Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

BACKGROUND: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. METHODS: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. FINDINGS: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. INTERPRETATION: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. FUNDING: US National Institutes of Health.

Surveillance in Barrett's Esophagus: Challenges, Progress, and Possibilities.

Endoscopic surveillance of Barrett's esophagus, aiming to detect prevalent dysplasia and adenocarcinoma, followed by effective endoscopic treatment, is an integral part of the esophageal adenocarcinoma prevention paradigm. However, several limitations, such as the subtle appearance of dysplasia, sampling error (inherent in current surveillance protocols), and noncompliance with surveillance recommendations, lead to missed dysplasia and neoplasia, reducing the effectiveness of surveillance as currently practiced. Careful endoscopic assessment with high-resolution white-light endoscopy, dye-based or electronic chromoendoscopy, and comprehensive sampling of the BE mucosa, remains the cornerstone of endoscopic surveillance. Emerging innovations in this area span the gamut of more efficient sampling methods, advanced imaging tools, artificial intelligence, and molecular marker-powered approaches as adjuncts, to identify prevalent and predict incident dysplasia or adenocarcinoma. Development and implementation of validated quality indicators will allow additional advancement of this critical field. These approaches will hopefully enable efficient and effective cancer prevention and treatment.

Prevalence and Predictors of Barrett's Esophagus After Negative Initial Endoscopy: Analysis From Two National Databases.

BACKGROUND & AIMS: Guidelines suggest a single screening esophagogastroduodenoscopy (EGD) in patients with multiple risk factors for Barrett's esophagus (BE). We aimed to determine BE prevalence and predictors on repeat EGD after a negative initial EGD, using 2 large national databases (GI Quality Improvement Consortium [GIQuIC] and TriNetX). METHODS: Patients who underwent at least 2 EGDs were included and those with BE or esophageal adenocarcinoma detected at initial EGD were excluded. Patient demographics and prevalence of BE on repeat EGD were collected. Multivariate logistic regression was performed to assess for independent risk factors for BE detected on the repeat EGD. RESULTS: In 214,318 and 153,445 patients undergoing at least 2 EGDs over a median follow-up of 28-35 months, the prevalence of BE on repeat EGD was 1.7% in GIQuIC and 3.4% in TriNetX, respectively (26%-45% of baseline BE prevalence). Most (89%) patients had nondysplastic BE. The prevalence of BE remained stable over time (from 1 to >5 years from negative initial EGD) but increased with increasing number of risk factors. BE prevalence in a high-risk population (gastroesophageal reflux disease plus ≥1 risk factor for BE) was 3%-4%. CONCLUSIONS: In this study of >350,000 patients, rates of BE on repeat EGD ranged from 1.7%-3.4%, and were higher in those with multiple risk factors. Most were likely missed at initial evaluation, underscoring the importance of a high-quality initial endoscopic examination. Although routine repeat endoscopic BE screening after a negative initial examination is not recommended, repeat screening may be considered in carefully selected patients with gastroesophageal reflux disease and ≥2 risk factors for BE, potentially using nonendoscopic tools.

Multicenter, Prospective Trial of Nonendoscopic Biomarker-Driven Detection of Barrett's Esophagus and Esophageal Adenocarcinoma.

