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.

Pathological changes in prostate lesions after androgen manipulation.

The number of newly diagnosed cases of prostate cancer has doubled in the past four years because of the aging of the population coupled with growing awareness of the importance of early detection. The issues of clinical understaging and resection limit positivity have led to the development of novel management practices, including neoadjuvant hormonal treatment, which aims to downstage the primary tumour and decrease the positive margin rate before definitive localised treatment (radical prostatectomy or definitive radiation treatment (neoadjuvant)). There is conflicting evidence regarding pathological downstaging, with some studies suggesting benefit and others no benefit of androgen manipulation before radical prostatectomy. The problem might be related to incomplete sampling of the prostates and difficulties associated with the pathological interpretation of morphological changes. The least controversial aspect of neoadjuvant treatment is its impact on surgical margins. Most series have shown that neoadjuvant treatment in clinical T2 tumours is associated with a 20-25% decrease in positive margins in radical prostatectomy specimens. In patients with clinical T3 tumours, the effects of neoadjuvant treatment on positive margins are less clear. Even if some early significant advantages can be observed following hormonal treatment this may not alter the metastatic spread and overall survival rate. Only long term follow up studies evaluating biological and clinical failures, time to progression, and survival will allow definitive conclusions from this approach.

Transurethral needle ablation of the prostate for treatment of benign prostatic hyperplasia: early clinical experience.

OBJECTIVES: Many attempts have been made to develop a method for treatment of benign prostatic hyperplasia (BPH) that is minimally invasive, efficacious, and low-cost. Transurethral needle ablation (TUNA) is a new, fast outpatient anesthesia-free procedure, using interstitial low-level radio frequency energy to produce a temperature above 100 degrees C. We describe our early clinical experience with TUNA as an outpatient procedure. METHODS: This technique was used in 20 patients with symptomatic BPH. All men were evaluated prior to treatment with flow rates, residual urine, International Prostate Symptom Score (IPSS), and quality of life. Follow-up occurred at 3 and 6 months after treatment, analyzing the same parameters. RESULTS: Tolerance using topical anesthetic and intravenous diazepam was excellent. Peak flow rate increased from a mean 9.5 +/- 3.3 mL/s to 14.7 +/- 6.3 mL/s (P < 0.05) at 3 months (19 patients) and to 15.0 +/- 4.9 mL/s (P < 0.05) at 6-month follow-up (12 patients). IPSS and quality of life improved from an average of 21.9 +/- 5.0 and 4.4 +/- 0.7 (P < 0.005) to 10.2 +/- 4.8 and 2.4 +/- 1.2 (P < 0.005), respectively, at 3-month follow-up. No significant complications were encountered. Retention was observed in 25% of the cases after the TUNA treatment. CONCLUSIONS: This initial study demonstrates the safety and effectiveness of TUNA. TUNA is a promising, anesthesia-free alternative treatment for men with symptomatic BPH. Long-term follow-up and randomized comparative studies with transurethral resection of the prostate (TURP) are planned to establish the place of this new alternative treatment of BPH in the urologist's armamentarium.

Study of human penile venous system and hypothesis on its behavior during erection.

To determine the role of the venous outflow restriction during human erection, we compared intracavernous pressure with deep dorsal vein pressure in 6 normal subjects during papaverine-induced erection and penile saline infusion. In addition, flows necessary to produce and maintain erection were measured in 10 cadavers before and after resection of the deep dorsal vein alone or together with ligation of the cavernous veins. Elongation of tunica albuginea was measured at the crural and mid portions of the penis. At rigidity there was complete blockage of the venous return through the emissary veins. The venous outflow through the cavernous veins was reduced but still persisted. The distention of the tunica albuginea was less important at the crural portion than at the distal portion and could explain why the cavernous veins were not blocked completely.

Systemic complication of intracavernous papaverine injection in patients with venous leakage.

