Barrett's esophagus pathophysiology: Difference between revisions

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{{Barrett's esophagus}}
{{Barrett's esophagus}}
{{CMG}}; {{AE}} {{AMK}}
{{CMG}}; {{AE}} {{AMK}}
==Overview==
Barrett's esophagus is marked by the presence of [[columnar epithelium]] in the lower [[esophagus]], replacing the [[normal]] [[squamous cell]] [[epithelium]]; an example of [[metaplasia]]. The [[columnar epithelium]] is better able to withstand the erosive action of the [[gastric]] [[secretions]]; however, this [[metaplasia]] confers an increased [[cancer]] risk of the [[adenocarcinoma]] type.
==Pathophysiology==
==Pathophysiology==
* [[Barrett's esophagus]] [[is]] [[marked]] [[by]] [[the]] [[presence]] [[of]] [[columnar epithelia]] [[in]] [[the]] [[lower]] [[esophagus]], [[replacing]] [[the]] [[normal]] [[squamous cell]] [[epithelium]] & mdash; [[an]] [[example]] [[of]] [[metaplasia]]. [[The]] [[columnar epithelium]] [[is]] [[better]] [[able]] [[to]] [[withstand]] [[the]] [[erosive]] [[action]] [[of]] [[the]] [[gastric]] [[secretions]]; [[however]], [[this]] [[metaplasia]] [[confers]] [[an]] [[increased]] [[cancer]] [[risk]] [[of]] [[the]] [[adenocarcinoma]] [[type]].<ref name="Fléjou_2005">{{cite journal |author=Fléjou J |title=Barrett's oesophagus: from metaplasia to dysplasia and cancer |journal=Gut |volume=54 Suppl 1 |issue= |pages=i6-12 |year=2005 |pmid=15711008}}</ref>


* [[The]] [[metaplastic]] [[columnar cells]] [[may]] [[be]] [[of]] [[two]] [[types]]: [[gastric]] ([[similar]] [[to]] [[those]] [[in]] [[the]] [[stomach]], [[which]] [[is]] [[NOT]] [[technically]] [[Barrett's esophagus]]) [[or]] [[colonic]] ([[similar]] [[to]] [[cells]] [[in]] [[the]] [[intestine]]s). [[A]] [[biopsy]] [[of]] [[the]] [[affected]] [[area]] [[will]] [[often]] [[contain]] [[a]] [[mixture]] [[of]] [[the]] [[two]]. [[Colonic]]-type [[metaplasia]] [[is]] [[the]] [[type]] [[of]] [[metaplasia]] [[associated]] [[with]] [[risk]] [[of]] [[malignancy]] [[in]] [[genetically]] [[susceptible]] [[people]].
===Pathogenesis===


* [[The]] [[metaplasia]] [[of]] [[Barrett's esophagus]] [[is]] [[visible]] [[grossly]] [[through]] [[a]] [[gastroscope]], [[but]] [[biopsy]] [[specimens]] [[must]] [[be]] [[examined]] [[under]] [[a]] [[microscope]] [[to]] [[determine]] [[whether]] [[cells]] [[are]] [[gastric]] [[or]] [[colonic]] [[in]] [[nature]]. [[Colonic]] [[metaplasia]] [[is]] [[usually]] [[identified]] [[by]] [[finding]] [[goblet cells]] [[in]] [[the]] [[epithelium]] [[and]] [[is]] [[necessary]] [[for]] [[the]] [[true]] [[diagnosis]] [[of]] Barrett's.
* Barrett's esophagus (BE) is the [[metaplasia]] which occurs due to change in [[epithelium]] from normal squamous cell epithelium to columnar cell epithelium in the lower end of esophagus due to the [[corrosive]] action of [[gastric]] [[secretions]] in the lower end of the [[esophagus]].<ref name="pmid11342767">{{cite journal| author=Glickman JN, Chen YY, Wang HH, Antonioli DA, Odze RD| title=Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett's esophagus. | journal=Am J Surg Pathol | year= 2001 | volume= 25 | issue= 5 | pages= 569-78 | pmid=11342767 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11342767  }} </ref><ref name="pmid2921087">{{cite journal| author=Gatermann S, Schulz E, Marre R| title=The microbiological efficacy of the combination of fosfomycin and vancomycin against clinically relevant staphylococci. | journal=Infection | year= 1989 | volume= 17 | issue= 1 | pages= 35-7 | pmid=2921087 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2921087  }} </ref> Barrett's esophagus has increased risk of developing into [[Esophageal cancer|esophageal adenocarcinoma]].<ref name="Fléjou_2005">{{cite journal |author=Fléjou J |title=Barrett's oesophagus: from metaplasia to dysplasia and cancer |journal=Gut |volume=54 Suppl 1 |issue= |pages=i6-12 |year=2005 |pmid=15711008}}</ref><ref name="pmid29066320">{{cite journal| author=Rumiato E, Boldrin E, Malacrida S, Realdon S, Fassan M, Morbin T et al.| title=Detection of genetic alterations in cfDNA as a possible strategy to monitor the neoplastic progression of Barrett's esophagus. | journal=Transl Res | year= 2017 | volume= 190 | issue=  | pages= 16-24.e1 | pmid=29066320 | doi=10.1016/j.trsl.2017.09.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29066320  }} </ref><ref name="pmid11353048">{{cite journal| author=Bian YS, Osterheld MC, Bosman FT, Benhattar J, Fontolliet C| title=p53 gene mutation and protein accumulation during neoplastic progression in Barrett's esophagus. | journal=Mod Pathol | year= 2001 | volume= 14 | issue= 5 | pages= 397-403 | pmid=11353048 | doi=10.1038/modpathol.3880324 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11353048  }} </ref>


