BACKGROUND & AIMS:Postprocedural pancreatitis is the most common adverse event (AE) associated with endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) using a lumen-apposing metal stent is emerging as a promising approach for managing malignant distal biliary obstruction, offering the potential to lower the risk of postprocedural pancreatitis. METHODS:This was a multicenter randomized study, enrolling consecutive patients admitted for obstructive jaundice due to malignant distal biliary obstruction with dilated common bile duct (≥15 mm). Patients were randomly allocated to receive EUS-CDS or ERCP for primary biliary drainage. This was a superiority trial with postprocedural acute pancreatitis as primary outcome. Other outcomes included technical success, clinical success, AEs, 6-month stent patency rate, and overall survival. Analyses were performed according to intention-to-treat principles. RESULTS:Between April 2021 and October 2023, 220 patients were enrolled in the study (EUS-CDS, 111; ERCP, 109). EUS-CDS group showed a lower risk for postprocedural acute pancreatitis (1.8% in EUS-CDS vs 7.3% in ERCP; relative risk, 0.25; 95% confidence interval, 0.07-0.88). Technical success was achieved in 94.6% in EUS-CDS group vs 78.9% ERCP group (P < .001), in a mean procedural time of 13.5 ± 11.6 minutes and 24.7 ± 14.9 minutes, respectively (P <.001). No differences were found in other AEs (19.8% in EUS-CDS vs 21.1% in ERCP; relative risk, 0.94; 95% confidence interval, 0.56-1.58), clinical success, stent patency, or overall mortality. CONCLUSIONS:EUS-CDS is superior to ERCP in reducing postprocedural acute pancreatitis risk. However, the overall risk of AEs was not significantly different and warrants further investigation. Additionally EUS-CDS showed improved technical success and comparable clinical efficacy. These results support a potential role of EUS-CDS as primary approach in selected patients with dilated common bile duct (ClinicalTrials.gov, Number: NCT04099862).

The Antigen Processing and Presentation Machinery (APM) is essential for immune surveillance by enabling the presentation of antigenic peptides to T lymphocytes and facilitating the elimination of infected or transformed cells. In cancer, the integrity of this process influences cancer immune responsiveness (CIR), defined as a tumour’s capacity to be recognised by the immune system and respond to immunotherapy. Tumours with intact antigen presentation pathways are more likely to generate effective antitumour responses, whereas APM defects promote immune escape and therapeutic resistance. Cancer cells frequently evade immune detection through altered antigen processing or reduced expression of major histocompatibility complex (MHC) class I molecules, limiting tumour antigen presentation to cytotoxic T lymphocytes. These alterations are increasingly recognised as determinants of response to immune checkpoint inhibitors and potential predictive biomarkers. APM defects may be reversible or irreversible. Interferon-mediated signalling can restore MHC class I expression and T-cell cytotoxicity in some tumours, whereas permanent genomic alterations affecting human leukocyte antigen (HLA) class I genes, β2-microglobulin (β2-m), or interferon-γ (IFN-γ) pathway components can severely impair antigen presentation. Emerging evidence highlights four mechanistic levels of APM perturbation: peptide generation, peptide loading, MHC class I integrity, and epigenetic regulation. Each contributes to distinct patterns of immune evasion. This review examines how MHC class I alterations influence CIR and contribute to immune evasion and immunotherapy resistance in gastrointestinal malignancies, while discussing therapeutic strategies to restore or bypass APM deficiencies.

