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Introduction: Numerous studies performed in recent years have shown protective effects of N-acetylcysteine (NAC) on cardiac and renal tissue damage following ischemia/reperfusion injury. We assessed the effectiveness of systemic administration of NAC, at a therapeutic dose, in a rat model of a 1-hour 720-degree testicular torsion/detorsion. Materials and Methods: Sprague-Dawley rats were divided into five groups, 14 animals in each: group 1 animals underwent sham operation as the control group; group 2 rats underwent torsion/detorsion and received saline injection, and the animals in groups 3, 4, and 5 received intraperitoneal injections of 150 mg/kg NAC 30 min before torsion, after torsion, and after detorsion, respectively. Markers of oxidative stress as well as germ cell apoptosis indices were assessed 4 and 24 h after detorsion, respectively. Results: The apoptosis indices were significantly higher in group 2 as compared with the control group. Four hours after detorsion, the testicular level of lipid peroxidation was significantly increased, and antioxidant enzyme activities were significantly decreased in group 2 as compared with the controls. Administration of NAC either 30 min before or after torsion (groups 3 and 4) significantly improved the germ cell apoptosis indices and oxidant/antioxidant balance. Administration of NAC after detorsion had no significant effect on biochemical markers or germ cell apoptosis. Conclusion: Administration of NAC prior to torsion or detorsion, but not after detorsion, induces protective effects against ischemia/reperfusion injury in a rat model of testicular torsion.

Background: The presence of lymph nodes (LN) within the prostatic anterior fat pad (PAFP) has been reported in several recent reports. These PAFP LNs rarely harbor metastatic disease, and the characteristics of patients with PAFP LN metastasis are not well-described in the literature. Our previous study suggested that metastatic disease to the PAFP LN was associated with less severe oncologic outcomes than those that involve the pelvic lymph node (PLN). Therefore, the objective of this study is to assess the oncologic outcome of prostate cancer (PCa) patients with PAFP LN metastasis in a larger patient population. Methods: Data were analyzed on 8800 patients from eleven international centers in three countries. Eighty-eight patients were found to have metastatic disease to the PAFP LNs (PAFP+) and 206 men had isolated metastasis to the pelvic LNs (PLN+). Clinicopathologic features were compared using ANOVA and Chi square tests. The Kaplan-Meier method was used to calculate the time to biochemical recurrence (BCR). Results: Of the eighty-eight patients with PAFP LN metastasis, sixty-three (71.6 %) were up-staged based on the pathologic analysis of PAFP and eight (9.1 %) had a low-risk disease. Patients with LNs present in the PAFP had a higher incidence of biopsy Gleason score (GS) 8–10, pathologic N1 disease, and positive surgical margin in prostatectomy specimens than those with no LNs detected in the PAFP. Men who were PAFP+ with or without PLN involvement had more aggressive pathologic features than those with PLN disease only. However, there was no significant difference in BCR-free survival regardless of adjuvant therapy. In 300 patients who underwent PAFP LN mapping, 65 LNs were detected. It was also found that 44 out of 65 (67.7 %) nodes were located in the middle portion of the PAFP. Conclusions: There was no significant difference in the rate of BCR between the PAFP LN+ and PLN+ groups. The PAFP likely represents a landing zone that is different from the PLNs for PCa metastasis. Therefore, the removal and pathologic analysis of PAFP should be adopted as a standard procedure in all patients undergoing radical prostatectomy.

Objectives. To evaluate the efficacy of botulinum toxin A in the treatment of children with detrusor hyperreflexia caused by myelomeningocele and the effects of this treatment on neuropathic bladder and bowel dysfunction. Methods. In a prospective study, 26 children with myelomeningocele (20 boys and 6 girls, mean age 6.9 years) were included. All patients had been nonresponders to medical treatment and required clean intermittent catheterization. Under cystoscopic guidance, 10 IU/kg of botulinum toxin A was injected into the detrusor muscle, sparing the trigone and ureteral orifices. In each patient, urinary incontinence grade and improvement in parameters of interest in the evaluation of bowel dysfunction were assessed before and 4 months after injection. Conventional urodynamic studies to determine maximal bladder capacity and maximal detrusor pressure and voiding cystoureterography were also performed. Results. Four months after procedure, 19 patients (73%) had become completely dry between clean intermittent catheterizations, and the total improvement in urine incontinence was 88%. The mean maximal detrusor pressure was decreased to 83.2 4.6 cm H2O from the baseline of 139.3 11.2 (P 0.01). The average maximal bladder capacity increased from 102.8 6.3 mL to 270.2 9.5 mL (P 0.01). Of the 15 patients who had varying degrees of vesicoureteral reflux before the procedure, 11 (73%) had decrease in the vesicoureteral reflux grade. Also, bowel dysfunction improved in 10 (66%) of the 15 patients. Conclusions. Botulinum toxin A appears to be a safe, minimally invasive procedure for the management of neuropathic bladder and bowel dysfunction in children with myelomeningocele. UROLOGY 68: 1091‐1097, 2006. © 2006 Elsevier Inc.

