Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by eosinophilic infiltration of the esophagus. It arises from a complex interplay of genetic predisposition (susceptibility loci), environmental triggers (allergens and dietary antigens), and a dysregulated immune response, mainly mediated by type 2 T helper cell (Th2)-released cytokines, such as interleukin (IL)-4, IL-5, and IL-13. These cytokines control eosinophil recruitment and activation as well as tissue remodeling, contributing to the characteristic features of EoE. The pathogenesis of EoE includes epithelial barrier dysfunction, mast cell activation, eosinophil degranulation, and fibrosis. Epithelial barrier dysfunction allows allergen penetration and promotes immune cell infiltration, thereby perpetuating the inflammatory response. Mast cells release proinflammatory mediators and promote eosinophil recruitment and the release of cytotoxic proteins and cytokines, causing tissue damage and remodeling. Prolonged inflammation can lead to fibrosis, resulting in long-term complications such as strictures and dysmotility. Current treatment options for EoE are limited and mainly focus on dietary changes, proton-pump inhibitors, and topical corticosteroids. Novel therapies targeting key inflammatory pathways, such as monoclonal antibodies against IL-4, IL-5, and IL-13, are emerging in clinical trials. A deeper understanding of the complex pathogenetic mechanisms behind EoE will contribute to the development of more effective and personalized therapeutic strategies.

Alterations in the human microbiota have been linked to carcinogenesis in several cancers. To date, few studies have addressed the role of the microbiota in cholangiocarcinoma (CCA). Our work aims to update the knowledge about the role of the microbiota in the CCA microenvironment, and to highlight possible novel insights for the development of new diagnostic, prognostic, or even therapeutic strategies. We thus conducted a review of the literature. In recent years, great progress has been made in understanding the pathogenesis, the clinical and histological behavior, and the molecular profile of CCA. Much evidence suggests that the bile microbiota plays an essential role in biliary diseases, including CCA. Some studies have demonstrated that alterations in the qualitative and quantitative composition of the intestinal commensal bacteria lead to overall cancer susceptibility through various pathways. Other studies suggest that the gut microbiota plays a role in the pathogenesis and/or progression of CCA. The clinical implications are far-reaching, and the role of the microbiota in the CCA microenvironment may lead to considering the exciting implications of implementing therapeutic strategies that target the microbiota-immune system axis.

Objectives: Our aim was to investigate the clinical outcome of patients with well-differentiated gastric, duodenal, and rectal neuroendocrine tumors after treatment with incomplete endoscopic resection due to the finding of microscopic positive resection margins (R1). Methods: This is a retrospective analysis of consecutive patients with type 1 gastric, non-ampullary non-functioning duodenal, or rectal neuroendocrine neoplasms with positive R1 margins after endoscopic resection. The rate of tumor recurrence and progression-free survival were considered to be the study’s main endpoints. Statistical analysis was performed using MedCalc^® v.17 software and a p-value of <0.05 was considered significant. A Cox proportional-hazard regression was performed to identify risk factors for disease recurrence/progression. Results: After evaluating 110 patients, a total of 58 patients were included in the final analysis (15 gastric NENs, 12 duodenal NENs, and 31 rectal NENs). After evidence of endoscopic R1 resection had been gathered, 26 patients (44.8%) underwent an endoscopic/surgical extension of the previous resection. Tumor progression (all local recurrences) occurred in five out of fifty-eight patients (8.6%) with a median PFS of 36 months. There were no tumor-related deaths. G2 grading and the gastric primary tumor site were the only features significantly associated with the risk of recurrence of the disease (HR: 11.97 [95% CI: 1.22–116.99], HR: 12.54 [95% CI: 1.28–122.24], respectively). Conclusions: Tumor progression rarely occurs in patients with microscopic positive margin excision (R1) after endoscopic resection and does not seem to affect patients’ clinical outcomes.

Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) and endoscopic ultrasound-directed transenteric endoscopic retrograde cholangiopancreatography (EDEE) are innovative endoscopic techniques developed to overcome the challenges of biliary access in patients with surgically altered gastrointestinal anatomy. EDGE facilitates the creation of a gastro-gastric anastomosis, enabling endoscopic access to the excluded stomach and subsequent duodenum for endoscopic retrograde cholangiopancreatography (ERCP) procedures. Similarly, EDEE involves creating a gastro-jejunal anastomosis, allowing endoscopic access to the jejunum and hepaticojejunostomy for ERCP. These procedures are primarily indicated for patients with Roux-en-Y gastric bypass or other complex gastrointestinal surgeries that render traditional ERCP unfeasible. The major advantages of EDGE and EDEE include minimally invasive access to the biliary system, reduced procedural morbidity, and the ability to perform complex biliary interventions without additional surgeries. Using lumen-apposing metal stents in these procedures has further improved their safety and efficacy. This comprehensive review delves into EDGE and EDEE’s technical nuances, clinical outcomes, and safety profiles. Our extensive literature searches reveal high procedural success rates and low complication incidences, establishing these methods as viable alternatives to traditional surgical and percutaneous approaches. We also discuss recent technological advancements, including developing enhanced stents and endoscopic ultrasound-guided instruments, which have refined these techniques and expanded their applications. Moreover, the review examines the integration of EDGE and EDEE with other therapeutic modalities, such as cholangioscopy and intraductal lithotripsy, to optimize treatment outcomes. Future directions emphasize the need for larger, multicenter trials to validate these findings further and create standardized protocols to ensure consistent procedural efficacy and safety. This review highlights the transformative potential of EDGE and EDEE in therapeutic endoscopy, advocating for their broader adoption in clinical practice and ongoing innovation in this rapidly evolving field.

Obesity is a chronic, relapsing disease representing a global epidemic. To date, bariatric surgery is the most effective treatment for morbid obesity in the long-term. Roux-en-Y gastric bypass (RYGB) is one of the most performed bariatric interventions, with excellent long-term outcomes. However, about one-third of patients may experience weight regain over time, as well as dumping syndrome. Both these conditions are challenging to manage and require a multidisciplinary and personalized approach. The dilation of the gastro-jejunal anastomosis is a recognized etiological factor for both weight regain and dumping syndrome. Dietary modifications, behavioral interventions, and medications represent the first therapeutic step. Revisional surgery is the traditional approach when non-invasive treatments fail. However, re-interventions may be technically difficult and are associated with increased morbidity and mortality. Transoral outlet reduction (TORe) is an endoscopic procedure aimed at reducing the size of the anastomosis and is proposed as a minimally invasive treatment of weight regain and/or dumping syndrome refractory to conservative therapies. This review is aimed at providing a narrative overview of the role of TORe as part of the multidisciplinary therapeutic toolkit nowadays available to approach weight regain and dumping syndrome after RYGB.