Favorable risk factors in patients with positive surgical margin after robot-assisted radical prostatectomy.

INTRODUCTION: Positive surgical margin (PSM) has classically been associated with biochemical recurrence (BCR) following radical prostatectomy (RP) and immediate adjuvant radiotherapy has been advocated based on two large randomized prospective clinical studies. However, a significant percentage of patients with PSM never experience BCR. This study evaluated factors potentially affecting risk of BCR among the patients with PSM after robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: From a prospectively maintained database, 699 patients with localized prostate cancer who underwent a RARP without any adjuvant therapy were identified. Median follow up was 46.0 months. To determine the pathologic and clinical factors that influenced BCR, univariate and multivariate analyses using the Cox proportional hazards model were performed. BCR-free survival curves were estimated with Kaplan-Meier method. RESULTS: Surgical margins were positive in 115 patients (16.5%), of whom 23 (20%) had BCR. In the univariate analyses, serum PSA level, surgical Gleason score (GS), and non-organ confined disease were significantly associated with BCR in men with PSM. Multivariate Cox analysis showed that BCR was significantly associated with PSA (p = 0.011), and the surgical GS (p = 0.008). In patients with lower PSA cutoff (5.3 ng/mL), GS ≤ 7, and organ-confined disease, there were no BCR. CONCLUSIONS: In this study, we identified favorable risk factors in patients with PSM following RARP. The results suggest that immediate adjuvant therapy for PSM may not be necessary in men with Gleason score 7 or less, organ-confined disease, and low preoperative PSA.

Inadvertent foley catheterization of the ureter.

We present a case of an 83-year-old woman with multiple sclerosis and chronic indwelling urethral catheter who was found to have a ureteral injury after inadvertent placement of a foley catheter into the proximal right ureter. Cystoscopy and retrograde ureteral stenting was attempted, but unsuccessful. The patient ultimately underwent successful antegrade ureteral stenting and nephrostomy placement. We review the limited literature on the topic of aberrant foley catheter placement into the ureter.

Prostate-specific antigen density toward a better cutoff to identify better candidates for active surveillance.

OBJECTIVE: To investigate the impact of prostate-specific antigen density (PSAD) on existing prostate cancer (PCa) active surveillance (AS) protocols. METHODS: Prospectively maintained database on men with PCa who underwent radical prostatectomy was reviewed retrospectively. Demographic data and pathologic characteristics of patients who fulfilled the AS inclusion criteria under the National Comprehensive Cancer Network (NCCN), Prostate Cancer Research International Active Surveillance (PRIAS), and University of California, San Francisco (UCSF) guidelines were examined. RESULTS: Of 930 patients, 231, 280, and 325 fulfilled the NCCN, PRIAS, and UCSF AS criteria, respectively. The frequencies of advanced disease on surgical pathology (upstaging and/or upgrading) were 31.6% (NCCN), 35.4% (PRIAS), and 34.2% (UCSF) of the study cohorts. PSAD was significantly higher in patients with advanced disease compared with that in patients with nonadvanced disease in all 3 AS schemas. Modifying the PRIAS and UCSF criteria using the NCCN's lower PSAD cutoff of 0.15 ng/mL(2) decreased the rates of the advanced disease significantly to 33.5% and 31.4%, respectively. Using the receiver operating characteristic curve analysis, the optimal PSAD cutoff level for the prediction of advanced disease was 0.085 ng/mL(2) (sensitivity/specificity of 76.7%/50.6% in NCCN and 75.6%/49.7% in PRIAS). CONCLUSION: Among patients with low-risk PCa who underwent radical prostatectomy, PSAD is a predictor of advanced disease at the time of surgery. Adopting a lower PSAD threshold of 0.085 ng/mL(2) decreased the risk of the advanced disease to 17.5%-21.7%. Therefore, PSAD should be part of all AS guidelines.

Concern for overtreatment using the AUA/ASTRO guideline on adjuvant radiotherapy after radical prostatectomy.

