Medicine (St Vincent's) - Theses
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ItemAn Australian population-based study of the incidence and outcomes of hepatocellular carcinoma: the Hepatomas of Melbourne Epidemiological Research (HoMER) study( 2019)Liver cancer, the world’s second highest cause of cancer death, is reportedly increasing in incidence in developed countries including Australia. Hepatocellular carcinoma (HCC), the predominant type of liver cancer, has a complex epidemiology involving the interplay of many dynamic risk factors including chronic viral hepatitis B and C, alcohol-related liver disease and non-alcoholic fatty liver disease. Recent trends in these risk factors, changes in Melbourne’s population demographics, together with advances in HCC diagnostics are thought to be increasing HCC incidence, although this may be currently underreported by the cancer registry. Accurate local epidemiology is required to inform healthcare policy for the appropriate allocation of resources for treatment, prevention and research that will improve clinical and economic outcomes. The major study of this thesis, to my knowledge, is the first in the world to determine the population incidence of HCC using clinical case capture independent of the cancer registry. In doing so, it is also the first study to validate the completeness and accuracy of a cancer registry in reporting HCC, which is critical given that the HCC epidemiology literature has been mostly dependent on local registry data. Over 12 months (July 2012 to June 2013), there were 272 new cases of HCC identified from multiple primary sources including multidisciplinary meeting reviews, hospital inpatient, outpatient and emergency attendance at any of Melbourne’s seven tertiary hospital networks, pathology, radiology and pharmacy databases. After cross- referencing with the Victorian Cancer Registry cases for the same period, the HCC incidence determined by this study was found to be twice as high as that reported by the registry. The recruited population-based prospective cohort of HCC patients then provided the opportunity to examine clinical outcomes across the breadth of presentation, demographics and institutional expertise. This allowed for the determination of factors associated with improved survival, in particular, the influence of HCC surveillance participation. The commonest risk factors for HCC were chronic hepatitis C (41%) and alcohol-related liver disease (39%) followed by chronic hepatitis B (22%). While participation rates were low (40%), surveillance was associated with earlier tumour stage at diagnosis, being offered curative therapies, and improved survival probability. In the era of advanced diagnostic imaging and therapeutics for HCC, only some of which is publicly funded, the economic cost of the HCC disease burden is an important consideration in cost-effectiveness analyses. This HCC incidence cohort provides the basis for the first direct costings study of HCC management in Australia, with associated clinical factors that determine high cost. The highest costs occurred at both of ends of the disease spectrum, with early stage disease curable by liver transplantation or surgical resection, as well as in the sickest patients with advanced disease and only palliative options available. Thus, investment of healthcare expenditure towards disease prevention and early detection would likely be most cost-effective with improved survival and reduced morbidity achieved. This world-first research, using a novel methodology for clinical case capture, determined the population-based incidence of HCC in Melbourne, confirmed the underreporting of incidence by the cancer registry and contributed to the correction of registry classification practices. For cancers with rapidly changing epidemiology such as HCC, accurate and contemporary local data is important in disease prevention and management and in guiding healthcare policy and research.
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ItemEpidemiology, natural history and impact of inflammatory bowel disease in Australia( 2010)The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the gastrointestinal tract. International studies have demonstrated a dramatic rise in the incidence of these conditions over the past several decades. There are no corresponding studies from Australia to determine the local incidence. CD has been shown to have a complicated disease course, with high requirements for surgery and progression to disability. Psychological morbidity is also common, with a negative impact on health related quality of life. International studies have also demonstrated high direct and indirect health economic costs associated with CD. Australian data in each of these areas is either limited or totally absent. The aim of this work was to address the deficiencies in each of these key areas. The first Australian population-based study of IBD incidence was conducted prospectively over a one-year period in the region of Barwon. This utilised an extensive capture-recapture methodology, with near complete case identification and rigorous verification of diagnosed cases. The IBD incidence rates observed are among the highest reported in the world literature. The natural history of CD was then assessed in a retrospective, inception cohort study over a five-year period from the time of diagnosis. There was the progressive development of a more complicated disease phenotype, with high requirements for surgery. The results from surgery were not durable, with 60 percent needing escalation of therapy within 5 years. 41 percent of the cohort met the definition of disabling disease, with the presence of perianal fistulae at diagnosis highlighted as a key risk factor. This was followed by two cross-sectional, questionnaire-based, cohort studies to assess psychological health and health related quality of life (HRQoL) in CD. The first study was conducted in patients from the Inflammatory Bowel Disease Clinic at St. Vincent’s Hospital, Melbourne. The second was in a cohort of patients from the same institution who had required the formation of an ileostomy for CD. Both studies revealed high rates of depression, anxiety and poor HRQoL. These negative factors were contributed to by increased disease activity, but the strongest predictive factor was found to be the use of a negative, maladaptive coping style. Some patients with a stoma have adapted well, but others found it to be a negative experience, with ongoing concerns regarding sexuality and body image. The health economic costs of CD were then established using prospective cost diaries. Both direct and indirect costs were high, in keeping with the complicated natural history of CD. These studies highlight that IBD is common in Australia, and that CD has a complicated natural history, with negative impacts on psychological health and HRQoL, and with high economic costs. There is a need for increased public awareness as well as ongoing research and funding to improve clinical care.