Chronic Proton Pump Inhibitor Therapy Associated with Increased Development of Fundic Gland Polyps

  • Mazer R. Ally
  • Ganesh R. VeerappanEmail author
  • Corinne L. Maydonovitch
  • Timothy J. Duncan
  • Joseph L. Perry
  • Eric M. Osgard
  • Roy K. H. Wong
Original Article



Fundic gland polyps (FGP) have been implicated with long-term proton pump inhibitor (PPI) use.


We attempted to investigate the impact of length and dosage of PPI therapy on the development of FGP.


A retrospective cohort study of all patients who had gastric polyps removed during elective upper endoscopy between March and September 2007 as part of a prior prospective study protocol was carried out. FGP were determined histologically. Prior to endoscopy, all patients completed a questionnaire regarding PPI use and length of therapy (no PPI use, 1–48 months, >48 months). The dosage of PPI was obtained via a thorough chart review of electronic medical records.


Three hundred and eighty-five patients completed upper endoscopy and a questionnaire reporting PPI use (252 [65.4%] patients on PPI). On endoscopy, 55 patients had polyps, with the majority (43/55, 78%) being FGP, resulting in an overall prevalence of 11.1% (43/385). On univariate analysis, FGP were associated with Caucasian race (15 vs. 6%; P = 0.009) and chronic PPI therapy (>48 months) (31.9 vs. 7.5%, P < 0.001). There was a significant linear-by-linear association between PPI dosage and FGP prevalence (no PPI use, 7.5%; once daily, 10.8%; twice daily 17.4%, P = 0.026). On logistic regression, the only independent predictor of FGP was duration of PPI use >48 months (P = 0.001, odds ratio [OR] 4.7 [2.0–12.9]).


The only independent predictor of FGP development in our study was duration of PPI therapy greater than 48 months. Increased dosage of therapy did not significantly impact the development of FGP.


Proton pump inhibitor Fundic gland polyps Prevalence Risk factors Duration of the therapy 