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 < 6.35 ng/ml and GS ≤ 7, only 3 developed BCR. CONCLUSIONS: Of the 163 patients who qualified for ART based on the current AUA/ASTRO guideline, only 27 (16.6%) developed BCR and received SRT. Therefore, using ART following RP using the current recommendation may be an overtreatment in an overwhelming majority of the patients.

Comprehensive analysis of sexual function outcome in prostate cancer patients after robot-assisted radical prostatectomy.

PURPOSE: The recovery of potency following radical prostatectomy is complex and has a very wide range. In this study, we analyzed in detail the precise pattern of recovery of potency following robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Prospectively collected database of patients with a minimum follow-up of 1 year after RARP were evaluated retrospectively. Of 503 patients identified, 483 patients completed the sexual health inventory for men (SHIM) preoperatively and postoperatively every 3 months for the first 12 months. Overall potency, usage of phosphodiesterase type-5 (PDE-5) inhibitors, and return to baseline erectile function were evaluated. Potency was defined as having erection that is sufficient for sexual intercourse more than 50% of attempts, while quality potency was defined as being potent without the use of PDE-5 inhibitors. RESULTS: Preoperatively, the overall potency and quality potency rate were 67.1% and 48.1%, respectively. Postoperatively, the overall potency rate was 61.4%, while the quality potency rate was 37.2%. In multivariate regression analysis, independent predictors of potency recovery were young age (<60), preoperative potency status, and bilateral preservation of neurovascular bundles (NVBs). In men with SHIM>21, the overall potency and quality potency rate were 79.7% and 41.2%, respectively. More importantly, only 21.4% of the men with normal erection preoperatively (SHIM>21) returned to baseline erectile function (SHIM>21) 12 months after surgery. CONCLUSIONS: This study indicates that young age (<60), preoperative potency, and bilateral preservation of NVBs were positive predictors of potency recovery following RARP. However, an overwhelming majority of men experience a deterioration in the overall quality of erection after RARP.

Absence of prostatic growth in large cohort of adult female patients with congenital adrenal hyperplasia.

PURPOSE: In girls with congenital adrenal hyperplasia the degree to which excess androgen exposure leads to the development of prostatic tissue is largely uncharacterized, except in rare case reports of prostatic growth and adenocarcinoma. Such growth yields concern for future malignant degeneration. MATERIALS AND METHODS: Chart review identified 43 adult women with congenital adrenal hyperplasia who had been longitudinally followed from birth, of whom 11 were available for history and physical examination, laboratory testing for androgen metabolites, and pelvic magnetic resonance imaging. RESULTS: Periurethral thickening was noted on digital rectal examination in 1 patient with increased 17-hydroxyprogesterone and tissue analogous to prostatic tissue was impalpable in the remaining 10. Prostate specific antigen was 0.2 ng/ml in another patient with notably increased testosterone, androstenedione, dihydrotestosterone and 17-hydroxyprogesterone, and was less than 0.1 ng/ml in the remaining patients. Magnetic resonance imaging revealed an absence of definitive prostatic tissue in all 11 patients despite evidence of genitourinary masculinization in all. Of the 11 women 7 had marked androgen excess. CONCLUSIONS: Despite androgen excess and genitourinary masculinization in patients with congenital adrenal hyperplasia, as well as case reports citing evidence of prostatic tissue and adenocarcinoma in these women, our study successfully documents the absence of notable prostatic growth in these patients. A better understanding of the timing and factors involved in prostatic growth would aid in identifying the degree to which adult women with congenital adrenal hyperplasia are at risk for adverse sequelae of Skene gland growth.

Cholestasis induced nephrotoxicity: the role of endogenous opioids.

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 20mg/kg of naltrexone or its vehicle, for 7days after BDL. In groups 3 and 4, BDL or Sham rats received no injections. In group 5, normal rats received subcutaneous injections of 20mg/kg/day of naltrexone for 7days. At the 7th day, 24h urine was collected to measure urinary N-acetyl-beta-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.

miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth.

