Faculty Bibliography

In order to determine the effects of therapeutic and supratherapeutic doses of silodosin on QT interval, healthy men (N = 186; aged 18-45 years) were randomized to receive silodosin (8 or 24 mg) or placebo for 5 days or moxifloxacin 400 mg (positive control, known to prolong QT) once on day 5. At baseline and on day 5, five ECGs were recorded 0.25 h before dosing and 1, 1.5, 2, 3, 4, 6, 8, 10, and 23.5 h after dosing. Adjusted mean differences (analysis of covariance) between silodosin and placebo in the change in individual heart rate-corrected QTc (QTcI) from baseline to day 5 were <5 ms at all times (all 90% confidence interval (CI) upper limits <10 ms). The QTcI difference for moxifloxacin compared with placebo often exceeded 5 ms, establishing assay sensitivity. For silodosin, no statistically or clinically significant correlation was seen between plasma concentration and QTcI, and no clinically important effects on heart rate, PR segment, QRS complex, or morphologic ECG data were observed

Context: Although open radical retropubic prostatectomy (ORRP) remains the gold standard, the past years have seen a rise in both laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP), and many patients seem to prefer the so-called minimally invasive procedures despite insufficient data demonstrating superiority over the established standard (ORRP). Objective: This article seeks to review the most recent data on a variety of aspects of the different techniques for performing prostatectomies, such as cost, oncologic outcomes, continence, quality of life, and marketing and propaganda as well as the learning curve for each. Evidence acquisition: A search of the most recent literature was performed using PubMed, and data from lectures and presentations given at international conferences were used. Evidence synthesis: The review showed that, overall, LRP and RARP outcomes have not proved superior to ORRP outcomes or resulted in anticipated benefits to patients. In addition, current data seem to suggest that results of any of the procedures depend more on the surgeon's ability than on the approach, with rates of blood loss, positive surgical margins, incontinence, and erectile dysfunction varying widely from surgeon to surgeon with all three techniques. The aggressive marketing associated with RARP has also led to significantly higher rates of dissatisfaction and regret in patients. Conclusions: Considering the evidence, ORRP remains the gold standard in radical prostatectomies. Moreover, although the differences among major outcomes are minor and associated with shorter lengths of stay, the costs associated with LRP and RARP are significantly higher than with ORRP. In the absence of solid scientific evidence, patient education, and counselling are crucial parts of the decision-making process, during which patients will opt for one treatment over another. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved

Prior to the description of the anatomic nerve sparing radical prostatectomy, most men were rendered impotent following radical perineal or retropubic prostatectomies. The fact that these 'erection' nerves were localized outside the prostate suggested the feasibility of totally eradicating localized prostate cancer with preservation of erectile function in selected cases. All of these studies collectively suggest that unilateral excision of neurovascular bundles will compromise potency rates in between 15% to 20% of cases. It seems logical to report the risk of extracapsular extension independently for the two sides of the prostate, especially since independent decisions are made relative to the nerve sparing status of the different sides. Extracapsular extension is a risk factor for positive surgical margins. Positive surgical margins represent an independent risk factor for biochemical recurrence following radical prostatectomy. The surgeon is left with the dilemma of whether to maximize potency at the risk of compromising cancer control. In cases with a 30% risk of side specific extracapsular extension, using the above assumption, the risk of developing a positive surgical margin and biochemical recurrence is only 4.7% and 2%, respectively

OBJECTIVE: Fluorocystography (FC) is the reference standard for assessing the integrity of the vesicourethral anastomosis after radical prostatectomy (RP). We describe a new technique, transperineal sonocystography (TPSC), as a cost-effective alternative and more informative than FC. METHODS: Between May 1, 2007, and October 1, 2008, 175 consecutive men underwent open or robotically assisted RP. Before Foley catheter removal, all men underwent both TPSC and FC, which were performed and interpreted by a single radiologist. Transperineal sonocystography was performed first with real-time imaging after gravity filling of the bladder with 150 mL of normal saline. Extravasation of saline was calculated by computer software after outlining the observed pooling of extravasated saline in the transverse and longitudinal views. Fluorocystography was performed after TPSC using our standard protocol, with qualitative classification of anastomotic leaks as none, slight, moderate, or severe. RESULTS: The mean extravasation volume +/- SEM was 16.3 +/- 2.9 mL. Of the 175 patients, 142 (81.2%) showed no anastomotic leaks on TPSC. Of the remaining 33 patients (18.8%), TPSC identified 20 (11.4%), 13 (7.4%), and 0 patients with slight, moderate, and severe leaks, respectively. Excellent concordance was shown between TPSC and FC. CONCLUSIONS: Transperineal sonocystography was equivalent to FC in detecting anastomotic leaks after RP. It provides a safe, inexpensive, and effective alternative to traditional FC for evaluating the integrity of the vesicourethral anastomosis after RP

