Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K, Hayashi S, Asaka M Japan Gast Study GEffect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet 372: 392-397

Department of Gastroenterology, Yamagata Prefectural Central Hospital, Yamagata, Japan.
The Lancet (Impact Factor: 45.22). 09/2008; 372(9636):392-7. DOI: 10.1016/S0140-6736(08)61159-9
Source: PubMed


The relation between Helicobacter pylori infection and gastric cancer has been proven in epidemiological studies and animal experiments. Our aim was to investigate the prophylactic effect of H pylori eradication on the development of metachronous gastric carcinoma after endoscopic resection for early gastric cancer.
In this multi-centre, open-label, randomised controlled trial, 544 patients with early gastric cancer, either newly diagnosed and planning to have endoscopic treatment or in post-resection follow-up after endoscopic treatment, were randomly assigned to receive an H pylori eradication regimen (n=272) or control (n=272). Randomisation was done by a computer-generated randomisation list and was stratified by whether the patient was newly diagnosed or post-resection. Patients in the eradication group received lansoprazole 30 mg twice daily, amoxicillin 750 mg twice daily, and clarithromycin 200 mg twice daily for a week; those in the control group received standard care, but no treatment for H pylori. Patients were examined endoscopically at 6, 12, 24, and 36 months after allocation. The primary endpoint was diagnosis of new carcinoma at another site in the stomach. Analyses were by intention to treat. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000001169.
At 3-year follow-up, metachronous gastric carcinoma had developed in nine patients in the eradication group and 24 in the control group. In the full intention-to-treat population, including all patients irrespective of length of follow-up (272 patients in each group), the odds ratio for metachronous gastric carcinoma was 0.353 (95% CI 0.161-0.775; p=0.009); in the modified intention-to-treat population, including patients with at least one post-randomisation assessment of tumour status and adjusting for loss to follow-up (255 patients in the eradication group, 250 in the control group), the hazard ratio for metachronous gastric carcinoma was 0.339 (95% CI 0.157-0.729; p=0.003). In the eradication group, 19 (7%) patients had diarrhoea and 32 (12%) had soft stools.
Prophylactic eradication of H pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma.
Hiroshima Cancer Seminar Foundation.

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    • "Overall Wong et al, 2004 (7) Fukase et al, 2008 (6) Subtotal Leung et al, 2004 (3) Correa et al, 2000 (1) Subtotal Wong et al, 2012 (9) "
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    ABSTRACT: The effect of Helicobacter pylori (H. pylori) eradication on gastric cancer (GC) prevention is controversial. Intestinal metaplasia (IM) seems to be a "point of no return" in the precancerous cascade. We performed a meta-analysis of randomized controlled trials (RCTs) to illustrate this issue. The MEDLINE, EMBASE, Cochrane Library were searched for relevant RCTs that were published in any language up to March 2014. By dividing participants into subgroups based on their baseline diagnoses as group <IM (normal, non-atrophic gastritis, atrophic gastritis) and group ≥IM(intestinal metaplasia, dysplasia), the relative risk (RR) of GC in each study compared treatment group with control group were pooled using Mantel-Haenszel fixed-effect model and publication bias analyses were performed. Ten studies from eight RCTs were included in this analysis, for a total of 7,955 participants. H. pylori treatment compared with control significantly reduced the risk of GC, with a pooled RR of 0.64 (95 % CI, 0.48-0.85). Subgroup analysis for patients with non-atrophic gastritis, atrophic gastritis (<IM) yielded a similar results (RR = 0.25, 95 % CI, 0.08-0.81). But this difference was not observed in patients with intestinal metaplasia, dysplasia (≥IM) (RR = 0.88; 95 % CI, 0.59-1.31). Our results suggested that patients with Intestinal metaplasia or dysplasia could not benefit from the H. pylori treatment on the risk of GC.
    No preview · Article · Jan 2015 · Gastric Cancer
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    • "For example, one model invokes the recruitment of stem cells from the bone marrow observed during H. pylori -mediated gastric inflammation (Houghton et al. 2004), while another proposes that chronic H. pylori -induced gastric inflammation makes the niche inhabitable, eliminates H. pylori, and supports other cancer-promoting microbial species (Plottel and Blaser 2011). This latter theory is contradicted by prevention of gastric carcinoma from prophylactic eradication of H. pylori after detection of early gastric cancer (Fukase et al. 2008), but this discrepancy may be indicative of the different modes of tumorigenesis that depend on cancer type. Interestingly, there is currently a lack of evidence showing any connection between immunodeficiency, such as acquired immunodeficiency syndrome, and uncontrollable H. pylori infections, despite this being a common situation with other pathogens (Pounder and Ng 1995). "
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    ABSTRACT: Understanding the transition of bacterial species from commensal to pathogen, or vice versa, is a key application of evolutionary theory to preventative medicine. This requires working knowledge of the molecular interaction among hosts and bacteria, ecological interactions among microbes, spatial variation in bacterial prevalence or host life history, and evolution in response to these factors. However, there are very few systems for which such broad datasets are available. One exception is the gram-negative bacterium, Helicobacter pylori, which infects upwards of 50% of the global human population. This bacterium is associated with a wide breadth of human gastrointestinal disease, including numerous cancers, inflammatory disorders, and pathogenic infections, but is also known to confer fitness benefits to its host both indirectly, through interactions with other pathogens, and directly. Outstanding questions are therefore why, when and how this bacterium transitions along the parasitism-mutualism continuum. We examine known virulence factors, genetic predispositions of the host, and environmental contributors that impact progression of clinical disease and help define geographical trends in disease incidence. We highlight the complexity of the interaction and discuss future therapeutic strategies for disease management and public health in light of the longstanding evolutionary history between the bacterium and its human host.This article is protected by copyright. All rights reserved.
    Full-text · Article · Oct 2014 · Evolutionary Applications
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    • "However, synchronous/metachronous GENs in the remaining lesion could develop at sites other than that of endoscopic resection. There have been several reports on the occurrence of metachronous cancer after endoscopic treatment.3,4,5,6 During the follow-up after endoscopic resection, metachronous tumor was found to develop at rate of 1% to 3% per year.7 Therefore, characterization of GEN with high risk for synchronous/metachronous lesion is required for follow-up and treatment of patients, who underwent endoscopic resection of GEN. "
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    ABSTRACT: Synchronous/metachronous gastric epithelial neoplasias (GENs) in the remaining lesion can develop at sites other than the site of endoscopic resection. In the present study, we aimed to investigate the predictive value of serum pepsinogen for detecting multiple GENs in patients who underwent endoscopic resection. In total, 228 patients with GEN who underwent endoscopic resection and blood collection for pepsinogen I and II determination were evaluated retrospectively. The mean period of endoscopic follow-up was 748.8±34.7 days. Synchronous GENs developed in 46 of 228 (20.1%) and metachronous GENs in 27 of 228 (10.6%) patients during the follow-up period. Multiple GENs were associated with the presence of pepsinogen I <30 ng/mL (p<0.001). Synchronous GENs were associated with the presence of pepsinogen I <30 ng/mL (p<0.001). Low pepsinogen I levels predict multiple GENs after endoscopic resection, especially synchronous GENs. Cautious endoscopic examination prior to endoscopic resection to detect multiple GENs should be performed for these patients.
    Full-text · Article · May 2014 · Gut and Liver
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