacy of ACT in patients with stage III CRC following curative resection. Our study strongly recommends reevaluating the clinical application of ACT using the AMUSE assay.

DOI： 10.1111/cas.16149

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記述言語：英語   出版者・発行元：Cancer Science  

Bromodomain and extraterminal domain (BET) family proteins are epigenetic master regulators of gene expression via recognition of acetylated histones and recruitment of transcription factors and co-activators to chromatin. Hence, BET family proteins have emerged as promising therapeutic targets in cancer. In this study, we examined the functional role of bromodomain containing 3 (BRD3), a BET family protein, in colorectal cancer (CRC). In vitro and vivo analyses using BRD3-knockdown or BRD3-overexpressing CRC cells showed that BRD3 suppressed tumor growth and cell cycle G1/S transition and induced p21 expression. Clinical analysis of CRC datasets from our hospital or The Cancer Genome Atlas revealed that BET family genes, including BRD3, were overexpressed in tumor tissues. In immunohistochemical analyses, BRD3 was observed mainly in the nucleus of CRC cells. According to single-cell RNA sequencing in untreated CRC tissues, BRD3 was highly expressed in malignant epithelial cells, and cell cycle checkpoint-related pathways were enriched in the epithelial cells with high BRD3 expression. Spatial transcriptomic and single-cell RNA sequencing analyses of CRC tissues showed that BRD3 expression was positively associated with high p21 expression. Furthermore, overexpression of BRD3 combined with knockdown of, a driver gene in the BRD family, showed strong inhibition of CRC cells in vitro. In conclusion, we demonstrated a novel tumor suppressive role of BRD3 that inhibits tumor growth by cell cycle inhibition in part via induction of p21 expression. BRD3 activation might be a novel therapeutic approach for CRC.

DOI： 10.1111/cas.16129

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

ブロモドメインとエクストラターミナル(BET)蛋白質ファミリーに属するブロモドメイン含有蛋白質3(BRD3)の大腸癌における臨床的および生物学的役割を検討した。その結果、BRD3ノックダウンまたはBRD3過剰発現大腸癌細胞を用いたin vitroおよびin vivo解析により、BRD3が腫瘍増殖と細胞周期G1/S相転移を抑制し、p21発現を誘導することが示された。当院およびThe Cancer Genome Atlasの大腸癌データセットの臨床解析から、BRD3を含むBETファミリー遺伝子が腫瘍組織で過剰発現していることが明らかになった。免疫組織化学的解析では、BRD3は主に大腸癌細胞の核で観察された。未治療の大腸癌組織におけるシングルセルRNAシーケンス解析では、BRD3は悪性上皮細胞で高発現しており、BRD3が高発現している上皮細胞では細胞周期チェックポイント関連経路が濃縮されていた。大腸癌組織の空間トランスクリプトーム解析とシングルセルRNAシーケンス解析から、BRD3の発現はp21の高発現と正の相関があった。さらに、BRD3の過剰発現とBRDファミリーのドライバー遺伝子のノックダウンの組み合わせにより大腸癌細胞に対する強い抑制が認められた。以上より、BRD3が部分的なp21の発現誘導を介して細胞周期を阻害することにより腫瘍増殖を阻害するというBRD3の新たな腫瘍抑制的役割が示唆された。

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

血漿中の微量な循環腫瘍DNA(ctDNA)のメチル化を検出することによりステージIIIの大腸癌患者の術後の微小残存病変(MRD)をモニターできるか評価した。公開データベースを解析し、FGD5、GPC6、MSC遺伝子のメチル化されたプロモーター領域を同定した。デジタルPCRを用いた特異的酵素を用いたメチル化部位のアンプリコンアッセイを「AMUSE」と名付けた。病理学的ステージIIIの大腸癌再発患者28例および無再発患者19例それぞれの術前術後の連続血漿検体、180検体および114検体を調べた。その結果、再発患者28例中22例がAMUSE陽性(感度78.6%)、無再発患者19例中17例がAMUSE陰性(特異度89.5%)であった。AMUSEはX線画像診断による従来の診断より208日早く再発を予測した。反応性応答による術後補助化学放射線療法(ACT)評価に関しては、2回目または3回目の採血でAMUSE陽性の患者19例は、他の患者より有意に予後不良であった。AMUSEアッセイにより、術後の腫瘍負荷の変化パターンによって4群に層別化された。以上より、AMUSEアッセイは、正確なMRDモニタリングに対する臨床的ニーズに対応し、普遍的な適用性、最小限の侵襲性、費用対効果により、タイムリーな再発の発見を可能にすることが示唆された。

記述言語：英語   出版者・発行元：Surgery Today  

Purposes: End-stage liver and kidney disease is an indication for simultaneous liver and kidney transplantation. However, in countries where deceased donor transplantation is not well established, living donor liver transplantation (LDLT) is a realistic option for patients on hemodialysis (HD). We investigated the outcomes of LDLT for patients on HD. Methods: We conducted a retrospective multicenter survey of patients on chronic HD who underwent LDLT in East Asian countries. The characteristics of donors and recipients and the short and long-term outcomes were analyzed. Results: Between 2001 and 2021, 45 patients on HD underwent LDLT and 11 of these patients also underwent kidney transplantation (KT). The overall survival rate at 5 years of the 34 patients who underwent only LDLT was 44.5%. Multivariate analysis identified a low graft recipient weight ratio (< 1%) (p = 0.048) and long HD duration (≥ 10 years) (p = 0.046) as independent predictors of poor overall survival. The major complication was posttransplant bleeding, which occurred in12 patients (35%). Conclusion: It is important to establish the indications for LDLT, taking into consideration graft size and HD duration in candidate patients on HD.

DOI： 10.1007/s00595-023-02751-4

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記述言語：英語   出版者・発行元：Ebiomedicine  

Background: Cell–cell interaction factors that facilitate the progression of adenoma to sporadic colorectal cancer (CRC) remain unclear, thereby hindering patient survival. Methods: We performed spatial transcriptomics on five early CRC cases, which included adenoma and carcinoma, and one advanced CRC. To elucidate cell–cell interactions within the tumour microenvironment (TME), we investigated the colocalisation network at single-cell resolution using a deep generative model for colocalisation analysis, combined with a single-cell transcriptome, and assessed the clinical significance in CRC patients. Findings: CRC cells colocalised with regulatory T cells (Tregs) at the adenoma–carcinoma interface. At early-stage carcinogenesis, cell–cell interaction inference between colocalised adenoma and cancer epithelial cells and Tregs based on the spatial distribution of single cells highlighted midkine (MDK) as a prominent signalling molecule sent from tumour epithelial cells to Tregs. Interaction between MDK-high CRC cells and SPP1+ macrophages and stromal cells proved to be the mechanism underlying immunosuppression in the TME. Additionally, we identified syndecan4 (SDC4) as a receptor for MDK associated with Treg colocalisation. Finally, clinical analysis using CRC datasets indicated that increased MDK/SDC4 levels correlated with poor overall survival in CRC patients. Interpretation: MDK is involved in the immune tolerance shown by Tregs to tumour growth. MDK-mediated formation of the TME could be a potential target for early diagnosis and treatment of CRC. Funding: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research; OITA Cancer Research Foundation; AMED under Grant Number; Japan Science and Technology Agency (JST); Takeda Science Foundation; The Princess Takamatsu Cancer Research Fund.

DOI： 10.1016/j.ebiom.2024.105102

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記述言語：英語   出版者・発行元：Liver Transplantation  

DOI： 10.1097/LVT.0000000000000308

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

東アジア各国で生体肝移植(LDLT)を受けた慢性血液透析(HD)患者を後ろ向きに検討した。2001年から2021年までにHD患者45名がLDLTを受け、うち11名は同時に腎移植(KT)を受けた。LDLT+KTを受けた11名の5年全生存率は100%であった。LDLTのみ受けた34名の5年全生存率は44.5%であった。LDLTのみ受けた患者の多変量解析で、グラフト/レシピエント体重比1%未満およびHD歴10年以上は全生存率不良の独立した予測因子であった。主な移植合併症である移植後出血は12名に発生した。HD患者に対するLDLTのために、グラフト肝サイズおよび透析歴を考慮した適応を確立する必要があると考えられた。

出版者・発行元：日本メディカルセンター  

DOI： 10.19020/cg.0000003026

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記述言語：英語   出版者・発行元：Liver International  

Background & Aims: Recently, the association between hepatocellular carcinoma (HCC) and ferroptosis has been the focus of much attention. The expression of long chain fatty acyl-CoA ligase 4 (ACSL4), a marker of ferroptosis, in tumour tissue is related to better prognosis in various cancers. In HCC, ACSL4 expression indicates poor prognosis and is related to high malignancy. However, the mechanism remains to be fully understood. Methods: We retrospectively enrolled 358 patients with HCC who had undergone hepatic resection. Immunohistochemistry (IHC) for ACSL4 was performed. Factors associated with ASCL4 expression were investigated by spatial transcriptome analysis, and the relationships were investigated by IHC. The association between ACSL4 and the tumour immune microenvironment was examined in a public dataset and investigated by IHC. Results: Patients were divided into ACSL4-positive (n = 72, 20.1%) and ACSL4-negative (n = 286, 79.9%) groups. ACSL4 positivity was significantly correlated with higher α-fetoprotein (p =.0180) and more histological liver fibrosis (p =.0014). In multivariate analysis, ACSL4 positivity was an independent prognostic factor (p <.0001). Spatial transcriptome analysis showed a positive correlation between ACSL4 and cancer-associated fibroblasts; this relationship was confirmed by IHC. Evaluation of a public dataset showed the correlation between ACSL4 and exhausted tumour immune microenvironment; this relationship was also confirmed by IHC. Conclusion: ACSL4 is a prognostic factor in HCC patients and its expression was associated with cancer-associated fibroblasts and anti-tumour immunity.