* [[There]] [[are]] [[many]] [[histologic]] [[mimics]] [[of]] [[Barrett's esophagus]] (i.e. [[goblet cells]] [[occurring]] [[in]] [[the]] [[transitional epithelium]] [[of]] [[normal]] [[esophageal]] [[submucosal gland ducts]], [["pseudogoblet cells"]] [[in]] [[which]] [[abundant]] [[foveolar]] [[(gastric)]] [[type]] [[mucin]] [[simulates]] [[the]] [[acid]] [[mucin]] [[true]] [[goblet cells]]). [[Assessment]] [[of]] [[relationship]] [[to]] [[submucosal glands]] [[and]] [[transitional-type epithelium]] [[with]] [[examination]] [[of]] [[multiple]] [[levels]] [[through]] [[the]] [[tissue]] [[may] [[allow]] [[the]] [[pathologist]] [[to]] [[reliably]] [[distinguish]] [[between]] [[goblet cells]] [[of]] [[submucosal gland ducts]] [[and] [[true]] [[Barrett's esophagus]] (specialized columnar [[metaplasia]]).  [[Use]] [[of]] [[the]] [[histochemical]] [[stain]] [[Alcian]] [[blue]] [[pH]] 2.5 [[is]] [[also]] [[frequently]] [[used]] [[to]] [[distinguish]] [[true]] [[intestinal-type]] [[mucins]] [[from]] [[their]] [[histologic]] [[mimics]]. [[Recently]], [[immunohistochemical]] [[analysis]] [[with]] [[antibodies]] [[to]] CDX-2 (specific for mid and [[hind-gut]] [[intestinal]] [[derivation]]) [[has]] [[also]] [[been]] [[utilized]] [[to]] [[identify]] [[true]] [[intestinal-type metaplastic cells]].  
* There are two types of [[cells]] occur in the [[Metaplasticity|metaplastic]] [[columnar epithelium]] of Barrett's esophagus: one is [[gastric]] type and other is colonic type. [[Gastric]] type resemble the same cells which line the gastric epithelium and colonic type resembles the same cells lining the [[intestinal]] [[epithelium]]. There will be combination of both type of [[cells]] seen on the [[biopsies]] taken from these [[patients]] during the [[endoscopy]]. The type of [[metaplasia]] in which there is increased chance of developing into Barrett's esophagus is colonic type [[metaplasia]] in patients with increased [[genetic]] risk.<ref name="pmid12171951">{{cite journal| author=Chak A, Lee T, Kinnard MF, Brock W, Faulx A, Willis J et al.| title=Familial aggregation of Barrett's oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults. | journal=Gut | year= 2002 | volume= 51 | issue= 3 | pages= 323-8 | pmid=12171951 | doi= | pmc=1773365 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12171951 }} </ref><ref name="pmid24480679">{{cite journal| author=Verbeek RE, Spittuler LF, Peute A, van Oijen MG, Ten Kate FJ, Vermeijden JR et al.| title=Familial clustering of Barrett's esophagus and esophageal adenocarcinoma in a European cohort. | journal=Clin Gastroenterol Hepatol | year= 2014 | volume= 12 | issue= 10 | pages= 1656-63.e1 | pmid=24480679 | doi=10.1016/j.cgh.2014.01.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24480679  }} </ref><ref name="pmid29073141">{{cite journal| author=Sun X, Chandar AK, Canto MI, Thota PN, Brock M, Shaheen NJ et al.| title=Genomic regions associated with susceptibility to Barrett's esophagus and esophageal adenocarcinoma in African Americans: The cross BETRNet admixture study. | journal=PLoS One | year= 2017 | volume= 12 | issue= 10 | pages= e0184962 | pmid=29073141 | doi=10.1371/journal.pone.0184962 | pmc=5657624 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29073141  }} </ref><ref name="pmid27486097">{{cite journal| author=Buas MF, He Q, Johnson LG, Onstad L, Levine DM, Thrift AP et al.| title=Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma. | journal=Gut | year= 2017 | volume= 66 | issue= 10 | pages= 1739-1747 | pmid=27486097 | doi=10.1136/gutjnl-2016-311622 | pmc=5296402 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27486097  }} </ref><ref name="pmid26783083">{{cite journal| author=Becker J, May A, Gerges C, Anders M, Schmidt C, Veits L et al.| title=The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk. | journal=Cancer Med | year= 2016 | volume= 5 | issue= 5 | pages= 888-91 | pmid=26783083 | doi=10.1002/cam4.641 | pmc=4864818 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26783083  }} </ref><ref name="pmid26414697">{{cite journal| author=Ek WE, Lagergren K, Cook M, Wu AH, Abnet CC, Levine D et al.| title=Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma. | journal=Int J Cancer | year= 2016 | volume= 138 | issue= 5 | pages= 1146-52 | pmid=26414697 | doi=10.1002/ijc.29863 | pmc=4715576 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26414697  }} </ref><ref name="pmid14518305">{{cite journal| author=Schneider PM, Hölscher AH, Wegerer S, König U, Becker K, Siewert JR| title=[Clinical significance of p53 tumor suppressor gene mutations in adenocarcinoma in Barrett esophagus]. | journal=Langenbecks Arch Chir Suppl Kongressbd | year= 1998 | volume= 115 | issue= Suppl I | pages= 495-9 | pmid=14518305 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14518305  }} </ref>


