The angiogenic switch for vascular endothelial growth factor-A and cyclooxygenase-2 in prostate carcinoma: correlation with microvessel density, androgen receptor content and Gleason grade.

OBJECTIVE: Angiogenesis is essential for tumor growth and metastasis; however, angiogenic factors are not uniformly expressed in prostate carcinoma. Our aim was to determine the expression of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) in prostate carcinomas in relation to intratumoral microvessel density (MVD), tumor grade and androgen receptor (AR) status. MATERIALS AND METHODS: The expression of AR, VEGF-A and COX-2 was immunohistochemically evaluated in 24 benign prostatic hyperplasia (BPH) and 139 prostate carcinoma cases. MVD was evaluated by CD34 immunostaining. RESULTS: Nuclear AR expression was inversely related to tumor grade (p < 0.001). MVD was strongly related to tumor grade, VEGF-A and COX-2 (p < 0.001 in all comparisons). VEGF-A expression increased with tumor grade (p < 0.01) and was inversely related to stromal AR expression. COX-2 was present in both BPH and prostate carcinoma, but its expression increased with tumor grade (p < 0.01). High-grade neoplasms presented low-to-moderate VEGF staining intensity compared to strong COX-2 expression. CONCLUSIONS: Both VEGF-A and COX-2 expression is positively correlated with tumor grade and MVD. However, in Gleason 8-10 tumors, VEGF expression is moderate while COX-2 immunostaining is intense, suggesting a possible switch in the role of these two angiogenic factors in poorly differentiated neoplasms.

Effect of alfuzosin on female primary bladder neck obstruction.

Our objective was to assess the effect of the selective alpha(1)-blocker alfuzosin on urodynamic parameters and quality of life in female patients with primary bladder neck obstruction (PBNO). Twenty-five women identified as having PBNO were included in the study. After the initial assessment of urodynamic parameters and bother score index, all patients were treated with alfuzosin 5 mg twice daily for 8 weeks. After this period of time, the patients were reassessed with the same methodology as pretreatment. Symptoms subjectively improved, and patients' satisfaction significantly increased in 64% of the patients (16 out of 25). Most urodynamic parameters were also significantly improved after treatment with alfuzosin. Alfuzosin significantly improved urodynamic parameters and alleviated bother score in almost two thirds of patients with PBNO and can be an effective first-line treatment of this situation.

Long-term treatment with intracavernosal injections in diabetic men with erectile dysfunction.

AIM: To assess the behavior of patients with diabetes mellitus (DM) and erectile dysfunction (ED) during 10 consecutive years of treatment with self-injection of vasoactive drugs. METHODS: Thirty-eight diabetic men, including 12 with type I and 26 with type II diabetes, were followed up regularly for 10 years after they began self-injecting for severe ED. Real time rigidity assessment was used for the objective determination of the initial dosage and then doses were regulated in order to introduce an erection suitable for penetration and maintenance of erection for approximately 30 min. Patients were followed up every two months, and doses were increased only when the treatment response was not satisfactory. RESULTS: The number of injections used per year by the patients was reduced each year (mean numbers: 50 in the first year and 22.5 in the 10th) and treatment shifted towards stronger therapeutic modalities (mixtures of vasoactive drugs instead of prostaglandin E1 alone). Type I diabetic men were standardized to a level of treatment as early as 5 years after the initiation of treatment. That level was finally reached by type II patients after another 4-5 years. CONCLUSION: Treatment with self-injections of vasoactive drugs in diabetic men with severe ED is a safe and effective alternative in the long term. Diabetic men of both types show the same preferences in quality and quantity of treatment after 10 years. The key point for maintenance in treatment is the adjustment of the therapeutic method and dosage to optimal levels for satisfactory erections.

The relationship between the perineal length measurements and the urodynamic stress incontinence.