INTRODUCTION: Preliminary data suggest that an encapsulated balloon (EsoCheck), coupled with a 2 methylated DNA biomarker panel (EsoGuard), detects Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with high accuracy. The initial assay requires sample freezing upon collection. The purpose of this study was to assess a next-generation EsoCheck sampling device and EsoGuard assay in a much-enlarged multicenter study clinically enhanced by using a Clinical Laboratory Improvement Amendments of 1988-compliant assay and samples maintained at room temperature. METHODS: Cases with nondysplastic BE (NDBE), dysplastic BE (indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia), EAC, junctional adenocarcinoma, plus endoscopy controls without esophageal intestinal metaplasia, were prospectively enrolled. Medical assistants at 6 institutions delivered the encapsulated balloon per orally with inflation in the stomach. The inflated balloon sampled the distal 5 cm of the esophagus and then was deflated and retracted into the capsule, preventing sample contamination. EsoGuard bisulfite sequencing assayed levels of methylated vimentin and methylated cyclin A1. RESULTS: A total of 243 evaluable patients-88 cases (median age 68 years, 78% men, 92% White) and 155 controls (median age 57 years, 41% men, 88% White)-underwent adequate EsoCheck sampling. The mean procedural time was approximately 3 minutes. Cases included 31 with NDBE, 16 with indefinite for dysplasia/low-grade dysplasia, 23 with high-grade dysplasia, and 18 with EAC/junctional adenocarcinoma. Thirty-seven NDBE and dysplastic BE cases (53%) were short-segment BE (<3 cm). Overall sensitivity was 85% (95% confidence interval 0.78-0.93) and specificity was 85% (95% confidence interval 0.79-0.90). Sensitivity for NDBE was 84%. EsoCheck/EsoGuard detected 100% of cancers (n = 18). DISCUSSION: EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.

Rates of Recurrent Intestinal Metaplasia and Dysplasia After Successful Endoscopic Therapy of Barrett's Neoplasia by Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection and Ablation: A Large North American Multicenter Cohort.

INTRODUCTION: Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. METHODS: Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. RESULTS: A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. DISCUSSION: Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.

EUS-guided coil injection therapy in the management of gastric varices: the first U.S. multicenter experience (with video).

BACKGROUND AND AIMS: Despite the significant morbidity associated with gastric variceal bleeding, there is a paucity of high-quality data regarding optimal management. EUS-guided coil injection therapy (EUS-COIL) has recently emerged as a promising endoscopic modality for the treatment of gastric varices (GV), particularly compared with traditional direct endoscopic glue injection. Although there are data on the feasibility and safety of EUS-COIL in the management of GV, these have been limited to select centers with particular expertise. The aim of this study was to report the first U.S. multicenter experience of EUS-COIL for the management of GV. METHODS: This retrospective analysis included patients with bleeding GV or GV at risk of bleeding who underwent EUS-COIL at 10 U.S. tertiary care centers between 2018 and 2022. Baseline patient and procedure-related information was obtained. EUS-COIL entailed the injection of .018 inch or .035 inch hemostatic coils using a 22-gauge or 19-gauge FNA needle. Primary outcomes were technical success (defined as successful deployment of coil into varix under EUS guidance with diminution of Doppler flow), clinical success (defined as cessation of bleeding if present and/or absence of bleeding at 30 days' postintervention), and intraprocedural and postprocedural adverse events. RESULTS: A total of 106 patients were included (mean age 60.4 ± 12.8 years; 41.5% female). The most common etiology of GV was cirrhosis (71.7%), with alcohol being the most common cause (43.4%). Overall, 71.7% presented with acute GV bleeding requiring intensive care unit stay and/or blood transfusion. The most common GV encountered were isolated GV type 1 (60.4%). A mean of 3.8 ± 3 coils were injected with a total mean length of 44.7 ± 46.1 cm. Adjunctive glue or absorbable gelatin sponge was injected in 82% of patients. Technical success and clinical success were 100% and 88.7%, respectively. Intraprocedural adverse events (pulmonary embolism and GV bleeding from FNA needle access) occurred in 2 patients (1.8%), and postprocedural adverse events occurred in 5 (4.7%), of which 3 were mild. Recurrent bleeding was observed in 15 patients (14.1%) at a mean of 32 days. Eighty percent of patients with recurrent bleeding were successfully re-treated with repeat EUS-COIL. No significant differences were observed in outcomes between high-volume (>15 cases) and low-volume (<7 cases) centers. CONCLUSIONS: This U.S. multicenter experience on EUS-COIL for GV confirms high technical and clinical success with low adverse events. No significant differences were seen between high- and low-volume centers. Repeat EUS-COIL seems to be an effective rescue option for patients with recurrent bleeding GV. Further prospective studies should compare this modality versus other interventions commonly used for GV.

The Ephrin B2 Receptor Tyrosine Kinase Is a Regulator of Proto-oncogene MYC and Molecular Programs Central to Barrett's Neoplasia.

