Silodosin for benign prostatic hyperplasia.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trials, and safety of silodosin, a recently approved alpha(1A)-adrenergic receptor (AR) antagonist for benign prostatic hyperplasia (BPH). DATA SOURCES: English-only articles obtained from MEDLINE (1966-October 2009) using the search terms silodosin and KMD-3213 were reviewed. In addition, a search of International Pharmaceutical Abstracts (1970-October 2009) was conducted. STUDY SELECTION AND DATA EXTRACTION: Available English-language articles were reviewed, as well as abstracts from available non-English articles. DATA SYNTHESIS: Silodosin reduces urinary symptoms associated with BPH in as little as 1 day after initiation. The largest clinical trial conducted to date demonstrated a decrease in International Prostate Symptom Score of -6.4 +/- 6.63 points compared to -3.5 +/- 5.84 in patients receiving placebo (p < 0.0001). Silodosin also improved urinary flow rates by approximately 2.8 +/- 3.44 mL/sec, which is comparable to other alpha(1)-AR antagonists. The usual dose of silodosin is 8 mg once daily and should be reduced to 4 mg for patients with moderate renal dysfunction. Use is contraindicated in patients with severe renal and hepatic impairment or taking strong CYP3A4 inhibitors. In clinical trials, the most prevalent adverse effects were ejaculatory disturbances, occurring in approximately 28% of patients, although only 2.8% of patients discontinued treatment due to this adverse effect. Preliminary data suggest that, similar to other third-generation alpha(1A)-AR antagonists, silodosin has little potential to cause significant cardiovascular adverse effects such as orthostatic hypotension or syncope. To confirm these findings, long-term studies are still needed, especially in patients taking antihypertensive agents and in those with a history of intolerance to other alpha(1)-AR antagonists. CONCLUSIONS: Silodosin was approved by the Food and Drug Administration in 2008. Long-term studies demonstrating improvement in clinically important outcomes of BPH have yet to be published. In addition, pharmacoeconomic analyses would assist in defining its current place in therapy. Until this information is available, silodosin may be best reserved as an alternative to other second- and third-generation alpha(1)-AR antagonists.

Outcome analysis of urethral wall stent insertion with artificial urinary sphincter placement for severe recurrent bladder neck contracture following radical prostatectomy.

PURPOSE: We present outcome and quality of life analyses for the treatment of post-radical prostatectomy bladder neck contracture with urethral wall stent insertion and subsequent artificial urinary sphincter placement. MATERIALS AND METHODS: A retrospective analysis from June 2001 to September 2007 identified 25 consecutive men who underwent urethral wall stent placement for severe, recurrent bladder neck contracture despite aggressive transurethral resection after radical prostatectomy. Assessment of symptoms and quality of life impact from urinary incontinence was conducted with a self-administered, standardized questionnaire. Nonparametric testing was used for comparing covariates among groups. Univariate Cox proportional hazards modeling was used to assess predictors of treatment failure. P values are double-sided and are considered statistically significant if

Artificial urinary sphincter infection: causative organisms in a contemporary series.

PURPOSE: Traditionally Staphylococcus epidermidis has been the primary organism responsible for genitourinary prosthetic infection. However, the increasing prevalence of S. aureus infection poses a serious problem. We determined the organisms that produce artificial urinary sphincter infection in a contemporary series. MATERIALS AND METHODS: A single-institution, retrospective study was performed examining men undergoing artificial urinary sphincter explantation surgery between January 1997 and January 2007. Patients with clinical signs of infection at surgery were selected for study. RESULTS: Infection was noted in 23 patients, including 5 implanted at other institutions. The median age was 72 years (IQR 70-76). The median interval from artificial urinary sphincter implantation or revision to explantation was 110 days (IQR 38-199). Culture of the periprosthetic fluid at the time of explantation was positive in 20 of 23 patients. Gram-positive cocci were cultured from 13 patients, including S. aureus in 7, S. epidermidis in 5 and Enterococcus in 1. Methicillin resistant S. aureus and S. epidermidis in 3 cases each represented a considerable proportion of isolated organisms (6 of 26 or 26%). Gram-negative bacilli were cultured from 6 patients and yeast was cultured from 1. CONCLUSIONS: In this contemporary series S. aureus was the most common organism producing artificial urinary sphincter infection. Methicillin resistant S. aureus and S. epidermidis are often cultured during artificial urinary sphincter explantation due to infection. Strategies to prevent artificial urinary sphincter infection should target methicillin resistant S. aureus and S. epidermidis as well as gram-negative pathogens.

