Reply.

Abstract

There is substantial evidence that acidity plays a major role in the pathophysiology of marginal ulceration in Roux-en-Y gastric bypass (RYGB), with the mainstay of treatment being proton pump inhibitors (PPIs). PPI capsules are designed to break down in the stomach. Patients with gastric bypass only have a small gastric pouch and rapid small-bowel transit, limiting the opportunity for capsular breakdown and medication absorption. Some capsules may even make their way to the colon before breakdown occurs. As such, we believe that these factors may lead to variable treatment effects, which may be overcome by use of a soluble form of PPI. In our recent publication,1Schulman A.R. et al.Clin Gastroenterol Hepatol. 2017; 15: 494-500.e1Abstract Full Text Full Text PDF Scopus (27) Google Scholar we compared time to healing of marginal ulceration in RYGB patients receiving PPIs in a soluble or intact capsule form. We found shorter ulcer healing times in patients taking soluble forms of this medication, as compared with patients who were taking standard intact capsules. Furthermore, when controlling for the use of sucralfate and risk factors that are known to lead to the development of marginal ulceration including nonsteroidal anti-inflammatory drug (NSAID) use, diabetes, presence of fistula, foreign material (suture/staple), smoking, and Helicobacter pylori infection, taking PPI capsules in a soluble form was the only independent predictor of time to ulcer healing. One of the major criticisms from the reviewer was in regard to differences between groups in comparing use of NSAIDs and sucralfate. We would like to point out that the difference in NSAID use between groups was not statistically significant (P > .05). In addition, in the final multivariable regression model, NSAID use was not an independent predictor of time to ulcer healing. There were differences in sucralfate use between the groups, however, the administration of sucralfate also was not an independent predictor of time to ulcer healing in the final multivariable model when controlling for other covariates. Furthermore, we ran subgroup analyses on patients receiving soluble-form vs intact PPI capsules, and excluded all patients who were receiving simultaneous sucralfate therapy. These analyses yielded the same results, further confirming our findings. In addition, these results are consistent with many previous studies showing a lack of definitive benefit to this medication. Regarding PPI formulations, because the study design was retrospective it had to account for several PPI dosages and methods of delivery. All patients were categorized as taking PPIs in a soluble or standard form. For the vast majority of patients, this was as open or closed capsules, with patients in the open-capsule group having been instructed to open capsules and place the contents (granules) into applesauce before ingesting. In general, we avoid putting contents into liquids for administration because the granules adhere to the bottom of the container, potentially affecting the dose. In addition, applesauce is preferred at our institution based on patient feedback, with this formulation being the most palatable. The small number of patients who were prescribed pantoprazole were in the intact-capsule group because this is prescribed only in tablet or intravenous form. In addition, lansoprazole has a dissolvable sublingual form that was used in a minority of patients. These patients were included in the soluble group. Group assignment was rigorous with the intent of comparing patients on more soluble PPIs with traditional administration. Furthermore, subgroup analyses were performed and showed that dose of PPI (ie, 1 dose 2 times per day, or 2 doses 2 times per day) did not predict time to healing of marginal ulceration in either group. We agree that a commercially available preparation of non–enteric-coated omeprazole powder in NaHCO3 might be the most appropriate PPI formulation for patients with RYGB anatomy, especially in light of the fact that absorption of omeprazole from that product is more rapid than from omeprazole granules.2Tansel A. et al.Clin Gastroenterol Hepatol. 2017; 15: 501-503Abstract Full Text Full Text PDF Scopus (7) Google Scholar Nevertheless, sublingual lansoprazole may be equally effective. Regardless, we believe that soluble forms of PPI administration result in better absorption and likely are responsible for the improved time to ulcer resolution shown in our study. Questions regarding optimal PPI formulation would best be addressed in a randomized controlled setting. Open vs Intact Proton Pump Inhibitor Capsules for Treatment of Marginal UlcersClinical Gastroenterology and HepatologyVol. 15Issue 9PreviewIn their recent publication, Schulman et al1 reported that patients with marginal ulcers following Roux-en-Y gastric bypass (RYGB) who were treated with opened proton pump inhibitor (PPI) capsules had faster ulcer healing than those who received intact PPI capsules. Their study was conducted retrospectively and the decision of how patients should take their PPI was at the discretion of individual physicians. Full-Text PDF