Endothelin-1 indicates unfavorable prognosis in primary high-grade non-muscle-invasive urothelial bladder cancer.

OBJECTIVE: To conduct a prospective study of the potential prognostic role of endothelin-1 (ET-1) in a cohort of primary high-grade non-muscle-invasive urothelial bladder cancer patients, who were treated with adjuvant intravesical Bacillus Calmette-Guérin (BCG). MATERIAL AND METHODS: Patients with primary high-grade nonmuscle- invasive urothelial bladder cancer, who received postoperatively induction and maintenance BCG therapy, were prospectively included. Recurrence and progression were histologically proven. Immunohistochemical staining for ET-1 was assessed. Epidemiological, pathological and clinical parameters as well as the expression of ET-1 in tumor specimens were statistically analyzed for recurrence, progression, recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: ET-1 associates significantly with recurrence (p = 0.000), progression (p = 0.000), RFS (p = 0.000) and PFS (p = 0.000). The patient's age is also significant for recurrence (p = 0.003, OR = 1.273 95% CI: 1.086-1.492) and RFS (p = 0.013). CONCLUSIONS: ET-1 seems to deteriorate prognosis in patients suffering from primary high-grade non-muscle-invasive urothelial bladder cancer, who are treated with adjuvant BCG instillations. Furthermore, the patient's age associates with an increased likelihood for recurrence.

Primary High-Grade Non-Muscle-Invasive Bladder Cancer: High NFκB Expression in Tumor Specimens Distinguishes Patients Who are at Risk for Disease Progression.

To investigate the potential prognostic role of NFκB expression in primary high-grade non-muscle-invasive bladder cancer. Patients with primary high-grade non-muscle-invasive bladder cancer who received induction and maintenance BCG therapy were retrospectively included. Recurrence and progression were histologically proven. Intensity and extent of immunochemistry were assessed. The final evaluation of the NFκB staining was done by combining intensity and extent as ΄΄product΄΄ and expressing it as ΄΄low NFκΒ expression΄΄ or ΄΄high NFκB expression΄΄. Epidemiological, pathological, clinical parameters and NFκB expression were statistically analyzed for recurrence (REC), progression (PR), recurrence-free survival (RFS) and progression-free survival (PFS). NFκB is significantly associated with disease progression (p < 0,001 in univariate analysis and p = 0,001, Odds Ratio = 14,484, 95% Confidence Interval = 3187-65,821 in multivariate analysis), but not with recurrence. The median value of NFκB expression as ΄΄product΄΄ is significantly higher for the patients with progression in comparison to patients with recurrence only (p = 0,003) and patients without recurrence or progression (p = 0,001). Patients' age is significantly associated (p = 0,001 in univariate analysis and p = 0,003, Odds Ratio = 1273, 95% Confidence Interval = 1086-1492 in multivariate analysis) with disease recurrence. High NFκB expression in primary high-grade non-muscle-invasive bladder cancer, treated with postoperative intravesical BCG immunotherapy, could represent an unfavorable prognostic factor.

Fascin determination in urothelial carcinomas of the urinary bladder: a marker of invasiveness.

CONTEXT: Invasion and the depth of invasion affect significantly the prognosis in urothelial carcinomas. The histopathologic evaluation of invasion may be problematic in some cases. Application of new immunohistochemical markers may facilitate the assessment of invasion. Fascin, one of these markers, is an actin-bundling protein involved in tumor cell migration. Fascin expression is increased in various carcinomas. Prior to this research, to our knowledge, only one study exists regarding fascin expression in urothelial carcinomas. OBJECTIVE: To characterize the expression of fascin in additional cases of urothelial carcinoma and to verify statistically a relationship between fascin overexpression and invasiveness in these tumors. DESIGN: We examined fascin immunoreactivity in 116 specimens of urothelial carcinomas obtained from 116 patients including 96 men and 20 women. Fifty-eight cases were ranked as low-grade carcinomas, pTa stage, and 58 cases were ranked as high-grade carcinomas--11 were ranked as stage pTa, 21 were ranked as pT1, and 26 were ranked as pT2 carcinomas. Fascin immunoreactivity was assessed semiquantitatively in tumor cells. In each case, we ascribed 3 immunoreactivity scores, one for extent, one for intensity, and a combined immunoreactivity score. RESULTS: The combined immunoreactivity score was significantly higher in invasive carcinomas. In addition, strong staining was observed exclusively in invasive carcinomas. None of the pTa tumors demonstrated intense staining, including those ranked at the higher grade. CONCLUSIONS: Our results point to an association between fascin immunostaining and urothelial carcinoma invasiveness and suggest that fascin overexpression may be a marker of aggressive urothelial carcinomas.

