Andrea Cestari

A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation.

PURPOSE We compared the efficacy of paroxetine alone and combined with sildenafil in patients complaining of premature ejaculation. MATERIALS AND METHODS Enrolled in this study were 80 consecutive potent men 19 to 47 years old (mean age 34) with premature ejaculation but without any obvious organic cause. Pretreatment evaluation included a history, self-administration of the International Index of Erectile Function (IIEF) questionnaire, physical examination and the Meares-Stamey test to exclude genital tract infection. The initial 40 patients received 10 mg. paroxetine daily for 21 days and then 20 mg. as needed, that is 3 to 4 hours before planned sexual activity, for 6 months (group 1). The other group of 40 men received 10 mg. paroxetine daily for 21 days and then 20 mg. as needed plus 50 mg. sildenafil as needed, that is 1 hour before planned sexual activity, for 6 months (group 2). Patients were followed 3 and 6 months after beginning therapy and were evaluated using several general assessment questions, IIEF and ejaculatory latency time. RESULTS Mean ejaculatory latency time +/- SE in group 1 was 0.33 +/- 0.04, 3.7 +/- 0.10 (p <0.01) and 4.2 +/- 0.03 (p <0.01) minutes at baseline, 3 and 6-month followup, while in group 2 it was 0.35 +/- 0.03, 4.5 +/- 0.07 (p <0.01) and 5.3 +/- 0.02 (p <0.001) minutes, respectively. When improvement in ejaculatory latency time was compared in the 2 groups, group 2 results proved to be significantly greater (p <0.05). Baseline, and 3 and 6-month mean intercourse satisfaction domain values of the IIEF were 9, 11 and 11 (p = 0.09, not significant), and 9, 11 and 14 (p <0.05) in groups 1 and 2, respectively. Group 2 patients reported significantly greater intercourse satisfaction than those in group 1 (p <0.05). At baseline, 3 and 6 months there was a mean of 0.9 +/- 0.1, 1.7 +/- 0.3 (not significant) and 2.5 +/- 0.3 (p <0.01) coitus episodes weekly in group 1, and 1 +/- 0.2, 2.3 +/- 0.3 (p <0.01) and 3.2 +/- 0.1 (p <0.001) in group 2, respectively. Group 2 patients reported a significantly higher number of coitus episodes weekly (p <0.05). Side effects in the 40 group 1 cases included anejaculation in 1 (2.5%), gastrointestinal upset and/or nausea in 5 (12.5%), headache in 4 (10%) and decreased libido in 2 (5%). Side effects in the 40 group 2 cases included anejaculation in 1 (2.5%), headache in 8 (20%), gastrointestinal upset and/or nausea in 6 (15%) and flushing in 6 (15%). Group 2 patients reported significantly more headaches (p <0.01) and flushing episodes (p <0.001) than those in group 1. After 6 months of treatment 33 men (82.5%) in group 1 and 36 (90%) in group 2 were willing to continue therapy (not significant). CONCLUSIONS Paroxetine combined with sildenafil appears to provide significantly better results in terms of ejaculatory latency time and intercourse satisfaction versus paroxetine alone in potent patients with premature ejaculation. However, combined treatment is associated with a mild increase in drug related side effects.

Contemporary Management of Small Renal Masses

CONTEXT An increasing number of small renal masses (SRMs) with heterogeneous histology and clinical behaviour are being detected with modern radiologic imaging. Although surgical removal is the standard of care for small renal tumours, alternative minimally invasive and conservative treatment options are possible in selected patients with shorter life expectancy. OBJECTIVE To systematically review indications, techniques, and outcomes of surgical and conservative treatments of SRMs. EVIDENCE ACQUISITION A literature search of English-language publications was performed using the Medline database from January 2000 to February 2011 using the terms renal mass and renal carcinoma in conjunction with the evaluated management options. The articles that provided the highest level of evidence were selected with the consensus of all the authors and reviewed. EVIDENCE SYNTHESIS Only one randomised controlled trial comparing the results of elective nephron-sparing surgery and radical nephrectomy for low-stage renal tumours is available. Few comparative studies of different treatment options for SRMs have been published. The assessment of oncologic outcomes is therefore based mainly on observational studies. Most series of nonsurgical therapies have strong selection biases and relatively short follow-up. Treatment selection is based on the clinical and histologic characteristics of SRMs, on patient age and comorbidities, and on personal preferences and experience of the urologist. CONCLUSIONS Partial nephrectomy (PN) is the standard treatment for solitary SRMs whenever it is technically feasible. Laparoscopic PN is an alternative to open PN in experienced hands. The rationale of ablative treatments is to treat incidental cortical SRMs in patients at high surgical risk with potentially reduced morbidity. Active surveillance is considered an appropriate strategy for the elderly or for patients with significant comorbidity who have a shorter life expectancy. Percutaneous biopsies are increasingly being used to establish histology of SRMs and support treatment decisions, especially for patients who are candidates for nonsurgical treatment.

