Raanan Tal

Erectile function recovery rate after radical prostatectomy: a meta-analysis.

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 >or=50 patients, >or=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 >or=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 >or=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.

The Functional and Structural Consequences of Cavernous Nerve Injury are Ameliorated by Sildenafil Citrate

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 Massons 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.

Outcomes of clomiphene citrate treatment in young hypogonadal men

Study Type – Therapy (case series)

ORIGINAL RESEARCH—PEYRONIE'S DISEASE: Peyronie's Disease Following Radical Prostatectomy: Incidence and Predictors

INTRODUCTION Both prostate cancer and Peyronies 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 < 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.

Significance of intraoperative ureteral evaluation at radical cystectomy for urothelial cancer

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.

Erectile Function Rehabilitation after Radical Prostatectomy: Practice Patterns among AUA Members

INTRODUCTION Despite a growing body of evidence supporting erectile function (EF) rehabilitation after radical prostatectomy (RP), there are no guidelines on this subject. AIM To explore EF rehabilitation practice patterns of American Urological Association (AUA) urologists. METHODS A 35-question instrument was constructed assessing physician demographics, training, and EF rehabilitation practices after RP, and was e-mailed to AUA members by the AUA Office of Education. Data were acquired by the AUA and analyzed by the investigators. MAIN OUTCOME MEASURE Percentage of responders who recommend EF rehabilitation practices following RP, characterization of prevalent rehabilitation practices. RESULTS Of the 618 urologists who completed the survey, 71% were in private practice, 28% considered themselves as sexual medicine specialists, although only 4% were fellowship-trained, 43% were urologic oncology specialists (14% fellowship-trained), 86% performed RP, and 86% of responders recommended rehabilitation practices. Being a sexual medicine or a urologic oncology specialist was not predictive of rehabilitation employment. Forty-three percent rehabilitate all patients, 57% only selected patients. Selection for rehabilitation was dependent upon preop EF by 66%, nerve-sparing status by 22%, and age by 5%. Eleven percent started rehab immediately after RP, 97% within 4 months. 24%, 45% and 18% ceased rehab at <12, 12-18, and 18-24 months, respectively. Eighty-nine percent of RP surgeons performed rehabilitation vs. only 66% who do not perform RP (P < 0.0001). Eighty-seven percent prefer phosphodiesterase type 5 inhibitors (PDE5i) as their primary strategy followed (in order) by vacuum erection device (VED), intracavernosal injection (ICI), and urethral suppositories. CONCLUSIONS Among the respondents, penile rehabilitation is a common practice. Urologic oncologists and RP surgeons are more likely to use rehabilitation practices. The most commonly employed strategy is regular PDE5i use for 12-18 months after RP. .

ORIGINAL RESEARCHORIGINAL RESEARCH—PEYRONIE'S DISEASE: Peyronie's Disease Following Radical Prostatectomy: Incidence and Predictors

INTRODUCTION Both prostate cancer and Peyronies 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 < 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.

The Effect of Hyperbaric Oxygen Therapy on Erectile Function Recovery in a Rat Cavernous Nerve Injury Model

INTRODUCTION Cavernosal oxygenation appears to be important for preservation of erectile tissue health. Hyperbaric oxygen therapy (HBOT) has been shown to improve tissue oxygenation and has neuromodulatory effects. AIM This study was designed to define the effects of HBOT on erectile function (EF) and cavernosal tissue in the rat cavernous nerve (CN) injury model. METHODS Four groups of Sprague-Dawley rats were studied: rats with bilateral CN crush, HBOT treated (Crush+/HBOT+); bilateral CN-crush/no HBOT (C+/H-); no crush/no HBOT (C-/H-); and no crush/HBOT (C-/H+). HBOT was delivered daily for 90 minutes at three atmospheres for 10 days commencing the day of CN crush. MAIN OUTCOME MEASURES Ten days after CN injury, the animals underwent CN stimulation measuring the maximal intracavernosal pressure/mean arterial pressure (ICP/MAP) ratios. Corporal tissue was harvested pre-sacrifice, and immunohistochemically stained for nerve growth factor (NGF), endothelial nitric oxide synthase (eNOS), and cluster of differentiation molecule (CD31). Histologic analysis was performed for Massons trichrome to assess the smooth muscle-collagen ratio. Terminal deoxynucleotidyl transferase Biotin-dUTP Nick End Labeling assay was used to define apoptotic indices (AIs). RESULTS The C+/H- group had significantly lower ICP/MAP ratios compared with C-/H- rats, (31% vs. 70%, P < 0.001). C+/H+ rats had significantly higher ICP/MAP ratio recovery compared with the C+/H- group (55% vs. 31%, P = 0.005). NGF and eNOS staining densities were higher in C+/H+ rats compared with C+/H- rats (P < 0.05 and P < 0.001, respectively). No difference was seen in CD31 expression. Staining density for MT displayed a trend toward higher smooth muscle preservation after HBOT. AIs were significantly increased by HBOT (P < 0.05). CONCLUSION HBOT following a CN injury improved EF preservation in this model, supporting the cavernosal oxygenation concept as protective mechanism for EF. The effects appear to be mediated via preservation of neurotrophic and endothelial factor expression.

