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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).)

Background: The natural history of branch-duct intraductal papillary mucinous cystic neoplasms (BD-IPMNs) in the pancreas remains unclear. This study aimed to answer this clinical question by focusing on the development of concomitant pancreatic ductal adenocarcinomas (cPDAC)., Methods: The Japan Pancreas Society conducted a prospective multicenter surveillance study of BD-IPMN every six months for five years. The primary endpoints were progression of BD-IPMN, progression to high-grade dysplasia/invasive carcinoma (HGD/IC), and cPDAC. Factors predicting the progression of BD-IPMN to HGD/IC and development of cPDAC were also assessed as secondary endpoints., Results: Among the 2104 non-operated patients, 348 (16.5 %) showed progression of primary BD-IPMN. Cumulative incidences of BD-IPMN with HGD/IC and cPDAC during the 5.17-year surveillance period were 1.90 % and 2.11 %, respectively, and standard incidence ratios of BD-IPMN with HGD/IC and cPDAC were 5.28 and 5.73, respectively. Of 38 cPDACs diagnosed during surveillance, 25 (65.8 %) were resectable. The significant predictive characteristics of BD-IPMN for progression to HGD/IC were larger cyst size (p = 0.03), larger main pancreatic duct size (p < 0.01), and mural nodules (p = 0.02). Significant predictive characteristics for the development of cPDAC were male sex (p = 0.03) and older age (p = 0.02), while the size of IPMN was not significant., Conclusion: Careful attention should be given to "dual carcinogenesis" during BD-IPMN surveillance, indicating the progression of BD-IPMN to HGD/IC and development of cPDAC distinct from BD-IPMN, although the establishment of risk factors that predict cPDAC development remains a challenge (UMIN000007349)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Pancreatic juice cytology is useful for diagnosing pancreatic duct strictures and cystic lesions. However, some cases cannot be diagnosed using cytology. This study aimed to evaluate the utility of the overnight-stored pancreatic juice cell block (CB) method for diagnosing pancreatic disease., Methods: This retrospective study included 32 patients who presented with pancreatic duct strictures or cystic lesions between 2018 and 2024. The sensitivity, specificity, and accuracy of the CB method and single/multiple pancreatic juice cytology were compared to evaluate the utility of the CB., Result: An endoscopic nasopancreatic drainage tube was placed in the main pancreatic duct, and pancreatic juice was collected to create a CB specimen. The median amount of pancreatic juice collected was 180(30-200) mL, and the median number of cytological examinations was three(2-8). Of the 32 cases, 13 were malignant, and 19 were benign (non-malignant). The sensitivity was significantly higher for the CB method (62 %) than for single cytology(15 %, P = 0.0414), and there was no significant difference between CB and multiple cytology(54 %, P = 1.0). The specificity and accuracy were not significantly different between the CB method and single or multiple cytology. When multiple cytology and CB were combined, sensitivity improved to 77 %. The pathological findings of the CB specimens were similar to the surgical specimens, including immunohistochemistry., Conclusion: The overnight-stored pancreatic juice CB method was more effective than single cytology, with similar sensitivities to multiple cytology and can also be used for immunohistochemistry. The pancreatic juice CB method is useful for pancreatic juice assessment., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX are widely used as first-line regimens for unresectable pancreatic cancer (PC). When GnP therapy is selected, considering patient age or condition, second-line FOLFIRINOX is sometimes difficult to administer owing to its toxicity. This study aimed to determine the recommended dose (RD) of S-IROX (S-1, oxaliplatin, and irinotecan combination) regimens in patients with unresectable PC after first-line GnP failure. This phase-I study used the "3 + 3" dose-escalation design with two dose levels. Patients who failed first-line GnP therapy for unresectable PC were enrolled. Oxaliplatin and irinotecan were administered on day 1, and S-1 was administered orally twice daily on days 1-7, followed by 7 days of rest. The primary endpoints were dose-limiting toxicities (DLTs) and determination of RD. The secondary endpoint was the evaluation of potential antitumor activity. Nine patients received the second-line S-IROX regimen. In level-0 (S-1, 80 mg/m 2 ; oxaliplatin, 85 mg/m 2 ; and irinotecan, 120 mg/m 2 ), no patient experienced DLT; however, one patient experienced grade 3 neutropenia. At level-1 (irinotecan increased to 150 mg/m 2 ), one of six patients experienced DLTs, including G3 diarrhea. The RD was confirmed at the level-1 dose. The response rate, disease control rate, median progression-free survival, and median overall survival were 33.3%, 77.8%, 172 (range:77-422) days, and 414 (101-685) days, respectively. One patient underwent surgery after the second-line S-IROX therapy. Second-line S-IROX treatment was deemed acceptable. The RD was set at level-1 dose (S-1, 80 mg/m 2 ; oxaliplatin, 85 mg/m 2 ; and irinotecan, 150 mg/m 2 )., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

The identification of anticancer therapies using next-generation sequencing (NGS) is necessary for the treatment of cholangiocarcinoma. NGS can be easily performed when cell blocks (CB) are obtained from bile stored overnight. We compared NGS results of paired CB and surgically resected specimens (SRS) from the same cholangiocarcinoma cases. Of the prospectively collected 64 bile CBs from 2018 to 2023, NGS was performed for three cases of cholangiocarcinoma that could be compared with the SRS results. The median numbers of DNA and RNA reads were 95,077,806 [CB] vs. 93,161,788 [SRS] and 22,101,328 [CB] vs. 24,806,180 [SRS], respectively. We evaluated 588 genes and found that almost all genetic alterations were attributed to single-nucleotide variants, insertions/deletions, and multi-nucleotide variants. The coverage rate of variants in SRS by those found in CB was 97.9-99.2%, and the coverage rate of SRS genes by CB genes was 99.6-99.7%. The NGS results of CB fully covered the variants and genetic alterations observed in paired SRS samples. As bile CB is easy to prepare in general hospitals, our results suggest the potential use of bile CB as a novel method for NGS-based evaluation of cholangiocarcinoma.

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.

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.)

