Erectile dysfunction and cardiovascular diseases.

Erection is a vascular phenomenon under a psychologic control in a hormonal environment. Erectile dysfunction is defined as the inability to obtain and to maintain sufficient erection for satisfactory intercourse. Organic erectile dysfunction results mainly from vascular problems due to atherosclerosis, a process that begins during childhood, and becomes clinically evident from middle age. Endothelial dysfunction is the first step of atherosclerosis. As the endothelial cells recover the sinusoid spaces in the cavernous tissue and because common risk factors for atherosclerosis have been frequently found in patients with erectile dysfunction, it is logical that vascular impotence presents the same pathophysiology of the other vascular diseases. They share a similar pathogenic involvement of nitric oxide pathway leading to impairment of endothelium dependent vasodilatation and structural vascular abnormalities. Circulating markers of endothelial cell damage have been reported in patients with erectile dysfunction while they have not yet presented any other vascular pathology. Endothelial progenitor cells of bone marrow origin that play a role in promoting endothelial repair are also reduced in vascular abnormalities.As penile arteries have the smallest diameter in the vascular network and because atherosclerosis is a systemic disease, erectile dysfunction could be a sentinel symptom of a more generalized vascular pathology. Modifications of reversible causes or risk factors at the base of the pathogenesis of atherosclerosis remain the first approach toward improving endothelial function and associated with chronic exposure to PDE5-I, they could improve or even cure ED and could avoid fatal cardiovascular attacks in the future.

Disfunción eréctil y enfermedades cardiovasculares / Erectile dysfunction and cardiovascular diseases

Erection is a vascular phenomenon under a psychologic control in a hormonal environment. Erectile dysfunction is defined as the inability to obtain and to maintain sufficient erection for satisfactory intercourse.Organic erectile dysfunction results mainly from vascular problems due to atherosclerosis, a process that begins during childhood, and becomes clinically evident from middle age.Endothelial dysfunction is the first step of atherosclerosis. As the endothelial cells recover the sinusoid spaces in the cavernous tissue and because common risk factors for atherosclerosis have been frequently found in patients with erectile dysfunction, it is logical that vascular impotence presents the same pathophysiology of the other vascular diseases. They share a similar pathogenic involvement of nitric oxide pathway leading to impairment of endothelium dependent vasodilatation and structural vascular abnormalities. Circulating markers of endothelial cell damage have been reported in patients with erectile dysfunction while they have not yet presented any other vascular pathology.Endothelial progenitor cells of bone marrow origin that play a role in promoting endothelial repair are also reduced in vascular abnormalities.As penile arteries have the smallest diameter in the vascular network and because atherosclerosis is a systemic disease, erectile dysfunction could be a sentinel symptom of a more generalized vascular pathology.Modifications of reversible causes or risk factors at the base of the pathogenesis of atherosclerosis remain the first approach toward improving endothelial function and associated with chronic exposure to PDE5-I, they could improve or even cure ED and could avoid fatal cardiovascular attacks in the future(AU)

OBJETIVO: La erección es un fenómeno bajo control fisiológico en un ambiente hormonal. La disfunción eréctil se define como la incapacidad de obtener y mantener una erección suficiente para una relación sexual satisfactoria.La disfunción eréctil orgánica es principalmente el resultado de problemas vasculares debidos a arterioesclerosis, un proceso que comienza durante la infancia y se hace clínicamente evidente en la edad media.La disfunción endotelial es el primer paso de la arterioesclerosis. Cómo las células endoteliales recubren los espacios sinusoidales en el tejido cavernoso y se han encontrado frecuentemente factores de riesgo de arterioesclerosis en pacientes con disfunción eréctil, es lógico que la impotencia vascular presente la misma fisiopatología de las otras enfermedades vasculares. De forma similar, comparten una participación patogénica de la vía del óxido nítrico que conduce a un empeoramiento de la vasodilatación dependiente del endotelio y a anomalías vasculares estructurales.Se ha publicado la presencia de marcadores circulantes de daño celular endotelial en pacientes con disfunción eréctil cuando todavía no han presentado ninguna otra patología vascular. Las células madre endoteliales con origen en la médula ósea, que juegan un papel en promover la reparación endotelial, también están reducidas en las anomalías vasculares. Cómo las arterias peneanas tienen el calibre más pequeño de la red arterial y la arteriosclerosis es una enfermedad sistémica, la disfunción eréctil podría ser un síntoma centinela de una patología vascular más generalizada.La modificación de causas o factores de riesgo reversibles en la base patogénica de la arteriosclerosis sigue siendo el primer abordaje para mejorar la función endotelial, y asociado con la exposición crónica a inhibidores de la PDE 5 podría mejorar o incluso curar la DE y podría evitar futuros ataques cardiovasculares fatales(AU)

A simple maneuver to replace dislodged laparoscopic port.

