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New Insight Into an Effective Treatment of Marginal Ulceration After Roux-en-Y Gastric Bypass
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EDITORIAL New Insight Into an Effective Treatment of Marginal Ulceration After Roux-en-Y Gastric Bypass he endoscopy service at the Brigham and Woman’s Hospital has extensive experience with complications of gastric bypass surgery.1 Marginal ulceration is one of the most common complications of Roux-en-Y gastric bypass.2,3 In their practice, all patients with marginal ulcers receive proton pump inhibitor (PPI) therapy, and endoscopy is repeated every 3 months until ulcer healing is confirmed.1 Some of their clinicians directed patients to open the PPI capsules; others prescribed intact PPIs. The median time for ulcer healing was 3 months in those receiving PPIs emptied from capsules compared with approximately 11 months in those receiving intact capsules. This observation is consistent with the notion that limited absorptive surface and residence time in the absorptive area limited the bioavailability of encapsulated PPIs.
T
Marginal Ulceration After Gastric Bypass Limited natural history data regarding post–gastric bypass are available because most centers restrict endoscopy to those with symptoms or complications. Natural history data come from prospective studies by Csendes at al,4 who performed endoscopy at 1 month after surgery in 441 post-bypass patients. In 71% of patients, endoscopy was routinely repeated a mean of 17 months after surgery. At 1 month, 5.6% of patients had marginal ulcers (4.1% of those with laparotomy and 12.3% with laparoscopic bypass). Seven ulcer patients (28%) were asymptomatic. At 17 months, 2 patients developed marginal ulcers including one without an early marginal ulcer (0.3%) and one with an early ulcer (4%). A subsequent follow-up of 550 patients included a questionnaire and upper endoscopy done between 1 and 8 years after surgery (mean, 40.5 months). They found 6 patients with marginal ulcers (1%).5 All healed with PPI therapy at a mean of 7 months; there was no placebo comparator.
Gastric Bypass Gastric bypass was originally investigated as a means of treating peptic ulcer disease.6,7 The operation eliminates the gastrin-related gastric phase of acid secretion because food bypasses the antrum. The empty stomach remains acidic, which caused permanent acidmediated downregulation of acid secretion, with the small amount of acid produced entering the duodenum.
Although gastric bypass was not a successful anti-ulcer operation, it proved effective for treatment of morbid obesity, and bariatric surgery has become one of the most common operations worldwide. Most marginal ulcers occur within 1 year of surgery. Ulcers that develop soon after surgery have many causes including acid-related as well as related to technical issues such as number of staples, type of suture, presence of tissue traction, or ischemia. Most of the technical difficulties related to pouch size, details of hand-sewn vs stapled anastomoses, and placement of the loop retrocolic or anti-colic have largely been resolved.8–11 Besides acid from the gastric pouch, dehiscence of the anastomosis between the stomach allows entry of gastric acid causing ulceration that frequently required surgical repair. This problem has become rare because of changes in technique including resection of the remaining stomach. Attempts at preventing ulcers in the early postoperative period by administration of histamine 2-receptor antagonists given as liquids or PPIs even as crushed omeprazole tablets likely reduced the incidence of ulcers but were unable to entirely prevent their development.12,13 Even today, many surgeons use antisecretory drugs often with sucralfate in the immediate perioperative period.2 Numerous studies have attempted to define patient characteristics associated with an increased marginal ulcer risk (eg, hypertensive, diabetic, Helicobacter pylori infection, use of ulcerogenic medications, smoking, and past peptic ulcer). Most seem less important than acid secretion, and even when acid secretion is not the critical variable, ulcer healing is enhanced by reducing acid secretion (eg, no acid, no ulcer).
The Gastric Pouch and Acid Secretion The modern gastric pouch is small (ie, typically between 5 and 6 cm in length) with a restricted outlet. After pouch creation, the mucosa remains normal where parietal cells are plentiful and the pouch does not dilate.14,15 Because the pouch contains a small amount of gastric corpus, the total amount of acid secreted is small.16,17 However, because parietal cells secrete approximately 150 mmol/L HCl (pH, w0.8), the intrapouch pH is generally low.7,18,19 The pouch is vagally innervated; any stimulus to acid secretion is largely restricted to the vagus.7 To our knowledge, the effects of vagal stimulation on pouch secretion have not been formally examined. Vagotomy was widely done during the era of surgical treatment of ulcer disease but has been discouraged in gastric bypass.20 Pouch-selective vagotomy is apparently not possible or has not been attempted. At least 1 attempt at transthoracic vagotomy has been reported, but local complications precluded further attempts.21 Clinical Gastroenterology and Hepatology 2017;-:-–-
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Clinical Gastroenterology and Hepatology Vol.
