Faculty Bibliography

BACKGROUND AND STUDY AIMS/UNASSIGNED:Cholangiocarcinoma (CCa) is a complex malignancy of the biliary tract, classified as intrahepatic, perihilar, or distal. Digital single-operator cholangioscopy (D-SOC) enhances evaluation of biliary strictures, although it remains limited by suboptimal biopsy yield and technical constraints. Artificial intelligence (AI), particularly convolutional neural networks (CNNs), has emerged as a promising adjunct. However, performance across anatomical subtypes is not well defined. This study evaluated diagnostic performance of an AI-based model in detecting CCa lesions by location. PATIENTS AND METHODS/UNASSIGNED:A YOLOv8-based CNN was trained and validated using 315,993 D-SOC images from 183 patients across six international high-volume centers. Images were labeled as benign or malignant based on expert consensus. Frame-based analysis assessed diagnostic performance using macro-average F1-score, precision, and recall. Subgroup analysis explored anatomical site-specific performance. RESULTS/UNASSIGNED:Among the included patients (mean age 66.1±12.1 years; 64.5% male), 43.2% had perihilar, 37.2% intrahepatic, and 19.7% distal biliary strictures. The model demonstrated high overall performance: F1 score 95.3%, precision 95.5%, and recall 95.1%. Site-specific analysis revealed an F1 score of 89.6% for distal strictures and 91.1% for perihilar strictures. Receiver operating characteristic curves showed areas under the curve of 0.980 for intrahepatic strictures and 0.990 for perihilar and distal strictures. CONCLUSIONS/UNASSIGNED:This is the first study to demonstrate AI-based diagnostic performance across CCa topography using a large, multicenter D-SOC dataset. Although anatomical complexity affects detection, the model's high precision and generalizability suggest potential for clinical utility. These results support application of an AI-enhanced algorithm decision algorithm for cholangioscopy.

INTRODUCTION/BACKGROUND:Endoscopic retrograde cholangiopancreatography (ERCP) is essential for pancreaticobiliary disease management; however, there are risks associated with the procedure, particularly post-ERCP pancreatitis (PEP). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in metabolic disease, possess anti-inflammatory and cytoprotective properties that may influence periprocedural outcomes. Their impact on ERCP adverse events remains unclear; therefore, we aimed to investigate whether GLP-1 influences short-term postprocedural outcomes using a large real-world database. METHODS:We conducted a retrospective cohort study using the TriNetX US Collaborative Network, identifying adults (18 y or older) who underwent ERCP between January 2015 and December 2024. Patients were categorized based on documented preprocedure GLP-1 receptor agonist exposure. Propensity score matching (1:1) was performed using demographic, clinical, procedural, and pharmacologic covariates to minimize confounding, yielding 2 well-balanced cohorts. Thirty-day post-ERCP outcomes-including acute pancreatitis, cholangitis, sepsis, gastrointestinal bleeding, biliary stricture, choledocholithiasis, and repeat ERCP-were assessed using ICD-10 and CPT codes. Risk ratios (RRs) and hazard ratios (HRs) with 95% CIs were calculated. RESULTS:Of 250,502 patients with ERCP screened, 21,818 propensity-matched individuals were included in the final analysis. Compared with matched nonusers, patients receiving GLP-1 receptor agonists had significantly lower 30-day rates of all major ERCP-related adverse events. GLP-1 RA exposure was associated with reduced risks of acute pancreatitis (RR: 0.47, 95% CI: 0.43-0.51), cholangitis (RR: 0.56, 95% CI: 0.50-0.62), sepsis (RR: 0.51, 95% CI: 0.46-0.57), gastrointestinal bleeding (RR: 0.49, 95% CI: 0.40-0.61), biliary stricture (RR: 0.52, 95% CI: 0.48-0.55), repeat ERCP (RR: 0.53, 95% CI: 0.48-0.58), and choledocholithiasis (RR: 0.66, 95% CI: 0.62-0.71). Results were consistent across time-to-event analyses over the 30-day follow-up period. CONCLUSIONS:In this large real-world analysis, preprocedure GLP-1 RA therapy was associated with markedly reduced 30-day ERCP-related adverse events, most notably PEP. These findings highlight a potential protective role of GLP-1 signaling in the periprocedural inflammatory response and support prospective studies evaluating GLP-1 RAs as adjunctive prophylactic agents in ERCP. Further prospective studies are needed.

