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Highly electrically and thermally conducting films of expanded graphite/polymer nanocomposites were fabricated using an approach based on solution mixing methods. The use of Hydroxyethylcellulose and benzylic alcohol based solutions provides efficient dispersion and better exfoliation of multilayer graphene (nanographite) flakes that are further aligned in extended 2D layers forming continuous conductive pathways during lamination (hot calendering) process. Very high electrical conductivity (190 S/cm) was obtained for fabricated layered films. In contrast, for films produced by a conventional mixing and deposition method with acrylic copolymer and the same nanographitic material, with flakes randomly distributed within the composite, much lower conductivities (2.4 S/cm) were obtained.

Competing Interests: Disclosure: The authors have nothing to disclose. Declaration of generative AI and AI-assisted technologies in the writing process: During the preparation of this work we used ChatGPT-4.0 to improve language and readability. After using this tool, all authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Background: Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities., Methods: Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA., Results: Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn's disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001)., Conclusions: We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC., (© 2024. The Author(s).)

Competing Interests: H. Isayama was supported by research grants from Boston Scientific Japan and FUJIFILM Corporation. The funding source had no role in the design, practice, or analysis of this study. S. Takahashi, K. Tomishima, Y. Takasaki, A. Suzuki, S. Ishii, and T. Fujisawa declare that they have no conflict of interest.

Competing Interests: H. Isayama was supported by research grants from Boston Scientific Japan and FujiFilm Corporation. The funding source has no role in the design, practice, or analysis of this study. D. Namima, T. Fujisawa, S. Takahashi, Y. Takasaki, K. Tomishima, and S. Ishii declare that they have no conflicts of interest to disclose.

Competing Interests: H. Isayama has received research grants from Boston Scientific Japan and FUJIFILM Corporation. The funding source had no role in the design, practice, or analysis of this study. A. Machida, Y. Takasaki, S. Takahashi, A. Suzuki, S. Ishii, and T. Fujisawa declare that they have no conflict of interest.

Competing Interests: H. Isayama was supported by research grants from Boston Scientific Japan and Fujifilm Corporation. The funding source had no role in the design, practice, or analysis of this study. K. Tomishima, A. Suzuki, K. Ito, S. Ishii, T. Fujisawa, and Y. Fukumura declare that they have no conflict of interest.

Background: The purpose of this study was to provide a detailed evaluation of the oncological advantages of surgery following neoadjuvant chemotherapy (NAC) for patients with borderline resectable (BR) or unresectable (UR) pancreatic ductal adenocarcinoma (PDAC), with a focus on minimizing biases. Recently, NAC has become the standard care for BR or UR locally advanced (UR-LA) PDAC, however, many studies have assessed survival benefits and favorable variables without consideration for biases, particularly immortal time bias., Patients and Methods: This study included patients diagnosed with BR or UR-LA PDAC at Juntendo University Hospital from 2019 to 2022. To mitigate bias, we applied methods such as propensity score matching (PSM), time-dependent covariate Cox proportional hazard regression analysis (TDC), landmark analysis, and multivariable Cox proportional hazards regression model., Results: The study analyzed 124 patients, dividing them into a surgery group (n = 57) and a chemotherapy-only group (n = 67). After PSM, there were 21 matched pairs. Survival analysis using TDC analysis showed that the surgery group had significantly better overall survival compared with the chemotherapy-only group in both the entire cohort and the matched pairs. Cox regression analysis of the entire cohort also revealed a similar superiority of surgery, while the landmark analysis showed varying results depending on the landmark setting., Conclusions: After careful adjustment for selection and immortal time biases, surgery following NAC appears to significantly extend survival in patients with BR or UR PDAC., (© 2024. Society of Surgical Oncology.)

Competing Interests: Author H. I. was supported by research grants from Boston Scientific Japan and FUJIFILM Corporation. These institutions have no role in the design, practice, or analysis of this study. The remaining authors have no conflicts of interest to disclose.

We started a registry for cases of immunoglobulin (Ig)G4-related disease (IgG4-RD) in December 2019 to clarify the clinical profile of IgG4-RD. In this study, clinical information from 854 cases registered by February 16, 2024 was analyzed from multiple perspectives. Diagnosis of IgG4-RD was made in 808 cases, comprising 638 definite, 38 probable, and 132 possible. The mean ± SD age at time of enrollment of the 808 cases was 67.9 ± 11.3 years, with 68.8% being male. The pancreas was the most frequently affected organ (49.8%), followed by the submandibular glands (46.2%) and lacrimal glands (30.6%). This study reconfirmed the pancreas and head-and-neck region as major affected areas in IgG4-RD. Clinically, submandibular adenitis and autoimmune pancreatitis often occur together in the same patient, but no association between the two organs was observed in our analysis. Regarding diagnosis, the comprehensive diagnostic criteria were most commonly used (63.6%). Storiform fibrosis and phlebitis obliterans were detected at different frequencies in different organs. In summary, this registry study identified clinical, imaging, hematologic, and pathologic findings in 808 Japanese patients with IgG4-RD. The frequency of affected organs and their characteristic pathological findings will be particularly useful for future practice.

