Predictors of disease specific survival include local disease at presentation, complete tumor resection and tumor grade, size, location and histological subtype. With adequate surgical treatment most patients who presented with primary disease and underwent complete surgical resection achieved prolonged disease specific survival.

Introduction Erectile function recovery (EFR) rates after radical prostatectomy (RP) vary greatly based on a number of factors, such as erectile dysfunction (ED) definition, data acquisition means, time-point postsurgery, and population studied. Aim To conduct a meta-analysis of carefully selected reports from the available literature to define the EFR rate post-RP. Main Outcome Measures EFR rate after RP. Methods An EMBASE and MEDLINE search was conducted for the time range 1985–2007. Articles were assessed blindly by strict inclusion criteria: report of EFR data post-RP, study population ≥50 patients, ≥1 year follow-up, nerve-sparing status declared, no presurgery ED, and no other prostate cancer therapy. Meta-analysis was conducted to determine the EFR rate and relative risks (RR) for dichotomous subgroups. Results A total of 212 relevant studies were identified; only 22 (10%) met the inclusion criteria and were analyzed (9,965 RPs, EFR data: 4,983 subjects). Mean study population size: 226.5, standard deviation = 384.1 (range: 17–1,834). Overall EFR rate was 58%. Single center series publications (k = 19) reported a higher EFR rate compared with multicenter series publications (k = 3): 60% vs. 33%, RR = 1.82, P = 0.001. Studies reporting ≥18-month follow-up (k = 10) reported higher EFR rate vs. studies with <18-month follow-up (k = 12), 60% vs. 56%, RR = 1.07, P = 0.02. Open RP (k = 16) and laparoscopic RP (k = 4) had similar EFR (57% vs. 58%), while robot-assisted RP resulted in a higher EFR rate (k = 2), 73% compared with these other approaches, P = 0.001. Patients <60 years old had a higher EFR rate vs. patients ≥60 years, 77% vs. 61%, RR = 1.26, P = 0.001. Conclusions These data indicate that most of the published literature does not meet strict criteria for reporting post-RP EFR. Single and multiple surgeon series have comparable EFR rates, but single center studies have a higher EFR. Younger men have higher EFR and no significant difference in EFR between ORP and LRP is evident.

Introduction Radical prostatectomy (RP) is associated with erectile dysfunction (ED). A single, placebo-controlled, human study has assessed the effects of regular sildenafil use after RP and demonstrated an increased chance of preservation of preoperative erectile function. Aim This study was undertaken to define the effects of such a regimen in an animal model. Methods Using the cavernous nerve (CN) crush injury model, animals were divided into a number of groups: no CN injury (sham), bilateral CN injury exposed to either no sildenafil (control) or sildenafil at two doses (10 and 20 mg/kg) subcutaneously daily for three different durations (3, 10, 28 days). Main Outcome Measures At these time points, CN electrical stimulation was used to assess erectile function by mean intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio. For the structural analyses, whole rat penes were harvested. Staining for Masson's trichrome was utilized to calculate the smooth muscle-collagen ratio. Immunohistochemical antibody staining was performed for endothelial (CD31 and eNOS) and neural (GAP43, NGF, and nNOS) factors and immunoblotting was performed to analyze the AKT/eNOS pathway. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay was used for the assessment of apoptotic indices and the CN architecture was evaluated by transmission electron microscopy (TEM). Results Erectile function was improved with sildenafil in a time- and dose-dependent fashion with maximization of erectile function recovery occurring with daily 20 mg/kg at the 28-day time point. Sildenafil use resulted in smooth muscle-collagen ratio protection and CD31 and eNOS expression preservation. Sildenafil reduced apoptotic indices significantly compared with control. Animals exposed to sildenafil had increased phosphorylation of akt and eNOS. Tem demonstrated distinct differences in architecture between control and sildenafil groups toward an increased amount of myelinized nerve fibers. Conclusions Sildenafil use in the CN crush injury model preserves erectile function that appears to be mediated predominantly through preservation of smooth muscle content and endothelial function as well as through reduction in apoptosis.

