Roles of bile acid in the pathogenesis of Barrett esophageal and esophageal adenocarcinoma

doi:10.3877/cma.j.issn.2095-2015.2022.03.007

Abstract

Abstract:

Objective

To explore the roles of bile acid in the pathogenesis of Barrett esophagus(BE)and esophageal adenocarcinoma(EAC), and to provide reference for the prevention and treatment of BE and EAC.

Methods

Patients with regurgitation disease questionnaire score>12 points were selected from August 10, 2017 to October 30, 2020 at Chiping People′s Hospital.The patients underwent painless gastroscopy, gastric juice was collected under gastroscope, and mucosa biopsy was performed in the lower esophagus(1 cm above the gastroesophageal junction). The concentration of bile acid in gastric juice and mucosa of lower esophagus was detected.

Results

Bile acid of different concentrations was detected in gastric juice of all patients, and the total bile acid concentration in gastric juice and lower esophageal mucosal tissues of BE and EAC patients was significantly higher than that in gastric juice and lower esophageal mucosal tissues of non-erosive reflux disease(NERD)and reflux esophagitis(RE)patients(both P<0.05).

Conclusion

The concentration of bile acid in gastric juice and lower esophageal mucosa of patients with BE and EAC is significantly higher than that of patients with gastroesophageal reflux diseases without Barrett esophagus, suggesting that bile reflux may be related to the malignant transformation of mucosal cells at the gastroesophageal junction, and inhibition of bile reflux may be a necessary intervention to prevent the occurrence of BE and EAC.

Key words: Barrett esophagus, Esophageal adenocarcinoma, Bile acid

Keli Yang, Yanjun Ding, Wansheng Ji. Roles of bile acid in the pathogenesis of Barrett esophageal and esophageal adenocarcinoma[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2022, 12(03): 154-157.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhxhbyyxzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-2015.2022.03.007