Inadvertent dislodgment of laparoscopic port can occur despite preventive measures. We describe a simple maneuver to replace a dislodged port using a palpation probe. The principle is analogous to that of using a laparoscopic grasping forceps. It is easy to perform, quick, reliable, safe, and particularly useful for the laparoscopists in training.

Handling and reporting of biopsy and surgical specimens of testicular cancer.

This paper is the result of a meeting of the European Association of Pathologists, Uropathology Division in Florence 2003. The aims of this meeting were to establish: guidelines for specimen handling by urologists and minimum requirements for data accompanying testicular specimens submitted to pathologists; a consensus on techniques for processing specimens by pathologists; the essential information required from pathology reports; areas where our standard practice is traditional rather than evidence based and where further studies are required. The general aims of histopathology are to give or confirm a diagnosis; assess established prognostic markers; identify changes associated with treatment; provide information for audit (i.e. imaging, urology and pathology) and maintain a permanent record (slides/blocks).

[Laparoscopy in urology]. / La laparoscopie en urologie.

Since the past 10 years, results have established laparoscopy's efficacy. It is actually a consistent surgical option for a lot of indications met in urology. The rational behind performing laparoscopic procedures includes shorter hospital stays, less postoperative pain and a more rapid return to usual activity. Drawbacks of laparoscopy include significant learning curve, longer operative times and higher overall costs. One particular focus is the oncologic applications of laparoscopy for nephrectomy and specially for radical prostatectomy. Laparoscopy become nowadays an usual part of the armamenturium of urological teams.

[Erectile dysfunction and phosphodiesterase type 5 inhibitors]. / La dysfonction érectile masculine et les inhibiteurs de la phosphodiestérase de type 5.

Erectile dysfunction affects 150 millions of men and its prevalence increases with age. The improvement of life expectancy will increase the worldwide prevalence to 300 million in 2025. Oral treatments are nowadays the first line therapy for the vast majority of people as they have a good reliability and tolerance and restore more spontaneity. The authors relate the widespread interest in phosphodiesterase type 5 inhibitors with the advent of sildenafil for the treatment of erectile dysfunction and present characteristics of 2 new phosphodiesterase type 5 inhibitors in Belgium, tadalafil and vardenafil.

Early prostate cancer: prevention, treatment modalities, and quality of life issues.

Our understanding of the screening, prevention and treatment of early prostate cancer is improving. This is a result of new data from clinical trials and the incorporation of efficacy measures based on risk assessment and quality of life (QoL). This review aims to examine completed and ongoing clinical trials that address issues in early prostate cancer, including screening, prevention, treatment, and QoL. Prostate-specific antigen (PSA) testing has a crucial and evolving role in detecting primary prostate cancer, evaluating prevention interventions and assessing the effectiveness of treatment. Questions remain about the optimal PSA parameters appropriate for primary screening and for diagnosing relapse. Emerging and established data provide evidence that early intervention with hormone therapy, either as immediate or adjuvant therapy, delays progression in prostate cancer patients with intermediate or poor prognosis. The impact of therapeutic modality on QoL has become better characterized, as QoL instruments have been developed, validated and applied.

Erectile dysfunction is associated with a high prevalence of hyperlipidemia and coronary heart disease risk.

OBJECTIVES: Erectile dysfunction (ED) is frequently of vascular origin. An association between ED and ischemic heart disease has been suggested as a consequence of endothelial disease of penile and coronary arteries. The role of serum lipid levels has been demonstrated in coronary heart disease (CHD), but the relationship with ED is poorly documented. We evaluated undiagnosed hyperlipidemia in ED patients and their coronary heart disease risk. METHODS: We prospectively compared a group of patients with ED to matched non-ED patients. Risk factors for ED and CHD were noticed and a serum lipid work up (total cholesterol [TC], triglycerides [TG], HDL-cholesterol [HDL-C], LDL-cholesterol [LDL-C] and TC/HDL-C ratio) was measured. We compared the prevalence of hyperlipidemia in the two groups and its impact as predictor of ED. We calculated the risk to develop CHD in patients with or without ED based upon commonly accepted variables of the Framingham Heart study. RESULTS: 215 patients had ED (mean age 57.6+/-9.6 years) and 100 no ED (mean age 59.7+/-8.3 years). The prevalence of hypercholesterolemia (TC >200 mg/dl or 5.17 mmol/l) was 70.6% vs. 52% in ED and non-ED groups respectively (p=0.06). After exclusion of confounding factors, logistic regression analyses showed HDL-C and TC/HDL-C ratio as significant predictors of ED (p=0.011 and 0.000 respectively). Increased 10-year CHD risk was found in 56.6% in the ED group compared to 32.6% in the control group (p<0.05). The median risk was 12.18% vs. 9.07% respectively with a significant age-related risk (p<001). CONCLUSIONS: Hyperlipidemia is common in ED patients. HDL-C and TC/HDL-C ratio are predictors of ED. These patients have a high risk of later developing CHD. Erectile dysfunction might therefore serve as sentinel event for coronary heart disease.

