title: Effects of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic treatment: analysis of molecular alterations by a randomised controlled trial.
abstract: BACKGROUND
  Whether Helicobacter pylori eradication actually suppresses the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) remains controversial. The aims of this study were to clarify (1) the molecular markers related to carcinogenesis in intestinal metaplasia (IM) by a cross-sectional study, and (2) the changes of those markers by an open-label, randomised controlled trial (RCT) of H. pylori treatment.
  
  
  METHODS
  First, we evaluated microsatellite instability (MSI), the methylation status at hMLH1, CDKN2A and APC genes, and immunoreactivity using the monoclonal antibody (mAb) Das-1 in IM in the background mucosa of 131 patients who underwent ER for gastric neoplasia and 22 chronic gastritis cases (control). Next, we performed an RCT to evaluate the changes of MSI between the H. pylori-eradicated (n=19) and non-eradicated patients (n=17) at 1 year among the H. pylori-positive patients.
  
  
  RESULTS
  Microsatellite instability and mAb Das-1 reactivity showed significantly higher incidences in both the H. pylori-positive and -negative patients compared with the control group, thus suggesting that MSI and mAb Das-1 reactivity are associated with gastric neoplasia (OR=5.06 for MSI; OR=2.51 for mAb Das-1 reactivity). The RCT showed that H. pylori eradication did not provide significant reversals of any molecular alterations including MSI (the primary end point) and other methylation statuses and mAb Das-1 reactivity (secondary end points).
  
  
  CONCLUSIONS
  H. pylori eradication did not produce significant changes in the molecular alterations related to carcinogenesis, suggesting that H. pylori treatment may not prevent the development of MGC in background mucosa with IM.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Kawanaka
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Watari
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kamiya
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Toyoshima
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Hisatomo
authors.initials: H
authors.lastname: Ikehara
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Tomita
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Oshima
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Fukui
authors.affiliation: Department of Biostatistics, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.affiliation: Division of Gastroenterology and Hepatology, Departments of Medicine and Pathology, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, MEB 478B, New Brunswick, NJ 08901, USA.
authors.forename: Kiron M
authors.initials: KM
authors.lastname: Das
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000032:analysis; D003430:Cross-Sectional Studies; D004724:Endoscopy; D044127:Epigenesis, Genetic; D005260:Female; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000209:etiology*; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics / Q000382:microbiology / Q000517:prevention & control / Q000601:surgery
chemical_list: D000906:Antibodies; C467479:DAS-1 protein, human