BACKGROUND:Endoscopic retrograde cholangiopancreatography (ERCP) quality measures are critical to define standards of care and guide improvement strategies. AIMS:This study aimed to determine risk-adjusted outcomes following ERCP for malignant biliary obstruction(MBO). METHODS:Using an intention-to-treat approach, we analyzed data from a multicenter database including 23 Italian hospitals (2017-2022). Inter-center heterogeneity was assessed with I² statistic. To account for case-mix confounding, multivariable mixed-effects models estimated risk-adjusted outcomes. RESULTS:Clinical and procedural characteristics showed considerable heterogeneity across centers (I²>75%). In the intention-to-treat cohort (n = 3148), the risk-adjusted technical success rate was 91.3%; the intraclass correlation coefficient (ICC) was 11.6%, suggesting that 11.6% of the outcome variance resides at the hospital level. In the per-successful-procedure cohort (n = 2665), the risk-adjusted technical success rate was 91.3% (ICC 22.7%). Post-ERCP pancreatitis occurred in 5.4% (ICC 12.9%), additional ERCPs were required in 23.7% (ICC 4.1%), and 30-day mortality was 4.2%. Treatment in high-volume hospitals (>350ERCPs/year) was associated with lower mortality(p = 0.001). CONCLUSIONS:Most variability in ERCP outcomes across hospitals reflects differences in patient selection and technical strategies. After risk adjustment, outcomes were similar across centers, supporting consistent quality of care. This study provides exploratory, risk-adjusted benchmarks derived from real-world practice for ERCP in MBO and supports their use for quality monitoring and referral planning.

Background:Biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) remains a critical yet challenging step, particularly in patients with a naïve papilla. The European Society of Gastrointestinal Endoscopy (ESGE) proposed a stepwise algorithm to guide cannulation strategies, but its real-world applicability and outcomes have not been systematically evaluated. This study aimed to assess the effectiveness and safety of ESGE algorithm-guided biliary cannulation during ERCP in a multicenter Italian cohort. Methods:This was a prospective observational study conducted across 11 Italian centers. Consecutive patients undergoing ERCP with naïve papilla were enrolled. Cannulation strategies were categorized based on adherence to the ESGE algorithm. Results:A total of 1435 patients were included and 1086 (75.7%) procedures adhered to the ESGE algorithm. Compared with nonadherence, adherence to the ESGE algorithm resulted in significantly higher biliary cannulation success (98.6% vs. 78.8%; P < 0.001) and shorter procedure duration (median 21 vs. 35 minutes; P < 0.001). Among difficult cannulation cases, success remained higher in the ESGE adherence group (93.1% vs. 78.8%; P < 0.001). At multivariable analyses, factors significantly associated with successful cannulation were adherence to the ESGE algorithm, prone position, degree of ERCP difficulty, and use of short guidewire. Rates of post-ERCP pancreatitis were comparable overall, but moderate-to-severe pancreatitis and perforation were less frequent in the ESGE adherence group. Conclusions:Adherence to the ESGE cannulation algorithm was feasible and was associated with higher cannulation success during ERCP.

INTRODUCTION:Learning curve of EUS-guided Gastroenterostomy (EUS-GE) has been explored through retrospective studies involving few elite senior endoscopists (SE), with procedural time as the main surrogate outcome. This study aims to evaluate the training of junior endoscopists (JE) approaching the technique and cover clinically relevant patient outcomes. METHODS:From a prospective single-center registry (PROTECT, ClinicalTrials.gov NCT04813055) of EUS-GE for malignant Gastric Outlet Obstruction using the Wireless Simplified [WEST] technique, the learning curve of 3 JE experienced in pancreatobiliary endoscopy was analyzed to identify changing points ("knots") applying linear and spline regression and cumulative sum control chart (CUSUM) on several continuous and dichotomic variables. EUS-GE performed by a SE and different indications were excluded. RESULTS:From a database of 165 EUS-GEs, 100 were performed by one novice endoscopist with prior EUS-GE exposure (JE1) and 35 by two naïve endoscopists (JE2/JE3). On the largest curve (JE1), procedural time and fluoroscopy time did not show any improvement. The use of fluoroscopy (median Air Kerma: 267 Gy [172-506]) showed a significant improvement after 57 interventions (spline regression) and 72 interventions (CUSUM), after which the curve stabilized. The need for supervision/backup of a SE showed a knot after 32 interventions. Technical success (99%), Clinical success (96%), Misdeployments (2%) and AEs (6%) were stable along the learning curve. Conversion from EUS-GE to enteral stenting (11%) tended to decrease over time. Despite naïve endoscopists required significantly higher fluoroscopy time (234 vs. 187 s, p = 0.009) and procedural time (55 vs. 43 min, p = 0.002) than JE1, efficacy and safety outcomes were not different from the general cohort. CONCLUSIONS:From a prospective registry, ≈30 EUS-GE seems required for independent practice, and ≈55-70 to minimize and stabilize the use of fluoroscopy. Endoscopists learning EUS-GE in high-volume institutions using a standardized technique do not compromise high clinical and safety standards.

