Main recommendations:BENIGN BILIARY STRICTURES. Main recommendations:1: ESGE suggests temporary insertion of multiple plastic stents (MPSs) to treat postcholecystectomy benign biliary strictures. A fully covered self-expandable metal stent (FCSEMS) can be considered in these patients when the stricture is located >2 cm distally from the main hepatic confluence or for patients who are noncompliant with repeated endoscopic retrograde cholangiopancreatographies (ERCPs). Main recommendations:2: ESGE suggests treating anastomotic biliary strictures following liver transplantation with either MPSs or temporary insertion of an FCSEMS when located >2 cm distally from the main hepatic confluence. Main recommendations:3: ESGE suggests treating biliary strictures secondary to chronic pancreatitis with temporary insertion (6-12 months) of an FCSEMS. Main recommendations:4: ESGE suggests using balloon dilation alone for high grade biliary strictures secondary to primary sclerosing cholangitis. There is no added benefit of stenting following balloon dilation, and stenting may increase the risk of adverse events. Main recommendations:5: ESGE suggests avoiding the insertion of uncovered SEMSs (USEMSs) for the drainage of extrahepatic biliary obstruction of unconfirmed etiology. Main recommendations:DISTAL MALIGNANT BILIARY STRICTURES. Main recommendations:6: ESGE recommends the endoscopic placement of a 10-mm diameter SEMS for preoperative biliary drainage (PBD) of extrahepatic malignant biliary obstruction (MBO). Main recommendations:7: ESGE recommends the endoscopic placement of a 10-mm diameter SEMS for neoadjuvant biliary drainage of extrahepatic pathologically confirmed MBO. Main recommendations:8: ESGE recommends endoscopic over surgical or percutaneous biliary drainage for primary decompression of inoperable, extrahepatic MBO. Main recommendations:HILAR MALIGNANT BILIARY STRICTURES. Main recommendations:9: ESGE recommends ERCP over percutaneous transhepatic biliary drainage (PTBD) for PBD in hilar malignant obstruction. Main recommendations:10: ESGE suggests palliative drainage of malignant hilar strictures by means of ERCP for Bismuth types I-II. For Bismuth III-IV, ERCP or a combination of ERCP with endoscopic ultrasound-guided biliary drainage (EUS-BD) is preferable over primary PTBD. Complementary drainage using PTBD might be required in some cases. Main recommendations:11: ESGE suggests obtaining drainage of more than 50%, and ideally 70% or more, of the viable nonatrophic liver volume for palliative drainage of proven malignant Bismuth II-IV strictures, using a multimodal approach (EUS-BD/PTBD if needed, as complementary methods to ERCP). Main recommendations:12: ESGE suggests using either plastic stents or USEMSs for palliative drainage of proven malignant hilar obstruction. ESGE suggests a plastic stent when the optimal drainage strategy has not been defined. ESGE suggests using a USEMS in expert centers to reduce the need for revisional procedures based on the patient's expected survival and the likelihood of achieving complete biliary drainage. Main recommendations:MALIGNANT BILIARY STRICTURE IN CASES OF FAILED OR UNFEASIBLE ERCP. Main recommendations:13: ESGE recommends EUS-BD over PTBD in cases of malignant biliary stricture following failed or unfeasible ERCP.In patients with distal stricture, ESGE suggests using EUS-guided hepaticogastrostomy (EUS-HGS) where a duodenal stricture is present, and either EUS-HGS or EUS-guided choledochoduodenostomy where there is no duodenal stricture.ESGE suggests using PTBD when EUS-BD fails or is not feasible.

