Miniprobe endoscopic ultrasonography (mEUS) combines high-resolution imaging of the gastrointestinal (GI) wall and bile ducts with ease of applicability during routine endoscopy. This narrative review aims to provide an overview of known and emerging fields of application for mEUS in gastrointestinal endoscopy. After its initial development in pancreatobiliary scenarios in the early 1990s, mEUS has been recently reconsidered a third-space endoscopic technique that is progressively developing and spreading for the treatment of early gastrointestinal neoplastic lesions. The high spatial resolution of mEUS provides an accurate assessment of the degree of submucosal invasion in early esophageal, gastric, and colorectal neoplasia, while the small caliber of catheters allows for mEUS employment in settings where standard echoendoscopes are impractical (e.g., severe stenoses or proximal colonic lesions). Beyond cancer staging, mEUS offers point-of-care characterization of subepithelial lesions by defining the layer of origin and echo-pattern, eventually defining endoscopic resectability, but definitive diagnosis remains histological. In pancreatobiliary diseases, miniprobe intraductal ultrasonography (IDUS) shows its strongest application for indeterminate biliary strictures when endoscopic retrograde cholangiopancreatography (ERCP)-based sampling strategies and brushing cytology show inconclusive diagnoses, and in choledocholithiasis, particularly for the detection of small stones/sludge and confirmation of duct clearance. IDUS is also valuable for the staging of ampullary tumors, for longitudinal extension mapping in hilar cholangiocarcinoma and for selected portal biliopathy scenarios. Overall, mEUS and IDUS are high-resolution adjuncts that can meaningfully refine local decision-making in the treatment of superficial epithelial/subepithelial tumors or lesions involving the bile ducts. Limitations include shallow penetration, lack of tissue acquisition capability, a relative increase in post-ERCP pancreatitis risk for intraductal use, and substantial cost with limited availability in lower-volume centers.

Per-oral flexible endoscopy has expanded minimally invasive options for the management of gastric subepithelial tumors (G-SETs). This narrative review appraises conventional and advanced endoscopic resections alongside hybrid laparoscopic–endoscopic procedures, within a size- and layer-based clinical framework. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) achieve high en bloc resection rates for small, intraluminal tumors arising from mucosa or submucosa. Traction strategies and dedicated traction devices may improve submucosal exposure, shorten procedure time, and reduce adverse events. Submucosal tunneling endoscopic resection (STER) has been developed to enucleate tumors originating from the muscularis propria while preserving mucosal integrity. However, tunnel creation and specimen retrieval become challenging for large tumors or for those located in the cardia or fundus. Endoscopic full-thickness resection (EFTR) enables controlled transmural excision of G-SETs arising from deeper wall layers. Exposed EFTR, combined with secure endoscopic closure, provides high en bloc and complete (R0) resection rates. Closure options range from through-the-scope clips—for small defects—to over-the-scope clips, endoloop-clip purse-string methods, reopenable-clip over-the-line techniques and endoscopic suturing systems—for larger defects. Non-exposed EFTR and device-assisted systems reduce the risk of peritoneal contamination, although complete resection rates are more variable. Hybrid approaches, including classical laparoscopic–endoscopic cooperative surgery (LECS) and non-exposure variants, combine endoscopic precision with the safety and closure capabilities of laparoscopic surgery, minimizing the amount of resected gastric wall. They are particularly suited to larger, awkwardly located or ulcerated G-SETs. Emerging traction platforms, flexible robotic systems, and AI-based tools may further broaden the role of per-oral flexible endoscopy for the treatment of G-SETs. However, evidence remains preliminary, and surgery continues to play a key role for large, extraluminal or anatomically prohibitive G-SETs.