The natural history of Peyronie's disease: an ultrasonography-based study.

OBJECTIVES: To define ultrasonographic patterns reflecting different states of Peyronie's disease (PD) and to use them to evaluate the natural history of the disease. MATERIAL AND METHODS: Diagnosis of PD was based on medical and sexual history, physical examination, intracavernosal injection test, and penile ultrasonography. Patients with penile fracture history were excluded from the study. Three groups were formed according to ultrasonographic patterns: solitary hyperechoic lesion without acoustic shadow (group A), moderately hyperechoic multiple scattered calcified lesions with acoustic shadows (group B), dense calcified hyperechoic plaque with acoustic shadow (group C). All patients entered a watchful waiting protocol for 1 yr followed by a new penile ultrasonography. RESULTS: Ninety-five 95 patients with PD were included in the study (mean age, 57.2+/-9.1 yr; mean duration of disease, 12.9+/-8.9 mo). Risk factors associated with cardiovascular disease were present in 79 of 95 patients (83.16%). Eleven (11.6%), 35 (36.8%), and 49 (51.6%) patients were classified into groups A, B and C, respectively. At the end of the study, in group A, reduction of fibrotic lesions and curvature angle was noticed in 9 of 11 (81.8%) patients, whereas plaque formation was noticed in 2 of 11 (18.2%) patients. In group B, plaque and curvature reduction was noticed in 15 of 35 (42.9%) and 12 of 35 (34.3%) respectively, whereas in the rest a dense calcified plaque was noticed. In group C, no ultrasonographic evidence of improvement was noticed; curvature angle was reduced in 4 of 49 (8.2%), owing to the extension of the plaque circumferentially. Significant hemodynamic changes were noticed at the two time points tested (30.53% diagnosed with vascular disease at baseline vs. 46.32% at the end of the study, p=0.03). CONCLUSIONS: Corporal ultrasonography in patients with PD allows objective evaluation and classification of disease. The density of echogenic areas and presence of acoustic shadows are predictors of disease stability.

Sildenafil failures may be due to inadequate patient instructions and follow-up: a study on 100 non-responders.

OBJECTIVE: The objective of this study was to identify factors that affect efficacy response rate to sildenafil in the clinical practice. MATERIAL AND METHOD: The study comprised 100 consecutive sildenafil non-responders. Mean patient age was 59+/-14.4 years and mean duration of ED 5.5+/-6.4 years. All patients underwent detailed medical and sexual history and completed the IIEF and a questionnaire regarding the previous use of sildenafil. When inadequate instructions were reported, information on the appropriate use of sildenafil was given and patients were asked to use at least 4 tablets at home. Pharmacologic efficacy was re-evaluated in a scheduled follow-up visit. RESULTS: Mean Erectile Function Domain (ED) of the IIEF score was 14+/-9.9. In 56 patients inappropriate use of sildenafil was recognized; 45 had never used the highest recommended dose (100 mg), 32 had taken the pill with a full stomach right after a meal, 22 had taken the pill just before the initiation of sexual activity and 12 were not aware that sexual stimulation was mandatory to achieve an erection. Furthermore, 8 patients had tried the 100mg dose, despite the presence of factors associated with sildenafil clearance reduction (renal insufficiency, cimetidine treatment). Only 34 patients reported that their physician had scheduled a follow-up visit. Following adequate dose titration and time adjustment, 31 patients responded to sildenafil; 10 patients used the 50 mg dose and 21 the 100 mg. Second and third-line treatment options were offered to the rest of the patients. CONCLUSIONS: ED patients may receive inadequate instructions with their prescriptions. Response rate to sildenafil may be maximized after receiving appropriate dose titration and instructions on administration. ED should be treated in the same way as other chronic conditions; follow-up is necessary to evaluate the appropriate application and pharmacologic efficacy of the proposed treatment.

