Roberto Ponchietti

Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time

Sildenafil is one of two oral drugs approved for first-line treatment of erectile dysfunction (ED). Anecdotally, some young healthy men who wish to enhance their sexual performance are requesting or abusing sildenafil. In this randomized double-blind, placebo-controlled clinical study, we investigated the effect of sildenafil in young men without ED. A total of 60 young healthy men age 20–40 y with no reported ED were enrolled for this single-dose home-use study. Subjects had used no medication in the 6 months prior to the study. All had been engaged in a stable relationship for at least 3 months. After completing the IIEF-5 questionnaire, patients were randomized in a double-blind fashion to receive either one 25 mg tablet of sildenafil (group 1) taken prior to intercourse, or an identical placebo tablet (group 2). All subjects completed a questionnaire relating to their erectile quality. There were no differences between the two groups in the reported improvement of erection quality, 12/30 sildenafil vs 10/30 placebo (Fishers test, P=0.79). Sildenafil caused a significant reduction of the postejaculatory refractory time (12/30 vs 4/30) (χ2 test, P=0.04). Sildenafil does not improve erections in young healthy men. Sildenafil should not be given to young healthy men to improve their erections and patients should be advised against recreational abuse of the drug. In this limited single-dose home study, sildenafil appears to reduce the postorgasmic refractory time. Although controlled studies are needed to evaluate the efficacy of erection-enhancing drugs in premature ejaculation, it is possible that sildenafil might be useful for this indication.

Hypospadias: Incidence and Effects on Psychosexual Development as Evaluated with the Minnesota Multiphasic Personality Inventory Test in a Sample of 11,649 Young Italian Men

Purpose: We evaluated the incidence of hypospadias and its effects on psychosexual development in a sample of 11,649 young Italian males. Over the last 30 years only about 30 major publications have addressed these issues and the results of many studies have been contrasting. Some defects in methodology, such as low response rates, heterogeneity of age ranges and the choice of controls, have been the main limitations. Our study was designed to take these problems into account. Materials and Methods: Forty-two hypospadic subjects and a random sample of 500 nonaffected males selected from the large sample of 11,649 young men (>90% of the 18-year-old males living in the Italian region of Tuscany) were screened by the Minnesota Multiphasic Personality Inventory (MMPI) test, psychological interview and clinical evaluation. Results: The incidence of hypospadias in this representative group of Italian men is 3.6/1,000. No difference was noted in the percentage with altered MMPI compared with the control group. The age at surgical corrections and the number of operations are not related to an abnormal global psychological adjustment. Severity of disease influences a more negative genital appraisal and the number of operations is correlated only with more difficulty in initiating contact with the opposite sex. Conclusions: Surgery for hypospadias has to be strongly pursued in as many cases as possible. In addition, we strongly recommend following up all hypospadics, independently of the severity of their genital malformations, through adolescence to early adulthood, to ensure early detection of subjects with impaired psychological profiles.

Estimation of prostate cancer volume by endorectal coil magnetic resonance imaging vs. pathologic volume.

Objective: Since tumor volume is recognized as an important predictor of clinical stage and disease outcome of prostate cancer, accurate preoperative estimation of tumor volume can play an important role in planning the appropriate treatment and establishing a patient’s prognosis. We performed this study to evaluate the accuracy of the endorectal coil magnetic resonance (MR) technique for reliable prediction of tumor volume in patients with prostatic cancer. Material and Methods: Endorectal coil MR imaging was performed in 57 consecutive men who were suspected to have prostate cancer. Subsequent ultrasound-guided transrectal biopsy revealed prostate cancer in 44 cases. The pathological volume of the surgical specimens of 25 selected patients who underwent radical prostatectomy was retrospectively compared to the volume estimated by endorectal coil MR studies, and the Pearson correlation coefficient was calculated. Results: In 15 patients the estimated size of the tumor was within 15% of the true tumor volume; in the remaining 10 cases MR imaging tended to underestimate large tumors and overestimate small ones. A significant correlation between the volumes as determined with MR imaging and measurements of surgical specimens was observed (r 0.94; slope 0.82). To our knowledge, this is the best correlation found between pathological volume and tumor volume as evaluated by any other imaging modality. Conclusions: Endorectal coil MR imaging is a powerful means of evaluating the prostate gland; however, further improvements in imaging and/or volume calculation are required to provide a more accurate preoperative assessment of prostate cancer volume.

