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FXR is a member of the nuclear receptor superfamily and bile acids are endogenous ligands of FXR. FXR activation has recently been reported to inhibit intestinal inflammation and tumour development. This study aimed to investigate whether the novel FXR agonist nelumal A, the active compound of the plant Ligularia nelumbifolia , can prevent colitis and colorectal carcinogenesis. In a mouse colitis model, dextran sodium sulfate-induced colonic mucosal ulcer and the inflammation grade in the colon significantly reduced in mice fed diets containing nelumal A. In an azoxymethane/dextran sodium sulfate-induced mouse inflammation-related colorectal carcinogenesis model, the mice showed decreased incidence of colonic mucosal ulcers and adenocarcinomas in nelumal A-treated group. Administration of nelumal A also induced tight junctions, antioxidant enzymes, and FXR target gene expression in the intestine, while it decreased the gene expression of bile acid synthesis in the liver. These findings suggest that nelumal A effectively attenuates colonic inflammation and suppresses colitis-related carcinogenesis, presumably through reduction of bile acid synthesis and oxidative damage. This agent may be potentially useful for treatment of inflammatory bowel diseases as well as their related colorectal cancer chemoprevention.

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.

Acute cholecystitis is frequently encountered in daily clinical practice, and early cholecystectomy is the standard therapy. In high‐risk surgical patients, such as those with advanced age, deteriorated performance status, or underlying diseases, conservative treatment is typically preferred to manage acute cholecystitis. However, in patients with a disease that is refractory to conservative treatment, drainage procedures are necessary to control the infection. At present, there are three basic approaches for gallbladder drainage: percutaneous transhepatic gallbladder drainage, endoscopic transpapillary gallbladder drainage, and endoscopic ultrasound gallbladder drainage. Each of these methods has advantages and disadvantages. Therefore, the appropriate treatment method is determined on a case‐by‐case basis, and no consistent strategy for gallbladder drainage has been established. This review aimed to summarize the characteristics of each drainage method and compare the clinical outcomes of the three procedures for acute cholecystitis in high‐risk surgical patients.

Background: Steroid therapy is the first-line treatment for autoimmune pancreatitis (AIP) with high response rates, although steroids can cause adverse events (AEs), such as diabetes mellitus (DM). The optimal initial steroid dose has not been well studied, and initiating high-dose steroid treatment may cause worsening of DM. Aims: The aim of this study was to evaluate the effect of the initial steroid dosage on treatment efficacy and diabetes mellitus in the management of autoimmune pancreatitis. Methods: A total of 81 AIP patients treated with steroids were divided into two groups based on the starting steroid dosage: a high-dose group (HD group; >0.4 mg/kg) and a low-dose group (LD group; ≤0.4 mg/kg). Treatment efficacy (response rate, pancreatic volume), relapse rate, and DM worsening rate were analyzed. Results: Among the 81 patients, 58 received HD steroids, and 23 received LD steroids. The treatment response rate was 100% in both groups (58 vs. 23, p = 1), and the overall relapse rate was 29% vs. 26% (17 vs. 6, p = 0.79), with no significant difference. At 1 year, DM worsening occurred in 50% vs. 16% (25 vs. 3, p = 0.007), significantly more in the HD group. The risk factors for DM worsening were starting HD steroid treatment (OR 6.52, 95% CI 1.41–30.2, p = 0.01) and older age (OR 1.10 per year, 95% CI 1.01–1.19, p = 0.03). Conclusions: No significant difference in treatment efficacy was found between HD and LD steroid treatment for AIP. LD treatment may prevent DM worsening.

