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Pancreatic cancer remains a highly lethal disease with a 5-year survival proportion of <10%. Chemoradiotherapy is a treatment option for unresectable locally advanced (UR-LA) or borderline resectable (BR) pancreatic cancer, but its efficacy is not sufficient. Induction of the synergistic effect of irradiation and immune checkpoint inhibitors can be an attractive strategy. An open-label randomized phase III trial has been conducted since October 2020 to confirm the superiority of nivolumab plus S-1-based chemoradiotherapy over S-1-based chemoradiotherapy alone in patients with UR-LA or BR pancreatic cancer. A total of 216 patients will be enrolled in 14 institutions within 3.5 years. The primary endpoint of the safety run-in part is dose-limiting toxicity, and that of the phase III part is overall survival. This trial was registered at the Japan Registry of Clinical Trials as jRCT2080225361 (https://jrct.niph.go.jp/latest-detail/jRCT2080225361)., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/objective: Caveolin-1 (Cav1) expressed in cancer cells (cCav1) or cancer-associated fibroblasts (fCav1) exerts either pro- or anti-tumorigenic effects depending on the cancer type or stage of cancer. We aimed to clarify the impact of cCav1 or fCav1 on survival, recurrence patterns, and efficacy of neoadjuvant chemotherapy (NAC) in resected pancreatic ductal adenocarcinoma (PDAC)., Methods: Tissue microarrays were constructed including 615 patients who underwent curative resection for PDAC. Cav1 expression was evaluated by immunohistochemistry. Patients were divided into two groups based on Cav1 expression in cancer cells (cCav1 high vs. cCav1 low ) or cancer-associated fibroblasts (fCav1 high vs. fCav1 low )., Results: Among all 615 patients, 40.7% were cCav1 high and 72.7% were fCav1 high . cCav1 high was associated with worse overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.001) than cCav1 low , and was an independent prognostic factor in multivariate analysis of OS and RFS (OS: p = 0.001, hazard ratio [HR] 1.361; RFS: p = 0.001, HR 1.348). Among 596 patients with resectable/borderline resectable PDAC, cCav1 high patients with NAC showed better OS than those without, while there was no significant difference between cCav1 low patients with NAC and those without. cCav1 high was associated with early recurrence (< 6 months) and liver metastasis after resection. Multivariate analysis revealed cCav1 high as an independent predictor of liver metastasis., Conclusions: cCav1 high correlated with worse survival, early recurrence, and liver metastasis after resection for PDAC, while NAC improved survival in cCav1 high patients. The Evaluation of cCav1 status could provide additional information contributing to the personalized management of PDAC., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Major hepatectomy (MH) can increase the risk of adverse events (AEs) owing to impaired drug metabolism due to decreased liver volume and surgical injury. Thus, we performed this subgroup analysis using data from JCOG1113, a phase III trial comparing gemcitabine plus S-1 (GS) and gemcitabine plus cisplatin (GC) in patients with advanced and recurrent biliary tract cancer (BTC), to evaluate the effect of MH on the safety and efficacy of GC and GS regimens in patients with recurrent BTC., Methods: Of the 354 patients with advanced BTC enrolled in JCOG1113, 76 patients with postoperative recurrence (30 in the MH group and 46 in the non-MH group) were analyzed., Results: Grade ≥ 3 platelet count decreased in both arms was more frequent in the MH group than in non-MH group (GC, 0.0 vs. 17.6%; GS, 3.9 vs. 15.4%). However, in the MH group, the white blood cell decreased (GC, 55.0 vs. 38.5%; GS, 23.1 vs. 7.7%) and anemia (GC, 15.0 vs. 11.8%; GS, 23.1 vs. 7.7%) were less common than in the non-MH group. The MH and non-MH groups showed no significant difference in overall survival (OS) in both GC [median OS, 23.0 in MH vs. 16.9 months in non-MH (hazard ratio, 0.857; 95% CI 0.387-1.899)], and GS [median OS, 21.5 vs. 14.9 months (hazard ratio, 0.670; 95% CI 0.310-1.447)] arms., Conclusions: The safety and efficacy of gemcitabine-based chemotherapy were comparable between patients who underwent MH and those who underwent other surgeries., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Identification of homologous recombination deficiency (HRD) remains a challenge in advanced pancreatic cancer (APC). We investigated the utility of circulating tumour DNA (ctDNA) profiling in the assessment of BRCA1/2 and ATM mutation status and treatment selection in APC., Methods: We analysed clinical and ctDNA data of 702 patients with APC enroled in GOZILA, a ctDNA profiling study using Guardant360., Results: Inactivating BRCA1/2 and ATM mutations were detected in 4.8% (putative germline, 3.7%) and 4.4% (putative germline, 0.9%) of patients, respectively. Objective response (63.2% vs. 16.2%) and PFS (HR 0.55, 95% CI 0.32-0.93) on platinum-containing chemotherapy were significantly better in patients with putative germline BRCA1/2 (gBRCA) mutation than those without. In contrast, putative gBRCA mutation had no impact on the efficacy of gemcitabine plus nab-paclitaxel. In 2 patients treated with platinum-containing therapy, putative BRCA2 reversion mutations were detected. Three of seven patients with somatic BRCA mutations responded to platinum-containing therapy, while only one of four with putative germline ATM mutations did. One-third of somatic ATM mutations were in genomic loci associated with clonal haematopoiesis., Conclusion: Comprehensive ctDNA profiling provides clinically relevant information regarding HRD status. It can be a practical, convenient option for HRD screening in APC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: The multi-hole self-expandable metal stent (MHSEMS) is a novel SEMS with multiple small side holes on the covering membrane to prevent stent migration while minimizing tumor ingrowth. This study aimed to evaluate the clinical outcomes of MHSEMS in comparison with conventional covered SEMS (c-CMS)., Methods: Consecutive patients with unresectable pancreatic cancer who underwent initial SEMS placement (MHSEMS or c-CMS) for malignant distal biliary obstruction were analyzed. Technical success, clinical success, causes of recurrent biliary obstruction (RBO), non-RBO adverse events, time to RBO (TRBO), and endoscopic reintervention were compared between groups., Results: A total of 65 patients were included (MHSEMS: 27, c-CMS: 38). The technical success, clinical success, and non-RBO adverse event rates were similar between groups. Although stent migration was less frequently observed in the MHSEMS group (0% vs. 17.6%, p = 0.032), overall RBO rates were similar between groups (53.8% vs. 55.9%, p > 0.99). The most common cause of RBO within 14 days in the MHSEMS group was non-occlusion cholangitis. Median TRBO was significantly shorter in the MHSEMS group (101 vs. 227 days, p = 0.030) and MHSEMS was an independent predictor for shorter TRBO in multivariate analysis (hazard ratio, 2.27; 95% confidence interval, 1.06-4.86; p = 0.034). Outcomes after endoscopic interventio were not significantly different between groups. Stent removal was successful in all attempted cases in both groups., Conclusions: MHSEMS was associated with a significantly shorter TRBO compared to c-CMS. Further modifications of the present MHSEMS may be needed., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Stent migration and sludge formation remain significant problems associated with covered self-expandable metal stents (CSEMSs). The EGIS biliary stent fully covered flare type (EGIS biliary stent), a new type of polytetrafluoroethylene-coated self-expandable metal stent with low axial force and an anti-migration system, was developed to overcome these disadvantages. We conducted this study to evaluate the efficacy and safety of this stent in comparison with conventional CSEMS (c-CSEMS)., Methods: We retrospectively analyzed consecutive patients with unresectable pancreatic cancer who received initial CSEMS for distal malignant biliary obstruction. The primary outcome was time to recurrent biliary obstruction (RBO). Secondary outcomes included technical success rate, functional success rate, stent-related adverse events, causes of RBO, and re-intervention., Results: A total of 40 patients were included (EGIS group: 20; c-CSEMS group: 20). The technical and functional success rates were similar between the two groups. Stent-related adverse event rates (20% vs. 15%, p > 0.99) and overall RBO rates (56% vs. 50%, p > 0.99) were not significantly different between the two groups. Stent migration was the most common cause of RBO in the EGIS group, while stent occlusion was in the c-CSEMS group. The median time to RBO (102 vs. 434 days, p = 0.10) was not significantly different between the two groups. Endoscopic transpapillary re-intervention was successful in most patients in both groups., Conclusions: The EGIS biliary stent was not associated with a longer time to RBO compared to c-CSEMS. Further improvements, especially against stent migration, are needed to improve its efficacy., Competing Interests: Tsuyoshi Takeda received honoraria from Boston Scientific Japan and SB‐Kawasumi Laboratories. Takashi Sasaki received honoraria from Boston Scientific Japan, Century Medical, SB‐Kawasumi Laboratories, JAPAN LIFELINE, and KANEKA MEDIX. Naoki Sasahira received honoraria from SB‐Kawasumi Laboratories., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Early tumor shrinkage (ETS) is a prognostic predictor for patients treated with chemotherapy in colorectal cancer, although scarce studies evaluated its potential in locally advanced pancreatic cancer (LAPC). In this exploratory analysis of JCOG1407, a randomized phase II study comparing modified 5-fluorouracil, levofolinate, irinotecan, and oxaliplatin (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP), we evaluated whether ETS can predict prognosis of patients with LAPC., Methods: Of the 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this study. ETS was defined as a ≥20 % reduction in tumor diameter compared with baseline at the initial imaging assessment 6-10 weeks after initiating chemotherapy. Patients were divided into the ETS (achieved ETS) and non-ETS (failed to achieve ETS) groups based on their ETS status. The impact of ETS on overall survival (OS) was compared using multivariable Cox regression analysis., Results: Fourteen of 55 (25.5 %) and 24 of 57 (42.1 %) patients in the mFOLFIRINOX and GnP arms, respectively, achieved ETS. In the overall population, mFOLFIRINOX arm, and GnP arm, the median OS in the ETS and non-ETS groups was 27.1 and 20.4, 29.8 and 20.6, and 24.1 and 20.4, months, respectively. The adjusted hazard ratios of OS for the ETS group in the overall population, mFOLFIRINOX arm, and GnP arm were 0.451 (95 % confidence interval [CI]: 0.270-0.754), 0.371 (95 % CI: 0.149-0.926), and 0.508 (95 % CI: 0.255-1.004), respectively., Conclusions: ETS may be a prognostic predictor in chemotherapy-naïve patients with LAPC treated with mFOLFIRINOX or GnP., Competing Interests: Declaration of competing interest JF reports grants from the Japan Agency for Medical Research and Development (AMED) and the National Cancer Center Research and Development Fund, during the study, as well as grants from Ono Pharmaceutical, MSD, J-Ph arma, Taiho Pharmaceutical, Takeda Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Eisai, Daiichi Sankyo, Sanofi, Sumitomo Dainippon, Astellas, Delta-Fly-Pharma, and Incyte Biosciences Japan and personal fees from Fujifilm, Delta-Fly-Pharma, Onco Therapy Science, Merck Biopharma, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical, Astellas, AstraZeneca, Incyte Biosciences Japan, J-Pharma, Eisai, Daiichi Sankyo, Eli Lilly Japan, Yakult Honsha, Nihon Servier, Novartis Pharma, Takeda Pharmaceutical, Bayer, Teijin Pharma, Terumo, and Incyte Biosciences Japan outside the submitted work. KN reports personal fees from Ono Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, AstraZeneca, and Taiho Pharmaceutical outside the submitted work. HI reports grants from Ono Pharmaceutical and Nihon Servier and personal fees from Nihon Servier, Yakult Honsha, Boston Scientific, Kaneka Medix, Medico's Hirata, and SB KAWASUMI LABORATORIES outside the submitted work. SS reports grants from AstraZeneca, Incyte Corporation, and Delta-Fly-Pharma outside the submitted work. SK reports personal fees from Yakult Honsha outside the submitted work. CM reports grants from Eisai, Yakult Honsha, Ono Pharmaceutical, Taiho Pharmaceutical, J-Pharma, AstraZeneca, Merck Biopharma, Daiichi Sankyo, HITACHI, and Boehringer Ingelheim and personal fees from Yakult Honsha, MSD, Nihon Servier, Boehringer Ingelheim, Taiho Pharmaceutical, Novartis Pharma, Teijin Pharma, Eisai, and AstraZeneca outside the submitted work. MU reports grants from Japan AMED and the National Cancer Center Research and Development Fund, during the study, as well as grants from Ono Pharmaceutical, Taiho Pharmaceutical, J-Pharma, AstraZeneca, Merck Biopharma, MSD, Astellas, Eisai, Boehringer Ingelheim, Delta-Fly-Pharma, Incyte Biosciences Japan, Chugai Pharmaceutical, and Novartis Pharma and personal fees from Yakult Honsha, MSD, Nihon Servier, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, Taiho Pharmaceutical, Novartis Pharma, J-Pharma, Incyte Biosciences Japan, Daiichi Sankyo, and AstraZeneca outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Outcomes of unresectable biliary tract cancer (BTC) with varying extents of liver involvement remain unclear. We evaluated characteristics and outcomes of BTC patients with liver metastases who underwent chemotherapy., Methods: We retrospectively reviewed consecutive BTC patients with synchronous or metachronous intrahepatic metastases who started first-line chemotherapy at our institution between January 2016 and December 2021., Results: Ninety-six patients were included, of which 57 only had liver metastases and 39 had multiorgan involvement. The liver only group had longer median overall survival (OS) (11.8 vs. 7.4 months, P = 0.006) and median progression-free survival (PFS) (4.1 vs. 2.7 months, P = 0.035) than the multiorgan group. Patients with oligometastases (defined as no more than three liver metastases) achieved longer OS than those with polymetastases (four or more liver metastases) in the entire cohort. Within the liver only group, there were no significant differences in OS or PFS between the oligometastasis and polymetastasis groups. Patients who underwent subsequent surgery had significantly longer median OS than those who did not (44.4 vs. 7.7 months, P < 0.001). Age ≥ 75 years, liver-only metastasis, modified Glasgow prognostic score ≥ 1 carcinoembryonic antigen ≥ 5 μg/L, and subsequent surgery were independent predictors of OS. Liver oligometastasis was only a significant predictor of longer OS in univariate Cox analysis., Conclusions: Outcomes in BTC patients with metastases limited to the liver, particularly those with oligometastasis, were more favorable than those with multiorgan metastases. Selected cases, generally with liver oligometastases, may achieve prolonged OS through subsequent surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: The optimal length of the uncovered portion of partially covered self-expandable metal stents (PCSEMSs) used in endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) remains unclear. This study investigated the safety and efficacy of PCSEMSs with different uncovered lengths, with a focus on stent migration and time to recurrent biliary obstruction (RBO)., Methods: Outcomes of patients undergoing EUS-HGS using PCSEMSs with 5-mm and 20-mm uncovered portions at our institution from January 2016 to December 2021 were compared., Results: Sixty-two patients underwent EUS-HGS using PCSEMS (5/20-mm uncovered portions: 32/30). Stent migration occurred only in the 5-mm group. There were no differences in RBO rates (28.1% vs. 40.0%) or median time to RBO (6.8 vs. 7.1 months) between the two groups. Median overall survival (OS) was longer in the 20-mm group (3.1 vs. 4.9 months, p=0.037) due to the higher number of patients that resumed chemotherapy after EUS-HGS (56.7% vs. 28.1%, p=0.029). Good performance status, absence of hepatic metastases, and chemotherapy after EUS-HGS were independent predictors of longer OS., Conclusions: No migration was observed in patients treated with PCSEMS with 20-mm uncovered portions. Patients treated with PCSEMS with 20-mm uncovered portions performed at least as well as those treated with 5-mm uncovered portions in all material respects.

