ABSTRACT

Background Screening efforts for Barrett’s Esophagus (BE) predominantly focus on performing upper endoscopy (EGD) on patients with gastroesophageal reflux disease (GERD) symptoms who have additional risk factors for BE. However, cost and invasiveness preclude EGD in those who have no prior GERD symptoms, despite having other risk factors, representing missed opportunities for BE screening in individuals who account for approximately 40% of the patients who eventually develop esophageal adenocarcinoma (EAC).

Aim The aim of this study was to evaluate if non-endoscopic methods can enable BE detection in an at-risk population without GERD symptoms.

Methods Patients presenting for colonoscopy who had not undergone previous EGD plus had ≥3 BE risk factors (from among age >50 years, male sex, white race, smoking history, family history of BE/EAC, or central obesity) without chronic GERD symptoms were prospectively recruited for non-endoscopic screening. Trained nurses administered the EsoCheck (Lucid Diagnostics) encapsulated balloon. Samples were assayed with the EsoGuard BE detection methylated DNA marker panel (Lucid Diagnostics). Patients with a positive result were offered standard-of-care EGD, while patients with a negative EG result were offered free of cost research EGD. Positive predictive value (PPV), negative predictive value (NPV), and BE prevalence were calculated.

Results The mean age of the 132 study subjects was 60.7 years, 129 (98%) were white, 124 (94%) were male, 71 (54%) had a prior smoking history, 46 (35%) were centrally obese, and 5 (4%) reported a family history. EsoCheck was successfully administered in 124 (94%) and the EsoGuard methylated DNA marker panel could be assayed in 120 (97%) of the samples. Thirty-four assays were positive of which 27 underwent a follow-up EGD and BE was identified in 9, PPV = 33% [17%, 54%] subjects. EGD was also performed in 22 of the 86 subjects whose assays were negative and none of them had BE, NPV = 100% [85%, 100%]. A logistic regression model fitted to impute the presence of BE estimated the PPV as 27% [13%, 44%], NPV as 98% [92%, 100%], and BE prevalence as 8.4% [4.5%, 14.3%].

Conclusion Patients without chronic GERD who have ≥3 BE risk factors have a moderately high prevalence of BE. Non-endoscopic detection can effectively identify BE, enabling expansion of screening to this larger at-risk population. Those with a negative EG assay have a low likelihood of BE.

Competing Interest Statement

SM, AC, JW are founders, shareholders, consultants to and have a royalty interest in technology licensed to Lucid Diagnostics. HM is a shareholder, consultant to and has a royalty interest in technology licensed to Lucid Diagnostics. SV is an employee of Lucid Diagnostics.

Funding Statement

Grant Support: NIH CA271867 (SM, AC, JW), CA295877 (SM, AC, JW), CA269019 (AC, JW), CA152756 (SM). EsoCheck devices and EsoGuard assays supported by Lucid Diagnostics.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

University Hospitals Cleveland Medical Center Institutional Review Board for Human Investigation

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Footnotes

Grant Support: NIH CA271867 (SM, AC, JW), CA295877 (SM, AC, JW), CA269019 (AC, JW), CA152756 (SM). EsoCheck devices and EsoGuard assays supported by Lucid Diagnostics.

Disclosures: SM, AC, JW are founders, shareholders, consultants to and have a royalty interest in technology licensed to Lucid Diagnostics. HM is a shareholder, consultant to and has a royalty interest in technology licensed to Lucid Diagnostics. SV is an employee of Lucid Diagnostics.

Data Availability

All data produced in the present work are contained in the manuscript

AbbreviationsBEBarrett’s EsophagusEACEsophageal AdenocarcinomaEGDEsophagogastroduodenoscopyHGDHigh Grade DysplasiaLGDLow Grade Dysplasia