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Background Barrett's oesophagus is regarded as the most important risk factor for development of oesophageal adenocarcinoma. According to current guidelines, treatment should be limited to symptomatic Barrett's oesophagus. Aim To evaluate the expression of Ki67, cyclooxygenase-2 (COX-2) and apoptosis in Barrett's oesophagus after 12 months of double-dose proton pump inhibitor therapy. The effectiveness of esomeprazole and pantoprazole was also compared. Methods Seventy-seven nondysplastic Barrett's oesophagus patients underwent baseline upper endoscopy. Patients were then randomised into two groups: one group was allocated to receive esomeprazole 40 mg b.d. and the other group pantoprazole 40 mg b.d. for 12 months. A follow-up endoscopy was performed at the end of treatment. Sixty-five of 77 patients agreed to undergo oesophageal manometry and 24-h pH-metry. Barrett's oesophagus biopsies, obtained at baseline and after treatment, were analysed using immunohistochemistry to assess Ki67 and COX-2 expression; apoptosis was evaluated using TUNEL. Results In the esomeprazole group, a significant decrease in Ki67 and COX-2 expression, as well as an increase in apoptosis, were observed (P < 0.05). By contrast, in the pantoprazole group Ki67, COX-2 and apoptosis did not vary significantly from baseline. By 24-h oesophageal pH-monitoring, a normal acid exposure time was recorded in patients treated with esomeprazole, while those allocated to pantoprazole displayed abnormal acid exposure (P < 0.05). Conclusions Treatment of Barrett's oesophagus patients with high-dose esomeprazole, but not pantoprazole, promoted a decrease in proliferative markers, concomitantly with a decrease in apoptotic cell death. Moreover, esomeprazole allowed a better oesophageal acid control than pantoprazole. [ABSTRACT FROM AUTHOR]