Intracavernous papaverine injection is often used in the diagnosis and treatment of male impotence. Prolonged erection and/or priapism are well known local complications. Systemic side-effects characterized by discomfort and dizziness due to rapid escape of the drug into the vascular circulation also can occur in patients with venous leakage. Thus, venous leakage should be ruled out prior to intracavernous injection of papaverine in the treatment of impotence. Ligation of the deep dorsal vein and the small veins around the tunica albuginea will lessen the problem.

Modified corporoplasty for penile curvature: 10 years' experience.

OBJECTIVES: To treat penile curvature, a modification of corporoplasty consisting of horizontal closing of a longitudinal incision of the corpora cavernosa was performed during the last 10 years in 55 patients. METHODS: The technique was used in congenital (32 patients) as well as acquired penile curvature patients (23 with Peyronie's disease). RESULTS: Successful results, up to 10-year follow-up, were achieved in 95% of the patients without any injury to the neurovascular bundle. CONCLUSIONS: The simplicity of this technique and its minimal aggressivity have the advantage of not removing corporeal tissue and being very flexible and adaptable to individual situations.

Cabanas approach: is sentinel node biopsy reliable for staging penile carcinoma?

In 1977 Cabanas proposed biopsy of a sentinel node which is considered the primary site of metastasis from penile carcinoma. If this node is not invaded by tumor, no further surgical treatment is necessary. We report on 2 patients in whom results of bilateral sentinel lymph node biopsies were negative and in whom pelvic lymph node metastasis developed within one year.

Preliminary results of a prospective randomized study comparing radical prostatectomy versus radical prostatectomy associated with neoadjuvant hormonal combination therapy in T2-3 N0 M0 prostatic carcinoma. The European Study Group on Neoadjuvant Treatment of Prostate Cancer.

OBJECTIVES: To evaluate the short- and long-term effects of neoadjuvant hormonal treatment in locally confined prostate cancer. METHODS: We report the preliminary results of 354 patients (199 with a clinical T2 tumor and 155 with a clinical T3 tumor) of whom 164 randomly received neoadjuvant total androgen deprivation using a luteinizing-hormone-releasing hormone (LHRH) analog (goserelin) plus flutamide for a period of 3 months. RESULTS: Serum prostate-specific antigen (PSA) levels and prostatic volume decreased from a mean of 19.9 ng/mL and 37.7 cm3 to a mean of 0.8 ng/mL and 26.5 cm3 after 3 months of neoadjuvant therapy. "Clinical down-staging" was seen in 32% in the neoadjuvantly treated group. "Pathological downstaging" percentages were 6% and 16% in the direct radical prostatectomy group and neoadjuvantly-treated group, respectively (P < 0.01). In patients with clinical T2 tumors, a significant difference in number of positive margins was shown in favor of the neoadjuvantly treated group (P < 0.01). In patients with clinical T3 tumors, a significant difference could not be detected (P = 0.14). In 215 patients with a mean follow-up time of 15 months, the calculated 95% confidence intervals of mean time of PSA progression-free survival were 26 to 35 months in the neoadjuvantly-treated group and 28 to 37 months in the direct radical prostatectomy group, indicating no significant differences between treatment groups. However, follow-up time is currently too short to draw definite conclusions. CONCLUSIONS: These early data confirm high understaging percentages in clinical staging. The clinical relevance of the statistically significant smaller numbers of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor will have to be confirmed when further follow-up allows an accurate evaluation of time to PSA progression, local recurrence, and distant metastases. Presently, neoadjuvant therapy is not advisable outside clinical research settings.

Blind-ending bifid and double ureters.

Bifid and double blind ureters are two rare congenital anomalies of the upper urinary tract. Usually they are incidental findings. Occasionally, they are associated with urinary tract infection, but the symptoms are not specific. The key to diagnosis is a careful urethral cystoscopy and retrograde pyelogram. Asymptomatic patients without urinary tract infection require no treatment. When symptoms or infection are present, excision of the blind branch is required with antireflux reimplantation of the normal ureter if needed.

Is one single prostate biopsy helpful for choosing a medical treatment of benign prostatic hyperplasia? A quantitative computerized morphometric study.