OBJECTIVE:To determine actual 5-year survival after neoadjuvant therapy and resection for pancreatic ductal adenocarcinoma (PDAC). BACKGROUND:Long-term outcomes after neoadjuvant therapy and resection for PDAC remain poorly defined, as current knowledge largely relies on actuarial estimates. METHODS:Retrospective cohort study of consecutive patients who underwent neoadjuvant therapy followed by curative-intent pancreatectomy for localized PDAC at 2 high-volume centers between January 2015 and February 2021. Only patients with complete follow-up (death or ≥5 y) were included. The primary endpoint was actual 5-year survival from surgery. RESULTS:Among 660 patients, actual 5-year survival was 34.5%. Recurrence occurred in 74.1% and was predominantly early, with nearly two-thirds of recurrences among patients who did not achieve 5-year survival occurring within 1 year after surgery. Long-term survivors had lower recurrence rates (92/228, 40.4%) and more commonly developed delayed (>2 y), locoregional, or pulmonary recurrence. The probability of achieving 5-year survival increased to 62.0% (95% CI: 56-67) and 81.9% (95% CI: 76-86) among patients who remained recurrence-free at 1 and 2 years, respectively. Actual 5-year survival was 42.5%, 29.0%, and 17.5% in patients with resectable, borderline-resectable, and locally advanced disease at diagnosis, respectively. Independent predictors of long-term survival included low comorbidity burden, baseline CA19-9 <200 U/mL, resectable disease at diagnosis, ypT0-1 stage, and R0 resection. CONCLUSIONS:Over one-third of patients undergoing neoadjuvant therapy and resection for localized PDAC were alive at 5 years, and most remained disease-free. Long-term outcomes were primarily determined by early systemic failure, whereas delayed oligometastatic recurrence identified a subgroup with prolonged survival.

Aims The biological progression of pancreatic neuroendocrine neoplasms (PanNENs) is significantly influenced by their grading and staging. Endoscopic ultrasound (EUS) preoperative grading of PanNENs, crucial for patient prognosis, often relies on EUS-guided biopsies. However, variations in methodologies across studies have led to inconsistent agreement rates between EUS assessments and final surgical findings, especially regarding the Ki-67 index. This inconsistency underscores the need for improved diagnostic techniques in EUS, a challenge addressed by integrating new technologies and advancing precision medicine through genomic analyses. The purpose of this subproject is to evaluate the feasibility of extracting RNA in sufficient quantity and quality to perform genomic analyses from specimens obtained through EUS-fine needle aspiration (EUS-FNA) of PanNENs, comparing three methods of RNA preservation and extraction.

Background and study aims Endoscopic ultrasound-guided choledochoduodenostomy using a lumen-apposing metal stent (EUS-CDSL) has been shown in randomized controlled trials (RCTs) to be effective compared with endoscopic retrograde cholangiopancreatography (ERCP) in patients with advanced malignant distal biliary obstruction (MDBO). We aimed to further ascertain safety of EUS-CDSL with greater statistical power. Patients and methods We undertook individual patient data (IPD) and aggregate meta-analyses following the PRISMA-IPD statement. A literature search was performed from January 2013 to November 2024 using OVID MEDLINE, EMBASE, Cochrane Library, and ISI Web of Science. Additional searches were performed for abstracts and the gray literature. RCTs comparing EUS-CDSL with ERCP were included. The primary outcome was odds of 30-day procedure related adverse events (AEs). Secondary outcomes included procedure-related 14-day severe or fatal AEs, technical success, clinical success, stent dysfunction, and procedure time. Results A total of 2679 citations were screened with three RCTs included (519 patients). The odds ratios (ORs) for 30-day AEs between EUS-CDSL and ERCP were similar (OR 0.72, 95% confidence interval [CI] 0.44-1.16). There was also no significant difference in severe or fatal AEs (OR 0.64, 95% CI 0.22-1.83). The ORs for technical success were greater for EUS-CDSL (OR 4.22, 95% CI 2.35-7.61) with shorter procedure time (mean difference -10.50 minutes (95% CI -15.28 to -5.73). No significant differences were noted in clinical success or stent dysfunction. Conclusions Our IPD meta-analysis demonstrates safety of EUS-CDSL as a first-line alternative to ERCP in MDBO and dilated biliary tree. In addition, EUS-CDSL is associated with higher technical success and shorter procedure time.