INTRODUCTION/BACKGROUND:Biliary strictures (BS) are a significant challenge, with malignant strictures frequently diagnosed at advanced stages, limiting curative options. Digital single-operator cholangioscopy (D-SOC) enables high-resolution, direct visualization of the bile duct, yet with suboptimal accuracy. Artificial intelligence (AI) has shown promise for detection and differentiation of BS in frame-level analysis and small clinical series. This study aimed to validate a deep learning model for AI-assisted D-SOC image analysis. METHODS:This multicenter study included 135 D-SOC exams from 129 patients (61 with malignant BS) across 14 centers in the United States, Brazil, Spain, Colombia, Australia, and Saudi Arabia. For each exam, up to 25 clinically relevant frames were selected and uploaded to a web-based platform for AI analysis. The model performed both detection and differentiation of BS: detection was assessed by comparing AI-generated bounding boxes with expert-defined annotations using intersection-over-union (IoU), while differentiation was benchmarked against histopathology. Performance metrics included accuracy, sensitivity, specificity, and positive and negative predictive values (PPV and NPV). RESULTS:At the patient level, malignant BS were identified with 86.0% accuracy, 84.1% sensitivity and 85.7% specificity, with an AUC of 0.904. The model demonstrated robust detection performance, achieving a mean IoU of 70.3%. Performance was maintained across demographic variables and centers. DISCUSSION/CONCLUSIONS:This first multicentric validation study demonstrates real-world performance of AI-assisted D-SOC analysis across multiples continents and devices, with robust accuracy for BS detection and differentiation. These findings support AI as an adjunctive tool in D-SOC, enhancing a more accurate evaluation of patients with indeterminate BS.

E-learning has revolutionized medical education by providing flexible, accessible, and interactive learning opportunities. This article explores the transformative impact of e-learning on gastroenterology education, highlighting the advancements and benefits brought by the American Society for Gastrointestinal Endoscopy (ASGE) platforms. ASGE's e-learning platforms offer specialized content, interactive tools, and continuous updates, enhancing the learning experience for gastroenterologists.

Neoadjuvant therapy (NAT) is increasingly used for pancreatic ductal adenocarcinoma (PDAC); yet most patients only achieve partial response. Pathological treatment response grading focuses on assessing residual tumor burden, often overlooking changes in tumor microenvironment (TME). To address this gap, we compared tumor cells and TME of 13 NAT-naïve and 23 post-NAT PDACs using integrated spatial pathomics and transcriptomics, with validation in an independent single-cell spatial dataset. NAT significantly reduced tumor burden (14.7%-6.2%, p = 0.004), but systemic comparison of 13 cytomorphometric features of tumor cells alone did not reliably distinguish between naïve and NAT cases. In contrast, NAT profoundly remodeled TME by increasing cancer-associated fibroblast (CAF) and CD8⁺ T cell densities, promoting CD8⁺ T cell-tumor cell proximity and fibrosis, reducing tumor-associated neutrophils, and redistributing tertiary lymphoid structures (TLSs). Spatial transcriptomics shows NAT induced apoptosis, DNA-damage response, and AGC-kinase (S_TK_X) signaling in tumor cells, and upregulated complement pathway, p53 signaling, and cellular senescence program in TME. Cross-platform single-cell spatial analysis revealed decreased regulatory T cells (Treg) and a shift from myofibroblastic (mCAF) to inflammatory CAF (iCAF). Importantly, post-NAT patients with more fibrosis had longer overall survival (p = 0.02), and higher B-cell density showed a favorable trend (p = 0.06). Together, these results suggest that beyond tumor debulking, NAT induces a coordinated TME remodeling characterized by fibroblast reprogramming, matrix fibrosis, and immune spatial reorganization. Incorporating assessment of NAT-induced stromal and immune changes into TRG may improve prognostication and guide more precise therapy in post-NAT PDAC.