Objective The efficacy of anamorelin in pancreatic cancer (PC) patients with a poor performance status (PS) is uncertain, as previous trials have excluded such patients. This study evaluated the efficacy of anamorelin in PC patients with a poor PS (2) compared with those with a good PS (0-1). Methods We retrospectively reviewed consecutive PC patients with cachexia who received anamorelin at our institution. The primary outcome was the proportion of responders, defined as those who maintained or gained body weight and appetite over 12 weeks. The secondary outcomes included anamorelin treatment duration, proportion of patients who discontinued anamorelin within 4 weeks (early discontinuation), and the overall survival. Results Forty-five patients (35/10) were included in this study. The proportion of responders was significantly lower in patients with a poor PS than in those with a good PS (0% vs. 37%, p=0.042). Moderate weight loss (5%-10%) and administration of pancreatic enzyme replacement therapy were associated with a response to anamorelin. A poor PS was significantly associated with a shorter treatment duration of anamorelin (14 vs. 93 days, p <0.001), a higher proportion of patients who discontinued anamorelin within 4 weeks (70% vs. 17%, p=0.003), and a reduced survival (62 vs. 188 days, p <0.001). A poor PS was associated with early discontinuation of anamorelin. Conclusions The efficacy of anamorelin is extremely limited in PC patients with a poor PS. Patients with PC with a poor PS may not be good candidates for anamorelin compared to those with a good PS.

Background: Pancreatic cancer has a high risk of developing osteoporosis. However, the impact of osteoporosis has not been well-studied. This study aimed to evaluate bone loss over time and risk of osteoporosis in patients with advanced pancreatic cancer., Methods: We retrospectively examined consecutive patients with unresectable pancreatic cancer who had evaluable computed tomography before treatment and at 1-year follow-up. Bone mineral density at the first lumbar vertebra was measured on computed tomography, and osteoporosis was defined as bone mineral density < 135 Hounsfield units. The prevalence and risk factors for osteoporosis, changes in bone mineral density over time and incidence of bone fractures were analyzed., Results: Three hundred eighty patients were included. Osteoporosis was associated with older age, female sex, low body mass index and poor performance status at baseline. A consistent decrease in bone mineral density was observed over time regardless of age, sex or disease status, resulting in an increase in the prevalence of osteoporosis over time (47% at baseline, 79% at 1 year, 88% at 2 years, 89% at 3 years, 95% at 4 years and 100% at 5 years). Changes in bone mineral density from baseline were greater in patients with locally-advanced pancreatic cancer, in those who received modified FOLFIRINOX or S-IROX for more than 3 months, and in those who received radiation therapy. Incident fractures developed in 45 patients (12%) during follow-up., Conclusions: Osteoporosis and osteoporotic fractures were highly prevalent in patients with advanced pancreatic cancer. This study highlights the importance of screening for osteoporosis in such patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The Japan Society of Clinical Oncology Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) have been published in accordance with the Minds Manual for Guideline Development 2014 and 2017. A specialized team independent of the working group for the revision performed a systematic review. Since GIST is a rare type of tumor, clinical evidence is not sufficient to answer several clinical and background questions. Thus, in these guidelines, we considered that consensus among the experts who manage GIST, the balance between benefits and harms, patients' wishes, medical economic perspective, etc. are important considerations in addition to the evidence. Although guidelines for the treatment of GIST have also been published by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), there are some differences between the treatments proposed in those guidelines and the treatments in the present guidelines because of the differences in health insurance systems among countries., (© 2024. The Author(s).)