OBJECTIVES: Individual differences in proportion of stroma, epithelium, and luminal space components prostatic hyperplasia (BPH) may explain the differences in clinical outcome of the patients treated with alpha-reductase inhibitors or alpha-blocking agents and other alternative treatments. Knowledge of the individual proportions of these elements may orient the clinician toward different therapeutic approaches. To determine whether a single prostate biopsy is representative of the whole adenoma, using quantitative morphometry, we have compared the percentage of smooth muscle cells and glandular cells in one prostate needle biopsy and in the corresponding prostate adenoma removed by open surgery. METHODS: Quantification was made using a computerized image analysis system and immunohistochemical staining (actin antiactin for the smooth muscle cells and anti-prostate-specific antigen (PSA) for the epithelial cells) in 14 patients who underwent retropubic prostatectomy. RESULTS: Mean percentage of smooth muscle fibers, glandular epithelium, and glandular lumina in the prostate biopsy were, respectively, 34% (range, 20% to 42%, SD 5.9), 29% (range, 13% to 42%, SD 7.2), and 20% (range, 13% to 30%, SD 4.8). In the corresponding prostate adenoma, they were, respectively, 38% (range, 28% to 45%, SD 4.7), 32% (range, 25% to 40%, SD 4.5), and 19% (range, 13% to 34%, SD 6.1). The mean percentages of epithelial or glandular cells in the prostate biopsy and the corresponding adenoma were not statistically different (P > 0.05), whereas those for the smooth muscle cell percentage were different (P = 0.02). However, a statistically significant correlation between the whole adenoma and the needle biopsy sample was found in the percentage of smooth muscle cells (P = 0.028). Analyzing the morphometric data in conjunction with the serum PSA level and the volume of the adenoma, we found a statistically significant positive correlation between the volume of the adenoma and the ratio (percentage of epithelial cells/serum PSA level) (P = 0.009, r = 0.67). CONCLUSIONS: Major differences are found in the primary tissue composition of different hyperplastic prostates. Computerized histologic quantification of the different components of BPH in the entire adenoma and a needle biopsy demonstrate that a single prostate biopsy is representative of the entire prostate adenoma. Morphometric data from a single biopsy of the prostate adenoma in combination with the serum PSA level and the volume of the prostate adenoma could therefore help to orient medical treatment of BPH by patient selection based on the knowledge of the distribution of the various components of BPH.

Prostate capsule: computerized morphometric analysis of its components.

OBJECTIVES: There is little objective information on what is designated as being the prostate capsule. We have quantified objectively with computerized image analysis the percentage of smooth muscle fibers (SMFs) surrounding the surgical specimens of radical prostatectomies. METHODS: Ten radical prostatectomy specimens were used. Six different parts from prostate lobe were analyzed. Thirty different fields were examined from each tissue section. For tissue sections, different stains were used: hematoxylin and eosin, Masson's trichrome, and immunohistochemical staining with antiactin for SMFs. RESULTS: The mean thickness of the prostate capsule was 0.5 to 2 mm. The mean percentages of SMFs in the different regions of the prostate capsule was 30.6%. No difference was noted between the percentage of SMFs in the prostatic capsule compared with that in the prostate parenchyma itself (30.7%). CONCLUSIONS: This study provides objective evidence to demonstrate that the prostate does not have a true capsule. This capsule represents a fibromuscular band that probably should be considered as the extension of the internal parenchyma.

Finasteride significantly reduces acute urinary retention and need for surgery in patients with symptomatic benign prostatic hyperplasia.

