Nearly one-third of patients with Barrett’s esophagus who reported no reflux symptoms while taking proton pump inhibitors (PPIs) still had abnormal levels of acid exposure in the esophagus, according to a multicenter study from Italy. These patients were about nine times more likely to have neoplasia than patients with controlled acid levels.
“A key step in improving and personalizing Barrett’s esophagus surveillance is identifying patients at risk of neoplastic progression, and the role of esophageal function testing in this setting is unexplored,” first author Edoardo Vespa, MD, of the division of gastroenterology and digestive endoscopy at IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues wrote in the retrospective study, which was published in Clinical Gastroenterology and Hepatology.
The researchers enrolled 135 patients with biopsy-confirmed Barrett’s esophagus who underwent high-resolution manometry and 24-hour pH-impedance monitoring while on stable PPI therapy. All patients were free of reflux symptoms at the time of testing and underwent endoscopic and tissue evaluations while receiving the same treatment regimen. The index endoscopy was performed a median of 6 months before esophageal function testing.
Abnormal acid exposure, defined as acid exposure time greater than 6%, was identified in 37 patients (27%). Another 14 patients (10%) had borderline acid exposure, while 84 patients (62%) had normal acid exposure below 4%. Of note, 25 of the 37 patients with abnormal reflux were receiving standard-dose PPI therapy, whereas 34 patients with normal acid exposure were also maintained on standard dosing.
Two variables emerged as independent predictors of abnormal acid exposure. Patients receiving standard-dose rather than maximal-dose PPI therapy had 3.5 times the odds of pathological reflux, and patients with type III esophagogastric junction morphology on manometry had 2.6 times the odds. Type III morphology is consistent with a hiatal hernia and was present in 41% of the cohort.
The most important clinical finding was the association between acid exposure and neoplasia. Thirteen patients (10%) had neoplastic changes detected at the initial endoscopy, including eight cases of low-grade dysplasia, three cases of high-grade dysplasia, and two cases of intramucosal adenocarcinoma.
Among these patients, 77% had abnormal acid exposure despite ongoing PPI therapy. Patients with neoplasia also had substantially higher median acid exposure times than those without neoplastic changes.
In multivariable analysis, abnormal acid exposure was the only independent predictor of neoplasia. Patients with acid exposure times greater than 6% were nearly 10 times more likely to have neoplastic changes than those with lower levels of acid exposure. Other factors commonly linked to disease progression, including Barrett’s segment length, body mass index, age, and sex, were not independently associated with neoplasia in this study.
Receiver operating characteristic analysis showed that an acid exposure time threshold of 6% predicted neoplasia with 77% sensitivity and 78% specificity. The authors noted that this cutoff aligns with the Lyon Consensus definition of pathological reflux, suggesting it may serve as a clinically meaningful marker of neoplasia risk in patients with Barrett’s esophagus receiving PPI therapy.
Study limitations included its retrospective design, referral-center population, lack of detailed data on PPI adherence and treatment duration, and insufficient follow-up to determine whether physiology-guided interventions reduce progression to dysplasia or cancer.
“Our findings advocate for routinary use of pH monitoring in patients with Barrett’s esophagus to improve personalized management, optimize anti-reflux treatment, and potentially prevent the progression to dysplasia and esophageal adenocarcinoma,” the researchers concluded.
Several authors reported consulting, speaking, advisory, or research relationships with pharmaceutical companies, including AbbVie, Pfizer, Takeda, Sanofi, Johnson & Johnson, and others.