Aggarwal, Manik

Background: The optimal self-expandable metallic stent (SEMS) choice for endoscopic drainage of unresectable extrahepatic malignant biliary obstruction (MBO) with endoscopic retrograde cholangiopancreatography (ERCP) remains unclear due to limited randomized controlled trial (RCT) evidence. Prior meta-analyses have relied on observational data, introducing heterogeneity and bias. To overcome these limitations, an RCT-only network meta-analysis (NMA) was performed to evaluate the efficacy and safety of SEMS types. Methods: A literature search was conducted to identify RCTs assessing fully covered SEMS (FCSEMS), partially covered SEMS (PCSEMS), and/or uncovered SEMS (UCSEMS) for ERCP drainage of unresectable extrahepatic MBO. Study outcomes included recurrent biliary obstruction (RBO), specific causes of RBO, overall survival (OS), and adverse events (AEs). A frequentist NMA was performed to estimate hazard ratios (HRs) and incidence rate ratios (IRRs) with their 95% confidence intervals and overall P-scores. Results: Ten RCTs (1,659 patients) were included. There were no significant differences in time to RBO, incidence of any RBO, or OS between stent types. UCSEMS had the lowest rates of stent migration, tumor overgrowth, and sludge occlusion, whereas FCSEMS most effectively prevented tumor ingrowth. AE rates were similar across groups; however, only FCSEMS, but not PCSEMS, had significantly higher rates of acute cholecystitis than UCSEMS in patients with an intact gallbladder. Conclusion: There were no differences in RBO, OS, or AE excluding acute cholecystitis between each SEMS type, although each type has its advantages and disadvantages. FCSEMS was associated with a higher risk of acute cholecystitis, emphasizing careful patient selection, particularly regarding gallbladder status.

Abstract Endoscopic retrograde cholangiopancreatography (ERCP)-based tissue acquisition is the cornerstone for assessment of suspected malignant biliary strictures. Conventional techniques, including biliary brush cytology and transpapillary forceps biopsy, are highly specific but are limited by modest sensitivity for detection of malignancy, often leaving a substantial proportion of individuals without a definitive diagnosis. To improve diagnostic sensitivity for cancer, several adjunctive approaches have been integrated into ERCP-based sampling. Peroral cholangioscopy (POC)-guided biopsies have become a reliable ERCP-based adjunctive modality, allowing direct visualization and targeted sampling, particularly in individuals with prior nondiagnostic procedures. Fluorescence in situ hybridization (FISH) is a technique used to improve diagnostic yield with biliary brushings by detecting chromosomal abnormalities, but is limited to specialized centers due to the need for specialized processing and training. Next-generation sequencing provides high sensitivity and can enable identification of actionable genomic alterations, while methylated DNA markers represent a promising, scalable molecular approach with strong diagnostic performance. Additional techniques include artificial intelligence–augmented direct visualization by POC and bile-based liquid biopsy. Current guidelines recommend multimodal ERCP-based sampling, combining at least two modalities where feasible, to optimize diagnostic accuracy. This review highlights the clinical performance, strengths, and limitations of established and emerging ERCP-guided techniques, emphasizing their evolving role in improving the diagnosis and management of malignant biliary strictures.

Malignant hilar biliary obstruction (MHBO) is most commonly caused by cholangiocarcinoma or gallbladder cancer and frequently presents with obstructive jaundice, pruritus, and/or cholangitis. These symptoms impair performance status and delay the initiation of chemotherapy, making biliary drainage essential for both palliation and oncologic treatment. Endoscopic transpapillary biliary stenting via endoscopic retrograde cholangiopancreatography is the standard approach for biliary decompression. In patients with unresectable disease, either plastic or self-expandable metal stents may be used. Optimal outcomes are achieved when drainage encompasses more than 50% of functional liver volume, while atrophic segments should be avoided. When transpapillary access is not feasible or unsuccessful, alternative approaches such as percutaneous transhepatic biliary drainage or endoscopic ultrasound-guided biliary drainage may be considered. Adjunctive therapies, including photodynamic therapy and radiofrequency ablation, are being investigated to enhance local tumor control and prolong stent patency. With continued advances in stent technology, imaging modalities, and endoscopic techniques, the management of MHBO is expected to become increasingly individualized and effective.

Background: Upper gastrointestinal bleeding (UGIB) is a common medical emergency associated with significant morbidity, mortality, and healthcare costs. Many patients undergo early endoscopy despite the absence of active bleeding. PillSense is a novel Food and Drug Administration (FDA)-cleared ingestible capsule that rapidly detects the presence of blood in the upper GI tract and may optimize triage decisions. Methods: We conducted a retrospective study evaluating the impact of PillSense on the management of suspected UGIB in an academic center. The primary outcome was the association between capsule results and clinical decision-making, including endoscopy deferral, prioritization, outpatient scheduling, and airway protection. Secondary outcomes included transfusion requirements, time-to-endoscopy, endoscopic intervention, and 30-day adverse events. Results: A total of 28 patients (mean age 64.4 ± 17.9 years, 82.7% male) were included. Compared with negative results, positive results were associated with higher transfusion requirements (median 3 (IQR 3–6) vs. 2 (IQR 1–3.25) units; p = 0.041) and shorter time-to-endoscopy (median 0.2 (IQR 0.01–1) vs. 2 (IQR 1–15.5) days; p = 0.017). In high-risk for sedated endoscopy patients, negative results were associated with EGD deferral in 53.8%, with no subsequent adverse events within 30 days. Endoscopic intervention was performed in 62.5% of positive-result patients versus 9.5% of negative-result patients. Conclusions: The PillSense results were associated with differences in triage and management of high-risk patients with suspected UGIB. Its rapid, accurate, and non-invasive results may reduce unnecessary urgent endoscopy procedures, improve resource utilization, and enhance patient safety, particularly in the highest-risk populations.