Background and Objectives: Malignant double obstruction, defined as the coexistence of malignant biliary obstructio (MBO) and malignant gastric outlet obstruction (mGOO), frequently complicates advanced pancreatic and periampullary malignancies. Because biliary and duodenal obstructions are anatomically and functionally interconnected, treatment of one may influence the outcome of the other. This review aims to summarize current evidence on endoscopic management strategies and to propose an anatomy-driven approach integrating conventional and endoscopic ultrasound (EUS)-guided techniques. Materials and Methods: A narrative review of the current literature was performed, focusing on endoscopic approaches for malignant biliary and gastric outlet obstruction. Available evidence regarding endoscopic retrograde cholangiopancreatography (ERCP), EUS-guided biliary drainage (EUS-BD), enteral self-expandable metal stenting, and EUS-guided gastroenterostomy (EUS-GE) was critically analyzed, focusing on technical feasibility, clinical outcomes, adverse events, and therapeutic sequencing. Results: ERCP remains an effective option when papillary access is preserved; however, duodenal obstruction, especially when involving the papilla, represents a major limitation. EUS-BD has emerged as a reliable alternative after failed ERCP and may provide a primary drainage strategy in selected patients. In the setting of concomitant gastric outlet obstruction, EUS-guided hepaticogastrostomy may offer advantages over choledochoduodenostomy by avoiding the obstructed duodenal pathway. For malignant gastric outlet obstruction, enteral stenting provides rapid symptom relief, but is associated with limited long-term durability. EUS-GE has demonstrated high technical and clinical success rates, lower rates of recurrent obstruction compared with enteral stenting, and outcomes comparable to surgical gastrojejunostomy with reduced invasiveness. These findings support an integrated EUS-based approach for selected patients. Conclusions: Malignant double obstruction should be considered a single anatomofunctional entity rather than two independent conditions. An individualized, anatomy-driven strategy combining EUS-guided biliary drainage and EUS-GE may represent the future direction of endoscopic palliation, allowing durable internal bypass and facilitating oncological management. Further prospective studies are required to define optimal treatment sequencing and patient selection.

Endoscopic ultrasonography represents a crucial aspect of the diagnosis of pancreatic lesions. The echo-endoscopic features of pancreatic lesions, particularly their contrast behavior with the advent of Contrast-Enhanced EUS (CE-EUS) and Contrast Enhanced Harmonic-EUS (CH-EUS), can predict a lesion's aggressiveness, depending on its nature. According to this, CH-EUS could be applied to structure an even more dedicated approach to patient care, for example, to ascertain eligibility for surgical intervention of a pancreatic ductal adenocarcinoma (PDAC) or the response to neoadjuvant chemotherapy in cases deemed borderline resectable. In addition to PDAC, other significant issues pertain to the management of small neuroendocrine tumors (NETs) and intraductal papillary mucinous neoplasms (IPMNs). In this context, CH-EUS can be crucial. The aim of this review is to underline the most recent evidence for EUS and CH-EUS applications in pancreatic lesion aggressiveness assessment and to focus on possible future research directions to further extend the application of CH-EUS in this field.

Abstract:BACKGROUND:  Endoscopic papillectomy is a viable treatment option for ampullary lesions. While many studies have reported low morbidity and acceptable outcomes, early attempts to pool data from these initial experiences have produced conflicting conclusions regarding key technical aspects. To address these uncertainties, we conducted a systematic review and pooled analysis to evaluate the safety and effectiveness of endoscopic papillectomy for ampullary lesions, identifying factors that may influence outcomes. Abstract:METHODS:  Electronic databases (Medline, Scopus, and Embase) were searched up to September 2024. Studies that included patients with endoscopically resected ampullary lesions were eligible. Effectiveness and safety outcomes were pooled by means of a random-effects model to obtain a proportion with 95 %CI. Subgroup analysis and univariable meta-regression analyses were conducted to explore potential factors affecting outcomes. Abstract:RESULTS:  61 studies (4935 lesions) published between 2002 and 2024 were analyzed. Complete resection was achieved in 85.9 % of cases, though intraductal involvement limited success. The recurrence rate was 15.2 %; however, the majority of patients (92.4 %) were managed endoscopically without surgery. The pooled adverse event rate was 30.0 %, with bleeding (12.8 %) and post-procedural pancreatitis (11.2 %) being the most common complications. Prophylactic stenting reduced pancreatitis risk, while intraductal involvement increased perforation risk. Adjunctive treatments for intraductal involvement posed an increased risk of papillary stricture. Abstract:CONCLUSION:  Endoscopic papillectomy is a safe and effective treatment for ampullary lesions; however, lesions with intraductal extension pose a higher risk of incomplete resection and perforation, warranting careful evaluation of the benefit-risk balance in these cases. While prophylactic pancreatic stenting may reduce the incidence of post-procedural pancreatitis, optimizing strategies to minimize overall adverse events remains a key focus for future research.