Antisecretory Therapy for Gastric Pouches PPIs require an acidic compartment in the parietal cell to become activated (ie, only activated parietal cells can be inhibited).22 Traditionally, PPIs are given before meals to allow meal-stimulated gastrin release to activate parietal cells that are then irreversibly inhibited. Full PPI effect takes 3 or more days because not all proton pumps available are inserted into the membrane after meals.22 As noted, gastric bypass prevents mealstimulated activation of parietal cells. Alert clinicians at Brigham and Woman’s Hospital thought that breaking the PPI capsules open would likely increase the bioavailability of PPIs. The barriers to bioavailability include capsule dissolution and release of the entericcoated granules of PPI, which must then dissolve, and all of this must occur within the short length of intestine available. However, improved absorptivity does not solve the need to activate parietal cells during the short time the PPI is in the plasma.
How To Best Deliver and Access Antisecretory Drug Therapy? The effectiveness of increasing PPI bioavailability could be assessed by measuring plasma PPI levels (absorption) or by assessing reduction in acid secretion directly or indirectly such as by changes in intrapouch pH. There is a considerable and detailed literature on the preparations of PPIs including granule dissolution for related conditions.23,24 We believe the easiest approach would be to administer non–enteric-coated PPI power with sodium bicarbonate, which is rapidly absorbed and available commercially with 20 or 40 mg omeprazole. Because antral exclusion makes it difficult to activate parietal cells and the plasma half-life of a PPI is very short, it would seem likely that 2 or 3 times a day dosing, possibly of smaller amounts, would be most effective.25 The best approach to assess effectiveness would likely be to compare the time the intrapouch pH remained greater than 4 after about 5–7 days of PPI therapy. When it becomes available, vonoprazan is likely to be superior to traditional PPIs in that activation of the parietal cell is not needed. Histamine 2-receptor antagonists are another option, although they are less effective in maintaining the intragastric pH above 4.
Summary The clinicians at Brigham and Woman’s Hospital are to be congratulated for showing that it is possible to reduce the healing time of post Roux-en-Y gastric-associated marginal ulcers. Many questions remain to be answered to understand and optimize the use of
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175 176 177 AYLIN TANSEL, MD Q6 178 179 Department of Medicine 180 Michael E. DeBakey VA Medical Center and 181 Baylor College of Medicine 182 Houston, Texas 183 184 DAVID Y. GRAHAM, MD 185 Department of Medicine 186 Michael E. DeBakey VA Medical Center and 187 Baylor College of Medicine 188 Houston, Texas 189 190 References 191 1. Schulman AR, Chan W, Devery A, et al. Opened proton pump 192 inhibitor capsules reduce time to healing compared to intact 193 capsules for marginal ulceration following Roux-en-Y gastric Q4 194 bypass. Clin Gastroenterol Hepatol (in press). 195 2. Steinemann DC, Bueter M, Schiesser M, et al. Management of 196 anastomotic ulcers after Roux-en-Y gastric bypass: results of an 197 international survey. Obes Surg 2014;24:741–746. 198 3. Sverden E, Mattsson F, Sonden A, et al. Risk factors for marginal ulcer after gastric bypass surgery for obesity: a population199 based cohort study. Ann Surg 2016;263:733–737. 200 4. Csendes A, Burgos AM, Altuve J, et al. Incidence of marginal 201 ulcer 1 month and 1 to 2 years after gastric bypass: a pro202 spective consecutive endoscopic evaluation of 442 patients 203 with morbid obesity. Obes Surg 2009;19:135–138. 