Association of abnormal preoperative laboratory values with survival after radical nephrectomy for clinically confined clear cell renal cell carcinoma.

OBJECTIVES: To determine whether preoperative laboratory values are independently associated with death from clinically confined clear cell renal cell carcinoma (RCC) after radical nephrectomy. METHODS: We identified 1707 patients with clinically confined (pNx/pN0, pM0), unilateral, sporadic clear cell RCC treated with radical nephrectomy between 1970 and 2002. Associations of abnormal preoperative laboratory values including hypercalcemia, anemia, elevated erythrocyte sedimentation rate (ESR), and elevated alkaline phosphatase with death from RCC were evaluated using Cox proportional hazards regression models, both univariately and multivariately by adjusting for known prognostic features of the 2002 primary tumor classification, tumor size, nuclear grade, and coagulative tumor necrosis. RESULTS: At last follow-up, 1009 patients had died, including 425 who died from RCC at a median of 3.0 years after surgery (range, 0 to 26 years). Even after adjusting for known prognostic features, 9% of patients with preoperative hypercalcemia exhibited significantly increased likelihood of dying from RCC compared with patients with normal or lower levels of serum calcium (relative ration [RR] 1.64; P = 0.002). Similarly, preoperative anemia (35% of patients; RR 1.27; P = 0.026) and elevated ESR (44% of patients; RR 1.66; P = 0.003) portended an increased risk of death from RCC even after multivariate adjustment. CONCLUSIONS: Abnormal preoperative laboratory values including hypercalcemia, anemia, and elevated ESR are independently associated with increased risk of cancer-specific death from clinically confined clear cell RCC. Consideration of these variables in future models may improve prognostic accuracy. We believe these factors should be routinely assessed and included in prospective studies of outcome in RCC patients.

Analysis of repeat nephron sparing surgery as a treatment option in patients with a solid mass in a renal remnant.

PURPOSE: We evaluated the safety and oncological efficacy of repeat nephron sparing surgery in a renal remnant. MATERIALS AND METHODS: We identified 18 patients who underwent 22 repeat nephron sparing surgeries at our institution between 1970 and 2003. Data regarding clinical characteristics, pathological characteristics and perioperative complication rates were collected. Using patients as their own controls, data from the initial nephron sparing surgery on a surgically naive kidney (group 1) were compared with data from the repeat nephron sparing surgery (group 2). RESULTS: A solitary remnant and von Hippel-Lindau disease at the time of repeat nephron sparing surgery were present in 12 (67%) and 7 (39%) patients, respectively. Median preoperative creatinine was 1.2 and 1.4 mg/dl, and median tumor size was 2.0 and 1.9 cm in groups 1 and 2, respectively. The 2002 primary tumor classification was similar between the 2 groups. There were no perioperative deaths in either group. There was at least 1 perioperative complication observed in 7 (39%) patients in group 1 vs 5 (28%) in group 2. Only 1 patient had chronic renal failure after the first procedure, while a second patient had chronic renal failure and 1 had chronic renal insufficiency after the second procedure. Overall and cancer specific survival at 5 years was 71% and 83%, respectively. CONCLUSIONS: Repeat nephron sparing surgery is a safe procedure that results in complication rates similar to those associated with nephron sparing surgery on a surgically naive kidney in carefully selected patients.

Robot-assisted laparoscopic transvesical diverticulectomy and simple prostatectomy.