Background: 10-mm self-expandable metal stents (SEMSs) are commonly used for preoperative biliary drainage in pancreatic cancer. However, smaller diameter SEMSs have attracted attention with the attempt to reduce stent-related adverse events (AEs)., Methods: We retrospectively analyzed consecutive borderline resectable pancreatic cancer patients who underwent neoadjuvant therapy and fully covered SEMS (FCSEMS) placement from April 2015 to May 2023. The primary outcome was stent-related non-event rate (NER), which was defined as the rate of completion of surgery without developing any preoperative events (recurrent biliary obstruction [RBO] or stent-related AEs). Secondary outcomes included stent-related AEs, causes of RBO, and cumulative incidence of RBO. Risk factors for pancreatitis, RBO, and stent migration were also examined., Results: A total of 76 patients were included (6-mm group: 23; 10-mm group: 53). Stent-related NER (57% vs. 64%, p = 0.610), stent-related AEs (4% vs. 15%, p = 0.263), overall RBO rates (39% vs. 23%, p = 0.168), cumulative incidence of RBO (hazard ratio, 2.24; 95% confidence interval, 0.95-5.25; p = 0.065) were not significantly different between the two groups. Tumor involvement of the pancreatic duct was identified as a risk-reducing factor for pancreatitis, while an FCSEMS diameter of 6 mm was not identified as a risk factor for RBO and stent migration., Conclusions: Stent-related NER was not significantly affected by FCSEMS diameter. Further studies are needed to confirm the usefulness of 6-mm diameter FCSEMS for preoperative biliary drainage in patients with borderline resectable pancreatic cancer., Competing Interests: Tsuyoshi Takeda and Takafumi Mie received honoraria from Boston Scientific Japan. Takashi Sasaki received honoraria from Boston Scientific Japan, Cook Medical Japan, and Century Medical., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background/aims: Hepaticojejunostomy anastomotic stricture (HJAS) is a feared adverse event associated with hepatopancreatobiliary surgery. Although balloon dilation for benign HJAS during endoscopic retrograde cholangiopancreatography with balloon-assisted enteroscopy has been reported to be useful, the treatment strategy remains controversial. Therefore, we evaluated the outcomes and risk factors of recurrent stenosis after balloon dilation alone for benign HJAS., Methods: We retrospectively analyzed consecutive patients who underwent balloon-assisted enteroscopy-endoscopic retrograde cholangiopancreatography for benign HJAS at our institution between July 2014 and December 2020., Results: Forty-six patients were included, 16 of whom had recurrent HJAS after balloon dilation. The patency rates at 1 and 2 years after balloon dilation were 76.8% and 64.2%, respectively. Presence of a residual balloon notch during balloon dilation was an independent predictor of recurrence (hazard ratio, 2.80; 95% confidence interval, 1.01-7.78; p=0.048), whereas HJAS within postoperative 1 year tended to be associated with recurrence (hazard ratio, 2.43; 95% confidence interval, 0.85-6.89; p=0.096). The patency rates in patients without a residual balloon notch were 82.1% and 73.1% after 1 and 2 years, respectively., Conclusion: Balloon dilation alone may be a viable option for patients with benign HJAS without residual balloon notches on fluoroscopy.

First-line chemotherapy has been established for advanced biliary tract cancer (BTC). However, few treatment options are available as second-line treatment. Advances in comprehensive genomic analysis revealed that nearly half of patients with BTC harbor targetable genetic alterations such as fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH), BRAF, human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI)-high, neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), and poly (adenosine diphosphate-ribose) polymerase (PARP). This review summarizes currently available options in precision medicine and clinical trials for patients with advanced BTC.

Background: Recent studies suggest that early tumor shrinkage (ETS) and depth of response (DpR) reflect outcomes of chemotherapy in various cancers. This study evaluated the association of ETS and DpR with clinical outcomes using data from JCOG1113, which demonstrated the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for chemotherapy-naïve advanced biliary tract cancer., Material and Methods: In total, 354 (289 with measurable target lesions) patients enrolled in JCOG1113 were divided into ETS-unachieved and ETS-achieved groups (≥20% tumor reduction at week 6) and DpR-low and DpR-high groups (≥40% maximum shrinkage) until 12 weeks after enrollment. The impact of ETS and DpR on survival outcome was evaluated using the multivariable Cox proportional hazard model., Results: The proportions of patients in the ETS-achieved and DpR-high groups were similar between the 2 treatment arms. The hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for the ETS-achieved group were 0.70 (95% confidence interval (CI), 0.52-0.93) and 0.60 (95%CI, 0.44-0.81), respectively. The HRs of PFS and OS for the DpR-high group were 0.67 (95%CI, 0.48-0.94) and 0.64 (95%CI, 0.46-0.90), respectively. In the subpopulation treatment effect pattern plot analysis, most patients in the ETS-achieved group in the GC arm did not experience disease progression after 12 weeks from the landmark., Conclusion: As on-treatment markers, ETS and DpR were effective tools. ETS was clinically useful, because it can be used to evaluate the outcomes of treatment early at a specific time., (© The Author(s) 2023. Published by Oxford University Press.)

Background/aims: Selective bile duct or pancreatic duct cannulation remains a significant initial hurdle in endoscopic retrograde cholangiopancreatography (ERCP) despite advances in endoscopy and accessories. This study evaluated our experience with a rotatable sphincterotome in cases of difficult cannulation., Methods: We retrospectively reviewed ERCP cases using TRUEtome, a rotatable sphincterotome, as a rescue device for cannulation at a cancer institute in Japan from October 2014 to December 2021., Results: TRUEtome was used in 88 patients. Duodenoscopes were used for 51 patients, while single-balloon enteroscopes (SBE) were used for 37 patients. TRUEtome was used for biliary and pancreatic duct cannulation (84.1%), intrahepatic bile duct selection (12.5%), and strictures of the afferent limb (3.4%). Cannulation success rates were similar in the duodenoscope and SBE groups (86.3% vs. 75.7%, p=0.213). TRUEtome was more commonly used in cases with steep cannulation angles in the duodenoscope group and in cases requiring cannulation in different directions in the SBE group. There were no significant differences in adverse events between the two groups., Conclusion: The cannulation sphincterotome was useful for difficult cannulations in both unaltered and surgically altered anatomies. It may be an option to consider before high-risk procedures such as precut and endoscopic ultrasound-guided rendezvous techniques.

Background: Pancreatic tail cancer (PTC) frequently displays splenic hilar involvement (SHI), but its impact on clinical outcomes remains unclear. We investigated the clinical impact of SHI in patients with unresectable PTC., Methods: We retrospectively reviewed all patients with unresectable PTC who received first-line therapy at our institution from 2016 to 2020., Results: Of the 111 included patients, 48 had SHI at diagnosis. SHI was significantly associated with younger age, liver metastasis, peritoneal dissemination, larger tumor size, modified Glasgow prognostic score of 1 or more, splenic artery involvement, gastric varices, and splenomegaly. Shorter median overall survival (OS; 9.3 vs. 11.6 months, p = 0.003) and progression-free survival (PFS; 4.3 vs. 6.3 months, p = 0.013) were observed in SHI patients. Poor performance status of 1 or 2, tumor size > 50 mm, hepatic metastasis, mGPS of 1 or 2, and SHI (hazard ratio: 1.65, 95% confidence interval: 1.08-2.52, p = 0.020) were independent predictors of shorter OS. Splenic artery pseudoaneurysm rupture and variceal rupture were rare and only observed in cases with SHI., Conclusions: Splenic hilar involvement is associated with worse outcomes in pancreatic tail cancer.

