In 204 symptomatic patients with RE, 42 preferred frequent liquid food intake and 162 preferred solid foods. In 67 silent patients with RE, 21 preferred frequent liquid foods and 46 preferred solid foods. No significant differences were found between the group of liquid and solid on the GERD symptoms (χ2 = 3.270, P = 0.095) [Table 4].
In 204 symptomatic RE, 169 (82.84%) patients suffered from typical GERD symptoms (163 were heartburn and 9 were regurgitation). Thirty-five (17.16%) patients suffered from atypical symptoms including 13 belching, six non-cardiac chest pain, five nausea, one vomit, eight distension, one abdominal pain, and one choking. A total of 102 (3.59%) patients fulfilled the Montreal silent RE definition.
In 67 silent patients with RE, 32 (47.76%) were RE with Los Angeles A grade and the rest 35 (52.24%) were grade B. In symptomatic RE, 83 (40.69%) were Los Angeles A grade, 103 (50.49%) were grade B and the rest 18 (8.82%) were grade C. There were no significant differences in RE grades between silent RE and symptomatic RE (grade A, χ2 = 1.033, P = 0.309; grade B, χ2 = 0.062, P = 0.804).
Multiple factors have been reported to be associated with GERD including age and gender, BMI, alcohol consumption, smoking, etc. In our study, the age, male gender, high BMI, and smoking (former smoker) were also found to be risk factors for RE. For NERD, only age was found independent risk factor. This is partly consistent with previous study in ordinary population. And the different risk factors between RE and NERD suggested that NERD may be not a mild type of RE but an independent disease from RE.
Frequent liquid food consumption was reported to be risk factor for RE. In Anyang, eating hot and/or liquid foods is popular in the residents’ lives. Frequent hot food consumption did not present to be risk factor for GERD. For so long time the liquid food has been suggested to be good for digestive disease patients. Some patients who have reflux symptoms may prefer liquid foods. It seems difficult to explain the causal relationship between liquid food and RE. However, our further analysis showed frequent liquid food consumption was also a risk factor for silent RE (OR [95% CI] 1.972 [1.135–3.428], P = 0.016). These subjects did not experience any symptoms and never underwent EGD before our surveillance. Thus frequent liquid food consumption should be a risk factor for RE. The pathogenic role of liquid food on esophageal mucosa injury was vague. We speculated liquid food increased the gastric volume and then gastric pressure in a short time, and in the following, it was emptied quickly thus resulted in the ineffectively neutralization of gastric acid.
A Chinese study reported 5.83% (60/1029) Montreal silent RE in 1029 inhabitants of Shanghai. In our current study, the prevalence of Montreal silent RE was 3.59% (102/2844). No consideration of atypical reflux symptoms, the Montreal definition may overestimate the ratio of silent RE. It is well known that many atypical symptoms are GERD related and respond to proton pump inhibitors therapy. We believe the subjects with atypical symptoms should be included in symptomatic RE. So we furtherly calculated the silent RE according to a more strict definition and found the prevalence of silent RE was 2.36% (67/2844). These data were similar to the report of the study conducted by Cho et al.  in Korea, who reported a rate of 2.74% of the silent RE in 5301 participants underwent health examination in Korea. The prevalence of 2.36% in natural population is not very low and furthermore, the silent RE present similar grades as that of symptomatic RE. Age and male gender were independent risk factors for silent RE when compared with controls as reported in previous studies. But frequent liquid food consumption was reported to be risk factor for silent RE. The role of liquid food on silent RE was not known yet. Following prospective study should be carried out to observe long-time outcome by avoiding liquid food.
The authors thank the following collaborators for their contributions to the field work done for this study, endoscopic examinations, pathologic diagnosis, and database establishment: Chuan-Hai Guo, Li-Xin Zhang, Ying Chen, Rong-Li Cui, He-Jun Zhang, Yu-Jie He, and Cai-Yun Wang from Peking University Cancer Hospital and Institute, Anyang Cancer Hospital, Peking University Third Hospital and School of Public Health, Peking University.
The work was supported by grants from the Chinese Charity Project of National Ministry of Health (No. 201202014) and the National Natural Science Foundation of China (No. 81400595).
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin
2016; 66:7–30. doi: 10.3322/caac.21332.
2. Kumagai H, Mukaisho K, Sugihara H, Miwa K, Yamamoto G, Hattori T. Thioproline inhibits development of esophageal adenocarcinoma induced by gastroduodenal reflux in rats. Carcinogenesis
2004; 25:723–727. doi: 10.1093/carcin/bgh067.
3. Ling ZQ, Mukaisho K, Yamamoto H, Chen KH, Asano S, Araki Y, et al. Initiation of malignancy by duodenal contents reflux and the role of ezrin in developing esophageal squamous cell carcinoma. Cancer Sci
2010; 101:624–630. doi: 10.1111/j.1349-7006.2009.01470.x.
