Severity of Gastric Intestinal Metaplasia Predicts the Risk of Gastric Cancer: a Prospective Multi-centre Cohort Study (GCEP)

Authors:
Jonathan LEE^1,2,19*, Feng ZHU^2,19*, Supriya SRIVASTAVA^2*, Stephen TSAO³, Christopher KHOR⁴, Khek Yu HO^1,2, Kwong Ming FOCK⁵, Wee Chian LIM³, Tiing Leong ANG⁵, Wan Cheng CHOW⁴, Jimmy B.Y. SO^6,19, Calvin KOH^1,2, Shijia Joy CHUA², Andrew WONG⁷, Jaideepraj RAO⁸, Lee Guan LIM⁹, Khoon Lin LING¹⁰, Chung King CHIA¹⁰, Choon-Jin OOI¹¹, Andrea RAJNAKOVA ¹⁰, Wai Ming YAP¹³, Manuel SALTO-TELLEZ¹⁴, Bow HO¹⁵, Richie SOONG¹⁶, Kee Seng CHIA¹⁷, Yik Ying TEO¹⁷, Ming TEH^18,19, Khay Guan YEOH^1,2,19


Affliations:
¹Division of Gastroenterology and Hepatology, National University Hospital, Singapore
²Dept. of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
³Dept. of Gastroenterology & Hepatology, Tan Tock Seng Hospital, Singapore
⁴Dept. of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
⁵Dept. of Gastroenterology & Hepatology, Changi General Hospital, Singapore
⁶Dept. of Surgery, National University of Singapore, Singapore
⁷Dept. of Surgery, Changi General Hospital, Singapore
⁸Dept. of Surgery, Tan Tock Seng Hospital, Singapore
⁹Raffles Medical Group, Singapore
¹⁰Mt. Elizabeth Medical Centre, Singapore
¹¹Gleneagles Medical Centre, Singapore
¹²Andrea's Digestive, Colon, Liver and Gallbladder Clinic Pte Ltd, Singapore
¹³Dept. of Pathology, Tan Tock Seng Hospital, Singapore
¹⁴Precision Medicine Centre of Excellence, Queen's University Belfast, UK
¹⁵Dept. of Microbiology, National University of Singapore, Singapore
¹⁶Cancer Science Institute, National University of Singapore, Singapore
¹⁷Saw Swee Hock School of Public Health, National University of Singapore, Singapore
¹⁸Dept. of Pathology, National University of Singapore, Singapore
¹⁹Singapore Gastric Cancer Consortium, Singapore
^*These authors contributed equally


Corresponding email address:
Khay Guan YEOH (mdcykg@nus.edu.sg)


Publication:
This article was published in Gut in May 2021 (PMID: 33975867)

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 multicenter study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardized 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 1.51-19.0; 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 20.77; 95% CI 6.39–103; 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 TFF3 distinguishes (AUROC 0.749) patients with OLGIM III-IV if they are negative for HP. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI; 1.60–33.7; p=0.02). A significant smoking history further increases the risk of EGN amongst patients with OLGIM stages II-IV.

Conclusion: 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.