scholarly journals Long-term use of proton-pump inhibitors and risk of gastric cancer: a review of the current evidence

2019 ◽  
Vol 12 ◽  
pp. 175628481983451 ◽  
Author(s):  
Ka Shing Cheung ◽  
Wai K. Leung
Keyword(s):  
Gastric Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Randomized Clinical Trials ◽  
Bacterial Overgrowth ◽  
Current Evidence ◽  
Neoplastic Progression ◽  
Increased Risk ◽  
H Pylori

Gastric cancer remains one of the leading cancers in the world with a high mortality, particularly in East Asia. Helicobacter pylori infection accounts for the majority of the noncardia gastric cancers by triggering gastric inflammation and subsequent neoplastic progression. Eradication of H. pylori can reduce, but not totally eliminate, subsequent risk of developing gastric cancer. Proton-pump inhibitors (PPIs) are one of the most widely prescribed medications worldwide. With their profound gastric-acid suppression, there are concerns about a possible carcinogenic role in gastric cancer, due to induced hypergastrinemia, gastric atrophy and bacterial overgrowth in the stomach. While randomized clinical trials to establish causality between long-term PPI use and gastric cancer are lacking, current evidence based on observational studies suggests PPIs are associated with an increased gastric cancer risk. However, opinions on causality remain divergent due to unmeasured and possible residual confounding in various studies. Our recent study has showed that even after H. pylori eradication, long-term PPI use is still associated with an increased risk of gastric cancer by more than twofold. Hence, long-term PPIs should be used judiciously after considering individual’s risk–benefit profile, particularly among those with history of H. pylori infection. Further well-designed prospective studies are warranted to confirm the potential role of PPIs in gastric cancer according to baseline gastric histology and its interaction with other chemopreventive agents like aspirin, statins and metformin.

scholarly journals Role of Bacterial Overgrowth in the Stomach as an Additional Risk Factor for Gastritis

2003 ◽  
Vol 17 (suppl b) ◽  
pp. 13B-17B ◽  
Author(s):  
Gregory Naylor ◽  
Anthony Axon
Keyword(s):  
Gastric Cancer ◽  
Cell Mass ◽  
Bacterial Overgrowth ◽  
Nitroso Compounds ◽  
Current Evidence ◽  
Additional Risk Factor ◽  
Proximal Small Bowel ◽  
Increased Risk ◽  
H Pylori

Gastric bacteria can either be ingested or ascend from the distal bowel; however, their survival is usually limited by gastric acidity and motility. A reduction in gastric acid can result in bacterial overgrowth in the stomach and proximal small bowel, and the number of organisms rises as the intragastric pH rises.The increased risk of noncardia gastric cancer seen in patients with hypochlorhydria may be explained by an excess of nitrites and N-nitroso compounds (NOCs). These compounds are found in the diet of populations with a high gastric cancer risk, but can also be produced by the organisms that exist in the hypochlorhydria stomach. It has long been hypothsized that nitrites and NOCs act as one of the triggers in the atrophy-metaplasia-dysplasia-carcinoma path. However, although indirect data have linked the premalignant changes of metaplasia and dysplasia to NOCs, direct measurement of gastric nitrites and NOCs has not confirmed such a link.The role ofHelicobacter pyloriin bacterial overgrowth is mainly as a cause of hypochlorhydria resulting from atrophic gastritis, leading to a reduction in the parietal cell mass.Acid-suppressing drugs can result in bacterial overgrowth and increased nitrites and NOCs, although there is no current evidence for an increased risk of gastric cancer in patients taking them. One explanation is that the stomach appears to be colonized by different organisms than those in patients with hypochlorhydria for other reasons. There is some evidence that bacterial overgrowth per se can cause gastric inflammation in mice; however, although in humans the degree of gastric inflammation is greater when overgrowth is more prominant this may simply reflect the greater degree of hypochlorhydria in patients with a more severe H pylori-induced inflammation.

Proton pump inhibitors and upper gastrointestinal cancers

2019 ◽  
Vol 12 (9) ◽  
pp. 526-530
Author(s):  
Monica Kumar
Keyword(s):  
Gastric Cancer ◽  
General Practice ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Cost Effective ◽  
Gastrointestinal Cancers ◽  
Increased Risk ◽  
The Uk ◽  
Upper Gastrointestinal

Proton pump inhibitors (PPIs) were introduced in the 1980s. They are now one of the most commonly prescribed drugs in general practice. They are cost-effective when used correctly; however, PPIs are often used beyond accepted clinical indications. Recent published studies performed outside the UK have suggested that adverse effects are associated with long-term use of PPIs; in particular, an increased risk of gastric cancer. This article will aim to systematically assess the evidence and discuss its application to our clinical practice.