BACKGROUND A differential diagnosis between mucinous and non-mucinous pancreatic cysts is critical for clinical decision making, as mucinous cysts have malignant potential. While intracystic carcinoembryonic antigen (CEA) remains widely used and molecular markers hold promise, intracystic glucose (IG) has emerged as a promising, easily assessable, and economical alternative. AIM To investigate the diagnostic performances of IG, alone or compared to CEA. METHODS A systematic review and meta-analysis was conducted until April 2025. Pooled estimates of diagnostic metrics and their comparisons were calculated using a random effects model. A bivariate summary receiver operating characteristic model was used. Subgroup analyses and risks of bias assessment were also conducted. RESULTS Sixteen studies (1398 patients) were included. Compared with CEA, IG showed higher pooled sensitivity (95% vs 57%) and accuracy (90% vs 72%), with a lower negative likelihood ratio (LR- 0.08 vs 0.46), whereas CEA demonstrated higher specificity (97% vs 85%) and a higher positive likelihood ratio (LR+ 11 vs 6). The area under the receiver operating characteristic was 0.96 for IG and 0.82 for CEA. Pairwise analysis confirmed the superiority of IG in terms of sensitivity [odd ratio (OR): 9.36] and accuracy (OR: 3.35), while specificity favored CEA (OR: 0.43). Specificity of CEA was influenced by many factors, even by the definitive diagnostic method (histology/cytology vs other modalities, 93% vs 98%, P = 0.02). CONCLUSION This study reinforced the current recommendations supporting the use of IG as a first-line rule-out biomarker for mucinous pancreatic cysts due to its high sensitivity, while CEA may retain a complementary role as a rule-in test in clinical scenarios where higher specificity is required, such as surgical referral.

BACKGROUND:Bacterial migration from the oral cavity to the upper gastrointestinal tract has been proposed as a contributor to pancreatic ductal adenocarcinoma (PDAC) onset and prognosis. Whether PDAC is associated with alterations of the oral-duodenal microbiome continuum remains unclear. METHODS:In this prospective study, we profiled matched saliva and duodenal brushings from 24 treatment-naïve PDAC patients without ducts obstruction and 24 age- and sex-matched healthy controls (HC). Microbial composition was assessed by 16S rRNA gene sequencing. α-Diversity was evaluated using Faith's phylogenetic diversity (PD), observed ASVs, and Pielou's evenness; β-diversity using UniFrac, Bray-Curtis, and distance-based redundancy analysis (db-RDA). Associations with overall survival were examined using Cox models and ROC-derived cut-offs, with leave-one-out cross-validation for robustness. RESULTS:Duodenal Faith's PD was significantly lower in PDAC than HC (q = 0.034), whereas richness and evenness did not differ; no α-diversity differences were observed in saliva. After adjustment for diabetes and periodontitis, lower duodenal Faith's PD (q = 0.048) and ASV richness (q = 0.030) in PDAC remained significant. β-Diversity was primarily driven by body site, but adjusted db-RDA revealed a small yet significant PDAC-HC difference in duodenal community composition (pseudo-F = 2.16, p = 0.002). Several genera showed differential abundance between groups. Higher salivary phylogenetic diversity predicted longer survival (aHR = 0.19, p = 0.001), along with specific genera associated with favourable prognosis. DISCUSSION:PDAC is associated with reduced duodenal phylogenetic diversity and subtle disease-related shifts in duodenal microbiota, independent of major confounders and in the absence of duct obstruction. Both α-diversity and selected genera may hold prognostic relevance, supporting further validation in larger, stage-stratified cohorts.

Background Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is usually contraindicated in perforated cholecystitis, although initial reports suggest feasibility in contained perforation. Methods This prospective single-center cohort study aimed to explore EUS-GBD outcomes in patients with acute cholecystitis with contained perforation (cp-AC; Niemeier classification type 2). A secondary exploratory comparison was performed with a contemporaneous cohort of patients with intact gallbladder walls. Results Between January 2021 and March 2025, 23 patients with cp-AC (39.7% of the overall EUS-GBD cohort) were enrolled. This subgroup showed high prevalence of underlying malignancy (87.0%) and previous endoscopic retrograde cholangiopancreatography with placement of metal stents (65.2%). Median operative space and interluminal distance were 30.5 mm (interquartile range [IQR] 26.0-37.0) and 5 mm (IQR 2-8), respectively. Technical and clinical success of EUS-GBD were 100% (95%CI 85.7-100) and 87.0% (95%CI 67.9-95.5), respectively. The adverse event rate was 21.7% (95%CI 9.7-41.9) and did not differ significantly from that in the cohort with intact gallbladder walls; however, two fatal events occurred in the cp-AC group. Conclusions EUS-GBD appeared to be technically feasible in patients with contained perforation, despite the additional complexity. However, this represents a particularly high-risk population, and the procedure may be considered only for carefully selected patients in expert centers.