Nondysplastic Barrett's Esophagus Research Articles

Sa1068 Predictors of Progression in Barrett's Esophagus: A Systematic Review and Meta-Analysis

Background: The overall risk of progression to esophageal adenocarcinoma (EAC) in BE subjects without dysplasia is lower than previously estimated. There is hence lack of consensus on the effectiveness of current surveillance programs. Stratification of risk of progression is appealing, as it may help identify BE patients at higher risk who can be monitored more intensively or offered endoscopic therapy. Though several studies have identified factors predicting progression, evidence on several clinically relevant risk factors influencing progression is not consistent. We aimed to identify the predictors of progression in BE subjects without high grade dysplasia by performing a systematic review and meta-analysis of relevant studies. Methods: A comprehensive search of several databases including PubMed, EMBASE, and Web of Science databases (earliest inception to July 28th, 2014) was performed and studies reporting outcomes of BE cohorts under surveillance were identified. We included studies that reported predictors of progression to HGD/ EAC as an outcome in patients with non-dysplastic BE (NDBE) and BE-low grade dysplasia (LGD). A pooled estimate (odds ratio) of the potential of age, sex, smoking, alcohol use, BMI, baseline LGD (vs NDBE), BE length, and medication use in predicting progression to HGD/EAC in NDBE/ LGD patients was calculated. Results: 23 studies reporting predictors of progression as an outcome were identified from the systematic review. 1231 events in 74943 patients in 204926.2 patient years of follow-up were analyzed. Table 1 shows the pooled odds ratio (OR) of predictors analyzed. Increasing age, male sex, ever smoking (current or past), and increasing BE segment length were predictive of increased risk of progression to HGD/EAC with low heterogeneity (9-13 studies). Patients with LGD had an almost four fold increased risk of progression compared to those with no dysplasia. NSAID and statin use were protective against progression to HGD/EAC without heterogeneity. Alcohol use and obesity as measured by BMI did not influence progression rates. Conclusion: Age, male sex, ever smoking (current or past), and BE length are predictive of increased risk of progression to HGD/ EAC. Subjects with baseline LGD are at 4 times increased risk of progression compared to those without dysplasia. These factors may be used to risk stratify BE subjects as part of a prediction score, to identify those who could potentially benefit from intensive surveillance or endoscopic therapy. Smoking is a modifiable risk factor for cancer prevention in BE subjects. Table 1: Pooled odds ratio (OR) of predictors of progression to HGD / EAC.

Reflux control is important in the management of Barrett’s Esophagus: results from a retrospective 1,830 patient cohort

It is unknown whether acid/reflux control prevents progression in Barrett's esophagus. In this study, we investigate whether medical or surgical control of reflux is associated with a decreased risk of progression to dysplasia/esophageal adenocarcinoma. We retrospectively collected and analyzed data from a cohort of Barrett's esophagus patients participating in this single-center study comprised of all patients diagnosed with Barrett's esophagus at NorthShore University Health System hospitals and clinics over a 10-year period. Patients were followed in order to identify those progressing from Barrett's esophagus to low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. We collected information from the patient's electronic medical records regarding demographic, endoscopic findings, histological findings, smoking/alcohol history, medication use including proton-pump inhibitors, and history of bariatric and antireflux surgery. Risk-adjusted modeling was performed using multivariable logistic regression. This study included 1,830 total Barrett's esophagus patients, 102 of which had their Barrett's esophagus progress to low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma (confirmed by biopsy) with an annual incidence rate of 1.1%. Mean follow-up period was 5.51 years (10,083 patient-years). Compared to the group that did not progress, the group that progressed was older (69.3 ± 13.7 vs. 63.9 ± 13.4 years. p < 0.001) and likely to be male (75 vs. 61%, p < 0.01). In the multivariable analysis, patients who had a history of antireflux surgery (n = 44) or proton-pump inhibitor use without surgery (n = 1,641) were found to progress at significantly lower rates than patients who did not have antireflux surgery or were not taking PPI's (OR 0.18, 95% CI 0.09-0.36). Reflux control was associated with decreased risk of progression to low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma. These results support the use of reflux control strategies such as proton-pump inhibitor therapy or surgery in patients with non-dysplastic Barrett's esophagus for the prevention of progression to dysplasia/adenocarcinoma.

