Levy, Michael J.

Abstract Background The authors previously developed an artificial intelligence (AI) to assist cytologists in the evaluation of digital whole‐slide images (WSIs) generated from bile duct brushing specimens. The aim of this trial was to assess the efficiency and accuracy of cytologists using a novel application with this AI tool. Methods Consecutive bile duct brushing WSIs from indeterminate strictures were obtained. A multidisciplinary panel reviewed all relevant information and provided a central interpretation for each WSI as being “positive,” “negative,” or “indeterminate.” The WSIs were then uploaded to the AI application. The AI scored each WSI as positive or negative for malignancy (i.e., computer‐aided diagnosis [CADx]). For each WSI, the AI prioritized cytologic tiles by the likelihood that malignant material was present in the tile. Via the AI, blinded cytologists reviewed all WSIs and provided interpretations (i.e., computer‐aided detection [CADe]). The diagnostic accuracies of the WSI evaluation via CADx, CADe, and the original clinical cytologic interpretation (official cytologic interpretation [OCI]) were compared. Results Of the 84 WSIs, 15 were positive, 42 were negative, and 27 were indeterminate after central review. The WSIs generated on average 141,950 tiles each. Cytologists using the AI evaluated 10.5 tiles per WSI before making an interpretation. Additionally, cytologists required an average of 84.1 s of total WSI evaluation. WSI interpretation accuracies for CADx (0.754; 95% CI, 0.622–0.859), CADe (0.807; 95% CI, 0.750–0.856), and OCI (0.807; 95% CI, 0.671–0.900) were similar. Conclusions This trial demonstrates that an AI application allows cytologists to perform a triaged review of WSIs while maintaining accuracy.

Background and Aims: Early identification of malignant biliary strictures (MBSs) is challenging, with up to 20% classified as indeterminants after preliminary testing and tissue sampling with endoscopic retrograde cholangiopancreatography. We aimed to evaluate the use of methylated DNA markers (MDMs) from biliary brushings to enhance MBS detection in a prospective cohort. Approach: Candidate MDMs were evaluated for their utility in MBS diagnosis through a series of discovery and validation phases. DNA was extracted from biliary brushing samples, quantified, bisulfite-converted, and then subjected to methylation-specific droplet digital polymerase chain reaction. Patients were considered to have no malignancy if the sampling was negative and there was no evidence of malignancy after 1 year or definitive negative surgical histopathology. Results: Fourteen candidate MDMs were evaluated in the discovery phase, with top-performing and new markers evaluated in the technical validation phase. The top 4 MDMs were TWIST1, HOXA1, VSTM2B, and CLEC11A, which individually achieved AUC values of 0.82, 0.81, 0.83, and 0.78, respectively, with sensitivities of 59.4%, 53.1%, 62.5%, and 50.0%, respectively, at high specificities for malignancy of 95.2%–95.3% for the final biologic validation phase. When combined as a panel, the AUC was 0.86, achieving 73.4% sensitivity and 92.9% specificity, which outperformed cytology and fluorescence in situ hybridization (FISH). Conclusions: The selected MDMs demonstrated improved performance characteristics for the detection of MBS compared to cytology and FISH. Therefore, MDMs should be considered viable candidates for inclusion in diagnostic testing algorithms.