Background and Aims: Covered self-expandable metallic stents have longer patency than uncovered self-expandable metallic stents for unresectable malignant distal biliary obstruction because of the prevention of tumor ingrowth, and they are removable during reintervention. One main cause of recurrent biliary obstruction in covered self-expandable metallic stents is sludge formation, which can be prevented by using large-bore stents. We evaluated the treatment results of 12-mm and 10-mm covered self-expandable metallic stents for unresectable malignant distal biliary obstructions using a randomized controlled trial., Methods: This study was conducted between May 2016 and January 2019 and included 81 consecutive patients with unresectable malignant distal biliary obstruction. The primary endpoint was the rate of nonrecurrent biliary obstruction at 6 months after stent placement., Results: The primary endpoint in the 12-mm group was significantly higher than that in the 10-mm group (P = .0369). Therefore, the median time to recurrent biliary obstruction was 172 days in the 12-mm group and 120 days in the 10-mm group. The median time to recurrent biliary obstruction in the 12-mm group was significantly longer than that in the 10-mm group (P = .0168). Using the 12-mm covered self-expandable metallic stents and receiving chemotherapy were factors affecting the rate of recurrent biliary obstruction in the multivariate analysis., Conclusions: The 12-mm covered self-expandable metallic stents provide a longer time to recurrent biliary obstruction than do 10-mm covered self-expandable metallic stents for managing unresectable malignant distal biliary obstruction. (Clinical trial registration number: UMIN000016911.)., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background/aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using a 19-gauge needle is an efficient sampling method for the diagnosis of lymphadenopathy. This study compared 19-gauge conventional and Franseen needles for the diagnosis of lymphadenopathy and classification of malignant lymphoma (ML)., Methods: Patient characteristics, number of needle passes, puncture route, sensitivity, specificity, and accuracy of cytology/histology for lymphadenopathy were analyzed in patients diagnosed with lymphadenopathy by EUS-FNA using conventional or Franseen needles., Results: Between 2012 and 2022, 146 patients met the inclusion criteria (conventional [n=70] and Franseen [n=76]). The median number of needle passes was significantly lower in the conventional group than in the Franseen group (3 [1-6] vs. 4 [1-6], p=0.023). There were no significant differences in cytological/histological diagnoses between the two groups. For ML, the immunohistochemical evaluation rate, sensitivity of flow cytometry, and cytogenetic assessment were not significantly different in either group. Bleeding as adverse events (AEs) were observed in three patients in the Franseen group., Conclusions: Both the 19-gauge conventional and Franseen needles showed high accuracy in lymphadenopathy and ML classification. Considering sufficient tissue collection and the avoidance of AEs, the use of 19-gauge conventional needles seems to be a good option for the diagnosis of lymphadenopathy.

Background: Extracorporeal shock wave lithotripsy (ESWL) is a common treatment for pancreatic stones in chronic pancreatitis. In contrast, peroral pancreatoscopy-guided lithotripsy (POPS-L) remains underexplored, with limited comparative studies to ESWL. This study compared the treatment outcomes of disposable POPS-L tools and ESWL for pancreatic stones., Methods: A retrospective analysis was conducted on 66 patients who had undergone pancreatic stone treatment at three institutions between 2006 and 2022. The treatment outcomes of POPS-L and ESWL were compared., Results: This study included 19 and 47 patients who had undergone POPS-L and ESWL, respectively. In a comparison between POPS-L and ESWL, the stone clearance rates were 78.9% vs. 70.2% ( p = 0.55), while the procedure-related complication rates were 21% vs. 6.3% ( p = 0.09). The median total session counts were 1 vs. 5 ( p < 0.01). The cumulative stone recurrence rates were comparable in both groups. Multivariate analysis revealed no significant factors influencing the stone clearance rates, and the choice between POPS-L and ESWL did not affect the stone clearance rates., Conclusions: POPS-L and ESWL exhibited comparable treatment outcomes in terms of stone clearance, complications, and recurrence rates. Furthermore, POPS-L is advantageous due to the need for fewer sessions to achieve pancreatic stone clearance.

Background: Although intraductal plastic stent (IS) placement is an effective treatment for unresectable malignant hilar biliary obstruction (UMHBO), the effectiveness of unilateral and bilateral IS drainage remains controversial. This retrospective study investigated the effectiveness of bilateral IS placement for UMHBO using the propensity score matching method., Methods: Patients who underwent transpapillary endoscopic stenting for UMHBO were analyzed for technical and clinical success, adverse events, and time to recurrent biliary obstruction (TRBO)., Results: A total of 321 patients were enrolled in the study with 27 patients in each unilateral and bilateral IS group in the propensity score-based cohort. Technical success was 100%, while clinical success was 93% and 96% in the unilateral and bilateral IS groups, respectively (p = 1.0). Cholecystitis occurred in 4% and 7%, respectively (p = 1.0). The median TRBO was shorter in the unilateral group (129 [5-383] days) than that in the bilateral group (226 [16-563] days) (p = .0281). Bilateral IS placement was an independent long TRBO factor (hazard ratio [HR] 0.46; 95% confidence interval [CI]: 0.21-0.97; p = .041)., Conclusions: Unilateral and bilateral IS placement had high technical and clinical success rates in primary stent placement. However, bilateral IS placement showed a longer TRBO. Bilateral IS placement may be a good option for initial UMHBO drainage., (© 2023 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Objectives: The placement of plastic stents (PS), including intraductal PS (IS), is useful in patients with unresectable malignant hilar biliary obstruction (UMHBO) because of patency and ease of endoscopic reintervention (ERI). However, the optimal stent replacement method for PS remains unclear., Methods: This retrospective study included 322 patients with UMHBO. Among them, 146 received PS placement as initial drainage (across-the-papilla PS [aPS], 54; IS, 92), whereas 75 required ERI. Eight bilateral aPS, 21 bilateral IS, and 17 bilateral self-expandable metallic stent (SEMS) placements met the inclusion criteria. Rates of technical and clinical success, adverse events, recurrent biliary obstruction (RBO), time to RBO (TRBO), overall survival, and secondary ERI were compared., Results: There were no significant intergroup differences in rates of technical or clinical success, adverse events, RBO occurrence, or overall survival. The median TRBO was significantly shorter in the aPS group (47 days) than IS (91 days; P = 0.0196) and SEMS (143 days; P < 0.01) groups. Median TRBO did not differ significantly between the IS and SEMS groups (P = 0.44). On Cox multivariate analysis, the aPS group had the shortest stent patency (hazard ratio 2.67 [95% confidence interval 1.05-6.76], P = 0.038). For secondary ERI, the median endoscopic procedure time was significantly shorter in the IS (22 min) vs. SEMS (40 min) group (P = 0.034)., Conclusions: Bilateral IS and SEMS placement featured prolonged patency after first ERI. Because bilateral IS placement is faster than SEMS placement and IS can be removed during secondary ERI, it may be a good option for first ERI., (© 2024 Japan Gastroenterological Endoscopy Society.)

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/).)

A 59-year-old man receiving sunitinib chemotherapy for postoperative recurrence of renal cell carcinoma (RCC) metastases was found to have multiple metastases on contrast-enhanced computed tomography (CECT). CECT revealed a typical hyperdense enhanced nodule in the arterial phase of the stomach and head and tail of the pancreas. However, in the uncinate process of the pancreas, CECT revealed an atypical image and a hypodense enhanced nodule in each phase. Both lesions were finally pathologically diagnosed as clear cell carcinoma. Treatment-modified pancreatic metastases from RCC may present with nonspecific images; therefore, caution is required when deciding on treatment strategies.

