K. Gyftopoulos

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.

Retrocaval ureter and associated abnormalities

Objective. To investigate the association of retrocaval ureter with other congenital abnormalities.Methods and patients. Two new cases of retrocaval ureter are discussed and a detailed electronic search of the literature was mainly focused on the concomitant abnormalities. The first of our patients had also a glandular hypospadias and a supernumerary lumbar vertebra, while the second one had syndactylia (fixed toes) in both feet.Results. The review of the literature revealed that 21% of the cases of retrocaval ureter present with concomitant abnormalities mainly from the cardiovascular system and the genitourinary tract.Conclusion. Diagnosis of retrocaval ureter should increase the awareness of the responsible physician on the possibility of concomitant malformations where treatment could prevent future symptoms.

Effects of finasteride and cyproterone acetate on hematuria associated with benign prostatic hyperplasia: a prospective, randomized, controlled study

OBJECTIVES To evaluate the influence of two differently acting antiandrogens, finasteride (FIN) and cyproterone acetate (CPA), on the natural history of hematuria associated with benign prostatic hyperplasia (BPH) in a prospective, randomized, controlled study. METHODS Forty-two patients with hematuria episodes due to BPH were randomly allocated to three subgroups of 14 patients each and treated daily with either 5 mg FIN or 100 mg CPA or were placed in a watchful waiting arm. Patients were evaluated at 3-month intervals, and 40 patients had at least 1 year of follow-up. RESULTS Four patients in the FIN group (30%) and three in the CPA group (23%) presented with recurrent hematuria. In both groups, the bleeding episodes were treated conservatively and required no hospitalization. In the control group, 8 patients (57%) presented with recurrent bleeding; in 4, the bleeding was severe and required some form of intervention (catheterization or transurethral prostatectomy). When the frequency and severity of the hematuria episodes were analyzed over time, a statistically significant difference for FIN versus control was present at 9 and 12 months (analysis of variance, P = 0.035 and P = 0.009, respectively). A similar difference was evident for CPA versus control at 9 and 12 months (P = 0.028 and P = 0.008, respectively). No statistically significant difference was present between the FIN and CPA groups. Interestingly, no statistically significant effect in bleeding recurrence for both CPA and FIN over controls was present at 3 and 6 months of follow-up. CONCLUSIONS Both FIN and CPA seem to exert a comparable control in hematuria recurrence in patients with BPH, thus confirming the rationale behind the use of antiandrogens for such a purpose. Our results support the hypothesis that any antiandrogen, irrespective of the mode of action, would alter the natural history of BPH-associated hematuria. Interestingly, our results indicate that the speed of action of FIN may not be as rapid as previously described.

Peyronie's disease: Epidemiology and clinical presentation of 134 cases

Objective: To investigate epidemiological and clinical features of Peyronies disease in an unselected group of patients not seen by a urologist before. Patients and methods: A series of 134 consecutive cases with Peyronies 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°) 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 Duputrens 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 Peyronies 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 Peyronies disease may have a normal life with satisfactory sexual function. In some selected cases surgery offers an effective result.

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.

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 E1 (PGE1) or mixtures of PGE1 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 PGE1 but over time need increasing doses of PGE1 or mixtures of PGE1 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.

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.

Immunohistochemical detection of retinoic acid receptor-alpha in prostate carcinoma: correlation with proliferative activity and tumor grade.

Background: The use of retinoids as differentiation therapy is a novel approach to prostate cancer. Retinoids act via their own nuclear receptors, RARs and RXRs, modulating gene activity, cell growth and differentiation. This study provides new data on the content and cellular distribution of RARα protein in prostate cancer specimens, in correlation to tumor grade and proliferative activity. Material and methods: A total of 84 cases of primary prostate carcinoma, divided into 3 subgroups according to tumor grade, were immunohistochemically evaluated for retinoic acid receptor-α (RARα) and Ki67 using the streptavidin/peroxidase method on formalin fixed, paraffin embedded tissues. Results: RARα positivity was detected in all cases of prostatic carcinoma, with a more profound expression in well differentiated cancers. A statistically significant correlation between RARα staining and tumor grade was found (ANOVA, p < 0.031). Ki67 immunoreactivity was present in 35.7% of cases, but no correlation with tumor grade was found. When RARα staining was correlated with Ki67 positivity, a statistically significant correlation was present (unpaired t-test, p < 0.003). Conclusions: These findings indicate that RARα expression is correlated to some extent with tumor grade and its presence is more profound in highly proliferative tumors. Further studies are needed to establish the possible clinical value of the immunohistochemical evaluation of RARα content in tumor specimens.

Cellular Distribution of Retinoic Acid Receptor–α in Benign Hyperplastic and Malignant Human Prostates: Comparison with Androgen, Estrogen and Progesterone Receptor Status

Objectives: Retinoids are unique modulators of gene activity, cell growth and differentiation by binding to a series of nuclear receptors, i.e. all–trans–retinoic acid receptors (RAR) or 9–cis–retinoid receptors (RXR). In this study, the expression of RARα was immunohistochemically evaluated in benign, hyperplastic and malignant prostatic tissue and correlated with sex steroid receptor status.Methods: Twenty–four cases of BPH and 139 cases of primary prostatic carcinoma were evaluated for RARα expression in correlation with androgen (AR), estrogen (ER) and progesterone (PGR) receptor staining, as well as with tumor grade.Results: RARα was detected in the nuclei of epithelial cells in both BPH and prostate carcinoma cases. A modest inverse relationship with grade was present, especially for grade I and grade II tumors. AR staining was intense and a strong inverse relationship with grade was revealed. Although ER and PGR showed nuclear staining in prostatic epithelium, the overall expression for these receptors was low. When RARα content was compared to the nuclear AR expression, at least two–fold higher RARα levels were observed in AR+ grade II and grade III tumors.Conclusions: RARα expression can be immunohistochemically evaluated in formalin–fixed paraffin–embedded prostatic tissue. RARα expression is significantly elevated in AR+ moderately and poorly differentiated prostate carcinomas. Immunohistochemical determination of RARα content may be useful in defining the patient subsets in which retinoid–based treatment may be of clinical value.

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.