Background and Aims: EUS-guided transmural drainage with on-demand endoscopic necrosectomy (EN) is increasingly used to manage walled-off necrosis (WON). It has not been fully elucidated how EN and its timing are correlated with treatment outcomes compared with the drainage-based approach., Methods: Within a multi-institutional cohort of 423 patients with pancreatic fluid collections, including 227 patients with WON, 153 patients were identified who received the step-up treatment after the initial EUS-guided drainage of symptomatic WON; this included 102 EN patients and 51 non-EN (drainage) patients. Using the competing-risks multivariable proportional hazards regression model with adjustment for potential confounders, we calculated subdistribution hazard ratios (SHRs) for clinical treatment success (WON resolution) according to use of EN and its timing., Results: Compared with drainage alone, the EN-based treatment was associated with a shorter time to clinical success with a multivariable SHR of 1.66 (95% confidence interval, 1.12-2.46). Despite a higher risk of procedure-related bleeding in the EN group, there were no differences in the rates of severe adverse events (7.8% vs 5.9% in the EN and non-EN groups, respectively) or mortality (6.9% vs 9.8%). In the EN-treated patients, the timing of EN was not statistically significantly associated with the time to clinical success (P trend  = .34)., Conclusions: Among patients receiving EUS-guided treatment of symptomatic WON, the use of EN in addition to drainage procedures was associated with earlier disease resolution. Further research is desired to determine the optimal timing of initiating EN considering a risk-benefit balance and cost-effectiveness., Competing Interests: Disclosure The following authors disclosed financial relationships: Dr Isayama received support from Boston Scientific Japan, FUJIFILM Corporation, Piolax Medical Devices, Century Medical, Gadelius Medical, FUJIFULM Healthcare, Japan Lifeline Co.,Ltd and ZEON MEDICAL INC. Paid speaker for Boston Scientific Japan, FUJIFILM Corporation, Piolax Medical Devices, Century Medical, CREATE MEDIC, Gadelius Medical, FUJIFULM Healthcare, Japan Lifeline Co., KANEKA MEDIX CORP, Kawasumi Laboratories, Olympus Medical, Sumitomo Bakelite Co., Ltd. and ZEON MEDICAL INC. Consulting for Kawasumi Laboratories. Y. Nakai: research funding and consulting for Boston Scientific Japan, Fujifilm, Gadelius Medical, Hitachi Medical, and Medico’s Hirata; research funding from Century Medical, HOYA Pentax Medical, and Kaneka; and consulting for Olympus Medical and J-MIT. All other authors disclosed no financial relationships. This work was supported by grants from the Japanese Foundation for Research and Promotion of Endoscopy (to Drs. Saito and Nakai). Dr Hamada was supported by the Japan Society for the Promotion of Science KAKENHI grants (JP19K08362 and JP22H02841) and grants from Takeda Science Foundation and Daiichi Sankyo Company. The funders had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: EUS-guided hepaticogastrostomy (EUS-HGS) carries a risk of serious adverse events (AEs). A newly designed, partially covered laser-cut stent with antimigration anchoring hooks and a thin tapered tip (7.2F), called a Hook stent (Zeon Medical, Tokyo, Japan), has been developed to prevent serious AEs associated with EUS-HGS. The present prospective multicenter clinical trial evaluated the efficacy and safety of the Hook stent for EUS-HGS after failure of ERCP in patients with unresectable malignant biliary obstruction., Methods: The primary endpoint was the rate of clinical success, and secondary endpoints were the rates of technical success, AEs, recurrent biliary obstruction (RBO), procedure success without using a tract dilation device, reintervention for RBO, time to RBO, and overall survival (OS)., Results: Thirty-eight patients underwent EUS-HGS using the Hook stent. The technical and clinical success rates in patients undergoing EUS-HGS were 100% and 92.1%, respectively. The procedure success rate without using a tract dilation device was 94.7%. Four patients (10.5%) developed early AEs, but there were no severe AEs such as stent migration. RBO developed in 26.3% of patients. Reintervention for RBO had a 100% success rate. The median time to RBO was not reached, and the median OS was 191 days., Conclusions: EUS-HGS using the Hook stent demonstrated a high clinical success rate, low rate of early AEs, and an acceptable stent patency. The Hook stent is safe and feasible for use in patients undergoing EUS-HGS. (Clinical trial registration number: jRCT2052210020.)., Competing Interests: Disclosure The following authors disclosed financial relationships: H. Isayama: Speaker for and research support from Fujifilm Corporation. M. Kitano: Speaker for Olympus Corporation; research support from Boston Scientific Corporation and Medicos Hirata Corporation. All other authors disclosed no financial relationships. Masayuki Kitano (the principal investigator), Takeshi Ogura, Hiroyuki Isayama, Mamoru Takenaka, Susumu Hijioka, and Hirotoshi Ishiwatari (the co-investigators) received the research support from the Japan Agency for Medical Research and Development and Zeon Corporation., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

The consensus-based TOKYO criteria were proposed as a standardized reporting system for endoscopic transpapillary biliary drainage. The primary objective was to address issues arising from the inconsistent reporting of stent outcomes across studies, which has complicated the comparability and interpretation of study results. However, the original TOKYO criteria were not readily applicable to recent modalities of endoscopic biliary drainage such as biliary drainage based on endoscopic ultrasound or device-assisted endoscopy. There are increasing opportunities for managing hilar biliary obstruction and benign biliary strictures through endoscopic drainage. Biliary ablation has been introduced to manage benign and malignant biliary strictures. In addition, the prolonged survival times of cancer patients have increased the importance of evaluating overall outcomes during the period requiring endoscopic biliary drainage rather than solely focusing on the patency of the initial stent. Recognizing these unmet needs, a committee has been established within the Japan Gastroenterological Endoscopy Society to revise the TOKYO criteria for current clinical practice. The revised criteria propose not only common reporting items for endoscopic biliary drainage overall, but also items specific to various conditions and interventions. The term "stent-demanding time" has been defined to encompass the entire duration of endoscopic biliary drainage, during which the overall stent-related outcomes are evaluated. The revised TOKYO criteria 2024 are expected to facilitate the design and reporting of clinical studies, providing a goal-oriented approach to the evaluation of endoscopic biliary drainage., (© 2024 The Author(s). Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Postoperative pancreatic fistulas (POPFs) are common adverse events that occur after pancreatic surgery. Endoscopic ultrasonography (EUS)-guided drainage (EUS-D) is a first-line treatment, similar to that for pancreatic fluid collection (PFCs) after acute pancreatitis. However, some POPFs do not develop fluid collections depending on the presence or location of the surgical drain, whereas others develop fluid collections, such as postoperative fluid collections (POPFCs). Although POPFCs are similar to PFCs, the strategy and modality for POPF management need to be modified according to the presence of fluid collections, surgical drains, and surgical type. As discussed for PFCs, the indications, timing, and selection of interventions or stents for EUS-D have not been fully elucidated for POPFs. In this review, we discuss the management of POPFs and POPFCs in comparison with PFCs due to acute pancreatitis and summarize the topics that should be addressed in future studies.