Background: Postoperative pancreatic fluid collections (POPFCs) are common adverse events (AEs) after pancreatic surgery and may need interventions. Endoscopic ultrasound (EUS)-guided drainage for POPFCs is increasingly reported, but its appropriate timing has not been fully elucidated. The aim of this meta-analysis was to evaluate treatment outcomes of POPFCs according to the timing of EUS-guided drainage., Methods: Using PubMed, Embase, Web of Science, and the Cochrane database, we identified clinical studies published until December 2022 with data comparing outcomes of early and delayed EUS-guided drainage for POPFCs. We pooled data on AEs, mortality, and technical and clinical success rates, using the random-effects model., Results: From 1415 papers identified in the initial literature search, we identified 6 retrospective studies, including 128 and 107 patients undergoing early and delayed EUS-guided drainage for POPFCs. The threshold of early and delayed drainage ranged from 14 to 30 days. Distal pancreatectomy was the major cause of POPFCs, ranging from 44 to 100%. The pooled odds ratio (OR) for AEs was 0.81 (95% confidence interval [CI] 0.40-1.64, P = 0.55) comparing early to delayed drainage. There was no procedure-related mortality. Technical success was achieved in all cases and a pooled OR of clinical success was 0.60 (95% CI 0.20-1.83, P = 0.37)., Conclusion: POPFCs can be managed by early EUS-guided drainage without an increase in AEs., (© 2023. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Therefore, indicators that can be used for the early prediction of the prognosis of PDAC are needed. Peroxiredoxin (PRDX) 4 is a secretion-type antioxidant enzyme located in the cytoplasmic endoplasmic reticulum. Recent studies have reported that it is closely related to the development and prognosis of many types of cancer. Perilipin (PLIN) 2 is a lipid droplet coating protein. The high expression of PLIN2 is known to be an indicator of some types of cancer and oxidative stress management. It is highly suggestive of the interplay between PRDX4 and PLIN2 to some degree. In this study, we collected 101 patients' clinical data and paraffin-embedded specimens with PDAC and analyzed them with immunohistochemical staining of PRDX4 and PLIN2. We found that the low expression of PRDX4 predicts longer survival and a better clinical condition in PDAC patients. Moreover, when the low expression of PRDX4 is combined with the low expression of PLIN2, the 3-year survival is significantly improved. Univariate and multivariate Cox proportional hazard analyses showed that the PRDX4 expression in PDAC was an independent prognostic factor for survival. Taken together, between PRDX4 and PLIN2, PRDX4 plays a main role in prognosis and has the potential to become a clinical prognostic indicator of PDAC., (©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Background and Aims: Intraductal plastic stent (IS) placement for unresectable malignant hilar biliary obstruction (UMHBO) is an effective option for biliary drainage. However, the effectiveness of bilateral IS placement compared with bilateral self-expandable metal stent (SEMS) placement remains unclear., Methods: Overall, 301 patients with UMHBO were enrolled; 38 patients underwent bilateral IS placement (IS group) and 38 patients underwent SEMS placement (SEMS group) in the propensity score-based cohort. Both groups were compared for technical and clinical success, adverse events (AEs), recurrent biliary obstruction (RBO), time to RBO (TRBO), overall survival (OS), and endoscopic reintervention (ERI)., Results: No significant differences were observed between the groups regarding technical and clinical success, AEs and RBO occurrence rates, TRBO, or OS. The median initial endoscopic procedure time was significantly shorter in the IS group (23 vs 49 minutes, P < .01). ERI was performed on 20 and 19 patients in the IS and SEMS groups, respectively. The median ERI procedure time was significantly shorter in the IS group (22 vs 35 minutes, P = .04). Median TRBO after ERI with plastic stent placement tended to be longer in the IS group (306 vs 56 days, P = .068). A Cox multivariate analysis showed that the IS group was the significant related factor for TRBO after ERI (hazard ratio, .31; 95% confidence interval, .25-.82; P = .035)., Conclusions: Bilateral IS placement can reduce the duration of the endoscopic procedure and provide sufficient stent patency both initially and after ERI stent placement, and the stents are removable. Bilateral IS placement is considered a good option for initial UMHBO drainage. (Clinical trial registration number: UMIN000050546.)., Competing Interests: Disclosure All authors disclosed no financial relationships. This work was supported by JSPS KAKENHI (grant no. JP23K14646, Mitsuru Okuno)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: Bilateral self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (UMHBO) is an effective option for biliary drainage with long-term stent patency. Laser-cut and braided SEMS can be used for bilateral SEMS placement. This study aimed to clarify any differences in the clinical features and proper use of the laser-cut and braided SEMS placement using the stent-in-stent method for UMHBO., Methods: In this study, 78 patients who underwent bilateral stent-in-stent SEMS placement for UMHBO were included. The patients were divided into the laser-cut (n = 33) and braided groups (n = 45). Both groups were compared for technical and clinical success, adverse events (AEs), time to recurrent biliary obstruction (TRBO), overall survival, and endoscopic reintervention (ERI)., Results: There were no significant differences in technical and clinical success rates (laser-cut vs. braided group, 97% vs. 95.6%, P = 1.0), AEs (21.2% vs. 15.6%. P = 0.56), median TRBO (242 days vs. 140 days, P = 0.36), and median overall survival (654 days vs. 675 days, P = 0.58). ERI was required in 15 patients in the laser-cut group and in 20 patients in the braided group. The technical and clinical success rates of ERI (60% vs. 85%) were not significantly different (P = 0.13); however, the median ERI procedure time was significantly longer in the laser-cut group (38 min) than in the braided group (22 min; P = 0.02)., Conclusion: No significant difference in initial SEMS placement was noted between the laser-cut and braided groups; however, the laser-cut group required a longer ERI procedure time than that required by the braided group. The use of braided SEMS may be a convenient option for ERI., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pancreatic fluid collections (PFCs) typically develop as local complications of acute pancreatitis and complicate the clinical course of patients with acute pancreatitis and potentially fatal clinical outcomes. Interventions are required in cases of symptomatic walled-off necrosis (WON) (matured PFCs with necrosis) and pancreatic pseudocysts (matured PFCs without necrosis). In the management of necrotizing pancreatitis and WON, endoscopic ultrasound-guided transluminal drainage combined with on-demand endoscopic necrosectomy (i.e. the step-up approach) is increasingly used as a less invasive treatment modality compared with a surgical or percutaneous approach. Through the substantial research efforts and development of specific devices and stents (e.g. lumen-apposing metal stents), endoscopic techniques of PFC management have been standardized to some extent. However, there has been no consensus about timing of carrying out each treatment step; for instance, it is uncertain when direct endoscopic necrosectomy should be initiated and finished and when a plastic or metal stent should be removed following clinical treatment success. Despite emerging evidence for the effectiveness of noninterventional supportive treatment (e.g. antibiotics, nutritional support, irrigation of the cavity), there has been only limited data on the timing of starting and stopping the treatment. Large studies are required to optimize the timing of those treatment options and improve clinical outcomes of patients with PFCs. In this review, we summarize the current available evidence on the indications and timing of interventional and supportive treatment modalities for this patient population and discussed clinical unmet needs that should be addressed in future research., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Endoscopic ultrasound-guided antegrade treatment (EUS-AG) and balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) have emerged as useful procedures for managing bile duct stones (BDS) in patients with surgically altered anatomy. However, the comparison between these two procedures has not been well studied. The aim of our study was to compare the clinical outcomes of EUS-AG and BE-ERCP for managing BDS in patients with surgically altered anatomy., Methods: The database was retrospectively evaluated at two tertiary care centers to identify patients with surgically altered anatomy who underwent either EUS-AG or BE-ERCP for BDS. Clinical outcomes were compared between the procedures. The success rate of each procedure was evaluated in three steps: endoscopic approach, biliary access, and stone extraction., Results: Among the 119 identified patients, 23 had EUS-AG, and 96 had BE-ERCP. The overall technical success rates of EUS-AG and BE-ERCP were 65.2% (15/23) and 69.8% (67/96), respectively (P = .80). The comparison of each step between the procedures EUS-AG versus BE-ERCP was as follows: endoscopic approach, 100% (23/23) versus 88.5% (85/96) (P = .11); biliary access, 73.9% (17/23) versus 80.0% (68/85) (P = .57); stone extraction, 88.2% (15/17) versus 98.5% (67/68) (P = .10). The overall adverse event rate was 17.4% (4/23) versus 7.3% (7/96) (P = .22)., Conclusions: Both EUS-AG and BE-ERCP are effective and relatively safe procedures in the management of BDS in patients with surgically altered anatomy. The challenging steps of each procedure might be different, which could help decide which one to use to manage BDS in patients with surgically altered anatomy., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Benign choledochojejunal anastomotic stricture (CJS) is a common complication of pancreaticoduodenectomy and choledochojejunostomy. CJS is generally treated with balloon dilation, using balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP); however, its long- and short-term outcomes have not been fully evaluated. Therefore, we evaluated the treatment outcomes of balloon dilation with BE-ERCP for CJS., Methods: We retrospectively analyzed 40 patients who had undergone balloon dilation with BE-ERCP for CJS between January 2009 and December 2022. The primary outcomes were technical and clinical success, and adverse event rates of balloon dilation using BE-ERCP for CJS. The secondary outcomes were long-term treatment outcomes for CJS recurrence, and evaluation of risk factors for recurrence., Result: Technical and clinical success rates were 93% (37/40) and 100% (37/37), respectively. CJS recurrence occurred in 32% (20/37). No procedure-related adverse events were observed. The significant risk factors of CJS after balloon dilation were its early occurrence after surgery (unit hazard ratio [HR] for month, 0.87; 95% confidence interval [CI], 0.76-0.99; p-value = 0.04) and residual waist during balloon dilation (HR, 5.46; 95% CI, 1.18-25.1; p-value = 0.03). Receiver operating characteristic curve analysis of time from surgery to balloon dilation revealed an area under the curve of 0.80 (95% CI, 0.65-0.94) and the cut-off value was 13.2 months., Conclusion: Treatment of CJS with balloon dilation was effective, although CJS recurrence occurred in one-third of the patients. The risk factors for recurrence were early occurrence of CJS after surgery and remaining waist circumference during balloon dilation., (© 2023. The Author(s).)