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Hypogonadism is a prevalent problem, increasing in frequency as men age. It is most commonly treated by testosterone supplementation therapy but in younger patients this can lead to testicular atrophy with subsequent exogenous testosterone dependency and may impair spermatogenesis. Clomiphene citrate (CC) may be used as an alternative treatment in these patients with hypogonadism when maintenance of fertility is desired. This study shows that CC is a safe and efficacious drug to use as an alternative to exogenous testosterone. Not only have we validated previous findings of other papers but have proven our findings over a much longer period (mean duration of treatment 19 months). This prospective study is the largest to date assessing both the objective hormone response to CC therapy as well as the subjective response based on a validated questionnaire. OBJECTIVE To prospectively assess the andrological outcomes of long‐term clomiphene citrate (CC) treatment in hypogonadal men. PATIENTS AND METHODS We prospectively evaluated 86 men with hypogonadism (HG) as confirmed by two consecutive early morning testosterone measurements <300 ng/dL. The cohort included all men with HG presenting to our clinic between 2002 and 2006 who, after an informed discussion, elected to have CC therapy. CC was commenced at 25 mg every other day and titrated to 50 mg every other day. The target testosterone level was 550 ± 50 ng/dL. Testosterone (free and total), sex hormone binding globulin, oestradiol, luteinizing hormone and follicle stimulating hormone were measured at baseline and during treatment on all patients. Once the desired testosterone level was achieved, testosterone/gonadotropin levels were measured twice per year. To assess subjective response to treatment, the androgen deficiency in aging males (ADAM) questionnaire was administered before treatment and during follow‐up. RESULTS Patients' mean (standard deviation [sd]; range) age was 29 (3; 22–37) years. Infertility was the most common reason (64%) for seeking treatment. The mean (sd) duration of CC treatment was 19 (14) months. At the last evaluation, 70% of men were using 25 mg CC every other day, and the remainder were using 50 mg every other day. All mean testosterone and gonadotropin measurements significantly increased during treatment. Subjectively, there was an improvement in all questions (except loss of height) on the ADAM questionnaire. More than half the patients had an improvement in at least three symptoms. There were no major side effects recorded and the presence of a varicocele did not have an impact on the response to CC. CONCLUSION Long‐term follow‐up of CC treatment for HG shows that it appears to be an effective and safe alternative to testosterone supplementation in men wishing to preserve their fertility.

BACKGROUND.Patients undergoing radical cystectomy (RC) for urothelial cancer are at increased risk for upper tract recurrence and anastomotic recurrence. In an attempt to reduce this recurrence risk, urologists employ intraoperative frozen sections to achieve an uninvolved ureteral margin. The utility of this surgical approach was examined.METHODS.A retrospective review identified 1330 bladder cancer patients from 1990 to 2004 with pathologic evaluation of their ureters. Using pathologic findings on permanent section as the reference standard, the accuracy of ureteral frozen sections was examined. Ureteral involvement and margin status were examined as risk factors for upper tract and anastomotic recurrence and overall survival.RESULTS.Of 2579 ureteral margins evaluated in 1330 patients, ureteral involvement was noted in 9% of ureters (13% of patients). The sensitivity and specificity of frozen section analyses were approximately 75% and 99%, respectively. The 5‐year probability of anastomotic and upper tract recurrences was low: 2% and 13%, respectively. Evidence of involvement of the ureter or at the ureteral anastomotic margin was associated with higher likelihood of upper tract recurrence but not anastomotic recurrence or overall survival. Furthermore, sequential resection of ureters to reach a negative anastomotic ureteral margin did not eliminate the risk of anastomotic or upper tract recurrence.CONCLUSIONS.Patients with involved ureters and/or ureteral anastomotic margins have a higher risk of upper tract recurrence. However, the overall risk of recurrence is low and is not clearly associated with overall survival. The data do not support routine intraoperative frozen sections to assess ureteral involvement. Cancer 2006. © 2006 American Cancer Society.