204 5. Csendes A, Torres J, Burgos AM. Late marginal ulcers after 205 gastric bypass for morbid obesity: clinical and endoscopic 206 findings and response to treatment. Obes Surg 2011; 207 21:1319–1322. 208 6. Mason EE. Ulcerogenesis in surgery for obesity. Obes Surg 209 1996;6:180–181. 210 7. Mason EE, Munns JR, Kealey GP, et al. Effect of gastric bypass 211 on gastric secretion. Am J Surg 1976;131:162–168. 212 8. Pope GD, Goodney PP, Burchard KW, et al. Peptic ulcer/stric213 ture after gastric bypass: a comparison of technique and acid 214 suppression variables. Obes Surg 2002;12:30–33. 215 9. Bhayani NH, Oyetunji TA, Chang DC, et al. Predictors of marginal ulcers after laparoscopic Roux-en-Y gastric bypass. J Surg 216 Res 2012;177:224–227. 217 10. Edholm D, Ottosson J, Sundbom M. Importance of pouch size in 218 laparoscopic Roux-en-Y gastric bypass: a cohort study of 14, 219 168 patients. Surg Endosc 2016;30:2011–2015. 220 11. Jiang HP, Lin LL, Jiang X, et al. Meta-analysis of hand-sewn 221 versus mechanical gastrojejunal anastomosis during laparo222 scopic Roux-en-Y gastric bypass for morbid obesity. Int J Surg 223 2016;32:150–157. 224 12. D’Hondt MA, Pottel H, Devriendt D, et al. Can a short course of 225 prophylactic low-dose proton pump inhibitor therapy prevent 226 stomal ulceration after laparoscopic Roux-en-Y gastric bypass? 227 Obes Surg 2010;20:595–599. 228 13. Plaeke P, Ruppert M, Hubens G. Benefits of prophylactic proton 229 pump inhibitors after Roux-en-Y gastric bypass surgery: a 230 retrospective study. Acta Chir Belg 2015;115:273–278. 231 14. Csendes A, Smok G, Burgos AM, et al. Prospective sequential endoscopic and histologic studies of the gastric pouch in 232 PPIs for marginal ulcers. These studies should be easy to perform, and we anticipate rapid further progress.
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2017
Editorial
3
130 morbidly obese patients submitted to Roux-en-Y gastric bypass. Arq Bras Cir Dig 2012;25:245–249.
22. Hunt RH. Importance of pH control in the management of GERD. Arch Intern Med 1999;159:649–657.
15. Siilin H, Wanders A, Gustavsson S, et al. The proximal gastric pouch invariably contains acid-producing parietal cells in Rouxen-Y gastric bypass. Obes Surg 2005;15:771–777.
23. Pilbrant A. Formulation of proton pump inhibitors: current status on targeted drug delivery to the gastrointestinal tract. Capsugel Library 1993;35–42. Available at, http://www.capsugel.com/ media/library/formulation-of-proton-pump-inhibitors.pdf.
16. Smith CD, Herkes SB, Behrns KE, et al. Gastric acid secretion and vitamin B12 absorption after vertical Roux-en-Y gastric bypass for morbid obesity. Ann Surg 1993;218:91–96. 17. Behrns KE, Smith CD, Sarr MG. Prospective evaluation of gastric acid secretion and cobalamin absorption following gastric bypass for clinically severe obesity. Dig Dis Sci 1994; 39:315–320. 18. Hedberg J, Hedenstrom H, Nilsson S, et al. Role of gastric acid in stomal ulcer after gastric bypass. Obes Surg 2005; 15:1375–1378. 19. Herbella FA, Vicentine FP, Del Grande JC, et al. Postprandial proximal gastric acid pocket in patients after Roux-en-Y gastric bypass. J Gastrointest Surg 2010;14:1742–1745. 20. Sapala JA, Wood MH, Schuhknecht MP. Vagotomy at the time of gastric bypass: can it be harmful? Obes Surg 2004;14:575–576. 21. Hunter J, Stahl RD, Kakade M, et al. Effectiveness of thoracoscopic truncal vagotomy in the treatment of marginal ulcers after laparoscopic Roux-en-Y gastric bypass. Am Surg 2012; 78:663–668.
24. Wensel TM. Administration of proton pump inhibitors in patients Q5 requiring enteral nutrition. P T 2009;34:143–160. 25. Blum RA, Hunt RH, Kidd SL, et al. Dose-response relationship of lansoprazole to gastric acid antisecretory effects. Aliment Pharmacol Ther 1998;12:321–327.