Background Colorectal cancer is the third leading cause of cancer death worldwide. Colonoscopy can prevent this complication but is imperfect because of missed adenoma. A device involving a variable-rigidity balloon has been developed: G-EYE colonoscopy (GEYEC). Only a few prospective studies on GEYEC are available. We compared GEYEC to standard colonoscopy (SC) during screening colonoscopy. Methods We performed a single-center back-to-back colonoscopy tandem randomized clinical trial. Patients older than 50 years were referred for screening colonoscopy, among whom one-third with a positive fecal immunochemical test were included. In Arm A, patients underwent SC followed by GEYEC; in Arm B, the opposite occurred. The primary objective was to assess and compare adenoma miss rate (AMR) between arms. The secondary objectives were to compare advanced AMRs (aAMRs), adverse events for each colonoscope and withdrawal stability rates for GEYEC. Results One hundred ninety-five patients were included between January 2020 and June 2023. A total of 164 patients (83 women, 51%) completed the two procedures, performed by six experienced operators. The mean AMRs were 0.438 in Arm A and 0.393 in Arm B ( p = 0.713). The mean aAMRs were 0.176 in Arm A and 0.036 in Arm B ( p = 0.76). The rate of significant adverse events (≥AGREE II) was 1.8%, and none were attributed to the GEYEC balloon. In 79% of cases, operators felt that GEYEC provided more stability during withdrawal. Conclusion Although it is reliable and safe, compared with SC, GEYEC does not reduce AMR or aAMR. However, it increases the comfort of scope withdrawal during screening.

Purpose:To analyze and compare the clinical outcomes of boost modality choice after external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) for anal canal cancers (ACC). Material and methods:162 patients with ACC were treated in our institution with two different boost modalities: EBRT boost (EBRTb) or high-dose-rate (HDR) interstitial brachytherapy boost (ISBT). Local relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS), colostomy-free survival (CFS), and toxicity rates were analyzed. Results:With a median follow-up (FU) of 66 months, thirteen (8%) local recurrences were reported, six in the ISBT and seven in the EBRTb groups. The 5-year LRFS rate for the entire cohort was 87% (80-92%), without differences in both groups: 88% in ISBT vs. 86% in EBRTb group (p = 0.7). The 5-year DFS, OS, and CFS rates for the overall population were 84% (78-89%), 93% (88-96%), and 92% (88-95%), respectively, without significant differences between ISBT and EBRTb groups. Multivariate analysis for gastrointestinal (GI) toxicity found a non-significant tendency between EBRTb and GI toxicity grade ≥ 2: odds ratio (OR) = 1.82 (0.88-3.78), p = 0.1060. Univariate analysis for fecal incontinence revealed that EBRTb was significantly associated with fecal incontinence grade ≥ 2 (p = 0.0005), and this tendency was confirmed in the multivariate analysis (p = 0.0012). Sensitivity analysis, excluding patients with theoretical brachytherapy contraindications, confirmed these results. Univariate and multivariate assessments found ISBT as an independent prognosis factor for better sphincter function: OR = 5.44 (1.57-18.91), p = 0.0077. Conclusions:CRT provide excellent rates of tumor control and colostomy-free survival. Compared with EBRTb, interstitial brachytherapy boost demonstrates a favorable profile in GI toxicity, with a low impact on fecal incontinence.

BACKGROUND AND AIMS:Barrett's esophagus (BE) is a common precancerous condition requiring surveillance or treatment at various stages. Low-grade dysplasia (LGD) increases the risk of progression to high-grade dysplasia or esophageal adenocarcinoma, but histopathological assessment is challenging, and progression is unpredictable. Endoscopic resection, through mucosal or submucosal techniques, offers high efficacy, low adverse event rates, and shorter treatment duration. This study evaluated the effectiveness and safety of endoscopic eradication therapy in patients with LGD BE. METHODS:This retrospective study included 119 patients with LGD BE treated at 3 tertiary centers. Patients underwent endoscopic mucosal resection (EMR) or, for nodular or retractile lesions, endoscopic submucosal dissection (ESD). The primary outcome was complete LGD eradication (CE-D), confirmed endoscopically and histologically. Secondary outcomes included adverse events, histopathology of resected specimens, treatment duration, and recurrence rates. RESULTS:Of the 119 patients (75% men; mean age 62 years), EMR was performed in 97% and ESD in 97.5% cases. LGD was confirmed by 2 different pathologists in 87% and by repeat biopsy in 70% before treatment. CE-D was achieved in 95% of patients. Histopathology revealed LGD in 50%, high-grade dysplasia in 9%, adenocarcinoma in 3%, and nondysplastic findings in others. Early adverse events occurred in 2.5%, and late adverse events in 12%, all managed conservatively or endoscopically. LGD recurred in 10% of patients over a median follow-up of 905 days. CONCLUSIONS:Endoscopic therapy with EMR or ESD appears effective and safe for selected patients with LGD in BE, with low recurrence rates. In addition to lesion eradication, it provides histological assessment, allowing detection of more advanced pathology in some cases. These findings suggest that resection may represent a valuable adjunct or alternative within current treatment strategies.

