Original Contribution

The American Journal of Gastroenterology (2007) 102, 21–23; doi:10.1111/j.1572-0241.2006.01033.x

The Evidence Base of Proton Pump Inhibitor Chemopreventative Agents in Barrett's Esophagus—The Good, The Bad, and The Flawed!

Simon Leedham MB, ChB (Lond), MRCP (UK)1 and Janusz Jankowski MB, ChB (Glasgow), MSc (Oxon), MD (Dundee), PhD (London), FRCP, FRCPE2

  1. 1Department of Histopathology, Cancer Research UK, London, United Kingdom
  2. 2Department of Clinical Pharmacology, University of Oxford, Oxford, United Kingdom, and Consultant Gastroenterologist, Leicester Royal Infirmary, Leicestershire, United Kingdom

Correspondence: Professor Janusz Jankowski, University of Oxford, Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE.

Received 18 October 2006; Accepted 20 October 2006.



Gastric acid is believed to be an important etiological factor in the pathogenesis of Barrett's esophagus. Pulsatile acid exposure increases cell proliferation in ex vivo Barrrett's tissue and normalization of esophageal pH reverses this. Proton pump inhibitors (PPIs) are the mainstay of therapy in Barrett's esophagus, and have numerous beneficial effects including symptom control, reduction of inflammation, and promotion of the development of squamous islands. However, PPI therapy causes hypergastrinemia and has not prevented recent increase in the incidences of esophageal cancer. Additionally, evidence presented here by Feagins et al. suggests that acid exposure has a p53-mediated, antiproliferative effect on a nondysplastic Barrett's epithelial cell line, an effect that acid suppression might abrogate. These complex pH, inflammation, and growth factor biological interactions can be most reliably tested in large clinical trials with hard end points like cancer conversion or all causes of mortality. Combining the anti-inflammatory effects of acid suppression with aspirin, a nonsteroidal anti-inflammatory agent, is the subject of the AspECT clinical trial, and this may be the future of chemoprevention in Barrett's.