Clinical School (Austin Health) - Research Publications
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ItemRadiotherapy-related complications presenting to a urology department: a more common problem than previously thought?Ma, JL ; Hennessey, DB ; Newell, BP ; Bolton, DM ; Lawrentschuk, N (WILEY, 2018-05-01)OBJECTIVE: To quantify the burden of the side effects of radiotherapy on a tertiary referral urology department. PATIENTS AND METHODS: A prospective study of all urology admissions to a public urology department at a tertiary hospital in a 6-month period was performed. Patients admitted with complications attributable to radiotherapy were included in the study. Data obtained included patient demographics, radiotherapy details, complication type and management required. RESULTS: A total of 1198 patients were admitted; 921 (77%) were elective and 277 (23%) were emergency admissions. Thirteen out of the 921 (1.4%) elective admissions and 20 out of the 277 (7.2%) emergency admissions were attributable to radiotherapy complications. Radiotherapy complications was the fourth most common reason for emergency admission, ahead of acute urinary retention. These 33 admissions were accounted for by 21 patients. A total of 39 separate complications attributable to radiotherapy were diagnosed, with some patients having multiple complications. The median (interquartile range) time to onset of complications was 4 (1-9) years. The surgical intervention rate was 67%. The commonest procedures were washout with/without clot evacuation or diathermy in theatre (15.8%) and urethral dilatation/bladder neck incision (15.8%). Two urinary diversions and two cystoprostatectomies plus urinary diversion were performed. CONCLUSION: Radiotherapy complications are consequential and account for a substantial proportion of a tertiary urology department's emergency workload. These complications generally occur years after radiotherapy and frequently require surgical intervention.
ItemNo Preview AvailableAdvances in ureteroscopyWetherell, DR ; Ling, D ; Ow, D ; Koonjbeharry, B ; Sliwinski, A ; Weerakoon, M ; Papa, N ; Lawrentschuk, N ; Bolton, DM (AME PUBL CO, 2014-09-01)Ureteroscopy (URS) is a procedure which has been constantly evolving since the development of first generation devices 40 years ago. Progress towards smaller and more sophisticated equipment has been particularly rapid in the last decade. We review the significant steps that have been made toward improving outcomes and limiting morbidity with this procedure which is central to the management of urolithiasis and other upper urinary tract pathology.
ItemNo Preview AvailableA multilingual evaluation of current health information on the Internet for the treatments of benign prostatic hyperplasiaChen, EC ; Manecksha, RP ; Abouassaly, R ; Bolton, DM ; Reich, O ; Lawrentschuk, N (ELSEVIER INC, 2014-12-01)PURPOSE: To compare the quality of current Internet information on benign prostatic hyperplasia (BPH) and its surgical and medical managements across four Western languages and a comparative analysis of website sponsors. BPH Internet information quality is particularly relevant in an era of expanding, minimally invasive and surgical therapies. However, no comprehensive analysis exists. METHODS: World Health Organization Health on the Net (HON) principles may be applied to websites using an automated toolbar function. Using a search engine (www.google.com), 9,000 websites were assessed using keywords related to BPH and its medical and surgical treatment in English, French, German, and Spanish. The first 150 websites in each language had HON principles measured whilst a further analysis of site sponsorship was undertaken. RESULTS: Very few BPH websites had greater than ten per cent HON accredited with significant differences (P<0.001) based on terms used for BPH, its medical and surgical management. Tertiles (thirds) of the first 150 websites returned differences in accredited websites (P<0.0001). English language had most accredited websites. Odds ratios for different terms returning accredited websites also were significantly different across terms (P<0.001). Websites were largely commercially sponsored. CONCLUSIONS: A lack of validation of most BPH sites should be appreciated with discrepancies in quality and number of websites across diseases, languages and also between medical and alternate terms. Physicians should participate in and encourage the development of informative, ethical and reliable health websites on the Internet and direct patients to them.
ItemGermline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectoriesTaylor, RA ; Fraser, M ; Livingstone, J ; Espiritu, SMG ; Thorne, H ; Huang, V ; Lo, W ; Shiah, Y-J ; Yamaguchi, TN ; Sliwinski, A ; Horsburgh, S ; Meng, A ; Heisler, LE ; Yu, N ; Yousif, F ; Papargiris, M ; Lawrence, MG ; Timms, L ; Murphy, DG ; Frydenberg, M ; Hopkins, JF ; Bolton, D ; Clouston, D ; McPherson, JD ; van der Kwast, T ; Boutros, PC ; Risbridger, GP ; Bristow, RG (NATURE PUBLISHING GROUP, 2017-01-09)Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC). This dysregulation is enriched in BRCA2-mutant PCa harbouring intraductal carcinoma (IDC). Microdissection and sequencing of IDC and juxtaposed adjacent non-IDC invasive carcinoma in 10 patients demonstrates a common ancestor to both histopathologies. Overall we show that localized castration-sensitive BRCA2-mutant tumours are uniquely aggressive, due to de novo aberration in genes usually associated with metastatic disease, justifying aggressive initial treatment.
ItemZinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α.Wetherell, D ; Baldwin, GS ; Shulkes, A ; Bolton, D ; Ischia, J ; Patel, O (Impact Journals, 2018-02-02)Zinc ions (Zn2+) are known to influence cell survival and proliferation. However the homeostatic regulation of Zn2+ and their role in prostate cancer (PC) progression is poorly understood. Therefore the subcellular distribution and uptake of Zn2+ in PC cells were investigated. Inductively coupled plasma mass spectroscopy and fluorescent microscopy with the Zn2+-specific fluorescent probe FluoZin-3 were used to quantify total and free Zn2+, respectively, in the normal prostate epithelial cell line (PNT1A) and three human PC cell lines (PC3, DU145 and LNCaP). The effects of Zn2+ treatment on proliferation and survival were measured in vitro using MTT assays and in vivo using mouse xenografts. The ability of Zn2+ to protect against oxidative stress via a HIF1α-dependent mechanism was investigated using a HIF1α knock-down PC3 model. Our results demonstrate that the total Zn2+ concentration in normal PNT1A and PC cells is similar, but PC3 cells contain significantly higher free Zn2+ than PNT1A cells (p < 0.01). PNT1A cells can survive better in the presence of high concentrations of Zn2+ than PC3 cells. Exposure to 10 µM Zn2+ over 72 hours significantly reduces PC3 cell proliferation in vitro but not in vivo. Zn2+ increases PC3 cell survival up to 2.3-fold under oxidative stress, and this protective effect is not seen in PNT1A cells or in a HIF1α-KD PC3 cell model. A state of Zn2+ dyshomeostasis exists in PC. HIF1α is an integral component of a Zn2+-dependent protective mechanism present in PC3 cells. This pathway may be clinically significant through its contribution to castrate-resistant PC survival.
ItemCurrent role of salvage robotic-assisted laparoscopic prostatectomyWetherell, D ; Bolton, D ; Kavanagh, L ; Perera, M (SPRINGER, 2013-06-01)OBJECTIVES: Salvage Robotic-Assisted Laparoscopic Prostatectomy (sRALP) is a treatment option for biochemical recurrence (BCR) in prostate cancer. It is a new and presently uncommonly performed procedure, which may be technically challenging. We aim to summarise the current literature regarding sRALP with specific reference to patient selection, complications and peri-operative functional and oncological outcomes. METHODS: A comprehensive and critical review of all peer-reviewed publications regarding sRALP. RESULTS: Within the body of literature, we identified six low-volume case-series studies analysing outcomes of sRALP. Overall, peri-operative outcomes were encouraging with low complication rates and estimated blood loss (EBL) equivocal to open and laparoscopic salvage radical prostatectomy (sRP). Long-term follow-up for functional and oncological outcomes was limited. From the limited follow-up data, the current sRALP studies show similar BCR compared to large-volume open sRP series. Potency outcomes were poor post-sRALP. CONCLUSIONS: Salvage Robotic-Assisted Laparoscopic Prostatectomy is a technically feasible operation with a low risk of significant associated complications. Robotic technology can aid the surgeon in salvage prostatectomy. Data on functional and oncological outcomes lack long-term information but initial results are encouraging. Larger series with longer follow-up periods are necessary to draw significant conclusions about the efficacy of sRALP.
ItemThree dimensional models in uro-oncology: a future built with additive fabricationManning, TG ; O'Brien, JS ; Christidis, D ; Perera, M ; Coles-Black, J ; Chuen, J ; Bolton, DM ; Lawrentschuk, N (SPRINGER, 2018-04-01)PURPOSE: Three-dimensional (3D) printing was invented in 1983 but has only just begun to influence medicine and surgery. Conversion of digital images into physical models demonstrates promise to revolutionize multiple domains of surgery. In the field of uro-oncology, researchers and clinicians have recognized the potential of this technology and are working towards making it an integral part of urological practice. We review current literature regarding 3D printing and other 3D technology in the field of urology. METHOD: A comprehensive assessment of contemporary literature was performed according to a modified PRISMA analysis for the purposes of this narrative review article. Medical databases that were searched included: Web of Science, EMBASE and Cochrane databases. Articles assessed were limited only to English-language peer-reviewed articles published between 1980 and 2017. The search terms used were "3D", "3-dimensional", "printing", "printing technology", "urology", "surgery". Acceptable articles were reviewed and incorporated for their merit and relevance with preference given for articles with high impact, original research and recent advances. RESULTS: Thirty-five publications were included in final analysis and discussion. CONCLUSIONS: The area of 3D printing in Urology shows promising results, but further research is required and cost reduction must occur before clinicians fully embrace its use. As costs continue to decline and diversity of materials continues to expand, research and clinical utilization will increase. Recent advances have demonstrated the potential of this technology in the realms of education and surgical optimization. The generation of personalized organs using 3D printing scaffolding remains the 'holy grail' of this technology.