Background: Fluorescence in situ hybridization (FISH) is recommended as part of multimodality sampling in the evaluation of biliary strictures, but can be false negative in 40%–50% cases. The aim of this study was to comprehensively assess predictors of false-negative FISH in patients with biliary strictures. Methods: Patients undergoing tissue sampling for biliary strictures from October 20 to February 22 were prospectively enrolled (NCT04572711). Procedural factors such as sampling techniques, order, and utilization of combination sampling were recorded. Results of an optimized pancreatobiliary FISH panel with locus-specific probes for 1q21, 7p12, 8q24, and 9p21 were reported per guidelines. Statistical analyses were performed using BlueSky Statistics v.10.3.1, R package v8.81. Results: Of 327 patients, 93 (28.5%) were diagnosed with malignancy. A false-negative pancreatobiliary fluorescence in situ hybridization (PB-FISH) was reported in 40 (43.1%) patients. A history of primary sclerosing cholangitis was associated with lower odds of having a false-negative PB-FISH (aOR=0.38, 95% CI=0.16–0.82, p=0.02), whereas a hilar stricture was associated with a significantly higher false-negative PB-FISH in those with cholangiocarcinoma (aOR=3.2 [1.4–7.9], p=0.009). Dilation of biliary strictures prior to brushing was not associated with a lower rate of false-negative PB-FISH. Conclusions: In this prospective study, hilar strictures were more likely to have false-negative PB-FISH. Dilation of strictures did not affect PB-FISH performance. These results can help guide PB-FISH interpretation.

Endoscopic ultrasound (EUS)-guided tissue sampling includes the techniques of fine needle aspiration (FNA) and fine needle biopsy (FNB), and both procedures have revolutionized specimen collection from the gastrointestinal tract, especially from remote/inaccessible organs. EUS-FNB has replaced FNA as the procedure of choice for tissue acquisition in solid pancreatic lesions (SPLs) across various society guidelines. FNB specimens provide a larger histological tissue core (preserving tissue architecture) with fewer needle passes, and this is extremely relevant in today’s era of precision and personalized molecular medicine. Innovations in needle tip design are constantly under development to maximize diagnostic accuracy by enhancing histological sampling capabilities. But, apart from the basic framework of the needle, various other factors play a role that influence diagnostic outcomes, namely, sampling techniques (fanning, aspiration or suction, and number of passes), collection methods, on-site evaluation (rapid, macroscopic, or visual), and specimen processing. The choice taken depends strongly on the endoscopist’s preference, available resources at the disposal, and procedure objectives. Hence, in this review, we explicate in detail the concepts and available literature at our disposal on the topic of EUS-guided pancreatic tissue sampling to best guide any practicing gastroenterologist/endoscopist in a not-to-ideal set-up, which EUS-guided tissue acquisition technique is the “best” for their case to augment their diagnostic outcomes.

Background and Aims: This systematic review and meta-analysis aims to compare the performance of UroVysion® FISH based on the different definitions of a positive result used in published literature with the goal of determining the optimal FISH definition for detecting pancreaticobiliary malignancy. Methods: A systematic literature search identified studies from database inception to Sept 2024 that evaluated the diagnostic performance of FISH in determining malignancy among patients with biliary strictures. All thresholds for positive FISH, as defined by the individual study, were included in this review. Subgroup analysis was performed based on the definitions of positive FISH as follows: (1) polysomy only; (2) polysomy, tetrasomy, or trisomy; and (3) polysomy or 9p deletion. Results: Eighteen studies comprising 2516 FISH specimens were analyzed, including 1133 (45.0%) with malignancy. Using a threshold for positivity as defined in individual studies, the overall sensitivity of FISH was 57.6% (95% confidence interval [CI], 49.4–65.4%), and the overall specificity was 87.8% (95% CI, 79.2–93.2%). Subgroup analysis showed that polysomy as the threshold for positive FISH yielded a sensitivity of 49.4% (95% CI, 43.2–55.5%), with an increased specificity of 96.2% (95% CI, 92.7–98.1%), while polysomy + tetrasomy/trisomy as positive FISH resulted in an increased sensitivity of 64.3% (95% CI 55.4–72.2%) but a decreased specificity of 78.9% (95% CI 64.4–88.5%). The addition of 9p deletion to polysomy as the criteria for a positive test resulted in a non-significant increase in sensitivity (54.7% (95% CI 42.4–66.5%) while maintaining specificity (95.1% (95% CI 84.0–98.6%). Conclusions: Based on these findings, polysomy only or polysomy/9p deletion should be considered as the criterion for defining a positive FISH test to improve diagnostic sensitivity while maintaining high specificity.