Filters
Availability
Publication Year
Resource Type
Faculty
School/Institute
Publication Search Results
Sort
Results per page
1 - 10 of 30
-
(2018)ThesisIntroduction: Skin disease is common in immunosuppressed solid organ transplant recipients (SOTRs) and skin cancer, in particular, is a major cause of morbidity and mortality in these patients. This study aims to determine the rates and risk factors for skin cancer in Australian heart and lung transplant recipients (HLTRs). It also aims to examine the spectrum of skin diseases encountered in HLTRs and their effect on quality of life (QOL). Methods: Ninety-four participants were recruited from the Dermatology Outpatient Clinic at St. Vincent’s Hospital Sydney between March and December 2016. Retrospective skin cancer diagnoses were obtained from medical records and participants were also examined prospectively for malignant and non-malignant skin disease. A questionnaire and the Dermatology Life Quality Index were administered to all participants. The probabilities of developing non-melanoma skin cancer (NMSC), squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) were estimated using Kaplan-Meier analysis. The association of risk factors with skin cancer development were examined using the Cox proportional hazards model. The association of examined variables with DLQI score were assessed using univariate and multivariate logistic regression analysis. Results: Retrospectively, there were 801 post-transplant skin cancers in 61% of participants. At 5 and 10 years post-transplantation the probabilities were 41% and 67% for developing NMSC, 27% and 53% for developing BCC, and 33% and 62% for developing SCC, respectively. A prospective dermatological diagnosis was made in 87% of the participants over the study period. Actinic keratosis was the most common diagnosis, affecting 53% of participants, followed by skin cancer in 44% and warts in 15% of participants. Other non-malignant skin diseases were less common. Risk factors significantly associated with skin cancer included older age at transplantation, history of pre-transplant skin cancer, and history of ≥5 post-transplant skin cancers. Fitzpatrick skin type 3-6 was associated with a decreased risk of NMSC. Skin disease had a negative effect on the QOL of a minority of HLTRs. The use of tacrolimus was associated with better QOL scores on multivariate analysis. Conclusion: Australian HLTRs have high rates of skin cancer that exceed the rates reported for other SOTRs.
-
-
-
-
-
-
-
-
-
(2007)ThesisOptimisation of the conventional tripartite of pancreatic cancer (PC) treatment have led to significant improvements in mortality, however further knowledge of the underlying molecular processes is still required. Transcript profiling of mRNA expression of over 44K genes with microarray technology demonstrated upregulation of secreted frizzled related protein 4 (sFRP4) and β-catenin in PC compared to normal pancreata. Their pathway – Wnt signalling is integral to transcriptional regulation and aberrations in these molecules are critical in the development of many human malignancies. Immunohistochemistry protocols were evaluated by two independent blinded examiners for antigen expression differences associated with survival patterns in 140 patients with biopsy verified PC and a subset of 23 normal pancreata with substantial observer agreement (kappa value 0.6-0.8). A retrospective cohort was identified from 6 Sydney hospitals between 1972-2003 and archival formalin fixed tissue was collected together with clinicopathological data. Three manual stepwise regression models were fitted for overall, disease-specific and relapse-free survival to determine the value of significant prognostic variables in risk stratification. The models were fitted in a logical order using a careful strategy with step by step interpretation of the results. Immunohistochemistry demonstrated increased sFRP4 membranous expression (> 10%) in 49/95 PC specimens and this correlated with improved overall survival (HR:0.99;95%CI:0.97-6.40;LRchi2=134.75; 1df; ρ< 0.001). Increased sFRP4 cytoplasmic staining (> 2/3) in 46/85 patients increased the disease-specific survival (HR:0.52;95%CI:0.31-0.89;LR test statistic =248.40;1df;ρ< 0.001). Increasing β-catenin membranous expression (< _60%) in 26/116 patients was associated with an increased risk of overall death (HR:3.18;95%CI:1.14-8.89;LR test statistic =4.61;1df,ρ< 0.05). Increasing cytoplasmic expression in 65/114 patients was protective and was associated with prolonged survival on univariate, but not multivariate analysis (Disease specific survival HR:0.75;95%CI:0.56-1.00;logrank chi2=3.91;1df; ρ=0.05). Increased nuclear β-catenin expression in 65/114 patients was associated with prolonged survival (disease-specific HR:0.92;95%CI:0.83-1.02; LR test statistic= 49.72;1df;ρ< 0.001). At the conclusion, 12 patients (8.6%) remained alive, 122 died of their disease (68 males versus 54 females). They were followed for a median of 8.7 months (range 1.0-131.3) months. The median age was 66.5 years (range 34.4-96.0, standard deviation 10.9) years. Pancreatic resection was achieved in 79 patients with 46.8% achieving RO resection. The 30 day post-operative mortality was 2.1%. The overall 1 year survival rate was (33.7% ; 95%CI: 25.78-33.79) with a 5 year survival of (2.87%, 95%CI: 2.83-6.01) and a median survival of (8.90 months; 95%CI: 7.5-10.2). The median disease-specific survival was (9.40; 95%CI: 7.9-10.5 months) and the median time to relapse was 1.2 months (95%CI 1.0-1.2 months). A central tenet of contemporary cancer research is that an understanding of the genetic and molecular abnormalities that accompany the development and progression of cancer is critical to further advances in diagnosis, treatment and eventual prevention. High throughput tissue microarrays were used to study expression of two novel tumour markers in a cohort of pancreatic cancer patients and identified sFRP4 and β-catenin as potential novel prognostic markers.