Phase II trial of weekly intravenous gemcitabine administration with interferon and interleukin-2 immunotherapy for metastatic renal cell cancer.

PURPOSE Since metastatic renal cell carcinoma has a poor prognosis and treatment strategies, including hormone therapy, chemotherapy and immunotherapy, have little impact on the quality of life and global survival statistics, new interest has recently focused on the combination of immuno-chemotherapy using pyrimidine analogues, such as gemcitabine. MATERIALS AND METHODS In a phase II study 16 patients with metastatic renal cell carcinoma were treated with 1,000 mg./m. gemcitabine intravenously on days 1, 8, 15 and 28 for 6 months, 3 MU (1 MU = 1 x 10(6) IU) interferon (IFN)-alpha intramuscularly 3 times a week and 4.5 million IU interleukin (IL)-2 subcutaneously daily for 5 days a week for 2 consecutive weeks every month for 6 months. Responding and nonprogressing cases were maintained on immunotherapy consisting of IFN-alpha and IL-2 for further 6 months. RESULTS In 15 evaluable patients overall response rate (1 complete response plus 3 partial response) was 28% while stable disease was achieved in 7 (47%). Median survival duration was 20 months (range, 9 to 26+) and median time to tumor progression was 14 months (6 to 26+). The complete response lasted 24+ months and partial response lasted 16 months. The regimen was well tolerated with only 1 case of neutropenia (WHO grade 3), while anorexia, fatigue and flu-like symptoms were the most common toxicity problems but were never greater than grade 2. CONCLUSIONS Despite the small sample size, this study demonstrates that gemcitabine combined with standard doses of IFN-alpha and low doses of IL-2 is effective treatment for metastatic renal cell carcinoma. This biotherapy was well tolerated and resulted in an optimum objective response and relatively long-term survival.

The use of RT–”nested” PCR of prostate specific antigen to detect hematogenous neoplastic cells in patients with prostate adenocarcinoma

Abstract The aim of this study was to determine the presence of hematogenous neoplastic cells in patients with prostate cancer. We used a reverse transcription (RT) ”nested” polymerase chain reaction (PCR) of prostate-specific antigen (PSA) mRNA to detect the presence of circulating tumor cells in 52 patients who underwent radical prostatectomy with lymphadenectomy. Blood samples were obtained before and after the surgical manipulation. Seven (13.5%) preoperative samples presented evidence of circulating neoplastic cells. All postoperative specimens studied presented a negative result at analysis 24 h after surgical manipulation. Although we did not find a statistical correlation between the PSA-PCR results and clinical-histopathological parameters, the presence of circulating prostate cells was strongly correlated with an elevated Gleason score of primary tumor (P<0.01). Thus our data show the positive effect of surgical treatment in removing the metastases source. The sensitive RT–nested PCR assay may play a crucial role in the administration of adjuvant therapy of patients with prostate adenocarcinoma.

Weekly paclitaxel and epirubicin in the treatment of symptomatic hormone-refractory advanced prostate carcinoma: report of a phase II trial.

The efficacy of weekly paclitaxel in androgen-independent prostate cancer and its addictive cytotoxicity with anthracycline derivatives led us to determine the safety and efficacy of a weekly schedule of paclitaxel and epirubicin. Between October 2000 and November 2002, 32 patients were enrolled in this study. Patients characteristics included a median age of 72 years (range 68–77), adequate hepatic, cardiac, renal and bone marrow functions, ECOG performance status of 1–2, and no prior chemotherapy. All patients had received hormonal manipulation and seven patients (22%) had received prior palliative radiation therapy. The regimen consisted of paclitaxel 70 mg/m2 i.v. infusion for 2 h and epirubicin 30 mg/m2 in bolus every week. Treatment was continued for 3 months or until disease progression or unacceptable toxicity were observed. During the study, prostate-specific antigen (PSA) was monitored and response was defined as a 50% reduction in PSA levels, to be confirmed 4 weeks later. Thirty-one patients were evaluable for toxicity and 21 for objective response. Seventeen patients (57%) had a decline above 50% in PSA level that lasted more than 4 weeks with a median time to PSA progression and a median duration of PSA response of approximately 5.5 months. Ten of the 21 patients with measurable disease (47%) had a confirmed objective response (one complete response and 20 partial responses). Thirteen of 25 symptomatic patients (56 %) had improvement in pain. The median time to disease progression was 7.6 months and the median survival was 12.9. The most prominent grade 3 toxicities were reversible myelosuppression and fatigue. Nausea, vomiting, diarrhea and peripheral edema were minimal. No evidence of cardiac toxicity was recorded. Alopecia was frequent, but reversible, in all patients. We conclude that despite the small sample size, this study demonstrates that the combination of weekly paclitaxel and epirubicin is a well-tolerated regimen for androgen-independent prostate cancer. The results imply that a combination of these agents in a weekly schedule may have clinical potential in prostate cancer treatment.