DOI： 10.1111/liv.15839

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出版者・発行元：金原出版  

DOI： 10.18888/op.0000003803

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記述言語：英語   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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記述言語：英語  

DOI： 10.1186/s40792-024-01820-1

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記述言語：英語   出版者・発行元：(一社)日本外科学会  

49歳男性。特に既往や家族歴、飲酒歴、ウイルス感染歴などなかった。定期検診の腹部超音波検査で肝S7/8に2cm径の腫瘍および軽度の脂肪肝を伴う低エコー病変が認められた。単純CTでは高吸収域を示した。MRIでは、腫瘍はT1強調画像で境界部に高信号、内部に低信号を呈し、T2強調画像では低信号を示した。Gd-EOB-DTPA造影MRIでは、病変に脂肪が含まれており、EOB取り込みも認められた。以上より高分化型肝細胞癌(HCC)を疑い、腹腔鏡下S7/8部分切除術を施行した。患者は術後10日目に合併症なく退院した。病理組織検査の結果、過形成性病変や腺腫などの腫瘍性病変は認められず、肝小葉壊死を伴う再生性肝変化と診断した。

出版者・発行元：金原出版  

DOI： 10.18888/op.0000003667

CiNii Research

記述言語：英語  

DOI： 10.1186/s40792-024-01807-y

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記述言語：英語   出版者・発行元：American Journal of Transplantation  

There are exceedingly uncommon but clearly defined situations where intraoperative abortions are inevitable in living-donor liver transplantation (LDLT). This study aimed to summarize the cases of aborted LDLT and propose a strategy to prevent abortion or minimize donor damage from both recipient and donor sides. We collected data from a total of 43 cases of aborted LDLT out of 13 937 cases from 7 high-volume hospitals in the Vanguard Multi-center Study of the International Living Donor Liver Transplantation Group and reviewed it retrospectively. Of the 43 cases, there were 24 recipient-related abortion cases and 19 donor-related cases. Recipient-related abortions included pulmonary hypertension (n = 8), hemodynamic instability (n = 6), advanced hepatocellular carcinoma (n = 5), bowel necrosis (n = 4), and severe adhesion (n = 1). Donor-related abortions included graft steatosis (n = 7), graft fibrosis (n = 5), primary biliary cholangitis (n = 3), anaphylactic shock (n = 2), and hemodynamic instability (n = 2). Total incidence of aborted LDLT was 0.31%, and there was no remarkable difference between the centers. A strategy to minimize additional donor damage by delaying the donor's laparotomy or trying to open the recipient's abdomen with a small incision should be effective in preventing some causes of aborted LDLT, such as pulmonary hypertension, advanced cancer, and severe adhesions.

DOI： 10.1016/j.ajt.2023.07.011

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記述言語：英語   出版者・発行元：(一社)日本外科学会  

症例は50歳代男性。非代償性アルコール性肝硬変のため肝移植を希望していた。ドナーはマルファン症候群(MS)に罹患していた50歳代男性で、脳動脈瘤による脳出血のため脳死と判定されていた。本ドナーにはMSに関連した大動脈解離の既往があり、過去に上行弓部大動脈全置換術、大動脈基部置換術、胸部下行大動脈置換術、腹部大動脈置換術、大動脈瘤切除術+人工血管置換術を受けていた。そのため、肝臓を切除する際、人工血管でない正常動脈まで肝臓を切除し、総肝動脈を再建に用いた。術中に肝動脈の生検を行ったところ正常であった。脳死肝移植は問題なく進行し、動脈吻合が完了した。手術時間は621分、出血量は804mlであった。術後経過は良好で、2週間毎日超音波ドップラー検査を行い、吻合血管の血流が正常であることを確認した。重大な術後合併症はみられず、術後18日目に退院した。術後1年経過時点でも全身状態に問題はなかった。

記述言語：英語   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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記述言語：英語   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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記述言語：英語   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   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：シュプリンガー・ジャパン(株)  

肝細胞癌(HCC)に対し2019年に日本肝臓学会が提唱した日本基準(JC、5-5-500基準)の妥当性を検討した。HCC再発に対し生体肝移植(LDLT)を施行した患者169例を対象とし、HCC再発時の至適治療法とLDLT前ダウンステージの有効性を検討した。単変量および多変量解析にて、LDLT後のHCC再発に関与する独立したリスク因子として、JC外および好中球/リンパ球比2.01超が示された。つぎに、JC内外でLDLT後の転帰を比較した結果、術後5、10、15年の無発生生存率および全生存率はJC内が有意に高かった。また、LDLT前にダウンステージを行いJC内となった患者の移植後成績はJC外よりも有意に良好であり、ダウンステージなしにJC内であった患者と同等であった。以上より、JCはHCC再発時の至適治療戦略構築に有効であることが示唆された。

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   出版者・発行元：John Wiley & Sons Australia, Ltd  

肝細胞癌(HCC)肝切除患者における術前アルブミン-リンパ球-血小板-C反応性蛋白質(ALPC)指数の予後予測能について検討した。2001年1月～2019年11月に根治的切除を受けたHCC患者のデータを後ろ向きに調べた。患者を訓練コホートと検証コホートに分け、再発に対する炎症マーカーの予測能を評価した。Cox比例ハザードモデルを用いてALPC指数と生存との関連を調べた。腫瘍標本を用いてリン酸化Nuclear factor-erythroid 2-related factor 2(p-Nrf2)の免疫組織化学的染色を行い、ALPC指数との関連を調べた。患者512例を解析した。訓練コホートで、術前ALPC指数の高さは血清アルブミン値の高さ、腫瘍サイズの小ささ、低分化率の低さ、孤立性腫瘍、Barcelona Clinic Liver Cancerステージの低さ、および顕微鏡的肝内転移率の低さと相関した。検証コホートでは、術前ALPC指数の高さは血清アルブミン値の高さ、血清α-フェトプロテイン値の高さ、腫瘍サイズの小ささ、低分化の割合の低さ、および顕微鏡的肝内転移率の低さと相関した。両コホートで術前ALPC指数の高さは無再発生存期間および全生存期間の独立予測因子であった。ALPC指数はp-Nrf2の発現と関連した。以上より、HCC肝切除患者において術前ALPC指数が独立予後因子であることが示唆された。

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

解糖を制御する酵素をコードしているTP53-induced glycolysis and apoptosis regulator(TIGAR)が、肝内胆管癌(ICC)に対し予後的影響を与えているか、そして同癌が示すフェロトーシス耐性に関し決定的な役割を果たしているか検討した。1993年5月～2020年12月に当院で原発性ICCに対し術前治療なしに肝切除術を施行した患者90名(男性64.4%、年齢33～87歳)を後ろ向きに組み入れた。TIGARを標的とした免疫組織化学解析の結果、22名(24.4%)は高発現群に、残りは低発現群に分類された。両群の背景因子には目立った違いは無かった。多変量解析の結果、TIGAR陽性は無病生存および全生存の点でみて独立予後因子となっていることが判明した。in vitro実験では、TIGARをノックダウンすることで細胞の運動性(細胞増殖、遊走、浸潤、コロニー形成能)は低下し、活性酸素種と脂質過酸化反応は増加することが示された。この結果は、TIGARのノックダウンによってフェロトーシスが誘導されたことを意味していた。TIGARのノックダウンをシスプラチンと併用するとフェロトーシスはさらに強く誘導された。結論として、TIGARはICC患者の予後不良、およびフェロトーシス耐性と関連していた。

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【目的】 High MELD患者に対する生体肝移植の適応限界に関しては議論の余地がある。今回High MELD患者に対する生体肝移植の妥当性について検討することを目的とした。</p><p>【方法】 1997年5月から2022年12月までの成人生体肝移植783症例を対象。レシピエントはL群(MELD＜25, n=685)、M群(25＜=MELD＜30, n=51)、H群(MELD＞=30, n=47)の3群に分類、移植時期を前期(-2009年)、後期(2010年-)に分類し比較検討。</p><p>【結果】グラフトタイプ(左葉/右葉/それ以外,%)は3群間で有意差は認めず、GV/SLV(%)や手術時間、出血量についても各群で有意差を認めなかった。GradeB以上の過小グラフト症候群(19.3%/36.2%/45.1%，p＜0.01)はH群で有意に高頻度に認めたが、敗血症の頻度や1年/5年グラフト生存率はL群(88.9/80.1%)、M群(90.2/86.0%)、H群(76.6/73.9%)と有意差を認めなかった。グラフトタイプによる1年生存率は、L群とM群で有意差は認めなかったが、H群において左葉グラフトは右葉に比べて有意に低値であった(61.9% vs. 94.1%，P＜0.05)。また全群において時代後期に1年グラフト生存率の改善を認めたが、特にH群(66.7% vs. 82.8%, P＜0.05)で顕著であった。</p><p>【まとめ】High MELD患者に対する生体肝移植の術後成績は、時代変遷とともに著明に改善しており正当化されうるが、十分なグラフト重量が確保可能な右葉グラフトを選択すべきと考えられた。</p>

DOI： 10.11386/jst.59.supplement_s199_2

CiNii Research

記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

DOI： 10.11241/jsmtmr.39.18

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【はじめに】肝移植後には種々の合併症が生じうるが、感染性合併症、特に敗血症は予後に関わる重篤な合併症である。当科での感染性合併症軽減の取り組みと周術期シンバイオティクス投与による敗血症予防効果について報告する。【方法】対象は2018年1月から2023年10月までの生体肝移植210例。周術期シンバイオティクス投与群34例と非投与群176例を後方視的解析した。シンバイオティクス投与方法：スーパーシンバイオティクスLBG-Pもしくはシンプロテック（ヤクルト本社）を術前後1日3回5日間ずつ投与した。【結果】シンバイオティクス群は男性ドナーが低頻度（p=0.011）、血液型不適合率が有意に高率であった（p=0.021）。他の術前、手術因子に有意差は認めなかった。シンバイオティクス群は敗血症と術後肺炎発症率が有意に低率であり（0% vs. 7.4%, p=0.029, 0% vs. 6.8%, p=0.036）、バクテリアルトランスロケーション由来敗血症、尿路感染症、腹腔内感染症の発症率が低い傾向であった。術後肝機能、急性拒絶や過小グラフト症候群等術後経過に影響なく、グラフト予後は同等であった（6ヶ月100% vs. 95.9%, p=0.24）。多変量解析において、術後敗血症発症の独立危険因子は65歳以上レシピエント及び周術期シンバイオティクス非投与（p=0.012, p=0.037）であった。【まとめ】周術期シンバイオティクス投与は生体肝移植術後敗血症発症を予防しうる。今後更なる検討を進める。</p>

