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Background and Aims: Liquid nitrogen spray cryotherapy (SCT) is an alternative to radiofrequency ablation (RFA) for eradication of dysplastic Barrett's esophagus (BE). We aimed to assess the safety, efficacy, and durability of SCT in a multicenter U.S. registry., Methods: This is a multicenter prospective registry of adults with BE treated with truFreeze Spray Cryotherapy (Steris, Mentor, Ohio, USA) (4 community and 11 academic sites, 2013-2022). Complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) were assessed in BE with dysplasia or intramucosal adenocarcinoma. Kaplan-Meier analysis of CEIM and CED was performed. Hazard ratios for CEIM stratified by baseline risk factors were calculated., Results: Among 138 subjects with low-grade dysplasia (24%), high-grade dysplasia (49%), and intramucosal adenocarcinoma (27%), 34% received prior RFA therapy. Subjects received a median of 2 SCT sessions. Adverse events were uncommon, with 5.5% reporting strictures and 0.7% a perforation. Rates of CEIM and CED, respectively, were 66% and 84% after 2 years and 67% and 92% after 3 years. In RFA-naïve patients, CEIM was 77% and CED was 96% at 3 years. Increasing BE length (per centimeter: adjusted hazard ratio, 0.90; 95% confidence interval, 0.83-0.96) and prior treatment with RFA (adjusted hazard ratio, 0.39; 95% confidence interval, 0.22-0.69) were associated with a lower rate of CEIM. Recurrence occurred in 8.8% (n = 6) at a mean follow-up of 2.5 years after CEIM., Conclusion: In this largest reported prospective cohort, liquid nitrogen SCT was safe and effective for the treatment of dysplastic and neoplastic BE. Response was lower in those with prior failed RFA; in that cohort, approximately 50% attained CEIM at 3 years., Competing Interests: Disclosure The following authors disclosed financial relationships: V. Kaul: Ad hoc consultant for Steris. B. Greenwald: consultant for Steris Endoscopy. N. J. Shaheen: grant support from Steris, Lucid, Pentax, Interpace, and CDx Medical. Consultant for Exact Sciences. All other authors disclosed no financial relationships. This study was supported by grants from CSA Medical, Steris, and National Institutes of Health award number K23DK121338 (to S. Eluri)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia., Methods: The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations., Results: The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics., Conclusions: This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: In the United States, clinical guidelines recommend daily use of proton pump inhibitors (PPIs) amongst individuals diagnosed with Barrett's esophagus to decrease the risk of progression to dysplasia and neoplasia. Prior studies documenting adherence to PPIs in this population have not characterized heterogeneity in adherence patterns. Factors that may relate to adherence are incompletely described., Methods: We used administrative claims data from the Merative MarketScan Commercial Claims and Encounters database to conduct a retrospective study of adherence to prescription PPIs. A cohort of individuals diagnosed with incident Barrett's esophagus between 2010 and 2019 was identified. Group-based trajectory models were generated to detect longitudinal adherence subgroups., Results: 79 701 individuals with a new diagnosis of Barrett's esophagus were identified. The best fitting model detected five distinct adherence trajectory groups: consistently high (44% of the population), moderate decline (18%), slow decline (12%), rapid decline (10%), and decline-then-increase (16%). Compared to individuals starting PPIs, those already using PPIs were less likely to have a declining adherence pattern. Other factors associated with membership in a declining adherence group included (but were not limited to): female sex, having a past diagnosis of anxiety or depression, and having one or more emergency department visits in the past year., Discussion: Using an exploratory method, we detected heterogeneity in adherence to prescription PPIs. Less than half of individuals were classified into the consistently high adherence group, suggesting that many individuals with Barrett's esophagus receive inadequate pharmacologic therapy., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Introduction: Despite societal recommendations supporting Barrett's esophagus (BE) screening, it is unknown what proportion of eligible patients is screened in primary care. We assessed the proportion of BE screening- eligible patients evaluated in the primary care setting receiving upper esophagogastroduodenoscopy (EGD) and identified factors associated with undergoing EGD., Methods: This was a retrospective study of BE screening-eligible patients, as defined by the American College of Gastroenterology's BE guidelines, in a multipractice healthcare network consisting of 64 internal medicine practices and 94 family medicine (FM) practices. The proportion undergoing EGD, prevalence of BE and esophageal adenocarcinoma (EAC) in this group, and patient and provider factors associated with undergoing EGD were assessed. Multivariable logistic regression was performed to identify independent predictors of undergoing EGD., Results: Of 1,127 screening-eligible patients, the mean age was 65.2 ± 8.6 years; 45% were obese; and 61% were smokers. Seventy-three percent were seeing FM; 94% were on proton pump inhibitors; and 44% took ≥1 gastroesophageal reflux disease (GERD) medication. Only 39% of patients (n = 436) had undergone EGD. The overall prevalence of BE or EAC was 9.9%. Of 39 (9%) referred for BE screening as the primary indication, BE/EAC prevalence was 35.1%. Factors associated with increased odds of having EGD were symptomatic GERD despite treatment (odds ratio [OR] 12.1, 95% confidence interval [CI] 9.1-16.3), being on ≥1 GERD medication (OR 1.4, 95% CI 1.0-1.9), and being an FM patient (OR 1.5, 95% CI 1.1-2.1)., Discussion: In this large, primary care population, only 39% of screening-eligible patients underwent EGD. Most of the examinations were triggered by refractory symptoms rather than screening referrals, highlighting a need for improved dissemination and implementation of BE screening., (Copyright © 2022 by The American College of Gastroenterology.)