We assessed the smooth muscle cell apoptosis along with changes in cellular and extracellular components of the ureteropelvic junction in 23 patients with unilateral obstruction and compared them with 25 autopsies from ureteropelvic junction regions of age matched cadavers.Tissue specimens obtained from pyeloplasty were divided into 3 sections-renal pelvis above the obstruction, obstructed ureteropelvic junction and ureter below the obstructed region. For the control group the normal ureteropelvic junctions of age matched infants were autopsied. In paraffin embedded sections we determined myocyte apoptosis index (using TUNEL assay), and the amount of muscular components and nerve terminals (using image analysis techniques after immunohistochemical staining). The collagen and elastin fibers were specifically stained for evaluation of changes in extracellular matrix.Smooth muscle cell apoptosis index was significantly increased at the site of ureteropelvic junction obstruction (5.68 +/- 0.18) compared to normal autopsied ureteropelvic junctions (3.60 +/- 0.11) and 2 other sections of obstructed ureteropelvic junction complex (renal pelvis 4.73 +/- 0.16, and ureter 3.97 +/- 0.16). The number of nerve terminals and the percentage of muscular component were significantly lower at the obstructed segments of affected patients compared to normal ureteropelvic junctions. Meanwhile, collagen fibers formed a significantly higher proportion of ureteral wall at the site of obstruction. Interestingly, there was negative correlation between myocyte apoptosis indices and number of nerve endings as well as amount of muscular components at the site of ureteropelvic junction obstruction. However, positive correlations were found between smooth muscle cell apoptosis and the percentage of collagen and elastin fibers.Our findings suggest an important role for myocyte apoptosis and defective neural development in the pathogenesis of congenital ureteropelvic junction obstruction that could pave the road for the emergence of new therapeutic modalities.

Recently many researchers have proposed a protective role for morphine against tumor growth and metastasis, especially through induction of apoptosis in tumoral cells. These findings may lead to underestimation of cytotoxic effects of opioid drugs which are usually expected only at high doses. The present study was conducted to clarify whether repeated morphine administration, which is commonly used for relief from chronic pain, would interfere with liver antioxidant defence and hepatocytes vitality. Morphine was injected repeatedly at doses that have been reported to relieve cancer pain and reduce tumor spread in mice (5 and 10 mg/kg/day for nine consecutive days). The changes in hepatic glutathione concentration, its synthesis pathway and enzymatic antioxidant defense revealed the pro-oxidant effects of chronic morphine treatment on the liver. None of these changes were observed in those mice that were co-treated with naltrexone (opioid antagonist) and same doses of morphine. However induction of liver conjugating enzymes following morphine treatment was not receptor mediated. Moreover, chronic morphine treatment induced hepatocytes apoptosis. Interestingly, the apoptotic changes were antagonized by co-administration of either naltrexone or thiol antioxidant. In conclusion, although hepatotoxic effects of morphine at high doses have been reported previously, our findings propose that repeated morphine administration even at lower doses would induce oxidative stress in the liver, which may contribute to induction of apoptosis in hepatocytes. Since many of the observed adverse effects were mediated by opioid receptors, our results suggest that other opioid analgesics should also be used more cautiously.

Previous data about the regulation of SOD activity as the key part of the endogenous antioxidant system by vitamin E is conflicting.We investigated the effect of different nontoxic doses of vitamin E on erythrocyte SOD activity and plasma total antioxidant capacity in rats, receiving 0 (control group), 100, 300 and 600 mg vitamin E/kilogram of body weight intramuscularly twice a week over 6-weeks.We observed a linear increase in SOD activity in the first dosing group, which was significant (p0.05) after 6th week compared to the control level. There was an increase in SOD activity at the end of 2nd and significant increase after 4th weeks, which was followed by a significant decrease at the end of 6th week in the second dosing group. In the third dosing group, there was a significant increase at the end of 2nd week and a significant decrease at the end of 4th and 6th weeks in the SOD activity. The changes in plasma antioxidant capacity were parallel to that of SOD activity with a significant and strong degree of correlation in the 4th and 6th weeks (r=0.7 and r=0.8, respectively). Serum levels of Vitamin E also increased in a time- and dose-dependent manner; the highest level was achieved in the 600 mg/kg dosing group after 6 weeks.Non-toxic doses of vitamin E at some levels can up-regulate SOD activity, but cumulative effect of the same doses can lead to attenuation of SOD activity and hence antioxidant defense.

Objectives To investigate the effects of morphine on reperfusion injury due to testicular torsion-detorsion (T/D). Methods We divided 36 adult male Sprague-Dawley rats into six groups. Testicular ischemia was achieved by twisting the right testis 720° counterclockwise for 1 hour, and reperfusion was allowed for 4 hours after detorsion. The baseline group was for basal normal values. The sham-operated group served as the control group. The T/D group underwent 1 hour of testicular torsion and 4 hours of detorsion. The morphine group received pretreatment with intravenous morphine sulfate (10 mg/kg) just before detorsion. The naltrexone group received an intravenous injection of naltrexone HCl (20 mg/kg) 15 minutes before detorsion. The naltrexone/morphine group received intravenous administration of naltrexone HCl (20 mg/kg) 15 minutes before detorsion and morphine sulfate (10 mg/kg) just before detorsion. Results The ipsilateral malondialdehyde levels in the T/D group were significantly greater than in the control and baseline groups. Moreover, the ipsilateral testicular malondialdehyde values in the morphine group were significantly lower than in the T/D and naltrexone/morphine groups. Also, significant decreases occurred in catalase and superoxide dismutase activities in the T/D group compared with the control and baseline groups. These values were significantly greater in the morphine group than in the T/D and naltrexone/morphine groups. The ipsilateral testes of all groups that underwent testicular torsion showed similar histopathologic changes. Conclusions Morphine increased the ipsilateral intratesticular antioxidant markers during the reperfusion phase after unilateral testicular torsion, which was eventually reflected in lower testicular malondialdehyde levels. Furthermore, this effect was mediated through the opioid receptors.

