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

Abstract

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 enrolment. 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.

Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus: a systematic review and meta-analysis

“…20 Systematic information on surveillance of BO was provided in only two studies. 1019 Three studies used record linkage with the pharmacy prescription database for exposure assessment 101120 ; three studies relied on medical record review 192122 and one on patient self-report. 18 …”

“…Four cohort studies reported the risk of progression to advanced neoplasia (OAC or BO-HGD) 10111922 (with no information on risk of progression to OAC or BO-HGD separately), and one study reported the risk of progression to any grade of neoplasia (OAC or BO-HGD or BO-LGD). 21 Two case–control studies included only patients with OAC as cases.…”

Barrett's oesophagus, proton pump inhibitors and gastrin: the fog is clearing

“…An Australian cohort study followed 350 patients with Barrett's oesophagus for a median 4.7 years. Patients who received PPI maintenance from the time of diagnosis had a subsequent five- to 20-fold decreased risk for development of dysplasia and cancer 6. A similar study from the US followed 236 patients with Barrett's oesophagus for an average 5 years 7.…”

Molecular changes in the progression of Barrett's oesophagus

“…[6][7][8] Nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin and perhaps proton pump inhibitor use show a negative correlation with the occurrence of oesophageal adenocarcinoma. [9][10][11] The increasing burden of this disease and poor prognosis has stimulated research in the area but molecular and cellular mechanisms responsible for the development of Barrett's oesophagus and its conversion to neoplasia in a subgroup of patients are not fully understood. Predictive factors need to be identified for timing of preventive interventions and for targeted designs for future studies.…”