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Introduction: Major hepatectomy (MH) may produce the impaired liver function and affect the feasibility of adjuvant chemotherapy in terms of early period after the surgery, but there have not been detailed investigations. JCOG1202 (UMIN000011688) is a randomized phase III trial demonstrating the superiority of adjuvant S-1 chemotherapy for biliary tract cancer (BTC). The aim of this study is to examine the influence of MH for BTC on adjuvant S-1., Materials and Methods: Of the total 424 patients, 207 received S-1 (S-1 arm) while the remaining 217 were not. We compared MH with non-major hepatectomy (NMH) for BTC., Results: In the S-1 arm, 42 had undergone MH, and 165 had undergone NMH. MH had similar pretreatment features to NMH, including the proportion of biliary reconstruction, to NMH, except for a lower platelet count (17.7 vs. 23.4 × 10 4 /mm 3 , p < 0.0001) and lower serum albumin level (3.5 vs. 3.8 g/dL, p < 0.0001). The treatment completion proportion tended to be lower for MH than for NMH (59.5 % vs. 75.8 %; risk ratio, 0.786 [95 % confidence interval, 0.603-1.023], p = 0.0733), and the median dose intensity was lower as well (88.7 % vs. 99.6 %, p = 0.0358). The major reasons for discontinuation were biliary tract infections and gastrointestinal disorders after MH. The frequency of grade 3-4 biliary tract infection was 19.0 % in MH vs. 4.2 % in NMH., Conclusion: The treatment completion proportion and dose intensity were lower in MH than in NMH. Caution should be exercised against biliary tract infections and gastrointestinal disorders during adjuvant S-1 after MH for BTC., Competing Interests: Declaration of competing interest MI has received grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Chiome Bioscience, Chugai, Eisai, Eli Lilly Japan, Delta-Fly Pharma, Invitae, J-Pharma, Merck biopharma, Merus N.V., MSD, Novartis, Nihon Servier, Ono, Pfizer, Takeda, and Yakult; and honoraria from AstraZeneca, AbbVie, Abbott Japan, Bayer, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly Japan, EA Pharma, Fujifilm Toyama Chemical, Incyte Biosciences Japan, MSD, Nihon Servier, Nippon Kayaku, Novartis, Otsuka, Teijin, Taiho, Taisho Pharmaceutical, Takeda, and Yakult. SH has received grant from Taiho Pharmaceutical. MU has received grants from Taiho Pharmaceutical, AstraZeneca, Merck Biopharma, Merck, Astellas Pharma, Eisai, Ono Pharmaceutical, Incyte Biosciences Japan, Chugai Pharmaceutical, Delta-Fly Pharma, and Daiich Sankyo and honoraria from Taiho Pharmaceutical, AstraZeneca, Merck Biopharma, Merck, NIHON SERVIER, Ono Pharmaceutical, Incyte Biosciences Japan, and Chugai Pharmaceutical. TO has received grants from AstraZeneca, Eisai, Merck, Syneos, EP-CRSU, Incyte Japan, and Dainippon Sumitomo Pharma; consulting fees from AstraZeneca, Eisai, Nihon Servier, FUJIFILM Toyama Chemical, Dainippon Sumitomo Pharma, and Bristol-Myers Squibb; and honoraria from AstraZeneca, Incyte Biosciences Japan, Eisai, Ono Pharmaceutical, Eli Lilly Japan, Yakult Honsha, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, Teijin Pharma, Nippon Shinyaku, NIHON SERVIER, Novartis Pharma, Pfizer, and Mundipharma. JF has received grants from the National Cancer Center Research and Development Fund and Health, Labour Sciences Research Grants for Clinical Cancer Research, Ono Pharmaceutical, Merck, Merck Biopharma, J-Pharma, Taiho Pharmaceutical, Takeda, Chugai Pharma, AstraZeneca, Yakult Honsha, Eisai, Daiichi Sankyo, Mochida, Sanofi, Sumitomo Dainippon Bayer, Astellas, and Incyte Biosciences Japan; consulting fees from Fuji Film, Onco Therapy Science, Merck Biopharma, Ono Pharmaceutical, Merck, Taiho Pharmaceutical, Chugai Pharma, Astellas, AstraZeneca, Delta-Fly-Pharma, and Incyte Biosciences Japan; and honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Ono Pharmaceutical, Bayer, Eisai, Eli Lilly Japan, Merck, Yakult Honsha, Chugai Pharma, Novartis Pharma, AstraZeneca, Pfizer, Takeda, Taiho Pharmaceutical, EA Pharma, Daiichi Sankyo, Teijin Pharma, NIHON SERVIER, Terumo, and Incyte Biosciences Japan. All other authors declare no competing interests., (© 2023 Published by Elsevier Ltd.)