BACKGROUND & AIMS: Mechanisms contributing to the onset and progression of Barrett's (BE)-associated esophageal adenocarcinoma (EAC) remain elusive. Here, we interrogated the major signaling pathways deregulated early in the development of Barrett's neoplasia. METHODS: Whole-transcriptome RNA sequencing analysis was performed in primary BE, EAC, normal esophageal squamous, and gastric biopsy tissues (n = 89). Select pathway components were confirmed by quantitative polymerase chain reaction in an independent cohort of premalignant and malignant biopsy tissues (n = 885). Functional impact of selected pathway was interrogated using transcriptomic, proteomic, and pharmacogenetic analyses in mammalian esophageal organotypic and patient-derived BE/EAC cell line models, in vitro and/or in vivo. RESULTS: The vast majority of primary BE/EAC tissues and cell line models showed hyperactivation of EphB2 signaling. Transcriptomic/proteomic analyses identified EphB2 as an endogenous binding partner of MYC binding protein 2, and an upstream regulator of c-MYC. Knockdown of EphB2 significantly impeded the viability/proliferation of EAC and BE cells in vitro/in vivo. Activation of EphB2 in normal esophageal squamous 3-dimensional organotypes disrupted epithelial maturation and promoted columnar differentiation programs, notably including MYC. EphB2 and MYC showed selective induction in esophageal submucosal glands with acinar ductal metaplasia, and in a porcine model of BE-like esophageal submucosal gland spheroids. Clinically approved inhibitors of MEK, a protein kinase that regulates MYC, effectively suppressed EAC tumor growth in vivo. CONCLUSIONS: The EphB2 signaling is frequently hyperactivated across the BE-EAC continuum. EphB2 is an upstream regulator of MYC, and activation of EphB2-MYC axis likely precedes BE development. Targeting EphB2/MYC could be a promising therapeutic strategy for this often refractory and aggressive cancer.

Timeline of Development of Pancreatic Cancer and Implications for Successful Early Detection in High-Risk Individuals.

BACKGROUND & AIMS: To successfully implement imaging-based pancreatic cancer (PC) surveillance, understanding the timeline and morphologic features of neoplastic progression is key. We aimed to investigate the progression to neoplasia from serial prediagnostic pancreatic imaging tests in high-risk individuals and identify factors associated with successful early detection. METHODS: We retrospectively examined the development of pancreatic abnormalities in high-risk individuals who were diagnosed with PC or underwent pancreatic surgery, or both, in 16 international surveillance programs. RESULTS: Of 2552 high-risk individuals under surveillance, 28 (1%) developed neoplastic progression to PC or high-grade dysplasia during a median follow-up of 29 months after baseline (interquartile range [IQR], 40 months). Of these, 13 of 28 (46%) presented with a new lesion (median size, 15 mm; range 7-57 mm), a median of 11 months (IQR, 8; range 3-17 months) after a prior examination, by which time 10 of 13 (77%) had progressed beyond the pancreas. The remaining 15 of 28 (54%) had neoplastic progression in a previously detected lesion (12 originally cystic, 2 indeterminate, 1 solid), and 11 (73%) had PC progressed beyond the pancreas. The 12 patients with cysts had been monitored for 21 months (IQR, 15 months) and had a median growth of 5 mm/y (IQR, 8 mm/y). Successful early detection (as high-grade dysplasia or PC confined to the pancreas) was associated with resection of cystic lesions (vs solid or indeterminate lesions (odds ratio, 5.388; 95% confidence interval, 1.525-19.029) and small lesions (odds ratio, 0.890/mm; 95% confidence interval 0.812-0.976/mm). CONCLUSIONS: In nearly half of high-risk individuals developing high-grade dysplasia or PC, no prior lesions are detected by imaging, yet they present at an advanced stage. Progression can occur before the next scheduled annual examination. More sensitive diagnostic tools or a different management strategy for rapidly growing cysts are needed.

Patients With Esophageal Adenocarcinoma With Prior Gastroesophageal Reflux Disease Symptoms Are Similar to Those Without Gastroesophageal Reflux Disease: A Cross-Sectional Study.