Abstract Background Visceral fat represents a metabolically active entity linked to adverse metabolic sequelae of obesity. We aimed to determine if celiac artery mesenteric fat thickness can be reliably measured during endoscopic ultrasound (EUS), and if these measurements correlate with metabolic disease burden. Methods This was a retrospective analysis of patients who underwent celiac artery mesenteric fat measurement with endosonography (CAMEUS) measurement at a tertiary referral center, and a validation prospective trial of patients with obesity and nonalcoholic steatohepatitis who received paired EUS exams with CAMEUS measurement before and after six months of treatment with an intragastric balloon. Results CAMEUS was measured in 154 patients [56.5% females, mean age 56.5 ± 18.0 years, body mass index (BMI) 29.8 ± 8.0 kg/m2] and was estimated at 14.7 ± 6.5 mm. CAMEUS better correlated with the presence of non-alcoholic fatty liver disease (NAFLD) (R2 = 0.248, P < 0.001) than BMI (R2 = 0.153, P < 0.001), and significantly correlated with metabolic parameters and diseases. After six months of intragastric balloon placement, the prospective cohort experienced 11.7% total body weight loss, 1.3 points improvement in hemoglobin A1c (P = 0.001), and a 29.4% average decrease in CAMEUS (−6.4 ± 5.2 mm, P < 0.001). CAMEUS correlated with improvements in weight (R2 = 0.368), aspartate aminotransferase to platelet ratio index (R2 = 0.138), and NAFLD activity score (R2 = 0.156) (all P < 0.05). Conclusions CAMEUS is a novel measure that is significantly correlated with critical metabolic indices and can be easily captured during routine EUS to risk-stratify susceptible patients. This station could allow for EUS access to sampling and therapeutics of this metabolic region.

Background and Aims: Endoscopic ultrasound shear wave elastography (EUS-SWE) is a novel modality for liver stiffness measurement. The aims of this study are to evaluate the performance and reliability of EUS-SWE for detecting advanced liver disease in a prospective cohort. Methods: EUS-SWE measurements were prospectively obtained from patients undergoing EUS between August 2020 and March 2023. Liver stiffness measurements were compared between patients with and without advanced liver disease (ALD), defined as stage ≥3, to determine diagnostic accuracy for advanced fibrosis and portal hypertension. Logistic regression was performed to identify variables that impact the reliability of EUS-SWE readings. Select patients underwent paired magnetic resonance elastography (MRE) for liver fibrosis correlation. Results: Patients with ALD demonstrated higher liver stiffness compared to healthy controls (left lobe: 17.6 vs. 12.7 kPa, P <0.001; median right lobe: 24.8 vs. 11.0 kPa, P <0.001). The area under the receiver operator characteristic (AUROC) for the detection of ALD was 0.73 and 0.80 for left and right lobe measurements, respectively. General anesthesia was associated with reliable EUS-SWE liver readings (odds ratio: 2.73, 95% CI: 1.07-7.39, P =0.040). Left lobe measurements correlated significantly with MRE with an increase of 0.11 kPa (95% CI: 0.05-0.17 kPA) for every 1 kPa increase on EUS-SWE. D. Conclusions: SWE is a promising technology that can readily be incorporated into standard EUS examinations for the assessment of ALD.

Background: Reports suggest that the rate of adverse events (AEs) post-endoscopic sphincterotomy (ES) to be as high as 10%, with gastrointestinal bleeding being most common after post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Objective: The aim of this study was to characterize the incidence of bleeding in patients with thrombocytopenia following ES. Design: Retrospective observational cohort study. Methods: Patients with thrombocytopenia (defined as <150,000 platelets/μL) who underwent ES between May 2017 and December 2020 were identified at a tertiary care medical center. The incidence of immediate (intraprocedural oozing >5 min or requiring intervention) or delayed (clinical bleeding with associated hemoglobin drop within 14 days) post-ES bleeding was determined via manual chart review. Results: A total of 221 patients with a mean platelet count of 108,000 ± 13,000 platelets/μL underwent ERCP with ES. Immediate bleeding occurred in 11 (5%) patients with no significant drop in hemoglobin or transfusion requirement. Two patients (0.9%), both of whom were noted to have immediate bleeding, also developed delayed bleeding. Presence of malignancy was associated with an increased risk of bleeding (36.4% versus 11.4%, p = 0.037) while platelet count was not. Conclusion: In a cohort of patients with thrombocytopenia, rates of immediate and delayed bleeding are similar to previously reported AE rates of ES in the general patient population. Careful attention should be given to patients with a history of active malignancy as well as those who develop immediate bleeding as they appear to be at increased risk for bleeding complications.