While patients with Barrett's esophagus without dysplasia may benefit from endoscopic surveillance, those with low-grade dysplasia may be managed with either endoscopic surveillance or endoscopic eradication. Patients with Barrett's esophagus with high-grade dysplasia and/or intramucosal adenocarcinoma will generally require endoscopic eradication therapy. The management of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma is predominantly endoscopic, with multiple effective methods available for the resection of raised neoplasia and ablation of flat neoplasia. High-dose proton-pump inhibitor therapy is advised during the treatment of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma. After the endoscopic eradication of Barrett's esophagus and associated neoplasia, surveillance is required for the diagnosis and retreatment of recurrence or progression., Competing Interests: Disclosure C.C. Cotton has no conflicts of interest. S. Eluri has no conflicts of interest. N.J. Shaheen has received research funding from Medtronic, Pentax, Steris, CDx Medical, Lucid, and Interpace Diagnostics and has worked as a consultant for Boston Scientific, Cernostics, Cook Medical, Aqua, Exact Sciences, and Phathom., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background & Aims: A non-endoscopic approach to Barrett's esophagus (BE) surveillance after radiofrequency ablation (RFA) would offer a less invasive method for monitoring. We assessed the test characteristics and cost-effectiveness of the Cytosponge (Medtronic, Minneapolis, MN) in post-RFA patients., Methods: We performed a multicenter study of dysplastic BE patients after at least one round of RFA. A positive Cytosponge before endoscopy was defined as intestinal metaplasia (IM) on cytological assessment and/or TFF3 immunohistochemistry. Sensitivity, specificity, and receiver operator characteristic (ROC) curves were calculated. Multivariable regression was used to estimate the odds of a positive Cytosponge in BE. A microsimulation cost-effectiveness model was performed to assess outcomes of various surveillance strategies: endoscopy-only, Cytosponge-only, and alternating endoscopy/Cytosponge., Results: Of 234 patients, Cytosponge adequately sampled the distal esophagus in 175 (75%). Of the 142 with both endoscopic and histologic data, 19 (13%) had residual/recurrent BE. For detecting any residual Barrett's, Cytosponge had a sensitivity of 74%, specificity of 85%, accuracy of 84%, and ROC curve showed an area under the curve of 0.74. The adjusted odds of a positive Cytosponge in BE were 17.1 (95% CI, 5.2-55.9). Cytosponge-only surveillance dominated all the surveillance strategies, being both less costly and more effective. Cytosponge-only surveillance required <1/4 th the endoscopies, resulting in only 0.69 additional EAC cases/1000 patients, and no increase in EAC deaths when compared to currently-practiced endoscopy-only surveillance., Conclusions: A positive Cytosponge test was strongly associated with residual BE after ablation. While the assay needs further refinement in this context, it could serve as a cost-effective surveillance examination., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) continues to rise, and risk stratification of patients with BE is needed. Impaired esophageal motility is associated with gastroesophageal reflux disease; however, whether esophageal dysmotility is a risk factor for dysplasia progression in BE is incompletely understood. This study aimed to characterize esophageal motility patterns in patients with BE and identify physiologic factors associated with dysplasia progression in BE., Methods: This multicenter retrospective study assessed data from adult patients with histologically confirmed BE who underwent high-resolution esophageal manometry from 1/2014 to 1/2018 at four tertiary care centers. Longitudinal data were collected when available among patients with non-dysplastic BE (NDBE) and separated as: no dysplastic progression or positive dysplastic progression. Multivariable logistic regression assessed for independent predictors of dysplasia progression., Results: Among 193 patients, histology at index endoscopy identified 152 (79%) NDBE, 23 (12%) low-grade dysplasia, 14 (7%) high-grade dysplasia, and 4 (2%) EAC. Ninety-eight (51%) had abnormal esophageal motor function on manometry. Longitudinal data were available for 84 of 152 patients with initial NDBE. Twelve (14%) exhibited dysplastic progression to low-grade (6) or high-grade (6) dysplasia. Mean esophageal distal contractile integral was lower for patients that progressed [455 mmHg s cm (SD 515)] compared with patients who did not progress [987 mmHg s cm (SD 953); aOR 1.21 (95% CI 1.01, 1.44)]., Conclusion: In this retrospective study of 193 BE patients, the majority exhibited abnormal esophageal motor function. Reduced esophageal contractility was independently associated with dysplastic progression in BE. Characterizing esophageal physiology in BE may help to risk stratify patients.

