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Background: Interleukin (IL)-17 is a newly identified T-cell-specific cytokine. In this study, we investigated the effects of IL-17 on colony-stimulating factor (CSF) release in human colonic subepithelial myofibroblasts (SEMFs).Methods: CSF release and mRNA expression were determined by enzyme-linked immunosorbent assay (ELISA) and Northern blotting, respectively. Nuclear factor (NF)-kappaB- and activating protein (AP-1)-DNA binding activities were evaluated by electrophoretic gel mobility shift assays (EMSAs).Results: Unstimulated cells secreted a small amount of granulocyte G- and granulocyte/macrophage (GM)-CSF, and a considerable amount of M-CSF. IL-17 weakly enhanced G-CSF release, but did not affect GM- and M-CSF release. IL-17 selectively enhanced tumor necrosis factor (TNF)-alpha-induced G- and GM-CSF release. The combination of IL-17 plus TNF-alpha induced a marked increase in NF-kappaB- and AP-1-DNA binding activities. The adenovirus-mediated transfer of a stable form of IkappaBalpha and/or a dominant negative mutant of c-Jun markedly inhibited the IL-17 plus TNF-alpha-induced G- and GM-CSF mRNA expression. Furthermore, a stability study showed that IL-17 plus TNF-alpha markedly enhanced the stability of G- and GM-CSF mRNA.Conclusions: IL-17 augments TNF-alpha-induced G- and GM-CSF release via transcriptional and posttranscriptional mechanisms. [ABSTRACT FROM AUTHOR]

Renal leiomyosarcoma metastasis to the pancreas is exceptionally rare. Here, we present a case of metastatic recurrence in the pancreas seven years after renal leiomyosarcoma resection. A 73-year-old female with a history of renal leiomyosarcoma surgery seven years prior presented with a well-defined 40 × 30 mm pancreatic tail tumor detected by a computed tomography (CT) scan. The tumor exhibited hypo-enhancement in the arterial phase and a progressive enhancement pattern toward the equilibrium phase, similar to pancreatic cancer. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) revealed bundles of spindle cells that matched those in the previously resected renal sample. Immunohistochemistry showed positive staining for desmin, confirming the diagnosis of pancreatic metastasis from renal leiomyosarcoma. The patient underwent a distal pancreatectomy to remove the metastatic lesion. The extended interval of seven years before the detection of metastasis underscores the challenges in monitoring and diagnosing metastatic patterns of renal leiomyosarcoma. EUS-FNB can assist in distinguishing metastatic pancreatic leiomyosarcoma from primary pancreatic cancer, thus influencing treatment decisions., (© 2024. Japanese Society of Gastroenterology.)

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

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

Sclerosing mesenteritis (SM) is a rare disorder that involves the mesenteric adipose tissue with chronic fibrosing inflammation. Few reports mention the natural history of severe SM cases. Here, we report a severe and relapsing SM case in which a long-term natural history could be followed. The patient had undergone surgery for small bowel stenosis of unknown cause 10 years earlier. He had stopped visiting the hospital at his discretion. He was admitted to the hospital 10 years later due to recurrent symptoms, and a close examination revealed multiple small intestinal strictures; thus, surgery was performed again. The pathological results revealed that the patient had SM, corticosteroid administration dramatically improved his symptoms, and he has maintained remission for a long time., (© 2024. Japanese Society of Gastroenterology.)