Background/Objectives: The presence of a mural nodule (MN) is one of the findings indicating malignant transformation of an intraductal papillary mucinous neoplasm (IPMN). It is difficult to distinguish true MNs from mucus clots (MCs) by endoscopic ultrasound (EUS) alone. This study aimed to evaluate the efficacy of contrast-enhanced (CE)-EUS for differentiating true MNs from MCs and carcinoma from adenoma. Methods: A total of 104 patients who were diagnosed as having branch duct-type IPMNs with MN-like structures by EUS and underwent CE-EUS between January 2016 and August 2022 were included. MN-like structures without perfusion on CE-EUS were defined as MCs and those with perfusion were defined as true MNs. This was a retrospective study with limited pathological confirmation, and diagnoses in non-surgical cases were based on imaging and follow-up. Results: CE-EUS showed MN-like structures with perfusion in 35 patients and without perfusion in 69 patients. Surgical resection was eventually performed in a total of 28 patients and the diagnostic sensitivity, specificity and accuracy of MNs among them were 100%, 66.7% and 96.4% in CE-EUS; 48%, 66.7% and 50% in CE-CT; and 61.9%, 33.3% and 58.3% in MRCP, respectively. Possible risk factors indicating malignancy were statistically evaluated and presence of an MN was the only significant factor. Among the 35 true MNs, the height of an MN in carcinoma was significantly higher than that of an adenoma. The ROC analysis for detecting carcinoma in true MNs showed an area under the curve of 0.92 with the optimal cut-off value of 7 mm. When this cut-off value was used for diagnosing carcinoma, the sensitivity, specificity, and accuracy were 94.1%, 83.3% and 88.6%, respectively. Conclusions: CE-EUS may be useful for differentiating true MNs from MCs, although diagnostic performance should be interpreted cautiously because most non-surgical cases lacked pathological confirmation.

Background/Objectives: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is a useful procedure for obtaining histological specimens. However, its utility in diagnosing autoimmune pancreatitis (AIP) has not yet been well studied. This study aimed to assess the diagnostic capability of EUS-FNB for AIP by comparing a 19-gauge Franseen needle (19FR) and a 22-gauge Franseen needle (22FR). Methods: This study included patients with a final diagnosis of AIP undergoing EUS-FNB for pancreatic lesions between January 2014 and February 2023. All patients underwent EUS-FNB with either 19FR or 22FR. Histological findings were evaluated according to the International Consensus Diagnostic Criteria (ICDC). The primary outcome was the diagnostic yield of Level 1 (≥3 ICDC items) or Level 2 (2 ICDC items). Results: The 19FR group included 31 patients, and the 22FR group included 36 patients. The Level 1 diagnostic rate was significantly higher in the 19FR group than in the 22FR group (90.3% vs. 61.1%, p = 0.010). No significant difference was observed in the Level 2 diagnostic rate. The 19FR group yielded significantly larger histological tissue samples than the 22FR group (median area: 9.19 mm2/session vs. 3.36 mm2/session, p < 0.001). The analysis demonstrated a positive correlation between tissue area and the number of histological diagnostic items obtained. Conclusions: EUS-FNB performed with the 19FR provided larger histological specimens and a higher histological diagnostic yield than the 22FR in the diagnosis of AIP. Obtaining a larger amount of tissue may facilitate a definitive diagnosis of AIP.

Introduction Bile leakage is one of the complications after hepatobiliary surgery, causing intra‐abdominal infections, and is sometimes difficult to treat. The purpose of our study was to investigate the factors related to severity and to evaluate the efficacy of endoscopic treatment. Methods This was a retrospective multicenter cohort study conducted at three tertiary care medical centers. The severity of bile leakage was classified per the International Study Group of Liver Surgery, and Grades B and C (requiring some intervention or reoperation) were considered as severe. Results The subjects were 59 patients. The surgical procedures were 31 cholecystectomies, 23 hepatectomies, and five pancreaticoduodenectomies. The severity was Grade A/B/C: 17/40/2. Multivariate logistic regression analysis found that age (unit odds ratio [UOR], 1.09; 95% confidence interval [CI], 1.0–1.19; p = 0.049) and days from surgery to bile leak (UOR, 1.18; 95% CI, 1.04–1.35; p = 0.012) were independent predictors of bile leak severity. Of 40 Grade B biliary leakage patients, 37 patients underwent endoscopic drainage, of which 11 also received intra‐abdominal abscess drainage. Eventually, bile leakage was successfully treated in all patients after several endoscopic drainage sessions, and the median drainage period was 18 days (inter‐quartile range: 13–35). Conclusion In the management of bile leakage after hepatobiliary surgery, elderly patients or patients with late onset of bile leak may be at high risk of severity. Endoscopic biliary drainage is considered a safe and effective treatment for severe patients.