Background: The Global Leadership Initiative on Malnutrition (GLIM), comprising several of the major global clinical nutrition societies, suggested the world's first criteria for diagnosis of the severity of malnutrition. However, the impact of the resulting diagnosis on patient outcomes for those with hepatocellular carcinoma (HCC) following liver resection (LR) has not been investigated., Methods: A retrospective analysis of 293 patients with HCC who underwent LR between January 2011 and December 2018 was performed. We compared overall survival (OS) and recurrence-free survival (RFS) and evaluated prognostic factors after LR using Cox proportional hazards regression models., Results: Preoperative patient nutritional status, n (%), was classified as follows: normal, 130 (44%), moderate malnutrition, 116 (40%), and severe malnutrition, 47 (16%). The median OS (129 vs. 43 months, p < 0.001) and median RFS (54 vs. 20 months, p = 0.001) were significantly greater in the normal group than in the severe malnutrition group. Multivariate analysis showed that severe malnutrition was a significant risk factor for OS (p = 0.006) and RFS (p = 0.010) after initial LR., Conclusion: Severe malnutrition, as diagnosed by the GLIM criteria, is a significant prognostic factor for survival and recurrence in patients with HCC after LR., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: S-1 has shown promising efficacy with a mild toxicity profile in patients with advanced biliary tract cancer. The aim of this study was to evaluate whether adjuvant S-1 improved overall survival compared with observation for resected biliary tract cancer., Methods: This open-label, multicentre, randomised phase 3 trial was conducted in 38 Japanese hospitals. Patients aged 20-80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone no local residual tumour resection or microscopic residual tumour resection were randomly assigned (1:1) to undergo observation or to receive S-1 (ie, 40 mg, 50 mg, or 60 mg according to body surface area, orally administered twice daily for 4 weeks, followed by 2 weeks of rest for four cycles). Randomisation was performed by the minimisation method, using institution, primary tumour site, and lymph node metastasis as adjustment factors. The primary endpoint was overall survival and was assessed for all randomly assigned patients on an intention-to-treat basis. Safety was assessed in all eligible patients. For the S-1 group, all patients who began the protocol treatment were eligible for a safety assessment. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry (UMIN000011688)., Findings: Between Sept 9, 2013, and June 22, 2018, 440 patients were enrolled (observation group n=222 and S-1 group n=218). The data cutoff date was June 23, 2021. Median duration of follow-up was 45·4 months. In the primary analysis, the 3-year overall survival was 67·6% (95% CI 61·0-73·3%) in the observation group compared with 77·1% (70·9-82·1%) in the S-1 group (adjusted hazard ratio [HR] 0·69, 95% CI 0·51-0·94; one-sided p=0·0080). The 3-year relapse-free survival was 50·9% (95% CI 44·1-57·2%) in the observation group compared with 62·4% (55·6-68·4%) in the S-1 group (HR 0·80, 95% CI 0·61-1·04; two-sided p=0·088). The main grade 3-4 adverse events in the S-1 group were decreased neutrophil count (29 [14%]) and biliary tract infection (15 [7%])., Interpretation: Although long-term clinical benefit would be needed for a definitive conclusion, a significant improvement in survival suggested adjuvant S-1 could be considered a standard of care for resected biliary tract cancer in Asian patients., Funding: The National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan., Competing Interests: Declaration of interests KN has received grants from Delta-Fly Pharma and honoraria from Eisai, Yakult, AstraZeneca, and Ono. MI has received research funding from Eisai, Merck Biopharma, Eli Lilly Japan, Yakult, Ono, J-Pharma, AstraZeneca, Pfizer, Merus NV, NIHON SERVIER, Delta-Fly Pharma, Chiome Bioscience, Chugai, Bristol-Myers Squibb, Novartis, Bayer, Merck, and Syneos Health and honoraria from Eisai, Merck, Eli Lilly Japan, Yakult, Teijin Pharma, Ono, Incyte Biosciences Japan, NIHON SERVIER, Taiho, Chugai, Bristol-Myers Squibb, Novartis, Bayer, Takeda, EA Pharma, AstraZeneca, AbbVie, Abbott Japan, and Fujifilm Toyama Chemical. SN has received grants from AstraZeneca and Amgen and honoraria from AstraZeneca, Chugai, and Kyowa Hakko. AT has received honoraria from Ono Pharmaceutical, Yakult Honsha, and Taiho Pharmaceutical. MU has received grants from Taiho Pharmaceutical, AstraZeneca, Merck Biopharma, Merck, Astellas Pharma, Eisai, Ono Pharmaceutical, Incyte Biosciences Japan, Chugai Pharmaceutical, Delta-Fly Pharma, and Daiichi Sankyo and honoraria from Taiho Pharmaceutical, AstraZeneca, Merck Biopharma, Merck, NIHON SERVIER, Ono Pharmaceutical, Incyte Biosciences Japan, and Chugai Pharmaceutical. HI has received consulting fees from Ono Pharmaceutical and honoraria from Yakult Honsha, Taiho Pharmaceutical, Novartis, Chugai Pharmaceutical, and Incyte Biosciences Japan. TO has received grants from AstraZeneca, Eisai, Merck, Syneos, EP-CRSU, Incyte Japan, and Dainippon Sumitomo Pharma; consulting fees from AstraZeneca, Eisai, Nihon