Conflicts of interest Dr Graham is a paid consultant for RedHill Biopharma regarding novel H pylori therapies and for BioGaia regarding use of probiotics for H pylori infections. Dr Tansel discloses no conflicts. Funding Dr Graham is supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service grant DK56338, which funds the Texas Medical Center Digestive Diseases Center. Dr Tansel is supported by the Public Health Service grant T32 DK083266-07. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the VA or NIH. http://dx.doi.org/10.1016/j.cgh.2016.12.025
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EDITORIAL New Insight Into an Effective Treatment of Marginal Ulceration After Roux-en-Y Gastric Bypass he endoscopy service at the Brigham and Woman’s Hospital has extensive experience with complications of gastric bypass surgery.1 Marginal ulceration is one of the most common complications of Roux-en-Y gastric bypass.2,3 In their practice, all patients with marginal ulcers receive proton pump inhibitor (PPI) therapy, and endoscopy is repeated every 3 months until ulcer healing is confirmed.1 Some of their clinicians directed patients to open the PPI capsules; others prescribed intact PPIs. The median time for ulcer healing was 3 months in those receiving PPIs emptied from capsules compared with approximately 11 months in those receiving intact capsules. This observation is consistent with the notion that limited absorptive surface and residence time in the absorptive area limited the bioavailability of encapsulated PPIs.
T
Marginal Ulceration After Gastric Bypass Limited natural history data regarding post–gastric bypass are available because most centers restrict endoscopy to those with symptoms or complications. Natural history data come from prospective studies by Csendes at al,4 who performed endoscopy at 1 month after surgery in 441 post-bypass patients. In 71% of patients, endoscopy was routinely repeated a mean of 17 months after surgery. At 1 month, 5.6% of patients had marginal ulcers (4.1% of those with laparotomy and 12.3% with laparoscopic bypass). Seven ulcer patients (28%) were asymptomatic. At 17 months, 2 patients developed marginal ulcers including one without an early marginal ulcer (0.3%) and one with an early ulcer (4%). A subsequent follow-up of 550 patients included a questionnaire and upper endoscopy done between 1 and 8 years after surgery (mean, 40.5 months). They found 6 patients with marginal ulcers (1%).5 All healed with PPI therapy at a mean of 7 months; there was no placebo comparator.
Gastric Bypass Gastric bypass was originally investigated as a means of treating peptic ulcer disease.6,7 The operation eliminates the gastrin-related gastric phase of acid secretion because food bypasses the antrum. The empty stomach remains acidic, which caused permanent acidmediated downregulation of acid secretion, with the small amount of acid produced entering the duodenum.
Although gastric bypass was not a successful anti-ulcer operation, it proved effective for treatment of morbid obesity, and bariatric surgery has become one of the most common operations worldwide. Most marginal ulcers occur within 1 year of surgery. Ulcers that develop soon after surgery have many causes including acid-related as well as related to technical issues such as number of staples, type of suture, presence of tissue traction, or ischemia. Most of the technical difficulties related to pouch size, details of hand-sewn vs stapled anastomoses, and placement of the loop retrocolic or anti-colic have largely been resolved.8–11 Besides acid from the gastric pouch, dehiscence of the anastomosis between the stomach allows entry of gastric acid causing ulceration that frequently required surgical repair. This problem has become rare because of changes in technique including resection of the remaining stomach. Attempts at preventing ulcers in the early postoperative period by administration of histamine 2-receptor antagonists given as liquids or PPIs even as crushed omeprazole tablets likely reduced the incidence of ulcers but were unable to entirely prevent their development.12,13 Even today, many surgeons use antisecretory drugs often with sucralfate in the immediate perioperative period.2 Numerous studies have attempted to define patient characteristics associated with an increased marginal ulcer risk (eg, hypertensive, diabetic, Helicobacter pylori infection, use of ulcerogenic medications, smoking, and past peptic ulcer). Most seem less important than acid secretion, and even when acid secretion is not the critical variable, ulcer healing is enhanced by reducing acid secretion (eg, no acid, no ulcer).
The Gastric Pouch and Acid Secretion The modern gastric pouch is small (ie, typically between 5 and 6 cm in length) with a restricted outlet. After pouch creation, the mucosa remains normal where parietal cells are plentiful and the pouch does not dilate.14,15 Because the pouch contains a small amount of gastric corpus, the total amount of acid secreted is small.16,17 However, because parietal cells secrete approximately 150 mmol/L HCl (pH, w0.8), the intrapouch pH is generally low.7,18,19 The pouch is vagally innervated; any stimulus to acid secretion is largely restricted to the vagus.7 To our knowledge, the effects of vagal stimulation on pouch secretion have not been formally examined. Vagotomy was widely done during the era of surgical treatment of ulcer disease but has been discouraged in gastric bypass.20 Pouch-selective vagotomy is apparently not possible or has not been attempted. At least 1 attempt at transthoracic vagotomy has been reported, but local complications precluded further attempts.21 Clinical Gastroenterology and Hepatology 2017;-:-–-
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Tansel and Graham
Clinical Gastroenterology and Hepatology Vol.