Pharmacological management of erectile dysfunction

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for treating ED; oral pharmacotherapy represents the first‐line option for most patients with ED. Sildenafil, an inhibitor of the enzyme phosphodiesterase type 5, is currently the most widely prescribed oral agent and has a very satisfactory efficacy‐safety profile in all patient categories. Apomorphine SL is a dopamine D1‐ and D2‐receptor agonist which has recently been approved for marketing in Europe. It is best selected for treating patients with mild to moderate ED. Vardenafil and tadalafil are new phosphodiesterase type 5 inhibitors which are expected to be approved this year. Both of them have significant positive efficacy‐safety profiles. Patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal and intraurethral therapy. Alprostadil is the most widely used drug, both for injection therapy and for the intraurethral route. The efficacy of second‐line treatment is high but the attrition rate remains significant.

Predictors of warm ischemia time and perioperative complications in a multicenter, international series of robot-assisted partial nephrectomy.

BACKGROUND Warm ischemia time (WIT) and complication rates are two important parameters for evaluating the perioperative results of robot-assisted partial nephrectomy (RAPN). Few data are available about the clinical predictors of WIT and overall complications. OBJECTIVE To identify clinical predictors of WIT and perioperative complications. DESIGN, SETTING, AND PARTICIPANTS This is a retrospective study including 347 patients who underwent RAPN for suspicious renal cell carcinoma (RCC) at four referral centers from September 2008 to September 2010. INTERVENTION All patients underwent RAPN using the da Vinci S Surgical System with hilar clamping. MEASUREMENTS WIT >20 min and overall complication rates were the main outcomes. Postoperative complications were classified according to the Clavien/Dindo system. Moreover, the following perioperative variables were considered: clinical tumor size, anatomical tumor characteristics according to Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification score, surgeon experience, console time, blood loss, and upper collecting system (UCS) repair. RESULTS AND LIMITATIONS WIT >20 min was reported in 125 (36%) cases. Intraoperative and postoperative complications were observed in 10 (2.9%) and 41 (11.8%) cases, respectively. Surgeon experience (odds ratio [OR]: 6.381; 95% confidence interval [CI], 3.687-11.042; p<0.001), clinical tumor size (OR: 1.022; 95% CI, 1.002-1.044; p=0.03), the other anatomic characteristics determined by the PADUA classification score (OR: 1.294; 95% CI, 1.080-1.549; p=0.005), and the UCS repair (OR: 2.987; 95% CI, 1.728-5.165; p<0.001) turned out to be independent predictors of WIT >20 min. Similarly, surgeon experience (OR: 3.937; 95% CI, 2.011-7.705; p<0.001), clinical tumor size (OR: 1.033; 95% CI, 1.009-1.058; p=0.007), and the other anatomical characteristics determined by the PADUA classification score (OR: 1.427; 95% CI, 1.149-1.773; p<0.001) turned out to be independent predictors of overall complication rates. The retrospective design is the main limitation of this multicenter, international study. Therefore, some patient characteristics and comorbidities were not recorded. CONCLUSIONS Anatomic tumor characteristics as determined by the PADUA classification score were independent predictors of WIT and overall complications, once adjusted for the effects of surgeon experience and clinical tumor size.

