Alessandro Natali

Peyronie’s Disease: Prevalence and Association with Cigarette Smoking

Objectives: We present a multicenter, population–based epidemiological survey aimed at assessing the prevalence of Peyronie’s disease (PD) and its potential risk factors in the general population. Methods: In each of the ten centers throughout Italy, a uroandrologist contacted all the men in the age range 50–69 years registered with a general practitioner (GP). The subjects recruited were evaluated on the basis of their medical history, including alcohol consumption and cigarette smoking. The following questionnaires were administered: IIEF, IIPSS symptom score, premature ejaculation and PD. Results: All the subjects registered with a GP were invited to participate in the study. Of the 1,180 subjects, 647 (53%) entered over survey. In this population, 46 cases of PD were identified, accounting for a prevalence of 7.1%. The prevalence rate increased with age even if the trend is not statistically significant. The multivariate analysis showed a significant correlation between cigarette smoking and PD, with an odds ratio (OR) of 4.6 (CL 95%) confidence limit 1.506– 14.287). Smoking as single variable had an OR of 7.2 (95% CL 2.34–24.93). No significant association was observed between PD and the other variables such as cardiovascular diseases, diabetes, hypertension and alcohol consumption. Conclusions: PD is a much more frequent condition in the general population than previously reported. According to our results, cigarette smoking may be considered a risk factor for developing PD. If further and more targeted studies confirm that giving up smoking may reduce the risk of developing PD, then there will be new prospects for primary and secondary prevention and for curbing the progression of the disease.

Penile Implantation in Europe: Successes and Complications with 253 Implants in Italy and Germany

INTRODUCTION Results for prosthesis implantation from everyday clinical practice within Europe are few. This report provides data on the most commonly used penile prostheses (the American Medical Systems [AMS] series). AIM The study aimed to assess, retrospectively, complications and patient satisfaction with AMS penile implants in 253 consecutive patients with erectile dysfunction from three European centers. METHODS Pre, intra- and postoperative data were obtained from chart review, with a mean follow-up of 60 months; 200 patients were available for evaluation. Patient satisfaction data were collected using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. MAIN OUTCOME MEASURE Complications and patient satisfaction were assessed. Patient satisfaction was evaluated using a standardized assessment tool (the modified EDITS questionnaire). RESULTS Major postoperative complications occurred in 40 (20%) patients, including 9 (22.5%) prosthesis infections, 18 (45%) mechanical failures, and 13 (32.5%) erosions. Patient satisfaction with the AMS 700CX, AMS Ambicor, and AMS 600-650 was 97%, 81%, and 75%, respectively; dissatisfaction was 0%, 5%, and 6%, respectively. Partner satisfaction with the AMS 700CX, AMS Ambicor, and AMS 600-650 was 91%, 91%, and 75%, respectively; dissatisfaction was 0%, 5%, and 6%, respectively. Erections were more natural (harder) than before with the AMS 700CX, AMS Ambicor, and AMS 600-650 in 91%, 85%, and 88%, respectively; hardness was the same as before in 9%, 15%, and 13%, respectively; no erections were less hard than before. CONCLUSIONS Postoperative complications differed from those reported in the literature, while patient satisfaction rates were roughly similar. The reporting of specific data for different implant types, plus the use of standardized assessment tools for patient satisfaction is significant as in the future, it will allow comparison of data between centers performing penile prosthesis implants using these devices.

Identification, localization and functional activity of oxytocin receptors in epididymis

Oxytocin (OT) is a neurohypophysial hormone with unclear physiological functions in the male. Several previous studies indicated that OT might have a role in the ejaculatory process, stimulating sperm release from the epididymal storage. In this study we investigated on the presence and function of OT receptor (OTR) in rabbit and human epididymis. By using RT-PCR, Western and binding studies, we found that OTR gene and protein is expressed in the human epididymis and stimulates in vitro contractility. The immunolocalization of OTR suggests that the receptor is not only present in the smooth muscle cells of the human epididymis but also in the epithelial compartment. Experiments performed in rabbit epididymal epithelial (rEE) cells in culture indicate that OT induces the release of an other potent stimulator of epididymal contractility, endothelin-1 (ET-1), Blocking the ET(A) subtype of the ET-1 receptors, by using a specific antagonist (BQ-123), partially counteracts the contractile effect of OT, suggesting positive interactions between the two peptides in regulating epididymal contractility. Finally, to investigate whether an acute OT administration increases sperm release also in humans, we treated oligozoospermic patients with an intravenous bolus of OT (2.5 IU), just before sperm collection. In a small, single blind study, we found that OT almost doubled sperm retrieval when compared with vehicle administration. Our results indicate that OT might have physiological functions also in the male, controlling epididymal motility and sperm progression through the male genital tract.