DOI： 10.11386/jst.59.supplement_s163_2

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【背景】 生体肝移植(LDLT)においてMELD高値は予後不良とされるが、MELD低値症例においてもグラフトロスをきたすことがあり注意を要する。低MELD症例におけるグラフトロスリスク因子に関する報告は少ない。【目的】 低MELD症例における術後成績及びグラフトロスのリスク因子を同定すること。【対象と方法】 1998年から2024年までに当院でLDLTを施行した低MELD(MELDスコア≦15)症例の術後成績を検討し、LDLT術後3ヶ月以内グラフトロスの予後不良因子を評価した。【結果】 低MELD症例は838症例中408例(48.7%)に認めた。低MELD群、高MELD群の1年/5年生存率はそれぞれ91.5/84.1%と86.5/77.9%であり、低MELD群は予後良好であった(p＜0.05)。3ヶ月以内グラフトロスに関して、多変量解析で手術関連合併症(p＜0.01, HR 7.46, 95% CI 2.35-23.7)、ドナーBMI≧25(p＜0.01, HR 4.97, 95% CI 1.53-16.2)、脾臓摘出なし(p＜0.05, HR 3.48, 95% CI 1.14-10.6)が独立予後不良因子であった。手術関連合併症では、肝動脈血栓症(44.4%)、術後出血(33.3%)、腸管穿孔(11.1%)などによりグラフトロスをきたしていた。上記3因子の該当数によって予後は層別化され、3ヶ月以内グラフトロスは1因子では7.3%、2因子以上では17.5%であった(p＜0.01)。【結語】 低MELD症例における予後不良因子を同定した。手術関連合併症の減少が予後改善に重要と考えられ、現在当科でも安全性に留意する手術に取り組んでいる。</p>

DOI： 10.11386/jst.59.supplement_s319_2

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【目的】生体肝移植(LDLT)の術前レシピエントの特徴は,低栄養,浮腫,筋萎縮,肝性脳症に加え,術後合併症を併発する頻度が高く,十分な耐久性の獲得に難渋する症例が多い.そこで本研究は,退院時運動耐容能に影響する周術期因子を検討した.【方法】対象は,2021年1月～2023年12月に消化器・総合外科でLDLTが施行された18歳以上の成人症例107例(女性53例,年齢55±11歳)．運動耐容能は,6分間歩行距離(6MD)を指標とした．患者属性及び術前因子は,年齢,性別,BMI,大腰筋断面積,生化学(ALB,PT％,T－Bil),腹水量,MELDscore,GNRI,CT値,最大握力,6MDとした.術中及び術後因子は,手術時間,出血量,グラフト体重比,ICU在院日数,術後離床開始日数,自立歩行獲得日数を診療録より調査した.統計解析はχ二乗検定及びMann－WhitneyU検定を用いて2群間をそれぞれ比較し,退院時運動耐容能に周術期因子が与える影響を重回帰分析した.有意水準は5%未満とした.【結果】退院時6MDと年齢(<i>p</i>=.01),性別(<i>p</i>=.02),BMI(<i>p</i>=.004),術前MELD(<i>p</i> =.02),術前最大握力(<i>p</i>=.0001),術前6MD(<i>p</i>=.0001),ICU在院日数(<i>p</i>=.006),術後自立歩行獲得日数(<i>p</i>=.0001)に有意差を認めた.また退院時6MDを目的変数とした重回帰分析では,年齢(<i>β</i>＝－.23,<i>p</i>=.021),術前6MD(<i>β</i>＝.52,<i>p</i>＝.0001)が抽出された.なおR2＝.56であった.【結論】退院時運動耐容能に影響度が大きい周術期因子は,術前6MDであり,術後の耐久性獲得のためには術前からのリハビリ介入が重要である.</p>

DOI： 10.11386/jst.59.supplement_s318_1

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【目的】成人生体肝移植(LDLT)において、グラフト選択は重要である。当科では、拡大左葉＋尾状葉(Lt)や右葉(Rt)がグラフト不適格と判断した症例においてのみ後区域グラフト(Post)の適応を検討している。本研究では、各グラフトにおける成績を比較し、Postの有用性について検討することを目的とする。【方法】2013年12月から2022年3月に当院で施行したLDLT325例(Rt 197例、Lt 121例、Post 7例)を対象とした。また同時期に当院受診するも、移植を施行しなかった64例の予後を検討した。【結果】Postのグラフト容積はLtより有意に大きく(500mL vs 382 ml、p＜0.05)、PostのRemnant liver donor weight rate (RLDWR)はRtより有意に高値で(10.7 vs 8.3、p＜0.05)、Ltと同程度であった。ドナー術後のT-BilとPT-INRの最高値はRLDWRと負の相関関係にあり(p＜0.05)、Postによる術後の良好な肝機能が示唆された。ドナーのGrade3以上の合併症はRt 5%、Lt 2.5%、Postでは1例も認めなかった。レシピエントの術後14日目のT-Bil及びPT-INRに有意差はなく、胆管合併症発生率も3群間で同等であった。レシピエントの生存率に関して、Rt及びLtを断念した非移植症例との比較では、Postで有意に生存率が良好であった(1年生存率 71.4% vs 29.7%)。【まとめ】後区域グラフトは、生体ドナーに対して安全に施行することができ、左右グラフトが不適合の症例に対するグラフト選択の一つとして有用であると考えられた。</p>

DOI： 10.11386/jst.59.supplement_s318_3

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【目的】近年の抗ウイルス治療の進歩によりウイルス性肝炎を原因とする肝移植は減少傾向となる一方、MASH肝硬変を原因とする肝移植は増加傾向にある。今回、日本肝移植学会のプロジェクト研究としてMASH肝硬変における肝移植症例を検討した。</p><p>【方法】MASH肝硬変に対して肝移植を行った272例を検討対象とした。観察期間の中央値は4.2年、MASH症例の経過、生命予後を検討した。また移植後の脂肪肝の有無を評価できた213例では脂肪肝、MASH再発の有無を検討した。</p><p>【成績】MASH肝移植例の1年生存率は91.2％、３年生存率は87.6％、5年生存率は82.2％、10年生存率は72％であった。Cox比例ハザードモデルでは2型糖尿病とMELDスコア17以上が生存に寄与する因子であった。脂肪肝の再発は213例中81例 (38%)に認め、脂肪肝再発までの期間の中央値は2.１年であった。Cox比例ハザードモデルにて脂肪肝の再発に寄与する因子は移植後の体重の増加であった（P＝0.010）。肝移植後脂肪肝再発例は非再発例と比較して予後良好であった（p=0.03）。脂肪肝症例81例中53例では肝生検が行われ、そのうちMASHは23例（37％）に認めた。</p><p>【結論】MASH由来肝硬変の移植症例は肝移植後の予後は比較的良好であった。また移植後脂肪肝の再発例(非MASH)では移植後の予後が良好であった。一方で肝移植後にMASHの再発を認める症例があり、注意を要すると考えられた。</p>

DOI： 10.11386/jst.59.supplement_s318_2

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>The increase in liver transplant (LT) recipients’ age and improved survival rates have led to more patients with pre-transplant malignancies (PTMs). Common risk factors, like obesity and alcohol use, often link nonhepatic cancer with chronic liver diseases. Immunosuppressive therapy in LT recipients raises the risk of post-transplant cancer recurrence, affecting survival rates. Although PTM’s impact is well-studied in kidney transplants, data for LT is limited. Patients with cirrhosis and cancer have outcomes influenced by cirrhosis severity and chemotherapy’s impact on liver function. This study examines LT eligibility and required waiting period for PTM patients, focusing on cancer type and treatment history. Comprehensive cancer history is essential for evaluating LT eligibility. Future research should gather extensive data on PTM’s effect on post-LT outcomes, identifying recurrence risk factors to improve management and survival.</p>

DOI： 10.11386/jst.59.2_119

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p><b>【Objective】</b> Postoperative prolonged ascites is a common complication after living-donor liver transplantation (LDLT). However, there is little evidence regarding the circulatory indicators as risk factors for ascites after LDLT. The aim was to evaluate the impact of trans tricuspid pressure gradient (TRPG) on postoperative prolonged ascites.</p><p><b>【Design】</b> Case-series.</p><p><b>【Method】</b> We collected data from 268 recipients who underwent LDLT for liver failure between 2008 and 2022. We excluded 7 recipients who died within 30 days after LDLT and divided the remainer into two groups by TRPG value.</p><p><b>【Results】</b> Of the 261 patients with liver failure, 98 (37.7%) were classified as the high TRPG group and 163 (62.3%) comprised the low TRPG group. There was a significant difference in the rate of intractable ascites between the two groups, but no significant difference in overall survival (OS). After PSM, univariate analysis detected two risk factors, high TRPG value and ascites at laparotomy ≥5000 mL. In the multivariate analysis, high TRPG value (<i>P</i>=0.0345, OR=11.4, 95% CI 1.19-108) and ascites at laparotomy ≥5000 (mL) (<i>P</i>=0.0067, OR=10.2, 95% CI 1.91-54.8) were identified as independent risk factors.</p><p><b>【Conclusion】</b> Preoperative TRPG elevation is a risk for prolonged ascites after LDLT, and it can be valuable to measure TRPG in the preoperative condition assessment.</p>

DOI： 10.11386/jst.59.1_37

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【はじめに】2022年4月に生体肝移植における外側区域グラフト採取に対して腹腔鏡下肝ドナー手術が保険収載となった。当院での腹腔鏡下生体肝ドナーグラフト採取術について報告する。【対象】2023年2月より腹腔鏡下肝外側区域グラフト採取術を導入。これまで11症例に施行した。【手術手技】臍部にOpen法でポート留置、4本の操作用ポート、Pringle法用ポート1本、通常気腹。左葉脱転、左グリソンをテーピング(アランチウス腹側)、Pringle法下で肝離断し、左肝静脈のテーピングを行う。肝門操作に移り、左肝動脈、門脈左枝をテーピング後、アランチウス管の剥離を行い、引き算法にて左胆管+肝門板をテーピング。胆道造影後に、左胆管、肝門板を切離。下腹部に約8cmの切開を加えた後、ヘパリン投与下に左肝動脈、門脈左枝、左肝静脈を切離し、グラフト採取。【結果】平均ドナー年齢35.8歳、男性3例、女性8例。5例でS3領域のreduce hepatectomyを行った。平均手術時間372分、平均出血量119分、温虚血開始までの平均時間243分、平均温虚血時間8.9分。術後平均在院日数8.9日で合併症は認めなかった。【結論】安全に腹腔鏡下生体肝ドナーグラフト採取術を施行した。今後は症例を蓄積し、その有用性について検証を行う必要がある。</p>

DOI： 10.11386/jst.59.supplement_s253_1

CiNii Research

記述言語：英語   出版者・発行元：Jgh Open  

Background and Aim: Many recent studies have shown a relationship between various systemic diseases and the gut microbiota (GM), with the gut–liver axis receiving particular attention. In contrast, no report has comprehensively shown the effects of GM on the pathophysiology of patients undergoing living donor liver transplantation (LDLT). Method: We enrolled 16 recipients who underwent LDLT for liver cirrhosis, and 17 donors constituted the reference group. We examined the differences in GM between recipients and donors. We also examined the relationships between GM, short-chain fatty acids, and portal vein pressure (PVP) in recipients. Results: There was no significant difference in alpha-diversity between the recipients and donors, but there was variation in beta-diversity among the recipients. The abundance of the phylum Bacteroidetes was significantly higher in recipients than in donors (P = 0.016), and it was positively correlated with PVP (r = 0.511, P = 0.043). Propionic acid, which is a component of short-chain fatty acids, was positively correlated with PVP (r = 0.544, P = 0.0295), the phylum Bacteroidetes (r = 0.677, P = 0.004), and total bilirubin concentration (r = 0.501, P = 0.048). Propionic acid was negatively correlated with serum albumin concentration (r = −0.482, P = 0.043). Conclusion: Our findings suggest relationships between fecal Bacteroidetes levels, propionic acid concentrations, and PVP in patients with liver cirrhosis undergoing LDLT.