Acquired bladder diverticula are often associated with bladder outlet obstruction (BOO). The increased voiding pressures required to overcome the BOO attenuate the detrusor and promote formation of diverticula. These patients may develop urinary tract infections, bladder stones, and incomplete bladder emptying. Effective treatment must address both the bladder diverticula and BOO. Reports of laparoscopic bladder diverticulectomy with concurrent transurethral resection of the prostate have demonstrated the feasibility of this minimally invasive approach. However, due to longer operative times and technical difficulty of the procedure, the gold-standard treatment remains the open surgical approach of bladder diverticulectomy and transvesical prostatectomy. With the advent of robotic-assisted laparoscopic surgery, application of open surgical principles is increasingly translated to the minimally invasive laparoscopic approach. We report, to our knowledge, the first case of robot-assisted laparoscopic transvesical diverticulectomy and concurrent transvesical simple prostatectomy.

Increased optical magnification from 2.5x to 4.3x with technical modification lowers the positive margin rate in open radical retropubic prostatectomy.

PURPOSE: We compared the positive surgical margin rate of 2.5x and 4.3x optical loupe magnification with associated technical improvement during open radical retropubic prostatectomy. MATERIALS AND METHODS: From January 2, 2004 to September 16, 2005, 511 consecutive patients underwent open radical retropubic prostatectomy, as performed by 1 surgeon. Because 10 patients refused authorization for a retrospective chart review, 501 were evaluable. For the first 265 patients 2.5x power loupes were used and for the subsequent 236 we used 4.3x power loupes. We used the chi-square test for univariate analysis, followed by multivariate logistic regression analysis adjusted for commonly recognized predictors of positive surgical margins in the 2 successive cohorts. Focusing on the apex, which was the most commonly reported site of positive surgical margins, we include operative video segments mimicking 4.3x magnification to demonstrate the surgical precision possible at 4.3x for managing the periurethral fascial bands of Walsh and urethral transection at the prostato-urethral junction. RESULTS: Positive surgical margins were identified in 39 of 265 patients (14.7%) at 2.5x and in 12 of 236 (5.1%) at 4.3x. Apical positive surgical margins were identified in 25 of 265 patients (9.4%) at 2.5x and in 5 of 236 (2.1%) at 4.3x. On multivariate analysis 4.3x magnification was independently associated with a 75% decrease in the odds of a positive surgical margin overall and in the apex alone (p <0.001 and 0.003, respectively). CONCLUSIONS: This exploratory retrospective study suggests that, compared with 2.5x magnification, the use of 4.3x magnification with technical refinements that are not possible or deemed safe at 2.5x resulted in a substantial decrease in the positive surgical margin rate.

Does preoperative topical antimicrobial scrub reduce positive surgical site culture rates in men undergoing artificial urinary sphincter placement?

PURPOSE: We determined if the incidence of a perioperative surgical site-positive culture was reduced by a 5-day topical antimicrobial scrub before implantation of an artificial urinary sphincter. MATERIALS AND METHODS: A single surgeon prospective cohort study was conducted of 100 consecutive artificial urinary sphincter implants placed between May 2003 and November 2005. We compared 50 men who performed preoperative topical antimicrobial scrub with 4% chlorhexidine to the abdominal site and perineal site with 50 men who used their normal hygiene (soap and water). All received povidone-iodine skin disinfection before incision, and bacterial cultures of the abdominal and perineal sites were collected immediately after skin disinfection and after artificial urinary sphincter implantation. Baseline comparisons between groups were done with the Wilcoxon rank sum and Fisher exact tests. Predictors of positive culture were identified using multivariate logistic regression analysis. RESULTS: The causes of incontinence were radical prostatectomy (90), radiation therapy (8) and transurethral resection of the prostate (2). There were no baseline differences between the groups including age, diabetes or previous urethral surgery. Overall 140 of the 400 cultures were positive with only 37% of the positive cultures (52 of 140) observed with topical antimicrobial scrub. For the perineal site the only factor affecting preoperative culture status was topical antimicrobial scrub (OR 0.23, p = 0.003). A positive postoperative culture was predicted by a positive preoperative perineal (OR 4.61, p = 0.003) and abdominal culture (OR 3.80, p = 0.013). CONCLUSIONS: Preoperative topical antimicrobial scrub resulted in a 4-fold reduction in preoperative perineal colonization rate and overall reduction in positive surgical site cultures. Given the low cost, safety and efficacy, topical antimicrobial scrub should be considered before artificial urinary sphincter placement.