Endothelium-dependency of yohimbine-induced corpus cavernosum relaxation.

Development and maintenance of penile erection requires the relaxation of the smooth muscle cells in the cavernous bodies and is essentially mediated by nitric oxide (NO). The penile flaccid state is conversely maintained by the alpha adrenergic neuroeffector system and by other vasoconstrictors, such as endothelin-1 (ET-1). In this study we examined the mechanisms involved in yohimbine-induced relaxation in human and rabbit corpora cavernosa (CC). We essentially found that yohimbine not only blocks contractions induced by adrenergic agonists, but also by non-adrenergic substances, such as ET-1. This effect was unrelated to antagonism at the level of ET receptors, because yohimbine did not affect ET-1-induced increase in intracellular calcium in isolated CC cells. Conversely, our data suggest that yohimbine counteracts ET-1-induced contractions by interfering with NO release from the endothelium. In fact, yohimbine-induced CC relaxation was inhibited by the mechanical removing of the endothelium and by blocking NO formation or signalling via guanylate cyclase and cGMP formation. Conversely, yohimbine activity was strongly increased by inhibiting cGMP degradation. In an experimental model of hypogonadism, performed on rabbits by chronic treatment with a long-lasting GnRH agonist, the relaxant yohimbine activity was also decreased, but completely restored by androgen supplementation. This effect was evident only in preparations in which the main source of NO was present (endothelium) or in which NO formation was not impaired by L-NAME. Our data indicate that the relaxant effect of yohimbine is both endothelium and androgen-dependent. This might justify the lack of efficacy of this drug in treatment of some form of organic erectile dysfunction.

STUDIES ON THE MECHANISMS INVOLVED IN THE ATP-INDUCED RELAXATION IN HUMAN AND RABBIT CORPUS CAVERNOSUM

The effect of ATP in human and rabbit corpus cavernosum (CC) smooth muscle was investigated. Strips of human CC were vertically mounted in an organ bath and the tonic tension was recorded. ATP (0.1-3 mM) induced a concentration-dependent relaxant effect, with a pD2 value of 3.01+/-0.3. The purine-induced relaxation was not affected by L-NAME (100 microM). In rabbit CC, ATP also induced a concentration-dependent relaxation, which was not influenced by L-NAME or by indomethacin (3 microM), with a pD2 value of 3.1 +/-0.4. The ATP-induced relaxant effect in rabbit CC was increased by both the inhibitor of adenosine reuptake, dipyridamole (3 microM) and by the inhibitor of adenosine deaminase, EHNA (0.3 microM). Moreover CGS 15943 (3 microM), an A2a adenosine antagonist, reduced the ATP-induced relaxation. UTP was not able to produce relaxation. The two ATP analogues 2-methylthioATP and alpha,beta-methylene ATP were able to induce relaxation in rabbit CC, with the following order of potency: 2-methylthioATP > ATP > alpha,beta-methylene ATP thus suggesting a role for P2y receptors. However, reactive blue (500 microM), an unspecific P2y antagonist, did not modify the ATP relaxant response. The inhibition of phospholipase C by U73122 (3 microM) and of the endoplasmic reticulum Ca2+ATPase by thapsigargin (1 microM) did not modify the ATP-induced relaxation. The P2x specific antagonist PPADS (30 microM) and suramine (500 microM) were not able to modify the ATP relaxation either in the absence or presence of CGS 15943 (3 microM). These results confirm that ATP acts as a potent and NO-independent relaxant agent of human and rabbit CC. Our findings also show that the ATP effect is partially attributable to the metabolic breakdown of ATP to adenosine, which acts through A2a receptor stimulation, but is also due to a direct stimulation of P2 receptors that are different from the classical P2y and P2X receptor subtypes for ATP.

An Assessment of New Sperm Tests for Male Infertility

The routine semen analysis, although used for more than 50 years, fails to accurately distinguish between fertile and infertile men. As a consequence, many tests of sperm function (TSF) have been developed. This review discusses both older and newer diagnostic TSF. It outlines the principles underlying each assay and reviews aggregate clinical data to determine its current relevance and utility. It concludes that the relevance of many older TSF is questionable, with the wide acceptance of intracytoplasmic sperm injection (ICSI). Newer TSF have the potential to deliver more clinically relevant information but require more extensive study to better understand their predictive role in the ICSI era.