OBJECTIVE: The purpose of this study was to assess the relationship between the length of perineal body, the anal position index, the total fourchette-coccyx distance and the anal-coccyx length and female urodynamic stress urinary incontinence (USUI). PATIENTS AND METHODS: The study included 57 women with USUI (group A) and 45 women without USUI as control (group B). All patients underwent a urodynamic evaluation and measurement of the length of perineal body (PB) and the distance between the fourchette and the inferior margin of coccyx (FC). PB is the distance between the fourchette and the center of anal orifice. The ratio PB/FC is the anal position index. Subtracting the PB length from FC distance equals the anal-coccyx (AC) length. RESULTS: The student's t-test showed no significant statistical difference between any of the measured lengths in the two groups. Moreover, in the USUI group, ANOVA did not show any significant relationship between the urodynamic parameters and the measured lengths. Regarding to the investigated urodynamic parameters only the maximum urethral pressure (Pura max) presented a significant statistical difference between the two groups (P = 0.009). CONCLUSION: Theoretically, a differentiation of perineal distances probably brings to the surface a laxity of the pelvic floor, a factor predisposing to USUI. Furthermore, the anterior position of anus can be a cause of constipation which also contributes to USUI. However, our study did not reveal any relationship between the perineal length measurements and USUI. Further investigation with longer series of patients is needed to show if this simple, inexpensive and non-invasive test could be added in the armamentarium of the diagnostic and prognostic investigation of USUI. Regarding to the urodynamic parameters, our results emphasize the importance of the Pura max parameter in the urodynamic evaluation of USUI.

Comparison of the efficacy of tolterodine and oxybutynin in different urodynamic severity grades of idiopathic detrusor overactivity.

OBJECTIVE: To compare the efficacy of tolterodine and oxybutynin in the treatment of specific, according to their urodynamic grade of severity, populations with overactive detrusor. METHODS: In this open, randomized, two-way crossover study 128 women with urodynamically confirmed, idiopathic detrusor overactivity were recruited. Patients were categorized in 4 grades of severity groups, according to the characteristics of the first overactive detrusor contraction during filling cystometrogram: high volume-low pressure (grade-group I), high volume-high pressure (grade-group II), low volume-low pressure (grade-group III) and low volume-high pressure (grade-group IV). The primary outcome measure was average volume of voided urine per micturition. RESULTS: 107 patients successfully completed the study protocol and were included in the analyses: 40 in group IV, 36 in III, 25 in II and 6 in group I. In groups IV and III both oxybutynin and tolterodine significantly increased the average volume of voided urine per micturition but the differences between the drugs were not significant (p > 0.05). In group II neither of the drugs achieved significant changes in the outcome measure (p > 0.05). CONCLUSIONS: Tolterodine and oxybutynin are clinically equipotent in treating detrusor overactivity in specific severity groups of patients, although urodynamic effects are somewhat different.

Vardenafil (Levitra) for erectile dysfunction: a systematic review and meta-analysis of clinical trial reports.

Trials of the efficacy and safety of vardenafil in the treatment of male erectile dysfunction (ED) were meta-analysed. All available databases were searched (January 1, 2001-November 30, 2003). Trials were eligible if they included men with ED, compared vardenafil with placebo, were randomized, were at least of 12 weeks duration, and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion. Nine trials (6809 men) met the inclusion criteria. In results pooled from seven fixed-dose trials, vardenafil increases the Erectile Function domain of the International Index of Erectile Function questionnaire by 6.18 units (weighted mean difference (WMD)). Vardenafil also increases the percentage of erections firm enough to allow vaginal penetration (WMD: 26) and the percentage of sexual attempts that were successful per participant (WMD: 29.8). The percentage of men agreeing with the statement that 'the treatment they have been taking over the past 4 weeks improved their erections', is also in favour of vardenafil (relative risk (RR): 3). These efficacy variables appeared greater at higher doses, although there are no significant differences between 10 and 20 mg dose. The same results were extracted for the two flexible 'as needed' dosing trials. Discontinuations are greater at the vardenafil groups compared to placebo (RR: 2.25). Specific adverse events with vardenafil included flushing, dyspepsia, headache, and rhinitis. Vardenafil was not significantly associated with serious cardiovascular events or death. Vardenafil, in all treatment regimens, shows to possess superior efficacy to placebo in the treatment of patients with erectile dysfunction. More data is needed on patients' subgroups.

Efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction. A comparative crossover study.

