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PPI metabolism may be altered in about one-third of bariatric surgery candidates



– Rapid proton pump inhibitor (PPI) metabolism was present in nearly one-third of patients who underwent bariatric surgery, results from a small, single-center study showed. Patients who were fast metabolizers also exhibited a higher, although not significant, incidence of early marginal ulceration following Roux-en-Y gastric bypass.

Dr. Sabrena F. Noria

“Roux-en-Y gastric bypass [RYGB] is one of the most effective surgical approaches to mitigating obesity and its attendant comorbidities including diabetes, hypertension, hyperlipidemia, reflux, and sleep apnea,” lead study author Sabrena F. Noria, MD, PhD, said in an interview at the annual Digestive Disease Week. “However, as with all surgeries, there are associated risks, the more common of which is marginal ulceration, or ulcer formation at the gastrojejunostomy, which occurs at a rate of 1%-16%.”

Dr. Noria, surgical research director of the comprehensive weight management, metabolic/bariatric surgery program at the Ohio State University’s Wexner Medical Center, noted that marginal ulcers (MUs) are divided into early (within 90 days) and late (more than 90 days), based on their time of onset after surgery, and are usually diagnosed during upper endoscopy on postoperative patients who complain of epigastric pain, dysphagia, nausea/vomiting, and/or dehydration.

“Given that MUs are associated with multiple hospital readmissions for pain and dehydration, multiple diagnostic and therapeutic endoscopic procedures, and escalation in both antiulcer and analgesic medication, their clinical impact cannot be overstated, especially since RYGB is the second most commonly performed bariatric procedure in the U.S.,” she said. “Given that the majority of marginal ulcers occur early after surgery, bariatric surgery programs have adopted the prophylactic use of proton pump inhibitors for up to 90 days postoperatively. While studies have demonstrated up to a two-fold decrease in ulcer formation, sample heterogeneity, in terms of combining both early and late ulcers, make it difficult to determine the effect on early ulcer formation.”

In an effort to compare preoperative endoscopic findings and MU formation in patients with and without altered PPI metabolism, the researchers prospectively enrolled 94 bariatric patients to undergo genetic testing pertinent to drug metabolism for a comprehensive panel of medications using a commercially available pharmacogenetic testing kit for the activity of cytochrome P450 in drug metabolism. They grouped patients by whether they were fast or normal metabolizers, and compared preoperative endoscopic findings for patients on PPIs at baseline and rates of early (within 90 days) and late ulceration (between 90 and 180 days).

Dr. Noria reported that 28 patients (30%) in the entire cohort met criteria for being fast metabolizers. The researchers observed no differences in baseline body mass index, age, gender, or former smoking status between both groups. Among those treated with a PPI at baseline, fast metabolizers demonstrated a trend toward a higher incidence of gastritis on preoperative endoscopy, compared with controls (89% vs. 65%, respectively; P = .12), while detection of Helicobacter pylori and Barrett’s esophagus were nonsignificant between groups. Eight patients (17%) who underwent RYGB developed marginal ulcers within 6 months of the index operation, of which four (50%) were diagnosed within 90 days and categorized as early ulcers. Development of early ulceration was higher among fast metabolizers, compared with controls (13% vs. 6%), but this did not reach statistical significance (P = .60). All late ulcerations occurred within the control group.

“While none of our findings are statistically significant given the small sample size, there were two findings I found clinically compelling,” Dr. Noria said. “First, in the group of patients who were on PPIs preoperatively, we found a 24% increase in the presence of pathologically diagnosed gastritis in the rapid-metabolizer group, during screening endoscopy. This suggests that either these patients were undertreated or were not treated with the appropriate medication. The second interesting finding was an over doubling of early ulcer formation in the RYGB group who were rapid metabolizers. However, again I would caution against drawing any real conclusions as our sample size was not powered to detect any difference.”

She also acknowledged that the study was limited by the inability to determine the effect of confounders such as surgical approach and the lack of randomization.

Anahita D. Jalilvand, MD, a general surgery resident, postdoctoral research fellow, and PhD candidate, was instrumental to this study, Dr. Noria said.

The trial was sponsored by Pathnostics, a pharmacogenetic testing company, who covered the cost of the tests. The researchers reported having no financial disclosures.

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