Background and Aim: Hot snare excision using electrocautery is widely used for large colorectal polyps (>10 mm); however, adverse events occur due to deep thermal injury. Colorectal polyps measuring 10-14 mm rarely include invasive cancer. Therefore, less invasive therapeutic options for this size category are demanding. We have developed hot snare polypectomy with low-power pure-cut current (LPPC HSP), which is expected to contribute to less deep thermal damage and lower risk of adverse events. This study aimed to evaluate the efficacy and safety of LPPC HSP for 10-14 mm colorectal polyps, compared with conventional endoscopic mucosal resection (EMR)., Methods: In this multicenter, retrospective, observational study, clinical outcomes of EMR and LPPC HSP for 10-14 mm nonpedunculated colorectal polyps between January 2021 and March 2022 were compared using propensity score matching., Results: We identified 203 EMR and 208 LPPC HSP cases. After propensity score matching, the baseline characteristics between the groups were comparable, with 120 pairs. The en bloc and R0 resection rates were not significantly different between EMR and LPPC HSP groups (95.8% vs 97.5%, P = 0.72; 90.0% vs 91.7%, P = 0.82). The rates of delayed bleeding and perforation did not differ between the groups., Conclusions: Compared with conventional EMR, LPPC HSP showed a similar resection ability without an increase in adverse events. These results suggest that LPPC HSP is a safe and effective treatment for 10-14 mm nonpedunculated colorectal polyps., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Elobixibat is a triple mode of action laxative that increases water secretion into the colon, promotes colonic motility, and reestablishes the defecation desire. This study aims to evaluate the effectivity and safety of elobixibat in chronic constipation (CC) patients refractory to conventional laxatives., Methods: A single-center retrospective observational study was conducted in refractory CC patients diagnosed according to the Rome IV criteria and received elobixibat between April 2018 and June 2022 at Osaka Saiseikai Nakatsu Hospital. Data were collected for spontaneous bowel movement (SBM), Bristol stool form scale (BSFS) scores, abdominal symptoms, and adverse events., Results: Eligible 311 patients were selected for the analysis. Two-week Elobixibat treatment significantly increased SBM (times/week) from 2.9 ± 1.9 to 4.3 ± 1.9 ( P  < 0.0001). The BSFS score improved significantly from 3.2 ± 1.7 to 4.4 ± 1.4 ( P  < 0.0001). The percentages of patients with hard stool were decrease and that with normal stools were increase. Improvements in abdominal symptoms (sensation of incomplete bowel evacuation, straining, abdominal pain and distention, and difficulty defecating) were also significant ( P  < 0.05). These constipation symptoms were improved irrespective of patient characteristics or previous laxatives. The 43.9% of previous laxatives were discontinued at the start of or after starting elobixibat treatment. A few adverse events were observed, elobixibat was well tolerated., Conclusion: Elobixibat was effective in patients who were refractory to other laxatives, irrespective of previous therapy or patient characteristics. Elobixibat may contribute to resolving polypharmacy with single mode of action laxatives., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Endoscopic ultrasound shear wave elastography (EUS-SWE) can facilitate an objective evaluation of pancreatic fibrosis. Although it is primarily applied in evaluating chronic pancreatitis, its efficacy in assessing early chronic pancreatitis (ECP) remains underinvestigated. This study evaluated the diagnostic accuracy of EUS-SWE for assessing ECP diagnosed using the Japanese diagnostic criteria 2019., Methods: In total, 657 patients underwent EUS-SWE. Propensity score matching was used, and the participants were classified into the ECP and normal groups. ECP was diagnosed using the Japanese diagnostic criteria 2019. Pancreatic stiffness was assessed based on velocity (Vs) on EUS-SWE, and the optimal Vs cutoff value for ECP diagnosis was determined. A practical shear wave Vs value of ≥50% was considered significant., Results: Each group included 22 patients. The ECP group had higher pancreatic stiffness than the normal group (2.31 ± 0.67 m/s vs. 1.59 ± 0.40 m/s, p < 0.001). The Vs cutoff value for the diagnostic accuracy of ECP, as determined using the receiver operating characteristic curve, was 2.24m/s, with an area under the curve of 0.82 (95% confidence interval: 0.69-0.94). A high Vs was strongly correlated with the number of EUS findings (rs = 0.626, p < 0.001). Multiple regression analysis revealed that a history of acute pancreatitis and ≥2 EUS findings were independent predictors of a high Vs., Conclusions: There is a strong correlation between EUS-SWE findings and the Japanese diagnostic criteria 2019 for ECP. Hence, EUS-SWE can be an objective and invaluable diagnostic tool for ECP diagnosis., Competing Interests: None., (© 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.)

Objectives: Cold snare polypectomy (CSP) is widely performed for small colorectal polyps. However, small colorectal polyps sometimes include high-grade adenomas or carcinomas that require endoscopic resection with electrocautery. This study aimed to evaluate the efficacy and safety of a novel resection technique, hot snare polypectomy with low-power pure-cut current (LPPC-HSP) for small colorectal polyps, compared with CSP and conventional endoscopic mucosal resection (EMR)., Methods: Records of patients who underwent CSP, EMR, or LPPC-HSP for nonpedunculated colorectal polyps less than 10 mm between April 2021 and March 2022 were retrospectively evaluated. We analyzed and compared the treatment outcomes of CSP and EMR with those of LPPC-HSP using propensity score matching., Results: After propensity score matching of 396 pairs, an analysis of CSP and LPPC-HSP indicated that LPPC-HSP had a significantly higher R0 resection rate (84% vs. 68%; p < 0.01). Delayed bleeding was observed in only two cases treated with CSP before matching. Perforation was not observed with either treatment. After propensity score matching of 176 pairs, an analysis of EMR and LPPC-HSP indicated that their en bloc and R0 resection rates were not significantly different (99.4% vs. 100%, p = 1.00; 79% vs. 81%, p = 0.79). Delayed bleeding and perforation were not observed with either treatment., Conclusions: The safety of LPPC-HSP was comparable to that of CSP. The treatment outcomes of LPPC-HSP were comparable to those of conventional EMR for small polyps. These results suggest that this technique is a safe and effective treatment for nonpedunculated polyps less than 10 mm., Competing Interests: None., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Cytokeratin (CK) is a specific marker of adenocarcinoma. However, cases of CK7-positive esophageal squamous cell carcinoma (ESCC) have only rarely been reported. We herein report a case of unresectable CK7-positive ESCC with aggressive liver metastasis following nivolumab treatment initiation. Nivolumab treatment was discontinued after one course because of complications. Notably, the liver metastases exhibited accelerated growth. Immunostaining of the necropsy specimens revealed diffuse positivity for forkhead box protein A1 (FOXA1)/CK7, thus indicating a potent poor immune response. The potential correlation between CK7 expression and the immune checkpoint inhibitor response may offer valuable insights into the development of effective therapeutic strategies.

