Barrett's oesophagus, proton pump inhibitors and gastrin: the fog is clearing

Kuipers, Ernst J.

doi:10.1136/gut.2009.191403

Cited by 10 publications

(7 citation statements)

References 7 publications

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“…840 However, Obszynska and colleagues demonstrated that, though gastrin enhances epithelial restitution in Barrett’s mucosa, it does not promote proliferation and expansion of Barrett’s segments during long-term PPI treatment. 4142 Hence, there is no evidence from preclinical and clinical studies that prolonged therapy with PPIs promotes oesophageal carcinogenesis, and this was also borne out in our review.…”

Section: Discussionmentioning

confidence: 91%

Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus: a systematic review and meta-analysis

Singh

Garg

Singh

et al. 2013

Gut

257

165

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Background and aims Acid-suppressive medications, particularly proton pump inhibitors (PPIs), may decrease the risk of oesophageal adenocarcinoma (OAC) in patients with Barrett’s oesophagus (BO). We performed a systematic review with meta-analysis of studies evaluating the association between acid-suppressive medications (PPIs and histamine receptor antagonists (H2RAs)) and risk of OAC or high-grade dysplasia (BO-HGD) in patients with BO. Methods We performed a systematic search of multiple electronic databases and conference proceedings up to June 2013 to identify studies reporting the association between use of acid-suppressive medications and risk of OAC and/or BO-HGD in patients with BO. Summary ORs with 95% CIs were estimated. Results We identified seven observational studies (2813 patients with BO, 317 cases of OAC or BO-HGD, 84.4% PPI users). On meta-analysis, PPI use was associated with a 71% reduction in risk of OAC and/or BO-HGD in patients with BO (adjusted OR 0.29; 95% CI 0.12 to 0.79). There was a trend towards a dose–response relationship with PPI use for >2–3 years protective against OAC or BO-HGD (three studies; PPI use >2–3 years vs <2–3 years: OR 0.45 (95% CI 0.19 to 1.06) vs 1.09 (0.47 to 2.56)). Considerable heterogeneity was observed. Two studies reported the association between H2RA use and risk of OAC and/or BO-HGD (1352 patients with BO, 156 cases of OAC, 25.4% on H2RAs), and both studies did not show a significant effect. Conclusions Based on meta-analysis of observational studies, the use of PPIs is associated with a decreased risk of OAC and/or BO-HGD in patients with BO. None of the studies showed an increased risk of OAC. PPI use should be considered in BO, and chemopreventive trials of PPIs in patients with BO are warranted.

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Section: Discussionmentioning

confidence: 91%

Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus: a systematic review and meta-analysis

Singh

Garg

Singh

et al. 2013

Gut

257

165

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“…Additionally, proposed beneficial effects of PPIs include anti-oxidant properties [9], effects on neutrophils, endothelial cells, epithelial cells [10], and anti-apoptotic cell modulation [11]. Moreover, PPIs are thought to inhibit binding to adhesion molecules in malignant cells and to suppress metastasis[12]. On the other hand, PPIs therapy interferes with esophageal exposure to secondary bile acids, and increases circulating gastrin levels, which may induce proliferation, COX-2 upregulation, and perhaps expansion of metaplasia.…”

Section: Introductionmentioning

confidence: 99%

Proton Pump Inhibitors Do Not Reduce the Risk of Esophageal Adenocarcinoma in Patients with Barrett’s Esophagus: A Systematic Review and Meta-Analysis

Sun

Hong

et al. 2017

PLoS ONE

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ObjectivesProton pump inhibitors (PPIs) have been used for treatment of Barrett's esophagus (BE) for many years. However, the connection between PPIs and esophageal adenocarcinoma (EAC) in patients with BE has still been controversial. The current systematic review and meta-analysis was designed to evaluate the association between PPIs and the risk of EAC or high-grade dysplasia (HGD) in patients with BE.MethodsA systematic literature search of studies reporting the association between PPIs and the risk of EAC and/or HGD in patients with BE was conducted in PubMed, Embase, Web of Science and the Cochrane Library. Next, literature was screened using previously established criteria and relevant data were extracted from included studies. Finally, the software program Review Manage 5.2 was applied to aggregate data and analyze the results.ResultsNine observational studies, comprising five cohort and four case-control studies (including a total of 5712 patients with BE), were identified. Upon meta-analysis, PPIs were found to have no association with the risk of EAC and/or HGD in patients with BE (unadjusted OR 0.43, 95% CI 0.17–1.08). Analysis for duration response relationship revealed no significant trend toward protection against EAC or HGD with PPIs usage for >2~3 years (one study using 7-year cutoff) when compared to usage for shorter time periods (PPIs usage >2~3 years vs. <2~3 years: OR 0.91 (95% CI 0.25–3.31) vs. 0.91 (0.40–2.07)).There also was considerable heterogeneity between studies.ConclusionNo dysplasia- or cancer-protective effects of PPIs usage in patients with BE were identified by our analysis. Therefore, we conclude that clinicians who discuss the potential chemopreventive effects of PPIs with their patients, should be aware that such an effect, if exists, has not been proven with statistical significance.

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“…We read with interest the study by Obszynska and co-workers1 on proton pump inhibitors (PPIs) and Barrett's oesophagus, and the accompanying editorial 2. The background for the study1 was whether PPIs are beneficial or harmful to patients with Barrett's oesophagus.…”

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confidence: 99%