In 2023, the Japan Pancreas Society (JPS) published the new eighth edition of the Japanese classification of pancreatic carcinoma. We present here an excerpted version in English, based on the latest edition. The major changes in this revision are as follows: In the eighth edition of the Union for International Cancer Control (UICC), the T category was changed to be based on tumor size; however, the eighth edition of the Japanese classification retains the previous T category based on local invasion factors. Lymph nodes have been renamed, and regional lymph nodes have been defined by location. Peritoneal cytology, which was not previously included in distant metastasis (M), has now been included in the M category. Moreover, significant additions have been made regarding the pathological diagnosis of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) and criteria for histological assessment of the effects after chemotherapy and radiation therapy. Although this classification is aimed at carcinoma originating in the pancreas, not in the bile duct or duodenum, if the differentiation of the primary organ is difficult, this classification should be applied. It is also desirable to describe tumors other than carcinoma and metastatic tumors to the pancreas in accordance with this classification., (© 2024 The Author(s). Journal of Hepato‐Biliary‐Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Hemosuccus pancreaticus (HP) is characterized by gastrointestinal bleeding from the papilla of Vater via the pancreatic duct. In this report, we describe a case of HP due to arterial perforation in a pancreatic pseudocyst and discuss the computed tomography (CT) findings and efficacy of stent graft placement. A 64-year-old man with a history of heavy alcohol use, situs inversus totalis, and total gastrectomy was hospitalized with hematochezia. Enhanced CT revealed a pseudoaneurysm in the common hepatic artery (CHA) with mildly high density in the main pancreatic duct. Subsequent CT revealed an enlarged cystic lesion with inflow of contrast medium. Angiography confirmed blood flow from the CHA into the pancreatic pseudocyst, and the patient was diagnosed with HP due to intrapancreatic pseudocyst perforation of the CHA pseudoaneurysm. Coil packing into the pseudocyst failed to block the blood flow, and a covered stent graft was placed into the CHA. The patient had an uneventful clinical course. The identification of a pseudoaneurysm and a high-density area in the main pancreatic duct on enhanced CT and changes in the pancreatic cyst diameter may indicate the acute phase of HP, and stent grafting is an effective treatment for intracystic arterial perforation., (© 2024. Japanese Society of Gastroenterology.)

Interventional endoscopic ultrasonography/endosongraphy (I-EUS) procedures have rapidly evolved since their introduction three decades ago; however, the classification and terminology for these procedures remain unstandardized. To address this, the Subcommittee for Terminology of I-EUS in the Japan Gastroenterological Endoscopy Society was established to define classifications and a glossary of I-EUS terms. They categorized I-EUS procedures into five types based on purpose and method: (i) EUS-guided sampling; (ii) EUS-guided through-the-needle examination; (iii) EUS-guided drainage/anastomosis (EUS-D/A); (iv) trans-endosonographically/EUS-guided created route (ESCR) procedures; and (v) EUS-guided delivery. EUS-guided sampling includes tissue acquisition and fluid sampling, classified by needle type into fine needle aspiration and fine needle biopsy. Through-the-needle examinations include imaging, measurements, and biopsies. EUS-D/A includes organ drainage/anastomosis, fluid collection drainage, and digestive tract anastomosis. In the EUS-D/A route, "anastomosis" is used for organ-to-organ procedures, whereas "tract" is for fluid drainage. ESCR is a newly proposed term for procedures via anastomosis or tract, such as endoscopic necrosectomy and EUS-guided antegrade stenting. The term "trans-luminal drainage/anastomosis stent" is used for stents that maintain the ESCR rather than treating strictures. EUS-guided delivery involves the delivery of substances, such as fluids, drugs, medical devices, and energy. This proposed categorization and terminology aimed to clarify I-EUS procedures and will require updates as new techniques and concepts emerge., (© 2024 Japan Gastroenterological Endoscopy Society.)

Introduction: Disconnected pancreatic duct syndrome (DPDS) is a pathological condition that causes various symptoms due to the continuous secretion of pancreatic enzymes from the pancreas upstream, which has been separated due to disconnection of the pancreatic duct (DPD) for various reasons.Acute necrotizing pancreatitis includes a certain probability of DPDS appearance, which makes it necessary to provide various treatments for DPDS. Furthermore, DPDS can impact long-term results, such as recurrence and impaired pancreatic function. Although the development of various modalities has contributed to diagnosis and treatment, especially less invasive endoscopic therapy, DPDS is often overlooked, and the diagnosis can be delayed due to the lack of consensus on its definition and classification. This review summarizes the current knowledge and challenges of DPDS and discusses the optimal strategy for its diagnosis and treatment, as well as future perspectives., Areas Covered: Given the lack of established definition, diagnosis, and treatment of DPDS, we conducted a thorough review of the existing literature., Expert Opinion: It is emphasized that a standardized definition and classification of DPDS is essential for designing and conducting clinical studies to address current unmet needs in managing patients with DPDS.