Barrett's oesophagus length is established at the time of initial endoscopy and does not change over time: results from a large multicentre cohort

ObjectiveIt is unclear whether Barrett's oesophagus (BO) length changes over time or whether the full length of the segment is established at the onset of disease recognition. The objectives of...

Screening and surveillance for Barrett esophagus.

Screening and surveillance for Barrett esophagus.

Diagnostic Accuracy of Mucosal Biopsy versus Endoscopic Mucosal Resection in Barrett's Esophagus and Related Superficial Lesions.

Background. Endoscopic surveillance for early detection of dysplastic or neoplastic changes in patients with Barrett's esophagus (BE) depends usually on biopsy. The diagnostic and therapeutic role of endoscopic mucosal resection (EMR) in BE is rapidly growing. Objective. The aim of this study was to check the accuracy of biopsy for precise histopathologic diagnosis of dysplasia and neoplasia, compared to EMR in patients having BE and related superficial esophageal lesions. Methods. A total of 48 patients with previously diagnosed BE (36 men, 12 women, mean age 49.75 ± 13.3 years) underwent routine surveillance endoscopic examination. Biopsies were taken from superficial lesions, if present, and otherwise from BE segments. Then, EMR was performed within three weeks. Results. Biopsy based histopathologic diagnoses were nondysplastic BE (NDBE), 22 cases; low-grade dysplasia (LGD), 14 cases; high-grade dysplasia (HGD), 8 cases; intramucosal carcinoma (IMC), two cases; and invasive adenocarcinoma (IAC), two cases. EMR based diagnosis differed from biopsy based diagnosis (either upgrading or downgrading) in 20 cases (41.67%), (Kappa = 0.43, 95% CI: 0.170–0.69). Conclusions. Biopsy is not a satisfactory method for accurate diagnosis of dysplastic or neoplastic changes in BE patients with or without suspicious superficial lesions. EMR should therefore be the preferred diagnostic method in such patients.

TissueCypher™: A systems biology approach to anatomic pathology

Background: Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC) methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making. Aims: Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE) and the potential use as an adjunctive tool in the diagnosis of BE are described. Patients and Methods: The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22) and Barrett's with high-grade dysplasia (HGD, n = 17). Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA. Results: Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA. Conclusions: The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional pathology in the assessment of BE.

Evaluation of human tissue kallikrein-related peptidases 6 and 10 expression in early gastroesophageal adenocarcinoma.

Kallikreins are a family of serine proteases that are linked to malignancy of different body organs with potential clinical utility as tumor markers. In this study, we investigated kallikrein-related peptidase 6 (KLK6) and KLK10 expression in early gastroesophageal junction adenocarcinoma and Barrett esophagus (BE) with and without dysplasia. Immunohistochemistry revealed significantly increased KLK6 expression in early invasive cancer compared with dysplastic (P = .009) and nondysplastic BE (P = .0002). There was a stepwise expression increase from metaplasia to dysplasia and invasive tumors. Significantly higher KLK10 was seen in dysplastic lesions compared with metaplasia but not between dysplastic lesions and invasive cancers. KLK6 staining intensity was increased at the invasive front (P = .006), suggesting its role in tumor invasiveness. Neither KLK6 nor KLK10 was significantly associated with other prognostic markers, including depth of invasion, indicating their potential as independent biomarkers. Our results should be interpreted with caution due to limited sample size. There was a significant correlation between KLK6 and KLK10 expression both at the invasive front and within the main tumor, indicating a collaborative effect. We then compared KLK6 and KLK10 messenger RNA expression between metaplastic and cancerous tissues in an independent data set of esophageal carcinoma from The Cancer Genome Atlas. KLK6 and KLK10 may be useful markers and potential therapeutic targets in gastroesophageal junction tumors.