https://zhxhbyyxzz.cma-cmc.com.cn/EN/Y2022/V12/I03/154

Figures/Tables 2

References 29

1	Konturek PC, Burnat G, Haln EG.Inhibition of Barret′s adenocarCinoma cell growth by simvastatin：involvement of COX-2 and apoptosis-related proteins[J]．Physiol Pharmacol，2007，58(Suppl 3)：141-148.
2	Blot W J, Devesa S S, Fraumeni Jr J F.Continuing climb in rates of esophageal adenocaurcioma：An update[J]．JAMA，1993，270(11)：1320.
3	杜倩．钠钙交换体亚型1介导CDX2上调促进Barrett食管发生发展的研究[D]．遵义：遵义医科大学，2020.
4	Shaheen NJ, Richter JE.Barrett′s oesophagus[J]．Lancet，2009，373(9666)：850-861.
5	Wild CP, Hardie LJ.Reflux，Barrett′s oesophagus and adenocarcinoma：burning questions[J]．Nat Rev Cancer，2003，3(9)：676-684.
6	国家消化系统疾病临床医学研究中心，中华医学会消化内镜学分会，中国医师协会消化医师分会．中国巴雷特食管及其早期腺癌筛查与诊治共识(2017年，万宁)[J]．中华消化内镜杂志，2017，34(9)：609-620.
7	中华医学会病理学分会消化疾病学组筹备组．胃食管反流病、Barrett食管和食管胃交界腺癌病理诊断共识[J]．中华病理学杂志，2017，46(2)：79-83.
8	Siewert JR, Stein HJ, Feith M．Adenocarcinoma of the esophagogastric junction[J]．Scand J Surg，2006，95(4)：260-269.
9	Xie SH, Lagergren J．Time trends in the incidence of oesophageal cancer in Asia：Variations across populations and histological types[J]．Cancer Epidemiol，2016，44：71-76.
10	Konturek PC, Burnat G Haln EG.Inhibition of Barret′s adenocarCinoma cell growth by simvastatin：involvement of COX-2 and apoptosis-related proteins[J]．Physiol Pharmacol，2007，58(Suppl 3)：141-148.
11	Buttar NS, Wang KK, Leontovich O，et al.Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett′s esophagus[J]．Gastroenterology，2002，122：1101-1112.
12	Miwa K, Sahara H, Segawa M，et al.Reflux of duodenal or gastroduodenal contents induces esophageal carcinoma in rats[J]．Int J Cancer，1996，67：269-274.
13	张茹，龚均，史冉庚，等．胆汁反流对大鼠食管黏膜炎症损伤和凋亡的作用[J]．四川大学学报(医学版)，2006，37(5)：750-753.
14	Sharma P．Clinical practice.Barrett′s esophagus[J]．N Engl J Med，2009，361：2548-2556.
15	Vaezi MF, Richter JE.Importance of duodeno-gastro-esophageal reflux in the medical outpatient practice[J]．Hepatogastroenterology，1999，46：40-47.
16	Stein HJ, Kauer WK, Feussner H，er al.Bile reflux in benign and malignant Barrett′s esophagus：effect of medical acid suppression and nissen fundoplication[J]．J Gastrointest Surg，1998，2(4)：333-341.
17	孙东峰．胆汁酸在Barrett食管发病机制中作用的研究[D]．济南：山东大学，2015：1-96.
18	Orlando RC.The integrity of the esophageal mucosa.Balance between offensive and defensivemechanisms[J]．Best Pract Res Clin Gastroenterol，2010，24(6)：873-882.
19	陈东风，杨洋．胆汁反流对食管胃黏膜屏障的损伤机制[J]．中华消化杂志，2016，36(6)：363-365.
20	Fein M, Fuchs K H, Stopper H, et al.Herderich.Duodenogastric reflux and foregut carcinogenesis：analysis of duodenal juice in a rodent model of cancer[J]．Carcinogenesis，2000，21(11)：2079-2084.
21	Wilson KT, Fu S, Ramanujam KS，et al.Increased expression of inducible nitric oxide svnthase and cvclooxygenase-2 in Barrett′s esophagus and associated adenocarcinomas[J]．Cancer Res，1998，58：2929-2934.
22	Coussens LM, Werb Z．Innammation and Cancer[J]．Nature，2002，420(6917)：860-867.
23	Chatelain Denis, Fléjou Jean-François.High-grade dysplasia and superficial adenocarcinoma in Barrett′s esophagus：histological mapping and expression of p53，p21 and Bcl-2 oncoproteins[J]．Virchows Archiv，2003，442(1)：18-24.
24	韩美玲，林轲羽，牛海静．胆汁酸在食管腺癌生发展中作用的研究进展[J]．中华实验外科杂志，2020，37(5)：985-989.
25	陈媚．脱氧胆酸介导IL-6/STAT3通路调控食管腺癌细胞重编程因子KLF4、OCT4表达[D]．广州：南方医科大学，2019.
26	唐丽明，宋宁，袁红霞．非酸反流与Barrett食管发生机制研究进展[J]．中国中西医结合外科杂志，2018，24(1)：118-120.
27	Bhardwaj Vikas, Horvat Andela, Korolkova Olga，et al.Prevention of DNA damage in Barrett′s esophageal cells exposed to acidic bile salts[J]．Carcinogenesis, 2016，37(12)：1161-1169.
28	Verbeek Romy E, Siersema Peter D, Vleggaar Frank P, et al.Toll-like Receptor 2 Signalling and the Lysosomal Machinery in Barrett′s Esophagus[J]．J Gastrointestin Liver Dis, 2016，25(3)：273-282.
29	Liu Runping, Xiaojiaoyang Li, Hylemon Phillip B，et al.Conjugated Bile Acids Promote Invasive Growth of Esophageal Adenocarcinoma Cells and Cancer Stem Cell Expansion via Sphingosine 1-Phosphate Receptor 2-Mediated Yes-Associated Protein Activation[J]．Am J Pathol，2018，188(9)：2042-2058.

组别	例数	食管下段黏膜组织胆汁酸浓度(μmol/g)	t值	P值
Barrett食管	61	0.035 3±0.008 5
非糜烂性反流病	107	0.031 0±0.003 2	17.321	<0.05
反流性食管炎	114	0.033 0±0.006 0	9.017	<0.05
食管腺癌	12	0.034 7±0.003 8	14.482	<0.05

组别	例数	食管下段黏膜组织胆汁酸浓度(μmol/g)	t值	P值
Barrett食管	61	0.035 3±0.008 5
非糜烂性反流病	107	0.031 0±0.003 2	17.321	<0.05
反流性食管炎	114	0.033 0±0.006 0	9.017	<0.05
食管腺癌	12	0.034 7±0.003 8	14.482	<0.05

组别	例数	胃液胆汁酸浓度(μmol/L)	t值	P值
Barrett食管	61	109.81±14.50
非糜烂性反流病	107	74.85±18.45	t₁＝11.175	<0.05
			t₃＝7.014
反流性食管炎	114	85.06±22.40	t₂＝4.374
			t₄＝3.152	<0.05
食管腺癌	12	98.55±17.16