Background: This study aimed to evaluate the outcomes and complications of secondary hepatolithiasis following choledochoenterostomy to guide suitable management., Methods: The study analyzed 127 patients from a 2017 national survey conducted by the Ministry of Health, Labor, and Welfare. The 2023 cohort study assessed residual stones, recurrences, cholangitis, cholangiocarcinoma, and prognosis., Results: The median follow-up duration was 48 months. Balloon endoscopy-assisted endoscopic retrograde cholangiography (BE-ERC) was the most common treatment, achieving complete stone clearance in 84.4% of patients. Anatomical hepatectomy was the most common surgery. Predictors of residual stones were stone number ≥10 (odds ratio [OR], 7.480; p = .028) and stone diameter ≥10 mm (OR, 5.280; p = .020). Predictors of stone recurrence during follow-up were biliary strictures (hazard ratio [HR], 3.580; p = .005) and cholangitis (HR, 2.700; p = .037). Predictors of cholangitis during follow-up were biliary stricture (HR, 5.016; p = .006) and dilatation (HR, 3.560; p = .029). Any treatment for hepatolithiasis reduced cholangitis occurrence (HR, 0.168; p = .042). Balloon dilation combined with stenting for ≥3 months improved biliary strictures in 57.1% of patients., Conclusion: This study recommends BE-ERC as the first-choice treatment for secondary hepatolithiasis. Stone removal and relief of biliary strictures and dilatation are crucial to prevent stone recurrence and cholangitis after treatment., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Objectives: The appropriate holistic management is mandatory for successful endoscopic ultrasound (EUS)-guided treatment of pancreatic fluid collections (PFCs). However, comorbidity status has not been fully examined in relation to clinical outcomes of this treatment., Methods: Using a multi-institutional cohort of 406 patients receiving EUS-guided treatment of PFCs in 2010-2020, we examined the associations of Charlson Comorbidity Index (CCI) with in-hospital mortality and other clinical outcomes. Multivariable logistic regression analysis was conducted with adjustment for potential confounders. The findings were validated using a Japanese nationwide inpatient database including 4053 patients treated at 486 hospitals in 2010-2020., Results: In the clinical multi-institutional cohort, CCI was positively associated with the risk of in-hospital mortality (P trend  < 0.001). Compared to patients with CCI = 0, patients with CCI of 1-2, 3-5, and ≥6 had adjusted odds ratios (95% confidence intervals) of 0.76 (0.22-2.54), 5.39 (1.74-16.7), and 8.77 (2.36-32.6), respectively. In the nationwide validation cohort, a similar positive association was observed; the corresponding odds ratios (95% confidence interval) were 1.21 (0.90-1.64), 1.52 (0.92-2.49), and 4.84 (2.63-8.88), respectively (P trend  < 0.001). The association of higher CCI with longer length of stay was observed in the nationwide cohort (P trend  < 0.001), but not in the clinical cohort (P trend  = 0.18). CCI was not associated with the risk of procedure-related adverse events., Conclusions: Higher levels of CCI were associated with a higher risk of in-hospital mortality among patients receiving EUS-guided treatment of PFCs, suggesting the potential of CCI in stratifying the periprocedural mortality risk., Trial Registration: The research based on the clinical data from the WONDERFULcohort was registered with UMIN-CTR (registration number UMIN000044130)., (© 2024 The Author(s). Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Patients with isolated IgG4-related sclerosing cholangitis (IgG4-SC) often undergo unnecessary resection. The aim of this study was to validate the revised Japanese diagnostic criteria for isolated IgG-4-SC and to improve awareness about this condition in the population., Methods: This was a Japanese retrospective multicenter study. We focused on the data and diagnostic yield obtained using the Japanese diagnostic criteria published initially in 2012 and revised later in 2020 for the diagnosis of isolated IgG4-SC., Results: Patients with isolated IgG4-SC could be classified into two groups based on the primary location of the lesion: the hilar type (n = 40) and the extrahepatic type (n = 13). In total, 10 patients with the hilar type had undergone unnecessary resection. The revised 2020 criteria are useful for the diagnosis of extrahepatic lesions, which are not included in the 2012 criteria. The need for a steroid trial was reduced from 37.7% when the diagnosis was based on the 2012 criteria to 7.6% when the diagnosis was based on the revised 2020 criteria. The diagnostic specificity also improved from 58.5% for the 2012 criteria to 88.7% for the revised 2020 criteria., Conclusion: Our validation of the 2020 criteria for the diagnosis of IgG4-SC could contribute to avoiding unnecessary resection in patients with isolated IgG4-SC, which can be classified into the hilar and extrahepatic types. The 2020 criteria can enhance the diagnosis rate of isolated IgG4-SC and uncover this tough-to-diagnose entity based on inclusion of the imaging findings and decrease the dependence on a steroid trial., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Aim: To investigate the outcomes of cabozantinib in patients with unresectable hepatocellular carcinoma (uHCC), focusing on dose setting and modification., Methods: We retrospectively analyzed 34 Japanese patients who received cabozantinib for uHCC. Trough concentrations (C trough ) of cabozantinib were also measured weekly for 6 weeks in the 18 patients., Results: Sixteen patients received ≥40 mg (high-dose group), and 18 patients received 20 mg (low-dose group). Dose escalations were performed in 27.8% of the patients in the low-dose group. Although median duration of the first dose reduction or interruption in the low-dose group was twice that in the high-dose group (28 vs. 14 days, p < 0.001), there were no significant differences in the relative dose intensity (RDI) during 6 weeks, progression free survival (PFS), and overall survival (p = 0.162, p = 0.950, p = 0.817, respectively) between the two groups. Patients who received RDI during 6 weeks ≥33.4% showed a trend toward longer median PFS (p = 0.054). Each serum aldolase value during the 6 weeks was significantly correlated with the C trough at any point (r = 0.500, p < 0.001). In multivariate analyses, aldolase ≥8.7 U/L within 2 weeks was significantly associated with the very early dose reduction or interruption (odds ratio 20.0, p = 0.002)., Conclusions: An initial dose of 20 mg cabozantinib could be a safe option in Japanese patients. The serum aldolase value could be useful for making appropriate dose modifications of cabozantinib., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Recently, there has been a significant increase in the utilization of self-expandable metallic stents (SEMSs) for treating malignant colorectal obstructions through colorectal stenting. The mechanical properties of SEMSs are usually considered to affect clinical outcomes of patients with malignant colorectal obstructions. Methods : This single-arm, prospective, multicenter study of SEMS with a lower axial force and high axial force zero-border included 200 patients with malignant colorectal obstruction. Technical and clinical success, stent patency, and adverse events associated with SEMS placement were evaluated. Results: One patient was excluded, and 199 patients were evaluated. The treatment intent was bridge-to-surgery in 129 and palliation in 70 patients. Technical and clinical success rates were 99.5% and 97.0%, respectively. The percentage of the ColoRectal Obstruction Scoring System scores of 3 or higher improved significantly from 19.2% before placement to 93.9% after placement. Clinical success was not achieved in five patients due to insufficient stent expansion in four patients and stent occlusion in one patient. Only one patient underwent emergency surgery for perforation of the proximal colon, far from where the stent was placed; the rescue procedure was not performed, despite no improvement in proximal dilatation due to insufficient stent expansion. Among the palliation cohort, 15 patients received chemotherapy, including molecular-targeted agents such as bevacizumab. There were no fatal cases related to stent placement. Conclusions : For management of malignant colorectal obstruction, this newly developed SEMS with low axial force and a high axial force zero-border showed high technical and clinical success rates, and an extremely low perforation rate (0.5%).