Objective: Pancreatic cancer with lung oligometastasis may have favourable overall survival. The aim of this study was to evaluate outcomes of pancreatic cancer with lung oligometastases including both synchronous and metachronous metastases., Methods: Consecutive pancreatic cancer patients with lung metastasis treated at our institution between February 2015 and December 2021 were identified from our prospectively maintained database. Clinical characteristics and outcomes were compared and analysed according to the extent of lung metastases. Predictors for overall survival were analysed using the Cox proportional hazards model., Results: A totoal of 171 patients were included (oligometastasis/polymetastasis/multi-organ metastasis: 34/50/87). Patients with oligometastases were more likely to undergo surgical resection (41% vs. 0% vs. 2%) and showed a longer median overall survival (41.3 vs. 17.6 vs. 13.1 months) compared with those with other types of metastases. Oligometastasis (hazard ratio, 0.43; 95% confidence interval, 0.24-0.76; P = 0.004) was identified as an independent factor predicting favourable overall survival in patients with lung-only metastasis. Disease status (synchronous vs. metachronous) was not associated with survival in patients with oligometastasis (29.4 vs. 41.3 months, P = 0.527) and polymetastasis (17.9 vs. 16.7 months, P = 0.545). Selected patients who underwent surgical resection showed a median overall survival of 52.7 months., Conclusions: Patients with lung oligometastases presented a favourable prognosis. Surgical resection in selected patients was associated with a long median overall survival., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The prognosis of advanced biliary tract cancer (BTC) patients remains poor due to limited efficacy of chemotherapy and difficulties in management. Thus, prediction of survival is crucial for the clinical management of advanced BTC. The aim was to develop and validate a nomogram to predict 6-month and 12-month survival in advanced BTC patients treated with chemotherapy. A multivariable Cox regression model was used to construct a nomogram in a training set (JCOG1113, a phase III trial comparing gemcitabine plus S-1 [GS] and gemcitabine plus cisplatin, n = 351). External validity of the nomogram was assessed using a test set (JCOG0805, a randomized, phase II trial comparing GS and S-1 alone, n = 100). Predictive performance was assessed in terms of discrimination and calibration. The constructed nomogram included lymph node metastasis, liver metastasis, carbohydrate antigen 19-9, carcinoembryonic antigen, albumin, and C-reactive protein. Uno's concordance index was 0.661 (95% confidence interval [CI] 0.629-0.696) in the training set and 0.640 (95% CI 0.566-0.715) in the test set. The calibration plots for 6-month and 12-month survival showed good agreement in the two analysis sets. The present nomogram can facilitate prediction of the prognosis of advanced BTC patients treated with chemotherapy and help clinicians' prognosis-based decision-making., (© 2023. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.

Background: Lenvatinib is an oral anticancer medication used to treat radioiodine-refractory thyroid cancer and unresectable hepatocellular carcinoma. The purpose of this study is to evaluate lenvatinib adherence by patients and to identify factors associated with decreased lenvatinib adherence., Methods: Among 153 patients who started treatment with lenvatinib for unresectable thyroid cancer or unresectable hepatocellular carcinoma between May 1, 2015 and August 31 2021 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 102 were eligible for this study (55 thyroid cancer, 47 hepatocellular carcinoma). The lenvatinib adherence rate in a treatment cycle was defined as the number of times a patient took lenvatinib in a 28-day cycle divided by the prescribed 28 doses. The rate was determined by pill counting and self-reporting at the pharmaceutical outpatient clinic. Reasons for non-adherence were established by interview and analyzed., Results: The median adherence rate of lenvatinib in the first cycle was 90.1% (n = 55) in thyroid cancer and 94.9% (n = 47) in hepatocellular carcinoma. In thyroid cancer, there were 255 incidents of lenvatinib non-adherence. Non-adherence was mainly associated with bleeding events (18.6%), followed by hand-foot skin reactions (10.6%). In hepatocellular carcinoma, there were 97 incidents of non-adherence. Hypertension accounted for 20.6%, followed by hoarseness (18.6%) and diarrhea (17.5%)., Conclusion: The adherence rate for lenvatinib in Japanese patients with thyroid and hepatocellular carcinoma in real-world clinical practice was more than 90% in this study. Hypertension was a major reason for non-adherence, followed by hand-foot skin reactions and diarrhea., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tateai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Osteosarcopenia is a newly described syndrome that has been reported to be associated with worse outcomes in various types of cancer. However, its impact on survival in biliary tract cancer remains unclear. This study evaluated the impact of osteosarcopenia on survival in patients with unresectable or recurrent biliary tract cancer., Methods: A total of 306 patients with unresectable or recurrent biliary tract cancer who initiated chemotherapy at our institution between 2015 and 2021 were retrospectively investigated. Skeletal muscle index and bone mineral density were measured using pretreatment cross-sectional computed tomography images. Baseline characteristics and survival outcomes were compared between patients with osteosarcopenia and those without. The Cox proportional hazards regression model was used to identify factors associated with survival., Results: Osteosarcopenia was present in 66 patients (22%) and was associated with older age (74 vs. 69 years, P < 0.001) and female sex (58 vs. 37%, P = 0.003). Patients with osteosarcopenia tended to have worse performance status (P = 0.098), higher modified Glasgow prognostic score (P = 0.082), higher neutrophil to lymphocyte ratio (P = 0.058) and were significantly less likely to receive combination chemotherapy (68 vs. 80%, P = 0.044) than those without. Osteosarcopenia was associated with reduced survival (8.9 vs. 14.0 months, P < 0.001) and was identified as an independent factor predicting shorter survival in multivariate analysis., Conclusions: Osteosarcopenia was associated with poor survival in unresectable or recurrent biliary tract cancer treated with chemotherapy. This study highlights the potential importance of screening for osteosarcopenia in patients with biliary tract cancer., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background/aim: FOLFIRINOX (FFX) is a standard treatment for patients with advanced pancreatic cancer. However, it often causes serious hematological adverse events. This study aimed to identify the risk factors for febrile neutropenia (FN) and grade 4 (G4) neutropenia during treatment with FFX in the real world., Patients and Methods: We analyzed data obtained from a nationwide multicenter observational study (JASPAC 06) that included 399 patients with unresectable or recurrent pancreatic cancer who received FFX at 27 institutions in Japan., Results: Nadir neutrophil counts occurred from day 8 to day 22 of cycle 1, and granulocyte colony-stimulating factor was administered to over a quarter of the patients in the first cycle. Of 399 patients, FN and G4 neutropenia occurred in 51 (13%) and 108 (27%) patients, respectively. Most FN (83%) and G4 neutropenia (75%) occurred in the first or second cycles. Multivariate logistic regression analyses showed that total bilirubin (TB) > the upper limit of normal range (ULN) and no dose modification from the original regimen were significantly associated with FN, and that TB > ULN, no dose modification from the original regimen, low platelet count (<15×10 4 /μl), and recurrent disease after pancreatectomy were independent risk factors for G4 neutropenia., Conclusion: No dose modification from the original regimen and TB > ULN were risk factors for FN and G4 neutropenia., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer displaying no definitive direction of differentiation. UC has been reported as a highly aggressive malignant neoplasm, with a median overall survival of <1 year, except for several surgical series. On the other hand, UC tissue sometimes contains non-neoplastic osteoclast-like giant cells (OGCs), and such cases have been reported to have relatively longer survival. Thus, the World Health Organization (WHO) classification histologically distinguishes UC with OGCs (UCOGCs) from UC, and UCs were subclassified into three subtypes: anaplastic UC, sarcomatoid UC and carcinosarcoma. However, still less is known about UC due to its rarity, and such situations lead to further difficulties in treatment for UC. To date, only surgical resection can offer curative treatment for patients with UC, and no clear evidence for chemotherapy exists for them. However, a retrospective cohort study and case reports showed that relatively promising results paclitaxel-containing regimens for treatment of patients with unresectable UC. Furthermore, high programmed cell death protein 1 expression has been reported in sarcomatoid UCs and UCOGCs, and promising responses to anti-programmed death-ligand 1 therapy have been described in case reports of UCOGCs. Recent advances in chemotherapeutic agents and molecular technologies are opening up the possibilities for expanded treatments., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: The efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) in the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) has been reported. NAC-GS is now assumed to be a standard regimen for resectable PDAC in Japan. However, the reason for this improvement in prognosis remains unclear., Methods: In 2019, we introduced NAC-GS for resectable PDAC. From 2015 to 2021, 340 patients were diagnosed with resectable PDAC (anatomical and biological [carbohydrate antigen (CA) 19-9 < 500 U/mL]) and were divided according to the treatment period (upfront surgery [UPS] group, 2015-2019, n = 241; NAC-GS group, 2019-2021, n = 80). We used "intention-to-treat" analysis to compare the clinical outcomes of NAC-GS to those of UPS., Results: Of the 80 patients with NAC-GS, 75 (93.8%) completed two cycles of NAC-GS, and the resection rate of the NAC-GS group was comparable to that of the UPS group (92.5 vs. 91.3%, P = 0.73). The R0 resection rate was significantly higher in the NAC-GS group than in the UPS group (91.3 vs. 82.6%, P = 0.04), even though the surgical burden was smaller. Progression-free survival tended to be better (hazard ratio [HR] = 0.70, P = 0.06), and overall survival was significantly better in the NAC-GS group than in the UPS group (HR 0.55, P = 0.02)., Conclusions: NAC-GS provided improvements in microscopic invasion leading to a high R0 rate and smooth administration and completion of adjuvant therapy, which might lead to an improved prognosis in patients with resectable PDAC., (© 2023. Society of Surgical Oncology.)