组别	例数	胃液胆汁酸浓度(μmol/L)	t值	P值
Barrett食管	61	109.81±14.50
非糜烂性反流病	107	74.85±18.45	t₁＝11.175	<0.05
			t₃＝7.014
反流性食管炎	114	85.06±22.40	t₂＝4.374
			t₄＝3.152	<0.05
食管腺癌	12	98.55±17.16

[1]	Hanni Lin, Guanming Li, Airun Zhang, Ningning Li, Xiaoyi Fang. Diagnosis and treatment of infant cholestasis caused by ABCB4 gene mutation combined with cytomegalovirus infection: a case report and literature review [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(01): 46-53.
[2]	Lili Tian, Jie Liu, Man Wan, Yun Xie, Bifang Wu, Ruizhang Su, Zhaoxu Tian, Xiumin Haung, Yiqun Hu. Diagnostic and prognostic value of blood routine inflammatory markers in intrahepatic cholestasis of pregnancy [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(01): 37-45.
[3]	Hanpeng Du, Wei Chen, Fandong Kong, Ming Wu. Effect of bile acid on expression of farnesoid X receptor, interleukin-6 and recovery of liver function after hepatectomy in rats with cirrhosis of liver [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2018, 13(06): 450-454.
[4]	Shiyang Yu, Dagang Yang, Yongning Li, Xianqiu Xiong, Futang Li, Rong Wang. Accelerated rehabilitation surgery in obstructive jaundice：metabolic interactions between bile acids and intestinal microbes [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(02): 230-234.
[5]	Ying Li, Ruoxi Zhang, Ting Liu, Diangang Liu. Improvement in mucosa and quality of life in patients with Barrett's esophagus complicated with sliding hiatal hernia after laparoscopic treatment [J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2022, 16(06): 663-667.
[6]	Cong Peng, Xiaoying Luo, Yangqiu Bai, Xiaoke Jiang, Bingyong Zhang. Research progress in the interaction between intestinal flora metabolites and mesenchymal stem cells [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2022, 12(06): 367-371.
[7]	Jiahao Chen, Xiaohong Kuang, Yuan Liao, Zhihuan Liu, Zhongcheng Chen, Wenying Zhou. Diagnostic value of serological parameters-based Logistic regression model for hepatocellular carcinoma [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2022, 11(06): 615-618.
[8]	Ning Mao, Yong Zhu. Pathogenesis and diagnosis of bile acid diarrhea [J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2022, 11(05): 425-428.
[9]	Tianyi Ma, Xishan Wang. Research progress on the involvement of bile acids in colon inflammation and colon cancer [J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2021, 10(02): 201-204.
[10]	Jinpeng Hu, Yan Zhou, Lirong Mo, Lulu Zheng, Jinfang Yang, Xue Zhang, Min Niu, Zhen Yang, Ling Zhang, Feihu Bai. Application of endoscopic radiofrequency ablation in digestive diseases [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2019, 09(02): 82-85.
[11]	Qingyao Du, Yingwen Cao, Jianxiong Lin, Run Hao, Jingmin Wang, Ruiquan Xu, Xiaoxia Kou. Mechanism of gut flora promoting Norovirus infection [J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2023, 11(04): 241-244,255.
[12]	Junli Wang, Wenping Zhang. Research progress of extracellular vesicles in the diagnosis and pathogenesis of Barrett esophagus and esophageal adenocarcinoma [J]. Chinese Journal of Diagnostics(Electronic Edition), 2021, 09(03): 207-210.
[13]	Jiancong Feng, Ningli Chai, Enqiang Linghu. Application of digestive endoscopic super minimally invasive surgery in esophageal neoplastic diseases [J]. Chinese Journal of Gastrointestinal Endoscopy(Electronic Edition), 2022, 09(01): 45-50.
[14]	Dan Lu, Ningyuan Fang, Haiya Wang. The relationship between bile acid and hypertension [J]. Chinese Journal of Geriatrics Research(Electronic Edition), 2021, 08(01): 41-44.
[15]	Tian Jin, Xiaoyun Yu. Diagnosis、treatment、and screening of Barrett's esophagus [J]. Chinese Journal of Gastroesophageal Reflux Disease(Electronic Edition), 2018, 05(03): 125-129.

Please choose a citation manager

Content to export