Nonsteroidal antiinflammatory drugs and cyclooxygenase inhibition in the gastrointestinal tract: a trip from peptic ulcer to colon cancer.

Aspirin was commercialized more than a 100 years ago. Today, this compound is still widely prescribed, and new mechanisms of action and indications are being tested. Inhibition of cyclooxygenase (COX)-1 and COX-2 by aspirin or its related compounds, nonsteroidal antiinflammatory drugs (NSAIDs), has been associated with both adverse and beneficial effects in the gastrointestinal (GI) tract. Inhibition of COX-1 has been linked to GI adverse effects. Adverse effects of NSAIDs and aspirin in the upper GI tract include esophagitis, peptic ulcer, peptic ulcer complications, and death. Effective preventive therapies are available that have been associated with a progressive decline in the rate of hospitalization due to upper GI complications. NSAIDs and aspirin can also damage the small bowel and the colon. NSAID enteropathy is frequent and in most cases subclinical (increased mucosal permeability, inflammation, erosion, ulcer). However, more serious clinical outcomes such as anemia, bleeding, perforation, obstruction, diverticulitis, and deaths have also been described. Prevention therapy of NSAID damage to the lower GI tract is not well defined. Inhibition of COX-2 by NSAIDs, coxibs, or aspirin seems to provide beneficial effects to the GI tract. Observational studies show that these compounds reduce the risk of both upper and lower GI cancers. Randomized controlled trials have shown that aspirin and coxibs reduce the recurrence rate of colonic polyps, and long-term cohort studies have shown that aspirin reduces the risk of colon cancer time and dose dependently. New studies will have to define the appropriate population that may benefit with these therapies.