Servier, FUJIFILM Toyama Chemical, Dainippon Sumitomo Pharma, and Bristol-Myers Squibb; and honoraria from AstraZeneca, Incyte Biosciences Japan, Eisai, Ono Pharmaceutical, Eli Lilly Japan, Yakult Honsha, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, Teijin Pharma, Nippon Shinyaku, NIHON SERVIER, Novartis Pharma, Pfizer, and Mundipharma. JF has received grants from the National Cancer Center Research and Development Fund and Health, Labour Sciences Research Grants for Clinical Cancer Research, Ono Pharmaceutical, Merck, Merck Biopharma, J-Pharma, Taiho Pharmaceutical, Takeda, Chugai Pharma, AstraZeneca, Yakult Honsha, Eisai, Daiichi Sankyo, Mochida, Sanofi, Sumitomo Dainippon Bayer, Astellas, and Incyte Biosciences Japan; consulting fees from Fuji Film, MudiPharma, Onco Therapy Science, Merck Biopharma, Ono Pharmaceutical, Merck, Taiho Pharmaceutical, Chugai Pharma, Astellas, AstraZeneca, Takara Bio, Delta-Fly-Pharma, and Incyte Biosciences Japan; and honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Ono Pharmaceutical, Bayer, Eisai, Eli Lilly Japan, Merck, Yakult Honsha, Chugai Pharma, Novartis Pharma, AstraZeneca, Pfizer, Takeda, Taiho Pharmaceutical, Sanofi, Mylan EPD, EA Pharma, Kyowa Hakko Kirin, Daiichi Sankyo, Teijin Pharma, NIHON SERVIER, and Incyte Biosciences Japan. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate even after curative resection. Lung recurrence may have better outcomes than other recurrences. However, its detailed clinicopathological features are unclear. We investigated the clinicopathological features and risk factors for lung recurrence after pancreatectomy for PDAC., Methods: The study included 161 patients with potentially and borderline resectable PDAC who had undergone R0 or R1 pancreatectomy between January 2008 and December 2016. We retrospectively examined the prognosis and predictors for lung recurrence after curative resection., Results: Seventeen patients (10.6%) had isolated lung recurrence. The median overall and recurrence-free survivals were 38.0 and 16.1 months, respectively. In multivariate analysis, para-aortic lymph node (PALN) metastasis (p = 0.006) and female sex (p = 0.027) were independent factors for lung recurrence., Conclusion: Lung recurrence had a better prognosis than other recurrences. PALN metastasis and female sex are independent risk factors for lung recurrence after curative resection for PDAC., Competing Interests: Declaration of competing interest The Authors declare no conflicts of interest., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: The present study aimed to assess the clinical features of patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC)., Methods: The clinical characteristics, adverse events, and radiological responses were evaluated for 51 consecutive patients., Results: Of the study subjects, 37 patients had Child-Pugh class A (CPA) liver function, and 14 patients had Child-Pugh class B (CPB) liver function. The overall response rates in the CPA and CPB groups were 42.9% and 25.0%, respectively, and disease control rates were 82.9% and 83.3%, respectively, without significant difference (p = 0.2621 and 0.9697). There was no significant difference between CPA and CPB groups regarding the incidence of adverse events, except for hepatic coma. No significant difference was observed in the relative dose intensity between the CPA and CPB groups, for the first month, 1-2 months, or 2-3 months (p = 0.2368, 0.9368, and 0.9293)., Conclusion: The comparable outcomes between the CPA and CPB groups suggest the acceptability of lenvatinib treatment in patients with impaired liver function, at least in the acute phase. With careful follow-up, the dose can be relatively intensified, even in patients with impaired liver function and this may contribute to offering comparable treatment., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS)., Patients and Methods: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea., Results: Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm., Conclusions: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC., Clinical Trial Number: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Post-operative pancreatic fistula (POPF) is one of the most common and serious complications after pancreaticoduodenectomy (PD). The aim of this study is to retrospectively compare clinically relevant (CR) POPF and other complications after pacreaticojejunostomy (PJ) after modified Kakita (m-Kakita) or modified Blumgart (m-Blumgart) anastomoses without stenting in a single institution., Methods: One hundred twenty-eight patients underwent PJ using m-Kakita anastomoses (two interrupted penetrating sutures) between January 2009 and December 2011. One hundred eighteen patients underwent m-Blumgart anastomoses (two transpancreatic/jejunal seromuscular sutures to cover the pancreatic stump with jejunal serosa) between January 2014 and December 2015. Demographics, clinical characteristics, and post-operative mortality and morbidity were retrospectively compared between the two groups., Results: There were no significant differences in demographics or clinical characteristics between the two groups except operative time. A significantly lower rate of CR-POPF was found