DOI： 10.1002/jgh3.13018

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：Surgical Endoscopy  

Background: In telementoring, differences in teaching methods affect local surgeons’ comprehension. Because the object to be operated on is a three-dimensional (3D) structure, voice or 2D annotation may not be sufficient to convey the instructor’s intention. In this study, we examined the usefulness of telementoring using 3D drawing annotations in robotic surgery. Methods: Kyushu University and Beppu Hospital are located 140 km apart, and the study was conducted using a Saroa™ surgical robot by RIVERFIELD Inc. using a commercial guarantee network on optical fiber. Twenty medical students performed vertical mattress suturing using a swine intestinal tract under surgical guidance at the Center for Advanced Medical Innovation Kyushu University. Surgical guidance was provided by Beppu Hospital using voice, 2D, and 3D drawing annotations. All robot operations were performed using 3D images, and only the annotations were independently switched between voice and 2D and 3D images. The operation time, needle movement, and performance were also evaluated. Results: The 3D annotation group tended to have a shorter working time than the control group (25.6 ± 63.2 vs. − 36.7 ± 65.4 min, P = 0.06). The 3D annotation group had fewer retries than the control group (1.3 ± 1.7 vs. − 1.1 ± 0.7, P = 0.006), and there was a tendency for fewer needle drops (0.4 ± 0.7 vs. − 0.5 ± 0.9, P = 0.06). The 3D annotation group scored significantly higher than the control group on the Global Evaluate Assessment of Robot Skills (16.8 ± 2.0 vs. 22.8 ± 2.4, P = 0.04). The 3D annotation group also scored higher than the voice (13.4 ± 1.2) and 2D annotation (16.2 ± 1.8) groups (3D vs. voice: P = 0.03, 3D vs. 2D: P = 0.03). Conclusion: Telementoring using 3D drawing annotation was shown to provide good comprehension and a smooth operation for local surgeons. Graphical abstract: [Figure not available: see fulltext.]

DOI： 10.1007/s00464-023-10521-z

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記述言語：英語  

DOI： 10.26508/lsa.202302116

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PubMed

記述言語：英語   出版者・発行元：Transplantation Proceedings  

Background: This study aimed to elucidate the effect of early enteral nutrition on graft loss within 12 h after living-donor liver transplantation (LDLT) using propensity score-matching analysis and subsequently examine the risk factors for graft loss after LDLT. Methods: We retrospectively reviewed the data of 467 LDLT patients who were assigned to the early and non-early groups based on the optimal cutoff value of 12 h for the starting time of early enteral nutrition after LDLT to predict graft loss. Results: The 1-year graft survival rate of the early group before propensity score-matching was 92.1%, whereas the 1-year graft survival rate of the non-early group was 86.2%. There was no significant difference between the 2 groups (P = .067). The incidences of early allograft dysfunction (EAD), small-for-size graft (SFSG) syndrome, acute cellular rejection (ACR), and sepsis were not statistically different between the 2 groups (P = .12, .91, .46, and .056, respectively). After propensity score-matching, the 1-year graft survival rate of the early group was 94.4%, whereas the 1-year graft survival rate of the non-early group was 85.4% (P = .034). The incidences of EAD, SFSG syndrome, and ACR were not statistically different between the 2 groups (P = .43, .81, and .24, respectively). However, the incidence of sepsis was statistically different between the 2 groups (non-early: 10.7% vs early: 3.6%, P = .038). Conclusion: Early enteral nutrition within 12 h after LDLT may contribute to better graft survival in LDLT patients by preventing sepsis.

DOI： 10.1016/j.transproceed.2023.07.029

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記述言語：英語   出版者・発行元：British Journal of Cancer  

Background: Intratumor heterogeneity (ITH) in microsatellite instability-high (MSI-H) colorectal cancer (CRC) has been poorly studied. We aimed to clarify how the ITH of MSI-H CRCs is generated in cancer evolution and how immune selective pressure affects ITH. Methods: We reanalyzed public whole-exome sequencing data on 246 MSI-H CRCs. In addition, we performed a multi-region analysis from 6 MSI-H CRCs. To verify the process of subclonal immune escape accumulation, a novel computational model of cancer evolution under immune pressure was developed. Results: Our analysis presented the enrichment of functional genomic alterations in antigen-presentation machinery (APM). Associative analysis of neoantigens indicated the generation of immune escape mechanisms via HLA alterations. Multiregion analysis revealed the clonal acquisition of driver mutations and subclonal accumulation of APM defects in MSI-H CRCs. Examination of variant allele frequencies demonstrated that subclonal mutations tend to be subjected to selective sweep. Computational simulations of tumour progression with the interaction of immune cells successfully verified the subclonal accumulation of immune escape mutations and suggested the efficacy of early initiation of an immune checkpoint inhibitor (ICI) -based treatment. Conclusions: Our results demonstrate the heterogeneous acquisition of immune escape mechanisms in MSI-H CRCs by Darwinian selection, providing novel insights into ICI-based treatment strategies.

DOI： 10.1038/s41416-023-02395-8

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記述言語：英語   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  

DOI： 10.1007/s13691-023-00618-6

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

症例は90歳女性。非B非C型肝炎であり、18ヵ月前に原発性肝細胞癌に対して腹腔鏡下肝切除術が施行された。術後6ヵ月、肝細胞癌再発に対して経カテーテル的肝動脈化学塞栓療法(TACE)が施行されたが、その1年後に2回目の再発が認められた。レンバチニブ(LEN)8mg/日投与を開始したところ、1週間後に極度の疲労や食欲不振などの重篤な有害事象(AE)が出現し、投与量を4mg/日に減量したがAEの管理は困難であった。そこで、LEN導入から1ヵ月後に化学療法をアテゾリズマブ+ベバシズマブ併用療法に変更した。その結果、副作用はほとんど認められず、腫瘍の退縮が認められた。本レジメンを8ヵ月間、10サイクル続け、最終的に完全奏効(CR)を達成した。CR達成後1年経過しても再発はみられていない。

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記述言語：英語   出版者・発行元：Liver Transplantation  

DOI： 10.1097/LVT.0000000000000116

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出版者・発行元：南江堂  

DOI： 10.15106/j_geka85_863

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出版者・発行元：南江堂  

DOI： 10.15106/j_geka85_489

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記述言語：英語   出版者・発行元：Cell Reports  

The cellular interactions in the tumor microenvironment of colorectal cancer (CRC) are poorly understood, hindering patient treatment. In the current study, we investigate whether events occurring at the invasion front are of particular importance for CRC treatment strategies. To this end, we analyze CRC tissues by combining spatial transcriptomics from patients with a public single-cell transcriptomic atlas to determine cell-cell interactions at the invasion front. We show that CRC cells are localized specifically at the invasion front. These cells induce human leukocyte antigen G (HLA-G) to produce secreted phosphoprotein 1 (SPP1)+ macrophages while conferring CRC cells with anti-tumor immunity, as well as proliferative and invasive properties. Taken together, these findings highlight the signaling between CRC cell populations and stromal cell populations at the cellular level.

DOI： 10.1016/j.celrep.2022.111929

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出版者・発行元：金原出版  

DOI： 10.18888/op.0000003119

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記述言語：英語   出版者・発行元：Transplantation Proceedings  

Recurrence of hepatocellular carcinoma (HCC) after living donor liver transplant (LDLT) is an essential factor defining prognosis, and surgical resection is the only curative treatment. However, the factors that define whether surgical resection is possible remain unclear. Here, we compared resectable and unresectable HCC recurrence cases after LDLT and examined factors that determine whether surgical resection is possible. Resectable (n = 17) and unresectable (n = 14) groups among 264 patients who underwent LDLT for HCC from January 1999 to March 2020 were compared and examined for recurrence type, prognosis, and clinicopathologic factors. Overall survival after LDLT (median, 8.5 vs 1.7 years, P < .01) was significantly longer in the resectable group. In univariate analysis, female recipient rate, lymphocyte to monocyte ratio (LMR) ≥2.75, and tumor size ≤5.0 cm were significantly higher in the resectable group. Younger donors, lower Model for End-Stage Liver Disease scores, lower graft volume, and lower graft volume to standard liver volume ratio were evident in the resectable group. In multivariate analysis, female recipient rate (P = .0034) and LMR ≥2.75 (P = .0203) were independent predictive factors for resectable HCC recurrence after LDLT. Female recipient and LMR ≥2.75 before transplant could predict the surgically resectable type of HCC recurrence after LDLT.

DOI： 10.1016/j.transproceed.2022.09.031

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記述言語：英語   出版者・発行元：Annals of Gastroenterological Surgery  

Aim: Gastric mucosal changes associated with chronic gastritis are known to be precancerous lesions of gastric cancer. We aimed to identify individuals with a high risk of gastric cancer by detection of microRNAs (miRNA) in the blood as biomarkers. Methods: Of 1206 individuals screened, 144 who were positive for Helicobacter pylori (H. pylori) by the serum antibody test and who underwent endoscopy were the subjects of this study. For the gross assessment of mucosal inflammation, we applied the Kimura–Takemoto classification, in which normal mucosa was defined as grade 0, and atrophy was categorized as grade 1 (C-1 and C-2), grade 2 (C-3 and O-1), and grade 3 (O-2 and O-3). Serum samples were divided into two phases and used for miRNA microarray profiling. We compared the expression of miRNAs in grade 3 mucosa and other grades. Expression in gastric cancer was confirmed with TCGA data. Results: miR-196b-3p was significantly upregulated, and miR-92a-2-5p was downregulated (P <.05 and q < 0.2). TCGA data showed a high expression of miR-196b-3p in gastric cancer cases (P <.001). Comparing grade 3 and the others, the area under the receiver operating characteristic curve using the detected miRNAs was as high as about 0.7. Furthermore, the combination of miRNAs resulted in higher accuracy. In terms of the significance of the combinatory mRNAs, the combination of three miRNAs (miR-196b-3p, miR-92a-2-5p, and miR-6791-3p) revealed high sensitivity and specificity, with the area under the curve exceeding 0.8. Conclusion: The identified combinatory miRNAs may represent promising biomarkers of precancerous lesions in gastric cancer.