Next-generation sequencing has overturned the dogma of biliary sterility, revealing low-biomass microbiota along the gut–biliary axis with metabolic and immunologic effects. This review synthesizes evidence on composition, function, and routes of colonization across benign and malignant disease. In cholelithiasis, Proteobacteria- and Firmicutes-rich consortia provide β-glucuronidase, phospholipase A2, and bile salt hydrolase, driving bile supersaturation, nucleation, and recurrence. In primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis, intestinal dysbiosis and disturbed bile acid pools modulate pattern recognition receptors and bile acid signaling (FXR, TGR5), promote Th17 skewing, and injure cholangiocytes; bile frequently shows Enterococcus expansion linked to taurolithocholic acid. Distinct oncobiomes characterize cholangiocarcinoma subtypes; colibactin-positive Escherichia coli and intratumoral Gammaproteobacteria contribute to DNA damage and chemoresistance. In hepatocellular carcinoma, intratumoral microbial signatures correlate with tumor biology and prognosis. We critically appraise key methodological constraints—sampling route and post-sphincterotomy contamination, antibiotic prophylaxis, low biomass, and heterogeneous analytical pipelines—and outline a translational agenda: validated microbial/metabolomic biomarkers from bile, tissue, and stent biofilms; targeted modulation with selective antibiotics, engineered probiotics, fecal microbiota transplantation, and bile acid receptor modulators. Standardized protocols and spatial, multi-omic prospective studies are required to enable risk stratification and microbiota-informed therapeutics.

BACKGROUND:Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. High-risk colorectal colitis-associated neoplasia (HR-CAN) can be difficult to treat using traditional endoscopic resection methods. This study evaluated the outcomes of endoscopic submucosal dissection (ESD) in patients with IBD and HR-CANs. METHODS:This retrospective multicenter study consecutively included patients with IBD who were referred to expert Italian endoscopy centers for ESD or hybrid ESD (hESD) of HR-CANs. The main outcomes were rates of en bloc, R0, and curative resections, adverse events, local recurrence, metachronous lesions, and post-resection surgery. Kaplan-Meier method was used to analyze survival rates. Risk factors associated with the main outcomes were investigated by univariable analysis. RESULTS:91 patients with colonic IBD (disease duration 15.3 [SD 8.7] years, 82.4 % with ulcerative colitis) with 96 HR-CANs (mean size 34.8 [SD 16.2] mm, 53.1 % high grade dysplasia/adenocarcinoma) were included. ESD and hESD were performed in 82.3 % and 17.7 %, respectively. En bloc, R0, and curative resections were achieved in 95.8 % (95 %CI 89.6-98.8), 85.4 % (95 %CI 76.7-91.7), and 83.3 % (95 %CI 74.3-90.1). Adverse events occurred in 12.5 % (95 %CI 6.6-20.8), which were all conservatively managed. After a mean follow-up of 23.4 (SD 16.1) months, local recurrence and metachronous lesions each occurred in 3.1 %. Post-resection surgery was required in 11.5 %. CONCLUSIONS:ESD of HR-CANs showed favorable outcomes on the medium- and long-term course in patients with IBD.

This video case underscores the feasibility of traction-assisted ESD for large gastric NETs in AAG. By providing stable exposure of the submucosal plane, traction can enable precise dissection and secure margin clearance while preserving muscular integrity. Such an approach may be particularly valuable in patients with chronic inflammatory conditions that predispose them to multiple or recurrent gastric lesions