INTRODUCTION: A substantial proportion of patients with esophageal adenocarcinoma (EAC) do not report gastroesophageal reflux disease (GERD) symptoms. This study aimed to compare the risk factor profiles and cancer stage at presentation of patients with EAC with and without prior GERD. METHODS: In this retrospective cross-sectional study, patients with EAC were divided into 2 cohorts: (i) EAC with prior GERD: patients who reported typical GERD symptoms (heartburn or regurgitation) ≥1 year before cancer diagnosis and (ii) EAC without prior GERD: patients who did not report prior GERD symptoms or reported symptoms within 1 year of their cancer diagnosis. Baseline demographics, risk factors, and cancer stage at presentation were compared between the 2 cohorts. In addition, the distribution of patients based on numbers of BE/EAC-associated risk factors (1, 2, 3, 4, and 5 or more) was examined in the symptomatic and asymptomatic cohorts. RESULTS: Over 13 years, 388 patients with EAC with prior GERD and 245 patients with EAC without prior GERD were recruited. Both groups had similar baseline demographics and risk factors, but patients with EAC with prior GERD were more likely to have a history of BE. Asymptomatic patients had more advanced disease. Patients with 3 or more BE/EAC-related risk factors formed the largest proportion of patients in both the symptomatic and asymptomatic cohorts. DISCUSSION: Patients with EAC with and without prior GERD symptoms are phenotypically similar, suggesting that BE screening efforts to prevent or detect early EAC should not be restricted to just those with GERD.

Role of through-the-scope catheter-based EUS in inflammatory bowel disease diagnosis and activity assessment.

BACKGROUND AND AIMS: Distinguishing Crohn's disease (CD) from ulcerative colitis (UC) may be difficult when the disease is limited to the colon. Transmural healing is an important adjunctive measure of inflammatory bowel disease activity. The aim of this study was to examine the role of EUS in differentiating CD versus UC and evaluating transmural disease activity. METHODS: This prospective cohort study enrolled 20 patients with CD (10 active [aCD], 10 inactive), 20 patients with UC (10 active [aUC], 10 inactive), and 20 control subjects who underwent colonoscopy from 2019 to 2021 at a tertiary care center. Measurements of bowel wall layer thickness from the rectum and cecum were obtained using a through-the-scope US catheter (UM-3R-3; Olympus, Center Valley, Penn, USA) at the time of colonoscopy. RESULTS: Compared with control subjects, patients with aCD had thicker rectal submucosa and total wall layer (submucosa median, 1.80 mm [interquartile range {IQR}, 1.40-2.00] vs .60 mm [IQR, .40-.70]; total wall median, 3.70 mm [IQR, 3.52-4.62] vs 2.10 mm [IQR, 1.70-2.40], respectively; P < .01). Similar significant findings were observed for the cecal wall layers. Compared with control subjects, patients with aUC had thicker rectal mucosa and total wall but not submucosa or muscularis propria layers (mucosa median, 1.35 mm [IQR, 1.12-1.47] vs .60 mm [IQR, .57-.70]; total wall median, 3.45 mm [IQR, 2.85-3.75] vs 2.10 mm [IQR, 1.70-2.40], respectively; P < .01). Patients with aCD compared with those with aUC had a significantly thicker rectal submucosa layer (median, 1.80 mm [IQR, 1.40-2.00] vs .55 mm [IQR, .40-.75], respectively, P < .01). Cutoff values of 1.1 mm for rectal submucosa in CD (sensitivity, 1.0; specificity, 1.0) and 1.1 mm for rectal mucosa in UC (sensitivity, .8; specificity, .9) were found to differentiate active from inactive disease. CONCLUSIONS: EUS measurements of colon wall layers can help diagnose aCD versus aUC and assess transmural disease activity. (Clinical trial registration number: NCT03863886.).

Endoscopic submucosal dissection with versus without traction for pathologically staged T1B esophageal cancer: a multicenter retrospective study.