Competing Interests: Conflict of Interest Y.N. and H.I. acknowledge research grants and honoraria from Boston Scientific Japan. This paper was not funded by this company. No other conflicts of interest exist. The other authors declare that they have no conflicts of interest.

Background: Endoscopic ultrasound (EUS)-guided transluminal drainage has become a first-line treatment modality for symptomatic pancreatic pseudocysts. Despite the increasing popularity of lumen-apposing metal stents (LAMSs), plastic stents may resolve non-necrotic fluid collections effectively with lower costs and no LAMS-specific adverse events. To date, there has been a paucity of data on the appropriate stent type in this setting. This trial aims to assess the non-inferiority of plastic stents to a LAMS for the initial EUS-guided drainage of pseudocysts., Methods: The WONDER-02 trial is a multicentre, open-label, non-inferiority, randomised controlled trial, which will enrol pancreatic pseudocyst patients requiring EUS-guided treatment in 26 centres in Japan. This trial plans to enrol 80 patients who will be randomised at a 1:1 ratio to receive either plastic stents or a LAMS (40 patients per arm). In the plastic stent group, EUS-guided drainage will be performed using two 7-Fr double pigtail stents. In the LAMS group, the treatment will be performed in the same way except for LAMS use. The step-up treatment will be performed via endoscopic and/or percutaneous procedures at the trial investigator's discretion. The primary endpoint is clinical success, which is defined as a decrease in a pseudocyst size to ≤ 2 cm and an improvement in inflammatory indicators (i.e. body temperature, white blood cell count, and serum C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, pseudocyst recurrence, and medical costs., Discussion: The WONDER-02 trial will investigate the efficacy and safety of plastic stents compared to a LAMS in EUS-guided treatment of symptomatic pancreatic pseudocysts with a particular focus on the non-inferior efficacy of plastic stents. The findings will help establish a new treatment algorithm for this population., Trial Registration: ClinicalTrials.gov NCT06133023 registered on 9 November 2023. UMIN000052647 registered on 30 October 2023. jRCT1032230444 registered on 7 November 2023., (© 2024. The Author(s).)

In recent years, the usefulness of endoscopic ultrasound (EUS) has been recognized in children. A dedicated pediatric EUS scope has not been developed; in our experience, however, an adult EUS scope can be used. The American Society for Gastrointestinal Endoscopy Technical Committee status assessment report on pediatric endoscopy equipment provides some guidance on the feasibility of EUS according to body size. Careful monitoring is required, keeping in mind potential adverse events such as cervical esophageal perforation and unstable breathing due to tracheal compression. Most devices designed for interventional pancreatobiliary endoscopy are also available for children. Sedation or intubated general anesthesia (GA) is mandatory when performing interventional EUS (I-EUS). I-EUS for children is generally performed using GA in the operating room, but sedation in the endoscopy room is also possible under appropriate monitoring by pediatricians. I-EUS in the operating room is sometimes difficult for endoscopists to perform because of the unsuitable fluoroscopic imaging and the lack of familiar equipment and staff. Compared to GA, sedation in the endoscopy room facilitates easier and quicker repetition of procedures when necessary. Adult pancreatobiliary endoscopists perform most I-EUS procedures in the pediatric population because most pediatric endoscopists have few opportunities to perform EUS-related procedures and thus have difficulty maintaining their skills. To popularize I-EUS techniques for children, it will be necessary to establish a training program for developing pediatric endoscopists., (© 2024 Japan Gastroenterological Endoscopy Society.)

Aim: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease., Methods: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected., Results: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination., Conclusion: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases., (© 2024 Japan Society of Hepatology.)