Background:Endoscopic retrograde cholangiopancreatography (ERCP) carries a risk of patient-to-patient transmission of multidrug-resistant organisms (MDROs) via contaminated duodenoscopes. Data on preprocedural MDRO carriage are limited and essential for guiding targeted prevention strategies, including the potential use of single-use duodenoscopes. This study assessed MDRO carriage among patients undergoing ERCP across four countries. Methods:In this international, multicentre, cross-sectional observational study, adults undergoing ERCP in tertiary care centres in the Netherlands, India, Italy, and the United States were screened for MDROs using preprocedural rectal and throat-nose swabs. Consecutive adult patients (aged ≥18 years) undergoing ERCP, regardless of indication, were eligible for inclusion. Exclusion criteria included cases in which ERCP was not performed, a duodenoscope was not used, or the rectal swab was not collected. MDROs screened included extended-spectrum beta-lactamase-producing Enterobacterales (ESBLE-E), carbapenemase-producing Enterobacterales (CPE), carbapenemase-producing Pseudomonas aeruginosa (CPPA), resistant Acinetobacter calcoaceticus baumannii complex (Acb-complex), vancomycin-resistant Enterococcus faecium (VRE), and methicillin-resistant S. aureus (MRSA). The primary outcome was the prevalence of MDRO among patients undergoing ERCP defined by growth of these organisms on preprocedural swab cultures. Secondary outcome was identification of risk factors for MDRO carriage through multivariable logistic regression analysis. Clinical and procedural variables, as well as microbiological results, were systematically retrieved from patients' medical records and institutional laboratory databases. This study is registered at ClinicalTrials.gov, NCT05303662. Findings:Between Jan 22, 2022, and Oct 09, 2024, 1244 patients were enrolled, of whom 798 (64.1%) were male and 446 (35.9%) were female. Among all participants, 462 (37.1%, 95% CI 34.5-39.9) carried an MDRO. Prevalence was highest in India (290/349, 83.1%, 78.8-86.7) and lowest in the Netherlands (37/343, 10.8%, 7.9-14.5), with intermediate rates in Italy (66/209, 31.5%, 25.7-38.2) and the United States (69/343, 20.1%, 16.2-24.7). MDRO species and resistance mechanisms varied by country. ESBL-E were most prevalent in India (245/349, 70.2%, 65.2-74.8) compared with Italy (42/209, 20.1%, 15.2-26.0), the Netherlands (35/343, 10.2%, 7.4-13.9), and the United States (15/343, 4.4%, 2.7-7.1) (p < 0.001). CPE were detected in 82/349 (23.5%, 19.4-28.2) patients in India but were uncommon in Italy (8/209, 3.8%, 1.9-7.4), rare in the United States (3/343, 0.9%, 0.3-2.5), and nearly absent in the Netherlands (1/343, 0.3%, 0.0-1.6) (p < 0.001). CPPA was only detected in 1/349 (0.3%, 0-1.6) patient in India, with none in the other centres (p = 0.46). Resistant Acb-complex was only detected in 1/209 (0.5%, 0-2.7) patient in Italy (p = 0.18). VRE was most frequent in the United States (37/343, 10.8%, 7.9-14.5), followed by Italy (20/209, 9.6%, 6.3-14.3) and India (26/349, 7.4%, 5.1-10.7), and was not detected in the Netherlands (p < 0.001). MRSA was detected primarily in the United States (27/343, 7.9%, 5.5-11.2), with lower prevalence in Italy (6/209, 2.9%, 1.3-6.1), India (5/349, 1.4%, 0.6-3.3), and the Netherlands (1/343, 0.3%, 0.0-1.6) (p < 0.001). Significant risk factors for MDRO carriage included country of inclusion, with higher odds observed in India (aOR 99.14, 95% CI: 48.21-203.86, p < 0.001) and Italy (aOR 6.58, 95% CI: 3.57-12.14, p < 0.001) compared with the Netherlands (reference), while the association for the United States was not statistically significant (aOR 1.61, 95% CI: 0.82-3.14, p = 0.17). Other significant risk factors were chronic lung disease (aOR 1.75, 95% CI:1.07-2.86, p = 0.025), congestive heart failure (aOR 2.20, 95% CI: 1.33-3.64, p = 0.002), and prior use of penicillins (aOR 1.66, 95% CI: 1.05-2.63, p = 0.031). Interpretation:This study shows global heterogeneity in MDRO carriage among patients undergoing ERCP, reflecting underlying differences in antimicrobial resistance, healthcare infrastructure, and infection control practices. Strategies to prevent endoscope-associated transmission should therefore be tailored to local resistance patterns rather than adopting a universal approach. Preprocedural screening and targeted infection prevention strategies should be integrated within broader, region-specific infection control frameworks. The study's limitations should be considered when interpreting the findings, including restriction to tertiary care centres, incomplete enrolment data, and inter-site variability in patient characteristics and microbiological methods, which may affect generalisability. Nevertheless, the results provide a robust foundation for developing targeted, evidence-based interventions and for future research evaluating the clinical value, cost-effectiveness, and sustainability of preprocedural screening and infection prevention policies across diverse healthcare settings. Funding:Boston Scientific International and Copan Italia SpA.