To compare the efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction (ED), 40 men were studied. Post-injection penile peak systolic velocity was greater than 25 cm s(-1). Twenty men started on apomorphine 2 mg and 20 on sildenafil 50 mg, the doses titrated up to 3 and 100 mg, respectively, if necessary. After a 1-week washout period each group switched to the other treatment mode. Efficacy was the percentage of attempts resulting in erections firm enough for intercourse, based on an event log data. The majority (85%) of the men had concomitant diseases, risk factors for ED and 95% were heavy smokers. The overall success rate of apomorphine was 62.7%, compared with 73.1% of sildenafil (Yates-corrected chi-square, P < 0.0004). The response to apomorphine 2 mg and sildenafil 50 mg was age related. Sildenafil was statistically more effective than apomorphine in impotent men with normal penile Doppler. Given the contraindication of sildenafil in men taking nitrates and the quick time of action of apomorphine, the two drugs are satisfactory first line therapeutic tools in such individuals and the choice should be based on patient's needs and preferences.

Erectile dysfunction in men with obstructive sleep apnea syndrome: a randomized study of the efficacy of sildenafil and continuous positive airway pressure.

The aim of this study was to compare the efficacy of sildenafil and continuous positive airway pressure (CPAP) in men with erectile dysfunction (ED) and obstructive sleep apnea syndrome (OSAS). In all, 30 men were randomly treated for 12 weeks either with sildenafil 100 mg before intercourse (15 men) or CPAP during night time sleep (15 men). Under sildenafil, 97/180 (53.9%) of attempted intercourses were successful compared to 33/138 (23.9%) under CPAP. The mean IIEF (erectile function domain score) was 12.9 and 9.3 after sildenafil and CPAP treatment, respectively (P=0.007), compared to 7.9 and 7 at baseline. In all, 53.3% of patients were satisfied with sildenafil and 20% with CPAP for ED treatment (P=0.058). Although sildenafil was superior to CPAP, comorbidities and OSAS per se possibly resulted in a lower effectiveness of sildenafil compared to that in the general population of ED men. While about half of the patients were not satisfied even with the more effective treatment, we conclude that a combination of the two therapeutic tools or a different therapeutic mode should be studied further.

A comparative, crossover study of the efficacy and safety of sildenafil and apomorphine in men with evidence of arteriogenic erectile dysfunction.

The aim of the study was to establish and compare the efficacy and safety of sildenafil and apomorphine in men with arteriogenic erectile dysfunction (ED). In all, 43 men with ED and postinjection max penile systolic velocity <25 cm/s in repeated Doppler ultrasonography were included. Of these, 24 men started on apomorphine 2 mg and 19 on sildenafil 50 mg, the doses titrated up to 3 and 100 mg according to effectiveness and tolerability. Safety was evaluated according to adverse events (AEs) and patient withdrawal. Efficacy was the percentage of attempts resulting in erections firm enough for intercourse, based on event log data. The incidence of AEs with apomorphine 3 mg was higher than with sildenafil 100 mg. Two men on apomorphine 3 mg discontinued treatment due to AEs. The overall success rate of sildenafil was 63.7% compared to 32.1% of apomorphine (Pearson chi(2), P<0.01). Of all men, 25 (58.1%) responded to sildenafil 50 mg without the need for dose increase, while only one responded to apomorphine 2 mg. The response to sildenafil 50 mg was age related (analysis of variance, p=0.04). Satisfaction was reported by 76.75 and 13.95% of patients for sildenafil and apomorphine, respectively, but 20.9% were not satisfied with any of the two drugs. In conclusion, this study provides clear evidence that sildenafil, even at 50 mg dose, is more effective than apomorphine 3 mg in men with arteriogenic ED. The fact that one out of five patients is not satisfied with the above-studied drugs shows that new oral agents need to be evaluated for the treatment of this disorder.

Long-term results of transvaginal colposuspension for the treatment of genuine stress incontinence combined with vaginal hysterectomy.