Background: Concomitant malignant gastric outlet obstruction (MGOO) and malignant biliary obstruction (MBO) represent a challenging clinical scenario in which the optimal endoscopic strategy remains unclear. Objectives: This study aimed to compare real-life combinations of endoscopic ultrasound-guided biliary drainage—hepatogastrostomy (EUS-HGS) or choledochoduodenostomy (EUS-CDS)—with gastric outlet obstruction management—EUS-guided gastroenterostomy (EUS-GE) or enteral stenting (ES). Design: This was an international multicenter retrospective cohort study involving 11 tertiary centers (2017–2023). Methods: Consecutive patients with MBO and MGOO were included. All patients underwent both biliary and gastric outlet drainage using one of four combinations: EUS-HGS/EUS-GE, EUS-HGS/ES, EUS-CDS/EUS-GE, or EUS-CDS/ES. The primary outcome was stent dysfunction (biliary or digestive). Secondary outcomes included clinical success and adverse events. Results: A total of 159 patients were included (median age 70 years; pancreatic cancer 64.8%). Stent dysfunction occurred in 12.0% of patients treated with EUS-HGS/EUS-GE versus 26.6% with EUS-CDS/ES, 36.7% with EUS-HGS/ES, and 50.0% with EUS-CDS/EUS-GE ( p = 0.059). At 12 months, stent obstruction-free survival was significantly higher with EUS-HGS/EUS-GE (84.0%) compared with EUS-CDS/ES (51.2%, p = 0.0466), EUS-CDS/EUS-GE (42.0%, p = 0.0377), and EUS-HGS/ES (52.3%, p = 0.0512). Severe adverse events were more frequent with EUS-HGS (15.0% in HGS/ES; 8.0% in HGS/EUS-GE) compared with EUS-CDS (1.6% in CDS/ES; 0% in CDS/EUS-GE; p = 0.014). Conclusion: In malignant obstruction, the choice of gastric outlet strategy appears to markedly influence biliary stent patency. When EUS-GE is performed, EUS-HGS may provide superior durability but at the cost of higher morbidity. Conversely, when ES is selected, EUS-CDS appears safer. These findings support a tailored approach integrating anatomical considerations and center expertise when selecting the optimal endoscopic double-drainage strategy.

Background and study aims: Biliary surgery is a common procedure, especially cholecystectomy (CCT). Its main adverse event (AE) is biliary duct injury (BDI). Management is poorly codified, particularly for complex BDIs not related to CCT (NONCCT-BDI). We decided to conduct a study in a tertiary center to evaluate clinical outcomes of BDI management. Patients and methods: A single-center retrospective study of patients diagnosed with a BDI between March 2002 and June 2022 was performed. The primary endpoint was the overall success rate for BDI management. Secondary endpoints were outcomes of BDI related to CCT (CCT-BDI) and non-CCT-BDI according to BDI location, need for a combination of procedures, and AEs. Results: Sixty-four patients were included. The overall success rate was 91.8%. Endoscopic retrograde cholangiopancreatography (ERCP) alone was efficient in 97.4% of patients. Endoscopy was key to successful treatment in 69% of patients. Forty-five percent of cases were non-CCT-BDI and the treatment success rate was 88.9%. The treatment success rate was significantly higher for Strasberg A BDIs (P = 0.0337). Conclusions: ERCP remains the best and least invasive treatment for hilar injuries, as evidenced by a high success rate. Management of NON-CCT-BDIs should be modeled after that of CCT-BDIs. Owing to the need for a combination of treatments, complex hilar injuries must be managed in expert centers.

