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Auburn ADED 7950 - 737128

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Rapid #: -12484662CROSS REF ID: 737128LENDER: MDU :: Health Sciences LibraryBORROWER: AAA :: Main LibraryTYPE: Article CC:CCGJOURNAL TITLE: GutUSER JOURNAL TITLE: GutARTICLE TITLE: Long-term proton pump inhibitors and risk of gastric cancer development after treatment forHelicobacter pylori: a population-based study.ARTICLE AUTHOR: Cheung, Ka ShingVOLUME:ISSUE:MONTH: 10YEAR: 2017PAGES: gutjnl-ISSN: 0017-5749OCLC #:Processed by RapidX: 11/3/2017 5:47:50 AMThis material may be protected by copyright law (Title 17 U.S. Code)1CheungKS, etal. Gut 2017;0:1–8. doi:10.1136/gutjnl-2017-314605AbstrActObjective Proton 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.Designs This 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.result Among 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.conclusion Long-term use of PPIs was still associated with an increased GC risk in subjects even after HP eradication therapy.IntrODuctIOnGastric cancer is the third leading cause of cancer-related mortality in the world.1 Although Helicobacter pylori eradication has been shown to reduce the risk of gastric cancer development by 33%–47%,2 3 a considerable proportion of these individuals continues to progress to gastric cancer even after eradication of H. pylori. Apart from baseline gastric histology at the time of eradica-tion,4 data are sparse on other modifiable risks of gastric cancer development, particularly on the role of concurrent medications.Proton pump inhibitors (PPIs) have been among the most commonly prescribed medications in the world since the first PPI became available in the 1980s.5 Although PPIs are generally consid-ered safe, recent data have demonstrated various adverse effects associated with long-term use of PPIs including bone fracture,6 Clostridium diffi-cile infection,7 pneumonia,8 myocardial infarction and even stroke.9 Apart from the systemic adverse effects, there are also concerns on the long-term safety profile of PPIs in the stomach. The use of PPIs is associated with profound acid suppres-sion, which could worsen atrophic gastritis.10 The risk is considerably high among individuals infected with H. pylori who are susceptible to the development of corpus atrophy.11 Moreover, PPIs stimulate the production of gastrin, which is a potent growth factor, and hypergastrinemia has been shown to induce hyperplasia of enterochro-maffin-like cells.11 A recent meta-analysis showed that the risk of gastric cancer is increased by 43% GI cancerORIGInAL ARTICLeLong-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-basedstudyKa Shing Cheung,1 esther W Chan,2 Angel Y S Wong,2 Lijia Chen,1 Ian C K Wong,2,3 Wai Keung Leung1to cite: CheungKS, ChaneW, WongAYS, etal. Gut Published Online First: [please include Day Month Year]. doi:10.1136/gutjnl-2017-3146051Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong2Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Hong Kong3UCL School of Pharmacy, University College London, London, UKcorrespondence toDrWai KeungLeung, Department of Medicine, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong; waikleung@ hku. hkReceived 1 June 2017Revised 27 August 2017Accepted 4 September 2017significance of this studyWhat is already known on this subject? ► Although Helicobacter pylorieradication has been shown to reduce the risk of gastric cancer development, a considerable proportion of these individuals continues to progress to gastric cancer even after successful eradication of H. pylori. ► Previous studies have shown that the risk of gastric cancer was increased by 43% among PPIs users but the major confounding factor, H. pylori, was not adjusted in these analyses and the causal relationship may be biased.What are the new findings? ► Long-term PPIs use was associated with a 2.4-fold increase in gastric cancer risk in H. pylori-infected subjects who had received eradication therapy. ► The risk of gastric cancer increases with the dose and duration of PPIs use.How might it impact on clinical practice in the foreseeable future? ► Physicians should exercise caution when prescribing long-term PPIs to H. pylori-infected individuals even after successful eradication of H. pylori. Gut Online First, published on October 31, 2017 as 10.1136/gutjnl-2017-314605Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd (& BSG) under licence. group.bmj.com on November 3, 2017 - Published by http://gut.bmj.com/Downloaded from2CheungKS, etal. Gut 2017;0:1–8. doi:10.1136/gutjnl-2017-314605Figure 1 Study patient selection flow diagram. GC, gastric cancer; GU, gastric ulcer.GI canceramong PPI users.12 However, these studies included both H. pylori-infected and H. pylori-negative subjects. Although previous short-term studies suggested the resolution of corpus atrophy with H. pylori eradication therapy in patients with GORD,13 14 it remains uncertain whether the potential risk of PPIs on gastric cancer development could be eliminated by clearance of H. pylori.This


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