{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:25:11Z","timestamp":1788431111668,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,12,2]],"date-time":"2016-12-02T00:00:00Z","timestamp":1480636800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Colorectal Disease"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>The pathogenesis of cryptoglandular anal fistula (<jats:styled-content style=\"fixed-case\">AF<\/jats:styled-content>) is still under debate. Tissue inflammation could play a primary role. The pathological process of epithelial mesenchymal transition (<jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>) might be involved but has never been investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In a prospective pilot study, 12 patients with an AF had a fistulectomy. The excised track was divided into proximal (intrasphincteric) and distal (extrasphincteric) parts which were subjected to standard histopathological examination. The cytokines <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101beta were analysed as markers of inflammation, while <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> was evaluated by expression of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010beta, Vimentin, Zeb\u20101, Snail and E\u2010cadherin. The <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein expression of these molecules was investigated by real\u2010time PCR (RT\u2010PCR), Western blot analysis and immunohistochemistry and was compared with that of the normal adjacent tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chronic inflammation and granulation tissue and a stratified epithelium were evident on standard histopathological examination. The cytokine <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 was more expressed in the proximal than the distal part of the track (fold increase 4.34 <jats:italic>vs<\/jats:italic> 3.60), while the reverse was found for <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101beta (fold increase 1.33 <jats:italic>vs<\/jats:italic> 2.01); both were more intensely expressed compared with the normal anal mucosa. <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> was demonstrated, in both proximal and distal parts of the track, with an increase of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010beta, Vimentin, Zeb\u20101 and Snail and a mean decrease of E\u2010cadherin. Western blot analysis and immunohistochemistry confirmed the protein expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The study suggests that chronic inflammation is present in cryptoglandular fistulas. The inflammatory pattern might be different in the proximal than in the distal part of the fistula track. The cytokines <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101beta and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 could play a possible role in fistula formation. The study demonstrates for the first time the potential importance of <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> in the pathogenesis of cryptoglandular AF.<\/jats:p><\/jats:sec>","DOI":"10.1111\/codi.13527","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T15:12:37Z","timestamp":1474384357000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Immunopathological characterization of cryptoglandular anal fistula: a pilot study investigating its pathogenesis"],"prefix":"10.1111","volume":"18","author":[{"given":"C.","family":"Ratto","sequence":"first","affiliation":[{"name":"Proctology Unit Department of Surgical Sciences Catholic University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Litta","sequence":"additional","affiliation":[{"name":"Proctology Unit Department of Surgical Sciences Catholic University 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