OBJECTIVES: A pooled analysis of all available randomized trials with 2-year follow-up data with finasteride and placebo was undertaken to further investigate recent observations that finasteride use may reduce the occurrence of acute urinary retention (AUR) and benign prostatic hyperplasia (BPH)-related surgical intervention. METHODS: Occurrences of AUR and surgical intervention were examined by treatment group in a pooled series of 4222 men with moderately symptomatic BPH. RESULTS: In total, 81 occurrences of AUR were reported, 24 (1.1%) of 2113 in the finasteride group and 57 (2.7%) of 2109 in the placebo group. The hazard ratio was consistent in all three studies, with a 57% decrease in the hazard rate for occurrence of AUR with finasteride compared with that for placebo present in the pooled data set over the 2-year study period (P < 0.001). Additionally, 227 surgical interventions were recorded over the 2-year study period, 89 (4.2%) of 2113 in the finasteride group and 138 (6.5%) of 2109 in the placebo group. The hazard ratio was consistent across the three studies, with a 34% reduction in the hazard rate for occurrence of surgery with finasteride compared with that for placebo (P < 0.002). Overall, there was 35% reduction in the two BPH-related end points (ie, AUR or surgery). CONCLUSIONS: Treatment with finasteride for up to 2 years more than halves the frequency of AUR and reduces surgical intervention by over one third relative to placebo in patients with moderate BPH. This is the first demonstration that long-term medical therapy can reduce clinically significant end points such as AUR or surgery, and these data have important implications for the long-term management of patients with BPH.

Transitional cell carcinoma of the bladder: evaluation of the role of human papillomaviruses.

OBJECTIVES: The study evaluated the conflicting results of the role of human papillomavirus (HPV) in the development of bladder carcinoma. METHODS: We analyzed the frequency of HPV types 6, 11, 16, 18, and 33 by using polymerase chain reaction on formalin-fixed, paraffin-embedded specimens, from 75 cases of transitional cell carcinoma (TCC) of the bladder. Fifteen samples of normal urothelium adjacent to TCC (10) or from normal bladder obtained at autopsy (5) served as negative controls. RESULTS: HPV type 16 deoxyribonucleic acid (DNA) was detected in 2 (2.7%) of the 75 cases of TCC and in none of the normal urinary bladder cases. The 2 patients with HPV type 16 were immunosuppressed after undergoing renal and cardiac transplantation. CONCLUSIONS: These results strongly suggest that HPVs play a minor role in the development of TCC of the bladder in the general population, although they can act as oncogenic agents in predisposed patients, such as those who are immunosuppressed.

Transperineal radiofrequency interstitial tumor ablation of the prostate: correlation of magnetic resonance imaging with histopathologic examination.

OBJECTIVES: Radiofrequency (RF) energy has recently been employed to destroy human tissue in vivo. The purpose of this study was to investigate the safety of this approach in localized carcinoma of the prostate (CaP) and specifically, the predictability of lesions obtained with radiofrequency interstitial tumor ablation (RITA). METHODS: Using RITA, a total of 21 lesions were induced in 10 patients with localized CaP (mean age 70.4 years). RF was delivered transperineally under transrectal ultrasound (TRUS) guidance. All patients underwent endorectal magnetic resonance imaging (MRI) before and after treatment. Radical prostatectomy was performed in all patients 1 to 7 days after RITA. Three of the patients were treated with local anesthesia only. The predictability of the thermal lesion was assessed by correlating the findings of intraoperative TRUS, pre- and post-RITA endorectal MRI, and the histologic examination of the specimen. RESULTS: Postoperatively, patients were catheterized for an average of 1.8 days (1 to 3 days). Lesions of 2 x 2 x 2 cm were targeted. Average lesion diameters obtained on MRI were 2.08 +/- 0.23 x 2.09 +/- 0.36 x 2.28 +/- 0.21 cm. Average lesion diameters defined by coagulative necrosis at histologic examination were 2.20 +/- 0.23 x 2.10 +/- 0.31 x 2.38 +/- 0.14 cm. There were no statistically significant differences (P = 0.377) between average lesion volume on MRI (5.37 +/- 1.83 cm3) and average lesion volume at histology (5.86 +/- 1.63 cm3). No complications or adverse events were noted. CONCLUSIONS: In this Phase I study, RITA was shown to be safe and feasible, and to result in lesions that were predictable in size and location. MRI accurately visualized and verified the area of coagulative necrosis as documented at histology. The procedure is technically simple and can even be performed under local anesthesia.

Early adjuvant adriamycin in superficial bladder carcinoma.

