Advertisement

Gastric intestinal metaplasia: An irreversible risk factor for gastric cancer?

      Abbreviations:

      GC (gastric cancer), IM (intestinal metaplasia)
      Gastric cancer (GC) remains the fifth most common malignancy globally, accounting for 6.8% of all cancers in a 2012 report.
      • Ferlay J.
      • Soerjomataram I.
      • Dikshit R.
      • et al.
      Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.
      This has led to mass screening in certain high-incidence groups (eg, East Asians), enabling detection of early GC and resulting in an improvement in patient outcomes. Despite the added cost and complexity of general screenings, the benefit conferred by early detection of GC, coupled with the existence of identifiable high-risk cohorts, justifies the need for mass screening abroad. In the West, the relatively low incidence of GC has led to the perception that mass screening is impractical, and clear guidelines for GC screening and surveillance are lacking in the United States. However, high-risk patient cohorts do exist in Western countries including the United States, and not only could they benefit from risk stratification by using endoscopic screening and surveillance but a case could be made for the creation of protocols designed to target automatic screening for these groups.
      • Kim G.H.
      • Liang P.S.
      • Bang S.J.
      • et al.
      Screening and surveillance for gastric cancer in the United States: Is it needed?.
      Critical to this idea is the medical community’s ability to clearly elucidate which risk factors result in a preponderance of GC cases and to identify which of those factors can be mitigated effectively in order to determine how screening can be implemented to improve patient outcomes.
      In this issue of Gastrointestinal Endoscopy, Shichijo et al
      • Shichijo S.
      • Hirata Y.
      • Niikura R.
      • et al.
      Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after Helicobacter pylori eradication.
      provide a thoughtful observational study designed to assess GC risk after eradication of Helicobacter pylori infection. Currently, known risk factors for developing GC include age, male sex, family history, ethnicity, H pylori infection, atrophic gastritis, and intestinal metaplasia (IM). Many of these risk factors are intrinsic to the patient and therefore can be considered constants in the assessment of risk. However, H pylori infection (despite some antibiotic resistance patterns) has long been considered a mitigable factor because affordable and effective treatments for H pylori infection exist, and eradication of H pylori was previously thought to significantly decrease the risk for GC. Unfortunately, recent evidence has shown that atrophy of the gastric mucosa (diagnosed on endoscopy and histology), as well as advancing age, confers risk of GC even after documented H pylori eradication,
      • Take S.
      • Mizuno M.
      • Ishiki K.
      • et al.
      Seventeen-year effects of eradicating Helicobacter pylori on the prevention of gastric cancer in patients with peptic ulcer; a prospective cohort study.
      complicating risk assessment in these patients. This retrospective analysis of a Japanese, university-based, medical center cohort by Shichijo et al
      • Shichijo S.
      • Hirata Y.
      • Niikura R.
      • et al.
      Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after Helicobacter pylori eradication.
      provides important quantification of this post-eradication risk and could contribute to the effort for establishment of clear guidelines for GC screening in high-risk populations. All patients were recommended to undergo annual follow-up EGD, and a total of 573 patients were assessed endoscopically after antibiotic treatment. Patients were classified by histologic findings into those lacking IM (group A), IM localized to the gastric antrum (group B), and IM involving the corpus ± antrum (group C). Additionally, endoscopic appraisal of atrophic extension patterns was grouped as none and/or mild, moderate, and severe according to the Kimura-Takemoto classification.
      • Kimura K.
      • Takemoto T.
      An endoscopic recognition of the atrophic border and its significance in chronic gastritis.
      Mean (± standard deviation) duration of follow-up was 6.2 ± 4.8 years. Ultimately, 21 patients developed GC, with 95% of the cases (n = 20) of the intestinal type.
      These results of Shichijo et al
      • Shichijo S.
      • Hirata Y.
      • Niikura R.
      • et al.
      Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after Helicobacter pylori eradication.
      suggest that endoscopic atrophic gastritis and histologic IM remain prominent risk factors for GC after H pylori eradication. In this report, both risk factors were assessed together, but the authors found that overall rates for GC were higher in patients with severe endoscopic atrophy and IM. With 20 of the total 21 cases of metachronous GC being the intestinal type, the authors’ findings support previous findings