* [[In]] [[the]] [[United States]], [[it]] [[is]] [[estimated]] [[that]] 8 - 12% [[of]] [[patients]] [[who]] [[are]] [[diagnosed]] [[with]] [[Barrett's esophagus]] [[have]] [[been]] [[misdiagnosed]]. [[This]] [[significant]] [[diagnostic]] [[error]] [[may]] [[result]] [[in]] [[higher]] [[rates]] [[of]] [[medical]] [[and]] [[life]] [[insurance]] [[rates]] [[for]] [[those]] [[misdiagnosed]]; [[as well as]] [[enrollment]] [[of]] [[patients]] [[in]] [[unnecessary]] [[surveillance]] [[programs]] (i.e. [[annual]] [[endoscopic]] [[evaluation]] [[and]] [[biopsy]] [[to]] [[monitor]] [[for]] [[the]] [[development] [[of]] [[Barrett's esophagus]]). [[Second]] ([[consulting]]) [[opinions]] [[on]] [[pathologic]] [[materials]] [[are]] [[easily]] [[available]] [[as]] [[slides]] [[and]] [[tissue blocks]] [[are]] [[retained]] [[for] 10 and 20 [[years]], [[respectively]]. [[To]] [[request]] [[a]] [[consultation]] [[opinion]], [[patients]] [[may]] [[contact]] [[their]] [[gastroenterologist]] [[for]] [[referral]] [[to]] [[a]] [[GI]] [[pathology]] [[specialty]] [[center]].
* Barrett's esophagus can be seen grossly by its red/light brown color of its [[mucosa]] as compared to the light pink color of normal [[mucosa]] of [[esophagus]] under [[endoscopic]] [[examination]], but it is very important to take [[biopsy]] specimens during [[endoscopic]] [[examination]] and should be microscopically examined to see what type of [[cells]] are present among both the types of [[gastric]] and colonic type of [[cells]]. To make the final [[diagnosis]] of Barrett's, it is very necessary to find the colonic [[metaplasia]] and which can be identified by finding of the [[goblet cells]] in the [[epithelium]] of the [[biopsy]] specimens.<ref name="pmid26783083" /><ref name="pmid26414697" /><ref name="pmid14518305" />