BACKGROUND AND AIMS: Positive vertical margins (VMs) are common after endoscopic submucosal dissection (ESD) of T1b esophageal cancer (EC) and are associated with an increased risk of recurrence. Traction during ESD provides better exposure of the submucosa and may allow deeper dissection, potentially reducing the risk of positive VMs. We conducted a retrospective multicenter study to compare the proportion of resections with positive VMs in ESD performed with versus without traction in pathologically staged T1b EC. METHODS: Patients who underwent ESD revealing T1b EC (squamous or adenocarcinoma) at 10 academic tertiary referral centers in the United States (n = 9) and Brazil (n = 1) were included. Demographic and clinical data were abstracted. ESD using either traction techniques (tunneling, pocket) or traction devices (clip line, traction wire) were classified as ESD with traction (Tr-ESD) and those without were classified as conventional ESD without traction. The primary outcome was a negative VM. Multivariable logistic regression was used to assess associations with negative VMs. RESULTS: A total of 166 patients with pathologically staged T1b EC underwent Tr-ESD (n = 63; 38%) or conventional ESD without traction (n = 103; 62%). Baseline factors were comparable between both groups. On multivariable analysis, Tr-ESD was found to be independently associated with negative VMs (odds ratio, 2.25; 95% confidence interval, 1.06-4.91; P = .037) and R0 resection (odds ratio, 2.83; 95% confidence interval, 1.33-6.23; P = .008). CONCLUSION: Tr-ESD seems to be associated with higher odds of negative VMs than ESD without traction for pathologically staged T1b EC, and future well-conducted prospective studies are warranted to establish the findings of the current study.

Evidence-Based Cognitive Endoscopy Simulators: Do They Exist? A Systematic Search and Evaluation of Existing Platforms.

BACKGROUND: The development of guidelines by gastroenterology societies increasingly stresses evidence-based endoscopic practice. AIMS: We performed a systematic assessment to determine whether endoscopic video teaching platforms incorporate evidence-based educational strategies and methods in order to disseminate guideline-based endoscopic management strategies. METHODS: Platforms with a video component were systematically identified using the Google search engine, Apple and Android application stores, and searching four major gastroenterology society websites and three known platforms, to identify all relevant platforms. Two video samples from each teaching platform were reviewed independently by two authors and assessed for use of a priori defined principles of evidence-based medicine, as determined by consensus agreement and for the use of simulation. RESULTS: Fourteen platforms were included in the final analysis, and two videos from each were analyzed. One of the 14 platforms used simulation and incorporated evidence-based medicine principles consistently. Nine of the 14 platforms were not transparent in regard to citation. None of the platforms consistently cited the certainty of evidence or explained how evidence was selected. CONCLUSIONS: Education of guideline-based endoscopic management strategies using principles of evidence-based medicine is under-utilized in endoscopic videos. In addition, the use of cognitive simulation is absent in this arena. There is a paucity of evidence-based cognitive endoscopy simulators designed for fellows that incorporate systematic evaluation, and efforts should be made to create this platform.

The Next EPISOD: Trends in Utilization of Endoscopic Sphincterotomy for Sphincter of Oddi Dysfunction from 2010-2019.

BACKGROUND & AIMS: For years, the endoscopic management of the disorder formerly known as Type III Sphincter of Oddi Dysfunction (SOD) had been controversial. In 2013, the results of the Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial demonstrated that there was no benefit associated with endoscopic sphincterotomy for patients with Type III SOD. We aimed to assess the utilization of endoscopic sphincterotomy for patients with SOD in a large population database from 2010-2019. METHODS: We searched a large electronic health record (EHR)-based dataset incorporating over 300 individual hospitals in the United States (Explorys, IBM Watson health, Armonk, NY). Using Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) we identified patients with a first-ever diagnosis of "disorder of Sphincter of Oddi" annually from 2010-2019. Subclassification of SOD types was not feasible using SNOMED-CT codes. Stratified by year, we identified the proportion of patients with newly-diagnosed SOD undergoing endoscopic sphincterotomy and those receiving newly-prescribed medical therapy. RESULTS: A total of 39,950,800 individual patients were active in the database with 7,750 index diagnoses of SOD during the study period. The incidence rates of SOD increased from 2.4 to 12.8 per 100,000 persons from 2010-2019 (P < .001). In parallel, there were reductions in the rates of biliary (34.3% to 24.5%) and pancreatic sphincterotomy (25% to 16.4%), respectively (P < .001). Sphincter of Oddi manometry (SOM) was infrequently utilized, <20 times in any given year, throughout the study duration. There were no significant increases in new prescriptions for TCAs, nifedipine, or vasodilatory nitrates. CONCLUSIONS: Among a wide range of practice settings which do not utilize routine SOM, a sudden and sustained decrease in rates of endoscopic sphincterotomy for newly-diagnosed SOD was observed beginning in 2013. These findings highlight the critical importance of high-quality, multi-center, randomized controlled trials in endoscopy to drive evidence-based changes in real-world clinical practice.

