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Wu C.,McMaster University | Kapoor A.,McMaster University | Kapoor A.,McMaster Institute of Urology
Expert Opinion on Pharmacotherapy

Introduction: Benign prostatic hyperplasia (BPH) is an age-related phenomenon associated with prostatic enlargement and bladder outlet obstruction that can cause significant lower urinary tract symptoms that greatly affect quality of life. Dutasteride is a selective inhibitor of type 1 and type 2 isoforms of 5-α-reductase, an enzyme responsible for the conversion of testosterone to 5-α-dihydrotestosterone, approved as a treatment for symptomatic BPH. Areas covered: This article will cover the efficacy and safety of dutasteride in the treatment of BPH, with focus on landmark trials conducted on this drug. Medical literature on the use of dutasteride in men with BPH were identified by searching databases since 1996 (including MEDLINE and EMBASE) as well as bibliographies from published literature, clinical trial registries and manufacturer and federal drug regulatory websites. Expert opinion: Dutasteride is an effective, safe and well-tolerated treatment either as monotherapy or in combination with an α-blocker, for the management of symptomatic BPH to improve symptoms, reduce the risk of acute urinary retention and risk for BPH-related surgery. A new prostate-specific antigen baseline should be established after 6 months of therapy for clinical decision making. The relationship between dutasteride and high-grade prostate cancer is not clear, and dutasteride is not approved for prostate cancer chemoprevention. © 2013 Informa UK, Ltd. Source

Benign prostatic hyperplasia (BPH) is an age-related phenomenon associated with prostatic enlargement and bladder outlet obstruction that can cause significant lower urinary tract symptoms (LUTS). These LUTS have a negative impact on an individual's quality of life, which is why treatment of symptomatic BPH has become a major priority. Although surgical interventions exist for treating BPH, pharmacological therapies are often preferred due to their minimal invasiveness and high degree of effectiveness. The three classes of drugs approved for treating BPH include α-blockers, 5-α-reductase inhibitors (5-ARIs) and phosphodiesterase 5 (PDE-5) inhibitors. Individually, each class of drug has been studied and shown to improve symptom relief through a variety of different mechanisms. A more recent focus has been on the development of combinatorial therapies that combine classes of drugs in order to provide maximal benefit. The mTOPS and CombAT studies were the first of their kind to examine whether the combination of 5-ARIs and α-blockers was more effective than monotherapy alone. Both studies found similar results in that the combinatorial therapy was superior to monotherapy. Over the last decade other combinatorial therapies have been at the forefront of investigation. One in particular is the combination of tadalafil, a PDE-5 inhibitor, with finasteride, a 5-ARI. Studies have shown that the combination of tadalafil and finasteride is a safe, effective, and well tolerated treatment for BPH. Evidence suggests that this combination may be particularly effective in reducing treatment-related sexual adverse events associated with 5-ARI treatments. The following review will explore in detail the current evidence surrounding treatment of BPH LUTS using tadalafil and finasteride. © 2016 The Author(s). Source

Deyoung L.,University of Western Ontario | Chung E.,University of Western Ontario | Kovac J.R.,McMaster Institute of Urology | Romano W.,University of Western Ontario | Brock G.B.,University of Western Ontario
Journal of Andrology

Diminished vascular endothelial function results in decreased vasodilator capacity and is associated with erectile dysfunction (ED) in patients afflicted with type 2 diabetes. The current study was designed to evaluate whether daily use of sildenafil could alter endothelial function and improve penile rigidity in a group of patients with diabetic ED. A double-blind, placebo-controlled, prospective trial was conducted with 24 men with type 2 diabetes who were randomized into 2 groups: one receiving daily sildenafil (50 mg, n = 12) and the other placebo (n = 12) for 10 weeks. Erectile function was captured subjectively using the International Index of Erectile Function (IIEF-5), and endothelial function was objectively monitored via brachial artery flow-mediated dilation. Among the placebo and sildenafil groups, there were no significant differences in average patient age, time from type 2 diabetes diagnosis, duration of ED, or baseline IIEF-5 scores. Past medical histories, including smoking, alcohol consumption, hypertension, and hyperlipidemia, were also similar. At the conclusion of the 10-week trial, patients who received daily sildenafil had significantly improved erectile rigidity as captured by IIEF-5 (P <.001) and increased endothelial function via brachial artery flow-mediated dilation (P <.01). Endothelial function in men with type 2 diabetes was enhanced with daily sildenafil. Improved erectile rigidity and enhanced vascular circulation was noted after 10 weeks of daily sildenafil use. © American Society of Andrology. Source

Kovac J.R.,McMaster Institute of Urology | Luke P.P.,University of Western Ontario
International Braz J Urol

Excision of renal cell carcinoma (RCC) with corresponding vena cava thrombus is a technical challenge requiring open resection and vascular clamping. A 58 year old male with a right kidney tumor presented with a thrombus extending 1 cm into the vena cava. Using a hand-assisted transperitoneal approach through a 7 cm gel-port, the right kidney was dissected and the multiple vascular collaterals supplying the tumor were identified and isolated. The inferior vena cava was mobilized 4 cm cephalad and 4 cm caudal to the right renal vein. Lateral manual traction was applied to the right kidney allowing the tumor thrombus to be retracted into the renal vein, clear of the vena cava. After laparoscopic ultrasonographic confirmation of the location of the tip of the tumor thrombus, an articulating laparoscopic vascular stapler was used to staple the vena cava at the ostium of the right renal vein. This allowed removal of the tumor thrombus without the need for a Satinsky clamp. The surgery was completed in 243 minutes with no intra-operative complications. The entire kidney and tumor thrombus was removed with negative surgical margins. Estimated blood loss was 300 cc. We present a laparoscopic resection of a renal mass with associated level II thrombus using a hand-assisted approach. In patients with minimal caval involvement, our surgical approach presents an option to the traditional open resection of a renal mass. Source

Bhan S.N.,McMaster University | Pautler S.E.,University of Western Ontario | Shayegan B.,McMaster Institute of Urology | Voss M.D.,McMaster University | And 2 more authors.
Annals of Surgical Oncology

Background: Patients with a cortical small (≤4 cm) renal mass often are not candidates for or choose not to undergo surgery. The optimal management strategy for such patients is unclear. Methods: A decision-analytic Markov model was developed from the perspective of a third party payer to compare the quality-adjusted life expectancy and lifetime costs for 67-year-old patients with a small renal mass undergoing premanagement decision biopsy, immediate percutaneous radiofrequency ablation or percutaneous cryoablation (without premanagement biopsy), or active surveillance with serial imaging and subsequent ablation if needed. Results: The dominant strategy (most effective and least costly) was active surveillance with subsequent cryoablation if needed. On a quality-adjusted and discounted basis, immediate cryoablation resulted in a similar life expectancy (3 days fewer) but cost $3,010 more. This result was sensitive to the relative rate of progression to metastatic disease. Strategies that employed radiofrequency ablation had decreased quality-adjusted life expectancies (82-87 days fewer than the dominant strategy) and higher costs ($3,231-$6,398 more). Conclusions: Active surveillance with delayed percutaneous cryoablation, if needed, may be a safe and cost-effective alternative to immediate cryoablation. The uncertainty in the relative long-term rate of progression to metastatic disease in patients managed with active surveillance versus immediate cryoablation needs to be weighed against the higher cost of immediate cryoablation. A randomized trial is needed directly to evaluate the nonsurgical management of patients with a small renal mass, and could be limited to the most promising strategies identified in this analysis. © 2013 Society of Surgical Oncology. Source

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