* [[After]] [[the]] [[initial]] [[diagnosis]] [[of]] [[Barrett's esophagus]] [[is]] [[rendered]], [[affected]] [[persons]] [[undergo]] [[annual]] [[surveillance]] [[to]] [[detect]] [[changes]] [[that]] [[indicate]] [[higher]] [[risk]] [[to]] [[progression]] [[to]] [[cancer]]: [[development]] [[of]] [[dysplasia]]. [[There]] [[is]] [[considerable]] [[variability]] [[in]] [[assessment]] [[for]] [[dysplasia]] [[among]] [[pathologists]].  [[Recently]], [[gastroenterology]] and [[GI]] [[pathology]] [[societies]] [[have]] [[recommended]] [[that]] [[any]] [[diagnosis]] [[of]] [[high]] [[grade]] [[dysplasia]] [[in]] [[Barrett's]] [[be]] [[confirmed]] [[by]] [[at]] [[least]] [[two]] [[fellowship]] [[trained]] [[GI]] [[pathologists]] [[prior]] [[to]] [[definitive]] [[treatment]] [[for]] [[patients]].
* One of the main causes of the Barrett's esophagus is [[GERD|gastroesophageal reflux disease (GERD)]]. It has been seen in many studies that chronic [[reflux]] caused by [[GERD]] induces a vicious circle of [[injury|injuries]] and repair cycle in the [[squamous epithelium]] of [[esophagus]]. By this process, it leads to change of epithelium from normal squamous epithelium to the [[columnar epithelium]] as [[columnar epithelium]] is less susceptible to the [[injury]] caused by the [[acid]] [[injury]] as compared to the [[squamous epithelium]].<ref>Spechler SJ. Barrett's esophagus. Semin Gastrointest Dis 1996; 7:51.</ref><ref name="pmid8705259">{{cite journal| author=Spechler SJ| title=Barrett's esophagus. | journal=Semin Gastrointest Dis | year= 1996 | volume= 7 | issue= 2 | pages= 51-60 | pmid=8705259 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8705259  }} </ref><ref name="pmid4146903">{{cite journal| author=Lavy UI, Funcke AB, van Hell G, Timmerman H| title=Pharmacological properties of ((3alpha-tropanyl)oxy)-5H-benzo(4,5)cycloheptal(1,2-b)-pyridine hydrogen maleate (BS 7723). | journal=Arzneimittelforschung | year= 1973 | volume= 23 | issue= 6 | pages= 854-8 | pmid=4146903 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4146903  }} </ref><ref name="pmid10929625">{{cite journal| author=von Schrenck T| title=[Diagnosis of gastroesophageal reflux and Barrett esophagus]. | journal=Zentralbl Chir | year= 2000 | volume= 125 | issue= 5 | pages= 414-23 | pmid=10929625 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10929625 }} </ref><ref name="pmid28336546">{{cite journal| author=Minacapelli CD, Bajpai M, Geng X, Cheng CL, Chouthai AA, Souza R et al.| title=Barrett's metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux. | journal=Am J Physiol Gastrointest Liver Physiol | year= 2017 | volume= 312 | issue= 6 | pages= G615-G622 | pmid=28336546 | doi=10.1152/ajpgi.00268.2016 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28336546  }} </ref>


* [[Recent]] [[evidence]] [[has]] [[pointed]] [[to]] [[a]] [[similar]] [[condition]] [[developing]] [[in]] [[the]] [[distal]] [[gut]] [[epithelium]].  [[Barrett's]] [[Anus]] [[is]] [[a]] [[metaplastic]] [[change]] [[in]] [[the] [[distal]] [[rectum]] [[whose]] [[cellularity]] [[is]] [[similar]] [[to]] [[that]] [[of]] [[the]] [[gastric]] [[mucosa]]. [[While]] [[the]] [[condition]] [[is]] [[stable]] [[for]] [[many]] [[years]], [[there]] [[has]] [[been]] [[recent]] [[evidence]] [[to]] [[show]] [[that]] [[it]] [[is]] [[the]] [[predisposing]] [[lesion]] [[to]] [[both]] [[anal]] [[teratoma]] [[and]] [[squamous cell carcinoma]] [[of]] [[the]] [[anus]]. [[Frequent]] [[bouts]] [[of]] [[steatorrhea]] [[are]] [[commonly]] [[cited]] [[as]] [[the]] [[most]] [[likely]] [[cause]] [[of]] [[Barrett's Anus]], [[but]] [[much]] [[more]] [[research]] [[needs]] [[to]] [[be]] [[done]] [[in]] [[order]] [[to]] [[rule out]] [[causes]] [[such]] [[as]] [[HPV]] 8,13.
* [[Patients]] with BE tend to have more severe [[GERD]].
* [[It]] [[appears]] [[that]] [[chronic]] [[GE]] [[reflux]] [[is]] [[causes]] [[the]] [[injury]] – [[repair]] [[cycle]] [[that]] [[stimulates]] [[squamous]] [[metaplasia]]. [[The]] [[columnar cells]] [[are]] [[more]] [[resistant]] [[to]] [[acid]] [[injury]] [[than]] [[the]] [[squamous cells]].
*:* [[Patients]] [[with]] BE [[tend]] [[to]] [[have]] [[more]] [[severe]] [[GERD]].
* [[Although]] [[one]] [[would]] [[think]] [[that]] BE [[develops]] [[over]] [[years]], [[with]] [[slow]] [[replacement]] [[of]] [[squamous cells]] [[by]] [[columnar cells]], [[it]] [[appears]] [[that]] [[this]] [[is]] [[not]] [[the]] [[case]]. BE [[tends]] [[to]] [[develop]] [[all]] [[at]] [[once]] [[with]] [[little]] [[or]] [[no]] [[progression]]. [[The]] [[reason]] [[for]] [[this]] [[is]] [[unknown]].
* Paull et.al. [[described]] [[three]] [[types]] [[of]] [[columnar epithelium]] [[that]] [[can]] [[be]] [[seen]] [[in]] BE:
*:* [[Gastric]] [[junctional]]-[[type]] [[epithelium]] [[which]] [[has]] [[a]] [[pitted]] ([[foveolar]]) [[surface]] [[and]] [[mucus-secreting cells]].
*:* [[Gastric]] fundus-type [[epithelium]] [[that]] [[also]] [[has]] [[a]] [[pitted]] [[surface]] [[lined]] [[by] [[mucus-secreting cells]], [[in]] [[addition]] [[to]] [[having]] [[a]] [[deeper]] [[glandular]] [[layer]] [[that]] [[contains]] [[chief]] [[and]] [[parietal cells]].
*:* [[Specialized]] [[intestinal]] ([[columnar]]) [[metaplasia]] [[that]] [[has]] [[a]] [[villiform]] [[surface]] [[with]] [[mucus]] [[secreting]] [[columnar cells]] [[and]] [[goblet cells]].