      Mori G, Nakajima T, Asada K, et al. Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan. Gastric Cancer. Epub 2015 Sep 29.

      that suggest a strong relationship between H pylori eradication and the mitigated risk of diffuse-type GC. Interestingly, the authors noted a lack of improvement in the distribution of IM after H pylori eradication, which is in contrast to the findings of previous studies that have shown an improvement in the grade of IM after H pylori eradication.
      • Kong Y.J.
      • Yi H.G.
      • Dai J.C.
      • et al.
      Histological changes of gastric mucosa after Helicobacter pylori eradication: a systematic review and meta-analysis.
      The clinical significance of the more recent finding, that is, static IM distribution after H pylori eradication, however, remains unclear. The histologic details of the cohort’s IM in the more recent study would have been helpful to include because complete-type IM (small-intestine phenotype) has a lower risk of progression to GC than incomplete-type IM (colon mucosal phenotype).
      • Gonzalez C.A.
      • Sanz-Anquela J.M.
      • Gisbert J.P.
      • et al.
      Utility of subtyping intestinal metaplasia as marker of gastric cancer risk. A review of the evidence.
      Additionally, the confidence interval (CI) for the group with severe endoscopic atrophy was 1.74 to 174, suggesting that further work with a larger cohort would potentially refine the CI. However, the central theme of the study still provides direct evidence of persistent GC risk after H pylori eradication and provides important data for the formulation of appropriate screening procedures for patients within this pool.
      Although mass screening for GC in a low-incidence country lacks cost-effectiveness,
      • Gupta N.
      • Bansal A.
      • Wani S.B.
      • et al.
      Endoscopy for upper GI cancer screening in the general population: a cost-utility analysis.
      if high-risk subpopulations exist, a structured regimen of surveillance may be valuable after appropriate risk factors for those subpopulations are identified. One meta-analysis in high-risk populations (Japan, Korea, China) found that screening and surveillance increased detection rates of early GC (pooled odds ratio, 3.90; 95% CI, 3.01-5.06; P < .0001) and demonstrated a significant improvement in the 5-year survival rate (hazard ratio = 0.56; 95% CI, 0.48-0.66; P < .0001),
      • Khanderia E.
      • Markar S.R.
      • Acharya A.
      • et al.
      The influence of gastric cancer screening on the stage at diagnosis and survival: a meta-analysis of comparative studies in the Far East.
      clearly demonstrating the value of applying screening protocols to an at-risk population. Yet, how do these findings apply to Western populations with a much lower incidence of GC? Studies that used Surveillance, Epidemiology, and End Results Program (SEER) data have shown greater incidence of GC in certain ethnicities, specifically Korean Americans (rate 42.5 cases per 100,000 individuals) over the non-Hispanic white population (rate 4.0 per 100,000 individuals) and higher mortality rates compared with other East Asian-American populations.
      • Kim G.H.
      • Bang S.J.
      • Ende A.R.
      • et al.
      Is screening and surveillance for early detection of gastric cancer needed in Korean Americans?.
      Although the risk of GC diminishes with each subsequent generation after immigration to the United States, the exact mechanism behind this observation is incompletely understood. Results of such population-based studies like that of Shichijo et al
      • Shichijo S.
      • Hirata Y.
      • Niikura R.
      • et al.
      Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after Helicobacter pylori eradication.
      may be generalizable to such U.S.–based cohorts. Early intervention and monitoring of first- and second-generation immigrants from high-incidence areas would benefit patients similarly to those subject to mass screening in endemic areas.
      Currently, the number of surgically resected early-stage GCs in the United States is only 20% (underperforming the 50% early-stage resection rate seen in Japan).
      • Noguchi Y.
      • Yoshikawa T.
      • Tsuburaya A.
      • et al.
      Is gastric carcinoma different between Japan and the United States?.
      This stark contrast in detection rates may be due to formalized screening programs present in Japan (and Korea) to which no Western counterpart exists. It is likely that the identification and screening of high-risk Western populations would not only decrease morbidity and mortality but may offer health-care system cost savings; early-stage cancers prove amenable to endoscopic resection (far preferable to costly and higher-risk surgical resection), which is increasingly available as the popularity of endoscopic submucosal dissection appreciates in Western practice. With assessment of existing intrinsic risks and a thorough analysis of subpopulations that possess these factors, we will have a firm foundation on which to construct appropriate surveillance practices for GC screening for at-risk patient populations in the United States, with a potential to greatly improve patient outcomes.
      In summary, Shichijo et al
      • Shichijo S.
      • Hirata Y.
      • Niikura R.
      • et al.
      Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after Helicobacter pylori eradication.
      have demonstrated that patients remain at risk for developing GC even after eradication of H pylori. These findings enhance our ability to identify patients at high risk for GC and enable the further development of screening and surveillance strategies that are impractical to implement over a general, low-incidence population. In the United States, this will further refine the construction of critical diagnostic paradigms that would closely monitor patients with risk factors for GC in a data-driven fashion. In the future, further (prospective data-based) studies are needed to improve screening recommendations for U.S. patient populations and to facilitate society-based guidelines. What also remains to be seen is whether screening and treating H pylori in high-risk populations before the development of IM will prevent the development of IM and reduce the incidence of GC.