Biopsy Core Number Represents One of Foremost Predictors of Clinically Significant Gleason Sum Upgrading in Patients With Low-risk Prostate Cancer

OBJECTIVES To examine the effect the number of biopsy cores taken has on the rate of clinically significant Gleason sum upgrading (GSU) in patients with low-risk prostate cancer. METHODS We analyzed the data from 301 patients with low-risk prostate cancer (clinical Stage T1c-T2a, prostate-specific antigen <or=10 ng/mL, and biopsy Gleason sum <or=6) who underwent an extended (>or=10-core) prostate biopsy. Prostate-specific antigen level, clinical stage, biopsy Gleason sum, prostate volume, year of diagnosis, number of biopsy cores taken, and number of positive cores were used as predictors in logistic regression models addressing the rate of clinically significant GSU (defined as upgrading from biopsy Gleason sum 5-6 to radical prostatectomy Gleason sum of >or=7). Regression coefficients were used to estimate the predictive accuracy of individual variables, as well as their combined effect in the prediction of GSU. RESULTS The median number of biopsy cores taken was 18. Upgrading was recorded in 96 (31.9%). In men assessed with 10-12 cores, the rate of GSU was 47.9% compared with 23.5% if >18 cores were taken (P < .001). In multivariate analyses, the consideration of the variable defining the number of cores added 9.0% (P < .001) to the ability to predict GSU. CONCLUSIONS Patients with low-risk prostate cancer assessed with fewer biopsy cores are at a substantially greater risk of GSU. The number of biopsy cores taken represents one of the foremost predictors of GSU and should be taken into consideration during clinical decision-making in patients who are candidates for watchful waiting, active surveillance, or brachytherapy.

Preoperative Prostate-Specific Antigen Isoform p2PSA and Its Derivatives, %p2PSA and Prostate Health Index, Predict Pathologic Outcomes in Patients Undergoing Radical Prostatectomy for Prostate Cancer

BACKGROUND Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are possible candidates for radical prostatectomy (RP). New biomarkers would be welcome. OBJECTIVE Test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivates, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology after RP. DESIGN, SETTING, AND PARTICIPANTS An observational prospective study was performed in 350 consecutive men diagnosed with clinically localised PCa who underwent RP. MEASUREMENTS We determined the predictive accuracy of serum total PSA (tPSA), free PSA (fPSA), fPSA-to-tPSA ratio (%fPSA), p2PSA, %p2PSA, and PHI. The primary end point was to determine the accuracy of these biomarkers in predicting the presence of pT3 disease, pathologic Gleason sum≥7, Gleason sum upgrading, and tumour volume<0.5 ml. INTERVENTION Open retropubic and robot-assisted laparoscopic RP was performed. Pelvic lymphadenectomy was performed according to baseline oncologic parameters and the surgeons judgement. RESULTS AND LIMITATIONS The %p2PSA and PHI levels were significantly higher in patients with pT3 disease, pathologic Gleason sum≥7, and Gleason sum upgrading (all p values<0.001). Conversely, %p2PSA and PHI levels were significantly lower in patients with tumour volume<0.5 ml (p<0.001). By univariate analysis, both %p2PSA and PHI were accurate predictors of pT3 disease, pathologic Gleason sum≥7, Gleason sum upgrading, and tumour volume<0.5 ml. By multivariate analyses, the inclusion of both %p2PSA and PHI significantly increased the predictive accuracy of a base multivariate model (excluding the tumour volume prediction for both variables, and Gleason sum upgrading for the model including %p2PSA) that included patient age, tPSA, fPSA, f/tPSA, clinical stage, and biopsy Gleason sum. CONCLUSIONS We found that p2PSA and its derivatives are predictors of PCa characteristics at final pathology after RP and are more accurate than currently available markers.

Trans-rectal Versus Trans-Perineal Saturation Rebiopsy of the Prostate: Is There a Difference in Cancer Detection Rate?

OBJECTIVE To test the hypothesis that there is no significant difference in the rate of prostate cancer (PCa) detection rate between the transrectal and transperineal approach in men undergoing a saturation (24-core) prostate rebiopsy. METHODS We evaluated 472 consecutive men who underwent a 24-core prostate rebiopsy at 2 tertiary referral centers. Of these, 70% (332) underwent a transrectal biopsy, and 30% (140) underwent a transperineal biopsy. Propensity score was used to match 280 patients with homogeneous characteristics; those represented the final study cohort. Univariable and multivariable logistic regression analyses were used to address the relationship between biopsy approach and PCa detection rate. Covariates consisted of age at biopsy, prostate-specific antigen, total prostate volume, digital rectal examination findings, histologic findings on previous biopsy, and the number of previous negative biopsy sets. RESULTS Overall, PCa detection rate was 28.6%. There was no statistically significant difference in PCa detection rate between the transrectal and transperineal approach (31.4% vs 25.7%, respectively; P = .3). The type of approach was not an independent predictor of PCa detection rate at multivariable analyses (odds ratio = 0.61, P = .1). CONCLUSIONS Transrectal and transperineal prostate saturation biopsies have a similar PCa detection rate in men undergoing a saturation rebiopsy. Both approaches can be offered to men undergoing a prostate rebiopsy without undermining the rate of PCa detection.

