Barrett’s Oesophagus - studies of novel opticaluddiagnostic tools and minimally invasive therapies

摘要

Dysplasia arising in Barrett’s oesophagus (BO) confers risk of progression toudoesophageal adenocarcinoma (OAC), but it is variable and confounded by sampling errorudand diagnostic inter-observer variability. There is a need for biomarkers to accuratelyuddefine risk and guide surveillance and treatment strategies. Oesophagectomy is theudpreferred treatment of high grade dysplasia (HGD), although this has been challenged byudthe emergence of endoscopic therapy.udThis thesis has shown image cytometric DNA ploidy analysis (ICDA) is accurate whenudcompared to flow cytometry. In a multi centre biomarker validation study, ICDAudpredicted cancer risk in non dysplastic BO. ICDA also predicted relapse followingudphotodynamic therapy (PDT).udNucleotyping (NT) is an imaging technique that evaluates textural changes of nuclei,udwhich correlate with chromatin content and organisation. In this thesis NT wasuddemonstrated to yield additional diagnostic information over ICDA alone, and theudcombination was highly accurate for dysplasia classification.udIn an experiment evaluating replication licensing factors in OAC, those representing theudS-G2-M phases of the cell cycle correlated with aneuploidy. Polo like kinase 1udupregulation had the strongest correlation, the first time this has been shown in BO.udElastic scattering spectroscopy detected DNA ploidy abnormalities with equal accuracyudusing a standard or near infra-red enhanced spectrometer. In a prospective in vivoudsurveillance study, fewer biopsies were taken without a change in the diagnostic yield foruddysplasia. A field carcinogenesis effect was also demonstrated, independent of bothuddysplasia and DNA ploidy abnormalities.udFinally, in a randomised control trial of PDT for HGD, patients with BO less than 7cmudhad significantly higher efficacy and better tolerability with ALA than photofrin.udRadiofrequency ablation was shown to be a safe and effective rescue therapy for patientsudthat failed PDT.udIn summary these studies advance our understanding of biomedical optics for the riskudstratification and treatment of Barrett’s oesophagus.