Background: Elevated serum retinol, CSF retinol, and serum retinol binding protein (RBP) levels have been found in some patients with idiopathic intracranial hypertension (IIH), but serum and CSF retinol levels have not been studied in matched serum and CSF samples in patients with IIH. Objective: To determine whether serum and CSF vitamin A concentrations are associated with IIH. Methods: The serum and CSF retinol concentrations were prospectively assessed in 20 patients with IIH and 20 control subjects. Results: CSF retinol concentration was higher in the patient group (median 575.91 n M ) vs the control group (median 63.35 n M ) ( p M ) and patients (median 1,002.62 n M ) ( p = 0.10). There was an association between higher vitamin A levels (>250 n M ) and IIH ( p = 0.039). There was a correlation between CSF and serum retinol levels in patients ( r = 0.82) and control subjects ( r = 0.66). Conclusion: Elevated CSF retinol concentration is associated with idiopathic intracranial hypertension (IIH), but serum retinol level is not associated with IIH.

Objective: We investigated causes of abducens nerve paralysis, the side of the involvements, age, and sex distribution of causes. Background: Abducens nerve paralysis is the most common nerve palsy among ocular motor nerves, which have not been investigated in Iran yet. Material and Methods: This is a retrospective case-series study performed from April 1995 to April 2000. We investigated 50 patients who attended to the Neuro-ophthalmology Clinic in Farabi Eye Hospital and were diagnosed as acquired isolated unilateral or bilateral abducens nerve paralysis. Results: The most common causes were ischemia (44%), tumors (18%), idiopathic intracranial hypertension (14%), and multiple sclerosis (8%). The less common causes were trauma, undetermined, arteriovenous fistula, aneurysm, syphilis, and temporal arteritis. The paralysis was seen in 28 women (56%) and 22 men (44%). Seventy percent of patients were older than 40 years of age, and also peak incidence of abducens nerve paralysis was at the sixth decade of ...

5063 Background: A 17 gene panel (Oncotype Dx Genomic Prostate Score, GPS) has been validated as an independent predictor of adverse pathology (AP, defined as pathological GS 4+3 or higher and/or pT3+) in men treated with radical prostatectomy (RP) for prostate cancer (PCa). Multiparametric Magnetic Resonance Imaging (mpMRI) may help guide prostate biopsies. We explored synergies between GPS and mpMRI to aid in PCa management decisions. Methods: A cohort of men with NCCN Low and Intermediate-Risk PCa who were managed with RP was identified from a clinical database. Patients were required to have had a simultaneous mpMRI-guided and systematic biopsy and to have undergone RP within 6 months. Biopsy tissue of the highest Gleason pattern was used for calculation of GPS. The primary endpoint was AP. Secondary endpoints included the range of GPS within UCLA prostate MRI risk groups and median GPS when there was discrepancy between MRI and systematic biopsy Gleason Score (GS). Logistic regression models were fit to evaluate the relationship between GPS (per 20 units) and AP. Results: 134 men met criteria for the primary endpoint. Median age was 62 years (range 46-77). NCCN Low & Intermediate-Risk PCa was present in 16%, and 84% of men, respectively. Biopsy GS 3+3/3+4/4+3 was present in 19%, 67%, and 13%, respectively. In a univariable model, GPS was associated with AP (OR 3.8, 95% CI 2.1 to 7.4, p < 0.001). After adjustment for highest biopsy GS and clinical T-stage, GPS remained significantly associated with AP (OR 3.4, 95% CI 1.8 to 6.8, p = 0.0004). A wide and overlapping distribution of GPS was noted across UCLA MRI prostate risk groups, indicating that GPS provides information that is distinct from what can be determined from mpMRI. When there was a discrepancy between mpMRI and systematic biopsy GS, mpMRI targeted lesions with higher GS had higher median GPS (33, range 13-70) than systematic biopsies with higher GS (median GPS 25, range 15-55). Conclusions: GPS provides independent and complementary prognostic information to mpMRI-guided biopsies. The combination of mpMRI for biopsy guidance and GPS for molecular analysis may optimize prediction of AP and improve patient selection for treatment versus surveillance.

Background Recently, three prospective randomized trials have shown that adjuvant radiotherapy (ART) after radical prostatectomy for the patients with pT3 and/or positive margins improves biochemical progression-free survival and local recurrence free survival. But, the optimal management of these patients after radical prostatectomy is an issue which has been debated continuously. The object of this study was to determine the necessity of adjuvant radiotherapy (ART) by reviewing the outcomes of observation without ART after radical prostatectomy (RP) in patients with pathologic indications for ART according to the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) guideline. Methods From a prospectively maintained database, 163 patients were eligible for inclusion in this study. These men had a pathological stage pT2–3 N0 with undetectable PSA level after RP and met one or more of the three following risk factors: capsular perforation, positive surgical margins, or seminal vesicle invasion. We excluded the patients who had received neoadjuvant hormonal therapy or adjuvant treatment, or had less than 24 months of follow-up. To determine the factors that influenced biochemical recurrence-free (BCR), univariate and multivariate Cox proportional hazards analyses were performed. Results Among the 163 patients, median follow-up was 50.5 months (24.0-88.2 months). Of those men under observation, 27 patients had BCR and received salvage radiotherapy (SRT). The multivariate Cox analysis showed that BCR was marginally associated with pre-operative serum PSA (P = 0.082), and the pathologic GS (HR, 4.063; P = 0.001) was an independent predictor of BCR. More importantly, in 87 patients with pre-operative PSA

However, no differences were observed in the BCR-free survival rates when patients with organ-confined disease and pathological Gleason score 6 (Group 1) were compared to those with organ-confined disease and pathological Gleason score 3+4 (Group 2; P1⁄40.4). CONCLUSIONS: Roughly a quarter of men of potential AS candidates harbors unfavorable disease at final pathology. While non organ confined and or Gleason score 4+3 patients had worse cancer control after RP, the upgrade from biopsy Gleason score 6 to pathological Gleason score 3+4 does not significantly increase the risk of BCR. Active therapy may be thus consider an overtreatment also in these men despite higher Gleason score (3+4). This may suggest the potential inclusion also of these men in prospective AS protocols.