Clinical performance of serum prostate-specific antigen isoform (-2)proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project

To test the sensitivity, specificity and accuracy of serum prostate‐specific antigen isoform [‐2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI.

EIGHT-YEAR EXPERIENCE WITH TRANSPERITONEAL LAPAROSCOPIC ADRENAL SURGERY

PURPOSE Laparoscopic adrenalectomy is currently the technique of choice for removing benign adrenal lesions. Various laparoscopic techniques and approaches have been reported using the transperitoneal or retroperitoneal approach. We present our 8-year experience with and long-term results of transperitoneal laparoscopic adrenalectomy. MATERIALS AND METHODS Between October 1992 and October 2000, 161 laparoscopic approaches to the adrenal gland were performed, including 145 unilateral and 10 bilateral adrenalectomies, and 6 conservative operations. Patients were placed in the 60-degree flank position with the bed flexed to increase the surgical field. To avoid hypertensive crisis, especially in patients with pheochromocytoma, the first step involved early ligation of the adrenal vein. RESULTS The laparoscopic procedure was successfully completed in all except 4 cases, which were converted to open surgery. Mean operative time was 160 minutes in the unilateral, 245 in the bilateral and 90 in the conservative group. Delayed complications included hemoperitoneum in 3 patients, which was drained surgically, severe blood loss in 3 treated with blood transfusion and wound infection in 2. Patients were ambulatory on the morning of postoperative day 1 and were discharged home 2.8, 5 and 1.8 days after unilateral, bilateral and conservative surgery, respectively. CONCLUSIONS Laparoscopic transperitoneal adrenalectomy is a safe, effective, minimally invasive approach in patients with benign functioning or nonfunctioning adrenal masses. This technique involves low morbidity, minimal postoperative analgesic requirements and a short hospital stay.

Oncologic Results of Laparoscopic Renal Cryoablation for Clinical T1a Tumors: 8 Years of Experience in a Single Institution

OBJECTIVES To review the oncologic outcomes of laparoscopic renal cryoablation (LRC) for small renal masses (SRMs) <4 cm. METHODS The present study was an observational, retrospective analysis of LRC in 123 patients. The indications for LRC were solid SRMs of the kidney <4 cm in diameter diagnosed on preoperative computed tomography or magnetic resonance imaging as an enhancing mass. Follow-up was determined using magnetic resonance imaging. Local recurrence after LRC was defined as an enlarging or persistently enhancing treatment site on follow-up imaging. RESULTS A total of 131 SRMs in 123 patients (91 men and 32 women) were treated from September 2000 to June 2008. The mean tumor size was 2.14 ± 0.86 cm (range 0.5-4). Biopsy cores from the 123 patients revealed clear cell renal cell carcinoma (RCC) in 69 patients (56.1%), papillary RCC in 8 (6.53%), chromophobe RCC in 3 (2.4%), mucinous, tubular, and spindle RCC in 1 (0.8%), oncocytoma in 27 (21.9%), angiomyolipoma in 5 (4.1%), and xanthogranulomatous pyelonephritis in 1 patient (0.8%). The biopsy findings were nondiagnostic (fibrotic/necrotic tissue) in 9 cases (7.3%). The mean follow-up was 46.04 ± 25.75 months (median 41, range 12-96). In 44 patients with RCC and a mean follow-up of 61.3 ± 13.76 months, the cancer-specific survival rate was 100% and the overall survival rate was 93.2%. None of the 53 patients (RCC plus those with nonmalignant lesions) who had follow-up >5 years developed radiographic recurrence. CONCLUSIONS Our findings have confirmed that LRC can be considered a safe and intermediate-term effective method to treat SRMs.