Proton‐pump inhibitor therapy and the development of dysplasia in patients with Barrett's oesophagus

OBJECTIVE: To examine whether proton-pump inhibitor (PPI) therapy influences the incidence and progression of dysplasia in patients with Barrett's oesophagus. DESIGN AND SETTING: Review of prospective data on patients undergoing surveillance with regular endoscopy and biopsy at a private endoscopy centre in Canberra, ACT, between 1981 and 2001. PATIENTS: 350 patients diagnosed with Barrett's oesophagus. INTERVENTIONS: PPI therapy was progressively introduced into clinical practice from late 1989. Once begun, PPI therapy was ongoing, with no attempt to reduce the dose. MAIN OUTCOME MEASURES: Relationship between development of dysplasia or adenocarcinoma and delay between diagnosis with Barrett's oesophagus and starting PPI therapy was determined by Cox regression analyses, stratified by year of enrollment. Age, sex, presence of macroscopic markers (severe oesophagitis, nodularity, Barrett's ulcer, stricture) and use of aspirin or non-steroidal anti-inflammatory drugs were considered as confounding factors in the regression analyses. RESULTS: The 350 patients had 1422 surveillance endoscopies, with a median follow-up of 4.7 years. Patients who delayed using a PPI for 2 years or more after diagnosis with Barrett's oesophagus had 5.6 times (95% CI, 2.0-15.7) the risk of developing low-grade dysplasia at any given time as those who used a PPI in the first year. Similar results were found for the risk of developing high-grade dysplasia or adenocarcinoma (hazard ratio, 20.9; 95% CI, 2.8-158). CONCLUSIONS: Use of ongoing PPI therapy appeared beneficial in the prevention of dysplasia and adenocarcinoma in patients with Barrett's oesophagus. We suggest that all patients with this condition, even those with no oesophagitis or symptoms, should be encouraged to continue long term PPI therapy.