INTRODUCTION AND OBJECTIVES: Selective Serotonin Reuptake Inhibitors (SSRI) like paroxetine and fluoxetine are known to induce erectile dysfunction in humans and rats. Dapoxetine, a selective SSRI, is approved in Europe for the management of premature ejaculation. The aim of this study was to assess the impact of dapoxetine on (1) erectile responses induced by electrical stimulation (ES) of the cavernous nerve and (2) on smooth muscle relaxations induced by sodium nitroprusside (SNP) or sildenafil (SF) in the isolated corpus cavernosum (CC). METHODS: Wistar rats were anaesthetized with urethane. The carotid artery, penis and jugular vein were catheterized for blood pressure and intracavernous pressure recordings (BP and ICP) and drug injection, respectively. The right cavernous nerve was mounted on bipolar stimulating electrodes. ES (3, 6 and 9 Hz) were performed before and at 4, 24, 44 and 64 min after intravenous (i.v.) injection of 1 or 3 mg/kg dapoxetine or saline in 3 independent groups of 6 animals. ICP values were normalized to BP. For in vitro experiments, CC strips from Wistar rats were mounted under 0.5 g of tension in organ baths with a modified Krebs solution. After 60 min of equilibration, dapoxetine 1 mM (or its solvent) was incubated for 20 min. Strips were then exposed to norepinephrine 30 mM. When contractions reached a plateau, cumulative concentration-response curves to SNP, SF or their common solvent were constructed. RESULTS: Erectile responses were dose-dependently decreased by dapoxetine from 4 to 44 min post-dosing at all frequencies of ES. The mean of ICPmean/BP at 6 Hz was 0.47 0.01 in the 3 groups before injection. At 44 min post-injection, ICPmean/BP at 6 Hz was 0.43 0.06, 0.30 0.08 and 0.13 0.04 after vehicle, 1 mg/kg and 3 mg/kg dapoxetine (P

To compare the clinicopathologic findings of African-American (AA) and White-American (WA) men with prostate cancer (PCa) who were candidates for active surveillance (AS) and underwent radical prostatectomy (RP).Prospectively maintained database of men who underwent RP from 2 academic centers were analyzed retrospectively. Postoperative pathologic characteristics of patients who met the AS inclusion criteria of the University of California, San Francisco (UCSF) and National Comprehensive Cancer Network (NCCN) were evaluated. After RP, the rate of pathological upstaging and Gleason upgrading were compared between AA and WA men.In the AA cohort, 196 and 124 men met the UCSF and NCCN criteria for AS, respectively. With respect to WA patients, 191 and 148 fulfilled the AS criteria for UCSF and NCCN, respectively. AA men had a higher percentage of maximum biopsy core than WA men (15.3%-20.4% vs 11.5%-15.0%, P .05, respectively) in both cohorts. In addition, a greater proportion of AA men had multiple positive biopsy cores compared to WA men (45.2% vs 33.1%, P = .046) under the NCCN criteria. A higher proportion of AA men were upstaged (≥pT3) compared to WA men (19.4% vs 10.1%, P = .037). A multivariate regression test revealed that age, preoperative PSA, and number of positive cores were independent predictors of more advanced disease (upstaging and/or upgrading) in AA men.AA men who were candidates for AS criteria had worse clinicopathological features on final surgical pathology than WA men. These results suggest that a more stringent AS criteria should be considered in AA men with prostate cancer.

PURPOSE: The increasing incidence of hypospadias is partly attributed to increased gestational exposure to endocrine disruptors. We investigated the effects of genistein, the primary phytoestrogen in soy, on the molecular program of male urethral development. MATERIALS AND METHODS: Female mice were fed diets supplemented with genistein (500 mg/kg diet) or control diets before breeding and throughout gestation. Urethras from embryonic day 17.5 male fetuses were harvested, and RNA was prepared, amplified, labeled and hybridized on whole genome microarrays. Data were analyzed using packages from the R/Bioconductor project. Immunohistochemical analysis and immunoblotting were used to confirm the activity of MAPK and the presence of Ntrk1 and Ntrk2 during urethral development. RESULTS: Gestational exposure to genistein altered the urethral expression of 277 genes (p

Aims Elevated levels of endogenous opioids play a pivotal role in several deleterious consequences of cholestasis. Renal dysfunction occurs in cholestasis but its exact mechanism is still unknown. In this study, we investigated the role of endogenous opioids in cholestasis induced nephrotoxicity. Main methods Thirty-five rats were divided into five groups. In groups 1 and 2 BDL rats received either daily subcutaneous 20 mg/kg of naltrexone or its vehicle, for 7 days after BDL. In groups 3 and 4, BDL or Sham rats received no injections. In group 5, normal rats received subcutaneous injections of 20 mg/kg/day of naltrexone for 7 days. At the 7th day, 24 h urine was collected to measure urinary N-acetyl-β-D-glucosaminidase (NAG) as an early marker of renal tubular injury. Kidney samples were then collected for light and electron microscopic studies. Key findings BDL significantly increased NAG activity compared to sham groups. Naltrexone significantly reversed NAG activity to normal levels in BDL animals. Naltrexone treatment in BDL animals also significantly reversed ALT and AST to their normal levels. In light and electron microscopic studies, there were significant structural alterations in BDL samples, which were mostly prevented in naltrexone treated BDL animals. Significance Significant changes in urinary NAG activity and renal morphology of cholestatic rats were reversed by naltrexone treatment. These results suggest a possible role for endogenous opioids in inducing cholestatic nephrotoxicity.

