Present aspects related to the physiopathogenesis of Barrett's esophagus
Keywords:
Barrett Esophagus, pathophysiologyAbstract
Introduction: Barrett's esophagus occurs when esophageal stratified squamous esophageal epithelium is replaced by columnar-type epithelium and the presence of intestinal metaplasia is confirmed by biopsy. Gastroesophageal reflux disease is its main risk factor. It is considered the only identifiable premalignant condition for esophageal adenocarcinoma. The progenitors of metaplastic cells are not well known and may be from mature squamous epithelial cells or from immature progenitor cells. Their development is influenced by environmental factors acting on an intrinsic genetic predisposition. Several investigations have been carried out by the international scientific community on the basis of animal and human models.Objective: to summarize what has been presented in the literature to serve as a reference tool.
Methods: a bibliographic search was carried out through PubMed and Google Scholar, in English and Spanish. Basically, scientific journals of recent years contained in the Medline database, others of similar quality but not included in Medline and some theses were consulted.
Conclusions: the understanding of the physiopathogenesis, which takes into account the cells that originate intestinal metaplasia and the early identification of the stages of progression to adenocarcinoma, has gained significant attraction in research through human and animal models during the last years. Knowledge of the immune response and the luminal environment on a genetic basis will allow resources to be placed on high-risk patients and avoid unnecessary procedures in lower-risk patients.
Downloads
References
1. Lowes H, Somarathna T, Shepherd N. Definition, Derivation, and Diagnosis of Barrett’s Esophagus: Pathological Perspectives. Adv Exp Med Biol [Internet]. 2016 [citado 13/11/2019];908:111-136. Disponible en: https://pubmed.ncbi.nlm.nih.gov/27573770/. https://doi.org/10.1007/978-3-319-41388-4_7
2. Kuipers EJ, Spaander MC. Natural History of Barrett’s Esophagus. Dig Dis Sic [Internet]. 2018 [citado 13/11/2019];63(8):1997-2004. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113676/. https://dx.doi.org/10.1007/s10620-018-5161-x
3. Offman J, Muldrew B, O'Donovan M, Debiram-Beecham I, Pesola F, Kaimi I, et al. Barrett's oESophagus trial 3 (BEST3): study protocol for a randomised controlled trial comparing the Cytosponge-TFF3 test with usual care to facilitate the diagnosis of oesophageal pre-cancer in primary care patients with chronic acid reflux. BMC Cancer [Internet]. 2018 [citado 13/11/2019];18(1):784. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091067/. https://dx.doi.org/10.1186/s12885-018-4664-3
4. De Jonge PJF, van Blankenstein M, Looman CWN, Casparie MK, Meijer GA, Kuipers EJ. Risk of malignant progression in patients with Barret´s oesophagus: a Dutch nationwide cohort study. Gut [Internet]. 2010 [citado 13/11/2019];59(8):1030-1036. Disponible en: https://pubmed.ncbi.nlm.nih.gov/20639249/. https://doi.org/10.1136/gut.2009.176701
5. Gross SA, Kingsbery J, Jang J, Lee M, Khan A. Evaluation of Dysplasia in Barrett Esophagus. Gastroenterol Hepatol (N Y) [Internet]. 2018 [citado 02/02/2020];14(4):233-239. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009185/
6. Drahos J, Ricker W, Parsons R, Pfeiffer R, Warren JL, Cook MB. Metabolic syndrome increases risk of Barrett esophagus in the absence of gastroesophageal reflux: an analysis of SEER-Medicare Data. J Clin Gastroenterol [Internet]. 2015 [citado 13/11/2019];49(4):282-288. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176548/. https://dx.doi.org/10.1097/mcg.0000000000000119
