Esophageal Function Testing Identifies Barrett’s Esophagus Patients With Pathological Acid Exposure at Risk for Neoplasia

Background & Aims Pathological esophageal acid exposure may persist in patients with Barrett’s esophagus (BE), despite proton pump inhibitor (PPI) administration and symptom control. We aimed to determine the role of esophageal function testing in assessing acid exposure in patients with BE on PPI therapy and predicting disease progression. Methods Multicenter retrospective study of asymptomatic patients with BE with high-resolution manometry and 24-hour pH impedance testing on PPI. Histological findings were recorded at index endoscopy while on the same therapeutic regimen. On pH monitoring, total acid exposure time (AET) >6% was defined as pathological reflux. Receiver operator characteristic analysis was performed to evaluate the predictive performance of AET for neoplasia, using Youden’s index to identify the optimal cutoff. Results A total of 135 patients were included (mean age, 58 ± 15 years; 73% male). Median BE length was C1M2, 56 (41%) had long-segment BE. Sixty-eight patients (50%) were on standard-dose PPI. Pathological reflux was identified in 37 patients (27%), of whom 25 (67%) were taking standard-dose PPI. Among the 84 patients (62%) with normal AET (<4%), 34 (40%) were taking standard-dose PPI. On multivariable analysis, standard-dose PPI (adjusted odds ratio [aOR], 3.53; P = .004) and type III esophagogastric junction morphology (aOR, 2.64; P = .036) were independently associated with pathological reflux. Thirteen patients (10%) had neoplasia at index endoscopy (8 low-grade dysplasia, 3 high-grade dysplasia, 2 adenocarcinoma). Pathological reflux was the only independent predictor of neoplasia (aOR, 9.62; P < .001). AET ≥6% predicted neoplasia well (area under the curve, 0.816; 77% sensitivity; 78% specificity). Conclusions Nearly one-third of asymptomatic patients with BE exhibit pathological reflux on pH-monitoring despite PPI treatment. Nonetheless, normal AET is found in another one-third of patients on standard-dose PPI. Pathological reflux is associated with a 9-fold increased risk of neoplasia.