BACKGROUND AND AIMS:Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is increasingly used; however, clinical application remains unstandardized. We assessed real-world practice among international users. METHODS:A cross-sectional 70-item survey was conducted. Results are presented descriptively (numbers, percentages). RESULTS:Overall, 91 of 175 invited physicians from Europe (74.4%), North America (13.3%), and Asia (12.2%) completed the survey. EUS-RFA was performed by 94.1% of respondents for insulinoma, with heterogeneous responses for other indications. Most physicians (96.3%) performed EUS-RFA under deep sedation or general anesthesia; marked variability was reported on antibiotic prophylaxis (57.5%), aggressive hydration (52.5%), generator power settings, ablation strategy, or probe selection. Lesions involving or located ≤ 1 mm from the main pancreatic duct were considered high risk by 97.5% and 85.0%, respectively, yet no standardized preventive strategy was identified. Post-procedural management and follow-up were heterogeneous, with a high proportion of responses for definitions of technical success (88.8%), clinical success in insulinoma (92.3%), and disease recurrence (97.5%), with high variability for definitions of partial ablation and post-RFA pancreatitis. CONCLUSIONS:Despite the global expansion of EUS-RFA, clinical practice remains highly heterogeneous and geographically skewed. The lack of standardized methodology and terminology poses significant barriers to generating high-quality evidence.

BACKGROUND AND AIMS:Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is the recommended treatment for high surgical risk patients with acute cholecystitis requiring drainage. Gallbladder perforation is a severe complication and is often considered a contraindication for endoscopic treatment. We report our experience with EUS-GBD in patients with perforated cholecystitis. METHODS:This retrospective study analyzed consecutive cases of high surgical risk patients with acute cholecystitis and gallbladder perforation treated with EUS-GBD at a tertiary referral center from September 2020 to October 2023. EUS-GBD was performed using electrocautery-enhanced lumen-apposing metal stents (LAMS). Primary outcomes were technical and clinical success. Adverse events (AEs) were considered secondary endpoints. RESULTS:Twelve patients (50% women, mean age 75.9 ± 15.2 years) were included. The median Charlson Comorbidity Index was 7. Reasons for EUS-GBD included age/comorbidities (33.3%), advanced malignancy (33.3%), and coagulopathy/dual antiplatelet therapy (33.3%). Technical success was achieved in all patients (100%), and clinical success was observed in 11/12 (91.7%), with significant improvement in localized and systemic infection. AEs occurred in one patient (8.33%) with pneumoperitoneum treated conservatively. The same patient experienced recurrent cholecystitis that required endoscopic stent revision 7 days after the initial procedure. Median follow-up was 173 days (range 4-820 days). CONCLUSION:EUS-GBD is both technically feasible and effective for patients with acute cholecystitis and gallbladder perforation. While the AEs rate appears low, further studies are needed to confirm these findings.

Ampullary composite gangliocytoma/neuroma and neuroendocrine tumor (CoGNET), previously called ampullary gangliocytic paragangliomas, is a rare entity, with only few reported cases in the literature. This is a multicentric retrospective cohort study of patients treated with endoscopy or surgery for ampullary CoGNET. A literature review of ampullary CoGNET was also performed. Fifteen patients were included, mostly female (n = 10) with a median age of 50 years. Patients were asymptomatic in seven cases. Four patients were treated with pancreatoduodenectomy, four with transduodenal ampullectomy, and eight with endoscopic papillectomy. Clavien-Dindo III-IV complications occurred in 2 of the 8 surgical cases, but no fatal adverse events were registered. There was only one moderate endoscopic adverse event. The median length of stay was 9 days. The median tumor size was 20 mm, the R0 resection rate was 93.8%, and two patients had nodal involvement. After a median follow-up of 29 months, there was no local or distant recurrence nor death from disease. The literature review confirmed the clinical presentation and excellent outcomes of ampullary CoGNET management, especially regarding survival, even for patients with nodal or distant metastases. Overall, ampullary CoGNET are rare tumors with excellent prognosis, even with incomplete resection or nodal involvement. Treatment should be as minimally invasive as possible, and a long-term follow-up is needed.