7. Brimhall B, Wani S. Current Endoscopic Approaches for the Treatment of Barrett Esophagus. J Clin Gastroenterol [Internet]. 2017 [02/02/2020];51(1):2–11. Disponible en: https://pubmed.ncbi.nlm.nih.gov/27941583/. https://doi.org/10.1097/mcg.0000000000000742
8. Singh S, Garg SK, Singh PP, Iyer PG, El-Serag HB. Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett’s oesophagus: a systematic review and meta-analysis. Gut [Internet]. 2014 [02/02/2020];63(8):1229-1237. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199831/. https://doi.org/10.1136/gutjnl-2013-305997
9. Peláez Luna M, Hernández Guerrero AI, Valdovinos Andraca F, Herrera Esquivel JJ, Martínez García CL, Aquino Pérez S. Guías de diagnóstico, vigilancia y manejo del esófago de Barrett. Asociación Mexicana de Endoscopia Gastrointestinal. Endoscopia [Internet]. 2017 [02/02/2020];29(2):97-112.Disponible en: http://revista.amegendoscopia.org.mx/index.php/endos/article/view/63
10. Shaheen NJ, Falk GW, Iyer PG, Gerson LB. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. AmJ Gastroenterol [Internet]. 2016 [02/02/2020];111(1):30-50. Disponible en: https://journals.lww.com/ajg/fulltext/2016/01000/acg_clinical_guideline__diagnosis_and_management.17.aspx. https://doi.org/10.1038/ajg.2015.322
11. Triadafilopoulos G, Friedland S. Precision care for Barrett's esophagus. Transl Gastroenterol Hepatol [Internet]. 2018 [citado 02/02/2020];3:67. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182039/. https://dx.doi.org/10.21037/tgh.2018.09.10
12. Souza RF. From Reflux Esophagitis to Esophageal Adenocarcinoma. Dig Dis [Internet]. 2016 [citado 02/02/2020];34(5):483–490.Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936412/. https://dx.doi.org/10.1159/000445225
13. Öberg S, Johansson J, Wenner J, Walther B. Metaplastic columnar mucosa in the cervical esophagus after esophagectomy. Ann Surg [Internet]. 2002 [citado 02/02/2020];235(3):338-345. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1422439/. https://dx.doi.org/10.1097/00000658-200203000-00005
14. Sharma P, Dent J, Armstrong D. Clinical practice. Barrett´s esophagus. N Engl J Med [Internet]. 2009 [citado 02/02/2020];361(26):2548-2556. Disponible en: https://pubmed.ncbi.nlm.nih.gov/20032324/. https://doi.org/10.1056/nejmcp0902173
15. Quante M, Graham TA, Jansen M. Insights Into the Pathophysiology of Esophageal Adenocarcinoma. Gastroenterology [Internet]. 2018 [citado 02/02/2020];154(2):406–420. Disponible en: https://pubmed.ncbi.nlm.nih.gov/29037468/. https://doi.org/10.1053/j.gastro.2017.09.046
16. Zhang W, Wang DH. Origins of Metaplasia in Barrett’s Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease? Dig Dis Sci [Internet]. 2018 [citado 02/02/2020];63(8):2005-2012. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783253/. https://doi.org/10.1007/s10620-018-5069-5
17. Schlottmann F, Molena D, Patti MG. Gastroesophageal reflux and Barrett’s esophagus: a pathway to esophageal adenocarcinoma. Updates Surg [Internet]. 2018 [citado 02/02/2020];70(3):339-342. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30039277/. https://doi.org/10.1007/s13304-018-0564-y
18. Wang DH, Souza RF. Transcommitment: paving the way to Barrett’s metaplasia. Adv Exp Med Biol [Internet]. 2016 [citado 02/02/2020];908:183–212. Disponible en: https://pubmed.ncbi.nlm.nih.gov/27573773/. https://doi.org/10.1007/978-3-319-41388-4_10
19. Naini BV, Souza RF, Odze RD. Barrett’s Esophagus: A Comprehensive and Contemporary Review for Pathologists. Am J Surg Pathol [Internet]. 2017 [citado 02/02/2020];40(5):e45–e66. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833583/. https://dx.doi.org/10.1097/PAS.0000000000000598