4. He YT, Hou J, Chen ZF, Qiao CY, Song GH, Meng FS, et al. Trends in incidence of esophageal and gastric cardia cancer in high-risk areas in China. Eur J Cancer Prev
2008; 17:71–76. doi: 10.1097/CEJ.0b013e3282b6fd97.
5. Song GH, Ma Q, Ma SR, Chen C, Wei WW. Analysis of the incidence and age characteristics of upper gastrointestinal cancer among 2003-2012 in the high incidence area of esophageal cancer, Cixian county, in Heibei province. Chin J Prev Med
2017; 51:398–402. doi: 10.3760/cma.j.issn.0253-9624.2017.05.006.
6. Abnet CC, Arnold M, Wei WQ. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology
2018; 154:360–373. doi: 10.1053/j.gastro.2017.08.023.
7. He J, Ma X, Zhao Y, Wang R, Yan X, Yan H, et al. A population-based survey of the epidemiology of symptom-defined gastroesophageal reflux disease
: the Systematic Investigation of Gastrointestinal Diseases in China. BMC Gastroenterol
2010; 10:94doi: 10.1186/1471-230X-10-94.
8. Richter JE, Rubenstein JH. Presentation and epidemiology of gastroesophageal reflux disease
2018; 154:267–276. doi: 10.1053/j.gastro.2017.07.045.
9. Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout AJPM, et al. Modern diagnosis of GERD: the Lyon Consensus. Gut
2018; 67:1351–1362. doi: 10.1136/gutjnl-2017-314722.
10. Cho JH, Kim HM, Ko GJ, Woo ML, Moon CM, Kim YJ, et al. Old age and male sex are associated with increased risk of asymptomatic erosive esophagitis: analysis of data from local health examinations by the Korean National Health Insurance Corporation. J Gastroenterol Hepatol
2011; 26:1034–1038. doi: 10.1111/j.1440-1746.2011.06686.x.
11. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease
: a global evidence-based consensus. Am J Gastroenterol
2006; 101:1900–1920. doi: 10.1111/j.1572-0241.2006.00630.x.
12. Zou D, He J, Ma X, Chen J, Gong Y, Man X, et al. Epidemiology of symptom-defined gastroesophageal reflux disease
and reflux esophagitis: the systematic investigation of gastrointestinal diseases in China (SILC). Scand J Gastroenterol
2010; 46:133–141. doi: 10.3109/00365521.2010.52188.
13. Goh KL, Ho SH. Silent gastroesophageal disease: clinical implications of an unknown disease. J Gastroenterol Hepatol
2011; 26:1034–1038. doi: 10.1111/j.1440-1746.2011.06738.x.
14. Fass R, Dickman R. Clinical consequence of silent gastroesophageal reflux disease
. Curr Gastroenterol Rep
2006; 8:195–201. doi: 10.1007/s11894-006-0075-8.
15. He Z, Liu Z, Liu M, Guo C, Xu R, Li F, et al. Efficacy of endoscopic screening for esophageal cancer in China (ESECC): design and preliminary results of a population-based randomized controlled trial. Gut
2019; 68:198–206. doi: 10.1136/gutjnl-2017-315520.
16. Liu M, Liu Z, Cai H, Guo C, Li X, Zhang C, et al. A model to identify individuals at high risk for esophageal squamous cell carcinoma and precancerous lesions in regions of high prevalence
in China. Clin Gastroenterol Hepatol
2017; 15:1538–1546. doi: 10.1016/j.cgh.2017.03.019.
17. Okimoto E, Ishimura N, Morito Y, Mikami H, Shimura S, Uno G, et al. Prevalence
of gastroesophageal reflux disease
in children, adults, and elderly in the same community. J Gastroenterol Hepatol
2015; 30:1140–1146. doi: 10.1111/jgh.12899.
18. Suzuki H, Matsuzaki J, Okada S, Hirata K, Fukuhara S, Hibi T. Validation of the GerdQ questionnaire for the management of gastro-oesophageal reflux disease in Japan. United European Gastroenterol J
2013; 1:175–183. doi: 10.1177/2050640613485238.
19. Xiong LS, Chen MH, Chen HX, Xu AG, He LJ, Hu PJ. A population-based epidemiologic study on gastroesophageal reflux disease
. Chin J Dig
2006; 26:239–242. doi: 10.3760/j.issn:0254-1432.2006.04.007.
20. El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut
2014; 63:871–880. doi: 10.1136/gutjnl-2012-304269.
21. Minatsuki C, Yamamichi N, Shimamoto T, Kakimoto H, Takahashi Y, Fujishiro M, et al. Background factors of reflux esophagitis and non-erosive reflux disease: a cross-sectional study of 10,837 subjects in Japan. PLoS One
2013; 8:e69891doi: 10.1371/journal.pone.0069891.