Effects of sildenafil on cardiopulmonary responses during stress.

PURPOSE: To investigate possible effects of sildenafil on the cardiopulmonary responses during sexual intercourse we evaluated cardiopulmonary responses during exercise in a group of impotent patients. MATERIALS AND METHODS: The study sample included patients with erectile dysfunction who underwent a cardiopulmonary exercise test before and after the administration of 100 mg. sildenafil citrate. Cardiopulmonary exercise test parameters at rest, at the anaerobic threshold, at peak exercise and at 1-minute recovery were recorded, including systolic and diastolic blood pressure, the heart rate, O2 consumption, CO2 production, ventilation and the respiratory rate. Furthermore, O2 consumption per kg. body weight, the ventilatory equivalent for O2 consumption (ventilation/O2 consumption) and CO2 production (ventilation/CO2 production), the respiratory quotient, metabolic equivalents metabolic equivalents, oxygen pulse (O2 consumption/heart rate) and the change in O2 consumption/change in heart rate were calculated. RESULTS: In 2 of the 43 patients enrolled in the study myocardial ischemia and high blood pressure were detected at rest in 2, respectively, who were excluded from analysis. In the remaining 41 patients with a mean age +/- SD of 52.3 +/- 8.6 years a statistically significant decrease in systolic and diastolic blood pressure was noted after sildenafil use at all stages tested (p <0.002 to 0.001). The heart rate mildly increased after sildenafil use at rest and at peak exercise (p = 0.018). The O2 pulse decreased at the anaerobic threshold (p = 0.003), peak exercise (p = 0.001) and recovery (p = 0.047). In the 11 patients with a mean age of 40.8 +/- 10.12 years who had psychogenic erectile dysfunction the only 2 parameters affected were an increased heart rate and decreased systolic blood pressure at rest, while O2 consumption/heart rate decreased at the anaerobic threshold. In the 18 patients with a mean age of 61.1 +/- 8.9 years who had organic erectile dysfunction and an unremarkable medical history a decrease was noted in systolic and diastolic blood pressure at rest and at peak exercise, and diastolic blood pressure also at recovery, while the heart rate increased at recovery. In the 12 patients with a mean age of 60.16 +/- 9.12 years who had treated cardiovascular disease systolic and diastolic blood pressure decreased at all states and O2 consumption/heart rate at the anaerobic threshold and at peak exercise, while increased values were noted for the respiratory rate at the anaerobic threshold and ventilation/CO2 production at recovery. CONCLUSIONS: Hemodynamic changes after sildenafil administration should be considered minimal in concert with patient health status. Younger patients without signs of systemic atherosclerosis compensate the vasodilatory effect of sildenafil during exercise, while in older patients with vasculogenic erectile dysfunction moderate changes may be noted regardless of cardiovascular disease in the medical history.

Management strategy for arterial priapism: therapeutic dilemmas.

PURPOSE: We present 7 cases of arterial high flow priapism and propose management algorithms for the condition. MATERIALS AND METHODS: We studied 2 children and 5 adults with posttraumatic arterial priapism. Blood gas analysis and color Doppler ultrasonography of the corpora cavernosa confirmed the diagnosis in 4 adults, while 1 patient had already undergone cavernous artery ligation in elsewhere. In the children perineal compression resulted in detumescence, a sign that is proposed to be indicative of the diagnosis of arterial priapism (piesis sign) complementing physical examination. Mechanical compressive force was applied to the perineum of 1 boy, while the other received a watchful waiting program. All adults participated in an observation regimen except 1, who decided to undergo immediate embolization of the internal pudendal artery. RESULTS: Perineal compression led to the resolution of priapism in 1 child, while spontaneous resolution was noted in the other. An adult noticed spontaneous penile detumescence 3 to 4 months after trauma, which was attributable to site specific venous leakage and decreased, inflow in the contralateral cavernous artery. The patient underwent venous surgery and is on an intracavernous injection regimen. Successful embolization of the internal pudendal artery was performed immediately in 1 man and in the other 4 months after trauma due to social inconvenience. Adult patient 3 is still on the watchful waiting protocol (42 months), while the one who underwent cavernous artery ligation is receiving treatment for erectile dysfunction. CONCLUSIONS: Absent of long-term damaging effects of arterial priapism on erectile tissue combined with the possibility of spontaneous resolution or progressive concomitant hemodynamic abnormalities associated with blunt perineal trauma are suggestive of the introduction of an observation period in the management algorithm of high flow priapism. Such a period may help avoid unnecessary intervention and determine the impact of priapism on patient personal life. Perineal compression may be also added as part of the physical examination as a sign specifically indicative of arterial priapism.

