Weranja Ranasinghe

Effects of bariatric surgery on urinary and sexual function.

Study Type – Symptom prevalence (non‐consecutive cohort)
Level of Evidence 4

HIF1α Expression under Normoxia in Prostate Cancer— Which Pathways to Target?

PURPOSE HIF1α over expression correlates with poor prognosis in a number of cancers. Although it is widely accepted that hypoxia induces HIF1α expression up-regulation by a reduction in oxygen dependent degradation, HIF1α up-regulation under normoxic conditions is noted with increasing frequency in many cancers. We reviewed the current knowledge of mechanisms of normoxic and hypoxic HIF1α up-regulation, and its therapeutic implications with a particular focus on its role as a potential biomarker in prostate cancer. MATERIALS AND METHODS Although the literature on the role of HIFs in cancer development and progression has been reviewed extensively, few publications have specifically considered the role of HIFs in prostate cancer. Therefore, we searched PubMed® and Google® with the key words prostate cancer, castration resistance, metastasis, hypoxia, HIF1α, HIF2α and regulation. Relevant articles, including original research studies and reviews, were selected based on contents and a synopsis was generated. RESULTS Normoxic expression of HIF1α has an important role in the development of prostate cancer chemoresistance, radioresistance and castrate resistance. Thus, HIF1α could serve as a potential biomarker. Furthermore, agents that target HIF1α could be used as adjuvant therapy to decrease resistance to conventional treatment modalities. HIF1α over expression in prostate cancer can be regulated at 3 levels, including transcription, translation and protein stability, by a number of mechanisms such as gene amplification, single nucleotide polymorphism, increased transcription of HIF1α mRNA, expression of truncated isoforms of HIF1α and stabilization of HIF1α. However, there is no definitive consensus and the intriguing question of how HIF1α is up-regulated in prostate cancer is still unanswered. CONCLUSIONS HIF1α over expression under normoxia could serve as a biomarker for chemoresistance, radioresistance and castrate resistance in prostate cancer. There is an urgent need to identify the cause of HIF1α over expression in castrate resistant prostate cancer cells and tumors to guide the choice of HIF inhibitors (transcription or translation based) that are best suited for treating castrate resistant prostate cancer.

Population-based analysis of prostate-specific antigen (PSA) screening in younger men (<55 years) in Australia.

To analyse the trends in opportunistic PSA screening in Australia, focusing on younger men (<55 years of age), to examine the effects of this screening on transrectal ultrasonography (TRUS)‐guided biopsy rates and to determine the nature of prostate cancers (PCas) being detected.

Trends in penile cancer: a comparative study between Australia, England and Wales, and the US

PurposeTo investigate and compare the trends in incidence and mortality of penile cancer between Australia, England and Wales, and the US, and provide hypotheses for these trends.MethodsCancer registry data from 1982 to 2005 inclusive were obtained from Australia, England and Wales, and the United States. From these data, age-specific, -standardised and mortality:incidence ratios were calculated, and compared.ResultsThe overall incidence of penile cancer in England and Wales (1.44 per 100,000 man-years) was higher than in Australia (0.80 per 100,000), and the US (0.66 per 100,000). Incidence of penile cancer in all three countries has remained relatively stable over time. Similarly, although the mortality rates were also higher in England and Wales (0.37 per 100,000 man-years) compared to Australia (0.18 per 100,000) and the US (0.15 per 100,000), the mortality/incidence ratios were similar for all three countries.ConclusionsPenile cancer incidence is low, affecting mainly older men. Rates differ between the three countries, being twice as common in England and Wales as in the other studied regions. Circumcision rates have a potential influence on these rates but are not the sole explanation for the variation.

Incidence of bladder cancer in sri lanka: analysis of the cancer registry data and review of the incidence of bladder cancer in the South asian population.

Purpose To investigate the incidence of bladder cancer (BC) in Sri Lanka and to compare risk factors and outcomes with those of other South Asian nations and South Asian migrants to the United Kingdom (UK) and the United States (US). Materials and Methods The incidence of BC in Sri Lanka was examined by using two separate cancer registry databases over a 5-year period. Smoking rates were compiled by using a population-based survey from 2001 to 2009 and the relative risk was calculated by using published data. Results A total of 637 new cases of BC were diagnosed over the 5-year period. Sri Lankan BC incidence increased from 1985 but remained low (1.36 and 0.3 per 100,000 in males and females) and was similar to the incidence in other South Asian countries. The incidence was lower, however, than in migrant populations in the US and the UK. In densely populated districts of Sri Lanka, these rates almost doubled. Urothelial carcinoma accounted for 72%. The prevalence of male smokers in Sri Lanka was 39%, whereas Pakistan had higher smoking rates with a 6-fold increase in BC. Conclusions Sri Lankan BC incidence was low, similar to other South Asian countries (apart from Pakistan), but the actual incidence is likely higher than the cancer registry rates. Smoking is likely to be the main risk factor for BC. Possible under-reporting in rural areas could account for the low rates of BC in Sri Lanka. Any genetic or environmental protective effects of BC in South Asians seem to be lost on migration to the UK or the US and with higher levels of smoking, as seen in Pakistan.