A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.

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.

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.

Biological markers in superficial bladder tumors and their prognostic significance.

This article reviews the literature on some of the available biomarkers such as p53 and its down-stream effector p21 on superficial bladder tumor biology and their prognostic significance. The role of p53 tumor suppressor gene is controversial in superficial bladder cancer, possibly because analyzing one single effector of a pathway might hide the role of downstream effectors. The aggressiveness of this condition is related to proliferative activity as measured by Ki-67. Further studies are still necessary to draw definitive conclusions about the role of these different biological markers in superficial bladder cancer.

Difference in glycohistochemical lectin staining of collagen fibers in the corpora cavernosa of normal and impotent men.

The objectives of this study were to investigate the value of glycohistochemical staining with three lectin types specific to a particular glycan structure (Arachis hypogaea [PNA], Triticum vulgare [WGA], and concanavalin A [Con A]) as a method of defining possible changes in the collagen structure in the corpora cavernosa in potent and impotent men. The study group consisted of 4 normal potent men and 22 men with various etiologies of impotence. The quantitative histochemical measurements were performed by means of a cell image processor. Two variables for each of the three types of lectins were studied. These were the mean optical density (MOD), which relates to glycohistochemical staining intensity, and the labeling index (LI), which is positively related to the percentage of immunostaining. Only WGA staining made it possible to discriminate significantly between the normal and pathological groups under study. The two parameters (LI, MOD) were significantly higher in the case of WGA staining in the normal group (P = 0.004 and 0.013, respectively). In contrast, only the mean LI value, in the case of the psychogenic and venogenic patients, reached a level of statistical significance (P = 0.005 and 0.001, respectively), when it increased from PNA through WGA to Con A histochemical staining. The two variables (LI, MOD) changed markedly from PNA through WGA to Con A in the arteriogenic patients (P = 0.003 and P < 0.001, respectively). WGA is of diagnostic value in distinguishing between normal and abnormal collagen in the corpora cavernosa. The difference in the lectin staining of the other groups, particularly the arteriogenic group, may be attributed to alterations in the glycosylation of the procollagen that are probably due to changes in the partial pressure of oxygen (PO2) level, an important cofactor in normal glycosylation. WGA staining may therefore be used as a marker to distinguish true psychogenic patients from those with organic diseases. Moreover, it may be used as an additional parameter in selecting the best candidates for penile revascularization.

Can careful ultrasound examination of the urinary tract exclude vesicoureteric reflux in the neonate?

The aim of the study was to determine whether a urinary tract appearing normal when assessed by meticulous ultrasound (US) examination may coexist with vesicoureteric reflux (VUR) and whether a normal US scan can be used to exclude VUR, thereby avoiding unnecessary voiding cystourethrography (VCUG). The US features of 35 neonates with known VUR were reviewed. Criteria studied included pelvic dilatation above 7 mm on a transverse scan, calyceal or ureteral dilatation, pelvic or ureteral wall thickening, absence of the corticomedullary differentiation (CMD) and signs of renal dysplasia (small kidney, thinned or hyperechoic cortex and cortical cysts); all signs that have been shown to result from or to be associated with VUR. 57 refluxing renal units (RRU) were found among the 35 patients. VUR was bilateral in 22. Among the 57 RRU, at least one US anomaly that would have prompted VCUG was present in 50 (87.7%). Pelvic dilatation above 7 mm was present in 29 RRU (50.9%) only. Calyceal dilatation was present in 24 RRU, the dilatation involving the calyces but not the renal pelvis in seven. Ureteral dilatation was observed in 15 RRU. Pelvic or ureteral wall thickening was present in seven RRU. CMD was absent in 32 RRU (56.1%). US signs of dysplasia were found in 19 RRU. No US anomaly was found in seven RRU (12.3%) in six patients. A careful and meticulous US examination of the neonatal urinary tract allows the detection of over 87% of RRU by showing at least one sonographic abnormality. It is concluded that a normal appearing urinary tract on US does not usually coexist with VUR and that in such cases VCUG is not necessary.