Effects of long‐term cyclo‐oxygenase 2 selective and acid inhibition on Barrett’s oesophagus

Abstract

Summary Background There is an overexpression of cyclo‐oxygenase 2 (COX‐2) in Barrett’s oesophagus (BO). Aim To determine the long‐term effect of a COX‐2 inhibitor on cellular mechanisms involved in BO. Methods A randomized controlled trial was conducted in BO patients allocated to continue the usual proton pump inhibitor (PPI) alone treatment, or PPI combined with rofecoxib (25 mg/day) for 6 months. Cell proliferation index and COX‐2 expression in BO glands was determined in biopsy specimens at baseline and after treatment. Cell apoptosis, cyclin D1, p53 and vascular endothelial growth factor (VEGF) expression was also explored in a subset of patients. Student‐ t test and the U‐Mann–Whitney test were used for quantitative and ordinal variables. Results Of 62 patients, 58 completed the study. A higher proportion of patients on rofecoxib + PPI exhibited a decrease in COX‐2 expression compared to those treated with PPI alone, but cell proliferation index was not affected. Unlike PPI alone, rofecoxib + PPI was associated with an increase in the apoptotic cell index, a decrease in p53 cell staining and VEGF expression in mucosal vessels. No effect on low‐grade dysplasia or cyclin D1 was observed. Conclusions The addition of rofecoxib to PPI therapy does not affect cell proliferation index in BO cells after 6 months of therapy, but does reduce COX‐2 and VEGF expression and increases cell apoptosis.