  1. 1.
    Freeman HJ. Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis. World J Gastroenterol. 2008;14:1318–1320.CrossRefPubMedGoogle Scholar
  2. 2.
    Raghunath AS, O’Morain C, McLoughlin RC. Review article: the long-term use of proton-pump inhibitors. Aliment Pharmacol Ther. 2005;22(Suppl 1):55–63.CrossRefPubMedGoogle Scholar
  3. 3.
    Laheij RJ, Sturkenboom MC, Hassing RJ, Dieleman J, Stricker BH, Jansen JB. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004;292:1955–1960.CrossRefPubMedGoogle Scholar
  4. 4.
    Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947–2953.CrossRefPubMedGoogle Scholar
  5. 5.
    Dial S, Alrasadi K, Manoukian C, Huang A, Menzies D. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case–control studies. CMAJ. 2004;171:33–38.PubMedGoogle Scholar
  6. 6.
    Van Vlierberghe H, De Vos M, De Cock G, Cuvelier C, Elewaut A. Fundic gland polyps: three other case reports suggesting a possible association with acid suppressing therapy. Acta Gastroenterol Belg. 1997;60:240–242.PubMedGoogle Scholar
  7. 7.
    Graham JR. Gastric polyposis: onset during long-term therapy with omeprazole. Med J Aust. 1992;157:287–288.PubMedGoogle Scholar
  8. 8.
    el-Zimaity HM, Jackson FW, Graham DY. Fundic gland polyps developing during omeprazole therapy. Am J Gastroenterol. 1997;92:1858–1860.PubMedGoogle Scholar
  9. 9.
    Choudhry U, Boyce HW Jr, Coppola D. Proton pump inhibitor-associated gastric polyps: a retrospective analysis of their frequency, and endoscopic, histologic, and ultrastructural characteristics. Am J Clin Pathol. 1998;110:615–621.PubMedGoogle Scholar
  10. 10.
    Jalving M, Koornstra JJ, Wesseling J, Boezen HM, de Jong S, Kleibeuker JH. Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy. Aliment Pharmacol Ther. 2006;24:1341–1348.CrossRefPubMedGoogle Scholar
  11. 11.
    Burt RW. Gastric fundic gland polyps. Gastroenterology. 2003;125:1462–1469.CrossRefPubMedGoogle Scholar
  12. 12.
    Abraham SC, Nobukawa B, Giardiello FM, Hamilton SR, Wu TT. Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations. Am J Pathol. 2000;157:747–754.PubMedGoogle Scholar
  13. 13.
    Carmack SW, Genta RM, Schuler CM, Saboorian MH. The current spectrum of gastric polyps: a 1-year national study of over 120,000 patients. Am J Gastroenterol. 2009;104:1524–1532.CrossRefPubMedGoogle Scholar
  14. 14.
    Marcial MA, Villafaña M, Hernandez-Denton J, Colon-Pagan JR. Fundic gland polyps: prevalence and clinicopathologic features. Am J Gastroenterol. 1993;88:1711–1713.PubMedGoogle Scholar
  15. 15.
    Torbenson M, Lee JH, Cruz-Correa M, Ravich W, Rastgar K, Abraham SC, Wu TT. Sporadic fundic gland polyposis: a clinical, histological, and molecular analysis. Mod Pathol. 2002;15:718–723.CrossRefPubMedGoogle Scholar
  16. 16.
    Abraham SC, Nobukawa B, Giardiello FM, Hamilton SR, Wu TT. Sporadic fundic gland polyps: common gastric polyps arising through activating mutations in the beta-catenin gene. Am J Pathol. 2001;158:1005–1010.PubMedGoogle Scholar
  17. 17.
    Domizio P, Talbot IC, Spigelman AD, Williams CB, Phillips RK. Upper gastrointestinal pathology in familial adenomatous polyposis: results from a prospective study of 102 patients. J Clin Pathol. 1990;43:738–743.CrossRefPubMedGoogle Scholar
  18. 18.
    Goodman AJ, Dundas SA, Scholefield JH, Johnson BF. Gastric carcinoma and familial adenomatous polyposis (FAP). Int J Colorectal Dis. 1988;3:201–203.CrossRefPubMedGoogle Scholar
  19. 19.
    Jalving M, Koornstra JJ, Boersma-van Ek W, de Jong S, Karrenbeld A, Hollema H, de Vries EG, Kleibeuker JH. Dysplasia in fundic gland polyps is associated with nuclear beta-catenin expression and relatively high cell turnover rates. Scand J Gastroenterol. 2003;38:916–922.CrossRefPubMedGoogle Scholar
  20. 20.
    Stolte M, Vieth M, Ebert MP. High-grade dysplasia in sporadic fundic gland polyps: clinically relevant or not? Eur J Gastroenterol Hepatol. 2003;15:1153–1156.CrossRefPubMedGoogle Scholar
  21. 21.
