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.

Preventing Metachronous Gastric Cancer after the Endoscopic Resection of Gastric Epithelial Neoplasia: Roles of <i>Helicobacter pylori</i> Eradication and Aspirin

“…87 However, there have been few reports on the changes of MSI and CIN (loss of heterozygosity, LOH) after H. pylori therapy. Our own previous studies 32,45 were exceptions, but in those reports we investigated MSI and LOH only in patients with IM and not in the context of atrophy. These molecular alterations in IM did not change significantly after the eradication, even in patients who underwent ER for early GC.…”

“…However, studies on the changes in the molecular phenotype in the background mucosa following H. pylori treatment in patients who have undergone ER for gastric neoplasms are limited. 31,32,38,41,45 Recently, the biomarkers for GC development after H. pylori eradication were discussed, and it was found that residual GC-related molecular events, even after H. pylori eradication, may be a surrogate marker of GC. 30,32,34,38,41,45,46 The CpG island methylator phenotype (CIMP), which is characterized by extensive hypermethylation of multiple CpG islands within the genome, is currently recognized as one of the major mechanisms in gastric carcinogenesis, 89 although there is no gold standard with respect to gene panels or the number of marker thresholds used to define CIMP.…”

Updated evidence on endoscopic resection of early gastric cancer from Japan

“…In addition to recurrence of and survival from the primary cancers, development of metachronous gastric cancers is an important issue, because the whole stomach is preserved after endoscopic resection. Although an RCT from Japan revealed H. pylori eradication after gastric endoscopic resection significantly reduced development of metachronous gastric cancers at the 3-year follow-up [41], it is still controversial whether H. pylori eradication would really reduce development of metachronous gastric cancers after gastric endoscopic resection from recent evidence [34,[42][43][44]. Further studies are necessary in this area, especially regarding appropriate prevention and surveillance of metachronous cancers.…”

“…Four studies regarding short-term and/or long-term outcomes in specific or general ESD patients were identified [31][32][33][34]. As the short-term outcomes in patients at high risk of thromboembolism who were regularly taking antiplatelet agents, Ono et al [31] reported a 26 % post-ESD ulcer bleeding rate, which led to early termination of the prospective cohort study.…”

“…For metachronous gastric cancer development, Kawanaka et al [34] revealed that H. pylori eradication did not produce significant changes in the molecular alterations related to carcinogenesis, including microsatellite instability, suggesting that H. pylori eradication might not prevent the development of metachronous gastric cancers in background mucosa with intestinal metaplasia where EGCs indicating ESD commonly develop.…”