OBJECTIVES: The development of fundic gland polyps (FGPs) is the most common side effect of long-term proton pump inhibitor (PPI) use; however, the effect of drug use characteristics and their impact on the risk of other gastric polyp development remain unclear. We aimed to identify the influence of PPI administration, as well as its duration and dose, in the development of gastric polyps. METHODS: A prospective cohort study was conducted on consecutive patients who underwent gastroscopy between September 2017 and August 2019. Detailed characteristics of gastric polyps, Helicobacter pylori infection, and PPI use were analyzed. RESULTS: Among the 2723 patients included, gastric polyps (75% FGPs, 22% hyperplastic) were detected in 16.4%, and 60% were prescribed PPI. The risk of FGPs and hyperplastic polyps according to the duration of PPI use were as follows: 2-5 years [odds ratio (95% confidence interval); 2.86 (2.00-4.11) and 2.82 (1.69-4.78)]; 6-9 years [7.42 (5.03-11.01) and 2.32 (1.05-4.78)]; ≥10 years [14.94 (10.36-21.80) and 3.52 (1.67-7.03)]. Multivariate analysis confirmed that the risk of FGPs was 17.16 (11.35-26.23) for ≥10 years of PPI use. Portal hypertension-related conditions were associated with hyperplastic polyps [4.99 (2.71-9.20)]. CONCLUSION: Duration of and indications for PPI use are the most predictive factors for the development of gastric polyps. Prolonged PPI use increases the risk of polyp development and the number of patients with polyps, which may burden endoscopic practice. Highly selected patients may require particular care despite minimal risk of dysplasia and bleeding generally.

Department of Internal Medicine and Gastroenterology University Hospital Brno

Department of Pathology University Hospital Brno Faculty of Medicine Masaryk University Brno Czech Republic

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno

Institute of Health Information and Statistics of the Czech Republic Prague

Zobrazit více v PubMed

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.

Zelter A, Fernández JL, Bilder C, Rodríguez P, Wonaga A, Dorado F, et al. Fundic gland polyps and association with proton pump inhibitor intake: a prospective study in 1,780 endoscopies. Dig Dis Sci 2011; 56:1743–1748.

Csontos AA, Fekete B, Lőrinczy K, Terjék O, Berczi L, Juhász M, et al. Prevalence of gastric polypoid lesions at an endoscopic facility. Orv Hetil 2013; 154:770–774.

Yacoub H, Bibani N, Sabbah M, Bellil N, Ouakaa A, Trad D, et al. Gastric polyps: a 10-year analysis of 18,496 upper endoscopies. BMC Gastroenterol 2022; 22:70.

Elhanafi S, Saadi M, Lou W, Mallawaarachchi I, Dwivedi A, Zuckerman M, et al. Gastric polyps: association with Helicobacter pylori status and the pathology of the surrounding mucosa, a cross sectional study. World J Gastrointest Endosc 2015; 10:995–1002.

Velázquez-Dohorn ME, López-Durand CF, Gamboa-Domínguez A. Changing trends in gastric polyps. Rev Invest Clin 2018; 70:40–45.

Martin FC, Chenevix-Trench G, Yeomans ND. Systematic review with meta-analysis: fundic gland polyps and proton pump inhibitors. Aliment Pharmacol Ther 2016; 44:915–925.

Tran-Duy A, Spaetgens B, Hoes AW, de Wit NJ, Stehouwer CDA. Use of proton pump inhibitors and risks of Fundic gland polyps and gastric cancer: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2016; 14:1706–1719.e5.

Kroupa R, Katinova I, Pavlik T, Kunovsky L, Prochazka V, Borilova Linhartova P, et al. Incidence trends of esophageal cancer in the Czech Republic by histological subtype and stage and prescription rate of acid suppressing drugs. Cancer Epidemiol 2020; 69:101853.

Cheung KS, Leung WK. Long-term use of proton-pump inhibitors and risk of gastric cancer: a review of the current evidence. Therap Adv Gastroenterol 2019; 12. doi: https://doi.org/10.1177/1756284819834511. DOI

Nawata Y, Ichihara S, Hirasawa D, Tanaka I, Unno S, Igarashi K, et al. A case of gastric adenocarcinoma considered to originate from a sporadic fundic gland polyp in a Helicobacter pylori-uninfected stomach. Clin J Gastroenterol 2020; 13:740–745.

Sano W, Inoue F, Hirata D, Iwatate M, Hattori S, Fujita M, et al. Sporadic fundic gland polyps with dysplasia or carcinoma: clinical and endoscopic characteristics. World J Gastrointest Oncol 2021; 13:662–672.

Foretová L, Navrátilová M, Svoboda M, Grell P, Nemec L, Sirotek L, et al. GAPPS - gastric adenocarcinoma and proximal polyposis of the stomach syndrome in 8 families tested at Masaryk Memorial Cancer Institute – prevention and prophylactic gastrectomies. Klin Onkol 2019; 32:109–117.

Repak R, Kohoutova D, Podhola M, Rejchrt S, Minarik M, Benesova L, et al. The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature. Gastrointest Endosc 2016; 84:718–725.