==Pathophysiology==
* Although one would think that BE develops over years, with [[slow]] replacement of [[squamous]] [[cells]] by columnar [[cells]], it appears that this is not the case. BE tends to develop all at once with little or no progression. The reason for this is unknown.


===Pathogenesis===
==Genetics==
*The exact pathogenesis of [disease name] is not fully understood.
*The development of [[Barrett's esophagus]] is the result of multiple genetic mutations including mutations on chromosome 11p in European ancestry, genetic mutation of MGST1, mutations of genes GDF7 and TBX5, polymorphisms in genes in the androgen pathway and genetic mutations in p53 tumor suppressor.<ref name="pmid12171951">{{cite journal| author=Chak A, Lee T, Kinnard MF, Brock W, Faulx A, Willis J et al.| title=Familial aggregation of Barrett's oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults. | journal=Gut | year= 2002 | volume= 51 | issue= 3 | pages= 323-8 | pmid=12171951 | doi= | pmc=1773365 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12171951  }} </ref><ref name="pmid24480679">{{cite journal| author=Verbeek RE, Spittuler LF, Peute A, van Oijen MG, Ten Kate FJ, Vermeijden JR et al.| title=Familial clustering of Barrett's esophagus and esophageal adenocarcinoma in a European cohort. | journal=Clin Gastroenterol Hepatol | year= 2014 | volume= 12 | issue= 10 | pages= 1656-63.e1 | pmid=24480679 | doi=10.1016/j.cgh.2014.01.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24480679  }} </ref><ref name="pmid29073141">{{cite journal| author=Sun X, Chandar AK, Canto MI, Thota PN, Brock M, Shaheen NJ et al.| title=Genomic regions associated with susceptibility to Barrett's esophagus and esophageal adenocarcinoma in African Americans: The cross BETRNet admixture study. | journal=PLoS One | year= 2017 | volume= 12 | issue= 10 | pages= e0184962 | pmid=29073141 | doi=10.1371/journal.pone.0184962 | pmc=5657624 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29073141  }} </ref><ref name="pmid27486097">{{cite journal| author=Buas MF, He Q, Johnson LG, Onstad L, Levine DM, Thrift AP et al.| title=Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma. | journal=Gut | year= 2017 | volume= 66 | issue= 10 | pages= 1739-1747 | pmid=27486097 | doi=10.1136/gutjnl-2016-311622 | pmc=5296402 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27486097  }} </ref><ref name="pmid26783083">{{cite journal| author=Becker J, May A, Gerges C, Anders M, Schmidt C, Veits L et al.| title=The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk. | journal=Cancer Med | year= 2016 | volume= 5 | issue= 5 | pages= 888-91 | pmid=26783083 | doi=10.1002/cam4.641 | pmc=4864818 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26783083  }} </ref><ref name="pmid26414697">{{cite journal| author=Ek WE, Lagergren K, Cook M, Wu AH, Abnet CC, Levine D et al.| title=Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma. | journal=Int J Cancer | year= 2016 | volume= 138 | issue= 5 | pages= 1146-52 | pmid=26414697 | doi=10.1002/ijc.29863 | pmc=4715576 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26414697  }} </ref><ref name="pmid14518305">{{cite journal| author=Schneider PM, Hölscher AH, Wegerer S, König U, Becker K, Siewert JR| title=[Clinical significance of p53 tumor suppressor gene mutations in adenocarcinoma in Barrett esophagus]. | journal=Langenbecks Arch Chir Suppl Kongressbd | year= 1998 | volume= 115 | issue= Suppl I | pages= 495-9 | pmid=14518305 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14518305  }} </ref>
OR
*It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
*The progression to [disease name] usually involves the [molecular pathway].
*The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Genetics==
*[Disease name] is transmitted in [mode of genetic transmission] pattern.
*Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
*The development of [disease name] is the result of multiple genetic mutations.
==Associated Conditions==
==Associated Conditions==
Barrett's esophagus is associated with following associated conditions:
* [[Gastroesophageal reflux disease]]<ref name="pmid10929625">{{cite journal| author=von Schrenck T| title=[Diagnosis of gastroesophageal reflux and Barrett esophagus]. | journal=Zentralbl Chir | year= 2000 | volume= 125 | issue= 5 | pages= 414-23 | pmid=10929625 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10929625  }} </ref><ref name="pmid28336546">{{cite journal| author=Minacapelli CD, Bajpai M, Geng X, Cheng CL, Chouthai AA, Souza R et al.| title=Barrett's metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux. | journal=Am J Physiol Gastrointest Liver Physiol | year= 2017 | volume= 312 | issue= 6 | pages= G615-G622 | pmid=28336546 | doi=10.1152/ajpgi.00268.2016 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28336546  }} </ref><ref name="pmid8705259">{{cite journal| author=Spechler SJ| title=Barrett's esophagus. | journal=Semin Gastrointest Dis | year= 1996 | volume= 7 | issue= 2 | pages= 51-60 | pmid=8705259 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8705259  }} </ref>
* [[Systemic Sclerosis]]<ref name="pmid16142744">{{cite journal| author=Wipff J, Allanore Y, Soussi F, Terris B, Abitbol V, Raymond J et al.| title=Prevalence of Barrett's esophagus in systemic sclerosis. | journal=Arthritis Rheum | year= 2005 | volume= 52 | issue= 9 | pages= 2882-8 | pmid=16142744 | doi=10.1002/art.21261 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16142744  }} </ref>
* [[Metabolic Syndrome]]<ref name="pmid26972225">{{cite journal| author=Drahos J, Li L, Jick SS, Cook MB| title=Metabolic syndrome in relation to Barrett's esophagus and esophageal adenocarcinoma: Results from a large population-based case-control study in the Clinical Practice Research Datalink. | journal=Cancer Epidemiol | year= 2016 | volume= 42 | issue=  | pages= 9-14 | pmid=26972225 | doi=10.1016/j.canep.2016.02.008 | pmc=4899201 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26972225  }} </ref><ref name="pmid24671095">{{cite journal| author=Drahos J, Ricker W, Parsons R, Pfeiffer RM, Warren JL, Cook MB| title=Metabolic syndrome increases risk of Barrett esophagus in the absence of gastroesophageal reflux: an analysis of SEER-Medicare Data. | journal=J Clin Gastroenterol | year= 2015 | volume= 49 | issue= 4 | pages= 282-8 | pmid=24671095 | doi=10.1097/MCG.0000000000000119 | pmc=4176548 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24671095  }} </ref><ref name="pmid27495039">{{cite journal| author=He Q, Li JD, Huang W, Zhu WC, Yang JQ| title=Metabolic syndrome is associated with increased risk of Barrett esophagus: A meta-analysis. | journal=Medicine (Baltimore) | year= 2016 | volume= 95 | issue= 31 | pages= e4338 | pmid=27495039 | doi=10.1097/MD.0000000000004338 | pmc=4979793 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27495039  }} </ref>


==Gross Pathology==
==Gross Pathology==
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*Normally the [[mucosa]] of normal [[esophagus]] is [[light]] pink [[color]] as seen from underlying picture.
*On [[gross]] [[pathology]], [[Barrett's esophagus]] looks like Red/light brown [[esophageal]] [[mucosa]].
[[File:Barretts esophagus.jpg|thumb|center|By Nephron [https://upload.wikimedia.org/wikipedia/commons/8/86/Barretts_esophagus.jpg Source: Libre Pathology]]]


==Microscopic Pathology==
==Microscopic Pathology==
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On microscopic histopathological analysis, gastric junctional type epithelium, gastric fundus type epithelium and specialized intestinal columnar metaplasia are characteristic findings of Barrett's esophagus.<ref name="pmid22943014">{{cite journal| author=Booth CL, Thompson KS| title=Barrett's esophagus: A review of diagnostic criteria, clinical surveillance practices and new developments. | journal=J Gastrointest Oncol | year= 2012 | volume= 3 | issue= 3 | pages= 232-42 | pmid=22943014 | doi=10.3978/j.issn.2078-6891.2012.028 | pmc=3418534 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22943014  }} </ref><ref name="pmid940579">{{cite journal| author=Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK| title=The histologic spectrum of Barrett's esophagus. | journal=N Engl J Med | year= 1976 | volume= 295 | issue= 9 | pages= 476-80 | pmid=940579 | doi=10.1056/NEJM197608262950904 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=940579  }} </ref>
 
