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Background and Aims We previously identified a 5 methylated DNA marker (MDM) panel for the detection of nonendoscopic Barrett’s esophagus (BE). In this study, we aimed to recalibrate the performance of the 5 MDM panel using a simplified assay in a training cohort, validate the panel in an independent test cohort, and explore the accuracy of an MDM panel with only 3 markers. Methods Participants were recruited from 3 medical centers. The sponge on a string device (EsophaCap; CapNostics, Concord, NC, USA) was swallowed and withdrawn, followed by endoscopy, in BE cases and control subjects. A 5 MDM panel was blindly assayed using a simplified assay. Random forest modeling analysis was performed, in silico cross-validated in the training set, and then locked down, before test set analysis. Results The training set had 199 patients: 110 BE cases and 89 control subjects, and the test set had 89 patients: 60 BE cases and 29 control subjects. Sensitivity of the 5 MDM panel for BE diagnosis was 93% at 90% specificity in the training set and 93% at 93% specificity in the test set. Areas under the receiver operating characteristic curves were .96 and .97 in the training and test sets, respectively. Model accuracy was not influenced by age, sex, or smoking history. Multiple 3 MDM panels achieved similar accuracy. Conclusions A 5 MDM panel for BE is highly accurate in training and test sets in a blinded multisite case-control analysis using a simplified assay. This panel may be reduced to only 3 MDMs in the future. (Clinical trial registration number: NCT 02560623.)

Introduction Nonendoscopic Barrett's esophagus (BE) screening may help improve esophageal adenocarcinoma outcomes. We previously demonstrated promising accuracy of methylated DNA markers (MDMs) for the nonendoscopic diagnosis of BE using samples obtained from a capsule sponge-on-string (SOS) device. We aimed to assess the accuracy of these MDMs in an independent cohort using a commercial grade assay. Methods BE cases had ≥ 1 cm of circumferential BE with intestinal metaplasia; controls had no endoscopic evidence of BE. The SOS device was withdrawn 8 minutes after swallowing, followed by endoscopy (the criterion standard). Highest performing MDMs from a previous study were blindly assessed on extracted bisulfite-converted DNA by target enrichment long-probe quantitative amplified signal (TELQAS) assays. Optimal MDM combinations were selected and analyzed using random forest modeling with in silico cross-validation. Results Of 295 patients consented, 268 (91%) swallowed the SOS device; 112 cases and 89 controls met the pre-established inclusion criteria. The median BE length was 6 cm (interquartile range 4-9), and 50% had no dysplasia. The cross-validated sensitivity and specificity of a 5 MDM random forest model were 92% (95% confidence interval 85%-96%) and 94% (95% confidence interval 87%-98%), respectively. Model performance was not affected by age, gender, or smoking history but was influenced by the BE segment length. SOS administration was well tolerated (median [interquartile range] tolerability 2 [0, 4] on 10 scale grading), and 95% preferred SOS over endoscopy. Discussion Using a minimally invasive molecular approach, MDMs assayed from SOS samples show promise as a safe and accurate nonendoscopic test for BE prediction.

High-resolution endoscopy with narrow band imaging (NBI) enhances the visualization of mucosal glandular and vascular structures. This study assessed whether narrow band targeted biopsies could detect advanced dysplasia using fewer biopsy samples compared with standard resolution endoscopy.We conducted a prospective, blinded, tandem endoscopy study in a tertiary care center with 65 patients with Barrett's esophagus undergoing evaluation for previously detected dysplasia. Standard resolution endoscopy was used first to detect visible lesions. Narrow band endoscopy was then used by another gastroenterologist to detect and biopsy areas suspicious for dysplasia. The lesions initially detected by standard resolution endoscopy were then disclosed and biopsied, after biopsy of the lesions targeted with NBI. Finally, random 4-quadrant biopsies were taken throughout the segment of Barrett's mucosa.Higher grades of dysplasia were found by NBI in 12 patients (18%), compared with no cases (0%) in whom standard resolution white light endoscopy with random biopsy detected a higher grade of histology (P.001). Correspondingly, narrow band directed biopsies detected dysplasia in more patients (n = 37; 57%) compared with biopsies taken using standard resolution endoscopy (n = 28; 43%). In addition, more biopsies were taken using standard resolution endoscopy with random biopsy compared with narrow band targeted biopsies (mean 8.5 versus 4.7; P.001).In patients evaluated for Barrett's esophagus with dysplasia, NBI detected significantly more patients with dysplasia and higher grades of dysplasia with fewer biopsy samples compared with standard resolution endoscopy.