Persistent Erectile Dysfunction Following Radical Prostatectomy: The Association between Nerve-Sparing Status and the Prevalence and Chronology of Venous Leak

INTRODUCTION . Failure to recover erectile function after radical prostatectomy (RP) may result from venous leak as a sequela of neuropraxia-induced erectile tissue damage. Venous leak portends a poor prognosis for erections recovery as well as phosphodiesterase type 5 inhibitor (PDE5i) response. AIMS To define the impact of RP nerve-sparing status on venous leak prevalence and chronology. METHODS STUDY POPULATION men who underwent RP for localized prostate cancer, had functional erections prior to RP, developed postoperative erectile dysfunction (ED), had a Doppler ultrasonography within 6 months of RP, and did not receive any ED treatment for the first 6 months after RP other than on-demand PDE5i. MAIN OUTCOME MEASURES Venous leak prevalence and erectile function recovery at different time-points. RESULTS Data on 142 patients were analyzed, mean age: 58 +/- 16 years. Sixty percent had bilateral nerve-sparing (BNS) surgery, 20% unilateral nerve-sparing (UNS) surgery, and 20% non-nerve-sparing (NNS) surgery. Eleven percent and 21% had venous leak by 3 and 6 months, respectively. Venous leak prevalence by 6 months was 7%, 11%, and 75% for BNS, UNS, and NNS surgery (P < 0.001). Mean end-diastolic velocity was 1.8, 2.1, and 7.2 cm/second for the three groups (P < 0.01). The only patients developing venous leak prior to 3 months were NNS patients, one-third of NNS-associated venous leak occurring before this time-point. At 18 months, the proportion of men having return of unassisted erections was 49%, 42%, and 7% with mean erectile function domain scores of 21, 18, and 12, and PDE5i response rates were 72%, 64%, and 12% for the three groups, respectively. CONCLUSIONS Nerve-sparing status impacts heavily upon the prevalence and the chronology of venous leak development post-RP. NNS RP is associated with early development of venous leak, increased prevalence of venous leak, and reduction in return of natural erections.

Peyronie's Disease in Teenagers

INTRODUCTION Peyronies disease (PD) is commonly seen in middle-aged men, and little is known about this condition in teenagers. AIM To investigate the characteristics of PD in teenagers. METHODS The findings were compared between patients with the disease who were teenagers with those over 40 years of age. Statistical analyses were conducted to define differentiating features between these two groups. MAIN OUTCOME MEASURES The demographics, clinical features, and associated comorbidities of patients with PD were reviewed. RESULTS Thirty-two teenaged males were evaluated for PD in a single institution over a 10-year period. The median age for our cohort was 18 (15-19) years. Forty-five percent of patients had already been seen by another urologist, and 28% had been told they did not have PD. The mean duration of PD before seeking medical care in our cohort was 3 ± 1 months. Sixteen percent of patients reported antecedent penile trauma, half of which happened during coitus or masturbation, and 18% of patients had hemoglobin (Hb) A1c levels > 5%. Dupuytrens contracture was not seen in this population. Twenty-two percent of patients presented with penile pain. Subsequent ED was seen in 37% of patients. Multiple noncontiguous plaques were seen in 37% of patients. Twelve percent were previously treated with vitamin E, while another 12% had previous intralesional verapamil. High distress was reported by 94% of patients. Thirty-four percent sought medical attention for anxiety/mood disorder, and 28% had a negative encounter with a sexual partner related to PD. All of the 32 patients had penile curvature with a mean of 32 ± 12 degrees. Seventy-two percent of the patients had dorsal curvature while 22% had an associated deformity. Using duplex Doppler ultrasound, 12% had a calcified plaque, while none of the patients had abnormal hemodynamics. When compared with PD in adults, teenagers had greater than seven times the prevalence of multiple noncontiguous plaques (37% vs. 5%). Also, the prevalence of HbA1c level > 5% was higher in the teenagers as well (18% vs. 5%). CONCLUSIONS PD does occur in teenagers often causing high distress levels. Compared to older adults, teenagers often present earlier, and more commonly have elevated HbA1c level and increased number of plaques at presentation.