We assessed the long-term efficacy of a modified transvaginal needle bladder neck suspension, combined with vaginal hysterectomy, for the treatment of female stress incontinence. Thirty-two women who underwent this procedure were followed up clinically and urodynamically 1 and 5 years postoperatively. A total of 27 women (84.4%) were cured 1 year postoperatively. Of the 29 women who were followed up 5 years postoperatively, 21 (72.4%) had a satisfactory result (p = 0.157). No significant differences were observed in maximum urine flow rate, residual volume of urine, and functional length of the urethra. On the contrary, the maximum urethral closure pressure was significantly decreased (p = 0.004). Although the results of our study show a decline in success rate by time, the overall long-term efficacy of this technique is undoubtedly satisfactory. This technique is promising as an easy and minimally invasive surgical procedure for bladder neck suspension.

Combination treatment with an alpha-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized, controlled study.

PURPOSE: We evaluate the effect of tolterodine combined with tamsulosin on quality of life in patients with bladder outlet obstruction and concomitant detrusor instability. MATERIALS AND METHODS: The study included 50 consecutive patients with urodynamically proven mild or moderate bladder outlet obstruction and concomitant detrusor instability. All patients were initially treated with 0.4 mg. tamsulosin orally once a day. A week later the patients were randomly allocated into group 1-25 who continued treatment with tamsulosin only and, group 2-25 who also received 2 mg. tolterodine orally twice daily. Reevaluation with a quality of life questionnaire and urodynamic study was performed after 3 months. RESULTS: Two patients from group 2 stopped tolterodine while 1 patient from each group stopped tamsulosin because of hypotension. Analysis revealed statistically significant improvement in quality of life scores only in group 2 patients (mean score 525.0 and 628.4 before and after treatment, respectively, 2-sided t test p = 0.0003). A significant difference was noted in both groups after treatment for maximum flow rate and volume at first contraction. Additionally, in group 2, a statistically significant difference was observed for maximum detrusor pressure and maximum unstable contraction pressure after treatment. CONCLUSIONS: Combination treatment with an alpha-blocker (tamsulosin) plus an anticholinergic (tolterodine) improves quality of life in patients with bladder outlet obstruction and concomitant detrusor instability. Interestingly, no acute urinary retention was observed and tolterodine did not affect the quality of urine flow or residual urine volume. The proposed combination appears to be an effective and relatively safe treatment option in patients with bladder outlet obstruction and detrusor instability.

Pseudomalignant spindle cell proliferation of the urinary bladder: an unusual cause of voiding symptoms in a young patient.

A case of an unusually large pseudomalignant spindle-cell proliferation (or inflammatory pseudotumor) of the urinary bladder in a young man is presented. The only symptom was urinary frequency. The clinical and radiologic evaluation (ultrasonography, computed tomography, and magnetic resonance imaging) revealed a massive tumor (11 x 7.5 x 5.5 cm) arising from the bladder wall that was eventually resected without compromising bladder function. Although the histologic findings initially suggested a sarcoma, the immunohistochemical findings were consistent with that of an inflammatory pseudotumor. The patient remained asymptomatic, without evidence of recurrence, after 12 months of follow-up. Awareness of this inflammatory pseudotumor and its immunophenotypic characteristics is important to avoid an erroneous diagnosis and unnecessarily aggressive therapy.

Switching from long-term treatment with self-injections to oral sildenafil in diabetic patients with severe erectile dysfunction.

OBJECTIVE: To assess the efficacy of oral sildenafil in diabetic men with severe erectile dysfunction (ED), who are successfully treated with intracavernous injections of vasoactive drugs. METHODS: 81 impotent diabetic men (29 with type 1 and 52 with type 2) were treated for 1-7 years with self-injections. 13 men were treated with 10 microg and 15 with 20 microg of prostaglandin E1 (PGE1), and 53 with a mixture of PGE1 20 microg and papaverine 7.5-40 mg (MIX). After a 1-week washout period, they changed to oral sildenafil in titrating doses up to 100mg. The change was successful if the man achieved an erection and penetration even once. RESULTS: Sildenafil was discontinued in 23 men because of insufficiency. Eleven men (13.6%), all with type 2 diabetes, responded to sildenafil (10 previously treated with 10 microg and 1 with 20 microg of PGE1, none treated with MIX). Thus, 39.2% of the treated with PGE1 responded to oral sildenafil. The response was influenced by the age, the type of diabetes (type 2) and the kind of the previously injected drug (PGE1 10 microg); it was not influenced by the duration of diabetes, ED and treatment with self-injections. CONCLUSIONS: Despite the well documented efficacy of sildenafil, self-injections continue to be the solely effective therapeutic modality in many diabetic men afflicted by severe ED. Only the younger men with non-insulin-dependent diabetes, treated with low doses of PGE1 are more likely to respond to oral sildenafil and change treatment. Men with insulin-dependent diabetes or treated with mixtures of vasoactive drugs are not likely to respond to oral sildenafil.