Patients with pT1 renal cell carcinoma who die from disease after nephrectomy may have unrecognized renal sinus fat invasion.

Prior studies suggest that the renal sinus permits early tumor spread in otherwise localized renal cell carcinoma (RCC) tumors. We hypothesized that renal sinus fat invasion may be unrecognized in pT1 patients who subsequently die from RCC. Between 1985 and 2002, we identified 577 patients who underwent radical nephrectomy for localized pT1 clear cell RCC as reviewed by a single urologic pathologist (J.C.C.). Among these patients, 49 died from RCC including 33 who had their original nephrectomy specimen stored in formalin. These specimens were then resectioned with thin cuts of the renal sinus and reviewed by the same pathologist. For comparison, 33 patients who did not die from RCC (controls) also had their original nephrectomy specimen resectioned. Among the 33 patients who died from seemingly localized RCC, 14 (42%) had previously unrecognized renal sinus fat invasion compared with 2 (6%) of the controls (P<0.001). In addition, 19 (58%) patients who died from RCC had renal sinus small vein (microscopic venous) invasion, a pathologic feature not currently incorporated into the TNM staging system for RCC. This feature was present in 7 (21%) of the controls (P=0.003). In total, 22 (67%) patients who died from RCC had unrecognized renal sinus fat or small vein invasion compared with 7 (21%) of the controls (P<0.001). We conclude that renal sinus fat invasion is an important adverse pathologic feature that is clearly underreported in the literature. Appropriate assessment of nephrectomy specimens should include proper sampling of the renal sinus even for seemingly localized tumors.

Tandem transcorporal artificial urinary sphincter cuff salvage technique: surgical description and results.

PURPOSE: Complications associated with placement of artificial urinary sphincter may make reoperation necessary. We present a surgical description and outcome data for tandem transcorporal artificial urinary sphincter salvage technique for nonmechanical artificial urinary sphincter failure. MATERIALS AND METHODS: A retrospective analysis from July 2002 to December 2005 identified 198 consecutive men who underwent artificial urinary sphincter placement by a single surgeon (DSE) for postoperative stress urinary incontinence. Tandem transcorporal salvage artificial urinary sphincter surgery was performed in 18 patients with 1 (10 of 18) or both (8 of 18) cuffs placed transcorporally. Etiology of previous artificial urinary sphincter failure leading to the insertion of both cuffs in the transcorporal position included 3 infections, 2 erosions, 2 impending erosions, and 1 failed male sling. A self-administered standardized questionnaire was used to assess continence and quality of life outcomes. RESULTS: At a median followup of 26 months (IQR 14 to 30), pad use decreased from a median of 5.0 (IQR 3.5 to 5) to 2.0 (IQR 1 to 3) (p<0.001). Two patients experienced explantation of the device (1 erosion, 1 infection) without reimplantation and, thus, were excluded from outcome analysis. Eleven (69%) required 2 or fewer pads daily, and 5 (31%) required 3 pads daily. Eleven (69%) reported being very or extremely improved. Of the 5 patients reporting some or no improvement 4 were also on androgen deprivation therapy, suggesting that the transcorporal technique may be less durable in this group of patients. CONCLUSIONS: Tandem transcorporal artificial urinary sphincter placement is an effective approach to salvage cases with a high risk of repeat erosion or infection after failed artificial urinary sphincter placement.