Several cases have been reported that suggest the efficacy of gel immersion endoscopic mucosal resection (GI-EMR) for gastric neoplasms. However, no study has evaluated treatment outcomes of GI-EMR for gastric neoplasms. This study aimed to investigate the efficacy and safety of GI-EMR for early gastric neoplasms. Nine patients (17 lesions) undergoing gastric GI-EMR were included, with a median lesion size of 10 mm (interquartile range [IQR] 5-13 mm). All lesions were protruding or flat elevated. The median procedure time was 3 minutes (IQR 2-5) and en bloc resection was achieved in all cases. Among 15 neoplastic lesions, the R0 resection rate was 86.7% (13/15 lesions). Adverse events included immediate bleeding requiring hemostasis in two cases, which was controlled endoscopically. No delayed bleeding or perforation occurred. In conclusion, GI-EMR may be a safe and effective treatment for early, small gastric neoplasms. However, due to the small sample in the present study, further investigation is required regarding the indication for this technique., Competing Interests: Conflict of Interest 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/).)

Background: The association between thiopurine use and testicular reproductive functions remains unclear. In this study, we investigated whether thiopurines affect testicular functions based on the NUDT15 genotypes using Nudt15 R138C knock-in mice., Methods: The male Nudt15 R138C knock-in mice (9-12 weeks) were treated with mercaptopurine (MP: 0.5 mg/kg/day) for 4 or 12 weeks. To examine reversibility, some mice were maintained for a further 12 weeks under MP-free condition., Results: After MP treatment for 4 weeks, Nudt15 R138C/R138C mice exhibited a significant reduction of testis weight compared to Nudt15 +/+ mice and Nudt15 +/R138C mice. The epithelial height and diameter of seminiferous tubules were significantly reduced in Nudt15 R138C/R138C mice compared to Nudt15 +/+ and Nudt15 +/R138C mice. Apoptotic cells were significantly increased in Nudt15 R138C/R138C mice, and most of apoptotic cells were spermatogonia. There were no significant changes in sperm counts and sperm morphology in MP-treated Nudt15 R138C/R138C mice after 4-week MP treatment. On the other hand, after MP treatment for 12 weeks, the Nudt15 +/R138C mice, but not Nudt15 +/+ mice, exhibited a significant reduction in the testis weight and atrophic changes of seminiferous tubules, but these changes disappeared after 12-week rearing under MP-free condition. Despite a significant increase in abnormal sperm rate, there were no changes in the ability to conceive. No differences in serum levels of follicle-stimulating hormone or testosterone were observed between MP-treated Nudt15 +/R138C and Nudt15 +/+ mice after 12-week MP treatment., Conclusions: Thiopurines exert harmful effects on testicular reproductive function according to host NUDT15 genotypes., (© 2023. Japanese Society of Gastroenterology.)

Background and Aims: Endoscopic placement of self-expandable metal stents (SEMSs) for malignant distal biliary obstruction (MDBO) may be accompanied by several types of adverse events. The present study analyzed the adverse events occurring after SEMS placement for MDBO., Methods: The present study retrospectively investigated the incidence and types of adverse events in patients who underwent SEMS placement for MDBO between April 2018 and March 2021 at 26 hospitals. Risk factors for acute pancreatitis, cholecystitis, and recurrent biliary obstruction (RBO) were evaluated by univariate and multivariate analyses., Results: Of the 1425 patients implanted with SEMSs for MDBO, 228 (16.0%) and 393 (27.6%) experienced early adverse events and RBO, respectively. Pancreatic duct without tumor involvement (P = .023), intact papilla (P = .025), and SEMS placement across the papilla (P = .037) were independent risk factors for acute pancreatitis. Tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis (P < .001). Use of fully and partially covered SEMSs was an independent risk factor for food impaction and/or sludge. Use of fully covered SEMSs was an independent risk factor for stent migration. Use of uncovered SEMSs and laser-cut SEMSs was an independent risk factor for tumor ingrowth., Conclusions: Pancreatic duct without tumor involvement, intact papilla, and SEMS placement across the papilla were independent risk factors for acute pancreatitis, and tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis. The risk factors for food impaction and/or sludge, stent migration, and tumor ingrowth differed among types of SEMSs., Competing Interests: Disclosure The following author disclosed financial relationships: M. Kitano: Speaker for Olympus Corporation; research support from Boston Scientific, Zeon Medical Inc, and Medico’s Hirata Inc. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Purpose: Although endoscopic ultrasound (EUS) has been widely used for diagnosing chronic pancreatitis (CP), the assessment of fibrosis using the Rosemont criteria (RC) is generally subjective. Shear wave elastography using EUS (EUS-SWE) has been advocated as an objective approach to evaluating pancreatic fibrosis; however, it is unknown which pancreatic region should be selected for measurement. This study aims to compare the diagnostic accuracy in diagnosing CP by measurement site., Methods: Fifty patients with CP or suspected CP who underwent EUS-SWE were retrospectively analyzed. As per the RC, they were classified into two groups: CP and non-CP. Pancreatic stiffness was evaluated by measuring the velocities of the shear wave (Vs) in addition to determining the relevant cutoff value of Vs for diagnosing CP. The correlation between Vs and RC, and the RC factors affecting pancreatic stiffness were evaluated., Results: In the CP group, the Vs were notably higher in all regions (P < 0.001). The Vs for diagnostic accuracy of CP were highest in the body [area under the curve (AUC): 0.87]. A significant correlation was seen between the number of RC and Vs in all regions, with the correlation coefficient being highest in the pancreatic body (rs = 0.55). Multivariate analysis revealed that lobularity with honeycombing was an independent factor for pancreatic stiffness (P = 0.02)., Conclusion: The pancreatic body is a suitable region for assessing pancreatic stiffness using EUS-SWE. Additionally, quantifying Vs is a valuable objective indicator for diagnosing CP., (© 2023. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Purpose: Impacted common bile duct stones cause severe acute cholangitis. However, the early and accurate diagnosis, especially iso-attenuating stone impaction, is still challenging. Therefore, we proposed and validated the bile duct penetrating duodenal wall sign (BPDS), which shows the common bile duct penetrating the duodenal wall on coronal reformatted computed tomography (CT), as a novel sign of stone impaction., Methods: Patients who underwent urgent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis due to common bile duct stones were retrospectively enrolled. Stone impaction was defined by endoscopic findings as a reference standard. Two abdominal radiologists blinded to clinical information interpreted CT images to record the presence of the BPDS. The diagnostic accuracy of the BPDS to diagnose stone impaction was analyzed. Clinical data related to the severity of acute cholangitis were compared between patients with and without the BPDS., Results: A total of 40 patients (mean age 70.6 years; 18 female) were enrolled. The BPDS was observed in 15 patients. Stone impaction occurred in 13/40 (32.5%) cases. Overall accuracy, sensitivity, and specificity were 34/40 (85.0%), 11/13 (84.6%), and 23/27 (85.2%), respectively; 14/16 (87.5%), 5/6 (83.3%), and 9/10 (90.0%) for iso-attenuating stones; and 20/24 (83.3%), 6/7 (85.7%), and 14/17 (82.4%) for high-attenuating stones. Interobserver agreement of the BPDS was substantial (κ = 0.68). In addition, the BPDS was significantly correlated with the number of factors in the systemic inflammatory response syndrome (P = 0.03) and total bilirubin (P = 0.04)., Conclusion: The BPDS was a unique CT imaging finding to identify common bile duct stone impaction regardless of stone attenuation with high accuracy., (© 2023. The Author(s) under exclusive licence to Japan Radiological Society.)