Background/Objectives: The management of non-lifting colorectal lesions (NLCLs), often resulting from previous unsuccessful treatments or biopsies, remains challenging due to submucosal fibrosis that prevents adequate lifting. Endoscopic submucosal dissection (ESD) is a viable option for achieving complete resection in such cases. However, when standard ESD is not feasible, conversion to hybrid ESD (H-ESD) has been proposed as a rescue strategy. This study aimed to assess ESD’s feasibility, effectiveness, and safety for NLCLs, including cases requiring conversion to H-ESD, when performed by experienced endoscopists in tertiary referral centers. Methods: In this multicenter retrospective study, data from patients with NLCLs treated by ESD/H-ESD between January 2009 and September 2022 were analyzed. The primary endpoint was the recurrence rate (RR). Secondary endpoints included the adverse event (AE) rate, technical success (TS) rate (en bloc resection regardless of technique), complete resection (CR), curative resection (cR) rates, and surgical intervention rate. Predictors of ESD technical success were identified. Results: In total, 178 patients with NLCLs were included (52 previously biopsied, 126 recurrent after previous resection). ESD was used in 111 (62.4%) and H-ESD in 67 (37.6%) cases. During a median follow-up of 373 days (IQR 540), the overall RR was 3.6%. The overall AE rate was 13.4%, and perforation was the most frequent (8.4%). All AEs were successfully managed endoscopically. The TS rate was 71.9%, significantly higher in previously biopsied lesions compared to recurrent ones (78.8% vs. 55.6%, p = 0.04). On multivariate analysis, rectal location (p < 0.001), F1 fibrosis (p = 0.026), and previously biopsied lesions (p = 0.006) predicted ESD TS without the need for conversion to H-ESD. Conclusions: ESD/H-ESD is feasible and safe for NLCLs when performed by experienced operators, with low RR amenable to endoscopic treatment. Previously biopsied lesions, rectal location, and low fibrosis predict ESD TS.

Chronic pancreatitis (CP) precipitates complex malnutrition through synergistic mechanisms: exocrine pancreatic insufficiency–driven maldigestion, duodenal or pancreatobiliary strictures limiting nutrient flow, cholestasis impairing micelle formation, alcohol-related anorexia, pain-induced hypophagia, proteolytic catabolism from type 3c diabetes, and a chronic inflammatory milieu that accelerates sarcopenia and bone demineralisation. Consequent calorie–protein depletion, micronutrient and fat-soluble vitamin deficits, and metabolic derangements markedly amplify morbidity. Pancreatic enzyme replacement therapy (PERT) with targeted micronutrient repletion is foundational; high-protein regimens co-administered with PERT curb muscle loss, and medium-chain triglycerides (MCTs) can augment caloric delivery by bypassing lipase dependence, although their benefit over personalised dietetic counselling is marginal. Optimal dietary fat thresholds and timing of escalation from oral to enteral or parenteral feeding remain unresolved. Comprehensive care also demands alcohol abstinence, effective analgesia and stringent glycaemic control. Serial monitoring—biochemical indices, densitometry, dual-energy X-ray absorptiometry and imaging-based body-composition metrics—permits early detection of high-risk patients and precision tailoring of interventions. Intensified multidisciplinary programmes already improve prognostic endpoints and are unveiling biomarkers of nutritional resilience. A structured, evidence-based strategy integrating PERT, macronutrient engineering, micronutrient repletion and metabolic surveillance is essential to mitigate nutrition-related morbidity, enhance long-term outcomes and optimise quality of life in CP.

Background: Endoscopic submucosal dissection (ESD) has emerged as the standard treatment for colorectal lesions. Considering the global population ageing, we aimed to assess the effectiveness and safety of colorectal ESD in patients aged ≥ 80 compared to 65-79 on a large Western cohort. Methods: We retrospectively enrolled patients aged >64 years undergoing colorectal ESD, classifying them into Very Elderly Group (VE-Group, age>80 yo) and Elderly group (E-Group, 65-79 yo). Procedure outcomes and safety were compared between VE-Group and E-Group and between patients with comorbidities and healthy (1-CM-Group and H-Group). Results: A total of 980 patients were included [269 (27,5%) in VE-Group and 711 (72,5%) in E-Group]. En-bloc, R0, and oncological curative resection rates did not differ, as well as intra and post-procedural adverse events (AEs). Delirium occurrence was registered in VE-group [6 (2.2%) in VE-Group vs 1 (0.1%) in E-Group; P=0.001; OR=16.2(95%CI:1.9-135.2)]. 1-CM-Group showed a higher rate of intraprocedural bleeding (P=0.001), delayed perforation (P=0.03) fever onset (P<0.001) and systemic infections (P=0.02) compared to the H-Group. Having one or more comorbidities was associated with increased overall AEs [P<0.001; OR:2.3(95%CI:1.5-3.6)]. Conclusion: Colorectal ESD is a feasible procedure for old patients. Physicians should consider delirium a possible AE in patients over 80. These findings, which bridge the gap between Asian and Western clinical data, underscore the importance of tailored pre- and post-procedural assessments in a global clinical context.

