A nonendoscopic screening approach using a swallowable cell collection device and molecular assay identified Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) in 12% of at-risk US veterans without a history of chronic gastroesophageal reflux disease (GERD), with 100% sensitivity and a 100% negative predictive value using endoscopy as the reference standard, according to data presented at Digestive Disease Week® (DDW) 2026.
In the prospective study, the EsoCheck device paired with the EsoGuard assay was compared with esophagogastroduodenoscopy (EGD) in 117 veterans who met professional guideline criteria for BE and EAC screening despite having no chronic reflux history. Sensitivity and specificity of EsoCheck/EsoGuard for EGD-detected disease were 100% and 62%, respectively, with a positive predictive value of 26% and a negative predictive value of 100%.
Anamay Sharma, MD, of Case Western Reserve University in Cleveland, presented the findings from research conducted at the Louis Stokes Cleveland Veterans Affairs Medical Center. The work targets a population that current screening paradigms often miss — patients with multiple BE risk factors but no chronic reflux symptoms — and tests whether an office-based, non-endoscopic tool can detect disease reliably enough to triage which patients need confirmatory endoscopy.
Of 430 eligible veterans, 117 (27%) accepted screening. Among those, 10 patients (9%) were unable to swallow the EsoCheck device, and four samples were insufficient for molecular analysis. Diagnostic accuracy was assessed in the 103 patients who completed both procedures.
The overall prevalence of BE or EAC was 12% (14 of 117 patients). Most newly diagnosed cases involved short-segment BE (11 of 14, 79%), and two patients had high-grade dysplasia. The mean number of risk factors per patient was 4.40. Anxiety levels decreased after study procedures, and the mean postprocedure acceptability score for the nonendoscopic method was 7.7 on a 10-point scale.
Dr. Sharma noted that the prevalence of BE in veterans with three or more non-GERD risk factors was similar to that observed in veterans with a history of GERD and above the expected prevalence range of the general population.
"Our data suggest outstanding sensitivity and negative predictive value of [EsoCheck/EsoGuard] in a screening population of veterans without history of chronic GERD," Dr. Sharma concluded.
The study was conducted at a single VA medical center, and roughly 12% of participants were either unable to swallow the device or provided samples insufficient for molecular analysis. The modest cohort size also produced wide confidence intervals around the diagnostic accuracy estimates.
The authors reported no disclosures.
DDW is AGA's annual meeting, jointly sponsored by AGA, AASLD, ASGE, and SSAT. Learn more at ddw.org.
Expert Insight
GI & Hepatology News invited study coauthor Shahin Ayazi, MD, to comment on the study’s findings.
Why does this study matter?
This study addresses a key gap in current Barrett's esophagus screening paradigms: whether individuals without classic reflux symptoms but with multiple established risk factors represent a clinically meaningful population for screening. Current guidelines frameworks from the American College of Gastroenterology and American Gastroenterological Association acknowledge low quality of evidence for risk factor–based screening and disagree on whether chronic GERD is a required risk factor.1,2 A recent study demonstrated that up to 55% of patients with esophageal cancer would not have qualified for screening based on current US and UK guidelines, with lack of GERD symptoms as the most common reason for not meeting the threshold for screening.3 By prospectively demonstrating a 12% prevalence of BE/EAC in asymptomatic veterans, this study supports risk factor–based screening independent of GERD symptoms, which has important implications for early detection strategies aimed at preventing progression to esophageal adenocarcinoma.
Also important is the evaluation of a non-endoscopic office-based screening approach (EsoCheck). Demonstrating excellent sensitivity and negative predictive value in a prospective setting supports the feasibility of scalable, less resource-intensive screening. Given the growing evidence that Barrett's esophagus screening protocols may need to accommodate more patients than just those with reflux symptoms, EsoCheck provides a potential pathway to expand screening while maintaining diagnostic reliability and reserving endoscopy for confirmation of positive results.
Is there anything surprising about this data?
The most striking finding is the relatively high prevalence of BE (12%) in a population explicitly lacking chronic GERD symptoms. This prevalence matches or exceeds rates typically reported in symptomatic populations undergoing targeted screening and challenges the long-standing clinical assumption that reflux symptoms are a necessary gateway to BE risk stratification.
The perfect sensitivity and negative predictive value of the EsoCheck/EsoGuard platform also stand out. While the wide confidence intervals reflect sample size limitations, the implication that a negative test could reliably exclude disease in this population is promising. At the same time, the modest specificity and low positive predictive value highlight that patients who test positive still require confirmatory endoscopy.
How might the findings influence clinical practice?
If validated in larger and more diverse populations, these findings could support a shift toward broader, risk factor–based screening strategies that are not contingent on GERD symptoms. From a practical standpoint, the integration of non-endoscopic tools like EsoCheck/EsoGuard could serve as a first-line screening modality, reserving endoscopy for confirmatory testing in positive cases. This tiered approach could improve cost-effectiveness, increase patient acceptance, and reduce procedural burden on endoscopy units. Further studies should evaluate non-endoscopic screening techniques in patients with known Barrett's esophagus to assess the feasibility of using them as a potential bridge to de-escalation of surveillance in this population.
Is there anything else you would like to say about this work?
This study also highlights the importance of patient-centered considerations in screening implementation. Despite identifying an at-risk population, only 27% of eligible veterans agreed to participate, underscoring persistent barriers to screening uptake. Encouragingly, procedure-related anxiety decreased after participation, and overall acceptability of the EsoCheck device was relatively high, suggesting that familiarity and education may improve engagement over time.
Over 90% of patients diagnosed with esophageal adenocarcinoma do not have a preceding diagnosis of Barrett's esophagus, highlighting major limitations in our current approach to preventing a disease with high morbidity and mortality.1 This work contributes to a growing body of evidence that challenges traditional screening paradigms and supports a more nuanced, risk-based, and patient-friendly approach to Barrett's esophagus screening.
References
Muthusamy V, Wani S, Gyawali C, et al. AGA Clinical Practice Update on New Technology and Innovation for Surveillance and Screening in Barrett's Esophagus: Expert Review. Clinical Gastroenterology and Hepatology. 2022;20:2696-2706.e1.
Shaheen NJ, Falk GW, Iyer PG, et al. Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. American Journal of Gastroenterology. 2022;117(4):559-587.
Sawas T, Zamani SA, Killcoyne S, et al. Limitations of heartburn and other societies' criteria in Barrett's screening for detecting de novo esophageal adenocarcinoma. Clinical Gastroenterology and Hepatology. 2022;20(8):1709-1718.