Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review and meta-analysis

Peng, Tzu‐Rong; Wu, Tingqing; Li, Chung-Hsien

doi:10.1007/s10147-022-02253-2

Cited by 14 publications

(10 citation statements)

References 39 publications

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“…In particular, associations of neoplasia with PPI therapy are situated in a heterogeneous data setting. Here, our balanced and conservative statistical approach detected no significant associations with gastric carcinomas and a continued PPI therapy, although it is frequently reported in other studies (44). However, our findings are in accordance with the results of a recent meta-analysis by Piovani et al (45).…”

Section: Discussionsupporting

confidence: 92%

Timely Cessation of Proton Pump Inhibitors in Critically Ill Patients Impacts Morbidity and Mortality: A Propensity Score-Matched Cohort Study*

Palmowski,

von Busch,

Unterberg

et al. 2024

Critical Care Medicine

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OBJECTIVE: Proton pump inhibitors (PPIs) are among the drugs most commonly used in critically ill patients. Although mainly applied temporarily for stress ulcer prophylaxis, their application is frequently not terminated. Potential adverse effects of PPI treatment could impact the outcome in case of unnecessary and, therefore, avoidable long-term continuation. We tested the hypotheses that nonindicated PPI therapy continued beyond hospital discharge is associated with increased morbidity, rehospitalization rate, and mortality. DESIGN: Nationwide retrospective cohort study considering critically ill patients treated on German ICUs between January, 2017, and December, 2018 with a 2-year follow-up. SETTING: A total of 591,207 patient datasets of a German healthcare insurer were screened. PATIENTS: We identified 11,576 ICU patients who received PPI therapy for the first time during their index ICU stay without having an indication for its continuation. INTERVENTIONS: The cohort was stratified into two groups: 1) patients without further PPI therapy and 2) patients with continuation of PPI therapy beyond 8 weeks after hospital discharge. MEASUREMENTS AND MAIN RESULTS: Frequency of predescribed adverse events associated with PPI therapy, 1-year rehospitalization rate, and 2-year mortality were determined. The proportion of patients with continued PPI therapy without an objectifiable indication was 41.7% (4,825 of 11,576 patients). These patients had a 27% greater risk of pneumonia (odds ratio [OR] 1.27; 95% CI, 1.15–1.39; p < 0.001) and a 17% greater risk of cardiovascular events (OR 1.17; 95% CI, 1.08–1.26; p < 0.001). Continued PPI therapy was associated with a 34% greater risk of rehospitalization (OR 1.34; 95% CI, 1.23–1.47) and a nearly 20% greater 2-year mortality risk (hazard ratio 1.17; 95% CI, 1.08–1.27; p = 0.006). CONCLUSIONS: These data demonstrate that an unnecessary continuation of PPI therapy after hospital discharge may significantly impact morbidity and mortality. To avoid potentially harmful overuse of a PPIs, intensivists should ensure timely cessation of a temporarily indicated PPI therapy.

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Section: Discussionsupporting

confidence: 92%

Timely Cessation of Proton Pump Inhibitors in Critically Ill Patients Impacts Morbidity and Mortality: A Propensity Score-Matched Cohort Study*

Palmowski,

von Busch,

Unterberg

et al. 2024

Critical Care Medicine

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“…This is consistent with the research results of Zeng et al (2021) (RR = 1.78, 95% CI: 1.38–2.31). Compared with the latest meta-analysis ( Peng et al, 2022 ), we excluded database duplication and specific population studies, so our research results are more robust and accurate. The results of subgroup analysis showed that the risk of gastric cancer increased significantly with the extension of PPI prescription time, and the patients who used PPI for more than 3 years had the highest risk of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Association of proton pump inhibitors with gastric and colorectal cancer risk: A systematic review and meta-analysis

Guo

Zhang

et al. 2023

Front. Pharmacol.

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Background: Proton pump inhibitors (PPI) are generally considered to be one of the well-established prescription drug classes and are commonly used to treat most acid-related diseases. However, a growing body of literature showing an association between gastric and colorectal cancer risk and PPI use continues to raise concerns about the safety of PPI use. Therefore, we aimed to investigate the association between proton pump inhibitor use and risk of gastric and colorectal cancer.Methods: We collected relevant articles using PubMed, Embase, Web of Science and Cochrane library from 1 January 1990 to 21 March 2022. The pooled effect sizes were calculated based on the random-effects model. The study was registered with PROSPERO (CRD42022351332).Results: A total of 24 studies (n = 8,066,349) were included in the final analysis in the screening articles. Compared with non-PPI users, PPI users had a significantly higher risk of gastric cancer (RR = 1.82, 95% CI: 1.46–2.29), but not colorectal cancer (RR = 1.22, 95% CI: 0.95–1.55). Subgroup analysis showed that there was a significant positive correlation between the use of PPI and the risk of non-cardiac cancer (RR = 2.75, 95% CI: 2.09–3.62). There was a significant trend between the duration dependent effect of PPI use and the risk of gastric cancer (<1 year RR = 1.56, 95% CI: 1.30–1.86; 1–3 years RR = 1.75, 95% CI: 1.28–2.37; >3 years RR = 2.32, 95% CI: 1.15–4.66), but not colorectal cancer (≤1 year RR = 1.00, 95% CI: 0.78–1.28; >1 year RR = 1.18, 95% CI: 0.91–1.54; ≥5 years RR = 1.06, 95% CI: 0.95–1.17).Conclusion: We found that PPI use increased gastric cancer risk, but not colorectal cancer risk. This result may be biased due to confounding factors. More prospective studies are needed to further validate and support our findings.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351332], identifier [CRD42022351332].