The usefulness of white light endoscopy, narrow band imaging, and magnification for the optimization of diagnosis in Barrett’s esophagus

Abstract The diagnosis of dysplasia and early neoplasia in Barrett’s esophagus by conventional endoscopy is based on a four- quadrant random biopsies protocol that is prone to sampling errors. Novel endoscopic techniques have been developed to enhance the detection of premalignant and malignant lesions by real time assessment of microvasculare architecture and mucosal structure. Chromoendoscopy with magnification has improved the visualization of lesions, but the dye application impairs a clear evaluation of vascular network. Narrow band imaging endoscopy enhances vascular imaging by using narrow bandwidth lights, with penetration to superficial mucosal structures. Different classification systems of mucosal and vascular patterns have been developed to improve the diagnostic accuracy of non-dysplastic and dysplastic BE, as well as of early esophageal cancer. This article is focused on both the clinical benefits and controversies surrounding conventional and advanced endoscopic methods used for screening and surveillance of patients with Barrett’s esophagus. Current evidence shows that the adoption of new technology in routine practice requires a high level of performance as well as the standardization of various classification systems.

Pros and Cons of Ablating Nondysplastic Barrett Esophagus

Best-care practice in screening and intervention for nondysplastic Barrett esophagus (BE) is undetermined. Two recognized experts in BE therapeutic

DCLK1 is detectable in plasma of patients with Barrett's esophagus and esophageal adenocarcinoma.

Doublecortin-like kinase 1 (DCLK1), a putative tumor stem cell marker has been shown to be highly expressed in the stromal and epithelial compartments in colon and pancreatic cancer as well as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). To prospectively investigate whether the immunohistochemical expression of DCLK1 was associated with detectable DCLK1 plasma expression in patients with existing BE and EAC. Immunohistochemistry was performed on paraffin-embedded sections using DCLK1 antibody and scored based on staining intensity and tissue involvement. Purified human plasma samples were subjected to Western blot and ELISA analysis. Forty (40) patients were enrolled: 10 controls (normal endoscopy) and 30 with BE/EAC (13 nondysplastic BE [NDBE], 9 dysplastic BE [DBE] and 8 EAC). Mean epithelial DCLK1 staining was as follows: controls = 0.11, NDBE = 3.83, DBE = 6.0, EAC = 7.17. Mean stromal DCLK1 staining was as follows: NDBE = 5.83, DBE = 5.375, EAC = 10.83. DCLK1 was detected by plasma Western blot in 1 control and in all patients with BE/EAC p < 0.0005. Plasma DCLK1 was elevated by ELISA in EAC compared to other groups, p < 0.05. Increased expression of DCLK1 was observed in the epithelium, stroma and plasma of patients with BE/EAC. Furthermore, the presence of detectable DCLK1 in plasma of BE/EAC patients may provide a less invasive, detection tool in those patients as well as represent a novel molecular marker distinguishing between normal esophageal mucosa and BE or EAC.

Sixteen-year follow-up of Barrett's esophagus, endoscopically treated with argon plasma coagulation.

The thermal destruction of non-dysplastic Barrett's esophagus (BE) and its replacement by squamous epithelium is an attractive, but unproven strategy to avoid further development of dysplasia or cancer. The goal of this study was to estimate the persistence of restoration of squamous epithelium and the risk of cancer in BE that was eradicated using argon plasma coagulation (APC) in the absence of high-grade dysplasia, 16 years after its application. We followed 32 patients with BE who underwent eradication of metaplastic epithelium using APC, up to 16 years later. At the end of the initial treatment, 25 of 32 patients (78%) had complete endoscopic eradication, there was partial squamous re-epithelialization in four patients (13%) and it was absent in three patients (9%). We observed buried metaplastic glands under new squamous epithelium in 6 of the 25 patients who had complete endoscopic eradication. At follow-up, sustained complete endoscopic eradication was observed in 16 of 32 patients (50%), partial eradication in 11 of 32 patients (35%); there were two patients (6%) lost to follow-up and three patients (9%) developed esophageal adenocarcinoma. Two of the latest cases arose from the buried glands under neosquamous epithelium after complete eradication and one arose from a small remaining Barrett's segment. We observed long-term re-epithelialization in the majority of patients who had previously had complete eradication of Barrett's esophagus. This did not provide protection against cancer development, as the incidence of cancers arising from buried glands or from residual Barrett's esophagus was similar to that observed in patients undergoing no specific treatment.