Diagnostic steps in the evaluation of patients with erectile dysfunction.

PURPOSE: The necessity for a thorough diagnostic evaluation for erectile dysfunction has been questioned after the availability of effective oral therapies. We determined the impact of the different diagnostic steps on the management strategy for erectile dysfunction. MATERIALS AND METHODS: The study included all patients who presented at an andrology outpatient clinic during a 4-year period. Baseline evaluation included medical and sexual history, blood tests, physical examination and intracavernous injection test. Patients with normal initial screening were evaluated with specific diagnostic procedures. The results were analyzed to identify the diagnostic potential of each screening step separately. RESULTS: Overall 1,644 patients presented at the clinic during the study period, of whom 368 (22.4%) were excluded from study due to severe psychiatric (5.2%) or cardiovascular (2.7%) disease, or to a history of erectile dysfunction less than 3 months in duration (14.5%). In the remaining 1,276 patients with a mean age plus or minus standard deviation of 56 +/- 14 years, and a mean duration of erectile dysfunction of 4.9 +/- 3.4 years medical history revealed erectile dysfunction associated medical conditions in 57%, blood tests identified previously undiagnosed medical conditions in 6.2%, and physical examination and the intracavernous injection test were diagnostic in 13.9% and 2.6%, respectively. Initial screening was negative in 259 cases (20.3%), in which specific diagnostic procedures identified an underlying vascular pathology in 165 (12.9%) and unfavorable penile geometry in 16 (1.3%). The remaining 78 men (6.1%) had no evidence of organic disease. CONCLUSIONS: Baseline diagnostic evaluation for erectile dysfunction can identify the underlying pathological condition or erectile dysfunction associated risk factors in 80% of patients. Such screening may diagnose reversible causes of erectile dysfunction and also unmask medical conditions that manifest with erectile dysfunction as the first symptom. Specific diagnostic procedures may be limited in patients with primary erectile dysfunction or those without risk factors. Such clinical data support previously published guidelines for erectile dysfunction management.

Corporoplasty using tunica albuginea free grafts for penile curvature: surgical technique and long-term results.

PURPOSE: A Nesbit or plication procedure for correcting penile deformities is associated with penile shortening, especially in patients with excessive curvature and/or rotation. On the other hand, grafting procedures are associated with poor postoperative results due to graft shrinkage and veno-occlusive dysfunction. To minimize penile shortening and preserve potency we describe a new surgical technique combining the Nesbit procedure with tunica albuginea free grafting. Long-term functional results and patient satisfaction are reported. MATERIALS AND METHODS: We treated 17 potent patients with a mean age plus or minus standard deviation of 46.1 +/- 14.5 years, including 4 with congenital penile deviation and 13 with stabilized Peyronie's disease. Opposite the point of maximal curvature a typical Nesbit procedure was performed. The excised tunica albuginea segment consequently served as a free graft. A symmetrical incision was made at the opposite site and the preserved elliptical tunica albuginea graft was placed in the defect. Further elliptical excisions and grafting followed as needed to correct the deformity. RESULTS: At a mean followup of 39.5 +/- 13.7 months (range 18 to 62) all patients reported penile straightening and functional erection, while ultrasonography of the corpora cavernosa revealed no changes in graft ultrastructure. There was penile shortening in 8 patients (47%) but only 2 (11.7%) considered it significant. All patients with a minimum 2-year followup were positive in regard to recommending the operation to others or repeating it if necessary. CONCLUSIONS: The newly described technique may be considered as a treatment option in patients with excessive penile curvature since shortening of the penile shaft is eliminated by 50% compared with the result of the Nesbit procedure. Tunica albuginea seems to be an appropriate grafting material since it prevents postoperative corporeal veno-occlusive dysfunction.