Background: The appropriate method of preoperative endoscopic biliary drainage (EBD) for cholangiocarcinoma with hilar biliary obstruction remains controversial. The inside-stent technique is a method of placing plastic stents entirely inside the bile duct. Several studies of patients with unresectable stage have reported longer stent patency compared with conventional endoscopic biliary stenting (EBS). Inside-stent techniques have been introduced as a bridge-to-surgery option and as an alternative to conventional EBS., Aims: We aimed to evaluate the clinical outcomes of inside stent use and conventional EBS., Methods: During this retrospective multicenter study, we reviewed consecutive patients with cholangiocarcinoma who underwent radical surgery after conventional EBS or inside-stent insertion. Adverse event (AE) rates after EBD and post-surgical AEs were compared. A multivariable analysis was performed to identify factors affecting cholangitis after EBD., Results: Conventional EBS and inside-stent procedures were performed for 56 and 73 patients, respectively. Patient backgrounds were similar between groups, except for percutaneous transhepatic portal vein embolization. The waiting time before surgery was similar between groups (28.5 days vs. 30 days). There were no significant differences in the cholangitis rate (21.4% vs. 26.0%; P = 0.68) and all AEs (25.0% vs. 30.1%; P = 0.56) between groups. The post-surgical AE rate was similar between the groups. The multivariable analysis found that preprocedural cholangitis was a risk factor for cholangitis after EBD (odds ratio: 5.67; 95% confidence interval: 1.61-19.9)., Conclusions: The outcomes of inside-stent techniques and conventional EBS for the management of preoperative EBD are comparable for patients with cholangiocarcinoma., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Current steerable catheters (SCs) for endoscopic retrograde cholangiopancreatography (ERCP) have performance limitations caused by an asymmetric multiple-slit tube design with a small maximum bend angle, lesser curvatures, and insufficient durability. We propose a wire-driven SC for balanced bidirectional bending using artificial blood vessel material to overcome these limitations. We assess the SC prototype's steerability using phantom and animal models., Methods: The SC prototype employed a slit-less and multiple-lumen seamless tube with a polytetrafluoroethylene (PTFE) body with stretch-retractable porous expanded PTFE at the distal end, and loop-formed control wires. We evaluated the wire routing design using a static model. The bending performance was compared with conventional SCs. Feasibility studies were performed, including major duodenal papilla insertions and ductal branch selections in desktop phantoms and a mini-pig model., Results: The proposed design reduced the wire contact force by 48% compared to the single wire configuration. The maximum bend angle was 162°, almost twofold larger than that for conventional SCs. The lateral tip position in the bent shape was maximally 56% smaller. The tip flexibility was comparable to conventional SCs, and the insertion resistance was similar to the passive catheters. Phantom studies showed that the SC prototype could perform the large and protuberant papilla insertions and fine ductal branch selections without breaking; the animal study was completed successfully., Conclusion: We propose a wire-driven SC design for ERCP using a multi-lumen seamless tube and two loop-formed control wires, different from the conventional SC design with a multiple-slit tube and single control wire. The SC prototype records balanced bidirectional bending with a maximum bending angle of ± 162° without breakage risk. The phantom and animal studies show that the prototype performance potentially facilitates papilla cannulations and intrahepatic ductal branch seeking., (© 2022. CARS.)