Walled-off necrosis (WON) develops as local complications after acute necrotizing pancreatitis. Although less invasive interventions such as endoscopic ultrasonography (EUS)-guided drainage and endoscopic necrosectomy are selected over surgical interventions, delayed and step-up interventions are still preferred to avoid procedure-related adverse events. However, there is a controversy about the appropriate timing of drainage and subsequent necrosectomy. The advent of large-caliber lumen-apposing metal stents has also brought about potential advantages of proactive interventions, which still needs investigation in future trials. When step-up interventions of necrosectomy and additional drainage are necessary, a structured or protocoled approach for WON has been reported to improve safety and effectiveness of endoscopic and/or percutaneous treatment, but has not been standardized yet. Finally, long-term outcomes such as recurrence of WON, pancreatic endocrine, and exocrine function are increasingly investigated in association with disconnected pancreatic duct syndrome. In this review we discuss current evidence and controversy on EUS-guided management of WON., (© 2024 Japan Gastroenterological Endoscopy Society.)

Background and study aims Pancreatitis is a potentially lethal adverse event of endoscopic transpapillary placement of a self-expandable metal stent (SEMS) for malignant biliary obstruction (MBO). Deep learning-based image recognition has not been investigated in predicting pancreatitis in this setting. Patients and methods We included 70 patients who underwent endoscopic placement of a SEMS for nonresectable distal MBO. We constructed a convolutional neural network (CNN) model for pancreatitis prediction using a series of pre-procedure computed tomography images covering the whole pancreas (≥ 120,960 augmented images in total). We examined the additional effects of the CNN-based probabilities on the following machine learning models based on clinical parameters: logistic regression, support vector machine with a linear or RBF kernel, random forest classifier, and gradient boosting classifier. Model performance was assessed based on the area under the curve (AUC) in the receiver operating characteristic analysis, positive predictive value (PPV), accuracy, and specificity. Results The CNN model was associated with moderate levels of performance metrics: AUC, 0.67; PPV, 0.45; accuracy, 0.66; and specificity, 0.63. When added to the machine learning models, the CNN-based probabilities increased the performance metrics. The logistic regression model with the CNN-based probabilities had an AUC of 0.74, PPV of 0.85, accuracy of 0.83, and specificity of 0.96, compared with 0.72, 0.78, 0.77, and 0.96, respectively, without the probabilities. Conclusions The CNN-based model may increase predictability for pancreatitis following endoscopic placement of a biliary SEMS. Our findings support the potential of deep learning technology to improve prognostic models in pancreatobiliary therapeutic endoscopy., Competing Interests: Conflict of Interest Y.N. and H.I. receive research funding and honoraria from Boston Scientific Japan. This work was not funded by this company. No other conflicts of interest exist. The other authors declare that they have no conflicts of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Endoscopic ultrasound (EUS)-guided pancreatic duct drainage includes two procedures: EUS-guided drainage/anastomosis (EUS-D/A) and trans-papillary drainage with EUS-assisted pancreatic rendezvous. EUS-guided pancreatogastrostomy is the most common EUS-D/A procedure and is recommended as a salvage procedure in cases in which endoscopic retrograde cholangiopancreatography fails or is difficult. However, initial EUS-D/A is performed in patients with surgically altered anatomy at our institution. It is one of the most difficult interventional EUS procedures and has a high incidence of adverse events. The technical difficulties differ according to etiology, and the incidence of adverse events varies between initial EUS-D/A and subsequent trans-endosonographically/EUS-guided created route procedures. Hence, it is important to meticulously prepare a procedure based on the patient's condition and the available devices. The technical difficulties in EUS-D/A include: (1) determination of the puncture point, (2) selection of a puncture needle and guidewire, (3) guidewire manipulation, and (4) dilation of the puncture route and stenting. Proper technical procedures are important to increase the success rate and reduce the incidence and severity of adverse events. The complexity of EUS-D/A is also contingent on the severity of pancreatic fibrosis and stricture. In post-pancreatectomy cases, determination of the puncture site is important for success because of the remnant pancreas. Trans-endosonographically/EUS-guided created route procedures following initial EUS-D/A are also important for achieving the treatment goal. This article focuses on effective strategies for initial EUS-D/A, based on the etiology and condition of the pancreas. We mainly discuss EUS-D/A, including its indications, techniques, and success-enhancing strategies., Competing Interests: Hiroyuki Isayama is supported by honoraria from the FUJIFILM Corporation, Tokyo, Japan and FUJIFILM Healthcare Corporation, Tokyo, Japan. The other authors declare no conflict of interest., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Objectives: For preoperative biliary drainage (PBD) of malignant hilar biliary obstruction (MHBO), current guidelines recommend endoscopic nasobiliary drainage (ENBD) due to the higher risk of cholangitis after endoscopic biliary stenting (EBS) during the waiting period before surgery. However, few studies have supported this finding. Therefore, we aimed to compare the outcomes of preoperative ENBD and EBS in patients with MHBO., Methods: Patients with MHBO who underwent laparotomy for radical surgery after ENBD or EBS were included from retrospectively collected data from 13 centers (January 2014 to December 2018). We performed a 1:1 propensity score matching between the ENBD and EBS groups. These patients were compared for the following: cholangitis and all adverse events (AEs) after endoscopic biliary drainage (EBD) until surgery, time to cholangitis development after EBD, postsurgical AEs, and in-hospital death after surgery., Results: Of the 414 patients identified, 355 were analyzed in this study (226 for ENBD and 129 for EBS). The matched cohort included 63 patients from each group. The proportion of cholangitis after EBD was similar between the two groups (20.6% vs. 25.4%, P = 0.67), and no significant difference was observed in the time to cholangitis development. The proportions of surgical site infections, bile leaks, and in-hospital mortality rates were similar between the groups., Conclusion: For PBD of MHBO, the proportion of AEs, including cholangitis, after EBD until surgery was similar when either ENBD or EBS was used., (© 2023 Japan Gastroenterological Endoscopy Society.)

