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DOI: 10.1055/s-0034-1376115
The effect of combined long term Aspirin and proton pump inhibitor therapy on the histological progression of Barrett's metaplasia
Introduction: It is known that the increase of the COX-2 expression is an early step in the sequence of malignant transformations leading to Barrett's metaplasia and esophageal adenocarcinoma. Furthermore retrospective studies have shown a decreased incidence of esophageal adenocarcinoma in patients on aspirin (ASA) treatment.
Aims: We aimed to determine changes of COX-2 expression and the chemopreventive effect in patients with esophageal metaplasia under ASA + proton pump inhibitor (PPI) treatment compared to PPI treatment alone.
Patients & Methods: 105 patients were followed prospectively (M/F: 51/54, mean age: 58 years (26 – 80) for a mean period of 53 (13 – 135) months. Patients were submitted to upper gastrointestinal endoscopy and biopsy on enrolment and later at every 3 – 6-12 months, depending on the histological stage of the disease. Treatment arms were PPI + ASA (40 mg pantoprazole b.i.d. + 300 mg acetyl-salicylic acid) or PPI alone (40 mg pantoprazole b.i.d.). The COX-2 activity was determined in the glandular mucosa by immunohistochemistry. The COX-2 staining intensity and the histological severity of dysplasia were scored between 0 and 3 by 2 independent histologists (adenocarcinoma had a score of 4). Primary endpoints were the change of COX-2 activity and the histological stage of the disease.
Results: The COX-2 activity did not change significantly in the glandular mucosa in the studied treatment groups. Delta of the dysplasia score was positive (histological progression) in the group of PPI treatment alone, in the same time PPI+ASA group had a negative value (histological regression). In the patients with intestinal metaplasia this results are close to significance after about 5 years of follow-up. (p = 0.06)
Conclusion: The administration of ASA had a limited effect on mucosal COX-2 activity in patients with esophageal metaplasia at the applied dose. Based on current data, ASA can have a chemopreventive effect after a long-term treatment. Correlating with previous studies our results show that more than 5 years long ASA treatment is needed to have significant chemopreventive effect on Barrett's dysplasia.
Perspectives: Longer attentive follow-up is needed to verify long-term chemopreventive effects of ASA in Barrett's metaplasia.