We studied the effect of the natural marine substance mimaquinone on the catalytic activities of reverse transcriptase from human immunodeficiency virus type 1. Illimaquinone inhibited the RNase H activity of the enzyme at concentrations of 5 to 10 ,ug/ml, whereas RNA-dependent DNA polymerase and DNA-dependent DNA polymerase activities were considerably less susceptible to this inhibition. Two synthetic derivatives of illimaquinone, in which the 6'-hydroxyl group at the ortho position to one of the carbonyl groups of the quinone ring was modified, proved ineffective in inhibiting the human immunodeficiency virus type 1 reverse transcriptase RNase H function, suggesting involvement of the 6'-hydroxyl group in blocking the enzymatic activity.Reverse transcriptases (RTs) are key enzymes in the life cycle of retroviruses, since they are responsible for the transcription of the viral RNA into the provirus DNA that is subsequently integrated into the host cell DNA (34). RT is a multifunctional enzyme; the same protein molecules exhibit both RNA-dependent DNA polymerase (RDDP) and DNAdependent DNA polymerase (DDDP) activities as well as an inherent RNase H activity (32). Drugs acting at the reverse transcription level block specifically the replication of human immunodeficiency virus (HIV), the human retrovirus that causes acquired immunodeficiency syndrome, by preventing the unique transcription of genomic viral RNA. Several compounds with diverse molecular structures, including various 2',3'-dideoxynucleosides (14, 21, 22) and 3'-azidothymidine (9, 23, 35) that inhibit the viral RT in the form of 5'-triphosphates, foscarnet (28, 33), suramine (2, 7), rifabutin (1), and HPA 23 (26), have been shown to be active against HIV RT in vitro. In contrast to the relatively large volume of research on the inhibition of the DNA polymerase activities associated with various retroviral RTs, there is a paucity of information on the inhibition of the RT-associated RNase H function. RNase H specifically degrades the RNA in the RNA-DNA heteroduplex after the minus-strand DNA has been synthesized. Removal of the RNA strand enables the synthesis of the plus strand of DNA and the formation of the proviral double-stranded DNA, which is subsequently inserted into the host cellular genome (34). The fact that there is a distinction between the DNA polymerase and RNase H activities of retroviral RTs, including that of HIV (11,25,30,31), could be utilized to develop drugs that will specifically inhibit the RNase H function without appreciably affecting the DNA-polymerizing function. Since the physiological significance of RNase H in mammalian cells is far from clear (6), it is possible that even a partial inhibition of this activity would have minimal effects on the metabolism of normal cells but a substantial inhibitory effect on the virus. The availability of large amounts of nearly authentic (560 amino acids long with an apparent molecular weight of * Corresponding author. 66,000) enzymatically active and soluble recombinant HIV type 1 (HI...

Introduction Both prostate cancer and Peyronie’s disease (PD) are prevalent in men after their fifth decade of life. The evidence to support or refute a link between radical prostatectomy (RP) and PD is limited. Aims To define the incidence of PD in men who had RP and determine possible predictors of PD development after RP. Methods A review of a prospectively built sexual medicine database, years 2002–2008, looking at subjects who had RP as a monotherapy for localized prostate cancer. We identified and characterized subjects who developed PD within 3 years after RP and compared them with subjects who did not. Main Outcome Measures The incidence of PD among men who attended a sexual medicine clinic after they had RP, predictors of PD development after RP. Results The study population included 1,011 subjects, and PD incidence in this population was 15.9%. Mean time to develop PD after RP was 13.9 ± 0.7 months. Mean curvature magnitude was 31+17 degrees. On univariate analysis, younger age (mean age of 59+7 in men with PD vs. 60+7 years in men without PD, P = 0.006) and white race (vs non-white, 18% vs. 7%, P &lt;0.001) were predictive of PD development after RP, but post-op erectile function was not a predictor of PD development. On multivariate analysis, younger age (odds ratio (OR)=1.3, for 5-year decrease in age) and white race (OR=4.1, vs. non-white) remained independent significant predictors. Conclusions Men presenting with sexual dysfunction after RP have higher PD incidence then the general population. Therefore, they should be routinely evaluated for PD. Younger men and men of white race are at increased risk for PD. Prospective controlled studies are needed to elucidate the incidence of PD following RP and to conclude if RP has a causative role in the pathogenesis of PD.

Laparoscopic intraperitoneal approach to postoperative ventral (incisional) hernia repair may be associated with significant complications and morbidity, which can be prevented in part by meticulous technique and liberal conversions. The justification of this procedure is the low recurrence rate, according to preliminary results.