BACKGROUND AND AIMS:The risk of postresection colorectal stenosis significantly increases when more than 90% of the circumference is involved. We aimed to evaluate postresection stenosis incidence and predictive factors in patients undergoing colorectal endoscopic submucosal dissection (ESD) for whole circumferential lesions. METHODS:We retrospectively analyzed prospective data from patients undergoing ESD for colorectal lesions involving ≥90% of the luminal circumference at 29 worldwide tertiary referral centers between June 2018 and September 2024. The primary end point was to evaluate the incidence and predictive factors of postresection stenoses. Secondary end points included assessing the effectiveness and safety of the ESD procedure. RESULTS:A total of 315 patients were included, with 269 (85.4%) rectal and 46 (14.6%) colonic lesions, and a median lesion size of 95 mm (IQR, 71-130). Complete (100%) circumferential involvement was observed in 116 cases (36.8%). En bloc, complete resection with negative margins, and oncological curative resection rates were 85.1%, 81.8%, and 80.3%, respectively. Of the 315 lesions, 31 (9.2%) were referred for surgery, and the remaining 284 (90.2%) were included in the final analysis. Stenosis occurred in 97 of 284 cases (34.2%), with a higher incidence for rectal than colonic lesions (38.2% vs 11.6%; P < .001). All stenoses were effectively managed with endoscopic treatments, achieving complete resolution of symptoms and luminal patency in all treated cases, with no need for surgical intervention. At multivariable analysis, rectal location (odds ratio [OR], 4.40; 95% CI, 1.62-12.06; P = .004), 100% circumferential resection (OR, 2.44; 95% CI, 1.41-4.21; P < .001), and larger lesion size (OR, 1.01; 95% CI, 1.01-1.02; P = .005) were independently associated with stenosis occurrence. CONCLUSIONS:The risk of stenosis after circumferential ESD for colorectal lesions ≥90% is high in the rectum but can be effectively managed endoscopically. Despite this, the technique remains highly feasible and safe.

Zenker’s Diverticulum (ZD) is the most common hypopharyngeal diverticulum; however, it is often underdiagnosed. It results from the herniation of the mucosa and submucosa through Killian’s Triangle. Dysphagia is the primary symptom, occurring in 80–90% of cases. The primary goal of treatment is to transect the cricopharyngeal muscle (CM) and connect the ZD cavity to the esophageal lumen. Traditional treatments include surgical open transcervical diverticulectomy and CM septomyotomy, using rigid or flexible endoscopes. However, surgery is burdened by technical difficulties and not negligible rates of adverse events (AEs). For this reason, endoscopic techniques for ZD treatment have gained traction in recent years. Flexible endoscopic septum division (FESD), introduced nearly 20 years ago, involves a full-thickness incision of the diverticular septum. The advent of third-space endoscopy has led to the application of these techniques to ZD treatment as well. Zenker-POEM (Z-POEM) and, subsequently, Per Oral Endoscopic Septomyotomy (POES) have been developed. Hybrid techniques, such as Peroral Endoscopic Diverticulotomy (POED) and tunneling-free methods, represent additional ZD treatment options. This review outlines the armamentarium of ZD endoscopic management, summarizing the characteristics of these techniques, their benefits and limitations, and highlighting future research directions.