Background: Treatments for patients with gastric outlet obstruction (GOO) due to unresectable pancreatic cancers (URPC) include gastrojejunostomy (GJJ) and endoscopic duodenal stent placement (EDSP). This study compared the efficacy and safety of GJJ and EDSP in patients with GOO due to URPC., Methods: This study retrospectively evaluated consecutive patients with GOO due to URPC who underwent GJJ or EDSP between April 2016 and March 2020. The efficacy and safety of GJJ and EDSP were compared with propensity score analysis. Subgroup analyses of overall survival (OS) were compared after propensity matching., Results: Data were obtained from 54 patients who underwent GJJ and from 73 who underwent EDSP at five tertiary care hospitals. After propensity matching, OS was significantly longer in patients who underwent GJJ than EDSP (110 vs. 63 days, respectively; p = 0.019). Evaluation of long-term adverse events showed that the frequency of cholangitis and obstructive jaundice was significantly lower in the matched GJJ than in the matched EDSP group (p = 0.012). Subgroup analyses showed that OS in patients with good performance status (PS; p = 0.041), biliary obstruction (p = 0.007), and duodenal obstruction near the papilla (p = 0.027), and those receiving chemotherapy (p = 0.010), was significantly longer in the matched GJJ group than in matched EDSP group., Conclusion: GJJ provides longer OS than EDSP for patients with GOO caused by URPC, especially for patients with good PS, biliary obstruction, and duodenal obstruction near the papilla, and those receiving chemotherapy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

While nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene polymorphism Arg139Cys (rs116855232) is known to be a risk factor for thiopurine-induced severe leukopenia, association with the NUDT15 gene polymorphism Arg139His (rs147390019) has not yet been clarified. In addition, the accuracy of TaqMan PCR to assess these two polymorphisms has not been investigated. In this study, we evaluated TaqMan PCR for detection of the NUDT15 single-nucleotide polymorphisms (SNPs) and examined the clinical impact of Arg139His on thiopurine-induced leukopenia. First, we demonstrated that a TaqMan PCR assay successfully detected the Arg139His polymorphism of NUDT15 in clinical samples. Next, the NUDT15 gene polymorphisms (Arg139Cys and Arg139His) were separately analyzed by TaqMan Real-Time PCR in 189 patients from August 2018 to July 2019. The incidences of leukopenia within 2 years were 16.2, 57.9, and 100% for arginine (Arg)/Arg, Arg/cysteine (Cys), and Arg/histidine (His), respectively. The leukopenia was significantly increased in Arg/Cys and Arg/His compared with Arg/Arg. This retrospective clinical study indicated that, in addition to Arg139Cys, Arg139His may be clinically associated with a high risk of leukopenia. Pharmacogenomics will help in selecting drugs and determining the individualized dosage of thiopurine drugs.

Background and Aim: Small intestinal bacterial overgrowth (SIBO) is diagnosed by using quantitative culture of duodenal aspirates and/or a hydrogen breath test. However, few studies have analyzed bacterial microbiota in Japanese patients with SIBO., Methods: Twenty-four patients with any abdominal symptoms and suspected SIBO were enrolled. Quantitative culture of duodenal aspirates and a glucose hydrogen breath test were performed on the same day. SIBO was diagnosed based on a bacterial count ≥ 10 3  CFU/mL or a rise in the hydrogen breath level of ≥ 20 ppm. The composition of the duodenal microbiota was analyzed by 16S rRNA gene sequencing., Results: Small intestinal bacterial overgrowth was diagnosed in 17 of the 24 patients (71%). The positive rates for the hydrogen breath test and quantitative culture of duodenal aspirates were 50% and 62%, respectively. Patients with SIBO showed significantly reduced α-diversity compared with non-SIBO patients, and analysis of β-diversity revealed significantly different distributions between SIBO and non-SIBO patients. In addition, the intestinal microbiome in SIBO patients was characterized by increased relative abundance of Streptococcus and decreased relative abundance of Bacteroides compared with non-SIBO patients., Conclusions: Duodenal dysbiosis was identified in patients with SIBO and may play a role in the pathophysiology of SIBO., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

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

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

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

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure in the diagnosis and treatment of biliopancreatic diseases. The most common adverse event of ERCP is post-ERCP pancreatitis (PEP), which can sometimes be severe. Our previous study suggested that injecting ice water at the end of ERCP suppressed PEP, and we decided to investigate this effect in a multicenter randomized controlled trial., Methods: This study is being conducted at eight hospitals in Japan starting in April 2022. Patients undergoing ERCP will be randomized to ice water group and control group. In the ice water group, 250 ml of ice water is injected toward the papilla at the end of ERCP. The next morning, a physical examination and blood tests are performed to evaluate for the development of pancreatitis. The goal is to have 440 cases in each group., Discussion: The main cause of PEP is thought to be papilla edema. Cooling the papilla, as everyone naturally does at the time of a burn, is expected to prevent its inflammation and edema. Various methods to suppress PEP have been reported, but so far none of them are reliable. The method we have devised is very simple, easy, and safe. We hope that our study will change the world's ERCP common practice., Trial Registration: UMIN000047528. Registered 20 April 2022, https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000053209., (© 2022. The Author(s).)