Antisecretory Therapy for Gastric Pouches PPIs require an acidic compartment in the parietal cell to become activated (ie, only activated parietal cells can be inhibited).22 Traditionally, PPIs are given before meals to allow meal-stimulated gastrin release to activate parietal cells that are then irreversibly inhibited. Full PPI effect takes 3 or more days because not all proton pumps available are inserted into the membrane after meals.22 As noted, gastric bypass prevents mealstimulated activation of parietal cells. Alert clinicians at Brigham and Woman’s Hospital thought that breaking the PPI capsules open would likely increase the bioavailability of PPIs. The barriers to bioavailability include capsule dissolution and release of the entericcoated granules of PPI, which must then dissolve, and all of this must occur within the short length of intestine available. However, improved absorptivity does not solve the need to activate parietal cells during the short time the PPI is in the plasma.
How To Best Deliver and Access Antisecretory Drug Therapy? The effectiveness of increasing PPI bioavailability could be assessed by measuring plasma PPI levels (absorption) or by assessing reduction in acid secretion directly or indirectly such as by changes in intrapouch pH. There is a considerable and detailed literature on the preparations of PPIs including granule dissolution for related conditions.23,24 We believe the easiest approach would be to administer non–enteric-coated PPI power with sodium bicarbonate, which is rapidly absorbed and available commercially with 20 or 40 mg omeprazole. Because antral exclusion makes it difficult to activate parietal cells and the plasma half-life of a PPI is very short, it would seem likely that 2 or 3 times a day dosing, possibly of smaller amounts, would be most effective.25 The best approach to assess effectiveness would likely be to compare the time the intrapouch pH remained greater than 4 after about 5–7 days of PPI therapy. When it becomes available, vonoprazan is likely to be superior to traditional PPIs in that activation of the parietal cell is not needed. Histamine 2-receptor antagonists are another option, although they are less effective in maintaining the intragastric pH above 4.
Summary The clinicians at Brigham and Woman’s Hospital are to be congratulated for showing that it is possible to reduce the healing time of post Roux-en-Y gastric-associated marginal ulcers. Many questions remain to be answered to understand and optimize the use of
-,
No.
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175 176 177 AYLIN TANSEL, MD Q6 178 179 Department of Medicine 180 Michael E. DeBakey VA Medical Center and 181 Baylor College of Medicine 182 Houston, Texas 183 184 DAVID Y. GRAHAM, MD 185 Department of Medicine 186 Michael E. DeBakey VA Medical Center and 187 Baylor College of Medicine 188 Houston, Texas 189 190 References 191 1. Schulman AR, Chan W, Devery A, et al. Opened proton pump 192 inhibitor capsules reduce time to healing compared to intact 193 capsules for marginal ulceration following Roux-en-Y gastric Q4 194 bypass. Clin Gastroenterol Hepatol (in press). 195 2. Steinemann DC, Bueter M, Schiesser M, et al. Management of 196 anastomotic ulcers after Roux-en-Y gastric bypass: results of an 197 international survey. Obes Surg 2014;24:741–746. 198 3. Sverden E, Mattsson F, Sonden A, et al. Risk factors for marginal ulcer after gastric bypass surgery for obesity: a population199 based cohort study. Ann Surg 2016;263:733–737. 200 4. Csendes A, Burgos AM, Altuve J, et al. Incidence of marginal 201 ulcer 1 month and 1 to 2 years after gastric bypass: a pro202 spective consecutive endoscopic evaluation of 442 patients 203 with morbid obesity. Obes Surg 2009;19:135–138. 204 5. Csendes A, Torres J, Burgos AM. Late marginal ulcers after 205 gastric bypass for morbid obesity: clinical and endoscopic 206 findings and response to treatment. Obes Surg 2011; 207 21:1319–1322. 208 6. Mason EE. Ulcerogenesis in surgery for obesity. Obes Surg 209 1996;6:180–181. 