Background/Objective : Interventional endoscopic ultrasound (I-EUS) is technically difficult and has risks of severe adverse events due to the scarcity of dedicated endoscopes and tools. A new EUS scope was developed for I-EUS and was modified to increase the puncture range, reduce the blind area, and overcome guidewire difficulties. We evaluated the usefulness and safety of a new EUS scope compared to a conventional EUS scope. Methods : All I-EUS procedures were performed at Juntendo University Hospital from April 2020 to April 2022. The primary outcomes included the procedure time and fluoroscopy time. The secondary outcomes included the technical success rate and the rates of procedure-related adverse events. Clinical data were retrospectively reviewed and statistically analyzed between the new and conventional EUS scopes. Results : In total, 143 procedures in 120 patients were analyzed. The procedure time was significantly shorter with the new EUS scope, but the fluoroscopy time was not different. Among the patients only undergoing EUS-guided biliary drainage (EUS-BD), 79 procedures in 74 patients were analyzed. Both the procedure time and fluoroscopy time were significantly shorter with the new EUS scope. Multivariate analysis revealed that a new EUS scope and use of covered metal stents could reduce the fluoroscopy time. The technical success rate and the adverse event rate were not significantly different between the total I-EUS and the EUS-BD only groups. However, the conventional scope showed stent deviation during stent placement, which did not happen with the new scope. Conclusions : The new EUS scope reduced procedure time for total I-EUS and fluoroscopy time for EUS-BD compared to a conventional EUS scope because of the improvement suitable for I-EUS.

Objectives: No comprehensive study has examined short- and long-term adverse outcomes of endoscopic ultrasound (EUS)-guided treatment of pancreatic fluid collections (PFCs) including walled-off necrosis (WON) and pseudocysts., Methods: In a multi-institutional cohort of 357 patients receiving EUS-guided treatment of PFCs (228 with WON and 129 with pseudocysts), we examined PFC type-specific risk factors for procedure-related adverse events (AEs), clinical failure, and recurrence. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using the logistic and Cox regression models, respectively, adjusting for potential confounders., Results: Adverse events were observed predominantly in WON, and risk factors were WON extension to the pelvis (OR 2.49; 95% CI 1.00-6.19) and endoscopic necrosectomy (OR 5.15; 95% CI 1.61-16.5). Risk factors for clinical failure in WON treatment included higher Charlson Comorbidity Index (OR for ≥3 vs. ≤2, 2.58; 95% CI 1.05-6.35), extension to the pelvis (OR 3.63; 95% CI 1.57-8.43), nonuse of a lumen-apposing metal stent (OR 2.88; 95% CI 1.10-7.54), and percutaneous drainage (OR 3.73; 95% CI 1.27-10.9). Patients with pseudocysts extending to the paracolic gutter and the need for more than two endoscopic/percutaneous procedures had ORs for clinical failure of 5.28 (95% CI 1.10-25.3) and 5.52 (95% CI 1.61-18.9), respectively. Pseudocysts requiring the multigateway approach were associated with a high risk of recurrence (HR 4.00; 95% CI 1.11-11.6)., Conclusion: The adverse outcomes at various phases of EUS-guided PFC treatment may be predictable based on clinical parameters. Further research is warranted to optimize treatment strategies for high-risk patients., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

The progress of endoscopic diagnosis and treatment for inflammatory diseases of the biliary tract and pancreas have been remarkable. Endoscopic ultrasonography (EUS) and EUS-elastography are used for the diagnosis of early chronic pancreatitis and evaluation of endocrine and exocrine function in chronic pancreatitis. Notably, extracorporeal shock wave lithotripsy and electrohydraulic shock wave lithotripsy have improved the endoscopic stone removal rate in patients for whom pancreatic stone removal is difficult. Studies have reported the use of self-expanding metal stents for stent placement for pancreatic duct stenosis and EUS-guided pancreatic drainage for refractory pancreatic duct strictures. Furthermore, EUS-guided drainage using a double-pigtailed plastic stent has been performed for the management of symptomatic pancreatic fluid collection after acute pancreatitis. Recently, lumen-apposing metal stents have led to advances in the treatment of walled-off necrosis after acute pancreatitis. EUS-guided biliary drainage is an alternative to refractory endoscopic biliary drainage and percutaneous transhepatic biliary drainage for the treatment of acute cholangitis. The placement of an inside stent followed by switching to uncovered self-expanding metal stents in difficult-to-treat cases has been proposed for acute cholangitis by malignant biliary obstruction. Endoscopic transpapillary gallbladder drainage is an alternative to percutaneous transhepatic gallbladder drainage for severe and some cases of moderate acute cholecystitis. EUS-guided gallbladder drainage has been reported as an alternative to percutaneous transhepatic gallbladder drainage and endoscopic transpapillary gallbladder drainage. However, it is important to understand the advantages and disadvantages of each drainage method and select the optimal drainage method for each case., (© 2024 Japan Gastroenterological Endoscopy Society.)