Long-Term Use of Proton Pump Inhibitors and Risk of Gastric Cancer Development after Treatment for H. Pylori : A Population-Based Study

2017 ◽  
Vol 152 (5) ◽  
pp. S833
Author(s):  
Michael K. Cheung ◽  
Angel Y. Wong ◽  
Lijia Chen ◽  
Esther W. Chan ◽  
Ian C. Wong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Population Based ◽  
Cancer Development ◽  
Population Based Study ◽  
H Pylori

scholarly journals Maintenance therapy with proton pump inhibitors and risk of gastric cancer: a nationwide population-based cohort study in Sweden

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e017739 ◽  
Author(s):  
Nele Brusselaers ◽  
Karl Wahlin ◽  
Lars Engstrand ◽  
Jesper Lagergren
Keyword(s):  
Gastric Cancer ◽  
Cohort Study ◽  
Maintenance Therapy ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Age Groups ◽  
Population Based ◽  
Background Population ◽  
Increased Risk

ObjectiveProton pump inhibitors (PPIs) are among the most commonly prescribed drugs. Concerns have been raised about a potentially increased risk of gastric cancer following long-term use. Our aim is to assess the risk of gastric cancer associated with PPI use, taking into account underlying indications.DesignThis is a population-based cohort study. Standardised incidence ratios (SIRs) and 95% CIs were calculated to compare the risk of gastric cancer among long-term PPI users with the corresponding background population, while taking confounding by indication into account.SettingPopulation-based study in Sweden (2005–2012).ParticipantsThis study included virtually all adults residing in Sweden exposed to maintenance therapy with PPIs.Exposure/InterventionMaintenance use of PPIs, defined as at least 180 days during the study period. Maintenance use of histamine 2 receptor antagonist was evaluated for comparison reasons.Outcome measuresGastric cancer (cardia and non-cardia), and subgroup analysis for gastric adenocarcinoma, as defined by the Swedish Cancer Registry.ResultsAmong 797 067 individuals on maintenance PPI therapy, the SIR of gastric cancer was over threefold increased (SIR=3.38, 95% CI 3.23 to 3.53). Increased SIRs were found in both sexes and all age groups, but were especially increased among PPI users younger than 40 years (SIR=22.76, 95% CI 15.94 to 31.52). Increased SIRs were found for each indication studied, including those without an association with gastric cancer, for example, gastro-oesophageal reflux (SIR=3.04, 95% CI 2.80 to 3.31), and those with a supposedly decreased risk, for example, aspirin users (SIR=1.93, 95% CI 1.70 to 2.18). The association was similar for cardia and non-cardia gastric cancer. Analyses restricted to adenocarcinoma showed similar results to those for all gastric cancers. Long-term users of histamine 2 receptor antagonists, which have the same indications as PPIs, were not at any increased risk.ConclusionsLong-term PPI use might be an independent risk factor for gastric cancer. This challenges broad maintenance PPI therapy, particularly if the indication is weak.

scholarly journals Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study

Gut ◽  
2017 ◽  
Vol 67 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Ka Shing Cheung ◽  
Esther W Chan ◽  
Angel Y S Wong ◽  
Lijia Chen ◽  
Ian C K Wong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Proportional Hazards Model ◽  
Absolute Risk ◽  
Eradication Therapy ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model

ObjectiveProton pump inhibitors (PPIs) is associated with worsening of gastric atrophy, particularly in Helicobacter pylori (HP)-infected subjects. We determined the association between PPIs use and gastric cancer (GC) among HP-infected subjects who had received HP therapy.DesignsThis study was based on a territory-wide health database of Hong Kong. We identified adults who had received an outpatient prescription of clarithromycin-based triple therapy between year 2003 and 2012. Patients who failed this regimen, and those diagnosed to have GC within 12 months after HP therapy, or gastric ulcer after therapy were excluded. Prescriptions of PPIs or histamine-2 receptor antagonists (H2RA) started within 6 months before GC were excluded to avoid protopathic bias. We evaluated GC risk with PPIs by Cox proportional hazards model with propensity score adjustment. H2RA was used as a negative control exposure.ResultAmong the 63 397 eligible subjects, 153 (0.24%) developed GC during a median follow-up of 7.6 years. PPIs use was associated with an increased GC risk (HR 2.44, 95% CI 1.42 to 4.20), while H2RA was not (HR 0.72, 95% CI 0.48 to 1.07). The risk increased with duration of PPIs use (HR 5.04, 95% CI 1.23 to 20.61; 6.65, 95% CI 1.62 to 27.26 and 8.34, 95% CI 2.02 to 34.41 for ≥1 year, ≥2 years and ≥3 years, respectively). The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess GC (95% CI 1.25 to 9.54) per 10 000 person-years.ConclusionLong-term use of PPIs was still associated with an increased GC risk in subjects even after HP eradication therapy.

