The effects of esomeprazole combined with aspirin or rofecoxib on prostaglandin E₂ production in patients with Barrett's oesophagus

Abstract

Summary Background Reducing mucosal cyclo‐oxygenase‐2 and prostaglandin E2 production and suppressing intraoesophageal acid may be effective chemopreventive strategies in patients with Barrett's oesophagus. Aim To compare the effects of aspirin and rofecoxib when administered with esomeprazole on prostaglandin E2 production, cyclo‐oxygenase‐2 expression and proliferating cell nuclear antigen expression in patients with Barrett's oesophagus. Methods This exploratory, multicentre, randomized, open‐label, four‐way crossover study in 45 patients with Barrett's oesophagus evaluated prostaglandin E2 content, proliferating cell nuclear antigen expression, and cyclo‐oxygenase‐2 expression after 10 days of sequential treatments with: esomeprazole 40 mg twice daily plus aspirin 325 mg once daily (E40 b.d. + A325); E40 b.d. plus rofecoxib 25 mg once daily (E40 b.d. + R25); E40 b.d.; and rofecoxib 25 mg once daily (R25). Results Prostaglandin E2 content reduction in Barrett's oesophagus tissue was significantly greater with E40 b.d. + A325 compared with E40 b.d. + R25, E40 b.d. or R25 (P < 0.05). All treatments containing E40 b.d. significantly decreased proliferating cell nuclear antigen expression from baseline (P < 0.05). None of the treatments significantly reduced cyclo‐oxygenase‐2 expression. Conclusions The combined treatment of esomeprazole 40 mg b.d. and aspirin 325 mg significantly decreased mucosal prostaglandin E2 content and all treatments containing esomeprazole significantly reduced proliferating cell nuclear antigen expression in patients with Barrett's oesophagus.

Impact of Acid Inhibition on Esophageal Mucosal Injury Induced by Low-Dose Aspirin

“…On the other hand, gastric prostaglandins (PGs) have important roles to protect the damage of gastric mucosa from gastric acid. The esophageal PGE 2 level, one of the main PGs, was also reported to significantly decrease by dosing of aspirin [33,34]. We speculate that low-dose entero-coated type aspirin makes the esophageal mucosa vulnerable with decreases in esophageal PG levels and that the exposure of refluxed gastric contents and gastric acid to esophageal mucosa will easily break up the barrier of the esophageal mucosa, as observed in gastric mucosa.…”

Cyclooxygenase-2 and Inflammation Mediators Have a Crucial Role in Reflux-Related Esophageal Histological Changes and Barrett’s Esophagus

“…On one hand, 10-day therapy with specific COX-2 inhibitors reduced COX-2 expression, PGE 2 release and cell proliferation [26]; on the other hand, no differences in the progression of BE dysplasia to cancer seems to be produced by 48-week treatment with celecoxib [27].…”

Esophageal COX-2 Expression Is Increased in Barrett’s Esophagus, Obesity, and Smoking

“…Previous studies reported conflicting results on the use of selective COX-2 inhibitors for EA chemoprevention in BE patients. A multicenter, randomized study of 45 participants demonstrated that 10 days of therapy with selective COX-2 inhibitors reduced COX-2 expression and cell proliferation in BE patients [30]. On the other hand, the chemoprevention of Barrett's Esophagus Trial, a multi-center, randomized placebo-controlled trial of 222 participants, revealed no differences in the progression of BE, low-grade dysplasia, and high-grade dysplasia to EA with treatment of 48 weeks with celecoxib, a selective COX-2 inhibitor, compared with placebo [31].…”