Diabetic impotence treated by intracavernosal injections: high treatment compliance and increasing dosage of vaso-active drugs.

AIMS: To compare patient compliance with treatment and the dosages of vaso-active drugs used, for the management of impotence in diabetic and non-diabetic patients. METHODS: Eighteen diabetic and a control group of 22 non-diabetic men were followed up regularly for 7 years after they had begun self-injections for severe erectile dysfunction. Rigiscan was used for the objective determination of the initial dosage and then doses were regulated in order to introduce an erection suitable for penetration and maintenance of erection for 30 min. RESULTS: Sixteen of 18 diabetic men are still using self-injections successfully after 7 years while of the 22 non-diabetic men, only 7 still continue injections. Compliance of diabetic men with treatment is significantly higher compared to the control group (p = 0.001). Doses of prostaglandin E(1) (PGE(1)) or mixtures of PGE(1) and papaverine (PAP) had to be increased over time. Although self-injections were a safe kind of treatment and no major complications were observed in both groups, a decrease in the frequency of injections was observed, particularly in the diabetic group, but this was not statistically significant (p = 0.15). CONCLUSIONS: Diabetic patients with severe erectile dysfunction have much higher compliance with self-injections than the non-diabetic patients. They respond initially to reasonable doses of PGE(1) but over time need increasing doses of PGE(1) or mixtures of PGE(1) and PAP. Frequent follow-up visits and the adjustment of dosage to continue the success of therapy may prevent patient dissatisfaction and drop-out from treatment. Patients treated with self-injections decrease the frequency of injections over time. They are satisfied with less frequent but successful intercourse and have a low risk of side-effects.

Excessive verumontanum hyperplasia causing infertility.

Retrograde ejaculation is an uncommon cause of infertility in otherwise healthy men. We hereby report a previously undescribed verumontanum hyperplasia as a cause of retrograde ejaculation in a 32-year-old male that was successfully treated by transurethral resection.

Effect of subinguinal varicocelectomy on sperm parameters and pregnancy rate: a two-group study.

OBJECTIVE: To evaluate the changes in semen parameters and pregnancy rates after varicocelectomy. METHODS: We evaluated the results of surgery in 146 men with primary infertility and palpable left varicoceles, compared with 62 men who refused surgery and were treated with tamoxiphene. Patients were selected with strict criteria in order to exclude any other infertility factor in the couple. They were followed up for at least 1 year after treatment. Statistical analyses were performed with the Wilcoxon signed rank test, Kolmogov-Smirnof two-sample test and paired samples t test. RESULTS: After 1 year, the differences in the median values were significant for all parameters. The partners of 62 of the operated men (46.6%) and 8 of the nonoperated (12.9%) became pregnant within 1 year (p<0.001). Thus, the difference between the true 1-year pregnancy rates was 33.7%. Overall, 83.2% of the operated men improved their semen parameters compared to 32.3% of the nonoperated. CONCLUSIONS: Varicocelectomy improves all semen parameters and pregnancy rates significantly. Palpable varicoceles should be operated upon when found in infertile couples.

Primary echinococcal disease of the kidney: the case for a more conservative approach.