Neoadjuvant therapy (NAT) is increasingly being used for pancreatic ductal adenocarcinoma (PDAC). This study investigates how NAT differentially impacts PDAC's carcinoma cells and the tumor microenvironment (TME). Spatial transcriptomics was used to compare gene expression profiles in carcinoma cells and the TME of 23 NAT-treated versus 13 NAT-naïve PDACs. Findings were validated by single-nucleus RNA sequencing (snRNA-seq) analysis. NAT induces apoptosis and inhibits proliferation of carcinoma cells and coordinately upregulates multiple complement genes (C1R, C1S, C3, C4B and C7) within the TME. Higher TME complement expression following NAT is associated with increased immunomodulatory and neurotrophic cancer-associated fibroblasts (CAFs); more CD4⁺ T cells; reduced immune exhaustion gene expression, and improved overall survival. snRNA-seq analysis demonstrates C3 complement is mainly upregulated in CAFs. These findings suggest that local complement dynamics could serve as a novel biomarker for prognosis, evaluating treatment response, and guiding therapeutic strategies in NAT-treated PDAC patients.

BACKGROUND:EUS-guided gastroenterostomy (EUS-GE) is a minimally invasive therapy for the management of gastric outlet obstruction (GOO). EUS-GE has demonstrated excellent short-term efficacy without the risks of surgical bypass. However, there is limited data on follow-up outcomes. In this study, we collected 6-month follow-up data on patients who underwent EUS-GE for benign and malignant etiologies, to aim to show the shift in paradigm in their management algorithm. METHODS:This was a retrospective multicenter study across 7 international centers of consecutive patients undergoing EUS-GE over a 4-year period who were entered in a dedicated registry. Demographic characteristics, procedure-related information, and follow-up data were collected. Primary outcome was the 6-month data on clinical resolution of GOO. RESULTS:Ninety-one patients were included (71 malignant and 20 benign cases). Technical success was 99% due to high expertise and volume. Clinical success at 48 hours was 97% (88/90) with an average procedure time of 47 minutes and length of stay of 5.86 days. At 3 months, 87 (95.6%) patients had achieved clinical resolution. At 6 months, 48 (53%) subjects were alive, 40 (44%) were deceased, 3 were lost to follow-up (3.3%) and 1 (1%) had a recurrence of GOO. Clinical success at 6 months follow-up was 98% (47/48). CONCLUSIONS:The majority of patients with GOO who undergo EUS-GE showed clinical resolution at 6-month follow-up. Patients with malignant etiology are appropriately palliated during their life span. Further prospective studies are necessary to obtain long-term data regarding EUS-GE for benign etiologies.

Gastric outlet obstruction (GOO) occurs due to anatomic blockage of the stomach or duodenum. GOO typically manifests with symptoms such as early satiety, nausea, vomiting, and weight loss, due to either underlying benign or malignant causes. Historically, the gold standard for managing GOO has been surgical gastrojejunostomy. However, this approach comes with considerable drawbacks including prolonged recovery times and the necessity for suitable surgical candidates. Endoscopically placed self-expanding metal stents emerged as a notable advancement in palliating symptoms associated with GOO. However, their long-term efficacy is hindered by the frequent occurrence of stent occlusion, necessitating the need for further intervention. Most recently, endoscopic ultrasound guided gastroenterostomy (EUS-GE) using lumen-apposing metal stents has been described with promising technical and clinical success rates. The advent of EUS-GE heralds a significant stride forward in the management of GOO, offering a less invasive yet effective alternative to conventional surgical approaches. EUS-GE has been associated with lower adverse events as compared with surgical gastrojejunostomy and lower recurrence and reintervention rates compared with enteral stenting. The advent of EUS-GE heralds a significant stride forward in the management of GOO, offering a less invasive yet effective alternative to conventional surgical approaches. EUS-GE is a promising evolving technique for treating GOO, and ongoing studies are necessary to validate its use in both benign and malignant GOO.