BACKGROUND:Management of presumed branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WF) or high-risk stigmata (HRS) remains controversial, particularly regarding the duration of surveillance. METHODS:We conducted a retrospective single-center study including patients with presumed BD-IPMNs without WF or HRS at diagnosis, followed between 2014 and 2023. Clinical, radiological, and pathological data were collected. Outcomes included malignant progression, surgery, and mortality. Subgroup analyses assessed patients with ≥5years of follow-up, potentially meeting discontinuation criteria. RESULTS:413 patients met inclusion criteria. Median age at diagnosis was 65 years; 64 % were women. Median cyst size was 10 mm, and median follow-up 36 months. WF developed in 20 % of patients and HRS in 0.7 %. Four patients (0.26/100 person-years) experienced malignant progression, all within 30 months from diagnosis; two underwent surgery, revealing adenocarcinoma in both. In 108 patients followed ≥5 years, 89 remained stable. None developed cancer, required surgery, or died from BD-IPMN. Seven developed WF after 5 years. Depending on criteria, 49 % according to Marchegiani and 63 % according to Kyoto would qualify for discontinuation of surveillance. CONCLUSIONS:In real-world practice, malignant progression of presumed BD-IPMNs without WF/HRS is rare and tends to occur early. After 5 years of stability, surveillance discontinuation may be safe in selected subgroups, although prospective validation is needed.

Background:Biliary drainage in patients with distal malignant biliary obstruction (DMBO) carries a higher risk of difficult biliary cannulation (DBC) during endoscopic retrograde cholangiopancreatography (ERCP). After the failure of standard cannulation, endoscopists may proceed with advanced cannulation techniques and/or with endoscopic ultrasound-guided biliary drainage (EUS-BD). Methods:This was a retrospective study of consecutive patients with DMBO and a dilated common bile duct (CBD; >12 mm) who underwent ERCP for endoscopic biliary drainage in four European centers. The rates of DBC, technical and clinical success, and procedure-related adverse events (AEs) were assessed. The predictive factors for AEs were also investigated through regression analysis. The EUS-BD approach was considered either as the first option after standard cannulation failure or as the final option after advanced cannulation failure. Results:1016 patients with DMBO were included in the study, with 524 (51.6%) matching the definition of DBC. Clinical success was achieved in 956 patients (94.1%). Procedure-related AEs were experienced by 167 patients (16.4%). Patients with DBC had a higher risk of AEs (P=0.003); however, patients undergoing “early” EUS-BD showed a risk of AEs comparable with those managed with standard cannulation (P=0.38). An attempt at any advanced cannulation technique was independently associated with the occurrence of AEs (P=0.001). Conclusions:The risk of AEs is higher in patients with DMBO and DBC, this appears to be mainly related to the advanced cannulation techniques. In patients with a dilated CBD (>12 mm), “early” EUS-BD may minimize the risk of AEs.