    Vieth M, Stolte M. Fundic gland polyps are not induced by proton pump inhibitor therapy. Am J Clin Pathol. 2001;116:716–720.CrossRefPubMedGoogle Scholar
  22. 22.
    Fossmark R, Jianu CS, Martinsen TC, Qvigstad G, Syversen U, Waldum HL. Serum gastrin and chromogranin a levels in patients with fundic gland polyps caused by long-term proton-pump inhibition. Scand J Gastroenterol. 2008;43:20–24.CrossRefPubMedGoogle Scholar
  23. 23.
    Masaoka T, Suzuki H, Hibi T. Gastric epithelial cell modality and proton pump inhibitor. J Clin Biochem Nutr. 2008;42:191–196.CrossRefPubMedGoogle Scholar
  24. 24.
    Koh TJ, Chen D. Gastrin as a growth factor in the gastrointestinal tract. Regul Pept. 2000;93:37–44.CrossRefPubMedGoogle Scholar
  25. 25.
    Synnerstad I, Holm L. Omeprazole induces high intraglandular pressure in the rat gastric mucosa. Gastroenterology. 1997;112:1221–1230.CrossRefPubMedGoogle Scholar
  26. 26.
    Cats A, Schenk BE, Bloemena E, Roosedaal R, Lindeman J, Biemond I, Klinkenberg-Knol EC, Meuwissen SG, Kuipers EJ. Parietal cell protrusions and fundic gland cysts during omeprazole maintenance treatment. Hum Pathol. 2000;31:684–690.CrossRefPubMedGoogle Scholar
  27. 27.
    Krishnamurthy S, Dayal Y. Parietal cell protrusions in gastric ulcer disease. Hum Pathol. 1997;28:1126–1130.CrossRefPubMedGoogle Scholar
  28. 28.
    Watanabe N, Seno H, Nakajima T, Yazumi S, Miyamoto S, Matsumoto S, Itoh T, Kawanami C, Okazaki K, Chiba T. Regression of fundic gland polyps following acquisition of Helicobacter pylori. Gut. 2002;51:742–745.CrossRefPubMedGoogle Scholar
  29. 29.
    Iida M, Yao T, Watanabe H, Imamura K, Fuyuno S, Omae T. Spontaneous disappearance of fundic gland polyposis: report of three cases. Gastroenterology. 1980;79:725–728.PubMedGoogle Scholar
  30. 30.
    Sekine S, Shibata T, Yamauchi Y, Nakanishi Y, Shimoda T, Sakamoto M, Hirohashi S. Beta-catenin mutations in sporadic fundic gland polyps. Virchows Arch. 2002;440:381–386.CrossRefPubMedGoogle Scholar
  31. 31.
    Hofgärtner WT, Thorp M, Ramus MW, Delorefice G, Chey WY, Ryan CK, Takahashi GW, Lobitz JR. Gastric adenocarcinoma associated with fundic gland polyps in a patient with attenuated familial adenomatous polyposis. Am J Gastroenterol. 1999;94:2275–2281.PubMedGoogle Scholar
  32. 32.
    Graham DY, Genta RM. Long-term proton pump inhibitor use and gastrointestinal cancer. Curr Gastroenterol Rep. 2008;10:543–547.CrossRefPubMedGoogle Scholar
  33. 33.
    Attard TM, Yardley JH, Cuffari C. Gastric polyps in pediatrics: an 18-year hospital-based analysis. Am J Gastroenterol. 2002;97:298–301.CrossRefPubMedGoogle Scholar
  34. 34.
    Zwick A, Munir M, Ryan CK, Gian J, Burt RW, Leppert M, Spirio L, Chey WY. Gastric adenocarcinoma and dysplasia in fundic gland polyps of a patient with attenuated adenomatous polyposis coli. Gastroenterology. 1997;113:659–663.CrossRefPubMedGoogle Scholar
  35. 35.
    Abraham SC, Park SJ, Mugartegui L, Hamilton SR, Wu TT. Sporadic fundic gland polyps with epithelial dysplasia: evidence for preferential targeting for mutations in the adenomatous polyposis coli gene. Am J Pathol. 2002;161:1735–1742.PubMedGoogle Scholar
  36. 36.
    Jalving M, Koornstra JJ, Götz JM, van der Waaij LA, de Jong S, Zwart N, Karrenbeld A, Kleibeuker JH. High-grade dysplasia in sporadic fundic gland polyps: a case report and review of the literature. Eur J Gastroenterol Hepatol. 2003;15:1229–1233.CrossRefPubMedGoogle Scholar

Copyright information

© US Government 2009

Authors and Affiliations

  • Mazer R. Ally
    • 1
    • 2
  • Ganesh R. Veerappan
    • 1
    • 2
    Email author
  • Corinne L. Maydonovitch
    • 1
    • 2
  • Timothy J. Duncan
    • 1
    • 2
  • Joseph L. Perry
    • 1
    • 2
  • Eric M. Osgard
    • 1
    • 2
  • Roy K. H. Wong
    • 1
    • 2
  1. 1.Gastroenterology Service, Department of MedicineWalter Reed Army Medical CenterWashingtonUSA
  2. 2.Uniformed Services University of the Health ServicesBethesdaUSA

Personalised recommendations