N. Tosi

Histopathologic Analysis of Peritumoral Pseudocapsule and Surgical Margin Status after Tumor Enucleation for Renal Cell Carcinoma

BACKGROUND The oncologic safety of blunt tumor enucleation (TE) of renal cell carcinoma (RCC) depends on the presence of a continuous pseudocapsule (PS) around the tumor and on the possibility of obtaining negative surgical margins (SMs). OBJECTIVE To investigate the PS and SMs after TE to define the real need to take a rim of healthy parenchyma around the tumor to avoid the risk of positive SMs. The risk of PS invasion related to other clinical and pathologic variables was also evaluated. DESIGN, SETTING, AND PARTICIPANTS Between September 2006 and December 2007, data were gathered prospectively from 187 consecutive patients who had kidney surgery. Overall, 90 consecutive patients who had TE for RCC were eligible for the study. All specimens were evaluated using an image analyzer by a dedicated uropathologist. INTERVENTION TE was done by blunt dissection using the natural cleavage plane between the tumor and the normal parenchyma. MEASUREMENTS PS, SM, and routinely available clinical and pathologic variables were recorded. RESULTS AND LIMITATIONS In 60 RCC tumors (67%) the PS was intact and free from invasion (PS-) while in 30 (33%) there were signs of penetration within its layers, with or without invasion beyond it. Indeed, 26.6% had PS that had been penetrated on the parenchymal side and 6.6% had penetration on the perirenal fat tissue side. The odds of having PS penetration increased significantly with an increase in clinical tumor size. PS penetration was also significantly associated with pathologic tumor dimensions and grade. In all cases the SMs were negative after TE. The present patients, followed for >2 yr, will enable us to correlate the risk of local recurrence with PS status. CONCLUSIONS The risk of PS penetration is associated with clinical and pathologic tumor dimensions and grade. If there is PS invasion into normal parenchyma, the presence of a thin layer of tissue allows for negative SM even if a TE is performed.

A Randomized, Placebo-Controlled Study to Assess Safety and Efficacy of Vardenafil 10 mg and Tamsulosin 0.4 mg vs. Tamsulosin 0.4 mg Alone in the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

INTRODUCTION Safety and efficacy of tamsulosin and vardenafil are well established: however, there is no report regarding combined therapy with these drugs for lower urinary tract symptoms (LUTSs) secondary to benign prostatic hyperplasia (BPH). AIM To compare the safety and efficacy of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus vardenafil 10 mg/day in patients with LUTS/BPH in a randomized trial with 12-week follow-up. METHODS We conducted a randomized, double-blind, placebo-controlled study on 60 men with persistent storage LUTS after 2-week run-in with tamsulosin. MAIN OUTCOME MEASURES International Prostate Symptom Score (IPSS), IPSS-bother, International Index of Erectile Function, Version 5 (IIEF-5) and Over Active Bladder questionnaire (OAB-q) scores, uroflowmetry data (Qmax, Qave), and postvoiding residual urine were recorded after run-in (baseline), and 2 and 12 weeks after treatment. Differences between vardenafil and placebo at different times were calculated with unpaired samples t-test. Between-group differences in change from baseline to 2 and 12 weeks were evaluated with analysis of variance. RESULTS We found a between-group significant difference from baseline to 12 weeks in the following: (i) Qmax (placebo: +0.07, vardenafil: +2.56, P = 0.034); (ii) Qave (placebo: -0.15, vardenafil: +1.02, P = 0.031); (iii) irritative-IPSS subscores (placebo: -1.67, vardenafil: -3.11, P = 0.039); and (iv) IIEF (placebo: +0.06, vardenafil: +2.61, P = 0.030). No patient reported any serious (grade ≥ 2) adverse event (AE). There were no differences in the incidence of common, treatment-related AEs between men undergoing combined therapy or tamsulosin alone. CONCLUSIONS The combination of tamsulosin and vardenafil for 12 weeks was well tolerated and more effective to improve both LUTS and erectile function, as compared with tamsulosin alone. Further studies are needed to assess the role of combined therapy of phosphodiesterase type 5 inhibitors and alpha blockers in treating LUTS/BPH.

Influence of serum testosterone on urinary continence and sexual activity in patients undergoing radical prostatectomy for clinically localized prostate cancer

