DISTAL ESOPHAGEAL ACID EXPOSURE AND POOR ESOPHAGEAL CLEARANCE ARE CORRELATED WITH 5-YEAR RISK OF PROGRESSION FROM NON-DYSPLASTIC BARRETT’S ESOPHAGUS TO HIGH-GRADE DYSPLASIA OR ESOPHAGEAL ADENOCARCINOMA

Introduction: Barrett’s esophagus (BE) guidelines recommend surveillance biopsies at up to 5-year intervals for non-dysplastic BE (NDBE). They have also questioned the value of biopsy from intestinal metaplastic (IM) segments <1cm due to low risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). These recommendations are based on pathology alone, yet biomarkers can provide further risk-stratification to better guide management. Esophageal physiology findings may also provide information to aid in risk stratification of these patients. The aim of this study was to correlate pH-monitoring and manometric factors with 5-year risk of progression to HGD/EAC in NDBE patients.

Methods: A cohort of patients with NDBE who underwent esophageal pH-monitoring and high-resolution manometry (HRM) was selected. Their pathology specimen was analyzed using a validated tissue systems pathology test with 9 biomarkers (TSP-9). This assay uses immunohistochemistry and digital pathology analysis to risk-stratify patients based on their 5-year risk of progression to HGD/EAC. Correlation analyses were performed between 5-year progression to HGD/EAC risk and individual pH-monitoring and HRM components. Sub-analysis was performed in patients with <1cm IM.

Results: The final study population consisted of 59 (52.5% male) patients with NDBE with a mean(SD) age of 59(14). The TSP-9 5-year risk of progression was 2.74(2) percent with a 95% confidence interval between 1.83(2) and 3.64 (2). The DeMeester score was 51.9(38) with an abnormal score of >14.7 in 90.9% of patients. Manometric characteristics included 14.0(23) % failed swallows and 41.2(36) % incomplete bolus clearance.
Risk of progression was directly correlated with DeMeester score (R=0.304, 95%CI: 0.01-0.55 p=0.045), % total time with pH < 4 (R=0.34, 95%CI: 0.05-0.58, p=0.025), and duration of longest reflux episode (R= 0.298, 95%CI: 0.01-0.55, p=0.049) on pH-monitoring, and % incomplete bolus clearance (R= 0.351, 95%CI: 0.04-0.60 p=0.028) on HRM.
There were 19 (32.2%) patients with <1cm IM. In this group, risk of progression was correlated with DeMeester score (R=0.65, 95%CI 0.27-0.86, p=0.003), % time with pH < 4 (R=0.67, 95% CI: 0.29-0.87, p=0.002), % supine time with pH<4 (R=0.70, 95%CI: 0.35-0.88, p=0.001), number of reflux episodes (R=0.502, 95%CI: 0.05-0.78, p=0.034) and number of episodes longer than 5 mins (R=0.56, 95%CI: 0.12-0.81, p=0.017) on pH-monitoring, and % failed swallows (R=0.68, 95%CI:0.31-0.87, p=0.004) and % incomplete bolus clearance (R=0.68, 95%CI:0.31-0.87, p=0.004) on HRM.

Conclusion: In patients with NDBE there is a direct correlation between 5-year risk of high-grade dysplasia or esophageal adenocarcinoma and distal esophageal acid exposure and poor esophageal clearance. This correlation is stronger in patients with <1cm segment Barrett’s esophagus.