Original articleSystematic reviews and meta-analysesUse of Proton Pump Inhibitors and Risks of Fundic Gland Polyps and Gastric Cancer: Systematic Review and Meta-analysis
Section snippets
Search Strategy and Eligibility Criteria
We searched PUBMED, EMBASE, and Cochrane Central Register of Controlled Trials to identify all English-language studies published from the inception until July 31, 2015 that assessed the association between PPI use and the risk of FGPs or gastric cancer. We used the search terms “proton pump inhibitor,” “omeprazole,” “esomeprazole,” “pantoprazole,” “lansoprazole,” “dexlansoprazole,” “rabeprazole,” “fundic gland polyps,” “fundus polyps” “gastric polyps,” “stomach polyps,” “gastric cancer,”
Results
Figure 1 shows the flow chart of the selection of studies. The search identified 1809 studies. After screening the titles, abstracts, and full text, 12 studies were considered eligible for complete data extraction. Of these, 1 RCT37 reported on the effect on gastric polyps (location not specified), 6 cohort38, 39, 40, 41, 42, 43 and 1 case-control studies44 reported on FGPs, and 1 cohort45 and 3 case-control studies46, 47, 48 reported on gastric cancer. Table 1 shows characteristics of the
Proton Pump Inhibitor Use and Risk of Gastric Polyps
The summary effect and its 95% CI based on the estimates from 1 RCT and 7 observational studies showed that the use of PPIs was associated with an increased risk of FGPs. The likelihood of this association was strengthened by the fact that the pooled OR and its lower bound of the 95% CI from studies with higher quality were much larger than those from studies with lower quality and from all studies. However, the magnitude of the mean effect size remains unclear. Of the 8 included studies, only 3
Conclusions
Long-term use of PPIs (≥12 months) is most likely associated with an increased risk of FGPs, but the clinical significance of this is currently unclear. Therapy with PPIs may also increase the risk of gastric cancer, but this association can be biased because of a limited number of available studies and possible confounding by indication and by other factors. Given the large number of patients receiving PPIs, more and higher quality studies are needed to confirm or repudiate any causal link
References (69)
- et al.
Gastric fundic gland polyps: a morphological study including mucin histochemistry, stereometry, and MIB-1 immunohistochemistry
Hum Pathol
(1996) - et al.
Incidence of fundic gland polyps in patients without familial adenomatous polyposis
Gastrointest Endosc
(1993) - et al.
Natural history of fundic gland polyposis in patients with familial adenomatosis coli/Gardner's syndrome
Gastroenterology
(1985) - et al.
Spontaneous resolution of multiple fundic gland polyps after cessation of treatment with lansoprazole and Nissen fundoplication: a case report
Gastrointest Endosc
(2002) - et al.
Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations
Am J Pathol
(2000) - et al.
Sporadic fundic gland polyps: common gastric polyps arising through activating mutations in the beta-catenin gene
Am J Pathol
(2001) - et al.
Long-term safety concerns with proton pump inhibitors
Am J Med
(2009) - et al.
Influence of Proton Pump Inhibitor Use in Gastrointestinal Polyps
Kaohsiung J Med Sci
(2010) - et al.
No Association Between Gastric Fundic Gland Polyps and Gastrointestinal Neoplasia in a Study of Over 100,000 Patients
Clin Gastroenterol Hepatol
(2009) Omeprazole and gastric polyposis in humans
Gastroenterology
(1993)
Fundic gland polyps and chronic PPI treatment: a prospective study
Gastroenterology
Gastric polyps in pediatrics: an 18-year hospital-based analysis
Am J Gastroenterol
Pharmacology of proton pump inhibitors
Curr Gastroenterol Rep
Frequency, location, and age and sex distribution of various types of gastric polyp
Endoscopy
Cystic 'hamartomatous' gastric polyps: a disorder of oxyntic glands
Histopathology
The histopathology of fundic gland polyps of the stomach
Am J Clin Pathol
Gastric polyposis: onset during long-term therapy with omeprazole
Med J Aust
Observation of gastric glandular cysts in the corpus mucosa of the stomach under omeprazole treatment
Z Gastroenterol
Fundic gland polyps: three other case reports suggesting a possible association with acid suppressing therapy
Acta Gastroenterol Belg
Gastric fundal polyps with cellular atypia in a patient using esomeprazole (Nexium)
Dig Dis Sci
Spontaneous resolution of multiple fundic gland polyps after cessation of treatment with omeprazole
Korean J Gastroenterol
A report of gastric fundic gland polyps
Gastroenterol Hepatol
Massive fundic gland polyposis caused by chronic proton pump inhibitor therapy. [Hungarian] Tartos protonpumpagatlo kezeles hatasara kialakulo massziv fundusmirigy-polyposis
Orv Hetil
The current spectrum of gastric polyps: A 1-year national study of over 120,000 patients
Am J Gastroenterol
Dysplasia and dysregulation of proliferation in foveolar and surface epithelia of fundic gland polyps from patients with familial adenomatous polyposis
Am J Surg Pathol
High-grade dysplasia in sporadic fundic gland polyps: a case report and review of the literature
Eur J Gastroenterol Hepatol
Enterochromaffin-like cell carcinoids of gastric mucosa in rats after life-long inhibition of gastric secretion
Digestion
Hypergastrinaemia during long-term omeprazole therapy: influences of vagal nerve function, gastric emptying and Helicobacter pylori infection
Aliment Pharmacol Ther
Effect of Helicobacter pylori status on intragastric pH during treatment with omeprazole
Gut
Helicobacter pylori infection potentiates the inhibition of gastric acid secretion by omeprazole
Gut
Non-Helicobacter pylori bacterial flora during acid-suppressive therapy: Differential findings in gastric juice and gastric mucosa
Aliment Pharmacol Ther
Double gastric infection with Helicobacter pylori and non-Helicobacter pylori bacteria during acid-suppressive therapy: increase of pro-inflammatory cytokines and development of atrophic gastritis
Aliment Pharmacol Ther
Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population
BMJ
Helicobacter pylori and Gastric Cancer: Factors That Modulate Disease Risk
Clin Microbiol Rev
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Conflicts of interest The authors disclose no conflicts.
Funding This study was supported by The Netherlands Organization for Health Research and Development (ZonMw; Rational Pharmacotherapy Program; Project number 836021018).