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

Abstract

Objective: To 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.

Methods: A 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).

Results: There 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.

Conclusions: We 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.

Keywords: gastric cancer; pre-malignancy - GI tract; surveillance.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

(A) Age-adjusted early gastric neoplasia (EGN) incidence rates stratified by baseline Operative Link on Gastric Intestinal Metaplasia (OLGIM) stages. (B) Box plot depicting the time (years) to develop EGN among patients with OLGIM II (orange) and OLGIM III–IV (red), with respective median time (midline) of 50.7 months (range 28.5–73.3) and 22.7 months (range 12.7–44.8). The 25th and 75th quartile are represented by the lower and upper end of the boxes. IM, intestinal metaplasia.

Figure 2

(A) Box plots of serum biomarkers concentrations (TFF3, MIF and pepsinogen I/II ratio) stratified by the negative status (HP−; left column) or positive status (HP+; right column) of HP serology across baseline OLGIM stages (x-axis). Serum concentrations are variance transformed using log2 units and statistical differences tested through ANOVA. (B) ROC diagrams of serum biomarkers (TFF3, MIF, Pepsinogen I/II ratio) stratified by stratified by the negative status (HP−; left column) or positive status (HP+; right column) of HP serology and the classification definitions of either (OLGIM II–IV vs OLGIM 0–I; top row) or (OLGIM III–IV vs OLGIM 0–II, bottom row).ANOVA, analysis of variance; FPR, false positive rate; HP, H. pylori; IM, intestinal metaplasia; MIF, macrophage migration inhibitory factor; OLGIM, Operative Link on Gastric Intestinal Metaplasia; ROC, receiver operating characteristic; TFF3, trefoil factor 3; TPR, true positive rate.

Figure 3

(A) Proportions of patients within Singapore Gastric Cancer Epidemiology and MolecularGenetics Programme (GCEP), stratified by baseline OLGIM stages (rows) and subsequent OLGIM stages (columns) at 5 years. Each cell represents the proportion (%) of patients of that baseline OLGIM stage with the corresponding end of study OLGIM stage. Cells are coloured to indicate transition states of no IM (grey), reversal (blue), low risk (light blue), intermediate risk (orange) and high risk (red). (B) Bar plot indicating the proportion (%) of patients from each baseline OLGIM stage (x-axis) with the resulting transition state: no IM (grey), reversal (blue), low risk (light blue), intermediate risk (orange) and high risk (red). (C) Alluvial flowchart diagram of patients within GCEP: only patients with gastric IM diagnosed in at least one endoscopy were included for this diagram. The flowchart follows each patients at baseline endoscopy (stratified by the OLGIM stage) and the patient’s subsequent OLGIM stage at visit 3 and visit 5, whereby the patients trajectory summarised by the corresponding transition state trajectory: no IM (grey), reversal (blue), low risk (light blue), intermediate risk (orange) and high risk (red). IM, intestinal metaplasia; OLGIM, Operative Link on Gastric Intestinal Metaplasia.