Barrett's oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel

ObjectiveReported malignant progression rates for low-grade dysplasia (LGD) in Barrett's oesophagus (BO) vary widely. Expert histological review of LGD is advised, but limited data are available on its clinical value....

Negative surveillance endoscopy occurs frequently in patients with short-segment non-dysplastic Barrett's esophagus.

Surveillance endoscopy of non-dysplastic Barrett's esophagus (NDBE) that fails to detect intestinal metaplasia (IM), or negative surveillance, is known to occur in clinical practice, although the frequency and possible outcomes in a large cohort in clinical practice is not well described. The goals of this study were to define frequency in which negative surveillance occurs and endoscopic outcomes in a screening cohort of short segment NDBE. A retrospective cohort (n = 184) of patients newly diagnosed with short segment NDBE at an outpatient academic tertiary care center between 2003 and 2011 were reviewed. Only those with one or more surveillance endoscopies were included to define a frequency of negative surveillance. Included patients were further assessed if they had two or more surveillance endoscopies and were classified into groups as sampling error or negative IM on consecutive surveillances based on the results of their surveillance endoscopies. The frequency of a negative surveillance endoscopy in all short-segment NDBE patients was 19.66% (92 endoscopic exams were negative for IM of 468 total surveillance exams). A negative surveillance endoscopy occurred in 40.76% (n = 75) patients. Sampling error occurred in 44.12% and negative IM on consecutive surveillance endoscopies in 55.88% of those with ≥ 2 surveillance endoscopies and an initially negative surveillance exam. The frequency of negative IM on consecutive surveillances was 19.00% of all patients who had two surveillance endoscopies. When the index diagnostic Barrett's esophagus segment length was < 1 cm, 32.14% (18/56) of all patients (with ≥ 2 surveillance endoscopies) had negative IM on consecutive surveillance endoscopies. Negative surveillance occurs frequently in short-segment NDBE. When an initial negative surveillance endoscopy occurs, it may be due to either a sampling error or lack of detectable IM on surveillance exam. When a <1 cm segment of NDBE is diagnosed, a significant proportion of patients may go on to have continuously undetected IM on consecutive surveillance endoscopic exams without intervention.

OC-017 Autofluorescence-targeted Optical Biopsy Accurately Diagnoses Dysplasia In Barrett’s Oesophagus And Can Detect The Field Of Molecular Change

IntroductionProbe-based confocal laser endomicroscopy (pCLE) allows optical biopsies in Barrett’s oesophagus (BO) to predict histological outcome but it is subject to sampling error if performed in a random fashion. We...

PTU-058 Machine Learning Creates A Simple Endoscopic Classification System For Detecting Dysplasia In Barrett’s Oesophagus With I-scan Imaging And Opens The Way To Standardised Training And Assessment Of Competence

IntroductionBarrett’s oesophagus (BE) is the pre-cursor for oesophageal adenocarcinoma. Endoscopic surveillance is performed to detect dysplasia in BE as it is likely to be amenable to curative treatment. Current surveillance...

Adherence to the 2011 American Gastroenterological Association medical position statement for the diagnosis and management of Barrett's esophagus.