Background and Aims: A novel EUS-guided fine-needle biopsy sampling (EUS-FNB) needle enabled physicians to obtain sufficient pathologic samples with fewer to-and-fro movements (TAFs) within the lesion. We compared the diagnostic yields of EUS-FNB with 3 and 12 TAFs at each puncture pass., Methods: The primary endpoint of this multicenter, noninferiority, crossover, randomized controlled trial involving 6 centers was diagnostic sensitivity. Secondary endpoints were diagnostic accuracy and quantity and quality evaluation of EUS-FNB specimens. Length of the macroscopically visible core (MVC) and microscopic histologic quantity were used for quantitative evaluation. Macroscopic visual and microscopic histologic evaluations were performed for qualitative evaluation., Results: Among 110 patients (220 punctures, 110 for 3 TAFs and 12 TAFs each), 105 (210 punctures) had malignant histology. Diagnostic sensitivity for malignancy of 3 TAFs (88.6%) was not inferior to that of 12 TAFs (89.5%; difference, -.9%; 95% confidence interval, -9.81 to 7.86). Diagnostic accuracy for malignancy was 92.7% for 3 TAFs and 94.6% for 12 TAFs. Overall median MVC length was 13.5 mm in both groups. The 3-TAF group had a significantly higher rate of score ≥3 on macroscopic visual quality evaluation than the 12-TAF group (71.8% vs 52.7%, P = .009). No significant intergroup differences existed in microscopic histologic quantity and quality evaluations (quantity evaluation, 88.2% for 3 TAFs vs 83.6% for 12 TAFs; quality evaluation, 90.0% for 3 TAFs vs 89.1% for 12 TAFs)., Conclusions: Diagnostic sensitivity and accuracy of EUS-FNB with 3 TAFs were not inferior to those with 12 TAFs for solid pancreatic lesions. The 3-TAF group showed significantly less blood contamination in sampled tissues than the 12-TAF group. (Clinical trial registration number: UMIN000037309.)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: With the increasing popularity of endoscopic ultrasound (EUS)-guided transmural interventions, walled-off necrosis (WON) of the pancreas is increasingly managed via non-surgical endoscopic interventions. However, there has been an ongoing debate over the appropriate treatment strategy following the initial EUS-guided drainage. Direct endoscopic necrosectomy (DEN) removes intracavity necrotic tissue, potentially facilitating early resolution of the WON, but may associate with a high rate of adverse events. Given the increasing safety of DEN, we hypothesised that immediate DEN following EUS-guided drainage of WON might shorten the time to WON resolution compared to the drainage-oriented step-up approach., Methods: The WONDER-01 trial is a multicentre, open-label, superiority, randomised controlled trial, which will enrol WON patients aged ≥ 18 years requiring EUS-guided treatment in 23 centres in Japan. This trial plans to enrol 70 patients who will be randomised at a 1:1 ratio to receive either the immediate DEN or drainage-oriented step-up approach (35 patients per arm). In the immediate DEN group, DEN will be initiated during (or within 72 h of) the EUS-guided drainage session. In the step-up approach group, drainage-based step-up treatment with on-demand DEN will be considered after 72-96 h observation. The primary endpoint is time to clinical success, which is defined as a decrease in a WON size to ≤ 3 cm and an improvement of inflammatory markers (i.e. body temperature, white blood cell count, and C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, and recurrence of the WON., Discussion: The WONDER-01 trial will investigate the efficacy and safety of immediate DEN compared to the step-up approach for WON patients receiving EUS-guided treatment. The findings will help us to establish new treatment standards for patients with symptomatic WON., Trial Registration: ClinicalTrials.gov NCT05451901, registered on 11 July 2022. UMIN000048310, registered on 7 July 2022. jRCT1032220055, registered on 1 May 2022., (© 2023. The Author(s).)