scholarly journals Long-term proton pump inhibitor use and the incidence of gastric cancer: A systematic review and meta-analysis

2020 ◽  
Vol 2 (1) ◽  
pp. 1-11
Author(s):  
Ju-Li Lin ◽  
Jian-Xian Lin ◽  
Chao-Hui Zheng ◽  
Jian-Wei Xie ◽  
Jia-bin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systematic Review ◽  
Proton Pump Inhibitor ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Meta Analysis ◽  
Inclusion Criteria ◽  
Risk Ratios

Background: There are controverted whether the long-term use of proton pump inhibitors (PPI) will increase the risk of gastric cancer. We performed a meta-analysis to assess the risk of gastric cancer in PPI users compared with non-PPI users. Methods: The main inclusion criteria were original studies reporting the incidence of gastric cancer in PPI users compared with non-PPI users. Key outcomes were the risk ratios (RR) for gastric cancer in association with PPI users or non-PPI users. Results: We analyzed data from 8 studies, comprising more than 927,684 patients. The risk of gastric cancer in PPI users was significantly higher than in non-PPI users [RR= 2.10, 95% CI (1.17-3.97)]. The risk of gastric cancer was similar between the 2 groups when the duration was ≤1 year [RR= 2.18, 95% CI (0.66-7.11)]. While the risk of gastric cancer for PPI users was higher than in non-PPI users when the duration was between 1-3 years, ≥1 year, ≥3 years and ≥5 years. The risk of non-cardiac gastric cancer for PPI users was higher than for non-PPI users [RR= 2.66, 95% CI (1.66 -4.27)], and the risk of non-cardiac gastric cancer for PPI users was higher than for non-PPI users when the duration ≥1 year [RR= 1.99, 95% CI (1.03-3.83)], but the risk for cardiac gastric cancer was similar between the 2 groups [RR= 1.86, 95% CI (0.71-4.89)]. Conclusions: We found the long-term use of PPI (duration ≥1 year) was significantly associated with a higher risk of non-cardiac gastric cancer.

Long-term use of proton pump inhibitors does not affect ectopic and metachronous recurrence of gastric cancer after endoscopic treatment

2020 ◽  
Vol 55 (2) ◽  
pp. 209-215
Author(s):  
Hirotaka Oura ◽  
Tomoaki Matsumura ◽  
Yohei Kawasaki ◽  
Kenichiro Okimoto ◽  
Kentaro Ishikawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Endoscopic Treatment

Proton Pump Inhibitors and Dabigatran Therapy: Impact on Gastric Bleeding and Dabigatran Plasma Levels

2019 ◽  
Vol 45 (08) ◽  
pp. 846-850 ◽  
Author(s):  
Tomáš Bolek ◽  
Matej Samoš ◽  
Ingrid Škorňová ◽  
Peter Galajda ◽  
Ján Staško ◽  
...  
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Levels ◽  
Thrombin Inhibitor ◽  
Gi Bleeding ◽  
Gastric Bleeding ◽  
Increased Risk ◽  
The Impact ◽  
Dabigatran Therapy

AbstractDabigatran etexilate, a direct thrombin inhibitor, is now frequently used for long-term pharmacological prevention of stroke or systemic embolism in patients with atrial fibrillation. However, such long-term dabigatran therapy (DT) significantly increases the risk of upper gastrointestinal (GI) bleeding. This increased risk of gastric bleeds might be reduced with gastroprotective agents, such as proton pump inhibitors (PPIs). PPIs coadministrated with dabigatran reduce the risk of upper GI bleeding in patients on long-term oral DT. Nevertheless, there is heated discussion regarding interactions between PPI and dabigatran that lead to decreases in dabigatran plasma levels. This article reviews up to date data about the risk of gastric bleeding on dabigatran, the impact of PPI on the reduction of gastric bleeding, and the interaction between PPI and dabigatran leading to decreased dabigatran plasma levels.

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