Surgery (Austin & Northern Health) - Theses
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ItemHealth economic analysis and the role of multiparametric magnetic resonance imaging in prostate cancer( 2023-08)Prostate cancer is the most common solid organ malignancy diagnosed in men. Its diagnosis has historically relied on clinical examination, prostate-specific antigen (PSA) screening and biopsy based on transrectal ultrasound. However, ultrasound is not sensitive in identifying abnormal, potentially cancerous areas in the prostate and therefore biopsy has been performed in a ‘random’ fashion that has led to missing clinically significant disease and over-diagnosing indolent disease. Developments in multiparametric magnetic resonance imaging (mpMRI) technology have suggested that it may be superior modality for local imaging of the prostate gland. This thesis will assess the role of mpMRI in the prostate cancer diagnostic pathway. The diagnostic accuracy of mpMRI was assessed to determine the sensitivity of abnormal mpMRI findings and the negative predictive value of a normal mpMRI. The latter is especially important in the proposal to use mpMRI as a tool to identify which men with an elevated PSA need to proceed to prostate biopsy. I will also assess which MRI findings in different populations of men should be recommended for biopsy. In addition, I will develop a nomogram to determine which men needed systematic sampling at the time of their prostate biopsy for accurate diagnosis of their disease and which men can be accurately diagnosed using targeted biopsy alone. Finally, I will perform an economic assessment to determine the cost-effectiveness of incorporating mpMRI in the primary biopsy setting and for men on active surveillance.
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ItemCommunication, technology and instruments in the modern contemporary setting of urology( 2018)The 2017 Sensis Social Media Report demonstrated an increase in Australians being involved in Social Media Platform. About 84% of Australians access the Internet on a daily basis with higher usage among the age group under 30 year old and less common among people age group of 40 and over. Delivering accurate medical information to patients or caregivers is essential in any medical practice. Having free access healthcare information with the unknown potential of having inaccurate medical information or unmoderated website for quality control while online consumers with health information-seeking behaviour could lead to false health information. Technological innovation has aided the growth in the healthcare industry. The wide expansion of modes of communication and surgical equipments, especially in urology has definitely changed the practice in the past few decades. It is one of the surgical specialty that has increasingly become a technology-driven specialty. With new innovative surgical instruments aiming to improve the outcomes for patients and the ease of accessibility of communication technology in medical practice has certainly improved in various ways within the healthcare setting. Technology has been part of medical and surgical practice and this continue to change the way medicine would be practice in the future. With regards to surgical instruments, the advancement of endoscopic procedures have shown to be a huge advantage in the surgical practice. Although it does not involve all types of surgery but it has been a turning point in some surgical cases. For example, open surgery was the conventional method of treating benign prostatic hyperplasia (BPH) but new treatments have been developed over the years without going through major surgery. BPH is a common condition for men as they get older which causes prostate enlargement which leads lower urinary tract symptoms (LUTS). The BPH prevalence examined in several autopsy studies showed that 20% for men stated to develop in their 40s, reaching between 50% to 60% for men in their 60s, and from 80% to 90% for men in their 70s and 80s. BPH If left untreated, this will eventually lead to blockage of the urinary tract, causing problems to bladder, urinary tract or kidney. The current "gold standard" of treating BPH surgically is transurethral resection of the prostate (TURP) using endoscopic method to remove prostate tissue. Although this method is an effective treatment clearing obstructive prostate tissue, the main side effects include bleeding. Laser surgical therapy for BPH was introduced for more than 20 years. To this date, there are various types of laser therapy that are readily available for surgical treatment of BPH with the unique properties of each laser to allow accurate treatment of BPH. The GOLIATH study demonstrated the GreenLightTM laser was noninferior to TURP in terms of the outcomes and had better results in length of catheterisation and length of hospital stay. The impact of technology in any surgical setting with the aim to improve outcomes in treating any disease while minimizing the risk of complication, or improving has changed significantly. With the rapid evolution of this of technology in the surgical field, however,needs thorough research to ensure high standards of care is delivered when utilizing latest surgical instruments. Essentially, the background outlined here not only highlights the core aim of this thesis: to observe the trend and understand the impact of technology in the current surgical practice. Given that this is will be a broad perspective, this thesis will be focusing on two parts, that is, one related to modes of communication using online technology and how it benefits the users and observing the risks involved. The other part of the thesis will be related to advancement of surgical instruments in urological surgery and the outcomes from the new equipments.
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ItemThe role of zinc in prostate cancer( 2018)Prostate cancer (PCa) is the most common cancer amongst Australian men. Zinc is an essential metal and is vital for normal function of the prostate gland. Castrate-resistant prostate cancer (CRPC) is becoming increasingly resistant and treatment options are limited in number and often associated with poor clinical outcomes. Therefore a pertinent clinical issue is to develop more effective treatment regimes. Zinc appears to play a role in PCa, but a true understanding leading to therapeutic developments is yet to be achieved. In particular evidence regarding cell proliferation and zinc uptake and levels in PCa cells is conflicting. HIF1α is a well-known prognostic marker in PCa associated with poor prognosis, resistance to treatment and development of metastatic disease, however the cause over-expression in CRPC remains a mystery. Therefore the ability of PCa cells to uptake and store zinc, and the role of zinc in PCa cell proliferation, tumour growth and HIF1α mediated survival was investigated in this thesis. CRPC-like human PC3 cells are significantly resistant to docetaxel chemotherapy and overexpress HIF1α protein, compared to normal prostate epithelial control cells (PNT1A). Cell proliferation assays (MTT) demonstrated that physiological zinc administered to PC3 cells significantly slowed growth compared to normal PNT1A and androgen-sensitive PCa (LNCaP) cells. The effect of zinc supplementation or zinc chelation (by TPEN) does not affect macroscopic growth in PC3 xenograft tumours. There is no significant difference in baseline total zinc concentration (measured by ICP-MS) between cell lines normal (PNT1A), androgen sensitive (LNCaP) and CRPC (DU145 and PC3) cells. However, CRPC-like PC3 cells contain significantly higher unbound free Zn2+ and Immunofluorescence Microscopy (IFM) subcellular distribution of Zn2+ in PC3 cells is unlike that seen in normal prostate epithelial cells. PC3 cells are resistant to oxidative stress injury. Zinc strongly induces HIF1α protein expression in these cells in a time and dose dependent manner. Zinc mediated oxidative protection in PC3 cells is a HIF1α dependent as demonstrated in a PC3 HIF1α-KD model. No such zinc protection was seen PNT1A cells. Zinc could be essential in the resistant nature of CRPC cells as Zn2+ ions rescue HIF1α protein expression and are implicated in the normoxic stabilisation of the HIF1α protein by competing with Fe2+ ions at the PHD binding sites. Therefore zinc dysregulation in CRPC cells is an important factor in the development of resistance, as well as potentially progression to metastatic disease and poor prognosis in PCa.