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Title: Novel technologies for the diagnosis and treatment of high risk patients with Barrett's oesophagus
Author: Mackenzie, Gary David
Awarding Body: (UCL) University College London
Current Institution: University College London (University of London)
Date of Award: 2009
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The incidence of oesophageal adenocarcinoma is rising rapidly in the UK with most, if not all, adenocarcinomas arising within Barrett's oesophagus (BO). Defining those patients at high risk is difficult because the histological diagnosis of high grade dysplasia (HGD) is imprecise. Surveillance is unlikely to prove to be of benefit to patients in its current form. Detection of aneuploidy may offer more accurate detection of patients at high risk but its measurement is not currently possible in routine clinical service. Until recently if a patient had HGD the only widely available option was oesophagectomy with all of its adherent risks. This thesis demonstrated that image cytometry can reliably diagnose aneuploidy, that this is correlated with histology and is accurate compared to flow cytometry performed in Seattle. Additionally, aneuploidy measured by image cytometry was validated in a case-control study of future risk of relapse following ablative therapy in BO. Elastic scattering spectroscopy (ESS) is a real-time in vivo technique sensitive to changes in the physical properties of tissue. This data demonstrated that ESS can reliably detect both HGD and aneuploidy in vivo in BO in algorithm generation and prospective testing. A proof of concept study also suggested that ESS could potentially be used for surveillance. Photofrin-PDT has led the way in minimally invasive therapy for HGD in BO. The best regimen of ALA-PDT identified in this thesis is 60mg/kg of ALA activated by 1000J/cm of red light. The early data from the RCT of ALA versus Photofrin-PDT appears to show that ALA may be a lower risk alternative with possibly a higher efficacy for the eradication of HGD. In summary these studies potentially offer the more accurate definition of high risk patients in BO and a reduction in the frequency of endoscopies for those at low risk. Additionally, it has advanced the understanding of ALA-PDT.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available