Meet EBE: The Development of an Evidence-Based Endoscopy Simulator.

BACKGROUND AND AIMS: In the digital era of evidence-based medicine, there is a paucity of video endoscopy teaching platforms that use evidence-based medicine principles, or that allow for cognitive simulation of endoscopic management strategies. We created a guideline-based teaching platform for fellows that incorporates these features, and tested it. METHODS: A pilot video module with embedded questions was drafted, and after incorporation of feedback from several attending gastroenterologists, an additional 2 modules were created. The embedded questions were designed to simulate cognitive management decisions as if the viewer were doing the endoscopy procedure in the video. A narrator explained the evidence behind the task being performed, and its certainty based on endoscopic guidelines. Quizzes and surveys were developed and administered to a sample of attendings and fellows who completed the video modules to test efficacy, usability, and likeability. RESULTS: Three video modules, named evidence-based endoscopy (EBE), incorporating low fidelity simulation, and utilizing evidence-based medicine principles, were created. Eight fellows and 10 attendings completed the video modules and all quizzes and surveys. Mean test scores improved from before to after completing the video modules (56% to 92%; mean difference = -35%; 95% confidence interval, 27%-47%). Surveys indicated that the product was viewed favorably by participants, and that there is a strong desire for this type of educational product. CONCLUSIONS: The EBE simulator is a unique, desirable, and effective educational platform based on evidence-based medicine principles that fills a gap in available tools for endoscopy education. Further studies are needed to assess whether EBE can aid in long-term knowledge retention and increase adherence to guideline recommendations.

Massively Parallel Sequencing of Esophageal Brushings Enables an Aneuploidy-Based Classification of Patients With Barrett's Esophagus.

BACKGROUND & AIMS: Aneuploidy has been proposed as a tool to assess progression in patients with Barrett's esophagus (BE), but has heretofore required multiple biopsies. We assessed whether a single esophageal brushing that widely sampled the esophagus could be combined with massively parallel sequencing to characterize aneuploidy and identify patients with disease progression to dysplasia or cancer. METHODS: Esophageal brushings were obtained from patients without BE, with non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (EAC). To assess aneuploidy, we used RealSeqS, a technique that uses a single primer pair to interrogate ∼350,000 genome-spanning regions and identify specific chromosome arm alterations. A classifier to distinguish NDBE from EAC was trained on results from 79 patients. An independent validation cohort of 268 subjects was used to test the classifier at distinguishing patients at successive phases of BE progression. RESULTS: Aneuploidy progression was associated with gains of 1q, 12p, and 20q and losses on 9p and 17p. The entire chromosome 8q was often gained in NDBE, whereas focal gain of 8q24 was identified only when there was dysplasia. Among validation subjects, a classifier incorporating these features with a global measure of aneuploidy scored positive in 96% of EAC, 68% of HGD, but only 7% of NDBE. CONCLUSIONS: RealSeqS analysis of esophageal brushings provides a practical and sensitive method to determine aneuploidy in BE patients. It identifies specific chromosome changes that occur early in NDBE and others that occur late and mark progression to dysplasia. The clinical implications of this approach can now be tested in prospective trials.

Characteristics of Patients Undergoing Endoscopic Retrograde Cholangiopancreatography for Sphincter of Oddi Disorders.