BackgroundLumen-apposing metal stents (LAMSs) are increasingly used for the endoscopic management of pancreatic fluid collections (PFCs), including walled-off necrosis (WON) and pancreatic pseudocysts (PCs).ObjectiveTo evaluate the nationwide impact of implementing an LAMS (approved in Japan in 2018) on clinical outcomes in real-world settings.DesignUsing a nationwide inpatient database, we identified 5885 patients who underwent endoscopic ultrasound (EUS)-guided treatment for PFCs at 550 hospitals between 2010 and 2023. We examined the association between treatment period (pre-LAMS vs post-LAMS implementation) and clinical outcomes. Multivariable logistic and linear regression analyses were performed to estimate ORs and coefficients, respectively. Findings were validated using a multi-institutional clinical cohort (n=618) from specialty hospitals with more detailed clinical parameters with data collection during the same period.ResultsIn the pre-LAMS period, 3787 cases were treated exclusively with plastic stents. After 2018, LAMS use stabilised at around 50% among 2098 cases treated between 2019 and 2023. Compared with the pre-LAMS period, patients treated during the post-LAMS period had a higher risk of bleeding with LAMS (adjusted OR, 1.81; 95% CI: 1.55 to 2.13), but not with plastic stents (adjusted OR, 0.96; 95% CI: 0.74 to 1.26). Rates of rescue surgery, in-hospital mortality and length of stay did not differ significantly (p>0.12). The post-LAMS period was associated with increased total costs (adjusted coefficient, US$2813; 95% CI: 1503 to 4122). In analyses stratified by PFC types (WON vs PC), the association of the post-LAMS period with bleeding risk appeared to be stronger for PCs than WON (pinteraction=0.015) and WON patients had a shorter length of stay and lower total costs in the post-LAMS period (pinteraction<0.001). In the validation cohort, the elevated bleeding risk with LAMS was confirmed (adjusted OR, 1.59; 95% CI: 0.86 to 2.95, vs pre-LAMS period), though not statistically significant.ConclusionsThe implementation of LAMS was not associated with improved key clinical outcomes but was linked to a higher risk of bleeding and increased healthcare costs. These findings do not support the routine use of LAMS for EUS-guided treatment of all PFCs in standard clinical practice but may restrict it to WON cases with clear indications.

Background A pathological diagnosis of pancreatic cancer should be performed as much as possible to determine the appropriate treatment strategy, but priorities and algorithms for diagnostic methods have not yet been established. In recent years, the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become the primary method of collecting tissues from pancreatic disease, but the effect of EUS-FNA on surgical results and prognosis has not been clarified. Aims To evaluate the diagnostic ability of EUS-FNA and its effect on the preoperative diagnosis, surgical outcome, and prognosis of pancreatic cancer. Methods Between January 2005 and June 2017, 293 patients who underwent surgical resection for pancreatic cancer were retrospectively evaluated. The outcomes of interest were the diagnostic ability of EUS-FNA and its influence on the surgical results and prognosis. Results The diagnostic sensitivity of EUS-FNA was 94.4%, which was significantly higher than that of endoscopic retrograde cholangiopancreatography (ERCP) (45.5%) ( p  < 0.001). The adverse event rate in ERCP was 10.2%, which was significantly higher than EUS-FNA (1.3%) ( p  = 0.001). Patients were divided into FNA group (N = 160) and non-FNA group (N = 133) for each preoperative diagnostic method. In the study of surgical curability R0 between the two groups, there was no significant difference in FNA group (65.0% [104/160]) and non-FNA group (64.7% [86/133], p  = 1.000). In the prognostic study, 256 patients with curative R0 or R1 had a recurrence rate was 54.3% (70/129) in the FNA group and 57.4% (73/127) in the non-FNA group. Moreover peritoneal dissemination occurred in 34.3% (24/70) in the FNA group and in 21.9% (16/73) in the non-FNA group, neither of which showed a significant difference. The median survival times of the FNA and non-FNA groups were 955 days and 799 days, respectively, and there was no significant difference between the two groups (log-rank p  = 0.735). In the Cox proportional hazards model, factors influencing prognosis, staging, curability, and adjuvant chemotherapy were the dominant factors, but the preoperative diagnostic method (EUS-FNA) itself was not. Conclusions EUS-FNA is a safe procedure with a high diagnostic ability for the preoperative examination of pancreatic cancer. It was considered the first choice without the influence of surgical curability, postoperative recurrence, peritoneal dissemination and prognosis.

ObjectivesBilateral 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.MethodsIn 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).ResultsThere 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).ConclusionNo 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.