An Open-Label, Randomized, Flexible-Dose, Crossover Study to Assess the Comparative Efficacy and Safety of Sildenafil Citrate and Apomorphine Hydrochloride in Men with Erectile Dysfunction

Introduction: We report the methodology and results of a study that compared a dopaminergic agonist, apomorphine, with a phosphodiesterase type-5 inhibitor, sildenafil, in terms of efficacy, tolerability, satisfaction and patient preference. Patients and Methods: This was a 20-week open- label, randomized, flexible-dose, crossover study to assess the comparative efficacy and safety of sildenafil and apomorphine. One sequence group received treatment with sildenafil followed by apomorphine and the other sequence group received treatment with apomorphine followed by sildenafil. The primary efficacy variable was the measurement of the score of the erectile function domain (the sum of questions 1–5 and 15) of the International Index of Erectile Function (IIEF) questionnaire. The secondary efficacy variables were: the responses to the Global Efficacy Assessment Questions; the score of the responses to all the questions of the IIEF questionnaire; the index score of the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, and the event log variables. Resultsand Conclusions: A marked increase in the mean IIEF score was observed after treatment with sildenafil, compared with a small increase following treatment with apomorphine. The mean baseline and final scores before and after treatment with sildenafil were 13.9 ± 5.2 and 24.1 ± 5.2, while the corresponding mean scores before and after treatment with apomorphine were 14.2 ± 5.1 and 16.8 ± 6.2. The comparison between treatments showed a statistically significant difference in favor of sildenafil. Furthermore, sildenafil was found to be significantly superior to apomorphine in all the other secondary variables, produced a high level of patient satisfaction, and a significantly larger number of patients indicated their preference for sildenafil compared to apomorphine.

Curriculum in Urology: Phimosis and Circumcision in Children

ly around the glans, but they are blocked in the midline on the ventrum by the incompletely developed urethra. This preputial fold rolls over the base of the glans and leaves a groove between the coronal sulcus and the primitive prepuce. At the same time, an ingrowth of epithelium with thick cells, known as glanular lamella, actively proliferates in the groove in order to form a sheet between the preputial fold and the glans. This active epithelial proliferation in the groove carries the ridge of the preputial fold distally with the help of the mesenchymal growth within the prepuce [1]. The preputial and urethral folds fuse on the ventrum of the glans as the frenulum. The urethra within the glans penis develops by canalization of the urethral plate and the urethral orifice reaches its final destination at the site of the former epithelial tag. Formation of the frenulum seems to be required for completion of glandular urethral development [2]. After the 4th month of gestation, the single epithelial The prepuce, also called the foreskin, is the double-faced covering of the glans of the flaccid penis. Its inner surface is mucosa and outer surface is penile skin. The junction of these two surfaces is known as the preputial ring. Disorders of the prepuce, such as balanitis and phimosis, receive only cursory attention even in urological textbooks and their exact etiopathogenesis still remains unclear. Knowing the development of the prepuce is important to better understand its disorders and surgery.

Experience with Omentoplasty

A 6-year experience with omentoplasty is presented. During this period pedicled omentum was used in 145 procedures of reconstructive urologic surgery. On the basis of this experience the authors conclude that omentoplasty is an essential part in urological reconstructive surgery.

Rupture of the bulb of the urethra: repair effectuated using a patch of human dura mater.

AbstractWe describe a case of traumatic rupture of the bulb of the urethra, which was repaired successfully using a patch of lyophilized dura mater.