Objective: JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment., Methods: All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil-lymphocyte ratio, at the baseline on overall survival. P values <0.1 for the interaction were regarded as denoting significant association., Results: Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95% confidence interval, 0.82-2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95% confidence interval, 0.24-1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein >10 mg/L and/or albumin <35 g/L) (n = 7/15) (P-interaction = 0.06). C-reactive protein alone and albumin alone also showed significant treatment interactions for overall survival., Conclusions: Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The safety and effectiveness of chemotherapy in elderly patients with biliary tract cancer (BTC) remain unclear. Therefore, we retrospectively reviewed patients who underwent chemotherapy for locally advanced, metastatic, or recurrent BTC at our institution from January 2016 to December 2021. Of the 283 included patients, 91 (32.5%) were aged 75 years or older when initiating chemotherapy. Elderly patients were more likely than non-elderly patients to receive monotherapy with gemcitabine or S-1 (58.7% vs. 9.4%, p < 0.001) and were less likely to experience grade 3-4 toxicities (55.4% vs. 70.2%, p = 0.015). The rates of termination due to intolerance (6.5% vs. 5.8%, p = 0.800) and transition to second-line chemotherapy (39.1% vs. 40.3%, p = 0.849) were similar between groups. In the overall cohort, age was not an independent predictor of overall survival (OS). Within the elderly cohort, there were no differences in severe adverse events between patients receiving monotherapy and combination therapy (50.0% vs. 63.2%, p = 0.211). Median OS was longer in the combination therapy group (10.4 vs. 14.1 months; p = 0.010); however, choice of monotherapy was not an independent predictor of overall survival. Monotherapy appears to be a viable alternative in selected elderly BTC patients.

Objective Anamorelin, a novel selective ghrelin receptor agonist, was approved in Japan for the treatment of cachexia in pancreatic cancer (PC), albeit with limited evidence. This study evaluated the efficacy and safety of anamorelin in PC and examined the impact of the extent of weight loss on the efficacy of anamorelin. Methods We retrospectively investigated consecutive PC patients with cachexia who received anamorelin at our institution between June 2021 and January 2022. Patients were divided into two groups: moderate-weight-loss group (5-10%) and severe-weight-loss group (>10%). The primary outcome was changes in body weight. The secondary outcomes were changes in appetite and laboratory measures as well as treatment-related severe adverse events. Results A total of 24 patients were included (moderate/severe weight loss: 8/16). The moderate-weight-loss group showed significantly more weight gain than the severe-weight-loss group. Improvements in appetite were consistently observed in each weight-loss group. Changes in laboratory markers were not significantly different between groups. Hyperglycemia (four patients) was the most common cause of severe adverse events, followed by abdominal distension, nausea, elevated liver function tests, and bulimia. Conclusion The efficacy of anamorelin was associated with the extent of weight loss. Although anamorelin improved appetite in each weight-loss group, it increased body weight only in the moderate-weight-loss group. Anamorelin was well-tolerated among advanced PC patients, although caution must be practiced when it is used in patients with concomitant diabetes mellitus.