Background & Aims: Endoscopic eradication therapy (EET) for Barrett's esophagus (BE) has unclear effects on the gastric cardia. We investigated the prevalence of intestinal metaplasia (IM) and dysplasia in the cardia after complete eradication of IM (CEIM) and the incidence of newly diagnosed cardia IM or dysplasia after EET., Methods: We performed a prospective study, from 2013 through 2016, of patients with previously successful EET undergoing surveillance after CEIM (cross-sectional group) and treatment-naïve patients with BE undergoing EET (longitudinal group). Standard biopsies were collected from multiple levels in the cardia and analyzed histologically. We calculated the prevalence (cross-sectional group) and the incidence (longitudinal group) of cardia IM or dysplasia after EET., Results: Of the 116 patients in the cross-sectional group, 17 (15%) had cardia IM or dysplasia after CEIM: 12 patients had IM, 2 patients were indefinite for dysplasia, and 3 patients had low-grade dysplasia. Cardia IM or dysplasia were most commonly found at the tops of gastric folds. Among 42 subjects in the longitudinal group, the pre-treatment prevalence of cardia IM or dysplasia was 28.5% (3 with non-dysplastic IM, 9 with dysplastic IM, 1 indefinite for dysplasia, 2 with low-grade dysplasia, 3 with high-grade dysplasia, and 3 with intramucosal cancer). All achieved CEIM. The incidence of cardia IM or dysplasia was 11.9% after 18 months of follow up. IM or dysplasia was more higher in the cardia after CEIM than in the tubular esophagus (P < .01)., Conclusions: In a prospective study, we found that cardia dysplasia becomes less, not more, common, after successful EET; recurrence of IM or dysplasia was more frequent in the cardia than the esophagus. Patients with BE undergoing EET should have careful examination of the cardia, with a single set of surveillance biopsies at the top of the gastric folds., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Risk stratification in Barrett's esophagus (BE) is challenging. We evaluated the ability of a panel of genetic markers to predict progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC)., Methods: In this case-control study, we assessed a measure of genetic instability, the mutational load (ML), in predicting progression to HGD or EAC. Cases had nondysplastic BE or low-grade dysplasia (LGD) at baseline and developed HGD/EAC ≥1 year later. Controls were matched 2:1, had nondysplastic BE or LGD, and no progression at follow-up. Formalin-fixed, paraffin-embedded tissue was microdissected for the epithelium. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were assessed. ML was calculated from derangements in 10 genomic loci. High-clonality LOH mutations were assigned a value of 1, low-clonality mutations were assigned a value of 0.5, and MSI 0.75 at the first loci, and 0.5 for additional loci. These values were summed to the ML. Receiver operator characteristic (ROC) curves were created., Results: There were 69 patients (46 controls and 23 cases). Groups were similar in age, follow-up time, baseline histology, and the number of microdissected targets. Mean ML in pre-progression biopsies was higher in cases (2.21) than in controls (0.42; P<0.0001). Sensitivity was 100% at ML ≥0.5 and specificity was 96% at ML ≥1.5. Accuracy was highest at 89.9% for ML ≥1. ROC curves for ML ≥1 demonstrated an area under the curve (AUC) of 0.95., Conclusions: ML in pre-progression BE tissue predicts progression to HGD or EAC. Although further validation is necessary, ML may have utility as a biomarker in endoscopic surveillance of BE.