Incidence of prostate cancer in Sri Lanka using cancer registry data and comparisons with the incidence in South Asian men in England

Study Type – Prevalence (retrospective cohort)

Normoxic regulation of HIF-1α in prostate cancer

The hypoxic microenvironment of tumours, acting via hypoxia inducible factor 1α (HIF‐1α), might promote the angiogenic stimulation required for cancer develop‐ ment, with a resultant aggressive cell pheno type and rapid malignant progres‐ sion.1 In their recent article, Marignol et al.2 described the importance of notch signalling pathways in differentiation, prolifer ation, angiogenesis, vascular remodel ling and apoptosis in prostate cancer (Marignol, L., Rivera‐Figueroa, K., Lynch, T. & Hollywood, D. Hypoxia, notch signalling, and prostate cancer. Nat. Rev. Urol. 10, 405–413; 2013). The Review high‐ lighted similarities between notch‐activated and hypoxic prostate cancer cells. We believe that normoxic HIF‐1α expression in pros‐ tate cancer, is equally important to—if not more important than—hypoxia mediated by HIF‐1α. Indeed, a better understanding of the former would lead to improved prognos‐ tication and, potentially, reduced treatment resistance in men with this disease. Although HIF‐1α has a key role in the physio logical response to hypoxia, its importance in cancers is less clear. High expression of HIF‐1α in some cancer cell lines (for example, renal and breast cancers) has been shown to increase angiogenesis and cancer cell survival, whereas in other cancers (such as ovarian carcinoma), high HIF‐1α concentrations contribute to increased apoptosis.3 In prostate cancer, HIF‐1α overexpression has been linked with shorter time to biochemical recurrence in patients receiving radiotherapy or surgery, castration resistance, chemo resistance and metastasis.4–6 Although hypoxia is a strong driver of HIF‐1α expression, and the presence of hypoxic regions has been shown in many human tumours, the local‐ ized expression of HIF‐1α and its down‐ stream targets only in the hypoxic areas of tumours has been difficult to demon strate.7 Furthermore, it has been consistently diffi‐ cult to demonstrate localized hypoxia, particularly in high‐grade prostate cancer; consequently, HIF‐1α expression is thought to be independent of hypoxia.8 Normoxic regulation of HIF‐1α in prostate cancer

A novel framework for automated, intelligent extraction and analysis of online support group discussions for cancer related outcomes

Cancer care requires an extensive network of support for each patient, from the first discussion of treatment options, subsequent treatment and post-treatment care to surveillance. These increasing expectations of cancer care are a formidable challenge to healthcare systems across the world. This elemental issue arises when allocating appropriate resources to address specific patient needs and expectations.

Modified supine versus prone percutaneous nephrolithotomy: Surgical outcomes from a tertiary teaching hospital

Purpose The traditional prone positioning of percutaneous nephrolithotomy (PCNL) is associated with various anesthetic and logistic difficulties. We aimed to compare the surgical outcomes of PCNLs performed using our modified supine position with those performed in the standard prone position. Materials and Methods A prospective group of 236 renal units (224 patients) undergoing PCNL were included in this 2 site study: 160 were performed in the modified supine position were compared with 76 undergoing PCNL in the prone position. The outcomes of radiation dose, radiation time, stone free rate, body mass index (BMI), stone size, operative time, length of stay (LOS), in hospital and complications were compared. Chi-square and t-tests were used. Results There were no significant differences in mean radiation time, radiation dose or stone size between the modified supine and prone groups. The supine group had a higher mean BMI (31 kg/m2 vs. 28 kg/m2, p=0.03), shorter mean surgical time (93 minutes vs. 123 minutes, p<0.001), shorter mean LOS (2 days vs. 3 days, p=0.005) and higher stone free rate (70% vs. 50%, p=0.005). There were no differences in septic or bleeding complications but the prone group had a higher rate of overall complications. Conclusions Modified supine PCNL has significantly lower operative time, shorter LOS and higher stone-free rate compared with prone in our series, while remaining a safe procedure.

Bladder carcinoma in situ (CIS) in Australia: a rising incidence for an under-reported malignancy

To investigate the incidence of carcinoma in situ (CIS) in Australia and examine implications for its diagnosis and management, as CIS of the urinary bladder is a non‐reportable disease in Australia.