Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP)

Abstract

ObjectiveTo investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC.MethodsA prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN).ResultsThere were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III–IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III–IV developed within 2 years (range: 12.7–44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III–IV if they are negative for H. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II–IV.ConclusionsWe suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III–IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.

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“…Among intestinal metaplasia (IM), the severe type of intestinal metaplasia is a significant risk factor for gastric cancer, because the age-adjusted early gastric cancer rate per 100,000 person-years with severe intestinal metaplasia is more than 5-fold that with moderate intestinal metaplasia and more than 20-fold that with mild intestinal metaplasia. Moreover, patients with severe intestinal metaplasia have shorter time intervals between the time at baseline endoscopy and the onset of subsequent early gastric cancer [ 43 ]. The gastric cancer dataset from references [ 44 , 45 ] contains cells from patients with early gastric cancer (EGC), intestinal metaplasia with severe level (IM-S), chronic atrophic gastritis (CAG), non-atrophic gastritis (NAG) and intestinal metaplasia with mild level (IM-M).…”

Response

“…We also agree that integrating more risk factors would improve the prediction model, as we and others have shown in a series of studies. [6][7][8][9] Whereas our newest model 2 includes a majority of established risk factors such as age, sex, smoking, Helicobacter pylori status, mediation use including proton pump inhibitors, comorbidities, and endoscopic and histologic findings, additional or different parameters may be needed for the prediction model for healthy populations. In any case, patients at high risk for GC should be carefully followed up endoscopically, but surveillance intervals could be better personalized in the future.…”

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“…Globally, gastric cancer (GC), the third leading cause of tumor-related mortalities and the fifth most prevalent carcinoma, had an approximated 1,089,103 new morbidities and 768,793 mortalities reported in 2020 ( Wang et al, 2021b ; Lee et al, 2021 ). Even though there are many treatment options for GC, prognostic outcomes for late stage GC are poor ( Wang et al, 2021b ).…”