In anorectal cancer, epithelial tumors frequently develop in transition zones (TZs) between the anal and the rectal epithelia, a region subjected to inflammation and wounds. However, whether inflammation and wounds contribute to tumor development in the anorectal region remain totally unknown. Using mice with KRASG12D mutation selectively at the TZ cells, we found that recurrent wound and its associated sustained inflammation are essential to promote tumor development. We characterized at the single-cell level the malignant events that occurred at the TZ all along tumor development from early neoplastic, hyperplastic, to malignant transition. We showed that this tumoral development was under the influence of interleukin (IL)-17, a cytokine highly secreted by a γδ T lymphocyte subset, allowing the recruitment of neutrophils at the TZ, which was crucial for tumor progression. Hence, this study reveals the importance of wound and its associated IL-17/neutrophil inflammatory axis in cancer progression.

Research on the oncological outcomes of complementary pancreatoduodenectomy (PD) following incomplete (R1) endoscopic papillectomy (EP) for early-stage ampullary adenocarcinoma (AA) is limited, despite the increasing use of endoscopic approaches and the risks associated with PD. This study aimed to assess short- and long-term outcomes in patients undergoing complementary PD after EP R1 for AA. Between January 2010 and December 2022, four patient groups were compared: patients with complete endoscopic resection (EP R0), those with R1 margins after EP closely followed up without complementary surgery (EP R1), those who underwent complementary PD after R1 EP (EP + PD), and those who underwent upfront PD (uPD). The primary endpoint was the difference in survival rates (overall [OS] and disease-free [DFS]) between the EP R1 and EP + PD groups and morbidity and mortality rate comparison between the EP + PD and uPD groups. In the EP cohort (n = 56), the major complication was intraluminal hemorrhage (29

Background:Endoscopic papillectomy is a standard treatment for ampullary lesions, which are typically small and confined to the papillary mound. Laterally spreading lesions (LSLs) of the papilla of Vater are a rare ampullary lesion subtype involving extensive duodenal mucosa. Data on endoscopic papillectomy outcomes for LSLs are limited. This study compared endoscopic papillectomy for ampullary LSLs and non-LSLs in matched cohorts. Methods:The ESAP study (Endoscopic papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for ampullary neoplasm) encompassed 1422 endoscopic papillectomies. Propensity score matching used the nearest-neighbor method for age, sex, co-morbidity, and histologic subtype as cofactors. The main outcomes were complete resection (R0), technical success, complications, and recurrences. Results:Propensity score-based matching identified 232 patients with ampullary lesions (116 non-LSL, 116 LSL) with comparable baseline characteristics. After first intervention, the R0 resection rate, the primary outcome measure, was significantly lower in the LSL group (54.3% [95%CI 45.3%–63.1%]) vs. 69.0% [95%CI 60.4%–76.6%]). Following repeated endoscopic interventions, technical success was similar in both groups (82.8%). After a 22-month median follow-up, the LSL group had significantly more recurrences (41.3% vs. 15.0%) and lower 1- and 3-year disease-free survival rates (61.1% and 44.0% vs. 86.1% and 81.6%, respectively). Complication rates did not differ significantly between the two groups (LSL 32.8% vs. non-LSL 26.7%). Conclusion:LSLs can be safely resected by endoscopic papillectomy, although repeated interventions are necessary to achieve complete resection. The higher risk of recurrence in LSLs necessitates a vigilant surveillance strategy.