22. Choi JM, Yang JI, Kang SJ, Han YM, Lee J, Lee C, et al. Association between anxiety and depression and gastroesophageal reflux disease
: results from a large cross-sectional study. J Neurogastroenterol Motil
2018; 24:593–602. doi: 10.5056/jnm18069.
23. Spechler SJ, Souza RF. Barrett's esophagus. N Engl J Med
2014; 371:836–845. doi: 10.1056/NEJMra1314704.
24. Wang K, Yang CQ, Duan LP, Yang XS, Xia ZW, Cui RL, et al. Changing pattern of adenocarcinoma of the esophagogastric junction in recent 10 years: experience at a large tertiary medical center in China. Tumori
2012; 98:567–573. doi: 10.1700/1190.13196.
25. Malfertheiner P, Nocon M, Vieth M, Stolte M, Jaspersen D, Koelz HR, et al. Evolution of gastro-oesophageal reflux disease over 5 years under routine medical care - the Pro GERD study. Aliment Pharmacol Ther
2012; 35:154–164. doi: 10.1111/j.1365-2036.2011.04901.x.
26. Savarino E, Marabotto E, Bodini G, Pellegatta G, Coppo C, Giambruno E, et al. Epidemiology and natural history of gastro-esophageal reflux disease. Minerva Gastroenterol Dietol
2017; 17: doi: 10.23736/S1121-421X.17.02383-2.
27. Fock KM, Talley N, Goh KL, Sugano K, Katelaris P, Holtmann G, et al. Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus. Gut
2016; 65:1402–1415. doi: 10.1136/gutjnl-2016-311715.
28. Wang K, Duan LP, Chen H, Xia ZW, Lin SR. Comparison of esophageal acid exposure characteristics between reflux oesophagitis and non-erosive reflux diseases (in Chinese). Chin J Intern Med
2005; 44:5–8. doi: 10.3760/j.issn:0578-1426.2005.01.004.
29. Savarino E, de Bortoli N, De Cassan C, Della Coletta M, Bartolo O, Furnari M, et al. The natural history of gastro-esophageal reflux disease: a comprehensive review. Dis Esophagus
2017; 30:1–9. doi: 10.1111/dote.12511.
30. Liu Y, Wang LD. Esophageal adenocarcinoma and esophageal squamous carcinoma of inpatient in high-and low-incidence areas for esophageal cancer from 1973-2012. Zhengzhou: Zhengzhou University. 2014.
31. Shao SZ, Zhao JJ, Yu XN, Zhang HX, Shen CF, Wang P, et al. Trends in incidence of esophageal and gastric cardia adenocarcinomas in Chongqing city over the past 30 years (in Chinese). Chongqing Medicine
2014; 10:3870–3872. doi: 10.3969/j.issn.1671-8348.2014.29.008.
32. Rubenstein JH, Shaheen NJ. Epidemiology, diagnosis, and management of esophageal adenocarcinoma. Gastroenterology
2015; 149:302–317. doi: 10.1053/j.gastro.2015.04.053.
33. Dore MP, Pes GM, Bassotti G, Farina MA, Marras G, Graham DY. Risk factors
for erosive and non-erosive gastroesophageal reflux disease
and Barrett's esophagus in Northern Sardinia. Scand J Gastroenterol
2016; 51:1281–1287. doi: 10.1080/00365521.2016.1200137.
34. Khan A, Kim A, Sanossian C, Francois F. Impact of obesity treatment on gastroesophageal reflux disease
. World J Gastroenterol
2016; 22:1627–1638. doi: 10.3748/wjg.v22.i4.1627.
35. Ness-Jensen E, Lagergren J. Tobacco smoking, alcohol consumption and gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol
2017; 31:501–508. doi: 10.1016/j.bpg.2017.09.004.
36. O’Connor A, O’Morain CA, Ford AC. Population screening and treatment of Helicobacter pylori
infection. Nat Rev Gastroenterol Hepatol
2017; 14:230–240. doi: 10.1038/nrgastro.2016.195.
37. Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, et al. Global prevalence
of Helicobacter pylori
infection: systematic review and meta-analysis. Gastroenterology
2017; 153:420–429. doi: 10.1053/j.gastro.2017.04.022.
38. Cui RL, Zhou LY. Helicobacter pylori
infection: an overview in 2013, focus on therapy. Chin Med J
2014; 127:568–573. doi: 10.3760/cma.j.issn.0366-6999.20132708.
39. Sugimoto M, Uotani T, Ichikawa H, Andoh A, Furuta T. Gastroesophageal reflux disease
in time covering eradication for all patients infected with Helicobacter pylori
in Japan. Digestion
2016; 93:24–31. doi: 10.1159/000441741.
40. Zerbib F. The prevalence
of oesophagitis in “silent” gastro-oesophageal reflux disease: Higher than expected? Dig Liver Dis
2015; 47:12–13. doi: 10.1016/j.dld.2014.10.006.