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Title: The incidence and pathogenesis of 'recurrent' Barrett's metaplasia following oesophagectomy (neo-Barrett's)
Author: Dunn, Lorna Jane
Awarding Body: University of Newcastle Upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2013
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Abstract:
Aims: Columnar metaplasia in the oesophageal remnant occurring after subtotal oesophagectomy (neo-Barrett’s) has been proposed as a human model for the development of Barrett’s oesophagus. This study aimed to assess the incidence of this phenomenon and it’s accuracy as a model as well as looking for evidence of field cancerisation in the oesophagus. Methods: Patients underwent prospective endoscopic evaluation having previously undergone oesophagectomy. The presence or absence of columnar epithelium above the surgical anastomosis was noted and biopsies taken. Specimens were stained using H&E and, where consent was granted, with immunohistochemical stains for proteins which have a well described expression pattern in Barrett’s oesophagus. Tumours and adjacent Barrett’s oesophagus from patients who subsequently developed neo-Barrett’s were screened for genetic mutations. Where these were present, subsequent neo-Barrett’s samples were evaluated for the presence of these mutatations. Results: Of 126 eligible patients, 45 (36%) had confirmed neo-Barrett’s. Median time from surgery was greater for patients with neo-Barrett’s (5.7 vs 2.2yrs, p<0.001). There were no cases of dysplasia. Non-intestinalised columnar epithelium occurred earlier than neo-Barrett’s with specialised intestinal metaplasia. Surgery for dysplastic Barrett’s or adenocarcinoma was associated with a similar prevalence of neo-Barrett’s to other indications (41% vs 27%, p=0.157). 37 samples underwent molecular analysis. Typical, Barrett’s like CK7/20 staining pattern was present in 23 cases (62%). Chromogranin A and trefoil factors 1 and 2 were were present in all cases. TFF3 expression was significantly associated with increasing time from surgery (median 8.1yrs vs 3.4yrs, p=0.004). Genetic mutations identified in the resection specimen were not present in the neo-Barrett’s tissue. Conclusions: Columnar metaplasia is common following oesophagectomy. Cellular protein expression is similar to that of sporadic Barrett’s suggesting this is an accurate model. Presence of intestinal metaplasia and TFF3 expression appear to represent later stages in the development of Barrett’s. No evidence of field cancerisation was found.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.632369  DOI: Not available
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