The concept that sphincter of Oddi dysfunction (SOD) can cause attacks of biliary-type pain in postcholecystectomy patients and those with unexplained recurrent acute pancreatitis, and that endoscopic sphincterotomy can ameliorate symptoms, remains unproven. The Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) study of patients without objective evidence for biliary obstruction showed no difference in outcomes between those who underwent sphincterotomy or sham treatment.1 To date, there have been no studies examining the characteristics of patients who still are being offered endoscopic retrograde cholangiopancreatography (ERCP) for SOD since the EPISOD publication, although the absolute number appears to have declined.2.

Prediction of neoplastic progression in Barrett's esophagus using nanoscale nuclear architecture mapping: a pilot study.

BACKGROUND AND AIMS: Nanoscale nuclear architecture mapping (nanoNAM), an optical coherence tomography-derived approach, is capable of detecting with nanoscale sensitivity structural alterations in the chromatin of epithelial cell nuclei at risk for malignant transformation. Because these alterations predate the development of dysplasia, we aimed to use nanoNAM to identify patients with Barrett's esophagus (BE) who might progress to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). METHODS: This is a nested case-control study of 46 BE patients, of which 21 progressed to HGD/EAC over 3.7 ± 2.37 years (cases/progressors) and 25 patients who did not progress over 6.3 ± 3.1 years (control subjects/nonprogressors). The archived formalin-fixed paraffin-embedded tissue blocks collected as part of standard clinical care at the index endoscopy were used. nanoNAM imaging was performed on a 5-µm formalin-fixed paraffin-embedded section, and each nucleus was mapped to a 3-dimensional (3D) depth-resolved optical path difference (drOPD) nuclear representation, quantifying nanoscale-sensitive alterations in the 3D nuclear architecture of the cell. Using 3D-drOPD representation of each nucleus, we computed 12 patient-level nanoNAM features summarizing the alterations in intrinsic nuclear architecture. A risk prediction model was built incorporating nanoNAM features and clinical features. RESULTS: A statistically significant differential shift was observed in the drOPD cumulative distributions between progressors and nonprogressors. Of the 12 nanoNAM features, 6 (mean-maximum, mean-mean, mean-median, entropy-median, entropy-entropy, entropy-skewness) showed a statistically significant difference between cases and control subjects. NanoNAM features based prediction model identified progression in independent validation sets, with an area under the receiver operating characteristic curve of 80.8% ± .35% (mean ± standard error), with an increase to 82.54% ± .46% when combined with length of the BE segment. CONCLUSIONS: NanoNAM can serve as an adjunct to histopathologic evaluation of BE patients and aid in risk stratification.

Wide-area transepithelial sampling for dysplasia detection in Barrett's esophagus: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Seattle protocol forceps biopsy sampling (FB) is currently recommended for surveillance in Barrett's esophagus (BE) but limited by sampling error and lack of compliance. Wide-area transepithelial sampling with 3-dimensional analysis (WATS3D; CDx Diagnostics, Suffern, NY, USA) is reported to increase BE dysplasia detection. We assessed the incremental yield and clinical significance of WATS3D for dysplasia detection over FB in a systematic review and meta-analysis. METHODS: We queried major scientific databases for studies using WATS3D and FB from 2000 to 2020. The primary outcome was the incremental yield of WATS3D-detected dysplasia (defined as a composite of indefinite for dysplasia, low- and high-grade dysplasia [HGD] and esophageal adenocarcinoma [EAC]) over FB. Secondary outcomes were incremental yields of HGD/EAC and rate of reconfirmation of WATS3D dysplasia on subsequent FB. RESULTS: Meta-analysis of 7 eligible studies demonstrated that FB diagnosed dysplasia in 15.9% of cases, whereas the incremental yield with WATS3D was 7.2% (95% confidence interval, 3.9%-11.5%; I2= 92.1%). Meta-analysis of 6 studies demonstrated that FB diagnosed HGD/EAC in 2.3% of patients, whereas the incremental yield with WATS3D was 2.1% (95% confidence interval, .4%-5.3%; I2= 92.7%). Notably, WATS3D was negative in 62.5% of cases where FB identified dysplasia. Two studies reported reconfirmation of WATS3D dysplasia with FB histology in only 20 patients. CONCLUSIONS: WATS3D increases dysplasia detection; however, the clinical significance of this increased dysplasia detection remains uncertain. Data from endoscopic follow-up to ascertain FB histology in patients with dysplasia based solely on WATS3D are needed to determine the optimal clinical application and significance of WATS3D-only dysplasia.