We report the indications, technique and outcome of a large series of children who underwent bladder neck transection for intractable urinary incontinence.We retrospectively reviewed demographics, operative details, complications and outcomes of 76 patients (47 males, 29 females) who underwent bladder neck closure at our institution between 1996 and 2006. Mean patient age at the time of the procedure was 12 years, 10 months. The most common diagnosis was bladder exstrophy. Of the patients 31 had undergone prior bladder neck reconstruction (30) or sling repair (1). All patients underwent concomitant augmentation and creation of a catheterizable stoma.A total of 50 patients had more than 12 months of followup (mean 44, range 12 to 128). Continence was achieved initially in 86% of the patients (43 of 50). Of the 7 primary failures 2 leaked via the urethra and 5 via the stoma. Six of these patients achieved dryness with revision, for a final continence rate of 98%. A single renal unit suffered significant loss of function during this period. New, nonobstructive hydronephrosis developed in 8 additional renal units. Stones developed in 30% of the patients. There were no spontaneous bladder ruptures.Bladder neck transection in combination with enterocystoplasty and creation of a continent catheterizable stoma is an effective approach to incontinent cases with severely damaged bladder outlets and poor quality bladders in which other reconstructive approaches either have failed or are deemed likely to fail. Specific concerns regarding the risk of poor renal outcomes and perforation seem unwarranted at present.

The objective of this work was to examine the time-dependent pro-oxidant versus antioxidant effect of various doses of vitamin E used commonly in experimental studies. Erythrocyte activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and plasma lipid peroxidation levels were investigated following biweekly intramuscular administration of 100, 300 and 600 mg/kg of vitamin E at a baseline time point, and additionally at 2, 4 and 6 weeks after initiating treatment. Vitamin E had an antioxidant effect when administered at low doses over short time periods, and increased the activity of antioxidant enzymes. At higher doses and over longer time periods, it increased the level of lipid peroxidation, and attenuated the activity of antioxidant enzymes. These results suggest that time-dependent variations in vitamin E effects should be considered in design and interpretation of experimental antioxidant studies, as well as during clinical trials.

We used current methods of screening for prostate cancer, digital rectal examination and serum prostate specific antigen as an initial assessment of risk in a young group of adult 46,XY patients affected by disorders of sex development.Adult intersex patients older than 21 years, under long-term followup at the Pediatric Endocrinology Clinic of the Johns Hopkins Hospital, with a diagnosis of male psuedohermaphroditism and raised as male or female were included in analysis. After written consent all participants underwent digital rectal examination and blood sampling for prostate specific antigen and testosterone measurements.Prostate specific antigen values were available for analysis in 26 patients. Diagnoses included micropenis (8), complete androgen insensitivity syndrome (3), partial androgen insensitivity syndrome (9) and mixed gonadal dysgenesis (6). Of the 26 patients 9 had been raised as female (complete androgen insensitivity syndrome in 3, partial androgen insensitivity syndrome in 3, micropenis in 2 and mixed gonadal dysgenesis in 1). Mean patient age was 38 years (range 24 to 57). Serum prostate specific antigen was less than 0.1 ng/ml in 18 patients including the 9 reared as female. The remaining 8 patients had a prostate specific antigen of 0.1 to 0.9 ng/ml, were reared as male and had a mean age of 39.6 years (range 33 to 44). The diagnoses in this group consisted of micropenis (4), partial androgen insensitivity syndrome (2) and mixed gonadal dysgenesis (2). All patients had a palpable, small prostate gland with no abnormalities noted on digital rectal examination.This study found measurable prostate specific antigen in a subset of male intersex patients that were comparable to controls matched for age and race. We recommend that patients with 46,XY disorder of sex development, reared as male, be screened for prostate cancer in a manner similar to men not affected by disorder of sex development.

The application of autologous myoblasts is an area of active research that may represent an improved alternative for the treatment of urinary incontinence. In this study we investigated the effectiveness of autologous myoblast injection for the treatment of urinary incontinence in children with classic bladder exstrophy.Seven boys and 1 girl with persistent urinary incontinence were entered in the study. All children had undergone staged bladder repair and bladder neck reconstruction, and 5 patients had received 1 to 3 transurethral injections of bulking agent. Autologous myoblasts were isolated from abdominal muscle biopsy and cultured before endourethral injection. After the procedure patients underwent pelvic floor electrical stimulation and continued pelvic floor exercises that had been started at least 1 year before injection. The clinical outcomes (based on a 24-hour voiding diary), and cystometric and urodynamic studies were evaluated. Followup ranged from 12 to 18 months (average 15.3).There was a significant, time dependent improvement in urinary continence. At final followup all 7 boys (88% of patients) were socially dry (daytime dryness more than 3 hours), including 3 (38%) who were completely dry. Urodynamic studies revealed an increase in mean bladder capacity (p0.001), detrusor leak point pressure (p0.001) and average maximum urinary flow (p0.01). All 7 boys (vs only 2 patients preoperatively) achieved normal voiding with demonstrable voiding detrusor contraction in the presence of a compliant stable bladder (p0.05).Our results suggest that transurethral autologous myoblast injection is a valid option for the treatment of structural urinary incontinence in children with classic bladder exstrophy. However, favorable preoperative urodynamic profiles and postoperative pelvic floor electrical stimulation may have contributed to the outcome in this series.