Background and Aims: Sludge occlusion is a primary reason for recurrent biliary obstruction (RBO) after self-expandable metallic stent (SEMS) placement. However, the efficacy of ursodeoxycholic acid (UDCA) for SEMS occlusion remains unexplored to date. This study aimed to evaluate the efficacy of UDCA after SEMS placement for malignant distal biliary obstruction (MDBO)., Methods: Three hundred fifty-four patients were included, of which 60 received UDCA. Additionally, we conducted a propensity score-matched cohort analysis on 110 patients with SEMS placement for MDBO to reduce selection bias. Patients were categorized into 2 groups of 55 each, based on whether they received UDCA. In the UDCA group, the treatment was administered for more than a month. The primary endpoint was the time to RBO (TRBO) after SEMS placement. The secondary endpoint was to evaluate SEMS occlusion rate and early adverse events (AEs)., Results: The cumulative SEMS occlusion rate was 41.8% and 18.2% in the groups with and without UDCA, respectively (P = .0119). Median TRBO was significantly longer in the control group than in the UDCA group (528 vs 154 days, P = .0381). In the multivariate analysis, UDCA administration was identified as the independent risk factor for reducing TRBO (hazard ratio, 2.28; 95% confidence interval, 1.06-4.88; P = .0348). The overall early AE rate showed insignificant differences between groups., Conclusions: Administering UDCA after SEMS placement was not efficacious for prolonging the TRBO in MDBO. Moreover, administering UDCA beyond a month might increase the risk of stent sludge occlusion. (Clinical trial registration number: UMIN000046862.)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Pancreatic fluid collections (PFCs) commonly develop as complications of acute pancreatitis and ductal disruption due to chronic pancreatitis. In the revised Atlanta classification, PFCs were classified based on the presence of necrosis and duration following the onset of acute pancreatitis. Interventions are required in cases of symptomatic pancreatic pseudocysts or walled-off necrosis (WON). In the management of these PFCs, endoscopic ultrasound-guided transluminal drainage and subsequent direct endoscopic necrosectomy for WON are increasingly utilized as less invasive treatment modalities compared to surgical debridement. To date, researchers have focused predominantly on the technical aspects of endoscopic therapy for symptomatic PFCs. Given the poor physical condition of patients receiving endoscopic treatment for PFCs, systemic support may have a substantial impact on the short- and long-term outcomes of these patients. A multidisciplinary approach is required to improve the clinical outcomes of patients with infected PFCs and their associated comorbidities. However, non-interventional support during the periprocedural period of endoscopic treatment of PFCs has not been fully discussed, and there have been considerable variations in the selection of treatment options between endoscopists and centers. To address these unmet needs in the clinical management of PFCs and promote future research to improve the clinical outcomes, we conducted a review of the literature within a multicenter consortium of expert endoscopists with specific expertise in the endoscopic treatment of PFCs. In this review, we summarize the current evidence on non-interventional supportive care (e.g., continuous lavage, medications, nutritional support, and antimicrobials) and propose potential topics for future research., (© 2022. Japanese Society of Gastroenterology.)

Video 1Management of ampullary perforation by endoscopic nasobiliary drainage tube placement through the perforation for suctioning out leaked intestinal juice and indicating the presence of the hepatic portal vein., (© 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