DOI： 10.1002/ags3.12610

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

本研究の目的は、血中マイクロRNA(miRNA)をバイオマーカーとして検出することで、胃癌リスクの高い症例を同定することである。スクリーニングを行った1206名のうち、血清抗体検査でヘリコバクター・ピロリ(H.pylori)陽性で、内視鏡検査を受けた144名を本研究の対象とした。粘膜炎症の肉眼的評価には、正常粘膜をグレード0、萎縮をグレード1(C-1、C-2)、グレード2(C-3、O-1)、グレード3(O-2、O-3)に分類する木村・竹本分類を適用した。血清サンプルは2相に分け、miRNAマイクロアレイプロファイリングに使用した。グレード3の粘膜とその他のグレードの粘膜におけるmiRNAの発現を比較した。胃癌における発現は、TCGAのデータで確認した。miR-196b-3pは有意に増加し、miR-92a-2-5pは減少していた(P<0.05、q<0.2)。TCGAのデータでは、胃癌症例においてmiR-196b-3pの発現が高いことが示された(P<0.001)。グレード3とそれ以外を比較すると、検出されたmiRNAを用いた受信者動作特性曲線下面積は0.7であった。さらに、miRNAを組み合わせることで、より高い精度が得られた。miRNAを組み合わせる場合、3種類のmiRNA(miR-196b-3p、miR-92a-2-5p、miR-6791-3p)の組み合わせが高い感度と特異性を示し、曲線下面積は0.8を超えていた。ここに示されたmiRNAの組み合わせは、胃癌の前癌病変のバイオマーカーとして有望である可能性がある。

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【背景・目的】肝移植後のsmall-for-size syndrome (SFSS)は予後不良の病態であり、周術期のportal modulation介入が必須である。2023年1月、ILTS consensus conference (India)においてSFSSの新基準及び重症度分類が提唱された。重症度分類(Grade A/B/C)では、特にportal hypertensive phaseであるSFSS Grade Bにおいてportal modulationを含めた周術期管理が重要とされている。当院におけるSFSS Grade B[(T-Bil＞10mg/dL or INR＞1.6(POD7)、もしくはT-Bil＞10mg/dL and腹水1L/日(POD14)]の成績につき考察する。</p><p>【対象・方法】当科施行の成人間生体肝移植(LDLT)783例を対象(2022年12月まで)。SFSSの重症度分類で特にGrade Bにおける臨床因子及び予後因子について検討を行った。</p><p>【結果】SFSS新基準においてSFSSを442例(56.4%)認めた。Grade A/B/Cの割合は60.0%/26.0%/14.0%であり、術後グラフト生存率(Grade A/B/C )は1年生存率90.2%/88.7%/46.2%であり、Grade Cが有意に予後不良であった(P＜0.05)。また、前期・後期に分類した場合、Grade A/Bのグラフト1年生存率は、前期 89.2%/80.3%(P＜0.05)、後期91.0%/91.3%(P=NS)と前期のみGrade Bのグラフト生存率が有意に低値であった。</p><p>【まとめ】SFSS新基準による重症度分類によって予後の層別化可能であった。Grade Bに関して、high volume centerにおける周術期管理の習熟、portal modulation介入による時代後期の予後改善が示唆された。</p>

DOI： 10.11386/jst.58.supplement_s207_2

CiNii Research

記述言語：英語   出版者・発行元：一般社団法人 日本移植学会  

<p>The aim of this study was to examine the influence of machine perfusion (MP) and normothermic regional perfusion (NRP) on the utilization and outcomes of liver transplantation (LT). Using US national data, 4642 donation after circulatory death (DCD) donors between 2016 and 2021 were analyzed. 4542 were with static cold storage(SCS), 79 were with MP(1.7%), and 21 were with NRP(0.5%).The utilization rates of liver in DCD with MP or NRP were significantly higher (P=0.001; 92.4% or 95.2% vs 70.4%). There were no graft failure with primary nonfunction or ischemic cholangiopathy after LT with MP or NRP. MP or NRP significantly increased the utilization rate of livers with favorable outcomes after LT. Increasing use of MP or NRP should be considered in low utilization donors to expand donor pool.</p>

DOI： 10.11386/jst.58.supplement_s127_1

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記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【目的】　移植後患者は新型コロナウイルス感染症（COVID-19）の重症化群であり、健常者よりCOVID-19への感染への恐怖が強いことが報告されている。本研究は、COVID-19禍における移植後患者の身体活動量と恐怖、感染予防行動との関連を明らかにすることを目的とする。【方法】対象者は2021年3～4月に当院通院中で肝、腎移植後6ヶ月以上の20歳以上の患者とした。身体活動量はInternational Physical Activity Questionnaireを用いて不活発群と活発群に分類した。COVID-19への恐怖と感染予防行動は、先行研究に基づき自記式質問紙で調査した。身体活動量と恐怖、感染予防行動との関連は活発群・不活発群の2群を従属変数としてロジスティック回帰分析を用いて分析した。【結果】対象者は204名で（肝136名、腎68名）、男性は98名（48%）、平均年齢は59.1±11.8歳、平均BMIは22.6±3.6kg/m²、平均移植後年数は6.6±5.5年であった。不活発群は113名（55.4%）であり、移植臓器による身体活動量に相違はなかった。不活発群は活発群と比較し、免疫抑制剤の内服が感染を悪化させることへの恐怖が強く（OR=1.48, p=0.08）、運動習慣（OR =0.35, p ＜ 0.001）や外出頻度が少なかった（OR=1.50 , p=0.009）。【考察】COVID-19禍で移植後患者の半数以上は不活発であることが示された。過度な恐怖は身体活動量の低下を招くため、医療者による正しい情報提供の必要性が示唆された。</p>

DOI： 10.11386/jst.58.supplement_s328_1

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【はじめに】肝移植では多様な重篤である術後合併症により非常に難渋する症例を経験する。</p><p>【症例】57歳男性、11年前にC型非代償性肝硬変、肝細胞癌に対し生体肝移植術施行。術後吻合部胆管狭窄から二次性非代償性胆汁うっ滞性肝硬変、肝腎症候群に伴う維持透析導入となり4ヶ月前に脳死登録。脳死肝腎移植術施行、著明な凝固機能障害、肝周囲中心の腹腔内癒着のため、手術時間1100分、出血量約27L。術後7日目に横行結腸穿孔に対し腹腔内洗浄ドレナージ、人工肛門造設術施行、以後ドレーン管理継続。術後23日目に肝酵素上昇、US・CTにて肝動脈閉塞症が疑われた。血管造影にて、固有肝動脈遠位での血流途絶を認めた(肝内動脈本幹は著明な血流低下認めるが遅延性に描出)。肝動脈再建施行も肝内動脈血流改善認めず、肝内動脈血確保目的に総肝動脈-肝円索吻合を行った。術後門脈圧亢進に伴う大量水様便等を認め水分・電解質補正、ドレーン管理継続。術後54日目にドレーン排液血性変化、CTで吻合部肝円索側の仮性瘤形成を認めた。緊急血管造影で仮性瘤より末梢血流は途絶、また以前の側副血行路の発達を認め良好な肝内動脈血流を認めたため仮性瘤はコイル塞栓施行。翌日より水様便減少し良好に経過した。リハビリを継続し、最終的に自宅退院となった。</p><p>【まとめ】綿密な術後管理と肝内動脈血確保の姑息的手段として総肝動脈-肝円索吻合により救命し得た症例を経験した。</p>

DOI： 10.11386/jst.58.supplement_s140_2

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記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>将来は専門に偏らず、様々な急患手術にも対応ができるような外科医になりたい、そんな夢を胸に医学部に入学した私が、肝移植の分野に興味を持ったのはベッドサイド実習で見学した生体肝移植の手術がきっかけだった。しかし、実際に肝移植を志すきっかけとなったのは、医師4年目に担当した2人の肝移植を受けた患者さんとの出会いであった。生体肝移植はドナーとなる家族が、そして脳死肝移植も提供を決意してくれたドナーやその家族がいてこそ成り立つ医療である。そのため、患者本人だけでなく、その家族とも深く関わる機会も多く、患者の回復には家族の支えが不可欠であることを痛感する。だからこそ、死を目前にしていた患者が、笑顔で家族と退院した時の感動が、肝移植の一番の魅力ではないかと思う。ただ、医師の働き方改革が進められる中、肝移植の分野では医師の負担もまだ大きく、家庭を有する女性医師が両立できるような体制が整っているとは言えない。だが、女性医師の割合が増加している現在、女性医師を敬遠してしまう環境では、肝移植分野の継続した発展は難しいのではないかとも考えられる。移植医療は、移植コーディネーターを始めとした多数の職種が協力することが不可欠な分野でもあることから、多職種のチーム体制を確立させ、より分業化することが、将来的に医師の多様な働き方に対応できるような環境づくりの一歩となるのではないかと考える。</p>

DOI： 10.11386/jst.58.supplement_s218_1

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記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【背景】三尖弁逆流圧較差(TRPG)は肺動脈圧をある程度反映するとされ、肺高血圧症のスクリーニングとして使用される。これまでに、TRPGと生体肝移植術後腹水量との関係を示した報告はない。【目的】TRPG値と術後遷延する腹水量との関係を評価する。【対象と方法】当院で2001年8月から2022年1月までに生体肝移植術を施行した症例の内、TRPG値を取得可能な268症例を対象とした。術後30日目腹水量500ml以上を術後遷延腹水と定義した。傾向スコアマッチングを用い、TRPG高値群(n=50)とTRPG低値群(n=50)について多変量解析を行った。 【結果】多変量解析では、TRPG高値(p=0.0307)、術中大量出血(p=0.0237)が独立に相関する因子であり、TRPG高値群において術中の出血量を抑えると術後遷延腹水の割合が減少することが示された(p＜0.01)。【考察】肝硬変患者では、末梢血管抵抗の減少、心拍出量の増大をきたす、Hyperdynamic circulation の状態にある。TRPG高値群で術後遷延腹水が多い理由として、TRPG高値が循環血漿量過多を示しており、これが術後遷延する腹水量に関与している可能性が考えられた。【結語】TRPG高値は生体肝移植術後の遷延腹水のリスク因子であった。術中の出血量を抑えることで、術後腹水の遷延を回避できる可能性が示唆された。</p>