Considerable variability exists in adherence to practice guidelines for Barrett's esophagus (BE). Rapid advances in management approaches to BE led to a new American Gastroenterological Association (AGA) medical position statement in 2011. Our aim was to assess how well members of the AGA Clinical Practice section adhered to these guidelines. A self-administered survey incorporating questions on diagnostic criteria, cancer risk estimates, screening, surveillance, and therapeutics for BE was distributed electronically to 5850 North American members of the AGA Clinical Practice section. The response rate was 470 of 2040 opened e-mails (23%). Intestinal metaplasia was required for diagnosis of BE by 90%, but the Prague classification was used by only 53% of those aware of it. The annual risk of progression to esophageal adenocarcinoma was reported as 0.1-0.5% by 76%. Screening practices were variable, with 35% screening all patients with chronic gastroesophageal reflux disease and 15% repeating endoscopy in patients with gastroesophageal reflux disease following a negative screening. Surveillance guidelines were followed by 79% for nondysplastic BE and 86% for low-grade dysplasia, with expert pathology confirmation of dysplasia reported by 86%. Proton pump inhibitor dosing was variable, with 18% administering twice-daily doses and 30% titrating dose to symptoms. Ablation therapy was recommended by 6% for nondysplastic BE, 38% for low-grade dysplasia, and 52% for high-grade dysplasia. There is satisfactory adherence to the new AGA guidelines with respect to diagnosis, cancer risk estimates, and surveillance intervals in a select group of respondents. However, adherence continues to be variable in the use of the Prague classification, screening, and dosing of antisecretory therapy. Use of ablation therapy increases with grade of dysplasia. The reason for continued variability in adherence to BE practice guidelines remains unclear, and more evidence-based guidance is required to enhance clinical practice.

Predicting regression of Barrett’s esophagus: results from a retrospective cohort of 1342 patients

Barrett's esophagus (BE) is the most predictive risk factor for development of esophageal adenocarcinoma (EAC), a malignancy with the fastest increasing incidence in the US. The aim of this study was to investigate differences in exposures, demographics, and comorbidities between regressing and non-regressing patients. We retrospectively collected and analyzed data from a cohort of BE patients participating in a single-center study comprised of all patients diagnosed with BE over a 10-year period. We collected information from the patient's electronic medical records regarding demographic data, endoscopic findings, histological findings, exposures, and history of antireflux surgery. This study included 1,342 BE patients, 505 (37.6%) of which experienced regression. The regressed group was 52.3% male, while the non-regressing group was 68.3% male (p < 0.001). Mean age was 65.2 ± 12.8 and 62.0 ± 13.1 years for non-regressing and regressing patients, respectively (p < 0.001). No difference was seen in BMI between regressing and non-regressing groups (27.5 ± 5.7 vs. 27.7 ± 5.4, p = 0.52). No difference was seen between groups with respect to PPI use (93.5% non-regressing vs. 94.1% regressed patients, p = 0.70), but regressed patients were more likely to take vitamin D than non-regressing patients (34.1 vs. 42.1%, p = 0.003). Regressed patients had an average segment length of 1.48 cm (±1.58 cm), in contrast to those not regressing (3.58 ± 3.09 cm (p < 0.001)). Interestingly, one patient in the regression group progressed to dysplasia, while 101 of the non-regressing patients progressed to dysplasia/EAC, a result found to be independent of segment length on multivariate analysis (p < 0.001). Currently, several studies have shown risk factors that can predict progression of non-dysplastic BE, but few investigate predictors for regression. Our study reports several factors that can be used to predict patients who will regress from BE and those who likely will not, tools that will be useful in tailoring therapeutic and surveillance strategies.

Sa1830 Efficacy, Durability and Safety of Radiofrequency Ablation for Nondysplastic Barrett's Esophagus At a University Referral Center

Sa1830 Efficacy, Durability and Safety of Radiofrequency Ablation for Nondysplastic Barrett's Esophagus At a University Referral Center

Mo1827 Radiofrequency Ablation of Esophageal Gastric Heterotopia Leads to Improvement in Atypical Reflux Symptoms As Well As Eradication of Oxyntic and Metaplastic Mucosa