* Paull et.al. described three types of [[columnar epithelium]] that can be seen in BE:
*:* [[Gastric]] junctional-type [[epithelium]] which has a pitted (foveolar) surface and mucus-secreting cells.
*:* [[Gastric]] fundus-type [[epithelium]] that also has a pitted surface lined by mucus-secreting cells, in addition to having a deeper [[glandular]] layer that contains [[chief]] and [[parietal cells]].
*:* Specialized [[intestinal]] (columnar) [[metaplasia]] that has a villiform surface with [[mucus]] secreting [[columnar]] [[cells]] and [[goblet cells]].
 
 
 
[[image:Esophagus with intestinal metaplasia -- intermed mag.jpg|thumb|center|Histology of Barrett's esophagus ([By Nephron (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons])]]


==References==
==References==
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Latest revision as of 16:59, 21 February 2018

Barrett's Esophagus Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

Overview

Barrett's esophagus is marked by the presence of columnar epithelium in the lower esophagus, replacing the normal squamous cell epithelium; an example of metaplasia. The columnar epithelium is better able to withstand the erosive action of the gastric secretions; however, this metaplasia confers an increased cancer risk of the adenocarcinoma type.

Pathophysiology

Pathogenesis

  • Although one would think that BE develops over years, with slow replacement of squamous cells by columnar cells, it appears that this is not the case. BE tends to develop all at once with little or no progression. The reason for this is unknown.

Genetics

  • The development of Barrett's esophagus is the result of multiple genetic mutations including mutations on chromosome 11p in European ancestry, genetic mutation of MGST1, mutations of genes GDF7 and TBX5, polymorphisms in genes in the androgen pathway and genetic mutations in p53 tumor suppressor.[6][7][8][9][10][11][12]

Associated Conditions

Barrett's esophagus is associated with following associated conditions:

Gross Pathology

By Nephron Source: Libre Pathology

Microscopic Pathology

  • On microscopic histopathological analysis, gastric junctional type epithelium, gastric fundus type epithelium and specialized intestinal columnar metaplasia are characteristic findings of Barrett's esophagus.[22][23]


Histology of Barrett's esophagus ([By Nephron (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons])