A shared care approach to the management of erectile dysfunction in the community.

Erectile dysfunction (ED) affects men of all ages and results in considerable distress and impact on quality of life for those who suffer from it. As ED is associated with a wide variety of under-lying conditions and cardiovascular co-morbidities, there is a requirement for diversity of treatment options and several factors must be considered to customise and optimise therapy. In the ideal holistic approach to management of the ED patient, both primary care and specialist physicians have an important role to play. This article reports on a sequential approach for the diagnosis and treatment of ED, with an emphasis on 'shared care'. The deliberations are based on a pan-European inter-disciplinary group that met at the Lygon Arms, UK on 22 February 2002.

Male andropause: myth, reality, and treatment.

A progressive decrease in androgen production is common in aging men. The physiological causes for this phenomenon seem to be multifactorial. The magnitude of the decline in testosterone with age and the prevalence of older men with low testosterone levels have not been well established. The extent to which an age-dependent decline in androgen levels leads to health problems that might affect or alter the quality of life remains under debate. In men older than middle age, total testosterone levels may be misleading because of an increase in sex hormone-binding globulin levels. The mechanism of the age-associated decrease of the endocrine testicular function is also essentially due to primary testicular failure, but important changes occur at the hypothalamopituitary level. The most prominent endocrinological alterations with aging are related to the sex steroids, but others, such as growth hormone, melatonin cortisol, and thyroxine, are also affected. The clinical picture of andropause syndrome is characterized by diminished sexual desire and erectile capacity, decrease in intellectual activity, fatigue, depression, decrease in lean body mass, skin alterations, decrease in body hair, decrease in bone mineral density that results in osteoporosis, and increase in visceral fat and obesity. Current medical treatments for androgen supplementation include oral tablets, intramuscular injections, and scrotal and nonscrotal patches. Unfortunately, none of these preparations mimic the circadian rhythm, even if some of them may approximate the circadian rhythm by dose adjustments. Moreover, the androgen supplementation could have adverse effects on different organs, namely, the liver, lipid profile, cardiovascular disease, prostate, sleep disorders, and emotional behavior. Clinical response is a better guide to dose requirements, regardless of serum testosterone levels. This important field must be actively investigated by the medical, behavioral, and social sciences.

Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop?

PURPOSE: We evaluated biochemical parameters and pathological features, as well as biopsy related morbidity of prostate cancer detected on biopsies 2, 3 and 4 in men with total serum prostate specific antigen (PSA) between 4 and 10 ng./ml. These features were compared to those detected on prostate biopsy 1. MATERIALS AND METHODS: In this prospective European Prostate Cancer Detection study 1,051 men with total PSA between 4 and 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy and 2 additional transition zone biopsies. All patients in whom biopsy samples were negative for prostate cancer underwent biopsy 2 after 6 weeks. If also negative, biopsies 3 and even 4 were performed at 8-week intervals. Those patients with clinically localized cancer underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either biopsy 1 or 2 and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. RESULTS: Cancer detection rates on biopsies 1, 2, 3 and 4 were 22% (231 of 1,051), 10% (83 of 820), 5% (36 of 737) and 4% (4 of 94), respectively. Overall, of the patients with clinically localized disease, which was 67% of cancers detected, 86% underwent radical prostatectomy and 14% opted for watchful waiting or radiation therapy. Overall, 58.0%, 60.9%, 86.3% and 100% of patients had organ confined disease on biopsies 1, 2, 3 and 4, respectively. Despite statistically significant differences in regard to multifocality (p = 0.009) and cancer location (p = 0.001), including cancer on biopsy 2 showing a lower rate of multifocality and a more apico-dorsal location, there were no differences in regard to stage (p = 0.2), Gleason score (p = 0.3), percent Gleason grade 4/5 (p = 0.2), serum PSA and patient age between biopsies 1 and 2. However, cancer detected on biopsies 3 and 4 had a significantly lower Gleason score (p = 0.001 and 0.001), lower rate of grade 4/5 (p = 0.02), and lower volume (p = 0.001 and 0.001) and stage (p = 0.001), respectively. CONCLUSIONS: Despite differences in location and multifocality, pathological and biochemical features of cancer detected on biopsies 1 and 2 were similar, suggesting comparable biological behaviors. Cancer detected on biopsies 3 and 4 had a lower grade, stage and volume compared with that on biopsies 1 and 2. Morbidity on biopsies 1 and 2 was similar, whereas biopsies 3 and 4 had a slightly higher complication rate. Therefore, biopsy 2 in all cases of a negative finding on biopsy 1 appears justified. However, biopsies 3 and 4 should only be obtained in select patients with a high suspicion of cancer and/or poor prognostic factors on biopsy 1 or 2.

