Drugs of Choice for Barrett's Esophagus

Barrett’s esophagus (BE) is a serious gastrointestinal condition in which acid reflux predisposes the esophagus to increased cell proliferation, decreased apoptosis, reactive oxygen species production, DNA damage, and proinflammatory and proproliferative cytokines.

BE is the focus of the June 2015 issue of Gastroenterology Clinics of North America, and one particular article is of great interest to pharmacists.

In this article, investigators from the University of Texas Southwestern Medical Center reviewed the use of proton pump inhibitors (PPIs) in BE.

Several professional organizations have published guidelines on PPI use in BE patients. Most recommend titrating the dose upward to the lowest effective measure that controls gastroesophageal reflux disease (GERD) symptoms and heals reflux esophagitis, acknowledging the required dose may be higher than what is normally used.

This review indicated clinicians should avoid routine esophageal pH testing to assess PPI acid suppression, and also veer away from routinely prescribing high-dose PPIs beyond what is needed to control GERD in BE patients.

During endoscopic ablative therapy, PPIs have been associated with better esophageal healing, and adequate acid suppression seems to improve ablative therapy’s outcomes. Although no randomized, controlled trials have confirmed that PPIs reduce the risk of neoplastic progression in BE, experts generally believe the drugs reduce the risk of esophageal cancer, based on indirect evidence.

PPIs appear to reduce reflux-induced abnormalities, such as the production of proinflammatory and proproliferative cytokines, since the drugs suppress acid and reduce inflammation. For this reason, the review authors suggested almost all BE patients should receive PPI therapy after careful counseling on the potential risks of long-term treatment.

Through their effect on serum gastrin levels, PPIs have been theorized to potentially increase cancer risk, the authors noted. In a negative feedback loop, gastrin release stimulates acid secretion, which inhibits further release of the growth hormone. PPIs interrupt this loop, increasing gastrin levels.

Gastrin can cause proliferation in Barrett’s metaplasia. Gastric acid suppression also allows more bacterial colonization in the stomach, and through a chain of reactions, it may increase the risk of cancer. Still, further research is needed to determine whether this theory is true.