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ItemSafety and efficacy of radial artery conduits for coronary artery bypass surgeryRuengsakulrach, Permyos ( 2001-06)Coronary artery bypass grafting (CABG) is the most common cardiac surgical operation performed in western countries, and is also increasingly being performed in developing countries. However the long-term results of CABG using the saphenous vein graft have not been satisfactory. Surgeons have therefore been seeking a better conduit. The radial artery (RA) is a potentially suitable alternative conduit and has to date provided good early results. This thesis investigates the utility of the RA as a coronary artery bypass graft from a number of perspectives. It demonstrates the safety of RA harvesting by examining hand collateral circulation using anatomical dissection, physical examination using the modified Allen test, measuring digital blood pressure, and examining the flow velocity in the digital artery using Doppler ultrasound. Anatomical examinations revealed consistent continuity between the RA and ulnar artery in the hand through either superficial or deep palmar arches. The modified Allen test was found to be useful as a screening test compared with the Doppler dynamic test and digital blood pressure index. A histological comparison was made between pre-existing intimal disease in the RA compared with that in the standard conduit the internal thoracic artery (ITA). The RA showed a higher prevalence and degree of intimal disease than ITA. Risk factors for intimal hyperplasia in the RA were age, diabetes, smoking and peripheral vascular disease. The only predictor for medial calcification was age. (For complete abstract open document)
ItemThe effect of laser induced thermal ablation on liver tumoursNIKFARJAM, MEHRDAD ( 2005-11)Laser thermal ablation (LTA) is an in situ ablative technique that induces heat destruction of liver tumours. Despite increasing clinical use of LTA, reports of long-term outcomes and limitation of treatment in specific cohorts of patients with liver tumours are lacking. In addition, the mechanisms of action of therapy have not been fully elucidated. This study highlights the long-term clinical results and limitations of LTA in the treatment of a cohort of patients with unresectable colorectal liver metastases and examines the mechanisms of action of thermal ablative injury in a murine model.
ItemHypoxia and angiogenesis in renal cell carcinomaLawrentschuk, Nathan Leo ( 2009)Hypoxia is one of the hallmarks of cancer. It was first postulated to occur in solid tumours by Thomlinson and Gray in 1955.1 The presence of hypoxia has been demonstrated in different types of solid tumours.2 Intratumoral hypoxia is caused by the lack of functional blood vessels in proliferating tumour tissue, resulting in low intratumoral oxygen concentrations. If hypoxia is severe or prolonged, cell death occurs.3 Malignant cells can undergo genetic and adaptive changes that allow them to escape from dying of oxygen deprivation. These changes are associated with a more aggressive malignant phenotype 4,5 conferring resistance to radiation 6,7 and chemotherapeutic agents.3,8,9 Hence hypoxia is known to be a key factor responsible for tumour resistance in humans. Invasive polarographic oxygen sensor measurements have demonstrated hypoxia in solid tumours and it is generally defined to occur at an oxygen tension less than ten mmHg.10 Perhaps of more importance is that hypoxia has been demonstrated to be a prognostic indicator for local control after treatment with radiotherapy in glioma, head and neck and cervical cancers.11-13 It has also been able to predict for survival and the presence of distant metastases in soft tissue sarcomas.14 Finally, the significance of hypoxia in the activation and induction of functional molecules such as hypoxia inducible factors (HIFs) and VEGF, the modulation of gene expression (e.g. carbonic anhydrase IX), increased proto-oncogene levels, activation of nuclear factors and accumulation of other proteins (e.g. TP53) although progressing, is yet to be defined.15,16 Thus, it is of clinical interest to understand the levels of hypoxia and numbers of hypoxic cell populations in tumours, particularly those resistant to radiation and chemotherapy. In doing so clinicians and researchers may formulate more accurate prognostic information and develop treatments targeting hypoxic cells. Renal cell carcinoma (RCC) is a tumour resistant to radiation and chemotherapy that is yet to have its oxygen status investigated. Although the “gold standard” of oxygen tension measurement is the Polarographic Oxygen Sensor (POS or Eppendorf pO2 histograph), non-invasive means of measuring oxygen status via imaging, immunohistochemistry or serum tumour markers are more practical. As highlighted by Menon and Fraker, it is imperative that reliable, globally usable, and technically simplistic methods be developed to yield a consistent, comprehensive, and reliable profile of tumour oxygenation. Until newer more reliable techniques are developed, existing independent techniques or appropriate combinations of techniques should be optimized and validated using known endpoints in tumour oxygenation status and/or treatment outcomes.17 Hanahan and Weinberg 18 surmised that the field of cancer research has largely been guided by a reductionist focus on cancer cells and the genes within them- a focus that has produced an extraordinary body of knowledge. Looking forward in time, they believe that progress in cancer research would come from regarding tumours as complex tissues in which mutant cancer cells have conscripted and subverted normal cell types (endothelial cells, immune cells, fibroblasts) to serve as active collaborators in their neoplastic agenda. The interactions between the genetically altered malignant cells and these supporting coconspirators will prove critical to understanding cancer pathogenesis and to the development of novel, effective therapies.18 Essentially, the background outlined here not only highlights the core aim of this thesis: to better understand the oxygen status of renal cell carcinoma and the relationship of this to angiogenesis so that better targeted therapies may be pursued in the future; but it also places this research in the context of the future proposed by Hanahan and Weinberg,18 by clearly focusing on collaborators in the neoplastic agenda, rather than just tumour cells themselves, to better understand RCC.