Long-term use of tamsulosin to treat lower urinary tract symptoms/benign prostatic hyperplasia.

PURPOSE: The long-term efficacy and safety of 0.4 mg. tamsulosin once daily were assessed in patients with lower urinary tract symptoms/benign prostatic hyperplasia treated for up to 4 years. MATERIALS AND METHODS: A total of 516 patients were enrolled from 2 European open label studies that were extensions of 3 double-blind controlled studies. RESULTS: Significant improvement in maximum urine flow and total Boyarsky symptom score during the controlled trials was sustained throughout the extension study for up to 4 years in patients who remained on therapy. The increase in mean maximum urine flow from baseline was 1.2 to 2.2 ml. per second (p <0.001) and it remained 11.5 to 12 ml. per second during followup. Total Boyarsky symptom score was decreased from baseline by 4.1 to 4.7 points (p <0.001). The incidence of treatment responders, defined as a 25% or greater decrease in total symptom score, remained stable throughout the 4-year period. Increasing the dose of tamsulosin from 0.4 to 0.8 mg. seemed to have no substantial additional benefit. During the 4 years of treatment 26% of patients had side effects that were considered possibly or probably drug related. However, only 5% of patients discontinued treatment because of drug related side effects. No clinically significant changes in blood pressure or pulse rate occurred during the study. CONCLUSIONS: Long-term treatment with tamsulosin is safe and well tolerated in patients with lower urinary tract symptoms/benign prostatic hyperplasia. Improved efficacy was sustained during 4 years of followup.

Extraperitoneal laparoscopic radical prostatectomy. Results after 50 cases.

INTRODUCTION: After an initial experience using transperitoneal laparoscopic radical prostatectomy as described by Vallancien and Guillonneau, we developed a pure extraperitoneal approach. This approach seems more comparable to the open technique and avoid potential risks of specific complications due to the transperitoneal approach. We evaluated the perioperative parameters (blood loss, operating time, transfusion rate) and postoperative results (oncological results, continence and potency) after our first 50 cases. MATERIAL AND METHOD: Between September 1999 and September 2000, we performed 50 laparoscopic radical prostatectomy. On average, patients were 63.3 years old (range 47-71), had preoperative mean PSA values of 9.14 ng/ml (1.1-23). Median Gleason score was 6 (4-10) with 2.5 (1-6) positive biopsies for a mean prostate volume of 40 cm(3) (17.5-95.0). Clinical stage was T1, T2a, T2b and T3 in 46.3, 41.5, 9.8 and 2.4% of the cases, respectively. We used a pure extraperitoneal approach and we performed a descending technique starting with the dissection at the bladder neck. The seminal vesicles dissection is comparable to the open approach. RESULTS: 42 extraperitoneal and 8 transperitoneal procedures were performed (2 in the initial experience, 3 because of previous abdominal surgery and 3 because of incidental peritoneal opening). Mean operative time was 317 min, mean blood loss 680 cm(3), transfusion rate of 13%. 1 patient/50 was converted to an open procedure. Pathological stage was pT1a, pT2a, pT2b, pT2c, pT3a and pT3b in 2.2, 8.5, 42.5, 2.2, 34 and 10.6% of cases, respectively. Positive surgical margins were observed in 22% of cases. The potency rate after neurovascular bilateral bundle preservation was 43% at 3 months (n = 7) and 67% at 6 months and (n = 6) without any further treatment. The continence rate (no pad) was 39% at 3 months and 85% at 6 months. Detectable postoperative PSA at 3 month was observed in 2 patients only. Two major complications occurred: one acute transient renal failure one uretrorectal fistula at day 20. CONCLUSIONS: The extraperitoneal laparoscopic radical prostatectomy results seem comparable to transperitoneal laparoscopic radical prostatectomy or open surgery. This approach is reproducible and seems to avoid the potential risks of intraperitoneal injury. Long-term follow up and comparative series are however necessary to further evaluate these new techniques.