Androgen receptor (AR)-mediated oncogenic pathways have not been fully elucidated. In this study, we used high-throughput microarray analysis on two AR-positive prostate cancer (CaP) cell lines to identify 16 AR-responsive microRNAs (miRNA). We focused on miR-21 because of its previously reported oncogenic activity in other cancers. We show androgen-induced AR binding to the defined miR-21 promoter, miPPR-21, suggesting direct transcriptional regulation. Inhibition of miR-21 diminished androgen-induced CaP cell proliferation, providing new evidence that miRNAs can contribute to androgen-driven cell growth. Elevated expression of miR-21 enhanced CaP tumor growth in vivo and, surprisingly, was sufficient for androgen-dependent tumors to overcome castration-mediated growth arrest. Thus, elevated miR-21 expression alone is sufficient to impart castration resistance. Moreover, quantitative reverse transcription-PCR analysis revealed elevated miR-21 expression in CaP when compared with adjacent normal tissue. These results suggest that miR-21 may contribute to CaP pathogenesis.

Bladder neck transection for intractable pediatric urinary incontinence.

PURPOSE: We report the indications, technique and outcome of a large series of children who underwent bladder neck transection for intractable urinary incontinence. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Complications of complex lower urinary tract reconstruction in patients with neurogenic versus nonneurogenic bladder--is there a difference?

PURPOSE: The complications of lower urinary tract reconstruction have been well documented in children with neurogenic bladders. While most series include small numbers of nonneurogenic diagnoses, this group is typically underrepresented. Despite a number of fundamental anatomical and functional differences, a direct comparison of surgical complications of lower urinary tract reconstruction in patients with neurogenic vs nonneurogenic bladders has not been performed. MATERIALS AND METHODS: We identified patients undergoing lower urinary tract reconstruction incorporating enterocystoplasty from 1996 to 2006. We performed a retrospective review of operative notes and medical records of patients who met inclusion criteria. Patients were divided into a neurogenic group and a nonneurogenic group based on the underlying diagnosis. The 2 groups were compared with respect to demographics, historical data, operative techniques, perioperative morbidity, long-term complications and need for surgical revision. RESULTS: Of the 127 patients who met inclusion criteria 72 were assigned to the nonneurogenic group and 55 to the neurogenic group. Overall the rates of significant perioperative morbidity (39%), long-term complications (54%) and need for surgical revision (39%) were substantial. The rates of catheter related complications, rehospitalization for dehydration and spontaneous bladder rupture were higher in the neurogenic group (p <0.05). CONCLUSIONS: Reconstruction of the lower urinary tract in children is associated with a considerable rate of complications and need for surgical revision regardless of whether the bladder is neurogenic or nonneurogenic. Children with neurogenic bladders are more prone to spontaneous rupture, catheter mishaps and early rehospitalization for dehydration.

Prostate screening in patients with 46,XY disorders of sex development--is it necessary?

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Transurethral autologous myoblast injection for treatment of urinary incontinence in children with classic bladder exstrophy.

PURPOSE: 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. MATERIALS AND METHODS: 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). RESULTS: 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 (p <0.001), detrusor leak point pressure (p <0.001) and average maximum urinary flow (p <0.01). All 7 boys (vs only 2 patients preoperatively) achieved normal voiding with demonstrable voiding detrusor contraction in the presence of a compliant stable bladder (p <0.05). CONCLUSIONS: 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.

Role of endogenous cannabinoids in ischemia/reperfusion injury following testicular torsion in rats.