Objectives: Interventions for necrotizing pancreatitis are generally postponed until 4 weeks after the onset of acute pancreatitis, but there remains controversy about whether we should always wait >4 weeks or can intervene early when necessary. This meta-analysis was conducted to evaluate treatment outcomes of necrotizing pancreatitis according to the cut-off defined in the revised Atlanta classification (≤4 vs. >4 weeks)., Methods: Using PubMed, Web of Science, and the Cochrane database, we identified clinical studies published until March 2022 with data comparing outcomes of early and delayed interventions of necrotizing pancreatitis. We pooled data on adverse events, mortality, technical and clinical success rates, and needs for necrosectomy and open surgery, using the random-effects model., Results: We identified 11 retrospective studies, including 775 patients with early interventions and 725 patients with delayed interventions. Patients with early interventions tended to be complicated by organ failure. The rate of adverse events was comparable (OR 1.41, 95% CI 0.66-3.01; p  = 0.38) but the rate of mortality was significantly higher (OR 1.70, 95% CI 1.21-2.40; p  < 0.01) in early interventions. Technical success rates were similarly high but clinical success rates tended to be low (OR 0.39, 95% CI 0.15-1.00; p  = 0.05) in early interventions, though not statistically significant. Pooled ORs for necrosectomy and open surgery were 2.14 and 1.23, respectively., Conclusions: Early interventions for necrotizing pancreatitis were associated with higher mortality rates and did not reduce adverse events or improve clinical success. However, our results should be confirmed in prospective studies., Competing Interests: Yousuke Nakai received research grants from Boston Scientific Japan, HOYA Corporation, and honoraria from Boston Scientific Japan, Fujifilm Corporation, and Olympus Corporation. Hiroyuki Isayama received research grants from Boston Scientific Japan, Fujifilm Corporation, Fujifilm Health Care Corporation, Gaderius Medical KK, 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., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: During endoscopic ultrasound-guided biliary drainage (EUS-BD), a combination of a 19-gauge needle and a 0.025-inch guidewire is generally used. However, a 19-gauge needle has poor maneuverability because of their stiffness and rigidity and might have poor penetrability in non-dilated bile ducts because of their large bore. In contrast, the application of a 22-gauge needle is expected to have improved maneuverability. However, only a 0.018-inch guidewire, which has less supportability, is applicable in the subsequent guidewire selection. This study aimed to evaluate the feasibility and safety of a dedicated bougie dilator for a 0.018-inch guidewire., Methods: From September 2019 to May 2020, 26 patients underwent fistula dilation using the dilator after accessing the bile duct using a 22-gauge needle and a 0.018-inch guidewire during EUS-BD. The success and adverse event rates of EUS-BD were evaluated., Results: Biliary access with a combination of a 22-gauge needle and a 0.018-inch guidewire was successful in all with a median bile duct diameter of 5 mm. Dilation of the fistula using the dedicated dilator was also successful in all cases. Subsequently, the dilator was successfully exchanged to an ERCP catheter that allowed for exchange to a 0.025-inch guidewire, except in one case where the catheter did not cross the fistula and a dilation balloon was inserted for an exchange to a 0.025-inch guidewire. The technical success rate of the EUS-BD was 100%. The adverse event rate was 19%., Conclusion: The application of the dedicated dilator for a 0.018-inch guidewire was considered feasible and safe for EUS-BD., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background & Aims: The efficacy of endoscopic sphincterotomy (ES) before endoscopic transpapillary biliary drainage in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been established. The aim of this study was to evaluate the effect of performing ES before biliary stent/tube placement on the occurrence of PEP., Methods: Three hundred seventy patients with biliary stricture requiring endoscopic biliary stenting were enrolled and randomly allocated to the ES group (n = 185) or non-ES group (n = 185). All participants were followed up for 30 days after the procedure. The data and occurrence of adverse events were prospectively collected. The primary outcome measure of this study was the incidence of PEP within 2 days of initial transpapillary biliary drainage. Secondary outcome measures were the incidence of other adverse events related to biliary stent/tube placement., Results: PEP occurred in 36 patients (20.6%) in the non-ES group and in 7 patients (3.9%) in the ES group (P < .001). The difference in the incidence of PEP between the 2 groups in the per-protocol population was 16.7% (95% confidence interval, 10.1%-23.3%), which was not within the noninferiority margin of 6%. Except for bleeding, the incidences of other adverse events were not significantly different between the groups., Conclusion: ES before endoscopic biliary stenting could have the preventive effect on the occurrence of PEP in patients with biliary stricture. University Hospital Medical Information Network Number, UMIN000025727.University Hospital Medical Information Network Clinical Trial Registry URL: https://www.umin.ac.jp/ctr/index.htm., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The specimen collection and subsequent pathological diagnosis of malignant biliary stricture (MBS) are difficult. This study aimed to determine whether the cell block (CB) method using overnight-stored bile is useful in the diagnosis of MBS. This trial was a single-arm prospective study involving a total of 59 patients with suspected MBS. The primary endpoint was cancer detectability and accuracy using the CB method, and a comparison with the detectability and accuracy achieved with bile cytology was made. The immunohistochemical sensitivity for maspin and p53 was also investigated in the CB and surgical specimens. We were able to collect bile from all 59 patients, and 45 of these patients were clinically diagnosed with MBS. The cancer detectability using the CB method (62.2%) was significantly higher than that using cytology (37.8%) ( p = 0.0344). When CB was combined with biopsy, the rates of cancer detectability (75.6%) and accuracy (81.4%) increased. In eight patients who received surgical therapy, maspin- and p53-immunohistochemistry was applied to the surgical and CB specimens, and cancer cells in both specimens showed positive cytoplasmic and nuclear staining for maspin and nuclear staining for p53. The CB method is, thus, useful for detecting malignancy (UMIN000034707).

Background: Expanding indications for neoadjuvant chemotherapy (NAC) for resectable pancreatic cancer prolong the period from diagnosis to surgery. In resectable pancreatic cancer with malignant biliary obstruction (MBO), the biliary drainage method without any biliary events is ideally required to safely perform NAC as planned. Plastic stents (PS) have been traditionally used for preoperative biliary drainage; however, recently, covered self-expandable metallic stents (CSEMS) have emerged as a tool for preoperative biliary drainage., Aims: To compare CSEMS with PS for preoperative biliary drainage in the management of resectable pancreatic cancer with MBO., Methods: In this multicenter retrospective cohort study, we compared CSEMS with PS for preoperative biliary drainage in patients with pancreatic cancer at three tertiary care centers between 2008 and 2019., Results: Of the 120 enrolled patients, 45 underwent CSEMS and 75 underwent PS. No significant difference was observed in the basic characteristics between the groups. The rate of recurrent biliary obstruction (RBO) was significantly lower and the time to RBO was significantly longer in the CSEMS group. In multivariate analysis, CSEMS was an independent factor for a longer RBO. However, pancreatitis and cholecystitis were more common in the CSEMS group. The surgery-related adverse events were not significantly different between the two groups, except for longer surgery time and time to discharge in the CSEMS group., Conclusions: CSEMS for preoperative endoscopic biliary drainage in patients with pancreatic cancer reduced RBO, although the risk for pancreatitis or cholecystitis could be increased.

Introduction: Image evaluation of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) and additional time-intensity curve (TIC) analysis enable qualitative and quantitative analyses of pancreatic tumor based on real-time perfusion imaging., Aims: To evaluate the efficacy of CEH-EUS with a combination of qualitative and quantitative analyses of pancreatic solid tumors., Methods: Patients were scheduled to undergo EUS-guided fine needle aspiration (FNA) for pancreatic solid tumors were prospectively enrolled between 11/2016 and 12/2018 and underwent CEH-EUS. The vascular and enhancement patterns were qualitatively evaluated and heterogeneous enhancement was defined to be indicative of malignancy. The echo intensity change during 60 s in the tumor was quantitatively evaluated by time intensity curve analysis., Results: In total, 100 patients were enrolled in this study. The final diagnoses were malignant lesions in 87 patients and benign legions in 13 patients. There were four categories of enhancement and patterns: hypovascular with heterogeneous, hypovascular with homogeneous, hypervascular heterogeneous, and hypervascular homogeneous enhancement. The diagnostic capability of qualitative analysis was the sensitivity, specificity, and accuracy of 89%, 62%, and 85%, respectively. With respect to time intensity curve analysis, the time to peak of malignant lesions was significantly shorter than those of benign lesions (P = 0.0009) with an optimal cutoff value of 12.81 s on the receiver operating characteristic curve analysis. With the combination of qualitative and quantitative analyses, the sensitivity, specificity, and accuracy were improved to 100%, 54%, and 94%, respectively., Conclusions: CEH-EUS with combined qualitative and quantitative analyses for pancreatic tumors might be useful as a complement for EUS-FNA. The UMIN Clinical Trials Registry (UMIN000025192)., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aim: Hemorrhage is often encountered after endoscopic submucosal dissection (ESD). In addition to active bleeding after resection, exposed blood vessels and blood clots without active bleeding on the post-dissection ulcer floor have been recognized within our department. We consider exposed and/or observable vessel findings and clots on the ulcer floor after re-section as important risk factors for hemorrhage. Here, we compared and examined the active bleeding frequency and "post-resection ulcer at risk of bleeding" on the day following ESD, in relation to their risk factors., Method: We retrospectively examined 447 patients who underwent second-look endoscopy in our department between August 2008 and March 2018. Logistic regression analyses were performed to determine the hazard ratio and 95% confidence interval. We compared the association of each factor mentioned above with active bleeding on the day after ESD and the presence of ulcers at risk of bleeding after resection., Results: Our retrospective analysis revealed that the risk factors were larger ulcer sizes and the administration of antithrombotic drugs. Additionally, the risk was low for upper body lesions but high for antral lesions., Conclusion: Our results may help determine whether second-look endoscopy should be performed to minimize active bleeding after ESD, reduce postoperative complications, and improve medical safety.

