Barrett's oesophagus, a significant complication of
gastro-oesophageal reflux disease (
GERD), is the single most important risk factor for oesophageal
adenocarcinoma. The strong association between Barrett's oesophagus and chronic
GERD suggests that abnormal oesophageal
acid exposure plays an important role in this condition. The progression of Barrett's oesophagus from specialized intestinal
metaplasia to dysplasia and finally invasive
carcinoma is incompletely understood, but increased and disordered proliferation is a key cellular event. In ex vivo organ culture experiments, cell proliferation is increased after exposure to short pulses of
acid, whilst proliferation is reduced in Barrett's oesophagus specimens taken from patients with oesophageal
acid exposure normalized by antisecretory
therapy. In long-term clinical studies, consistent and profound intra-oesophageal
acid suppression with
proton pump inhibitors decreases cell proliferation and increases differentiation in Barrett's oesophagus, but the clinical importance of such favourable effects on these
surrogate markers is not clear. In clinical practice,
proton pump inhibitors relieve symptoms and induce partial regression to squamous epithelium, but abnormal oesophageal
acid exposure and the risk for dysplasia or
adenocarcinoma persist in many patients. The ability of
proton pump inhibitors to suppress
acid profoundly and consistently may be critical in the long-term management of Barrett's oesophagus.