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Title: Aspects of the pathophysiology of oesophageal cancer
Author: Stacey, Bernard Stephan Frank
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2010
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Part 1 Introduction: Stent insertion to palliate malignant dysphagia is becoming more common as the incidence of oesophageal cancer rises and there are several studies demonstrating the effectiveness of this technique in improving symptoms. However, palliation of dysphagia may be incomplete, poor or become a recurrent need. Upper gastrointestinal endoscopy forms the mainstay of both investigation and treatment for these patients but it is invasive, has a morbidity and mortality attached and does not always aid in the diagnosis of inadequately palliated or recurrent dysphagia, which is sometimes due to disordered motility and not loss of luminal patency. Methodology: Using oesophageal scintigraphy we first validated the technique in ten normal controls on two separate occasions and then applied the technique to patients before and one month after oesophageal stenting. In addition, other objective measurements including weight loss, body fat, quality of life and swallow scores were recorded in order to assess the validity of the technique for the longer term follow up of patients being treated for inoperable oesophageal cancer. Results: It was found that the technique was valid and reproducible in normal subjects and, when applied to patients with oesophageal cancer it was well tole~ated and that the percentage distance covered in 10 and 30 seconds was a measure of luminal patency and regional dysmotility respectively. Whilst stenting demonstrably improved oesophageal transit in most cases this was mirrored by an arrest in decline, rather than an improvement in quality of life scores. Conclusions: Oesophageal scintigraphy is a well . tolerated technique for assessing swallowing in health and disease but has limited practical applications as no effective treatments currently exist for the treatment of regional dysmotility in cancer. Arising from this work we have developed a novel technique that allows for the quantitative investigation and follow up of patients with delayed oesophageal transit based upon oesophageal scintigraphy and subsequent data analysis using image analysis and 3-D graphing software. The term given to this was 'Functional Oesophageal Mapping' and the process is described in detail and a clinical example given. Part 2 Introduction: We tested the hypothesis that HER-2 protein over-expression occurs in oesophageal adenocarcinoma and that this is associated with HER-2 gene amplification, histopathological tumour characteristics and clinical outcome, similar to the situation in breast cancer. Methodology: Blocks from 100 resected oesophageal adenocarcinoma specimens were retrieved and stained for the presence of c-erbB-2 protein using immunohistochemistry and HER-2 gene amplification using fluorescence in situ hybridization respectively. These are the same kits that are used in FDA-approved methods for predicting trastuzumab response in breast cancer. A minimum of five years of clinical follow up was available and patient demographic information was recorded in all the cases. Histopathological tumour and patient characteristics and survival were determined. Results: The survival of groups with chromosome 17 polyploidy and HER-2 gene amplification was significantly worse than groups that were diploid for chromosome 17 without HER-2 amplification Conclusions: The reduced survival in patients with chromosome 17 polyploidy and with HER-2 gene amplification suggests an avenue for additional treatments in these cases with trastuzumab (Herceptin). This is currently used in patients with breast cancers displaying similar characteristics.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available