[Can we prevent prostatic cancer: role of nutrition?]. / Peut-on prevenir le cancer de la prostate: role de la nutrition?

The present paper gives a comprehensive overview of recent data, especially prospective randomized trials, which support an important role for nutrition in the development of prostate cancer. Prostate cancer seems to be an ideal candidate for chemoprevention, in order to interfere by modification of nutritional habits with its onset, its incidence and ultimately with its progression, especially in high risk groups.

Pathological features of prostate cancer detected on initial and repeat prostate biopsy: results of the prospective European Prostate Cancer Detection study.

PURPOSE: We evaluated pathological features of prostate cancer detected on repeat prostate biopsy in men with a serum total prostate-specific antigen (PSA) level between 4 and 10 ng/ml who were diagnosed with benign prostatic tissue after an initial biopsy and compared them to those cancers detected on initial prostate biopsy. MATERIALS AND METHODS: In this prospective European prostate cancer detection study, 1,051 men with a total PSA level between 4 and 10 ng/ml underwent transrectal ultrasound (TRUS)-guided sextant biopsy and two additional transition zone biopsies. All subjects whose biopsy samples were negative for prostate cancer (CaP) underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either initial or repeat biopsy and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. RESULTS: Initial biopsy was positive (CaP) in 231 of 1,051 enrolled subjects and negative (benign histology) in 820 subjects. Of these 820 subjects, CaP was detected in 10% (83/820) upon repeat biopsy. Of cancers detected on initial and repeat biopsy, 148/231 (64%) and 56/83 (67.5%) had clinically localized disease, respectively, and were offered radical prostatectomy. 10/148 (6.7%) and 3/56 (5.3%), respectively, opted for radiation therapy and thus, 138/148 (93.3%) and 53/56 (94.7%), respectively, underwent radical retropubic prostatectomy. There were statistically significant differences with respect to multifocality (P = 0.009) and cancer location (P < 0.001) with cancers on repeat biopsy showing a lower rate of multifocality and a more apico-dorsal location. In contrast, there were no differences with respect to stage (P = 0.2), Gleason score (P = 0.36), percentage Gleason grade 4/5 (P = 0.1), serum PSA (P = 0.62), and patient age (P = 0.517). CONCLUSIONS: At least 10% of patients with negative prostatic biopsy results will be diagnosed with CaP on repeat biopsy. Despite differences in location and multifocality, pathological and biochemical features of cancers detected on initial and repeat biopsy are similar, suggesting similar biological behavior and thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy. Cancers missed on initial biopsy and subsequently detected on repeat biopsy are located in a more apico-dorsal location. Repeat biopsies should thus be directed to this rather spared area in order to improve cancer detection rates.

Long-term aspects of medical treatment of BPH.

Acute urinary retention (AUR) is an important complication of benign prostatic hyperplasia (BPH) and can affect 0.4-25% of men seen in urological practice each year. AUR is also one of the main indications for surgery, being the presenting features of 25-30% of transurethral resection of the prostate (TURP). However, TURP conducted under these conditions is associated with higher morbidity. A number of risk factors for AUR have been identified including severity of LUTS, reduced peak flow rate, prostate volume, post-void residual volume (PVR) and old age. Medical therapy for BPH can impact on prostate size, increased PVR and previous AUR episodes. Finasteride has been shown to reduce prostate size and consequently reduce the risk of AUR. Studies on the alpha(1) blocker, alfuzosin, also report a reduced incidence of AUR compared with placebo. In addition, alfuzosin has proven effective in a trial without catheter in patients with AUR, thus potentially reducing the need for prostate surgery or allowing elective surgery to be conducted without preoperative catheterisation. Both options are highly beneficial to the patient.

4-Year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer.

OBJECTIVES: To evaluate the long-term effects of 3-month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer. METHODS: We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only. RESULTS: 'Clinical downstaging' was seen in 30% of cases in the neoadjuvantly treated group (NEO). 'Pathological downstaging' occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41). CONCLUSIONS: In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings.