Abstract
BACKGROUND: The risk of progression from non-dysplastic Barrett's esophagus (NDBE) to high grade dysplasia or esophageal adenocarcinoma (HGD/EAC) is low but variable. Biomarker assays can aid with risk stratification to optimize surveillance for NDBE. The role of diagnostic esophageal testing in prognosticating progression is unclear. The aim of this study was to evaluate whether esophageal physiology parameters correlate with a validated biomarker for BE risk progression. METHODS: Patients with NDBE, including histology confirmed intestinal metaplasia < 1 cm, had their pathology specimen analyzed using a validated tissue systems pathology test with 9 biomarkers (TSP-9). This assay uses immunohistochemistry and digital pathology analysis to provide a 5-year risk of progression to HGD/EAC. These patients also underwent esophageal pH-monitoring and high-resolution impedance manometry (HRIM). Correlation analyses were performed between TSP-9 risk percent and esophageal testing. RESULTS: A total of 59 patients [52.5% male; mean (SD) age 59 (14)] were included (40 NDBE, 19 < 1 cm IM) between 2021 and 2023. The median (IQR) TSP-9 value for 5-year risk of progression was low at 2.0% (2.0-3.0%). There were 8 (13.6%) statistical outliers with higher risk ranging from 5.0 to 10.0%. Risk of progression in the entire cohort was directly correlated with physiology testing parameters including DeMeester score (R = 0.30), acid exposure time (AET) (R = 0.34), duration of longest reflux episode on pH-monitoring (R = 0.30), and % incomplete bolus clearance on HRIM (R = 0.35) (p < 0.05 for all). In a subgroup of 19 patients with < 1 cm IM, risk of progression had a stronger correlation with DeMeester score (R = 0.65), AET (R = 0.67), supine AET (R = 0.70), number of reflux episodes on pH-monitoring (R = 0.50) and % incomplete bolus clearance on HRIM (R = 0.68) (p < 0.05 for all). CONCLUSION: There was a direct correlation between 5-year risk of progression to HGD/EAC using TSP-9 and distal esophageal acid exposure and poor esophageal clearance among patients with NDBE that was even stronger in those with < 1 cm of IM. These findings suggest that esophageal physiology testing may have value in predicting risk progression in BE.