PURPOSE: To evaluate conservative management of renal echinococcosis in cases with normal renal function and active disease. PATIENTS AND METHODS: From a series of 12 consecutive patients with primary renal echinococcosis, nephrectomy was suggested to 4 patients because of kidney destruction. One patient who denied surgery and 5, in whom serological tests were positive, were given mebendazole for 30 days. 3 patients with no evidence of active disease were not given any medication. RESULTS: The patient who denied nephrectomy and 1 out of 5 with positive serological tests did not respond to mebendazole treatment. The latter underwent a cyst excision. Thus, 4 responders to mebendazole and 3 who were not given any medication, avoided surgery and continue to have negative serological tests for more than 3 years. CONCLUSION: Conservative management and long term follow up are proposed for the non-active or mebendazole-responsive patients. For the non-respondents or the cases with kidney destruction, surgery is the only hope for cure.

Peyronie's disease: epidemiology and clinical presentation of 134 cases.

OBJECTIVE: To investigate epidemiological and clinical features of Peyronie's disease in an unselected group of patients not seen by a urologist before. PATIENTS AND METHODS: A series of 134 consecutive cases with Peyronie's disease was evaluated regarding to the age at diagnosis, the symptoms and signs of the disease, and the site and formation of the scar. The medical history which could be possibly related with the onset of the disease was investigated as well. RESULTS: The disease mainly affected middle-aged men. While all men had a palpable scar, only 51 (38%) had noticed the induration. Curvature (mean: 35 degrees) appeared in 87 men (65%) and caused sexual dysfunction due to severe penile deformity in 16 men (11.9%). 53 patients (39.5%) referred painful erections. In 11 men (8.2%) the onset of the disease was noticed after auto-injections of vaso-active drugs for the treatment of previous erectile dysfunction, while 18 (13.4%) had a history of penile trauma during sexual intercourse or manipulation. No specific relation with diabetes mellitus and Duputren's contracture was identified. Scars, like elongated indurations with vague bounds, were mainly formed (77.6%) in the dorsal midline. CONCLUSIONS: The mean age of patients at diagnosis, the site of penile scars, and the activities of the affected men could advocate the hypothesis that trauma is the main causal factor for Peyronie's disease. In 21.6% of the patients, the lesion occurred after a traumatic activity. Sexual dysfunction due to severe penile curvature affected a small proportion of the patients. Thus, due to the diminution of pain spontaneously or after treatment, the patients with Peyronie's disease may have a normal life with satisfactory sexual function. In some selected cases surgery offers an effective result.

Sildenafil test: changes in the diagnostic and therapeutic management of erectile dysfunction.

OBJECTIVE: To assess the efficacy of sildenafil as a first-step diagnostic and therapeutic tool for erectile dysfunction (ED) and to evaluate the consequent changes in the management of male sexual insufficiency. MATERIALS AND METHODS: Sildenafil in titrating doses up to 100 mg was prescribed to 50 men presenting to a sexual dysfunction clinic with medically documented ED. They had not undergone any specific diagnostic test before starting sildenafil. RESULTS: Of the 50 men, 24 (48%) responded to sildenafil. Of these, 8 (33.3%) responded to 50 mg and 16 (66.7%) to 100 mg of sildenafil. Of the responders, 9 representing 18% of all studied men were discharged achieving spontaneous erections in a mean follow-up of 5.3 months. Men with no medical history, men with hypertension and men with mild coronary artery disease responded better. CONCLUSIONS: The sildenafil test revealed that 48% of men responded to this therapy with no requirement for more invasive tests and that 18% of men required no further treatment at all. In addition this test reduced the overall cost of the diagnostic investigation. It is proposed that the sildenafil test should be used in cases with no significant medical history or in men with hypertension or mild coronary artery disease although almost all men with ED could be categorized as sildenafil-responders or sildenafil-resistant. It is also suggested that the sildenafil test would result in the ability for more men with ED to be managed exclusively in the primary care sector.

Pheochromocytoma of the urinary bladder presenting only with macroscopic hematuria.

Pheochromocytoma of the bladder is an unusual tumor that typically presents with hypertensive crises related to micturition. We describe a case of bladder pheochromocytoma in a 42-year-old female in which macroscopic hematuria was the only alarming symptom. The diagnostic and operative issues of this type of tumor are discussed, along with the challenging treatment option of transurethral resection. Diagnosis, treatment and follow-up trends of this rare tumor are reviewed.