Background: Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer., Methods: KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m 2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m 2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636., Findings: Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group; n=533) or placebo plus gemcitabine and cisplatin (placebo group; n=536). Median study follow-up at final analysis was 25·6 months (IQR 21·7-30·4). Median overall survival was 12·7 months (95% CI 11·5-13·6) in the pembrolizumab group versus 10·9 months (9·9-11·6) in the placebo group (hazard ratio 0·83 [95% CI 0·72-0·95]; one-sided p=0·0034 [significance threshold, p=0·0200]). In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4. 31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events., Interpretation: Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA., Competing Interests: Declaration of interests RKK, MU, CY, RSF, JF, ZR, TY, H-JK, SLC, MO, CV, MB, JOP, OB, UP, JWV, JE, and AV report funding to their institution from Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA (MSD), to support conduct of this study. All authors received medical writing and editorial support for the preparation of this manuscript from MSD. RKK additionally reports advisory committee membership for MSD; grants or contracts to their institution from Agios, AstraZeneca, Bayer, BMS, Eli Lilly, EMD Serono, Genentech/Roche, Loxo Oncology, MSD, Novartis, Partner Therapeutics, QED, Relay Therapeutics, Surface Oncology, and Taiho; consulting fees (advisory board payments) to themself from Compass Therapeutics, Kinnate, Exact Sciences, Regeneron, and Tyra Biosciences; consulting fees (advisory board or steering committee payments) to their institution from Agios, AstraZeneca, Exelixis, Ipsen, and MSD; travel support from AstraZeneca and MSD; participation on a data safety monitoring board (uncompensated) for Genentech/Roche and MSD; being a scientific and medical advisory board co-chair (uncompensated) for the Cholangiocarcinoma Foundation; and member of governance board (uncompensated) for the International Liver Cancer Association. MU additionally reports grants or contracts to their institution from Taiho Pharmaceutical, AstraZeneca, Merck Biopharma, MSD, Astellas Pharma, Eisai, Ono Pharmaceutical, Daiichi Sankyo, Novartis, Boehringer Ingelheim, and J-pharma; and payment or honoraria to themself from Taiho Pharmaceutical, AstraZeneca, Yakult Honsha, MSD, Nihon Servier, Ono Pharmaceutical, Incyte, Chugai Pharmaceutical, Boehringer Ingelheim, J-pharma, Takeda Pharmaceutical, Mylan EPD, Delta-Fly Pharma, and Novartis. CY additionally reports grants or contracts to themself from Servier, Bayer, AstraZeneca, Ono Pharmaceuticals, Celgene, Ipsen, Boryung Pharmaceuticals, Ildong Pharmaceuticals, CKD Pharmaceuticals, and HK inno.N; consulting fees to themself from Servier, Bayer, AstraZeneca, MSD, Eisai, Celgene, Bristol Myers Squibb, Debiopharm, Ipsen, Kyowa Kirin, Novartis, Boryung Pharmaceuticals, Merck Serono, Mundipharma, Roche, and Janssen; and payment or honoraria to themself from Servier, Bayer, AstraZeneca, MSD, Eisai, Celgene, Bristol Myers Squibb, Debiopharm, Ipsen, Kyowa Kirin, Novartis, Boryung Pharmaceuticals, Merck Serono, Mundipharma, Roche, and Janssen. RSF additionally reports grants or contracts to their institution from Adaptimmune, Bayer, Bristol Myers Squibb, Eisai, Eli Lilly, Pfizer, Roche, and Genentech; consulting fees to themself from AstraZeneca, Bayer, Bristol Myers Squibb, Exelixis, Cstone, Hengrui, Eisai, Eli Lilly, MSD, Pfizer, Roche, and Genentech; payment or honoraria to themself from Genentech; and participation on a data safety monitoring or advisory board from AstraZeneca, and Hengrui. JF additionally reports grants or contracts from Astellas, AstraZeneca, Incyte Biosciences Japan, Eisai, MSD, Ono Pharmaceutical, Sanofi, J-Pharma, Daiichi Sankyo, Sumitomo Dainippon, Taiho Pharmaceutical, Takeda, Delta-Fly Pharma, and Chugai Pharma; payment or honoraria from Ono Pharmaceutical, Chugai Pharmaceutical, Incyte Biosciences Japan, Eisai, Eli Lilly Japan, AstraZeneca, Yakult Honsha, Servier Japan, MSD, Novartis Pharma, Takeda, Bayer, Taiho Pharmaceutical, EA Pharma, Teijin Pharma, Daiichi Sankyo, and Terumo; and participation on a data safety monitoring board or advisory board from Onco Therapy Science, Chugai Pharma, Astellas, AstraZeneca, Takara Bio, Merck Bio, MSD, and Taiho Pharmaceutical. ZR additionally reports consulting fees from MSD, AstraZeneca, and Roche and payment or honoraria for lectures from Bayer, MSD, and Roche. TY additionally reports consulting fees from BMS, MSD, AstraZeneca, Eisai, and Ipsen; support for attending meetings or travel from Roche and Bayer; stock or stock options in Moderna; medical writing support from Taiho and Ispen; and payments to their institution for clinical trial investigatorship from BMS, MSD, Exelixis, Eli Lilly, AstraZeneca, Roche, and Taiho. H-JK additionally reports payment or honoraria to their institution from MEDtalks and Ipsen and payments made to their institution for participation on an advisory board from AstraZeneca, Janssen, MSD, and Ipsen. SLC additionally reports consulting fees to themself from MSD, AstraZeneca, Eisai, Roche, and Bayer; payment or honoraria to themself from MSD, AstraZeneca, Eisai, Roche, and Bristol Myers Squibb; and support for attending meetings or travel from Ipsen and Novartis. MO additionally reports payment or honoraria from Taiho Pharmaceutical, Yakult Honsha, MSD, Ono Pharmaceutical, Nihon, Servier, Bayer, and Pfizer. CV additionally reports consulting fees from Bayer, MSD, Roche, Ipsen, and AstraZeneca; and payment or honoraria from Bayer, MSD, Roche, Ipsen, and AstraZeneca. MB additionally reports consulting fees from Bayer Pharma, MSD, Eisai, Sirtex Medical, BMS, Roche, and AstraZeneca; and payment or honoraria from Bayer Pharma, MSD, Sirtex Medical, BMS, Roche, and AstraZeneca. JOP additionally reports grants or contracts from BMS (Celgene), Servier, MedPacto, Eutilex, and ABL Bio; support for attending meetings or travel from Minneamrita Therapeutics; and participation on a data safety monitoring board or advisory board for AstraZeneca, Adicet, and Merck Serono. JWV additionally reports consulting fees to themself from Ipsen, Novartis, AstraZeneca, Merck, Pfizer, PCI Biotech, Incyte, Keocyt, QED Therapeutics, Pieris Pharmaceuticals, Genoscience Pharma, Mundipharma, Wren Laboratories, Nucana, Debiopharm Group, Imaging Equipment Limited, Hutchison MediPharma, Zymeworks, Aptitude Health, Sirtex Medical, Baxter, Medivir, Cantargia AB, Autem Medical, Taiho Oncology, Servier, and Boehringer Ingelheim; payments to themself for speakers bureaus from Novartis, Ipsen, Nucana, Imaging Equipment Limited, Mylan, Incyte, Servier, and Delcath Systems; and support for attending meetings or travel from Nucana, Lilly, Roche, and AstraZeneca/MedImmune. LY reports salary for full-time employment from MSD. UM reports salary for full-time employment from MSD and stock ownership in Merck & Co, Rahway, NJ, USA. ABS reports salary for full-time employment from MSD and stock ownership in Merck & Co, Rahway, NJ, USA. JE additionally reports grants or contracts from BMS, Beigene, and Boston Scientific; and payment or honoraria from MSD, Eisai, BMS, AstraZeneca, Bayer, Roche, Ipsen, Basilea, Merck Serono, Incyte, Servier, Beigene, Taiho, and Boston Scientific. AV additionally reports consulting fees to themself from AstraZeneca, Amgen, Beigene, Böhringer Mannheim, BMS, BTG, Daiichi Sankyo, Eisai, Incyte, Ipsen, MSD, Pierre Fabre, Roche, Servier, Sirtex, Taiho, and Terumo; payment or honoraria to themself from AstraZeneca, Amgen, Beigene, Böhringer Mannheim, BMS, BTG, Daiichi Sankyo, Eisai, GSK, Imaging Equipment (AAA), Incyte, Ipsen, Jiangsu Hengrui Medicines, MSD, Pierre Fabre, Roche, Servier, Sirtex, Taiho, and Terumo; and participation on a data safety monitoring board or advisory board from AstraZeneca, Amgen, Beigene, Böhringer Mannheim, BMS, BTG, Daiichi Sankyo, Eisai, Incyte, Ipsen, MSD, Pierre Fabre, Roche, Servier, Sirtex, Taiho, and Terumo. OB and UP report no additional competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: This study investigates the use of serum DUPAN-2 in predicting the PC progression in CA19-9 nonsecretors., Background: Although we previously reported that serum CA19-9 >500U/ mL is a poor prognostic factor and an indication for enhanced neoadjuvant treatment, there is not a biomarker surrogate that equivalently predicts prognosis for CA19-9 nonsecretors., Methods: We evaluated consecutive PC patients who underwent pancreatectomy from 2005 to 2019. All patients were categorized as either nonsecretor or secretor (CA19-9 ≤ or >2.0U/mL)., Results: Of the 984 resected PC patients, 94 (9.6%) were nonsecretors and 890 (90.4%) were secretors. The baseline characteristics were not statistically different between the 2 groups except for the level of DUPAN-2 (720 vs. 100U/mL, P < 0.001). Survival curves after resection were similar between the 2 groups (29.4 months vs. 31.3 months, P = 0.900). Survival curves of patients with DUPAN-2 >2000U/mL in the nonsecretors and patients with CA19-9 >500U/mL in the secretors were nearly equivalent as well (hazard ratio 2.08 vs. 1.89). In the multivariate analysis, DUPAN-2 >2000U/mL (hazard ratio 2.53, P = 0.010) was identified as independent prognostic factor after resection., Conclusion: DUPAN-2 >2000U/mL in CA19-9 nonsecretors can be an unfavorable factor that corresponds to CA19-9 >500U/mL in CA19-9 secretors which is an indicator for enhanced neoadjuvant treatment. The current results shed light on the subset of nonsecretors with poor prognosis that were traditionally categorized in a group with a more favorable prognosis group., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The use of duckbill-type anti-reflux metal stents (DMS) in reinterventions after covered metal stent (CMS) dysfunction has been reported in patients with distal malignant biliary obstruction (MBO). However, the superiority of DMS over conventional CMS (c-CMS) has not been established. Therefore, we conducted this retrospective study to evaluate the long-term efficacy and safety of DMS as a second stent in comparison with c-CMS., Methods: We investigated consecutive patients with distal MBO due to unresectable pancreatic cancer who underwent reintervention after dysfunction of initial biliary CMS at our institution. We compared causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates of DMS and c-CMS in this stenting., Results: A total of 76 patients were included (DMS 41 and c-CMS 35). While overall RBO rates were similar between the two groups (46% vs. 63%, p = 0.172), RBO due to non-occlusion cholangitis tended to be less frequent in the DMS group than in the c-CMS group (2% vs. 14%, p = 0.089). Median TRBO was significantly longer in the DMS group (286 days vs. 112 days, p = 0.029). DMS was identified as the only significant risk factor for TRBO (hazard ratio, 0.52; p = 0.044). Overall AE rates were significantly lower in the DMS group (2% vs. 23%, p = 0.010), with non-occlusion cholangitis being the most common AE in the c-CMS group. Endoscopic reintervention was successfully performed in all patients in both groups, despite failed stent removal in 15% of patients in DMS group., Conclusions: DMS was associated with a significantly longer TRBO and lower rate of AEs compared with c-CMS in reinterventions after initial CMS dysfunction. DMS may be preferable to c-CMS as a second stent after biliary CMS dysfunction., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Tumor rupture has been indicated as a risk factor for recurrence of gastrointestinal stromal tumors (GISTs). The universal definition of tumor rupture was proposed. This study evaluated whether the universal definition was more accurate in identification of GISTs with high recurrent risk than subjective judgment., Methods: The study included 507 patients with high-risk GISTs who underwent complete resection between December 2012 and December 2015. We conducted a questionnaire survey in participating institutes to re-diagnose tumor rupture based on the universal definition according to their surgical and pathological findings. We compared the clinical outcomes of tumor rupture based on the definition to those based on the surgeon's judgment and clarified the clinical importance of the rupture., Results: Sixty-four patients were initially registered to have tumor rupture by surgeon's judgment, and it became 90 patients who had tumor rupture after reevaluation. Although there were significant differences in recurrence-free survival (RFS) between no rupture and rupture for both initial registration and reevaluation ( p  = 0.002, <0.001, respectively), a significant difference in overall survival was only observed after reevaluation ( p  = 0.011). Tumor rupture was significantly associated with large tumor size, mixed cell type in histology, R1 resection, frequent adjuvant therapy and recurrence, but not with location, mitosis, and genotype. Adjuvant therapy more than 3 years improved RFS of patients with tumor rupture., Conclusion: This study suggested that tumor rupture based on the universal definition more accurately identified GISTs with poor prognostic outcomes than the subjective judgment., Competing Interests: One of the co‐authors of this manuscript is Editor in Chief of Annals of Gastroenterological Surgery. Coauthor Y. K. is Editor in Chief of Annals of Gastroenterological Surgery. Coauthor M. O. was supported by lecture fees etc. from Taiho Pharmaceutical, Yakult Honsha, MSD, Ono Pharmaceutical, Nihon Servier, Bayer and Pfizer. Coauthor Y. K. was supported by lecture fees etc. from Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, and Chugai Pharmaceutical, and by research expenses or scholarship donations (grants) from Ono Pharmaceutical, IQVIA, Astellas, Taiho Pharmaceutical, Daiichi Sankyo, Chugai Pharmaceutical, EPS, Shionogi, Nippon Zoki, Asahi Kasei and Nippon Kayaku. Coauthor H. C. was supported by research expenses or scholarship donations (grants) from Novartis., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Background: Osteosarcopenia, defined as the combination of osteoporosis and sarcopenia, has recently gained attention as a novel prognostic factor for survival in patients with cancer. This study aimed to evaluate the prognostic impact of osteosarcopenia in metastatic pancreatic cancer (PC)., Methods: We retrospectively investigated consecutive metastatic PC patients receiving first-line gemcitabine plus nab-paclitaxel (GnP). Skeletal muscle index at the third lumbar vertebra and bone mineral density at the first lumbar vertebra were measured using pretreatment computed tomography. Treatment outcomes of osteosarcopenia and non-osteosarcopenia groups were compared and analyzed. Multivariate analysis was performed to identify variables associated with survival., Results: Among 313 patients, osteosarcopenia was present in 59 patients (19%). The osteosarcopenia group was associated with older age, higher proportion of females, worse performance status, and higher modified Glasgow prognostic scores (mGPS). Response rates to chemotherapy, progression-free survival (3.5 months vs. 6.4 months, p < 0.001), and overall survival (5.6 months vs. 13.0 months, p < 0.001) were significantly better in the non-osteosarcopenia group. Osteosarcopenia, performance status of 1-2, mGPS score of 1-2, carcinoembryonic antigen ≥10 ng/mL, and carbohydrate antigen 19-9 ≥ 1000 IU/mL were identified as independent factors predicting shorter survival. Grade 3 or higher anemia and febrile neutropenia occurred more frequently in the osteosarcopenia group., Conclusions: Osteosarcopenia was associated with poor survival in metastatic PC treated with first-line GnP. Screening for osteosarcopenia may be helpful for better management of metastatic PC., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: Clinical Practice Guidelines for Pancreatic Cancer was first published in 2006 by the Japan Pancreas Society, and revised in 2009, 2013, 2016, and 2019. In July 2022, Clinical Practice Guidelines for Pancreatic Cancer was newly revised in Japanese., Methods: For this revision, we developed an entirely new guideline according to the Minds Manual for Guideline Development 2020, which includes the concepts of GRADE-Grading Recommendations Assessment, Development, and Evaluation, to enable a better understanding of the current guidelines. Patients and the public were actively involved in both the development and implementation of the guideline., Results: The guideline includes algorithms for diagnosis, treatment, chemotherapy, and precision medicine of pancreatic cancer, and addresses 7 subjects: diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, stent therapy, and supportive & palliative medical care. It includes 73 clinical questions and 112 statements. The statements correspond to the clinical questions, evidence levels, recommendation strengths, and agreement rates., Conclusions: This guideline represents the most standard clinical and practical management guideline available until date in Japan. This is the English synopsis of the Clinical Practice Guidelines for Pancreatic Cancer 2022 in Japanese, and is an attempt to disseminate the Japanese guideline worldwide to introduce the Japanese approach to the clinical management of pancreatic cancer., (© 2023. The Author(s).)