The aim of the present study was to evaluate how serum testosterone level (T) can affect urinary continence and erectile function in patients undergoing radical prostatectomy (RP). We included 257 patients with clinically localized prostate cancer, those who had filled out preoperative quality of life questionnaires (University of California, Los Angeles Prostate Cancer Index, International Index of Erectile Function (IIEF)), and those who had T and total PSA sampled the day before surgery. We calculated correlations between T and age, body mass index (BMI), PSA, urinary function or bother (UF, UB) and sexual function or bother (SF, SB) and IIEF-5 in the whole population and in sub-populations with normal (⩾10.4 nmol l−1) and low (<10.4 ng ml−1) T using Pearsons and Spearmans correlation coefficients. We evaluated differences in these parameters between patients with low and normal T using the unpaired samples t-test and Mann–Whitney test, and finally the correlation between UF and SF, UB and SB, and between PSA and T in the overall population, and separately in patients with low and normal T using the Pearsons correlation coefficient. Mean preoperative T was 13.5 nmol l−1 and 23.7% of patients presented a low T. Mean age, mean BMI and mean preoperative total PSA at RP were 64.3 years, 25.9 kg m−2 and 9.0 ng ml−1, respectively. BMI was negatively correlated with T in the overall population (r=−0.266; P=0.02); moreover, patients with normal T presented lower BMI compared with patients with low T (25.7 vs 27.6: P=0.02). We found a significant correlation between SF scores and T in patients with normal T (r=0.1777: P=0.05). SF was significantly higher in patients with normal T compared with those with low T (74.8 vs 64.8: P=0.05). Furthermore, UF and UB were significantly correlated with SF (r=0.2544: P<0.01) and SB (r=0.2512: P=0.01), respectively, in men with normal T. Serum T was significantly correlated with PSA in men with low T (r=0.3874: P=0.0029), whereas this correlation was missed in the whole population and in men with normal T. The correlation between preoperative PSA and T in men with low T is in agreement with the ‘saturation’ model proposed by Morgentaler. The correlation between basal T and preoperative erectile function and urinary continence underlines the importance of assessing T before RP.

Prognostic Role of Perineural Invasion in 239 Consecutive Patients with Pathologically Organ-Confined Prostate Cancer

Objective: The aim of our study was to analyze the role of perineural invasion (PNI) as a predictive parameter of outcome after radical prostatectomy (RRP) in pathologically organ-confined prostate cancer (PCa) and to assess its possible correlation with other well-known prognostic features. Patients and Methods: At our institution between January 2000 and December 2007, we prospectively collected data from 251 consecutive patients with pathologically localized PCa after antegrade RRP. In our analysis 239 patients were included. PNI was defined as adenocarcinoma within the perineural space adjacent to a nerve. We evaluated the biochemical progression-free survival rate using the Kaplan-Meier method to establish the correlation between PNI and prognosis, the log-rank test to verify the statistical significance, and χ2 test to investigate the correlation between PNI and other clinicopathological parameters. Results: We found intraprostatic PNI in 157 patients (65.7%). The PNI rate was 73% (149/204) in pT2b–c vs. 26% (8/35) in pT2a surgical specimens (p < 0.001), and it was 78.5% (73/93) in patients with a Gleason score of 7–10 vs. 57% (84/146) in a Gleason score of 2–6 (p < 0.01). The mean follow-up was 65.4 (median 62, range 24–118) months. Overall, 11/239 (4.6%) patients presented biochemical recurrence after surgery and 7 (63.6%) of these patients showed PNI, but this was not statistically higher than in patients free from progression (150/228, 65.7%). The actuarial biochemical progression-free survival rate for all patients was 96.9 and 93.5% at 60 and 84 months, respectively, and the stratification based on the presence or absence of PNI did not allow us to identify different prognostic groups. Conclusions: Perineural infiltration frequently takes part in the pathway of extraprostatic extension. In our series, patients with pathological T2 stages and PNI were found to present a higher pT2 stage and Gleason score, even though our early biochemical-free outcome was not significantly higher than in patients without PNI.

Changes in sex hormone levels after radical prostatectomy: Results of a longitudinal cohort study.

The changes in testosterone and gonadotropin levels in patients who have undergone radical prostatectomy (RP) for clinically localized prostate cancer (PCa) remain unclear. The aim of the present study was to prospectively evaluate the changes in serum testosterone (Te), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the early months after RP for PCa and the correlation between these hormones at various follow-up times. A total of 100 male patients with clinically localized PCa were consecutively included in the study. The serum levels of Te, LH and FSH were measured prior to RP (baseline) and at 1 and 3 months post-operatively. Changes in the levels of Te, LH and FSH between the baseline and at 1 and 3 months after RP were analyzed with paired sample t-tests. The correlations between LH and Te levels at the various follow-up times were evaluated with a Spearman’s rank correlation coefficient. At 1 month subsequent to RP, the Te levels were significantly decreased (baseline vs. 1 month, P=0.021) and subsequently recovered to the pre-operative value at 3 months (baseline vs. 3 months, P=0.372). The mean Te level at baseline was 15.3 nmol/l, while at 1 and 3 months it was 13.8 and 14.4 nmol/l, respectively. By contrast, the levels of LH and FSH were significantly increased at 1 and 3 months post-surgery, compared with the baseline value (baseline vs. 1 or 3 months, P<0.0001). The pre-operative correlation between LH and Te was lost 1 month after RP and recovered after 3 months. Notably, the LH level at 1 month was markedly correlated with the Te levels recorded after 3 months. In the present study, patients developed compensated hypergonadotropic hypogonadism 3 months after RP.