20. Biswas S, Quante M, Leedham S, Jansen M. The metaplastic mosaic of Barrett's oesophagus. Virchows Arch [Internet]. 2018 [citado 12/02/2020];472(1):43-54. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849653/. https://dx.doi.org/10.1007/s00428-018-2317-1
21. Gharahkhani P, Fitzgerald R, Vaughan TL, Palles C, Gockel I, Tomlinson I, et al. Genome-wide association studies in oesophageal adenocarcinoma and Barrett’s oesophagus: a large-scale meta-analysis. Lancet Oncol [Internet]. 2016 [citado 12/02/2020];17(10):1363–1373.Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052458/. https://dx.doi.org/10.1016/s1470-2045(16)30240-6
22. Palles C, Chegwidden L, Li X, Findlay JM, Farnham G, Castro Giner F, et al. Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett’s esophagus. Gastroenterology [Internet]. 2015 [citado 12/02/2020];148(2):367–378. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315134/. https://dx.doi.org/10.1053/j.gastro.2014.10.041
23. Phelan JJ, MacCarthy F, O'Toole D, Ravi N, Reynolds JV, O'Sullivan J. The Mitochondrial Genes BAK1, FIS1 and SFN are Linked with Alterations in Mitochondrial Membrane Potential in Barrett's Esophagus. Int J Mol Sci [Internet]. 2018 [citado 12/02/2020];19(11):3483. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275077/. https://doi.org/10.3390/ijms19113483
24. Horvath B, Singh P, Xie H, Thota PN, Sun X, Liu X. Expression of p53 predicts risk of prevalent and incident advanced neoplasia in patients with Barrett's esophagus and epithelial changes indefinite for dysplasia. Gastroenterol Rep (Oxf) [Internet]. 2016 [citado 5/03/2020];4(4):304-309. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193059/. https://doi.org/10.1093/gastro/gov045
25. Ross-Innes CS, Becq J, Warren A, Cheetham RK, Northen H, O'Donovan M, et al. Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma. Nat Genet [Internet]. 2015 [citado 08/03/2020];47(9):1038-1046. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556068/. https://doi.org/10.1038/ng.3357
26. Weaver JMJ, Ross-Innes CS, Shannon N, Lynch AG, Forshew T, Barbera M, et al. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat Genet [Internet]. 2014 [citado 08/03/2020];46(8):837-843. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116294/. https://dx.doi.org/10.1038/ng.3013
27. Corning B, Copland AP, Frye JW. The Esophageal Microbiome in Health and Disease. Curr Gastroenterol Rep [Internet]. 2018 [citado 08/03/2020];20(8):39. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30069679/. https://doi.org/10.1007/s11894-018-0642-9
28. Gorkiewicz G, Moschen A. Gut microbiome: a new player in gastrointestinal disease. Virchows Arch [Internet]. 2018 [citado 08/03/2020];472(1):159-172. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849673/. https://doi.org/10.1007/s00428-017-2277-x
29. Lynch KL. Is Obesity Associated with Barrett’s Esophagus and Esophageal Adenocarcinoma? Gastroenterol Clin North Am [Internet]. 2016 [citado 08/03/2020];45(4):615–624. Disponible en: https://pubmed.ncbi.nlm.nih.gov/27837776/. https://doi.org/10.1016/j.gtc.2016.07.002
30. Parasa S, Mahankali Sridhar AR. Metabolic Syndrome, GERD, Barrett’s Esophagus. In: Ahima RS, editors. Metabolic Syndrome. Cham: Springer; 2015 [citado 18/04/2020]. Disponible en: https://link.springer.com/referenceworkentry/10.1007%2F978-3-319-12125-3_37-1. https://doi.org/10.1007/978-3-319-12125-3_37-1
