Tsung-Hsien Chiang1,2,3, Masahiro Maeda4, Harumi Yamada4, Chang-Chuan Chan5,6, Sam Li-Sheng Chen7, Sherry Yueh-Hsia Chiu8,9, Yen-Nien Chen10, Yi-Hsuan Chou10, Chun-Fu Shieh11, Cheng-Ying Liu12, Han-Mo Chiu1,13, Hung Chiang14, Chia-Tung Shun15, Ming-Wei Lin16, Ming-Shiang Wu1, Jaw-Town Lin1,17, Hsiu-Hsi Chen5,13, Toshikazu Ushijima4, David Y Graham18, Yi-Chia Lee1,5,13,19. 1. Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. 2. Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei, Taiwan. 3. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. 4. Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan. 5. Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, National Taiwan University, Taipei, Taiwan. 6. Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan. 7. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan. 8. Department of Health Care Management and Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan. 9. Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. 10. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 11. Health Bureau of Lienchiang County, Nangan Township, Lienchiang County, Matsu, Taiwan. 12. Lienchiang County Government, Nangan Township, Lienchiang County, Matsu, Taiwan. 13. Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. 14. Taipei Institute of Pathology, Taipei, Taiwan. 15. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan. 16. Institute of Public Health, National Yang-Ming University, Taipei, Taiwan. 17. Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan. 18. Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, Texas, USA. 19. Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
Abstract
BACKGROUND AND AIM: The reliable method to stratify the gastric cancer risk after Helicobacter pylori eradication remains an elusive goal. METHODS: Mass eradication of H. pylori began in 2004 in a high-risk population. After eradication, a screening program involving first-stage serological tests (pepsinogen-I, pepsinogen-II, H. pylori immunoglobin G, and gastrin-17) and second-stage endoscopic examination was launched in 2015-2018. Index lesions included gastric cancer or extensive premalignant lesions. We evaluated the performance of the serological tests to "rule in" and "rule out" the risk based on positive and negative likelihood ratios, respectively. The methylation levels of microRNA-124a-3 in the stomach were measured to indicate genetic damage. RESULTS: Among 6512 invited subjects, 3895 (59.6%) participated. Both gastrin-17 and pepsinogen tests were normal in 3560 (91.4%) subjects; 206 (5.3%) gastrin-17 and 129 (3.3%) pepsinogen tests were abnormal. Years after eradication, the severity of gastritis had fallen greatly, and extensive premalignant lesions or gastric cancer frequently occurred in newly non-atrophic-appearing mucosa. Pepsinogen testing could moderately predict atrophic gastritis (positive likelihood ratio: 4.11 [95% confidence interval: 2.92-5.77]; negative likelihood ratio: 0.14 [0.10-0.19]). Gastrin-17 was not useful (0.66 and 1.20, respectively). However, pepsinogen testing poorly predicted the index lesions (2.04 [1.21-3.42] and 0.57 [0.34-0.95]). DNA methylation levels in the post-eradication mucosa were more discriminative for predicting index lesions (3.89 [2.32-6.54] and 0.25 [0.15-0.42]). CONCLUSIONS: After eradication, pepsinogen false-negative results become more frequent because histology is improved but genetic damage may persist. Direct testing for genetic damage offers better discrimination.
BACKGROUND AND AIM: The reliable method to stratify the gastric cancer risk after Helicobacter pylori eradication remains an elusive goal. METHODS: Mass eradication of H. pylori began in 2004 in a high-risk population. After eradication, a screening program involving first-stage serological tests (pepsinogen-I, pepsinogen-II, H. pylori immunoglobin G, and gastrin-17) and second-stage endoscopic examination was launched in 2015-2018. Index lesions included gastric cancer or extensive premalignant lesions. We evaluated the performance of the serological tests to "rule in" and "rule out" the risk based on positive and negative likelihood ratios, respectively. The methylation levels of microRNA-124a-3 in the stomach were measured to indicate genetic damage. RESULTS: Among 6512 invited subjects, 3895 (59.6%) participated. Both gastrin-17 and pepsinogen tests were normal in 3560 (91.4%) subjects; 206 (5.3%) gastrin-17 and 129 (3.3%) pepsinogen tests were abnormal. Years after eradication, the severity of gastritis had fallen greatly, and extensive premalignant lesions or gastric cancer frequently occurred in newly non-atrophic-appearing mucosa. Pepsinogen testing could moderately predict atrophic gastritis (positive likelihood ratio: 4.11 [95% confidence interval: 2.92-5.77]; negative likelihood ratio: 0.14 [0.10-0.19]). Gastrin-17 was not useful (0.66 and 1.20, respectively). However, pepsinogen testing poorly predicted the index lesions (2.04 [1.21-3.42] and 0.57 [0.34-0.95]). DNA methylation levels in the post-eradication mucosa were more discriminative for predicting index lesions (3.89 [2.32-6.54] and 0.25 [0.15-0.42]). CONCLUSIONS: After eradication, pepsinogen false-negative results become more frequent because histology is improved but genetic damage may persist. Direct testing for genetic damage offers better discrimination.