Background and Aims: This large multicenter randomized controlled trial compared the diagnostic yields of 22-gauge standard and 22-gauge Franseen needles for EUS-guided tissue acquisition (EUS-TA) of solid pancreatic lesions., Methods: Consecutive patients with solid pancreatic lesions were prospectively randomized to EUS-TA using standard or Franseen needles. Samples obtained with the first needle pass and with second and subsequent passes were evaluated separately. The primary endpoint was the rate of accuracy for diagnosis of malignancy. Other endpoints were technical success rate, sample cellularity, adverse events, diagnostic accuracy in patient subgroups, and the diagnostic accuracy and numbers of second and subsequent needle passes., Results: Of 523 patients undergoing EUS-TA, 260 were randomized to using standard 22-gauge needles and 263 to 22-gauge Franseen needles. The technical success rate in each group was 99.6%, with similar adverse event rates in the standard (1.5%) and Franseen (.8%) needle groups. First-pass EUS-TA using the Franseen needle resulted in significantly greater diagnostic accuracy (84.0% vs 71.2%, P < .001) and sensitivity (82.4% vs 66.7%, P < .001) than first-pass EUS-TA using a standard needle and also resulted in superior diagnostic accuracy in patients requiring immunostaining. Second and subsequent EUS-TA using Franseen needles showed significantly greater accuracy (94.7% vs 90.0%, P = .049) and sensitivity (94.0% vs 88.6%, P = .047) and required fewer needle passes (1.81 vs 2.03, P = .008) than using standard needles., Conclusions: EUS-TA with the Franseen needle is superior to EUS-TA with a standard needle with respect to diagnostic accuracy per pass, particularly in patients who require immunostaining, and number of passes when using macroscopic on-site evaluation. (Clinical trial registration numbers: UMIN000030634 and jRCTs052180062.)., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background/aims: Crosstalk between the gut microbiota and bile acid plays an important role in the pathogenesis of gastrointestinal disorders. We investigated the relationship between microbial structure and bile acid metabolism in the ileal mucosa of Crohn's disease (CD)., Methods: Twelve non-CD controls and 38 CD patients in clinical remission were enrolled. Samples were collected from the distal ileum under balloon-assisted enteroscopy. Bile acid composition was analyzed by liquid chromatography-mass spectrometry. The gut microbiota was analyzed by 16S rRNA gene sequencing., Results: The Shannon evenness index was significantly lower in endoscopically active lesions than in non-CD controls. β-Diversity, evaluated by the UniFrac metric, revealed a significant difference between the active lesions and non-CD controls (P=0.039). The relative abundance of Escherichia was significantly higher and that of Faecalibacterium and Roseburia was significantly lower in CD samples than in non-CD controls. The increased abundance of Escherichia was more prominent in active lesions than in inactive lesions. The proportion of conjugated bile acids was significantly higher in CD patients than in non-CD controls, but there was no difference in the proportion of primary or secondary bile acids. The genera Escherichia and Lactobacillus were positively correlated with the proportion of conjugated bile acids. On the other hand, Roseburia, Intestinibacter, and Faecalibacterium were negatively correlated with the proportion of conjugated bile acids., Conclusions: Mucosa-associated dysbiosis and the alteration of bile acid composition were identified in the ileum of CD patients. These may play a role in the pathophysiology of ileal lesions in CD patients.

Objectives: Distally located small common bile duct stones are often difficult to treat or grasp endoscopically. Therefore, multiple devices, such as baskets or balloon catheters, are frequently used in such cases. However, it is desirable to use a single device for stone extraction from the perspective of cost-effectiveness. In this multicenter study, we evaluated the efficacy of a new eight-wire basket catheter for extracting small (≤10 mm) common bile duct stones., Methods: We retrospectively analyzed the records of 144 patients who underwent stone extraction using the eight-wire basket catheter for common bile duct stones ≤10 mm. The success rate of complete stone extraction and the risk factors for the difficulty in stone extraction with the eight-wire catheter alone were mainly evaluated., Results: The success rate of stone extraction with the eight-wire catheter alone was 86.1%. The final rate of complete stone extraction was 98.0%. The mean of the maximum diameter of the common bile duct and the largest stone dimension were 10.5 ± 3.5, and 5.1 ± 2.1 mm, respectively. Common bile duct diameter ≥12 mm and stone diameter ≥6 mm were identified as independent risk factors for the difficulty in stone extraction with the eight-wire catheter alone., Conclusions: The success rate of the new eight-wire basket for small common bile duct stone extraction was acceptable. The device is beneficial and could be used from the start for the extraction of small stones < 6 mm., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Backgrounds: Optimal concentration of ustekinumab (UST) predicting endoscopic remission has not been fully investigated in Crohn's disease (CD). We aimed to identify the optimal UST trough levels predicting clinical, laboratory and endoscopic remission in CD patients., Methods: Twenty-eight patients with CD were enrolled and investigated (27 patients by enteroscopy and 1 by colonoscopy). The endoscopic activity was assessed using the scoring system that applied the Rutgeerts score to observed intestine. Serum UST trough levels and anti-UST antibodies (AUAs) levels were determined by in-house immunoassays., Results: Endoscopic activity was negatively correlated with serum UST trough levels (Spearman's rank correlation coefficient (ρ) = - 0.66, P = 0.0001) and serum albumin levels (ρ = - 0.60, P = 0.0007). The endoscopic activity was positively and significantly correlated with CRP (ρ = 0.59, P = 0.0009) and ESR (ρ = 0.44, P = 0.033). There was no significant association between the endoscopic score and AUA levels and/or Crohn's disease activity index (CDAI). Serum UST trough levels and albumin levels were significantly higher in the endoscopic remission group (scores of 0 and 1) than in the non-endoscopic remission group (UST trough, mean 3.3 vs. 1.8 μg/mL). No significant difference was observed in AUAs between the endoscopic remission and non-remission groups. Receiver operation curve (ROC) analysis revealed that the optimal cutoff value of UST trough levels predicting normal CRP and serum albumin levels was 1.7 μg/mL for each, and the optimal cutoff value predicting endoscopic remission was 2.0 μg/mL (AUC: 0.80, 95% CI 0.64-0.96)., Conclusion: Achievement of endoscopic remission requires higher UST trough levels than required for normalization of CRP and serum albumin levels., (© 2022. The Author(s).)