      Disclosure

      All authors disclosed no financial relationships relevant to this publication.

      References

        • Ferlay J.
        • Soerjomataram I.
        • Dikshit R.
        • et al.
        Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.
        Int J Cancer. 2015; 136: E359-E386
        • Kim G.H.
        • Liang P.S.
        • Bang S.J.
        • et al.
        Screening and surveillance for gastric cancer in the United States: Is it needed?.
        Gastrointest Endosc. 2016; 84: 18-28
        • Shichijo S.
        • Hirata Y.
        • Niikura R.
        • et al.
        Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after Helicobacter pylori eradication.
        Gastrointest Endosc. 2016; 84: 618-624
        • Take S.
        • Mizuno M.
        • Ishiki K.
        • et al.
        Seventeen-year effects of eradicating Helicobacter pylori on the prevention of gastric cancer in patients with peptic ulcer; a prospective cohort study.
        J Gastroenterol. 2015; 50: 638-644
        • Kimura K.
        • Takemoto T.
        An endoscopic recognition of the atrophic border and its significance in chronic gastritis.
        Endoscopy. 1969; 1: 87-97
      1. Mori G, Nakajima T, Asada K, et al. Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan. Gastric Cancer. Epub 2015 Sep 29.

        • Kong Y.J.
        • Yi H.G.
        • Dai J.C.
        • et al.
        Histological changes of gastric mucosa after Helicobacter pylori eradication: a systematic review and meta-analysis.
        World J Gastroenterol. 2014; 20: 5903-5911
        • Gonzalez C.A.
        • Sanz-Anquela J.M.
        • Gisbert J.P.
        • et al.
        Utility of subtyping intestinal metaplasia as marker of gastric cancer risk. A review of the evidence.
        Int J Cancer. 2013; 133: 1023-1032
        • Gupta N.
        • Bansal A.
        • Wani S.B.
        • et al.
        Endoscopy for upper GI cancer screening in the general population: a cost-utility analysis.
        Gastrointest Endosc. 2011; 74: 610-624.E612
        • Khanderia E.
        • Markar S.R.
        • Acharya A.
        • et al.
        The influence of gastric cancer screening on the stage at diagnosis and survival: a meta-analysis of comparative studies in the Far East.
        J Clin Gastroenterol. 2016; 50: 190-197
        • Kim G.H.
        • Bang S.J.
        • Ende A.R.
        • et al.
        Is screening and surveillance for early detection of gastric cancer needed in Korean Americans?.
        Korean J Intern Med. 2015; 30: 747-758
        • Noguchi Y.
        • Yoshikawa T.
        • Tsuburaya A.
        • et al.
        Is gastric carcinoma different between Japan and the United States?.
        Cancer. 2000; 89: 2237-2246

      Linked Article