Barrett's oesophagus, dysplasia and pharmacologic acid suppression

Barrett's oesophagus, a significant complication of gastro-oesophageal refl ux disease (GERD), is the single most important risk factor for oesophageal adenocarcinoma. The strong association between Barrett's oesophagus and ch ronic GERD suggests that abnormal oesophageal acid exposure plays an import ant role in this condition. The progression of Barrett's oesophagus from sp ecialized 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 proliferat ion is increased after exposure to short pulses of acid, whilst proliferati on is reduced in Barrett's oesophagus specimens taken from patients with oe sophageal acid exposure normalized by antisecretory therapy. In long-term clinical studies, consistent and profound intra-oesophageal ac id suppression with proton pump inhibitors decreases cell proliferation and increases differentiation in Barrett's oesophagus, but the clinical import ance of such favourable effects on these surrogate markers is not clear. In clinical practice, proton pump inhibitors relieve symptoms and induce part ial regression to squamous epithelium, but abnormal oesophageal acid exposu re and the risk for dysplasia or adenocarcinoma persist in many patients. T he ability of proton pump inhibitors to suppress acid profoundly and consis tently may be critical in the long-term management of Barrett's oesophagus.