References

  1. ↑ Glickman JN, Chen YY, Wang HH, Antonioli DA, Odze RD (2001). "Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett's esophagus". Am J Surg Pathol. 25 (5): 569–78. PMID 11342767.
  2. ↑ Gatermann S, Schulz E, Marre R (1989). "The microbiological efficacy of the combination of fosfomycin and vancomycin against clinically relevant staphylococci". Infection. 17 (1): 35–7. PMID 2921087.
  3. ↑ Fléjou J (2005). "Barrett's oesophagus: from metaplasia to dysplasia and cancer". Gut. 54 Suppl 1: i6–12. PMID 15711008.
  4. ↑ Rumiato E, Boldrin E, Malacrida S, Realdon S, Fassan M, Morbin T; et al. (2017). "Detection of genetic alterations in cfDNA as a possible strategy to monitor the neoplastic progression of Barrett's esophagus". Transl Res. 190: 16–24.e1. doi:10.1016/j.trsl.2017.09.004. PMID 29066320.
  5. ↑ Bian YS, Osterheld MC, Bosman FT, Benhattar J, Fontolliet C (2001). "p53 gene mutation and protein accumulation during neoplastic progression in Barrett's esophagus". Mod Pathol. 14 (5): 397–403. doi:10.1038/modpathol.3880324. PMID 11353048.
  6. ↑ 6.0 6.1 Chak A, Lee T, Kinnard MF, Brock W, Faulx A, Willis J; et al. (2002). "Familial aggregation of Barrett's oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults". Gut. 51 (3): 323–8. PMC 1773365. PMID 12171951.
  7. ↑ 7.0 7.1 Verbeek RE, Spittuler LF, Peute A, van Oijen MG, Ten Kate FJ, Vermeijden JR; et al. (2014). "Familial clustering of Barrett's esophagus and esophageal adenocarcinoma in a European cohort". Clin Gastroenterol Hepatol. 12 (10): 1656–63.e1. doi:10.1016/j.cgh.2014.01.028. PMID 24480679.
  8. ↑ 8.0 8.1 Sun X, Chandar AK, Canto MI, Thota PN, Brock M, Shaheen NJ; et al. (2017). "Genomic regions associated with susceptibility to Barrett's esophagus and esophageal adenocarcinoma in African Americans: The cross BETRNet admixture study". PLoS One. 12 (10): e0184962. doi:10.1371/journal.pone.0184962. PMC 5657624. PMID 29073141.
  9. ↑ 9.0 9.1 Buas MF, He Q, Johnson LG, Onstad L, Levine DM, Thrift AP; et al. (2017). "Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma". Gut. 66 (10): 1739–1747. doi:10.1136/gutjnl-2016-311622. PMC 5296402. PMID 27486097.
  10. ↑ 10.0 10.1 10.2 Becker J, May A, Gerges C, Anders M, Schmidt C, Veits L; et al. (2016). "The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk". Cancer Med. 5 (5): 888–91. doi:10.1002/cam4.641. PMC 4864818. PMID 26783083.
  11. ↑ 11.0 11.1 11.2 Ek WE, Lagergren K, Cook M, Wu AH, Abnet CC, Levine D; et al. (2016). "Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma". Int J Cancer. 138 (5): 1146–52. doi:10.1002/ijc.29863. PMC 4715576. PMID 26414697.
  12. ↑ 12.0 12.1 12.2 Schneider PM, Hölscher AH, Wegerer S, König U, Becker K, Siewert JR (1998). "[Clinical significance of p53 tumor suppressor gene mutations in adenocarcinoma in Barrett esophagus]". Langenbecks Arch Chir Suppl Kongressbd. 115 (Suppl I): 495–9. PMID 14518305.
  13. ↑ Spechler SJ. Barrett's esophagus. Semin Gastrointest Dis 1996; 7:51.
  14. ↑ 14.0 14.1 Spechler SJ (1996). "Barrett's esophagus". Semin Gastrointest Dis. 7 (2): 51–60. PMID 8705259.
  15. ↑ Lavy UI, Funcke AB, van Hell G, Timmerman H (1973). "Pharmacological properties of ((3alpha-tropanyl)oxy)-5H-benzo(4,5)cycloheptal(1,2-b)-pyridine hydrogen maleate (BS 7723)". Arzneimittelforschung. 23 (6): 854–8. PMID 4146903.
  16. ↑ 16.0 16.1 von Schrenck T (2000). "[Diagnosis of gastroesophageal reflux and Barrett esophagus]". Zentralbl Chir. 125 (5): 414–23. PMID 10929625.
  17. ↑ 17.0 17.1 Minacapelli CD, Bajpai M, Geng X, Cheng CL, Chouthai AA, Souza R; et al. (2017). "Barrett's metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux". Am J Physiol Gastrointest Liver Physiol. 312 (6): G615–G622. doi:10.1152/ajpgi.00268.2016. PMID 28336546.
  18. ↑ Wipff J, Allanore Y, Soussi F, Terris B, Abitbol V, Raymond J; et al. (2005). "Prevalence of Barrett's esophagus in systemic sclerosis". Arthritis Rheum. 52 (9): 2882–8. doi:10.1002/art.21261. PMID 16142744.
  19. ↑ Drahos J, Li L, Jick SS, Cook MB (2016). "Metabolic syndrome in relation to Barrett's esophagus and esophageal adenocarcinoma: Results from a large population-based case-control study in the Clinical Practice Research Datalink". Cancer Epidemiol. 42: 9–14. doi:10.1016/j.canep.2016.02.008. PMC 4899201. PMID 26972225.
  20. ↑ Drahos J, Ricker W, Parsons R, Pfeiffer RM, Warren JL, Cook MB (2015). "Metabolic syndrome increases risk of Barrett esophagus in the absence of gastroesophageal reflux: an analysis of SEER-Medicare Data". J Clin Gastroenterol. 49 (4): 282–8. doi:10.1097/MCG.0000000000000119. PMC 4176548. PMID 24671095.
  21. ↑ He Q, Li JD, Huang W, Zhu WC, Yang JQ (2016). "Metabolic syndrome is associated with increased risk of Barrett esophagus: A meta-analysis". Medicine (Baltimore). 95 (31): e4338. doi:10.1097/MD.0000000000004338. PMC 4979793. PMID 27495039.
  22. ↑ Booth CL, Thompson KS (2012). "Barrett's esophagus: A review of diagnostic criteria, clinical surveillance practices and new developments". J Gastrointest Oncol. 3 (3): 232–42. doi:10.3978/j.issn.2078-6891.2012.028. PMC 3418534. PMID 22943014.
  23. ↑ Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK (1976). "The histologic spectrum of Barrett's esophagus". N Engl J Med. 295 (9): 476–80. doi:10.1056/NEJM197608262950904. PMID 940579.

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