A gastric inlet patch (GIP), also known as a cervical inlet patch or gastric heterotopia, is a discrete island of columnar mucosa in the cervical esophagus. Its origin may be congenital or acquired. GIPs, seen in up to 10% of patients on upper endoscopy, are usually asymptomatic. In some patients, acid secretion from oxyntic mucosa within a GIP may create symptoms including globus sensation, hoarseness, dysphagia or even reflux. Cases of Barrett's esophagus, high grade dysplasia and adenocarcinoma arising from GIPs have been reported. These findings suggest a role for continued acid exposure of the surrounding squamous mucosa generating a metaplasia to dysplasia to neoplasia sequence, similar to what occurs in the distal esophagus in patients with gastroesophageal reflux disease and Barrett's metaplasia. Given the potential to both cause symptoms and progress to malignancy, eradication of GIPs using endoscopic ablation has been considered. We present a series of 3 cases from our institution of successful radiofrequency ablation of these lesions. All 3 patients in this series presented for evaluation of upper GI complaints including atypical reflux symptoms such as hoarseness, globus sensation and dysphagia. Each patient underwent upper endoscopy, where a GIP was identified. Biopsies obtained from each patient confirmed the presence of gastric-type mucosa. In two cases, the presence of oxyntic mucosa with parietal cells within the GIP was confirmed. Intestinal metaplasia consistent with non-dysplastic Barrett's esophagus was confirmed in one case where oxyntic mucosa was present. This patient had mild reflux esophagitis without Barrett's metaplasia on distal esophageal biopsies and only mildly increased distal esophageal acid exposure on 48 hour pH capsule testing. The other 2 patients had negative pH testing off proton pump inhibitors (PPI) with either 24 hour pH/impedance catheter or a 48 hour pH capsule study. Given the presence of symptoms suspected to be related to the GIP, as well as the presence of Barrett's esophagus, endoscopic treatment with radiofrequency ablation (RFA) was planned for all 3 patients. Each patient underwent either 1 or 2 ablation sessions using the Barrx-90 device (Covidien GI Solutions, Sunnyvale, CA). Follow-up endoscopy confirmed successful eradication of all GIPs. All three patients reported significant improvement in their upper gastrointestinal symptoms, even after discontinuation of PPI therapy. These cases demonstrate the ability of RFA to eradicate esophageal gastric heterotopia. Concurrent improvement in atypical reflux symptoms, even off PPI therapy, suggests RFA can generate symptomatic improvement as well as reduce the risk of neoplastic progression. With more widespread availability of RFA, we should reconsider the role of endoscopic surveillance and intervention for GIPs.

231 Reflux Control Is an Important Component of the Management of Barrett's Esophagus – Results From a Retrospective Cohort of 1834 Patients

Introduction: Barrett's esophagus (BE) is the most predictive risk factor for development of esophageal adenocarcinoma, a malignancy with the fastest increasing incidence rate in the US. Based on the assumption that all patients progress through low-grade dysplasia (LGD) to high-grade dysplasia (HGD) and finally to esophageal adenocarcinoma (EAC), we were interested in studying factors that may affect the rate of progression to LGD or greater. We were particularly interested in investigating the question of whether control of reflux, either surgically or medically, protects patients from progression to dysplastic disease or adenocarcinoma. Methods: We retrospectively collected and analyzed data from a cohort of BE patients participating in this single-center study comprised of all patients diagnosed with BE at a single health system's hospitals and clinics over a 10 year period. Patients were followed in order to identify those progressing from BE to LGD, HGD, and EAC. Mean follow up period was 5.4 years (9903 patient-years). We collected information from the patient's electronic medical records regarding demographic data, endoscopic findings, histological findings, smoking and alcohol history, medication use including PPI's, and history of bariatric and antireflux surgery. Risk adjusted model was performed using multivariable logistic regression in SAS 9.3 (Cary, NC). Results: This study included 1834 total BE patients, 105 of which had their BE progress to LGD, HGD, or EAC (confirmed by biopsy) with an annual incidence rate of 1.1%. Compared to the group that did not progress, the group that progressed was older (63.8±13.5 vs. 68.8±13.1. p<.001) and likely to be male (61% vs. 69%, p=0.098). In the multivariable analysis, patients who had a history of antireflux surgery (n=44) or PPI use without surgery (n=1708) were found to progress at lower rates than patients who did not have antireflux surgery or were not taking PPI's (OR=0.23, 95% CI 0.12-0.42). Conclusions: In patients with BE without dysplasia, reflux control was associated with decreased risk of progression to LGD, HGD, or EAC. The results support the use of reflux control strategies such as PPI therapy or surgery in patients with non-dysplastic BE.