Interleukin (IL)-38 exerts an anti-inflammatory function by binding to several cytokine receptors, including the IL-36 receptor. In this study, we evaluated IL-38 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and investigated its functions. IL-38 mRNA expression in endoscopic biopsy samples was evaluated using quantitative PCR. IL-38 protein expression was analyzed using immunohistochemical technique. Dextran sulfate sodium-induced colitis was induced in C57BL/6 background IL-38KO mice. The IL-38 mRNA and protein expression were enhanced in the active mucosa of ulcerative colitis, but not in Crohn's disease. The ratio of IL-36γ to IL-38 mRNA expression was significantly elevated in the active mucosa of UC patients. Immunofluorescence staining revealed that B cells are the major cellular source of IL-38 in the colonic mucosa. IL-38 dose-dependently suppressed the IL-36γ-induced mRNA expression of CXC chemokines (CXCL1, CXCL2, and CXCL8) in HT-29 and T84 cells. IL-38 inhibited the IL-36γ-induced activation of nuclear-factor kappa B (NF-κB) and mitogen-activated protein kinases in HT-29 cells. DSS-colitis was significantly exacerbated in IL-38KO mice compared to wild type mice. In conclusion, IL-38 may play an anti-inflammatory and protective role in the pathophysiology of IBD, in particular ulcerative colitis, through the suppression of IL-36-induced inflammatory responses., Competing Interests: AA received lecture fee from Janssen, Takeda, AbbVie, Tanabe-Mitsubishi. All other authors declare that they have no conflict of interest in this study., (Copyright © 2022 JCBN.)

Objective: The aim of this study was to identify the incidence of and risk factors for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) after emergency endoscopic retrograde cholangiopancreatography (ERCP)., Methods: We performed a prospective multicenter observational study of 3914 patients who underwent ERCP. We compared the incidence of PEP after emergency and elective ERCP., Results: A total of 3410 patients were enrolled in this study. Post-ERCP pancreatitis occurred in 44 of 800 patients (5.5%) and in 190 of 2418 patients (7.9%) in the emergency and elective groups, respectively. No significant difference was noted between the groups (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.52-1.03; P = 0.07). Multivariate analysis showed that the following factors increased the risk for PEP after emergency ERCP: contrast medium injection into the pancreatic duct (OR, 2.56; 95% CI, 1.30-5.03; P = 0.005), >4 cannulation attempts (OR, 5.72; 95% CI, 2.61-12.50; P < 0.001), and endoscopic papillary balloon dilatation (OR, 9.24; 95% CI, 2.13-40.10; P < 0.001)., Conclusions: No significant difference was noted in the incidence of PEP in patients after emergency and elective ERCP. We may prevent PEP even after emergency ERCP by avoiding contrast injection into the pancreatic duct, multiple cannulation attempts, and endoscopic papillary balloon dilatation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Vedolizumab is a humanized monoclonal antibody against the α4β7 integrin and is approved for treatment of inflammatory bowel diseases. In this study, we evaluated the immunogenicity of vedolizumab using a simple drug-tolerant assay developed in our laboratory. Serum vedolizumab trough levels and anti-vedolizumab antibody (AVA) levels were measured using new immunoassays in 37 patients with ulcerative colitis (UC) under vedolizumab maintenance therapy. The median vedolizumab trough level at week 30 was 16.0 μg/ml (interquartile range, 7.3-24.4). The vedolizumab trough level of the patients with clinical remission (partial Mayo score ≤1) was significantly higher than that of clinically active patients (16.7 μg/ml vs 6.8). The cut-off value of vedolizumab level predicting clinical remission at week 30 was 7.34 μg/ml. The median AVA level of patients under vedolizumab maintenance therapy was similar to that of healthy controls ( n  = 20) (0.032 μg/ml-c vs 0.022). One of 37 patients (2.7%) was judged to be AVA positive. There was no significant difference in serum AVA and vedolizumab trough levels between biologics-naïve ( n  = 19) and biologics-switched (prior anti-TNFα-exposed) patients ( n  = 18). In conclusion, the simple drug-tolerant assay developed in our laboratory demonstrated low immuno-genicity of vedolizumab. Prior use of anti-TNFα drugs did not affect the immunogenicity of vedolizumab., Competing Interests: AA received lecture fee from Janssen, Takeda, AbbVie, and Tanabe-Mitsubishi. All other authors declare that they have no conflict of interest in this study., (Copyright © 2022 JCBN.)