DOI： 10.11386/jst.58.supplement_s275_2

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【背景・目的】生体肝移植術(LDLT)において術前運動耐容能と術後自立歩行獲得日数との関連性は明らかではない.今回,術前運動耐容能が術後自立歩行にどの程度影響しているか検討し,機能予後の予測因子となりえるか明らかにする.【方法】対象は,当院で施行したLDLT105例.術前運動耐容能は,6分間歩行距離(6MD)を指標とした.(1)術後自立歩行獲得日数により早期群と遅延群に分類し,以下の臨床因子(年齢,性別,BMI,MELDscore,GNRI,腹水量,手術時間,出血量,グラフト体重比,人工呼吸器装着日数,術後せん妄及び術後敗血症合併の有無,術後端坐位及び歩行開始到達日数,術後在院日数)を2群間で比較検討した.(2)遅延群に関するリスク因子をロジスティック回帰分析にて検討した.【結果】(1)術前運動耐容能を測定し得た解析可能症例は42例であった.術後自立歩行獲得日数は,中央値9(6-14)日であり,歩行早期群19例及び歩行遅延群23例に分類された.両群間の比較にて,遅延群において術前因子では,6MDが低値,MELDscoreが高値,術後因子では,せん妄,敗血症合併,人工呼吸器装着日数,術後在院日数が有意に延長を認めた.(2)歩行遅延群のリスク因子として,6MD(OR1.02,95%CI:0.97-0.99,p＜0.05;カットオフ350m)が同定され,術前6MDは術後自立歩行獲得日数に有意に逆相関した.【結論】LDLTにおいて術前運動耐容能は術後の自立歩行獲得日数の指標となり,LDLT後の機能予後予測因子となることが示唆された.</p>

DOI： 10.11386/jst.58.supplement_s274_3

CiNii Research

記述言語：英語   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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記述言語：英語   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   出版者・発行元：International Journal of Clinical Oncology  

Background: There is little evidence concerning survival after surgery in patients with hepatocellular carcinoma who have received lenvatinib treatment. The aim of this study was to evaluate whether post-lenvatinib surgical treatment in patients with hepatocellular carcinoma improves overall survival. Methods: The cohort of this retrospective study comprised 55 patients with hepatocellular carcinoma who had undergone lenvatinib treatment. We classified them into two groups according to post-lenvatinib surgical treatment status and compared clinicopathologic factors and prognosis between the two groups with the aim of identifying predictors of overall survival. Results: The median duration of lenvatinib administration was 5.8 months (range, 0.4–24.0 months). Twelve of the 55 patients underwent surgery after receiving lenvatinib. There was no significant difference in assessed clinicopathological factors between patients who did and did not undergo surgery after being treated with lenvatinib. Multivariate analysis revealed that older age was associated with a significantly worse overall survival (hazard ratio: 2.332; 95% confidence interval 1.062–5.168; P = 0.0369) and that surgery after treatment with lenvatinib achieved better overall survival than other forms of treatment (hazard ratio: 0.121; 95% confidence interval 0.016–0.901; P = 0.0393). Conclusions: Surgical treatment after lenvatinib administration may be a useful therapeutic option for select patients with hepatocellular carcinoma.

DOI： 10.1007/s10147-022-02229-2

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

レンバチニブ投与後に手術を受けた肝細胞癌(HCC)患者の生存率を調査した。レンバチニブ投与期間の中央値は5.8ヵ月(範囲0.4～24.0ヵ月)であった。レンバチニブ投与を受けたHCC患者55例のうち、12例(年齢41～77歳)はレンバチニブ投与後に手術(肝切除術8例、転移病変切除3例、生体肝移植1例)を受け、43例(年齢36～88歳)は手術を受けなかった。手術例と非手術例の間で臨床病理学的因子に有意差はなかった。多変量解析の結果、高齢は全生存率の有意な低下と関連し(ハザード比2.332、95%CI 1.062～5.168、P=0.0369)、レンバチニブ投与後の手術は他の治療方法よりも全生存率が優れていた(ハザード比0.12、95%CI 0.016～0.901、P=0.0393)。以上より、レンバチニブ投与後の手術は、一部の肝細胞癌患者にとって有用な治療選択肢となる可能性があった。

記述言語：英語   出版者・発行元：Plos One  

Background Colorectal cancer (CRC) can be classified into four consensus molecular subtypes (CMS) according to genomic aberrations and gene expression profiles. CMS is expected to be useful in predicting prognosis and selecting chemotherapy regimens. However, there are still no reports on the relationship between the morphology and CMS. Methods This retrospective study included 55 subjects with T2 CRC undergoing surgical resection, of whom 30 had the depressed type and 25 the protruded type. In the classification of the CMS, we first defined cases with deficient mismatch repair as CMS1. And then, CMS2/3 and CMS4 were classified using an online classifier developed by Trinh et al. The staining intensity of CDX2, HTR2B, FRMD6, ZEB1, and KER and the percentage contents of CDX2, FRMD6, and KER are input into the classifier to obtain automatic output classifying the specimen as CMS2/3 or CMS4. Results According to the results yielded by the online classifier, of the 30 depressed-type cases, 15 (50%) were classified as CMS2/3 and 15 (50%) as CMS4. Of the 25 protruded-type cases, 3 (12%) were classified as CMS1 and 22 (88%) as CMS2/3. All of the T2 CRCs classified as CMS4 were depressed CRCs. More malignant pathological findings such as lymphatic invasion were associated with the depressed rather than protruded T2 CRC cases. Conclusions Depressed-type T2 CRC had a significant association with CMS4, showing more malignant pathological findings such as lymphatic invasion than the protruded-type, which could explain the reported association between CMS4 CRC and poor prognosis.

DOI： 10.1371/journal.pone.0273566

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記述言語：英語  

DOI： 10.1186/s40792-022-01533-3

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出版者・発行元：Hepatology Communications  

The quality and size of liver grafts are critical factors that influence living-donor liver transplantation (LDLT) function and safety. However, the biomarkers used for predicting graft quality are lacking. In this study, we sought to identify unique graft quality markers, aside from donor age, by using the livers of non-human primates. Hepatic gene microarray expression data from young and elderly cynomolgus macaques revealed a total of 271 genes with significantly increased expression in the elderly. These candidate genes were then narrowed down to six through bioinformatics analyses. The expression patterns of these candidate genes in human donor liver tissues were subsequently examined. Importantly, we found that grafts exhibiting up-regulated expression of these six candidate genes were associated with an increased incidence of liver graft failure. Multivariable analysis further revealed that up-regulated expression of LRRN2 (encoding leucine-rich repeat protein, neuronal 2) in donor liver tissue served as an independent risk factor for graft failure (odds ratio 4.50, confidence interval 2.08–9.72). Stratification based on graft expression of LRRN2 and donor age was also significantly associated with 6-month graft survival rates. Conclusion: Up-regulated LRRN2 expression of liver graft is significantly correlated with graft failure in LDLT. In addition, combination of graft LRRN2 expression and donor age may represent a promising marker for predicting LDLT graft quality.

DOI： 10.1002/hep4.2033

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記述言語：英語   出版者・発行元：Anticancer Research  

Background/Aim: Alternative splicing plays a vital role in cancer development and progression. The splicing C complex is involved in alternative splicing. However, the role of PRKR-interacting protein 1 (PRKRIP1), a component of the splicing C complex, in colorectal cancer (CRC) remains unclear. This study aimed to determine the clinicopathological, biological and prognostic significance of PRKRIP1 expression in CRC. Materials and Methods: We used a bioinformatics approach to screen for oncogenes using The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) datasets and identified PRKRIP1 as a driver gene on chromosome 7q. The mRNA expression of PRKRIP1 was measured using reverse transcription-quantitative PCR in 165 surgically resected CRC samples in our hospital, and its localization was determined using immunohistochemical staining. Gene Set Enrichment Analysis (GSEA) was performed using TCGA dataset. Results: High PRKRIP1 expression was significantly associated with poor prognosis in both the samples and TCGA dataset. A positive correlation was observed between copy number variation and PRKRIP1 expression in TCGA and CCLE datasets, and the frequency of PRKRIP1 mutations was less than 5%. Immunohistochemistry revealed that PRKRIP1 was located in the cytoplasm of tumor cells. GSEA revealed that PRKRIP1 expression was correlated with apoptosis-related gene sets. Conclusion: PRKRIP1 overexpression may be a poor prognostic biomarker for CRC. Although it is known that PRKRIP1, a spliceosome factor, is essential for splicing, we now revealed the way by which its expression accelerates CRC progression.

DOI： 10.21873/anticanres.15974

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記述言語：英語   出版者・発行元：Hepatology Research  

Aim: Liver transplantation (LT) is the only curative therapy for decompensated liver cirrhosis. For recipients of living donor LT (LDLT), restoration of liver function after transplantation is highly dependent on liver regenerative capacity, which requires large amounts of intracellular energy. Mitochondrial metabolism provides a stable supply of adenosine 5′-triphosphate (ATP) for liver regeneration. Mitophagy is a selective process in which damaged, non-functional mitochondria are degraded and replaced with new functional mitochondria. We investigated the relationship between expression of Syntaxin17 (STX17), a key protein in mitophagy regulation, in donor livers and graft survival. Methods: We examined STX17 expression in grafts from 143 LDLT donors who underwent right lobe resection and investigated the relationship between STX17 expression and graft function. We investigated the correlations among STX17 expression, mitochondrial membrane potential and cell proliferation, using a STX17-knockdown hepatocyte cell line. Results: Recipients transplanted with low STX17-expression grafts had significantly lower graft survival rates than recipients transplanted with high STX17-expression grafts (88.9% vs. 100%, p < 0.01). Multivariate analysis showed that low STX17 expression (HR: 10.7, CI: 1.29–88.0, p < 0.05) and the absence of splenectomy (HR: 6.27, CI: 1.59–24.8, p < 0.01) were independent predictive factors for small-for-size graft syndrome, which is the severe complication in LDLT. In the vitro experiments, the percentage of depolarized damaged mitochondria was increased in the STX17-knockdown hepatocyte cell line, suggesting decreased mitophagy and ATP synthesis. Cell proliferation was significantly decreased in the STX17-knockdown hepatocyte cell line. Conclusion: STX17 contributes to mitophagy and maintenance of mitochondrial function in hepatocytes and may be a predictor of graft dysfunction in LDLT patients.