Rudloff U. Gastric adenocarcinoma and proximal polyposis of the stomach: diagnosis and clinical perspectives. Clin Exp Gastroenterol 2018; 11:447–459.

Nasser SC, Slim M, Nassif JG, Nasser SM. Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes. World J Gastroenterol 2015; 21:4599–4606.

Graham DY, Tansel A. Interchangeable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol 2018; 16:800–808.e7.

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.

Ally MR, Veerappan GR, Maydonovitch CL, Duncan TJ, Perry JL, Osgard EM, et al. Chronic proton pump inhibitor therapy associated with increased development of fundic gland polyps. Dig Dis Sci 2009; 54:2617–2622.

Huang C, Lai R, Mai L, Zhou H, Chen H, Guo H. Relative risk factors associated with the development of fundic gland polyps. Eur J Gastroenterol Hepatol 2014; 26:1217–1221.

Fukuda M, Ishigaki H, Ban H, Sugimoto M, Tanaka E, Yonemaru J, et al. No transformation of a fundic gland polyp with dysplasia into invasive carcinoma after 14 years of follow-up in a proton pump inhibitor-treated patient: a case report. Pathol Int 2018; 68:706–711.

Lloyd IE, Kohlmann WK, Gligorich K, Hall A, Lyon E, Downs-Kelly E, et al. A Clinicopathologic evaluation of incidental fundic gland polyps with dysplasia: implications for clinical management. Am J Gastroenterol 2017; 112:1094–1102.

Genta RM, Schuler CM, Robiou CI, Lash RH. No Association between gastric fundic gland polyps and gastrointestinal neoplasia in a study of over 100,000 patients. Clin Gastroenterol Hepatol 2009; 7:849–854.

www.svod.cz. ZN žaludku. n.d. https://www.svod.cz/report.php?diag=C16 . [Accessed 20 October 2020].

Tacheci I, Repak R, Podhola M, Benesova L, Cyrany J, Bures J, et al. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) – a helicobacter-opposite point. Best Pract Res Clin Gastroenterol 2021; 50–51:101728.

Notsu T, Adachi K, Mishiro T, Ishimura N, Ishihara S. Fundic gland polyp prevalence according to Helicobacter pylori infection status. J Gastroenterol Hepatol 2020; 35:1158–1162.

Hongo M, Fujimoto K; Gastric Polyps Study Group. Incidence and risk factor of fundic gland polyp and hyperplastic polyp in long-term proton pump inhibitor therapy: a prospective study in Japan. J Gastroenterol 2010; 45:618–624.

Cats A, Schenk BE, Bloemena E, Roosedaal R, Lindeman J, Biemond I, et al. Parietal cell protrusions and fundic gland cysts during omeprazole maintenance treatment. Hum Pathol 2000; 31:684–690.

Bureš J, Kopáčová M, Koupil I, Seifert B, Skodová Fendrichová M, Spirková J, et al. Significant decrease in prevalence of Helicobacter pylori in the Czech Republic. World J Gastroenterol 2012; 18:4412–4418.

Nam SY, Lee SW, Jeon SW, Kwon YH, Lee HS. Helicobacter pylori eradication regressed gastric hyperplastic polyp: a randomized controlled trial. Dig Dis Sci 2020; 65:3652–3659.

Lemmers A, Evrard S, Demetter P, Verset G, Gossum AV, Adler M, et al. Gastrointestinal polypoid lesions: a poorly known endoscopic feature of portal hypertension. United European Gastroenterol J 2014; 2:189–196.

Topal F, Akbulut S, Karahanli C, Günay S, Saritaş Yüksel E, Topal FE. Portal hypertensive polyps as gastroscopic finding in liver cirrhosis. Gastroenterol Res Pract 2020; 2020:9058909.

Nelson M, Ganger D, Keswani R, Grande D, Komanduri S. Endoscopic resection is effective for the treatment of bleeding gastric hyperplastic polyps in patients with and without cirrhosis. Endosc Int Open 2016; 4:E874–E877.

Banks M, Graham D, Jansen M, Gotoda T, Coda S, Pietro M, et al. British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma. Gut 2019; 68:1545–1575.

Takeda T, Asaoka D, Tajima Y, Matsumoto K, Takeda N, Hiromoto T, et al. Hemorrhagic polyps formed like fundic gland polyps during long-term proton pump inhibitor administration. Clin J Gastroenterol 2017; 10:478–484.

Rodríguez-de-Santiago E, Frazzoni L, Fuccio L, van Hooft JE, Ponchon T, Hassan C, et al. Digestive findings that do not require endoscopic surveillance - reducing the burden of care: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy 2020; 52:491–497.

de Boer WB, Ee H, Kumarasinghe MP. Neoplastic lesions of gastric adenocarcinoma and proximal polyposis syndrome (GAPPS) are gastric phenotype. Am J Surg Pathol 2018; 42:1–8.

Tanaka M, Kataoka H, Yagi T. Proton-pump inhibitor-induced fundic gland polyps with hematemesis. Clin J Gastroenterol 2019; 12:193–195.