Localized insulinoma is an uncommon entity that can result in substantial morbidity due to the associated hypoglycemia. Recent studies have suggested an increase in the incidence of insulinoma in recent decades that may possibly be secondary to increased awareness, incidental diagnoses, and better diagnostic methods. Diagnosing and localizing insulinoma within the pancreas can be challenging, but advances in nuclear imaging may improve diagnostic accuracy. Delays in diagnosis are common, but once a localized insulinoma is diagnosed and appropriately treated, the long-term prognosis is excellent. Surgical resection is considered the standard of care management option for localized insulinoma, but tumor ablation with endoscopic ultrasound guidance has also been shown to be an effective and safe method for therapy.

Abstract Background and study aims The risk of bleeding with endoscopic ultrasound-guided tissue acquisition (EUS-TA) in patients on uninterrupted antithrombotic agents is unknown. This study aimed to assess the safety of EUS-TA without discontinuing direct oral anticoagulants. Methods Twenty pigs were randomized (1:1) to oral apixaban or placebo. Treatment was administered for 3 days before and 3 days after EUS-TA of the pancreas. Primary endpoint was occurrence of clinically significant bleeding events (CSBEs), defined as a composite outcome of drop in hemoglobin ≥ 2 g/dL and evidence of intraprocedural or post-procedure bleeding. Secondary outcome was cytopathological adequacy of acquired specimens. Endoscopists and pathologists were blinded to the treatment arm. Results Total of 80 tissue samples were obtained. CSBE occurred in one animal with apixaban levels above the upper limit (P = 1). Intraprocedural bleeding occurred in five animals (25 %), four of which from the apixaban group. Hematoma at necropsy was found in 10 animals (50 %), six of which were on apixaban. Median drop in hemoglobin was similar in both groups. Adequacy of specimens for cytology and pathology evaluation was confirmed in 20 of 20 and 19 of 20 animals, respectively. Conclusions In this pilot preclinical trial, EUS-TA under apixaban showed a trend toward higher minor bleeding events but did not increase CSBE or prevent adequate cytopathological evaluation.

Abstract Background and study aims Gastric outlet obstruction (GOO) is traditionally managed with surgical gastroenterostomy (surgical-GE) and enteral stenting (ES). Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is now a third option. Large studies assessing their relative risks and benefits with adequate follow-up are lacking. We conducted a comparative analysis of patients who underwent EUS-GE, ES, or surgical-GE for GOO. Patients and methods In this retrospective comparative cohort study, consecutive patients presenting with GOO who underwent EUS-GE, ES, or surgical-GE at two academic institutions were reviewed and independently cross-edited to ensure accurate reporting. The primary outcome was need for reintervention. Secondary outcomes were technical and clinical success, length of hospital stay (LOS), and adverse events (AEs). Results A total of 436 patients (232 EUS-GE, 131 ES, 73 surgical-GE) were included. The median duration of follow-up of the entire cohort was 185.5 days (interquartile range 55.25–454.25 days). The rate of reintervention in the EUS-GE group was lower than in the ES and surgical-GE groups (0.9 %, 12.2 %, and 13.7 %, P < 0.0001). Technical success was achieved in 98.3 %, 99.2 %, and 100 % (P = 0.58), and clinical success was achieved in 98.3 %, 91.6 %, and 90.4 % (P < 0.0001) in the EUS-GE, ES, and surgical-GE groups, respectively. The EUS-GE group had a shorter LOS (2 days vs. 3 days vs. 5 days, P < 0.0001) and a lower AE rate than the ES and surgical-GE groups (8.6 % vs. 38.9 % vs. 27.4 %, P < 0.0001). Conclusion This large cohort study demonstrates the safety and palliation durability of EUS-GE as an alternative strategy for GOO palliation in select patients.