DOI： 10.1111/hepr.13809

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記述言語：英語   出版者・発行元：(一社)日本外科学会  

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   出版者・発行元：John Wiley & Sons Australia, Ltd  

ドナー肝でのシンタキシン17(STX17)の発現と移植片の生着率および機能との関連について検討した。2005年10月～2019年4月に生体ドナー肝移植(LDLT)を受けた患者を後ろ向きに調べた。右葉移植片レシピエント143例を対象とし、移植片でのSTX17の発現を調べ、発現量の中央値をカットオフ値として患者を2群に分けた。STX17ノックダウン肝細胞株を用いて、STX17の発現、ミトコンドリア膜電位、細胞増殖の関連を評価した。STX17が低発現の移植片レシピエント(低群73例)は、高発現の移植片レシピエント(高群70例)よりも移植片生着率が有意に低かった(88.9%対100%、p<0.01)。多変量解析で、LDLTの重度合併症である過小グラフト症候群の独立予測因子はSTX17の低発現および脾臓摘出術非施行であった。STX17ノックダウン肝細胞株では脱分極損傷ミトコンドリアの割合が増加し、マイトファジーとATP合成の減少が示唆された。STX17ノックダウン肝細胞株での細胞増殖は有意に減少した。以上より、STX17は肝細胞のマイトファジーとミトコンドリア機能の維持に寄与し、移植片機能障害の予測因子である可能性が考えられた。

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記述言語：英語   出版者・発行元：Annals of Gastroenterological Surgery  

Aim: This study aimed to clarify the clinical effects of the indocyanine green (ICG)-fluorescence imaging (FI) technique for determination of liver transection lines during laparoscopic partial liver resection for liver tumors. Methods: This was a retrospective study including 112 patients who underwent laparoscopic partial liver resection for liver tumors. These enrolled patients were divided into an ICG-FI group (n = 55) and a non-ICG-FI group (n = 57) according to the availability of the ICG-FI. The clinicopathological characteristics of patients between two groups were compared before and after propensity score matching. Results: The ICG-FI and non-ICG-FI groups differed at baseline in terms of ICG retention rate at 15 min. After propensity score matching, two comparable groups of 32 patients each were obtained. The negativity rated of the pathological surgical margins were comparable between the two groups before and after propensity score matching. However, the surgical margins were significantly wider in the ICG-FI group before and after propensity score matching (P =.039 and P =.047, respectively). Conclusion: The ICG-fluorescence imaging technique may offer clinical benefits in terms of a secure surgical margin in laparoscopic partial liver resection.

DOI： 10.1002/ags3.12563

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

検討対象は肝腫瘍に対して腹腔鏡下肝部分切除を施行した112例で、インドシアニングリーン蛍光画像(ICG-FI)を使用した55例(ICG-FI群)と使用しなかった57例(非ICG-FI群)を後方視的に比較検討した。2群の臨床病理学的因子を、傾向スコアマッチ前後の両方で比較した。ICG-FI群と非ICG-FI群には、ICG15分停滞率に差が認められた。傾向スコアマッチング法により各群より32例を検討対象とした。病理学的断端陰性率は、傾向スコアマッチ前後ともに、両群とも同等であった。傾向スコアマッチ前後ともに、切除断端距離はICG-FI群の方が非ICG-FI群と比較して有意に大きかった(P=0.039、P=0.047)。ICG-FIは、より確実に切除断端陰性とすることに貢献する可能性がある。

記述言語：英語   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   出版者・発行元：Clinical Transplantation  

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

DOI： 10.1111/ctr.14739

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

肝細胞癌において、チロシンキナーゼ阻害剤レンバチニブによる細胞毒性のメカニズムや核因子赤芽球2関連因子2(Nrf2)の関与を検討した。肝細胞癌由来のHep3BおよびHuH7細胞にて、レンバチニブはシステムXc(xCT)とグルタチオンペルオキシダーゼ4(GPX4)の発現を抑制した。xCTとGPX4のシスチン取り込み活性を阻害すると、脂質活性酸素種(ROS)が蓄積された。FGFR4をサイレンシングすると、xCTとGPX4の発現が抑制され、脂質ROSレベルが増加した。Nrf2をサイレンシングした肝細胞癌細胞は、レンバチニブに対して感受性を示し、脂質ROSレベルが亢進した。Nrf2を発現する肝細胞癌細胞では、レンバチニブに対して抵抗性を示し、脂質ROSレベルは低かった。FGFR4が低発現の再発肝細胞癌病変に対するレンバチニブの有効性はFGFR4が高発現している病変に比べて有意に低かった。FGFR4陽性肝細胞癌の患者では、FGFR4陰性肝細胞癌の患者よりも無増悪生存期間が有意に長かった。レンバチニブは、FGFR4を阻害することによってフェロプトーシスを誘導した。以上より、Nrf2は肝細胞癌のレンバチニブに対する感受性に関与していた。

記述言語：英語   出版者・発行元：Cancer Science  

The tyrosine kinase inhibitor lenvatinib is used to treat advanced hepatocellular carcinoma (HCC). Ferroptosis is a type of cell death characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS). Nuclear factor erythroid-derived 2-like 2 (Nrf2) protects HCC cells against ferroptosis. However, the mechanism of lenvatinib-induced cytotoxicity and the relationships between lenvatinib resistance and Nrf2 are unclear. Thus, we investigated the relationship between lenvatinib and ferroptosis and clarified the involvement of Nrf2 in lenvatinib-induced cytotoxicity. Cell viability, lipid ROS levels, and protein expression were measured using Hep3B and HuH7 cells treated with lenvatinib or erastin. We examined these variables after silencing fibroblast growth factor receptor-4 (FGFR4) or Nrf2 and overexpressing-Nrf2. We immunohistochemically evaluated FGFR4 expression in recurrent lesions after resection and clarified the relationship between FGFR4 expression and lenvatinib efficacy. Lenvatinib suppressed system X<inf>c</inf>⁻ (xCT) and glutathione peroxidase 4 (GPX4) expression. Inhibition of the cystine import activity of xCT and GPX4 resulted in the accumulation of lipid ROS. Silencing-FGFR4 suppressed xCT and GPX4 expression and increased lipid ROS levels. Nrf2-silenced HCC cells displayed sensitivity to lenvatinib and high lipid ROS levels. In contrast, Nrf2-overexpressing HCC cells displayed resistance to lenvatinib and low lipid ROS levels. The efficacy of lenvatinib was significantly lower in recurrent HCC lesions with low-FGFR4 expression than in those with high-FGFR4 expression. Patients with FGFR4-positive HCC displayed significantly longer progression-free survival than those with FGFR4-negative HCC. Lenvatinib induced ferroptosis by inhibiting FGFR4. Nrf2 is involved in the sensitivity of HCC to lenvatinib.

DOI： 10.1111/cas.15378

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PubMed

記述言語：英語   出版者・発行元：Hepatology Research  

Background: Early recurrence (ER) of hepatocellular carcinoma (HCC) (within 1 year after resection) is known to be a poor prognostic factor. The aim was to identify the risk factors associated with ER after HCC resection. Methods: Data were analyzed retrospectively from patients who underwent primary resection for HCC from two hospitals. For cross-validation, HCC resection cases were divided into the training and testing cohort. The clinicopathological factors between the ER and non-ER groups and factors for predicting ER and prognosis after HCC resection were compared. Results: Out of 173 patients in the training dataset, 33 patients had ER and the ER group showed larger tumor size, more intrahepatic metastasis (IM), and a higher ratio of serum des-gamma-carboxy prothrombin (DCP) to tumor volume (TV) (DCP/TV) than the non-ER group. Out of 203 patients in the testing dataset, 30 patients had ER and the ER group demonstrated larger tumor size, more IM, and higher serum alpha-fetoprotein, AFP/TV, DCP/TV, AFP/tumor maximum diameter (TMD), and DCP/TMD than the non-ER group. The patients were divided into high and low DCP/TV groups and high serum DCP/TV was associated with unfavorable overall survival in the training and testing dataset. Multivariate analysis confirmed that high serum DCP/TV and IM were independently associated with ER. Conclusion: Preoperative high serum DCP/TV may be useful for stratifying patients at risk of early HCC recurrence after curative resection.

DOI： 10.1111/hepr.13750

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PubMed

記述言語：英語   出版者・発行元：Hepatology Communications  

We examined phosphorylated nuclear factor erythroid 2–related factor 2 (P-NRF2) expression in surgically resected primary hepatocellular carcinoma (HCC) and investigated the association of P-NRF2 expression with clinicopathological features and patient outcome. We also evaluated the relationship among NRF2, cancer metabolism, and programmed death ligand 1 (PD-L1) expression. In this retrospective study, immunohistochemical staining of P-NRF2 was performed on the samples of 335 patients who underwent hepatic resection for HCC. Tomography/computed tomography using fluorine-18 fluorodeoxyglucose was performed, and HCC cell lines after NRF2 knockdown were analyzed by array. We also analyzed the expression of PD-L1 after hypoxia inducible factor 1α (HIF1A) knockdown in NRF2-overexpressing HCC cell lines. Samples from 121 patients (36.1%) were positive for P-NRF2. Positive P-NRF2 expression was significantly associated with high alpha-fetoprotein (AFP) expression, a high rate of poor differentiation, and microscopic intrahepatic metastasis. In addition, positive P-NRF2 expression was an independent predictor for recurrence-free survival and overall survival. NRF2 regulated glucose transporter 1, hexokinase 2, pyruvate kinase isoenzymes L/R, and phosphoglycerate kinase 1 expression and was related to the maximum standardized uptake value. PD-L1 protein expression levels were increased through hypoxia-inducible factor 1α after NRF2 overexpression in HCC cells. Conclusions: Our large cohort study revealed that P-NRF2 expression in cancer cells was associated with clinical outcome in HCC. Additionally, we found that NRF2 was located upstream of cancer metabolism and tumor immunity.