31. Hoyo C, Cook MB, Kamangar F, Freedman ND, Whiteman DC, Bernstein L, et al. Body mass index in relation to oesophageal and oesophagogastric junction adenocarcinomas: a pooled analysis from the International BEACON Consortium. Int J Epidemiol [Internet]. 2012 [citado 18/04/2020];41(6):1706–1718. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535758/. https://doi.org/10.1093/ije/dys176
32. Thrift A, Shaheen NJ, Gammon MD, Bernstein L, Reid BJ, Onstad L, et al. Obesity and risk of esophageal adenocarcinoma and Barrett’s esophagus: a Mendelian randomization study. J Natl Cancer Inst [Internet]. 2014 [citado 18/04/2020];106(11):dju252. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200028/. https://dx.doi.org/10.1093/jnci/dju252
33. Hsieh YH, Wu MF, Yang PY, Liao WC, Hsieh YH, Chang YJ, et al. What is the impact of metabolic syndrome and its components on reflux esophagitis? A cross-sectional study. BMC Gastroenterol [Internet]. 2019 [citado 18/04/2020];19(1):33. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381695/. https://dx.doi.org/10.1186/s12876-019-0950-z
34. Iijima K, Henry E, Moriya A, Wirz A, Kelman AW, McColl KEL. Dietary nitrate generates potentially mutagenic concentrations of nitric oxide at the gastroesophageal junction. Gastroenterology [Internet]. 2002 [citado 18/04/2020];122(5):1248-1257. Disponible en: https://pubmed.ncbi.nlm.nih.gov/11984511/. https://doi.org/10.1053/gast.2002.32963
35. Asanuma K, Huo X, Agoston A, Zhang X, Yu C, Cheng E, et al. In oesophageal squamous cells, nitric oxide causes S-nitrosylation of Akt and blocks SOX2 (sex determining region Y-box 2) expression. Gut [Internet]. 2016 [citado 18/04/2020];65(9):1416-1426. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651671/. https://doi.org/10.1136/gutjnl-2015-309272
36. Erőss B, Farkas N, Vincze Á, Tinusz B, Szapáry L, Garami A, et al. Helicobacter pylori infection reduces the risk of Barrett's esophagus: A meta-analysis and systematic review. Helicobacter [Internet]. 2018 [citado 18/04/2020];23(4):e12504. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055671/. https://dx.doi.org/10.1111/hel.12504
37. Ness-Jensen E, Lagergren J. Tobacco smoking, alcohol consumption and gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol [Internet]. 2017 [citado 18/04/2020];31(5):501-508. Disponible en: https://pubmed.ncbi.nlm.nih.gov/29195669/. https://doi.org/10.1016/j.bpg.2017.09.004
38. Watari J, Oshima T, Fukui H, Tomita T, Miwa H. Carcinogenesis of Barrett’s esophagus: a review of the clinical literature. Clin J Gastroenterol [Internet]. 2013 [citado 18/04/2020];6(6):399-414. Disponible en: https://pubmed.ncbi.nlm.nih.gov/26182128/. https://doi.org/10.1007/s12328-013-0412-z
Downloads
Published
How to Cite
Issue
Section
License
Authors who have publications with this journal agree to the following terms:
- Authors will retain their copyright and assign to the journal the right of first publication of their work, which will simultaneously be subject to a Creative Commons License / Attribution-Noncommercial 4.0 International (CC BY-NC 4.0) that allows third parties to share the work as long as its author and first publication in this journal are indicated.
- Authors may adopt other non-exclusive license agreements for distribution of the published version of the work (e.g., depositing it in an institutional repository or publishing it in a monographic volume) as long as the initial publication in this journal is indicated.
- Authors are allowed and encouraged to disseminate their work through the Internet (e.g., in institutional telematic archives or on their web page) before and during the submission process, which can produce interesting exchanges and increase citations of the published work. (See The effect of open access).
15 junio 2025