We compared the cellular and ultrastructural changes in the urethral wall following application of different hemostasis techniques in a rabbit model of hypospadias surgery.Rabbits were allocated into 5 groups. In group 1 animals underwent surgery without application of any hemostasis technique; in group 2 continuous penile tourniquet was applied for 30 minutes; in group 3, 3 intermittent periods of 10-minute penile tourniquet were applied with 3-minute intervals of reperfusion; in group 4 epinephrine was injected to maintain a 30-minute period of hemostasis; and in group 5 epinephrine vehicle (normal saline) was injected during the procedure. Early urothelium ultrastructural damage was studied 1 hour postoperatively with electron microscopy. Apoptotic damage and histopathological changes were determined 48 hours following the procedure. Late onset complications were assessed with retrograde urethrography and evaluation of tissue fibrosis at 8 weeks postoperatively.Electron microscope studies demonstrated urothelium ultrastructural damage in all hemostasis groups compared to controls. However, the changes were most prominent in group 4. The apoptosis index of urethral wall myocytes in groups 1 and 5 was significantly lower compared to other groups. Moreover, the number of apoptotic myocytes in epinephrine injected animals was significantly higher than in the continuous or intermittent tourniquet group as well as the normal saline injected group. At 8 weeks postoperatively collagen deposition in the urethral wall of rabbits in group 4 was higher than that in group 1. Although urethrocutaneous fistula was found in only 1 rabbit in group 4, the difference was not significant.Hemostasis techniques applied for maintaining a bloodless surgical field during hypospadias repair may lead to ischemia/reperfusion tissue damage in the urethral wall. Our findings suggest that epinephrine injection may result in more prominent cellular changes compared to tourniquet techniques. However, further experimental and human studies are required to draw a firm conclusion.

489 Background: Adrenal cancers have traditionally been treated using an open surgical approach. With advances in minimally invasive surgery (MIS), adrenal tumors have become more amenable to MIS resection. We report a study on the utilization and outcomes of surgery for adrenal cancers on a national level. Methods: Data on patients who underwent open, laparoscopic, or robotic adrenalectomy for adrenal cancer (ICD-9 code 194.0) from 2003-2013 were extracted from the nationally representative Premier Hospital Database. Surgeon specialty, patient demographics, hospital characteristics, intraoperative and perioperative data, and complications were compared. Data were analyzed using univariate and multivariate logistic regression analyses. Results: 4,781 adrenalectomies were performed for malignant disease. Surgery was more commonly performed in patients >50 years of age (83%), men (64%), and white race (80%). There was no significant difference in rate of adrenalectomy with regards to comorbidities, insurance status, teaching vs. non-teaching hospital, hospital bed size, or geographic region. Adrenalectomy for malignant disease was more commonly performed by non-urologists (66 vs. 34%; p=0.011). Among non-urologists, open surgery was most common followed by laparoscopic and robotic approaches (56.3% vs. 37.4% vs. 6.4%, respectively) as compared to urologists (48.8% vs. 38.4% vs. 12.9%, respectively). There was no difference in complication rate or operative time between surgeon types. On multivariate regression analysis, the best predictor of major complication was a Charlson Comorbidity Index (CCI) >2 (OR 6.1, 95% CI 2.9-12.5; p2 was associated with a higher rate of post-op complications, while surgical approach did not influence complication rate. These findings indicate that MIS can be performed safely for adrenal cancers. Prospective study of MIS for adrenal cancer is needed to evaluate its oncologic efficacy.

355 Background: Radical cystectomy is known to be associated with a relatively high incidence of postoperative morbidity and mortality. We evaluated the complication rates of a population-based cohort of patients with uncontrolled diabetes who underwent radical cystectomy. Methods: The data for this analysis was captured from the NIS (Nationwide Inpatient Sample) 2002-2009. Among patients who underwent radical cystectomy (ICD-9 diagnosis code 188.x and 57.71), we selected those with uncontrolled diabetes, which is defined by the billing physician (ICD-9 diagnosis code 250.02) and compared to patients without diabetes. We also identified postoperative complications. Patient socio-demographic characteristics, principal and secondary diagnoses, principal and secondary procedures, comorbid diseases, disposition of patient at discharge, hospital length of stay, and hospital cost for our analysis. A chi-square test was employed for categorical variables and Student’s t-test for continuous variables. A multivariable logistic regression analysis was also employed with computing OR and 95% CI. P