DOI： 10.1002/hep4.1838

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PubMed

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

単発肝細胞癌に対して治癒的肝切除を受けた日本人患者の早期再発(ER)に関連する危険因子を後方視的に検討した。2つの病院で肝細胞癌に対して一次切除を受けた患者をトレーニングコホートとテストコホートに分けた。トレーニングコホート173例中33例がERを経験し、ER群は非ER群に比べて、腫瘍サイズが大きく、肝内転移(IM)が多く、血清デス-ガンマ-カルボキシプロトロンビン(DCP)の腫瘍体積(TV)に対する比率(DCP/TV)が高かった。テストコホート203例のうち、30例がERを経験し、ER群は非ER群に比べて、腫瘍サイズが大きく、IMが多く、血清αフェトプロテイン(AFP)、AFP/TV、DCP/TV、AFP/腫瘍最大径(TMD)、DCP/TMDが高かった。トレーニングとテストコホートの患者を高いDCP/TV群と低いDCP/TV群に分けて比較したところ、高いDCP/TVは全生存率低下と関連していた。多変量解析では、高いDCP/TVとIMが独立してERと関連していた。以上より、術前の高いDCP/TVは、治癒的切除後の早期肝細胞癌再発のリスクを有する患者の層別化に有用である可能性が示唆された。

記述言語：英語  

DOI： 10.1038/s41598-022-07893-y

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PubMed

記述言語：英語   出版者・発行元：Surgery Today  

Purposes: Lenvatinib (LEN) is a molecular-target drug, used for unresectable hepatocellular carcinoma (HCC). It is associated with adverse events (AEs), including hypertension, proteinuria, fatigue, and anorexia, which may force dose reduction or discontinuation. Ninjin’yoeito (NYT) is a Chinese–Japanese herbal compound that can effectively treat fatigue and anorexia, and which has been used for chronic liver diseases. NYT reduces AEs and improves the liver function in patients treated with sorafenib but its effect on LEN is unclear. Methods: The present study included 46 patients (male, n = 32; female, n = 14) who received LEN for HCC at our hospital. Their median age was 70 years (range 36–88 years), and their median body weight was 61.5 kg (range 38.4–97.0 kg). Patients were divided into two groups, depending on whether they received NYT medication. Their AEs and liver function were examined one month after starting LEN. Results: The NYT group suffered less fatigue (63.6% vs. 11.4%, P = 0.0014) and showed elevated aspartate aminotransferase levels (45.5% vs. 14.3%, P = 0.0433) in comparison to the non-NYT group. The non-NYT group also showed a significantly exacerbated albumin-bilirubin (ALBI) grade (P = 0.0342) and ALBI score (average change: + 0.232, P = 0.0001) at 1 month in comparison to baseline. Conclusion: NYT apparently suppressed LEN-induced fatigue and helped maintain liver function in patients with HCC.

DOI： 10.1007/s00595-021-02358-7

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PubMed

記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

レンバチニブ(LEN)を投与された肝細胞癌(HCC)患者に対する人参養栄湯(NYT)の有効性を検討した。LENを投与されたHCC患者46例をNYT投与群35例(男性24例、女性11例、年齢中央値70歳)と非投与群11例(男性8例、女性3例、年齢中央値68歳)に分類し、LEN投与開始1ヵ月後における有害事象(AE)の発現と肝機能を評価した。LENは体重60kg未満の患者には8mg/日、60kg以上の患者には12mg/日を投与し、NYTは3gを1日3回投与した。AEの全発現率に関してNYT投与群と非投与群の間に有意差はみられなかったが、疲労、AST上昇はNYT投与群の方が有意に少なかった。グレード3以上のAEの発現率に群間差はなかった。また、肝機能を表すアルブミン-ビリルビン(ALBI)グレードの増悪を呈したのはNYT投与群が20.0%、非投与群が63.6%と有意差がみられ、NYT投与群のうち2ヵ月後にも投与を継続していた31例において、ALBIスコアに有意な変化は認められなかった。LENを投与されているHCC患者に対するNYT投与によって、有害事象としての疲労の軽減が得られ、肝機能も維持されることが示された。

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出版者・発行元：Pancreas  

DOI： 10.1097/MPA.0000000000001976

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記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

DOI： 10.11241/jsmtmr.38.24

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【背景・目的】　生体肝移植（LDLT）ではレシピエントの骨格筋の量的・質的低下はレシピエントの予後に影響することが報告されているが、ドナーの骨格筋の量的・質的影響については十分に検討されていない。今回、ドナー骨格筋のskeletal muscle mass index(SMI)とintramuscular adipose tissue content(IMAC)を測定しグラフト機能との関連性を検討した。</p><p>【対象・方法】　当科にて2007年1月から2018年5月までに生体肝移植術を施行した350組を対象とした。術前ドナーCT検査を用いて第3腰椎レベルでSMIとIMACを測定した。SMI/IMACのカットオフ値は男女別にROC曲線により制定し高値と低値の2群に分類した。SMI/IMACとグラフト機能としてレシピエントの術後14日目のT-bil値、PT-INR、腹水量と6ヶ月グラフト生存率との関係性を評価した。</p><p>【結果】　SMIはグラフト機能との関連性を示さず、IMACでは低値群で高値群に対しグラフト機能は不良であり(低値 vs 高値: T-bil; 6.2 mg/dL vs 4.5mg/dL, p=0.004, PT-INR; 1.2 vs 1.1, p=0.004, 腹水量; 425 mL vs 228 mL, p=0.0030)、 男女ともに低値群でグラフト生存率は不良であった(男性ドナー; 87.7% vs 95.9%, p=0.02, 女性ドナー; 83.0% vs99.0%, p<0.0001)。 多変量解析ではIMAC低値は6ヶ月グラフト生存における独立した予後予測因子であった(HR: 5.4, CI: 2.1-13.8, p=0.0004)。</p><p>【結語】　Donor骨格筋のIMACはLDLTにおけるグラフト生存予測因子となる可能性がある。</p>

DOI： 10.11386/jst.57.supplement_s379_1

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>移植医療は、手術手技の確立や免疫抑制療法を含めた周術期管理の進歩などにより発展を続けてきた。治療成績の向上、移植適応の拡大・適応疾患患者の増加により肝移植待機症例は増え続けているのが現状である。一方、現実的には移植医の不足や脳死移植の増加に伴う現場の疲弊が問題となっている施設も多数存在する。</p><p>私は2005年に九州大学を卒業後、九州大学消化器・総合外科（吉住朋晴教授）に入局し、肝移植外科・肝胆膵外科を中心に修練を積んできた。その過程には、入局前の熱意ある勧誘、手術や周術期管理についての熱いご指導、論文作成・研究・留学への導きなど多分に医局の先輩方にお世話になっており大変感謝している。今度は、我々の世代が意欲ある肝移植外科医を勧誘し指導することが我々の最低限の責務だと理解している。そうすることで移植外科としてのチーム医療、ひいては日本の移植医療に貢献することだと考える。</p><p>本発表では、医師18年目としての私のこれまでの経歴やこれからの抱負・課題など、日本移植学会第8回次世代リーダー養成コース(2022年7月)に参加した経験なども踏まえて発表させて頂きたい。</p>

DOI： 10.11386/jst.57.supplement_s242_1

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p><b>背景:</b></p><p>肝移植後の患者は、術創が大きいことや免疫抑制状態にあることから、創傷治癒が遅延し術後腹壁瘢痕ヘルニアが発症しやすいと考えられている。生体肝移植後の腹壁瘢痕ヘルニアの発生率は1.7%から32.4%との報告があるが、本邦での報告は限られており詳細は不明である。</p><p><b>対象と方法: </b></p><p>1997年から2016年までに当科で施行した成人生体肝移植症例561例を対象とし、後方視的検討を行い、生体肝移植術後の腹壁瘢痕ヘルニアの発生頻度、発生に関わる因子、およびその有効な治療法について検討をおこなった。</p><p><b>結果: </b></p><p>対象症例における1年生存率は87.9％（493例/561例）であり、生存群での腹壁瘢痕ヘルニアの発生率は4.5%（22例/493例）であった。腹壁瘢痕ヘルニアが発生した症例は、発生しなかった症例に比べ術後1年経過時のBMIが高かった（26.7 vs 22.1kg/m²： 発生あり群 vs 発生なし群； p<0.01）。治療法に関しては、前方アプローチが3例、腹腔鏡アプローチ腹腔内メッシュ法が19例に施行された。術後合併症は両群伴に認めなかったが、前方アプローチ群で有意に再発率が高かった（66.6%（2例/3例） vs 5.2％（1例/19例））。</p><p><b>結語: </b></p><p>生体肝移植術において、術後の体重増加は、術後腹壁瘢痕ヘルニアの発生の危険因子であることが示唆された。生体肝移植後においても腹腔鏡アプローチによる腹壁瘢痕ヘルニア修復術は安全に施行可能であり、メッシュを使用しない前方アプローチによる治療では再発率が高かったが、今後さらなる症例の蓄積が必要である。</p>

DOI： 10.11386/jst.57.supplement_s391_2

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【背景】生体肝移植における門脈走行異常や肝動脈破格、胆管に対する再建術は高度な手技が必要とされる。【目的】今回静脈グラフトを用いた門脈再建術、バックテーブルでの肝動脈形成を用いた再建術及び動注療法によりレシピエント肝動脈が使用不可能であった症例及び顕微鏡下胆管再建について報告する。【方法】症例1：先天性門脈欠損症に対して拡張右胃大網静脈-左内頸静脈グラフトを用いて門脈再建した。症例2：アラジール症候群の1歳男児に対して、外側区域グラフトを用いて生体肝移植を施行した。肝グラフトにおいてA2（右胃動脈から派生）及びA3＋4＋胆嚢動脈の2本の肝動脈を認めた。症例3：肝癌に対する動注療法後肝動脈が再建不能であった症例を報告する。【結果】症例1では門脈再建後血流量は460mL/min、術後1年3ヶ月で経過良好である。症例2ではバックテーブルで顕微鏡を用いて１穴に形成し、レシピエント右肝動脈とin-situで再建した。再建後エコー血流は良好だった。症例3では術中判断で右胃大網動脈を用いた再建を施行し、肝動脈血流量は110mL/minと良好だった。胆管再建について顕微鏡下胆管再建を供覧する。【まとめ】門脈再建には十分な術前評価と術中所見に基づいた再建が必要とされる。肝動脈複数再建の必要な生体肝移植において、顕微鏡下バックテーブル動脈形成は有効である可能性があり、複数回の動注療法後では、他の再建動脈を常に選択肢としておく必要がある。</p>

DOI： 10.11386/jst.57.supplement_s195_2

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開催地：松山市   国名：日本国  

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記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

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記述言語：日本語  

記述言語：日本語  

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記述言語：日本語  

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