After an abdominal injury, a woman in her 20s presented to our hospital with abdominal pain. Pancreatic trauma was discovered on computed tomography, along with a pancreatic duct injury and pancreatic juice leakage. Endoscopic retrograde pancreatography revealed a 10-mm rupture of the pancreatic body's main pancreatic duct (MPD) and intraperitoneal leakage of contrast enzyme from the MPD. The pancreatic injury was treated with the placement of a 5-Fr endoscopic nasopancreatic drainage tube in the ruptured distal side of the pancreatic duct;however, 3 months later, the MPD stenosis occurred. The MPD stenosis was improved using a 7-Fr pancreatic stent, and finally, placement of the pancreatic stent was not required for MPD drainage.

Background: Endoscopic transpapillary gallbladder drainage (EGBD) has been reported as an effective gallbladder drainage treatment option for acute cholecystitis in high-risk surgical patients. However, the long-term outcomes such as cholecystitis' recurrence rate after placement of EGB stenting (EGBS) have not been well studied yet., Aims: The aim of the present study was to compare the long-term outcome of EGBS and removal of gallbladder drainage after percutaneous transhepatic gallbladder drainage (PTGBD) or endoscopic nasogallbladder drainage (ENGBD) for acute cholecystitis in high-risk surgical patients and clarify the usefulness of long-term placement of EGBS., Methods: We retrospectively studied 180 high-risk surgical patients with acute cholecystitis between January 2010 and December 2018. The patients were divided into two groups: EGBS group (long-term placement of EGBS) or Removal group (removal of drainage tube after PTGBD or ENGBD). Clinical outcomes, including long-term results, were compared between the groups., Results: The cumulative late adverse event (AE) rates were 5.0% and 22.1% in the EGBS and Removal group (P = .002), with a median follow-up period of 375 and 307 days in the two groups, respectively. The cumulative cholecystitis recurrence rate was 5.0% (2/40) in the EGBS group and 16% (21/131) in the Removal group (P = .024), respectively. In the multivariate analysis for late AE, only EGBS was an independent risk factor with a decreasing value., Conclusion: The permanent EGBS in high-risk surgical patients with acute cholecystitis was considered effective in reducing the risk of late AE., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background and study aims  Preoperative assessment of the superficial ductal spread (SDS) of perihilar cholangiocarcinoma (PCCA) is important for determining its resectability. A virtual endoscopic imaging method, magnetic resonance cholangioscopy (MRCS), wherein a three-dimensional image is created from magnetic resonance imaging (MRI) data, can evaluate all aspects of arbitrary bile ducts. Patients and methods  Overall, 15 patients with PCCA who underwent preoperative MRI were enrolled. All patients underwent surgical treatment. Results  MRCS could be performed based on preoperative MRI data in all patients. MRCS could not be used in one patient due to debris in the obstructed bile duct. The remaining 14 patients (93 %) were diagnosed with obstructed bile duct or irregular surface of the bile duct, signifying tumor invasion. The accuracy rate of diagnosing the SDS was 93 % (14/15). Seven patients underwent preoperative peroral cholangioscopy; the scope could not pass through the tumor in three patients. In these three patients, MRCS was able to be use dtoevaluate the obstructed side of the bile duct and faciliated accurate diagnosis of SDS. Conclusions  MRCS can be used to noninvasively evaluate the bile duct in all directions. This novel method makes it easy to create virtual images and can be useful for diagnosing the preoperative SDS of PCCA., Competing Interests: Competing interests The authors declare that they have no conflict 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/).)

Video 1After insertion of the cholangioscope into the common bile duct, electrohydraulic lithotripsy was performed. All common bile duct stones were shattered and successfully removed using a basket and balloon catheter., (© 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

(1) Background: Endoscopic management of hilar biliary obstruction is still challenging. Compared with unilateral drainage, bilateral drainage could preserve larger functional liver volume and potentially improve clinical outcomes. To evaluate the effectiveness of bilateral drainage, we conducted this multicenter randomized controlled study. (2) Methods: Patients with unresectable malignant hilar biliary obstruction were assigned to unilateral or bilateral group. At first, patients underwent endoscopic nasobiliary drainage (ENBD), and subsequently underwent self-expandable metallic stent (SEMS) deployment. Primary outcomes were the functional success rate of ENBD and time to recurrent biliary obstruction (TRBO) after SEMS deployment. (3) Results: During the study period, 38 and 39 patients were enrolled in the unilateral and bilateral groups. The functional success rate was similar in the uni- and bi-ENBD group (57% vs. 56%; p = 0.99), but the rate of additional drainage was higher in uni-ENBD group. Although TRBO and overall survival time after SEMS deployment were not different between the groups ( p = 0.11 and 0.78, respectively), the incidence of early adverse events tended to be higher in the bi-SEMS group (5.3% vs. 28%; p = 0.11). (4) Conclusions: Our study failed to demonstrate the superiority of bilateral over unilateral biliary drainage in terms of functional success rate and TRBO.