Purpose: We report the results of corporeal tunica vaginalis free graft for single stage correction of severe chordee in children with proximal hypospadias. Materials and Methods: A total of 18 children with proximal hypospadias and severe chordee underwent tunica vaginalis free graft for correction of chordee and urethroplasty. The graft was anastomosed to the ventral surface of the corpus cavernosum to correct severe penile curvature without dorsal plication of the corpus cavernosum. Single stage urethroplasty was then performed. In cases where the urethral plate was too short for urethral reconstruction a transverse preputial island flap was used for single stage urethroplasty. If the incised urethral plate did not have a well vascularized and supple appearance or the prepuce was not sufficient for phallic coverage, we transected the urethral plate and staged urethroplasty was done. Results: Mean followup was 27.5 months. In 13 patients ventral chordee was corrected using tunica vaginalis free graft without transecting the urethral plate, and urethroplasty was performed in 1 stage. In 3 patients the urethral plate was transected and a transverse preputial island flap was used for single stage urethroplasty. In 2 patients the urethral plate was transected and interposed with dermal graft and tunica vaginalis free graft, followed by staged urethroplasty. There was mild residual chordee in 2 cases. One child had a urethrocutaneous fistula at 2 weeks postoperatively, and 1 presented with obstructive pattern uroflowmetry due to meatal stenosis. Conclusions: In this preliminary report the majority of patients with proximal hypospadias and severe chordee were successfully treated with single stage repair using tunica vaginalis free graft for correction of severe chordee.

We report the evolution of endoscopic treatment of ectopic ureteroceles from the unroofing technique to a novel approach using concomitant ureterocele double puncture and intraureterocele fulguration. We also compare the results of different endoscopic modalities at a single center.We reviewed the records of 46 children with ectopic ureteroceles who were treated endoscopically between 1995 and 2005. The patients were divided into 2 main groups. Group 1 included 17 patients who underwent common endoscopic treatments, including ureterocele incision (4 patients), single ureterocele puncture (4), and single puncture with insertion of a Double-J stent (9). Group 2 included 29 children who underwent ureterocele double puncture and fulguration of the anterior and posterior walls of the collapsed ureterocele after insertion of a Double-J stent into both punctured sites. We also managed concomitant vesicoureteral reflux by endoscopic injection of tricalcium phosphate ceramic into the subureteral region.Total success rates in group 1 were 0%, 25% and 33% in patients who underwent ureterocele incision, single ureterocele puncture and single puncture with insertion of a stent, respectively. Total success rate in group 2 was 90% (p0.05). New onset vesicoureteral reflux developed in 8 patients (47%) in group 1, of which 6 were in ureterocele moieties, and in 8 patients (28%) in group 2, with none in a ureterocele moiety (p0.01). A total of 13 patients (76%) in group 1 required open surgical intervention, compared to 3 (10%) in group 2 (p0.05).This new endoscopic approach is highly effective in the treatment of children with ectopic ureteroceles.

Objectives To determine the time-dependent regeneration of different cellular components in the bladder acellular matrix graft (BAMG) and the involvement of hematopoietic stem cells in BAMG vascular regeneration. Methods and Materials Thirty-three male Sprague Dawley rats underwent partial cystectomy and the acellular matrices were grafted to the remaining host bladder. At 4, 7, 14, 30, 60, 90, and 180 d after grafting, animals were sacrificed and their bladders were excised and paraffin-embedded. Tissue sections were stained for determination of CD3, CD20, CD34, CD31, CD68, smooth muscle cell (SMC) α-actin, and neurofilament protein as well as elastin fibers and collagen typing. Cystometric evaluation of grafted bladders was also performed 3 mo after procedure. Results In acellular matrices, there was no expression of cellular markers and type-1 collagen fibers were predominant. One month after surgery, all grafted matrices were completely lined with urothelium. Polymorphonuclear cells and lymphocytes densely infiltrated BAMG during the first 2 wk after grafting; however the inflammation resolved by the first post-surgical mo. CD34+ endothelial progenitor cells (EPCs) were found in all grafts 4 d after surgery. The number of CD34+ cells increased continuously and peaked 2 mo after grafting. The increment in number of CD31+ microvessels in grafted matrices followed that of CD34+ cells and reached 144.5% of control values at third post-surgical mo. The mean number of CD34+ and CD31+ cells returned to control ranges by 6 mo after grafting. Expression of SMC α-actin was first visualized on day 4 and α-actin intensity reached to control values 6 mo after grafting. Neural elements appeared 1 wk after grafting and just 60% of normal intensity was achieved by the sixth post-surgical mo; however complete nerve bundles were found in all grafted matrices after 1 mo. Cystometric studies revealed higher bladder capacity and compliance but lower maximum intravesical pressure in grafted bladders in comparison with controls, 3 mo after surgery. Conclusions Our results demonstrate the effective cellular regeneration in BAMG and propose a considerable role for the CD34+ EPCs in the neo-vasculogenesis of the grafts.

Purpose The application of muscle derived stem cells is an area of active research that may represent an improved alternative for the treatment of urinary incontinence. We investigated the effectiveness of autologous muscle precursor cell transplantation as a treatment option for urinary incontinence due to sphincter incompetence in children with the bladder exstrophy/epispadias complex (BEEC). Material and Methods Twelve patients with BEEC (11 boys and 1 girl) with persistent urinary incontinence entered the study. All patients had undergone staged bladder repair and bladder neck reconstruction and all of them (except 1) had received 1-3 transurethral injections of bulking agents with minimal effects. Muscle precursor cells were isolated from each patient's abdominal skeletal muscle, and cultured before endourethral injection. The effectiveness of treatment was evaluated with particular emphasis on clinical outcome (based on a 24-hour voiding diary), cystometric and urodynamic studies. Results Eight Patients had a mean follow-up of 11.3 (from 8 to 14 months), The remaining 4 cases with less than 6 months follow-up are not presented in this data. There was a significant time-dependent improvement in patients' urinary continence. At the final follow-up, all 7 (88%) boys were socially dry (day-time dryness >3 hours) – including 3 (38%) completely dry. Urodynamic studies revealed an increase in mean bladder capacity (p Conclusions Autologous myoblast transplantation may be a safe, effective and attractive alternative treatment option for structural urinary incontinence, with possible ability for functional regeneration of urethral sphincter.