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“…In this study, we showed that PPI is a risk factor for development of map‐like redness after eradication. PPI generally affects gastric condition, such as intragastric pH, dysbiosis of gut microbiota, 33 progress of gastric musical atrophy and increased risk of gastric cancer 34,35 . Because map‐like redness is a risk factor for gastric cancer after eradication, patients with severe atrophy are expected to have high incidence rate of map‐like redness after eradication.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, situation in neutral intragastric pH value attained with PPI/vonoprazan is similar with patients with severe atrophy, and may associate with development of map-like redness. In addition, because PPI therapy for long-tern period progress severity of gastric mucosal atrophy and increase a risk of gastric cancer, 34,35 PPI may cause to develop intestinal metaplasia and map-like redness in relation with advancement of atrophy. However, at present, the detail mechanism underlying the development of map-like redness in patients receiving PPIs is unknown and should be considered as a topic for future investigation.…”

Section: Map-like Redness and Gastric Cancer In Patients After Eradic...mentioning

confidence: 99%

“…PPI generally affects gastric condition, such as intragastric pH, dysbiosis of gut microbiota, 33 progress of gastric musical atrophy and increased risk of gastric cancer. 34,35 Because map-like redness is a risk factor for gastric cancer after eradication, patients with severe atrophy are expected to have high incidence rate of map-like redness after eradication. In general, intragastric pH in patients with severe atrophy is higher than that with mild atrophy, due to loss of ability for acid secretion.…”

Section: Map-like Redness and Gastric Cancer In Patients After Eradic...mentioning

confidence: 99%

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Risk of map‐like redness development after eradication therapy for Helicobacter pylori infection

Matsumoto,

Sugimoto,

Fukuzawa

et al. 2024

Helicobacter

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BackgroundMap‐like redness is a newly identified endoscopic risk factor for gastric cancer in patients who received Helicobacter pylori eradication therapy. However, the incidence rate of map‐like redness in patients who received eradication, and the risk factors for the development of map‐like redness remain unclear. We hence aimed to investigate the incidence rate of map‐like redness at 1‐year post H. pylori eradication, and evaluated its associations with map‐like redness and gastric cancer in relation with gastric condition.Materials and MethodsEndoscopic severity of gastritis and map‐like redness were retrospectively evaluated according to the Kyoto Classification of Gastritis in patients who had undergone endoscopy before and after H. pylori eradication therapy.ResultsThe incidence rate of map‐like redness for all 328 patients at a mean of 1.2 ± 0.6 years after eradication was 25.3% (95% confidence interval [CI]: 20.7%–30.4%). Patients who developed map‐like redness were older, had more severe atrophy and intestinal metaplasia, a higher total score of the Kyoto Classification of Gastritis both before and after eradication, and a higher rate of gastric cancer history than patients who did not have map‐like redness. On multivariate analysis, risk of map‐like redness was increased in patients with intestinal metaplasia (odds ratio [OR]: 2.794, 95% CI: 1.155–6.757) and taking acid inhibitors (OR: 1.948, 95% CI: 1.070–3.547). Characteristics of H. pylori‐positive patients with gastric cancer history were patients who were older (OR: 1.033, 95% CI: 1.001–1.066), taking acid inhibitors (OR: 4.456, 95% CI: 2.340–8.484), and with occurrence of map‐like redness after eradication therapy (OR: 2.432, 95% CI: 1.264–4.679).ConclusionsMap‐like redness is observed in one fourth of patients at 1‐year post eradication. Patients who developed map‐like redness were found to have severe intestinal metaplasia and taking acid inhibitors, and hence such patients require increased attention at surveillance endoscopy.

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Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review and meta-analysis

Cited by 14 publications

References 39 publications

Timely Cessation of Proton Pump Inhibitors in Critically Ill Patients Impacts Morbidity and Mortality: A Propensity Score-Matched Cohort Study*

Timely Cessation of Proton Pump Inhibitors in Critically Ill Patients Impacts Morbidity and Mortality: A Propensity Score-Matched Cohort Study*

Association of proton pump inhibitors with gastric and colorectal cancer risk: A systematic review and meta-analysis

Risk of map‐like redness development after eradication therapy for Helicobacter pylori infection

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