Study Type - Therapy (case series) Level of Evidence 4 OBJECTIVE To determine the mechanism for delayed healing of the urinary anastomosis after radical retropubic prostatectomy (RRP). PATIENTS AND METHODS The volumes of the para-anastomotic haematoma (PHV) and anastomotic extravasation were measured by ultrasonography in 95 men after RRP. The performance characteristics of PHV for predicting urinary extravasation were ascertained and compared with that of postoperative blood loss, measured as the difference between the haematocrit immediately after RRP and that at discharge. RESULTS The sensitivity and specificity of PHV for predicting urinary extravasation at a threshold of 37 mL was 100% and 96%, respectively. PHV was superior to postoperative blood loss in predicting anastomotic extravasation, as shown by an area under the receiver operating curve of 0.99 vs 0.91, respectively. CONCLUSIONS Our findings provide compelling evidence that delayed healing of the anastomosis after RRP is due to distraction forces secondary to a pelvic haematoma. The accuracy of PHV as a predictor of anastomotic extravasation suggests that this measurement might replace cystography for assessing anastomotic integrity after RRP

Open radical prostatectomy (ORP) is the reference standard for the surgical management of localized prostate cancer. With wider availability of minimally invasive radical prostatectomy techniques, there is a debate regarding the standard treatment of the management of localized prostate cancer. Therefore, we reviewed the current status of laparoscopic radical prostatectomy (LRP) and robotic-assisted laparoscopic radical prostatectomy (RALRP) as compared with ORP. Because no prospective, randomized trials comparing the different techniques have been performed, outcomes must be assessed from published series by centers that focus on ORP, LRP, and RALRP. Aside from reducing the amount of blood loss, current data suggest that the most significant outcomes (cure, continence, and potency) are no better with LRP or RALRP than with conventional ORP. Therefore, in experienced hands, ORP remains the gold standard procedure. However, there is a trend toward consistently better outcomes following RALRP in comparison with LRP. In the end, individual patient outcomes can be maximized by choosing the best modality based on the patient's comorbid medical conditions, cancer characteristics, and surgeon experience. Future studies are needed to further investigate long-term cancer control as well as functional outcomes for RALRP series

Defects in pRb tumor suppressor pathway occur in approximately 50% of the deadly muscle-invasive urothelial carcinomas in humans and urothelial carcinoma is the most prevalent epithelial cancer in long-term survivors of hereditary retinoblastomas caused by loss-of-function RB1 mutations. Here, we show that conditional inactivation of both RB1 alleles in mouse urothelium failed to accelerate urothelial proliferation. Instead, it profoundly activated the p53 pathway, leading to extensive apoptosis, and selectively induced pRb family member p107. Thus, pRb loss triggered multiple fail-safe mechanisms whereby urothelial cells evade tumorigenesis. Additional loss of p53 in pRb-deficient urothelial cells removed these p53-dependent tumor barriers, resulting in late-onset hyperplasia, umbrella cell nuclear atypia, and rare-occurring low-grade, superficial papillary bladder tumors, without eliciting invasive carcinomas. Importantly, mice deficient in both pRb and p53, but not those deficient in either protein alone, were highly susceptible to subthreshold carcinogen exposure and developed invasive urothelial carcinomas that strongly resembled the human counterparts. The invasive lesions had a marked reduction of p107 but not p130 of the pRb family. Our data provide compelling evidence, indicating that urothelium, one of the slowest cycling epithelia, is remarkably resistant to transformation by pRb or p53 deficiency; that concurrent loss of these two tumor suppressors is necessary but insufficient to initiate urothelial tumorigenesis along the invasive pathway; that p107 may play a critical role in suppressing invasive urothelial tumor formation; and that replacing/restoring the function of pRb, p107, or p53 could be explored as a potential therapeutic strategy to block urothelial tumor progression

Context: The immunology of the prostate has developed into a new field of research in urology. The leukocyte population increases are not yet fully understood, but it has been demonstrated that most resected prostate tissue shows signs of inflammatory response. Objective: This article reviews recent findings and discusses the complex mechanisms involved in the prostatic inflammatory response and the immunologic functions of the prostate, and the roles the prostatic inflammatory response in the cause of prostate disease such as benign prostatic hyperplasia (BPH). Evidence acquisition: We performed a search of the medical literature with PubMed, using keywords such as prostate cancer, inflammation of the prostate, leukocytes, estrogen, and cytokine and genetic expression of inflammation. Articles and data were reviewed as to their relevance, and inclusion and exclusion criteria were determined prospectively. Evidence synthesis: Evidence showing that inflammation of the prostate plays a role in prostate cancer (PCa) is mounting. Different types of inflammation exist and are distinguished according to the distribution and location of leukocytes and the histology of the surrounding tissue. Most resected prostate tissue shows signs of inflammatory response, and a relationship between T-cell infiltration and stromal proliferation can be found. Evidence for the importance of estrogen and proinflammatory cytokine interleukin (IL; IL-6, IL-8, IL-15, IL-17) also can be found. Early stages of investigation of the immunologic function of the prostate show that both prostatic epithelial and stromal cells express members of the toll-like receptor family and are therefore capable of recognizing foreign incoming antigens. Conclusions: Although this area of study is new, the immunology and inflammatory responses of the prostate are seen as important components of further study of prostate diseases such as PCa and BPH. Data supporting the role of immunology and activated leukocytes in malignant cells are also an important finding and can possibly lead to new knowledge about malignant cells. (C) 2009 Published by Elsevier B. V. on behalf of European Association of Urology