210 7. Mason EE, Munns JR, Kealey GP, et al. Effect of gastric bypass 211 on gastric secretion. Am J Surg 1976;131:162–168. 212 8. Pope GD, Goodney PP, Burchard KW, et al. Peptic ulcer/stric213 ture after gastric bypass: a comparison of technique and acid 214 suppression variables. Obes Surg 2002;12:30–33. 215 9. Bhayani NH, Oyetunji TA, Chang DC, et al. Predictors of marginal ulcers after laparoscopic Roux-en-Y gastric bypass. J Surg 216 Res 2012;177:224–227. 217 10. Edholm D, Ottosson J, Sundbom M. Importance of pouch size in 218 laparoscopic Roux-en-Y gastric bypass: a cohort study of 14, 219 168 patients. Surg Endosc 2016;30:2011–2015. 220 11. Jiang HP, Lin LL, Jiang X, et al. Meta-analysis of hand-sewn 221 versus mechanical gastrojejunal anastomosis during laparo222 scopic Roux-en-Y gastric bypass for morbid obesity. Int J Surg 223 2016;32:150–157. 224 12. D’Hondt MA, Pottel H, Devriendt D, et al. Can a short course of 225 prophylactic low-dose proton pump inhibitor therapy prevent 226 stomal ulceration after laparoscopic Roux-en-Y gastric bypass? 227 Obes Surg 2010;20:595–599. 228 13. Plaeke P, Ruppert M, Hubens G. Benefits of prophylactic proton 229 pump inhibitors after Roux-en-Y gastric bypass surgery: a 230 retrospective study. Acta Chir Belg 2015;115:273–278. 231 14. Csendes A, Smok G, Burgos AM, et al. Prospective sequential endoscopic and histologic studies of the gastric pouch in 232 PPIs for marginal ulcers. These studies should be easy to perform, and we anticipate rapid further progress.
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2017
Editorial
3
130 morbidly obese patients submitted to Roux-en-Y gastric bypass. Arq Bras Cir Dig 2012;25:245–249.
22. Hunt RH. Importance of pH control in the management of GERD. Arch Intern Med 1999;159:649–657.
15. Siilin H, Wanders A, Gustavsson S, et al. The proximal gastric pouch invariably contains acid-producing parietal cells in Rouxen-Y gastric bypass. Obes Surg 2005;15:771–777.
23. Pilbrant A. Formulation of proton pump inhibitors: current status on targeted drug delivery to the gastrointestinal tract. Capsugel Library 1993;35–42. Available at, http://www.capsugel.com/ media/library/formulation-of-proton-pump-inhibitors.pdf.
16. Smith CD, Herkes SB, Behrns KE, et al. Gastric acid secretion and vitamin B12 absorption after vertical Roux-en-Y gastric bypass for morbid obesity. Ann Surg 1993;218:91–96. 17. Behrns KE, Smith CD, Sarr MG. Prospective evaluation of gastric acid secretion and cobalamin absorption following gastric bypass for clinically severe obesity. Dig Dis Sci 1994; 39:315–320. 18. Hedberg J, Hedenstrom H, Nilsson S, et al. Role of gastric acid in stomal ulcer after gastric bypass. Obes Surg 2005; 15:1375–1378. 19. Herbella FA, Vicentine FP, Del Grande JC, et al. Postprandial proximal gastric acid pocket in patients after Roux-en-Y gastric bypass. J Gastrointest Surg 2010;14:1742–1745. 20. Sapala JA, Wood MH, Schuhknecht MP. Vagotomy at the time of gastric bypass: can it be harmful? Obes Surg 2004;14:575–576. 21. Hunter J, Stahl RD, Kakade M, et al. Effectiveness of thoracoscopic truncal vagotomy in the treatment of marginal ulcers after laparoscopic Roux-en-Y gastric bypass. Am Surg 2012; 78:663–668.
24. Wensel TM. Administration of proton pump inhibitors in patients Q5 requiring enteral nutrition. P T 2009;34:143–160. 25. Blum RA, Hunt RH, Kidd SL, et al. Dose-response relationship of lansoprazole to gastric acid antisecretory effects. Aliment Pharmacol Ther 1998;12:321–327.
Conflicts of interest Dr Graham is a paid consultant for RedHill Biopharma regarding novel H pylori therapies and for BioGaia regarding use of probiotics for H pylori infections. Dr Tansel discloses no conflicts. Funding Dr Graham is supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service grant DK56338, which funds the Texas Medical Center Digestive Diseases Center. Dr Tansel is supported by the Public Health Service grant T32 DK083266-07. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the VA or NIH. http://dx.doi.org/10.1016/j.cgh.2016.12.025
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