OBJECTIVES: The role of endogenous cannabinoids in ischemia/reperfusion induced germ cell apoptosis in rats was investigated. METHODS: Baseline group was for basal normal values. The Sham operated group served as a control group. The torsion/detorsion (T/D) group underwent torsion (1 h) and detorsion; AN1, AN2, and AN3 groups received anandamide (10 mg/kg) 30 min before torsion, 30 min after torsion, and just after detorsion, respectively. In the AM251 group, AM251 (0.5 mg/kg) was injected 45 min before torsion and in the AN/AM group, AM251 and anandamide were injected 45 and 30 min before torsion, respectively. Lipid peroxidation, antioxidant enzymes, and germ cell apoptosis was determined. RESULTS: Malondialdehyde (MDA) levels in the T/D group were significantly higher than the control group. Moreover, MDA values in the AN1, AN2, and AN3 groups were significantly lower than T/D. There were significant decreases in catalase and superoxide dismutase activities in the T/D group versus the control group. These values in the AN1, AN2, and AN3 groups were significantly higher than T/D. It was also shown that MDA levels in the AN/AM group were significantly higher than the AN1 group. In the AN/AM group, catalase and superoxide dismutase activities were significantly lower versus the AN1 group. The mean germ cell apoptosis scores in all animals with testicular T/D were significantly higher than the control group. There was no difference between the apoptotic indices in the AN1, AN2, AN3, and T/D groups. Apoptosis scores in AM251 and AN/AM were significantly higher compared with the T/D and AN1 groups. CONCLUSIONS: Although anandamide increased antioxidant markers, it failed to reduce germ cell apoptosis. AM251 worsened the antioxidant defense system, which is reflected as higher germ cell apoptosis.

Dose-dependent modulation of systemic lipid peroxidation and activity of anti-oxidant enzymes by vitamin E in the rat.

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.

Protective effects of sildenafil administration on testicular torsion/detorsion damage in rats.

PURPOSE: We assessed the effectiveness of sildenafil administration during ischemic period in a rat model of testicular torsion/detorsion (T/D). MATERIAL AND METHODS: Sprague-Dawley rats were divided into four groups (n = 10). In those animals that underwent T/D, right testes were rotated 720 degrees for 1 h. Base line group was for basal normal values. Sham operated group was served as a control group. T/D group underwent 1 h testicular torsion. Sildenafil group received sildenafil (0.7 mg/kg) intraperitoneally 30 min after initiation of ischemic period. For measurement of lipid peroxidation and antioxidant enzyme activities, right testes of five animals in each group were excised after 4-h reperfusion. Germ cell apoptosis indices were determined 24 h following detorsion in right testes of remaining five animals in each group. RESULTS: Malondialdehyde (MDA) levels in T/D group were significantly higher versus control and base line groups. Moreover, testicular MDA values in sildenafil group were significantly lower than T/D. There were also significant decreases in catalase and superxide dismutase activities in T/D group compared with control and base line groups. These values were significantly higher in sildenafil group versus T/D. Germ cell apoptosis indices were significantly higher in both groups that experienced T/D in comparison to control and base line groups; however, sildenafil treatment significantly reduced the apoptosis in sildenafil group compared with T/D group. CONCLUSION: Sildenafil administration during testicular torsion decreased ischemia/reperfusion cellular damage. The results of biochemical studies suggest that, reduction of oxidative stress by sildenafil may have a major role in its cytoprotective effects.

Comparison of different techniques for hemostasis in a rabbit model of hypospadias repair.

PURPOSE: We compared the cellular and ultrastructural changes in the urethral wall following application of different hemostasis techniques in a rabbit model of hypospadias surgery. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Salutary effects of N-acetylcysteine on apoptotic damage in a rat model of testicular torsion.

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.

Proximal hypospadias with severe chordee: single stage repair using corporeal tunica vaginalis free graft.

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.

Evolution of endoscopic management of ectopic ureterocele: a new approach.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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% (p<0.05). 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 (p<0.01). A total of 13 patients (76%) in group 1 required open surgical intervention, compared to 3 (10%) in group 2 (p<0.05). CONCLUSIONS: This new endoscopic approach is highly effective in the treatment of children with ectopic ureteroceles.

Time-dependent neovasculogenesis and regeneration of different bladder wall components in the bladder acellular matrix graft in rats.

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) alpha-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 alpha-actin was first visualized on day 4 and alpha-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.