Aims Risk of branch duct intraductal papillary-mucinous neoplasms (BD-IPMNs) to harbor malignancy is not clearly understood, especially in relation to unfavorable evolutions after long periods of stability. Therefore, follow up (FU) is often continued indefinitely, resulting in significant healthcare costs. However, a recent multicenter study showed that the risk of developing cancer in presumed BD-IPMNs without worrisome features (WF) or high-risk stigmata (HRS) after 5 years of stability is equivalent to an age-matched population based on cyst size. The authors proposed to discontinue the FU after 5 years of stability in patients 75 years or older with cysts<30 mm and in patients 65 years or older with cysts≤15mm. Aim of this study is to evaluate the risk of malignant transformation, surgery and death related to BD-IPMN without WF/HRS at diagnosis, in a real-life cohort of patients under surveillance, particularly after 5 years of FU and among patients that potentially fulfilled criteria for discontinuing surveillance.

Background and objectives: Subepithelial lesions (SELs) of the gastrointestinal (GI) tract present a diagnostic challenge due to their heterogeneous nature and varied clinical manifestations. Usually, SELs are small and asymptomatic; generally discovered during routine endoscopy or radiological examinations. Currently, endoscopic ultrasound (EUS) is the best tool to characterize gastric SELs. Materials and methods: For this review, the research and the study selection were conducted using the PubMed database. Articles in English language were reviewed from August 2019 to July 2024. Results: This review aims to summarize the international literature to examine and illustrate the progress in the last five years of endosonographic diagnostics and treatment of gastric SELs. Conclusions: Endoscopic ultrasound is the preferred option for the diagnosis of sub-epithelial lesions. In most of the cases, EUS-guided tissue sampling is mandatory; however, ancillary techniques (elastography, CEH-EUS, AI) may help in both diagnosis and prognostic assessment.

Gastrojejunostomy is the principal method of palliation for unresectable malignant gastric outlet obstructions (GOO). Gastrojejunostomy was traditionally performed as a surgical procedure with an open approach butrecently, notable progress in the development of minimally invasive procedures such as laparoscopic gastrojejunostomies have emerged. Additionally, advancements in endoscopic techniques, including endoscopic stenting (ES) and endoscopic ultrasound-guided gastroenterostomy (EUS-GE), are becoming more prominent. ES involves the placement of self-expandable metal stents (SEMS) to restore luminal patency. ES is commonly the first choice for patients deemed unfit for surgery or at high surgical risk. However, although ES leads to rapid improvement of symptoms, it carries limitations like higher stent dysfunction rates and the need for frequent re-interventions. Recently, EUS-GE has emerged as a potential alternative, combining the minimally invasive nature of the endoscopic approach with the long-lasting effects of a gastrojejunostomy. Having reviewed the advantages and disadvantages of these different techniques, this article aims to provide a comprehensive review regarding the management of unresectable malignant GOO.

Introduction: EUS-guided choledochoduodenostomy (EUS-CDS) is a minimally invasive procedure used to treat malignant biliary obstruction (MBO) by the transduodenal placement of a lumen-apposing metal stent (LAMS) into the extrahepatic bile duct. In order to identify the factors that contribute to safe and effective EUS-CDS procedures using LAMS we performed a systematic review of the literature with meta-analysis. Methods: The methodology of our analysis was based on PRISMA recommendations. Electronic databases (Medline, Scopus, EMBASE) were searched up to November 2022. Full articles including patients with distal malignant biliary obstruction who underwent EUS-CDS using LAMS after failed ERCP were eligible. Random-effect meta-analysis was performed reporting pooled rates of Ttechnical success, clinical success, and adverse events were pooled by means of a random model. Multivariate meta-regression and subgroup analysis werewas performed to assess possible associations between the outcomes and selected variablesto assess the correlation between outcomes and different variables. The results were also stratified according to stent size. Results: Twelve studies with 845 patients were included in the meta-analysis. Pooled technical and clinical success rates were 96% (95%CI: 94%-98%; I2=52.29%) and 96% (95%CI: 95%-98%), respectively, with no significant association with baseline characteristics, such are sex, age, common bile duct (CBD) diameter and stent size. The pooled AE rate was 12% (95%CI: 8%-16%; I2=71.62%). The AE rate was significantly lower when using an 8x8mm stent as compared to a 6x8 mm LAMS (OR 0.59, 0.35-0.99; p=0.04), with no evidence of heterogeneity (I2=0%). Conclusion: EUS-CDS with LAMS is confirmed to be a safe and effective option for relief of MBO. The selection of appropriate stent size is crucial for achieving optimal safety outcomes.