Background/purpose: Unresectable distal malignant biliary obstruction (DMBO) in patients with surgically altered anatomy is traditionally managed with percutaneous transhepatic biliary drainage (PTBD) and stenting because the anatomical features complicate the endoscopic approach to the biliary orifice. EUS-guided approaches recently emerged as alternative treatments; however, limited data comparing the procedures are available. The aim of this study was to compare EUS-antegrade biliary stenting (ABS) with PTBD for DMBO in patients with surgically altered anatomy., Methods: The medical records of patients who underwent EUS-ABS or PTBD for the management of DMBO and had a history of upper intestinal surgery at two tertiary centers between 2007 and 2019 were retrospectively evaluated. The study outcomes were technical, clinical, and internalization success rates and adverse event rates., Results: Of the 64 enrolled patients, 35 underwent EUS-ABS and 29 had PTBD. Basic characteristics including age, sex, performance status, primary malignancy, and reconstruction method did not differ significantly between groups. The technical, clinical, and internalization success rates in the EUS-ABS and PTBD groups were 97.1% vs 96.6% (P = 1.00), 97.1% vs 93.1% (P = .586), and 97.1% vs 75.9% (P = .01), respectively. The adverse event rate was 11.4% vs 27.6% (P = .119). No significant long-term difference was seen in time to recurrent biliary obstruction and survival. Multivariate analysis confirmed EUS-ABS was not an independent risk factor for survival., Conclusions: Similar to PTBD, EUS-ABS can effectively and safely manage DMBO in patients with surgically altered anatomy. Further well-designed trials are warranted to confirm these findings., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

BACKGROUND : Endoscopic papillary large balloon dilation (EPLBD) has been increasingly used for the management of large common bile duct (CBD) stones. Although EPLBD is often preceded by endoscopic sphincterotomy (EST), EPLBD alone without EST has been increasingly reported as an alternative to EST for large CBD stones. METHODS : This multicenter randomized trial was conducted at 19 Japanese institutions to compare the efficacy and safety of EPLBD alone versus EST for the removal of large (≥ 10 mm) CBD stones. The primary end point was complete stone removal in a single session. The secondary end points included: overall complete stone removal, lithotripsy use, procedure time, adverse events, and cost. RESULTS:  171 patients with large CBD stones were included in the analysis. The rate of single-session complete stone removal was significantly higher in the EPLBD-alone group than in the EST group (90.7 % vs. 78.8 %; P  = 0.04). Lithotripsy use was significantly less frequent in the EPLBD group than in the EST group (30.2 % vs. 48.2 %; P  = 0.02). The rates of early adverse events were comparable between the two groups: rates of overall adverse events were 9.3 % vs. 9.4 % and of pancreatitis were 4.7 % vs. 5.9 % in the EPLBD and EST groups, respectively. The procedure costs were $1442 vs. $1661 in the EPLBD and EST groups, respectively ( P  = 0.12). CONCLUSION : EPLBD without EST for the endoscopic treatment of large CBD stones achieved a significantly higher rate of complete stone removal in a single session compared with EST, without increasing adverse events., Competing Interests: Century Medical Inc.,: speaker fee, research grant. Boston Scientific Corp.: speaker fee, research grant., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background/purpose: Endoscopic transpapillary gallbladder drainage (ETGBD), including endoscopic nasogallbladder drainage (ENGBD) and endoscopic gallbladder stenting (EGBS), has been reported to be an effective treatment for acute cholecystitis. However, ETGBD is considered to be more difficult than percutaneous transhepatic gallbladder drainage (PTGBD), and few studies have evaluated the factors that affect technical success of the procedure. We investigated the factors predicting its technical success from among patient characteristics and image findings before treatment., Methods: Three hundred twenty three patients who underwent ETGBD for acute cholecystitis from November 2006 to December 2018 were analyzed retrospectively., Results: The technical success rate was 72.8% (235/323). The technical success rate by cystic duct direction was as follows: proximal/distal, 65.9%/93.6%; right/left: 74.0%/65.2%; cranial/caudal, 83.5%/20.0%. The clinical response rate was 96.2% (226/235). Adverse events were encountered in 5.9% of cases (19/323), including cystic duct injury (11 patients), pancreatitis (five patients), and bleeding (three patients). In both univariate and multivariate analysis, presence of cystic duct stone, dilation of the common bile duct (CBD), and cystic duct direction (proximal and caudal branches) were identified as significant factors affecting technical failure of ETGBD., Conclusion: Although ETGBD was an effective and safe procedure for acute cholecystitis, it has a limited success rate. The presence of cystic duct stone, dilation of CBD, and cystic duct direction (proximal and caudal branches) can serve as important predictors of ETGBD difficulties. These findings should be considered before procedures and the necessary adaptation of ETGBD made., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Intestinal perforation is a severe adverse event during pancreaticobiliary endoscopy. The use of over-the-scope clip (OTSC) has recently increased; however, the efficacy of OTSC during pancreaticobiliary endoscopy has not been well studied., Aims: To evaluate the efficacy of OTSC for the closure of gastrointestinal iatrogenic perforation during pancreaticobiliary endoscopy., Patients and Methods: This was a retrospective multicenter cohort study conducted at 3 tertiary care centers. The inclusion criteria were patients who had gastrointestinal perforation during endoscopic procedures for pancreaticobiliary diseases and underwent perforation closure using OTSC. The primary outcome was the clinical success rate. Secondary outcomes were technical success rates, adverse event rates, and the duration until the start of oral intake after OTSC., Results: Ten patients were treated by OTSC from January 2013 to December 2017. In 2 out of 10, the perforations could not be closed completely. In the remaining 8, perforations were closed completely, but intestinal obstruction caused by OTSC occurred in 1 patient. The clinical success rate was 80% (8/10). The technical and adverse event rates were 80% (8/10) and 10% (1/10), respectively. A median resumption timing of oral intake was 5 days (range, 3 to 10 d)., Conclusion: OTSC is considered as effective management for perforations during pancreaticobiliary endoscopy, although careful consideration is required for the indication of OTSC.

Background: Recently, a novel 22-gauge needle with three symmetric needle points and crown-shaped cutting heels, known as a Franseen needle, has been developed for endoscopic ultrasound-guided fine needle biopsy (EUS-FNB)., Aim: To assess the histological material acquisition rate and histological diagnostic capability of the 22-gauge Franseen needle (AC22) during EUS-FNB for solid lesions., Methods: This study was designed as an open-label, multicenter, prospective, single-arm pilot study of EUS-FNB using AC22 for the diagnosis of solid lesions. Three passes of FNB using AC22 were performed for all lesions. The primary endpoints were the histological material acquisition rate and histological diagnostic capability. The secondary endpoints were the technical success rate, quality of histological samples, number of passes for diagnosis, and safety., Results: Between September 2017 and May 2018, 75 patients were enrolled. The final diagnoses were malignancy in 65 and benign in 10. Three passes of FNB were technically successful in all patients. The sensitivity, specificity, and accuracy for the malignancy of histological analyses were 92.3% (60/65), 100% (10/10), and 93.3% (70/75), respectively, for the first pass and 95.4% (62/65), 100% (10/10), and 96% (72/75), respectively, for combined three passes. The diagnostic yield plateaued after the second pass. Sufficient tissue samples for histological interpretation were obtained in 96% (72/75) and 100% (75/75) patients for the single pass and combined three passes, respectively. Two patients (2.7%) developed mild pancreatitis as an adverse event., Conclusion: EUS-FNB using AC22 showed high histological diagnostic capability with the high first pass yield., Clinical Trials Registry: UMIN Clinical Trials Registry (UMIN ID: UMIN000036641).