{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T09:10:00Z","timestamp":1758705000730,"version":"3.37.3"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T00:00:00Z","timestamp":1490054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Proton pump inhibitors and laparoscopic anti\u2010reflux surgery (<jats:styled-content style=\"fixed-case\">LARS<\/jats:styled-content>) offer long\u2010term symptom control to patients with gastro\u2010oesophageal reflux disease (<jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the process of \u2018normalisation\u2019 of the squamous epithelium morphology of the distal oesophagus on these therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the <jats:styled-content style=\"fixed-case\">LOTUS<\/jats:styled-content> trial<jats:bold>,<\/jats:bold> 554 patients with chronic <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> were randomised to receive either esomeprazole (20\u201340 mg daily) or <jats:styled-content style=\"fixed-case\">LARS<\/jats:styled-content>. After 5 years, 372 patients remained in the study (esomeprazole, 192; <jats:styled-content style=\"fixed-case\">LARS<\/jats:styled-content>, 180). Biopsies were taken at the Z\u2010line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki\u201067 immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A gradual improvement in all variables over 5 years was noted in both groups, at both the Z\u2010line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (<jats:italic>P<\/jats:italic> &lt; 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki\u201067 expression were observed (<jats:italic>P<\/jats:italic> &lt; 0.001, all comparisons). No significant differences were found between esomeprazole treatment and <jats:styled-content style=\"fixed-case\">LARS<\/jats:styled-content>. Neither baseline severity score nor Ki\u201067 expression predicted the risk of treatment failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are \u2018normalised\u2019 in patients with chronic <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content>, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.14038","type":"journal-article","created":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T15:06:57Z","timestamp":1490195217000},"page":"1339-1349","source":"Crossref","is-referenced-by-count":7,"title":["The dynamics of the oesophageal squamous epithelium \u2018normalisation\u2019 process in patients with gastro\u2010oesophageal reflux disease treated with long\u2010term acid suppression or anti\u2010reflux surgery"],"prefix":"10.1111","volume":"45","author":[{"given":"L.","family":"Mastracci","sequence":"first","affiliation":[{"name":"Department of Anatomic Pathology University of Genova and IRCCS S.Martino\/IST University Hospital Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-6185","authenticated-orcid":false,"given":"R.","family":"Fiocca","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology University of Genova and IRCCS S.Martino\/IST University Hospital Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Engstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Surgery Sahlgrenska University Hospital Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Attwood","sequence":"additional","affiliation":[{"name":"Department of Surgery North Tyneside General Hospital North Shields UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Ell","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Dr Horst Schmidt\u2010Hospital Wiesbaden Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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