Background/objectives: The association between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) remains controversial. This study aimed to clarify the long-term prognosis and risk of malignancies in AIP patients in Japan., Methods: We conducted a multicenter retrospective cohort study on 1364 patients with type 1 AIP from 20 institutions in Japan. We calculated the standardized incidence ratio (SIR) for malignancies compared to that in the general population. We analyzed factors associated with overall survival, pancreatic exocrine insufficiency, diabetes mellitus, and osteoporosis., Results: The SIR for all malignancies was increased (1.21 [95 % confidence interval: 1.05-1.41]) in patients with AIP. Among all malignancies, the SIR was highest for PC (3.22 [1.99-5.13]) and increased within 2 years and after 5 years of AIP diagnosis. Steroid use for ≥6 months and ≥50 months increased the risk of subsequent development of diabetes mellitus and osteoporosis, respectively. Age ≥65 years at AIP diagnosis (hazard ratio [HR] = 3.73) and the development of malignancies (HR = 2.63), including PC (HR = 7.81), were associated with a poor prognosis, whereas maintenance steroid therapy was associated with a better prognosis (HR = 0.35) in the multivariate analysis. Maintenance steroid therapy was associated with a better prognosis even after propensity score matching for age and sex., Conclusions: Patients with AIP are at increased risk of developing malignancy, especially PC. PC is a critical prognostic factor for patients with AIP. Although maintenance steroid therapy negatively impacts diabetes mellitus and osteoporosis, it is associated with decreased cancer risk and improved overall survival., Competing Interests: Declaration of competing interest None., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Competing Interests: H. Isayama has received research funding from Boston Scientific Japan, Fujifilm, and Piolax Medical Devices; honoraria from Boston Scientific Japan, Century Medical, Create Medic, Fujifilm, Gadelius Medical, Hitachi Medical, Japan Lifeline, Kaneka, Kawasumi Laboratories, Olympus Medical, Piolax Medical Devices, Sumitomo Bakelite, UMIDAS, and Zeon Medical; and contributions from Boston Scientific Japan, Gadelius Medical, Japan Lifeline, and Zeon Medical. This paper was not funded by any of these companies. T. Saito, T. Hamada, H. Shiomi, and A. Sakai declare that they have no conflict of interest.

Background: Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC., Methods: This retrospective multi-institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC., Results: Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19-9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un-matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS ( p  = 0.001), DSS ( p  = 0.001), and RFS ( p  = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p  < 0.001)., Conclusion: Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival., Competing Interests: Author SH was supported by grants from the Japan Pancreas Society. Author MU was supported by grants from Taiho Pharma, however, the funding source had no role in the design, practice, or analysis of this study. Author SS was supported by grants from Nihon Servier, Amino‐Up co, however, the funding source had no role in the design, practice, or analysis of this study. Authors HN, KH, and HY are editorial board members of Annals of Gastroenterological Surgery. Authors SH, IE, and AH are associate editors of Annals of Gastroenterological Surgery., (© 2024 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Background and study aims Recent advances in endoscopic transmural treatment have improved the clinical outcomes of patients with pancreatic fluid collections (PFCs). However, there is still a debate about the preventive effect of long-term placement of a transmural plastic stent (PS) on recurrence after successful endoscopic ultrasound (EUS)-guided treatment of PFCs. We conducted a systematic review and meta-analysis to evaluate PFC recurrence rates with and without a transmural PS after EUS-guided treatment. Patients and methods A systematic literature search of PubMed, Embase, and the Cochrane database was conducted to identify clinical studies comparing outcomes with and without transmural PS published until September 2022. Data on PFC recurrence and adverse events (AEs) were pooled using a random-effects model. Results Nine studies including 380 patients with long-term transmural PS and 289 patients without PS were identified. The rate of PFC recurrence was significantly lower in patients with transmural PS (pooled odds ratio [OR] = 0.23, 95% confidence interval [CI] [0.08-0.65], P = 0.005). In a subgroup analysis limited to studies focusing on patients with disconnected pancreatic duct syndrome, which has been reported to be a risk factor for PFC recurrence, the OR was numerically lower than that for the entire cohort (OR = 0.14, 95% CI [0.04-0.46]). The rate of AEs was significantly higher with long-term transmural PS (OR = 14.77, 95% CI [4.21-51.83]). Conclusions In this meta-analysis, long-term PS placement reduced the risk of PFC recurrence. Given the potential AEs of indwelling PS, further research is required to evaluate the overall benefits of long-term PS placement., Competing Interests: Conflict of Interest YN received research grants from Boston Scientific Japan, Fujifilm Corporation, and HOYA Corporation, and honoraria from Boston Scientific Japan, Fujifilm Corporation, Olympus Corporation, and Gadelius Medical. HI received research grants from Boston Scientific Japan, Fujifilm Corporation, Fujifilm Health Care Corporation, Gadelius Medical KK, and Zeon Medical Inc., and honoraria from Boston Scientific Japan, Fujifilm Corporation, Taewoong Medical Devices, Olympus Corporation, Century Medical Inc., and Cook Medical Japan G.K. Other authors have no conflicts of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Aims: There is a lack of biliary epithelial molecular markers for primary sclerosing cholangitis (PSC). We analyzed candidates from disease susceptibility genes identified in recent genome-wide association studies (GWAS)., Methods: Expression levels of GWAS genes were analyzed in archival liver tissues of patients with PSC and controls. Immunohistochemical analysis was performed to evaluate expression levels in the biliary epithelia of PSC (N = 45) and controls (N = 12). Samples from patients with primary biliary cholangitis (PBC) were used as disease controls (N = 20)., Results: Hepatic expression levels of ATXN2, HHEX, PRDX5, MST1, and TNFRSF14 were significantly altered in the PSC group. We focused on the immune-related receptor, TNFRSF14. Immunohistochemistry revealed that high expression of TNFRSF14 in biliary epithelial cells was observed only in the PSC group. In addition, the expression of LIGHT, which encodes a TNFRSF14-activating ligand, was increased in PSC liver. Immunohistochemistry showed that high expression of LIGHT was more common in PSC biliary epithelia (53%) than in the PBC (15%) or control (0%) groups; moreover, it was positively associated with fibrotic progression, although it was not an independent prognostic factor., Conclusions: TNFRSF14 and LIGHT are promising candidate markers for PSC., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)