Outcomes for endoscopic submucosal dissection of pathologically staged T1b esophageal cancer: a multicenter study.

BACKGROUND AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) for T1b esophageal cancer (EC) and its recurrence rates remain unclear in the West. Using a multicenter cohort, we evaluated technical outcomes and recurrence rates of ESD in the treatment of pathologically staged T1b EC. METHODS: We included patients who underwent ESD of T1b EC at 7 academic tertiary referral centers in the United States (n = 6) and Brazil (n = 1). We analyzed demographic, procedural, and histopathologic characteristics and follow-up data. Time-to-event analysis was performed to evaluate recurrence rates. RESULTS: Sixty-six patients with pathologically staged T1b EC after ESD were included in the study. A preprocedure staging EUS was available in 54 patients and was Tis/T1a in 27 patients (50%) and T1b in 27 patients (50%). En-bloc resection rate was 92.4% (61/66) and R0 resection rate was 54.5% (36/66). Forty-nine of 66 patients (74.2%) did not undergo surgery immediately after resection and went on to surveillance. Ten patients had ESD resection within the curative criteria, and no recurrences were seen in a 13-month (range, 3-18.5) follow-up period in these patients. Ten of 39 patients (25.6%) with noncurative resections had residual/recurrent disease. Of the 10 patients with noncurative resection, local recurrence alone was seen in 5 patients (12.8%) and metastatic recurrence in 5 patients (12.8%). On univariate analysis, R1 resection had a higher risk of recurrent disease (hazard ratio, 6.25; 95% confidence interval, 1.29-30.36; P = .023). CONCLUSIONS: EUS staging of T1b EC has poor accuracy, and a staging ESD should be considered in these patients. ESD R0 resection rates were low in T1b EC, and R1 resection was associated with recurrent disease. Patients with noncurative ESD resection of T1b EC who cannot undergo surgery should be surveyed closely, because recurrent disease was seen in 25% of these patients.

Endoscopic submucosal dissection vs. endoscopic mucosal resection for early Barrett's neoplasia in the West: a retrospective study.

BACKGROUND: The difference in clinical outcomes after endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for early Barrett's esophagus (BE) neoplasia remains unclear. We compared the recurrence/residual tissue rates, resection outcomes, and adverse events after ESD and EMR for early BE neoplasia. METHODS: We included patients who underwent EMR or ESD for BE-associated high grade dysplasia (HGD) or T1a esophageal adenocarcinoma (EAC) at eight academic hospitals. We compared demographic, procedural, and histologic characteristics, and follow-up data. A time-to-event analysis was performed to evaluate recurrence/residual disease and a Kaplan-Meier curve was used to compare the groups. RESULTS: 243 patients (150 EMR; 93 ESD) were included. EMR had lower en bloc (43 % vs. 89 %; P < 0.001) and R0 (56 % vs. 73 %; P = 0.01) rates than ESD. There was no difference in the rates of perforation (0.7 % vs. 0; P > 0.99), early bleeding (0.7 % vs. 1 %; P > 0.99), delayed bleeding (3.3 % vs. 2.1 %; P = 0.71), and stricture (10 % vs. 16 %; P = 0.16) between EMR and ESD. Patients with non-curative resections who underwent further therapy were excluded from the recurrence analysis. Recurrent/residual disease was 31.4 % [44/140] for EMR and 3.5 % [3/85] for ESD during a median (interquartile range) follow-up of 15.5 (6.75-30) and 8 (2-18) months, respectively. Recurrence-/residual disease-free survival was significantly higher in the ESD group. More patients required additional endoscopic resection procedures to treat recurrent/residual disease after EMR (EMR 24.2 % vs. ESD 3.5 %; P < 0.001). CONCLUSIONS: ESD is safe and results in more definitive treatment of early BE neoplasia, with significantly lower recurrence/residual disease rates and less need for repeat endoscopic treatments than with EMR.