Intraductal self-expandable metal stent (SEMS) placement may prolong stent patency by reducing duodenobiliary reflux. This study aimed to evaluate the efficacy and safety of this biliary drainage method in patients with unresectable distal malignant biliary obstruction (MBO). Consecutive patients with unresectable MBO who underwent initial covered SEMS placement between 2015 and 2022 were retrospectively reviewed. We compared the causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates between two biliary drainage methods (SEMSs placed above and across the papilla). A total of 86 patients were included (above: 38 and across: 48). Overall RBO rates (24% vs. 44%, p = 0.069) and median TRBO (11.6 months vs. 9.8 months, p = 0.189) were not significantly different between the two groups. The frequency of overall AEs was similar between the two groups in the entire cohort, but was significantly lower in patients with non-pancreatic cancer (6% vs. 44%, p = 0.035). Reintervention was successfully performed in the majority of patients in both groups. Intraductal SEMS placement was not associated with a prolonged TRBO in this study. Larger studies are warranted to further evaluate the benefit of intraductal SEMS placement.

Aim: We compared the efficacy of modified 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) with that of gemcitabine plus nab-paclitaxel (GnP) for locally advanced pancreatic cancer (LAPC)., Methods: Patients with untreated LAPC were randomly assigned (1:1) to receive mFOLFIRINOX or GnP. One-year overall survival (OS) was the primary endpoint. The major secondary end-points included progression-free survival (PFS), response rate (RR), carbohydrate antigen 19-9 (CA19-9) response, and adverse events. The sample size was 124 patients to select a more effective regimen with a minimum probability of 0.85 and to examine the null hypothesis of the 1-year OS <53%., Results: Of the 126 patients enrolled from 29 institutions, 125 were deemed eligible. The 1-year OS was 77.4% (95% CI, 64.9-86.0) and 82.5% (95% CI, 70.7-89.9) in the mFOLFIRINOX and GnP arms, respectively. The median PFS was 11.2 (95% CI, 9.9-15.9) and 9.4 months (95% CI, 7.4-12.8) in the mFOLFIRINOX and GnP arms, respectively. The RR and CA19-9 response rate were 30.9% (95% CI, 19.1-44.8) and 57.1% (95% CI, 41.0-72.3) and 42.1% (95% CI 29.1-55.9) and 85.0% (95% CI, 70.2-94.3) in the mFOLFIRINOX and GnP arms, respectively. Grade 3-4 diarrhoea and anorexia were predominant in the mFOLFIRINOX arm., Conclusion: GnP was considered the candidate for a subsequent phase III trial because of its better RR, CA19-9 response, and mild gastrointestinal toxicities. Both regimens displayed higher efficacy in the 1-year survival than in the historical data of gemcitabine monotherapy., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Duckbill-type metal stent (DMS) was the first laser-cut biliary metal stent with an anti-reflux valve. Removal of DMS is believed to be difficult and relevant reports are scarce. This study aims to investigate the feasibility of DMS removal., Methods: We retrospectively analyzed patients who underwent DMS removal between June 2019 and March 2022 to evaluate success rates and factors affecting outcomes. In addition, six different methods of DMS removal were reproduced in vitro, varying removal devices, angle of applied force, and grasped location. Extraction resistance, the distance of forceps stroke, and stent length after removal were compared., Results: Forty patients were enrolled, and DMS removal was successful in 31 cases (78%). No adverse events were observed. Tumor ingrowth was evident in 78% (7/9) of failed cases. Patients receiving biliary metal stents for the first time (naïve cases), long indwelling time, longer stent, and stent tearing during removal were associated with unsuccessful stent removal. In the in vitro study, a larger force was required to remove the stent at an extraction angle of 120° than at 0°. Among cases in which force was applied at 120°, the load tended to be lower when rat-tooth forceps were applied horizontally across the stent., Conclusions: Stent removal was possible in a majority of cases. Deployment of additional stents inside DMS may be preferable to forceful removal in the presence of factors associated with difficult stent removals, such as tumor ingrowth, naïve cases, longer stents, long indwelling time, and stent tearing during removal., Competing Interests: Three staff members of SB‐Kawasumi Laboratories, Inc (Keisuke Yatsuo, Tomoaki Yokota, and Tomokazu Mukai) conducted in vitro study with two doctors (Yuto Yamada and Takashi Sasaki). All these staff members of SB‐Kawasumi Laboratories, Inc were not involved in data interpretation or manuscript writing. The authors except for the staff members of SB‐Kawasumi Laboratories, Inc declare no conflict of interest., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Perivascular epithelioid cell tumors, also known as PEComas, are rare mesenchymal tumors composed mainly of epithelioid cells found in perivascular tissue. PEComas occur most frequently in the kidney, uterus, the gastrointestinal tract, liver, and retroperitoneum; those originating in the biliary tree are extremely rare. We report a case of benign PEComa of the cystic duct with positive TFE3 staining on immunohistochemistry.A 66-year-old woman was referred for a 20 mm mass adjacent to the common bile duct discovered incidentally on abdominal ultrasound. Laboratory data including tumor markers were unremarkable. The tumor appeared to arise from the cystic duct, showed early enhancement, and compressed the common bile duct on imaging studies. Endoscopic ultrasound-guided fine-needle aspiration revealed round- and spindle-shaped atypical cells with eosinophilic cytoplasm and brown deposits suggestive of melanin granules. Histological examination of the resected specimen revealed a tumor consisting of epithelioid cells forming an alveolar structure, with melanin pigmentation. Immunohistochemistry was positive for HMB-45 and TFE3, consistent with benign pigmented PEComa of the cystic duct. Melanotic, myogenic, and TFE3 staining are helpful when diagnosing PEComas arising in unusual locations., (© 2022. Japanese Society of Gastroenterology.)