in the m-Blumgart group relative to the m-Kakita group (10% vs. 19%, p = 0.038). Univariate and multivariate analyses revealed that the m-Blumgart anastomosis and fistula risk category (Negligible, Low) were independently protective against CR-POPF (p < 0.05)., Conclusion: This retrospective single-center study demonstrated that the modified Blumgart method without pancreatic duct stenting was associated with a lower rate of CR-POPF., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Background/objective: Although single-incision laparoscopic cholecystectomy (SILC) has no advantage over conventional laparoscopic cholecystectomy (LC), except for better cosmesis, few reports have discussed the criteria for SILC. The aim of this study was to evaluate the suitability of our criteria for SILC., Methods: During the study period, SILC was performed at our institution under the following criteria. The inclusion criteria were elective surgery, age of < 60 years, and body mass index of < 30 kg/m 2 . The exclusion criteria were a thick gallbladder wall, history of choledocholithiasis, previous abdominal surgery, and serious concomitant disease. We reviewed data regarding consecutive patients who underwent LC at our institution from November 2009 to March 2016. The data were assessed with respect to patient characteristics, operative data, and postoperative outcomes., Results: A total of 1093 patients underwent elective LC, and 232 (21.2%) of these patients underwent SILC using our criteria. Fourteen patients (6.0%) who underwent SILC required extra ports. Among the patients aged < 60 years, 50.2% (232/462) underwent SILC. There were few adverse events, including intra- and postoperative complications, among the patients who underwent SILC., Conclusion: The above-mentioned criteria are safe, necessary, and sufficient for SILC over conventional LC., (Copyright © 2016. Published by Elsevier Taiwan.)

This paper reported the occurrence and concentrations of macrocyclic-, polycyclic- and nitro musks in cosmetics and household commodities collected from Japan. The high concentrations and detection frequencies of Musk T, habanolide, and exaltolides were found in commercial products, suggesting their large amounts of production and usage in Japan. Polycyclic musks, HHCB and OTNE, also showed high concentrations in cosmetics and products. The estimated dairy intakes of Musk T and HHCB by the dermal exposure to commercial products were 7.8 and 7.9 μg/kg/day in human, respectively, and perfume and body lotion are dominant exposure sources. We also analyzed synthetic musks in house dusts. Polycyclic musks, HHCB and OTNE, showed high concentrations in samples, but macrocyclic musks were detected only in a few samples, although these types of musks were highly detected in commercial products. This is probably due to easy-degradation of macrocyclic musks in indoor environment. The dairy intakes of HHCB by dust ingestions were 0.22 ng/kg/day in human, which were approximately five orders of magnitudes lower than those of dermal absorption from commercial household commodities., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background/aims: Our policy for the surgical treatment of hepatocellular carcinoma (HCC) has been to minimize the extent of liver resection using a microwave tissue coagulator (MTC) and to not perform Pringle's maneuver for the prevention of ischemic injury to the liver routinely. We verify the safety of liver resection using MTC in HCC patients with poor liver functional reserve, and clarify the long-term outcome of HCC patients who underwent curative resection using MTC., Methodology: One hundred sixty-eight patients who underwent curative resection using MTC between 1992 and 2001 were divided into two groups according each patient's score in the Indocyanin Green Retension 15 Test (ICG-R15 test). The high (ICG-R15 values>20) and low ICG-R15 groups (ICG-R15 values<20) included 100 and 68 HCC patients, respectively. Clinical characteristics of each group were evaluated, and operative mortality and morbidity, as well as overall and disease-free survival rates, were compared between the two groups to determine risk factors for overall and disease-free survival., Results: Although there were significant differences in liver function-related parameters between the low and high ICG-R15 groups, no differences in surgical or tumor factors were found. No patients in this study developed post-operative liver failure, and there was no significant difference in morbidity between the low and high ICG-R15 groups. The overall survival rate of the low ICG-R15 group was significantly longer than the high ICG-R15 group (p=0.0003). Cox's multivariate analysis showed that an ICG-R15 value less than 20 was the only significant independent factor for overall survival. Disease-free survival rates in the low ICG-R15 group were significantly longer than in the high ICG-R15 group (p=0.0007). Multivariate analysis showed that serum albumin level and number of tumors were significant independent factors for disease-free survival., Conclusion: The long-term outcome of HCC patients with low ICG-R15 following curative resection using MTC was acceptable. This procedure was safe even for patients with high ICG-R15.