Purpose To evaluate the efficacy of antioxidant administration starting at the onset of fever detection in reducing renal scars in an animal model of acute pyelonephritis (APN), and comparing the effectiveness of Allopurinol and vitamin E in the prevention of renal scaring. Material and methods Twenty male Wister rats divided to 4 groups. Group 1 to 3 underwent direct inoculation of 0.1 ml of E-coli suspension into the parenchyma of the right kidney. Group 4 received 0.1 ml of saline. Group I were treated with ceftriaxone for 5 days, starting 3 days after bacterial inoculation; group II & III received Allopurinol and vitamin E as soon as animal's body temperature rose above 37°C. followed by the administration of daily ceftriaxone 3 says after inoculation for five days. Six weeks later all rats were sacrificed; both kidneys examined histopathologically for scarring. Renal cell apoptosis index was determined in paraffin embedded kidneys (using TUNEL assay). Results The fever started 4.6±1.3 hours (measured by continues digital rectal thermometer) after inoculation in all rats. Histopathologically, subsequent scar formation had occurred in all rats of the group 1 which didn't receive antioxidant agents. The inflammation and fibrosis was mildest in group 2 and 3 (Allopurinol and Vitamin E); whereas it was significantly lower in group 3 than in group 2 (p Conclusions Initiation of the antioxidant agents following detection of fever can be effective in reducing the severity of scarring in APN. Comparing the total scar scores in experimental groups, vitamin E has more protective effect against renal damage due to APN than Allopurinol.

Purpose Incontinence is still a challenging problem in children with the exstrophy-epispadias complex (EEC) and satisfactory results using conventional management has not yet been achieved. Recent advances in cell therapy and tissue engineering techniques have been promising. We investigated autologous, heterotopic targeted muscle precursor cell donation in the recovery of external urethral sphincter function in children with the EEC and urinary incontinence (UI). Material and methods Following extensive animal model studies at our laboratory and approval of the study protocol by the local bioethical committee, 5 children (4 boys and 1 girl, mean age: 9.6 years) with severe urinary incontinence due to exstrophy/epispadias were enrolled in May 2006. Autologous skeletal muscle precursor cells were obtained from the pelvic floor and cultured in vitro for cell expansion. Before transurethral injection of the cells into the sphincter, microbiological control and karyotyping were performed. The continence status of the patients prior to and following satellite injection was evaluated according to incontinence score, biochemical parameters, urodynamic studies and changes in quality of life. Results An average of 0.2-8x10 7 cells (>70% Pax7+/ MyoD+/ Desmin+) were obtained after a mean period of 18 days and implanted uneventfully. Neither microbial infection nor chromosomal change was detected in the specimens prior to cell implantation. During 4 months follow-up the incontinence score improved in 4 patients but 1 female patient with a very short urethral length and fibrosis had no change in continence status. Conclusions This data confirms the potential application and outcome of satellite cell transplantation in functional reconstruction in UI by compensating for the cell loss. Although it can provide a new therapeutic approach for incontinence therapy with a reasonable success rate, long-term follow-up is still required.

Background The presence of lymph nodes (LN) within the prostatic anterior fat pad (PAFP) has been reported in several recent reports. These PAFP LNs rarely harbor metastatic disease, and the characteristics of patients with PAFP LN metastasis are not well-described in the literature. Our previous study suggested that metastatic disease to the PAFP LN was associated with less severe oncologic outcomes than those that involve the pelvic lymph node (PLN). Therefore, the objective of this study is to assess the oncologic outcome of prostate cancer (PCa) patients with PAFP LN metastasis in a larger patient population. Methods Data were analyzed on 8800 patients from eleven international centers in three countries. Eighty-eight patients were found to have metastatic disease to the PAFP LNs (PAFP+) and 206 men had isolated metastasis to the pelvic LNs (PLN+). Clinicopathologic features were compared using ANOVA and Chi square tests. The Kaplan-Meier method was used to calculate the time to biochemical recurrence (BCR). Results Of the eighty-eight patients with PAFP LN metastasis, sixty-three (71.6 %) were up-staged based on the pathologic analysis of PAFP and eight (9.1 %) had a low-risk disease. Patients with LNs present in the PAFP had a higher incidence of biopsy Gleason score (GS) 8–10, pathologic N1 disease, and positive surgical margin in prostatectomy specimens than those with no LNs detected in the PAFP. Men who were PAFP+ with or without PLN involvement had more aggressive pathologic features than those with PLN disease only. However, there was no significant difference in BCR-free survival regardless of adjuvant therapy. In 300 patients who underwent PAFP LN mapping, 65 LNs were detected. It was also found that 44 out of 65 (67.7 %) nodes were located in the middle portion of the PAFP. Conclusions There was no significant difference in the rate of BCR between the PAFP LN+ and PLN+ groups. The PAFP likely represents a landing zone that is different from the PLNs for PCa metastasis. Therefore, the removal and pathologic analysis of PAFP should be adopted as a standard procedure in all patients undergoing radical prostatectomy. Electronic supplementary material The online version of this article (doi:10.1186/s12894-015-0070-1) contains supplementary material, which is available to authorized users.