A 44-year-old man with a history of chronic alcoholic pancreatitis and Crohn's disease presented with abdominal pain. Computed tomography revealed pancreatic calculi in the head of the pancreas and a dilated pancreatic duct. The patient was diagnosed with an acute exacerbation of chronic pancreatitis due to the impact of pancreatic calculi on the main pancreatic duct. During the clinical course, the movement of pancreatic calculi to the major papilla was confirmed, leading to obstructive jaundice. Endoscopic treatment with sphincterotomy of the pancreatic duct was successful. Herein, we report the case of an unusual clinical course involving obstructive jaundice caused by the movement of pancreatic calculi.

Objectives: Acute pancreatitis is the most critical complication of endoscopic retrograde cholangiopancreatography (ERCP). In this study, we investigated the association between the volume/fat content of the pancreatic head and the incidence of post-ERCP pancreatitis (PEP)., Methods: We retrospectively enrolled 157 patients who underwent ERCP. The volume and fat content of the pancreas were calculated by multislice computed tomographic imaging by using a volume analyzer. Multivariate analysis was performed to identify risk factors for PEP., Results: The mean volumes of the whole pancreas and pancreatic head were significantly larger, and the fat content of the pancreatic head was significantly higher in the PEP group (P < 0.01). There were no significant differences in the mean volume and fat content of the pancreatic body and tail in the PEP group. Multivariate analysis revealed that the pancreatic guidewire placement (odds ratio [OR], 12.4; P < 0.01), pancreatic head volume (OR, 5.3; P < 0.01), and the pancreatic head fat content (OR, 4.8; P < 0.01) were independent risk factors for PEP., Conclusions: The pancreatic head volume and fat content were independent predicting factors of PEP. Quantitative assessment of the pancreas may contribute to the prediction of PEP onset., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aim: International consensus on the definition and classification of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) has been reached. However, the diagnosis and severity of PEP are often assessed according to the diagnostic criteria and classification for acute pancreatitis (AP). This study determined the incidence, severity, and risk factors of PEP diagnosed according to the diagnostic criteria and classification for AP in a large cohort., Methods: This prospective, multicenter, observational cohort study conducted at five high-volume centers included 1932 patients who underwent ERCP-related procedures. The incidence, severity, and risk factors for PEP were evaluated., Results: PEP occurred in 142 patients (7.3%); it was mild in 117 patients (6.0%) and severe in 25 patients (1.3%). According to the Cotton criteria, PEP occurred in 87 patients (4.5%); it was mild in 54 patients (2.8%), moderate in 20 patients (1.0%), and severe in 13 patients (0.7%). In the multivariate analysis, female sex (odds ratio [OR] 2.239; 95% confidence interval [CI] 1.546-3.243), naïve papilla (OR 3.047; 95% CI 1.803-5.150), surgically-altered gastrointestinal anatomy (OR 2.538; 95% CI 1.342-4.802), procedure time after reaching the papilla (OR 1.009; 95% CI 1.001-1.017), pancreatic duct injection (OR 2.396; 95% CI 1.565-3.669), and intraductal ultrasonography (OR 1.641; 95% CI 1.024-2.629) were independent risk factors., Conclusion: According to the diagnostic criteria and classification for AP, the incidence of PEP was higher than that according to the Cotton criteria and the severity of PEP tended to be severe., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The thiopurine drugs azathioprine and 6-mercaptopurine are widely used for the maintenance of clinical remission in steroid-dependent inflammatory bowel disease (IBD). Thiopurines are recommended to be continued throughout pregnancy in IBD patients, but conclusive safety data in pregnant patients remain still insufficient. On the other hand, a strong association between a genetic variant of nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15 p.Arg139Cys) and thiopurine-induced myelotoxicity has been identified. Pharmacokinetic studies have revealed that thiopurine metabolism is altered in pregnant IBD patients and suggested that the fetus may be exposed to the active-thiopurine metabolite, 6-thioguaninetriphosphate, in the uterus. A recent study using knock-in mice harboring the p.Arg138Cys mutation which corresponds to human p.Arg139Cys showed that oral administration of 6-MP at clinical dose induces a severe toxic effect on the fetus harboring the homozygous or heterozygous risk allele. This suggests that NUDT15 genotyping may be required in both women with IBD who are planning pregnancy (or pregnant) and their partner to avoid adverse outcomes for their infant. The risk to the fetus due to maternal thiopurine use is minimal but there are some concerns that are yet to be clarified. In particular, a pharmacogenomic approach to the fetus is considered necessary., (© 2021. Japanese Society of Gastroenterology.)