Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial

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

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    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.
    Gastric Cancer 01/2015; DOI:10.1007/s10120-015-0462-7 · 4.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Helicobacter pylori, a pathogen responsible for gastric and duodenal diseases, absorbs various steroid compounds into the cell membrane even though some are toxic to this bacterium. An earlier study by our group has demonstrated that progesterone is bactericidal to H. pylori. In this study, we newly synthesized a steroid compound, 17α-hydroxyprogesterone linoleic acid ester (17hPL), to examine antibacterial activity against H. pylori. As expected, 17hPL acted as a bactericidal agent to H. pylori and had no effect on the survival of other common bacterial species. This steroidal substance interacted with phosphatidylethanolamine (PE) on the outer membrane of H. pylori to induce the release of PE from the bacterial cell membrane and to ultimately lyse the bacterial cells. One of the hormonal effects of progesterone is the inhibition of nitric oxide (NO) production from mouse macrophages activated by lipopolysaccharide (LPS). We therefore examined the inhibition effect of 17hPL on the NO production of RAW 264.7 cells, a murine macrophage-like cell line, stimulated with LPS and demonstrated that 17hPL is relatively weaker in its capability to inhibit NO production in LPS-activated cells than progesterone. These results suggest the possibility that 17hPL could be an oral medicine for selectively treating patients infected with H. pylori.
    The Journal of steroid biochemistry and molecular biology 11/2013; 140. DOI:10.1016/j.jsbmb.2013.10.023 · 4.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Many micro-RNAs (miRNAs) are differentially expressed in Helicobacter pylori-infected gastric mucosa and in gastric cancer tissue and previous reports have suggested the possibility of serum miRNAs as complementary tumour markers. The aim of the study was to investigate serum miRNAs and pepsinogen levels in individuals at high risk for gastric cancer both before and after H. pylori eradication. Methods: Patients with recent history of endoscopic resection for early gastric cancer and the sex- and age-matched controls were enrolled. Serum was collected from subjects before or after eradication and total RNA was extracted to analyse serum levels of 24 miRNAs. Serum pepsinogen (PG) I and II levels were measured using enzyme-linked immunosorbent assay kits. Results: Using miR-16 as an endogenous control, the relative levels of miR-106 and let-7d before and after H. pylori eradication and miR-21 after eradication were significantly higher in the high-risk group than in the controls. H. pylori eradication significantly decreased miR-106b levels and increased let-7d only in the control group. After eradication, the combination MiR-106b with miR-21 was superior to serum pepsinogen and the most valuable biomarker for the differentiating high-risk group from controls. Conclusion: Serum miR-106b and miR-21 may provide a novel and stable marker of increased risk for early gastric cancer after H. pylori eradication.
    British Journal of Cancer 10/2013; 109(9):2323-2330. DOI:10.1038/bjc.2013.596 · 4.82 Impact Factor