Acid suppression and chemoprevention in Barrett's oesophagus.
Barrett's oesophagus is a pre-malignant condition affecting 1% of the population in the West. Even though most patients with Barrett's will not develop oesophageal cancer, the incidence of adenocarcinoma is 0.45-1%, conferring a 40-fold increased risk compared with the general population. The risk rises to 40-50% within 5 years for those with high grade dysplasia. Currently, the only strategies available to diminish adenocarcinoma rates are surveillance endoscopy, endoscopic thermal or photodynamic ablation or tissue resection. The latter options are reserved for those who already have dysplasia. 10-50% of patients undergoing oesophagectomy for high grade dysplasia have been shown to have adenocarcinoma. Therefore approaches are needed to be that either remove or prevent stimuli propelling patients down the dysplasia-adenocarcinoma pathway. Both gastric acid and bile acids have been reported as potential insults involved in the pathogenesis of Barrett's oesophagus. This is thought to be mediated by a range of molecules including cyclo-oxygenase-2, c-myc and mitogen-activated protein kinase signalling. Proton pump inhibitors not only suppress acid but also bile reflux, although symptom control is a poor guide as to adequacy of acid suppression. There is some evidence that proton pump inhibitors cause partial regression in Barrett's oesophagus length, although the data is contradictory. Proton pump inhibitors have also been shown to increase cell differentiation and apoptosis, reduce proliferation and COX-2 levels, with the supposition that this may diminish cancer risk. However this role in decreasing cancer risk has not yet been evaluated. The use of NSAIDS and aspirin, most likely via inhibition of COX-2 and other inflammatory pathways, is associated with a reduction of adenocarcinoma rates. Both PPIs and NSAIDs/Aspirin may therefore be potential chemopreventative agents but further studies are required to appraise their use.
Raj
Anita
A
Digestive Diseases Centre, Leicester Royal Infirmary, Leicester, UK.
Jankowski
Janusz
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000473:pathology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D011230:Precancerous Conditions; D054328:Proton Pump Inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D001241:Aspirin