Heavy smoking is an important risk factor for erectile dysfunction in young men

Clinical and basic science studies provide strong indirect evidence that smoking may affect penile erection. The objective of this retrospective research was to investigate the role of smoking for erectile dysfunction (ED) in order to obtain some insight into the prevention of ED. We reviewed the data from 860 male patients aged between 18 and 44 visited during the period January 1999 to December 2002. The patients were divided into three groups: smokers, never smokers and former smokers. All patients were submitted of medical history, such as, IIEF 5 Questionnaire, physical examination, serum levels of glucose, cholesterol, prolactin and free testosterone. Our data were compared with ISTAT (Italian Institute of Statistics) and data on the Italian population of smokers. We have stratified the data by age and area of residence. The 860 patients, mean age 32.4 y old (range 18–44), are distributed into three groups: smokers 460 (53.5%), never smokers 320 (37.2%) and former smokers 80 (9.3%). Current smokers in our series are 460 (53.5%) in comparison to 34.7% of male current smokers in Italy, in the same range (18–44). Out of 860, 337 are patients who smoked more than 20 cigarettes per/day (39.2%) and these data are extremely interesting; while comparing the same aged men through ISTAT, it is found that only 4% are heavy smokers. On analysing the incidence of heavy smoking in middle-aged patients affected by ED with the whole Italian population by means of ISTAT, taking into account males with the same age range and area of residence, it was shown that the data of our population (sample) compared all Italian middle-aged patients are 39.2 vs 4%; this explains the need for education within a comprehensive smoking cessation programme, and should be reserved especially for young smokers, in order to be aware and informed of the effect of tobacco on erectile function.

Urethral Carcinoma Recurrence in Ileal Orthotopic Neobladder: Urethrectomy and Conversion in a Continent Pouch with Abdominal Stoma

A patient who had previously undergone ileal neobladder with Studer technique presented an urethral recurrence of a transitional cell carcinoma. Further surgical treatment consisted of urethrectomy and creation of an intussuscepted ileal loop which was anastomosed to the pouch and provided a continence mechanism allowing self-catheterization.

Measurement of testosterone and its 5-alfa-reduced metabolites in human prostatic tissue using isotope dilution mass spectrometry

5 alpha-Dihydrotestosterone (DHT) has been widely measured in human prostatic tissue using RIA since it is found to be involved in pathogenesis of human prostatic hyperplasia (BHP) and to be the best index for the follow-up of patients affected by prostatic cancer under endocrine treatment. A GC/MS method for the simultaneous determination of testosterone (T), dihydrotestosterone (DHT), 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol) and 5 alpha-androstan-3 beta-17 beta-diol (3 beta-diol) in prostatic tissue was developed based on the isotopic dilution technique. Trideuterated internal standards of each compound were previously synthesized in our laboratory. After previous extraction and purification on Sep-Pak C-18 cartridges and Lipidex DEAP columns, T and its metabolites were measured as heptafluorobutyric esters (HFB). Quantitative analysis was performed on a VG 7070 EQ mass spectrometer equipped with a fused silica capillary column using the Selected Ion Monitoring technique. Steroid values (means +/- SD; ng/g tissue) found in 9 human hypertrophic prostates were: T, 0.71 +/- 0.43; DHT, 4.46 +/- 1.41; 3 alpha-diol, 0.34 +/- 0.23; 3 beta-diol, 0.14 +/- 0.32.

Rare Case of Atypical Epitelioid Hemangioma of Penis Initially Misdiagnosed as Peyronie's Disease: Report With Clinical, Radiologic, and Immunohistochemical Analysis

We report a rare case of atypical epithelioid hemangioma of the penis in a 42-year-old man with a painful penile dorsal nodule, first misdiagnosed on simple penile ultrasonography as Peyronies disease. Even though the patient underwent treatment, the lesion improved and a penile echo-color Doppler scan showed abundant vascularization. After local excision, the pathologic diagnosis was atypical epithelioid hemangioma (central epithelioid cells bordered by immature vessels), with immunohistochemical positivity for CD31 and CD34 and negativity for epithelial membrane antigen. At 12 months after surgery, the patient was free of disease. Penile echo-color Doppler ultrasonography is essential to perform a differential diagnosis between Peyronies disease from other penile nodular diseases.