Background: Liver oligometastatic pancreatic cancer (PC) may have favorable outcomes. This study aims to evaluate outcomes and factors associated with overall survival (OS) of these patients., Methods: We retrospectively investigated consecutive PC patients with liver metastasis treated at our institution between 2013 and 2020. Clinical characteristics and outcomes were compared and analyzed according to the extent of liver metastasis. Cox proportional hazards model was used to identify prognostic factors for OS., Results: A total of 417 patients were included (multi-organ metastasis/polymetastasis/oligometastasis 174/158/85). Oligometastasis showed a longer OS compared to other types of metastases (7.7 vs 8.2 vs 13.1 months). Age <70 years, performance status of 0, modified Glasgow prognostic score of 0, carbohydrate antigen 19-9 <1000 U/mL were identified as significant prognostic factors for OS. A prognostic index consisting of these four factors successfully stratified the prognosis of these patients (prognostic index; high vs low, 19.9 vs 8.3 months). Highly selected patients who underwent surgical resection showed a median OS of 54.6 months., Conclusions: Oligometastasis presented a relatively favorable outcome. Our new prognostic index was useful in stratifying the prognosis of these patients. Multimodal treatment including surgery may have additional survival benefits for highly selected patients., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The usefulness of duckbill-type anti-reflux metal stent (DMS) in self-expandable metal stent-naïve pancreatic cancer (PC) patients has not been well-studied. This study aimed to evaluate the efficacy and safety of DMS in such patients., Methods: We analyzed consecutive patients with unresectable PC who received a covered metal stent (CMS) as the initial self-expandable metal stent at our institution. Technical success, functional success, causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates were compared between DMS and conventional CMS (c-CMS)., Results: A total of 69 patients were included (DMS: 28, c-CMS: 41). Technical success, functional success, and AEs were similar between groups. Tumor ingrowth was more common in the DMS group (18% vs. 0%, p = 0.009), while non-occlusion cholangitis tended to be more common in the c-CMS group (0% vs. 15%, p = 0.074). Median time to RBO was similar between groups (276 vs. 273 days, p = 0.915). The anti-reflux valve of DMS was found torn in 56% of patients. Endoscopic reintervention was successful in all cases, despite failed stent removal in 88% of patients in the DMS group., Conclusions: DMS was not associated with longer time to RBO compared to c-CMS in self-expandable metal stent-naïve patients., Competing Interests: None., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Outcomes and prognostic factors of second-line gemcitabine plus nab-paclitaxel (GnP) after modified FOLFIRINOX (mFFX) for unresectable pancreatic cancer were unclear. We retrospectively analyzed consecutive patients with unresectable pancreatic cancer treated with GnP after first-line mFFX treatment between March 2015 and March 2022 at our hospital. A total of 103 patients were included. Median overall survival (OS) from the start of first-line and second-line treatments was 14.9 months and 7.2 months, respectively. Median progression-free survival (PFS) was 3.6 months. Performance status, modified Glasgow prognostic score, and neutrophil-to-lymphocyte ratio were independently associated with OS. Our prognostic model using these parameters classifies patients into good (n = 70) and poor (n = 33) prognosis groups. Median OS and PFS were longer in the good prognosis group than in the poor prognosis group (OS: 9.3 vs. 3.8 months, p < 0.01; PFS: 4.1 vs. 2.3 months, p < 0.01). Grade 3/4 adverse events were observed in 70.9% of patients, with neutropenia being the most frequent. While GnP as second-line treatment was well-tolerated, efficacy of second-line gemcitabine plus nab-paclitaxel was notably limited, particularly in the poor prognosis group.

Background: Outcomes of partially covered self-expandable metal stents (SEMS) as an additional stent after recurrent duodenal obstruction (RDO) have not been elucidated. In this study, we compared outcomes of partially covered and uncovered SEMS placement after RDO in patients with malignant duodenal obstruction and explored factors affecting re-recurrent obstruction and overall survival in this population., Methods: We conducted a retrospective study of patients undergoing SEMS placement for RDO at a cancer institute in Japan from July 2014 to June 2021. Clinical variables and outcomes of patients undergoing partially covered and uncovered SEMS placement were compared., Results: Sixty-one patients underwent SEMS placement after RDO, for which the COMVI stent was used in 38 cases and uncovered stents were used in 23 cases. Stent ingrowth was the most common cause of RDO (51.4%). Stent migration only occurred after partially covered stent placement (20% vs. 0%, p = 0.018). Choice of SEMS had no impact on time to re-RDO (median 2.8 vs. 4.1 months, p = 0.776) or overall survival (median 2.6 vs. 2.4 months, p = 0.703). Median overall survival was longer in patients receiving chemotherapy after second stenting (4.6 vs. 1.8 months, p < 0.001) and shorter in those with early RDO, regardless of the SEMS used. Use of the partially covered stent had no impact on survival or time to RDO., Conclusions: While outcomes after partially covered SEMS placement for RDO were not significantly different from uncovered SEMS, migration remains a concern when they are used as a second stent. Chemotherapy after second stenting was associated with longer overall survival but not with longer time to re-RDO., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate long-term outcomes of endoscopic double stenting using anti-reflux metal stents (ARMS) for combined malignant biliary and duodenal obstruction., Methods: Consecutive patients with advanced pancreatic cancer who received endoscopic double stenting with self-expandable metal stents (SEMS) for combined malignant biliary and duodenal obstruction at our institution between July 2014 and March 2021 were evaluated. Patients were divided into the ARMS group, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) group, and covered metal stent-transpapillary (CMS-transpapillary) group. A Duckbill-type metal stent was used in all ARMS cases., Results: Thirty-eight patients were enrolled: ARMS group (n = 16), EUS-HGS group (n = 13), and CMS-transpapillary group (n = 9). Overall survival among three groups were not significantly different. Recurrent biliary obstruction (RBO) rates of the ARMS, EUS-HGS, and CMS-transpapillary groups were 12.5%, 61.5%, and 88.9% (P < .01) and median time to recurrent biliary obstructions (TRBOs) were not reached, 125 days, and 7 days (P < .01). Median TRBOs of ARMS-choledochoduodenostomy and ARMS-transpapillary were not statistically different. Major causes of RBO were stent occlusion and symptomatic stent migration in the ARMS group, hyperplasia in the EUS-HGS group, and non-occlusion cholangitis in the CMS-transpapillary group., Conclusions: Endoscopic double stenting with ARMS might be an option for combined malignant biliary and duodenal obstruction., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Neoadjuvant chemotherapy (NAC) is widely used to treat borderline resectable pancreatic cancer. This study aimed to evaluate the serum carbohydrate antigen (CA)19-9 response, in association with survival, after four cycles of NAC-gemcitabine plus nab-paclitaxel., Methods: From 2015 to 2018, patients with borderline resectable pancreatic cancer were treated with NAC. Patients were stratified into two groups after excluding CA19-9 non-secretor: Group L (CA19-9 ≥2 and ≤500 U/mL) and Group H (CA19-9 >500 U/mL). The CA19-9 decrease during NAC was evaluated as a response of NAC and was assessed in association with survival concomitant with other prognosis factors., Results: Eighty-seven patients were evaluated (Group L: n = 43, Group H: n = 44). In intention-to-treat-based analysis, Group L exhibited significantly better progression-free survival (PFS) than Group H (median PFS: 24 vs 14months). In resection cohort, no correlation was detected between the CA19-9 decrease and survival in Group L. In Group H, the CA19-9 decrease ≤80% was associated with unfavorable survival in multivariate analysis [Hazard ratio: 4.738 (P = 0.007)]., Conclusion: In patients with pre-treatment CA19-9 >500 U/mL, the CA19-9 decrease ≤80% was strongly associated with poor survival and new strategy should be reconsidered for these patients., Competing Interests: Conflict of interest All authors have no conflicts of interest related to this article. As a relevant financial activity outside this work, Naoki Sasahira received research funding from Taiho Pharmaceutical., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective The coronavirus disease (COVID-19) pandemic has altered the delivery of medical care. The present study evaluated the impact of COVID-19 on the outcomes of unresectable pancreatic cancer (PC) patients who received end-of-life care. Methods We retrospectively compared the management of PC patients during the COVID-19 pandemic (from April 2020 to March 2021) to the preceding year, which was unaffected by the pandemic (from April 2019 to March 2020), based on a prospectively maintained institutional database. Results A total of 178 patients were included in the COVID-19-exposed group and 201 patients were included in the COVID-19-unexposed group. The median overall survival was similar between the groups (exposed vs. unexposed: 12.6 vs. 11.9 months, p=0.174). Treatment regimens and relative dose intensities and the progression-free survival of GnP (gemcitabine in combination with nab-paclitaxel) and mFOLFIRINOX as first- and second-line chemotherapy did not differ significantly between the two groups. Only 9.0% of patients died at home in the COVID-19-unexposed group, compared to 32.0% in the COVID-19-exposed group (p<0.001). A multivariate analysis revealed that death during the COVID-19 exposed period was independently associated with home death (odds ratio: 4.536, 95% confidence interval: 2.527-8.140, p<0.001). Conclusions While the COVID-19 pandemic did not seem to influence chemotherapeutic treatment for PC patients at our institution, it had a large impact on end-of-life care. These findings may promote discussion about end-of-life care in Japan.

Background: To compare the treatment outcomes of nanoliposomal-irinotecan (nal-IRI) plus fluorouracil and leucovorin (5-FU/LV) and modified FOLFIRINOX (mFFX) as second-line treatment after gemcitabine with nab-paclitaxel (GnP) for metastatic and recurrent pancreatic cancer., Methods: We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer treated with nal-IRI plus 5-FU/LV or mFFX after first-line GnP treatment between March 2014 and October 2021 in our hospital. Patient characteristics, treatment outcomes and adverse events were extracted for comparison., Results: Two hundred sixteen patients were included (nal-IRI plus 5-FU/LV/mFFX: 50/166). Patients in the nal-IRI plus 5-FU/LV group were older, had poorer ECOG PS, and a higher rate of peritoneal metastasis than those in the mFFX group. Median overall survival was 9.5 and 9.8 months (P = 0.97), respectively, and the median progression-free survival was 4.5 vs 4.8 months (P = 0.61), respectively. Anorexia, fatigue and peripheral neuropathy were more common in the mFFX group, but there was no difference in grade 3/4 adverse events between the two groups., Conclusions: There was no significant difference in efficacy between nal-IRI plus 5-FU/LV and mFFX after GnP. Nal-IRI plus 5-FU/LV appears to be a viable alternative to mFFX as second-line treatment after GnP., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)