Treatment utilization and overall survival in patients receiving radical nephroureterectomy versus endoscopic management for upper tract urothelial carcinoma: evaluation of updated treatment guidelines.

PURPOSE: While radical nephroureterectomy (RNU) is the gold standard treatment for upper tract urothelial carcinoma (UTUC), select patients may benefit from endoscopic treatment (ET). European Association of Urology guidelines recommend ET for patients with low-risk (LR) disease: unifocal, < 2 cm, low-grade lesions without local invasion. To inform the utility of ET, we compare the overall survival (OS) of patients receiving ET and RNU using current and previous guidelines of LR disease. MATERIALS AND METHODS: Patients with non-metastatic, cT1 or less UTUC diagnosed in 2004-2012 were collected from the National Cancer Database. OS was analyzed with inverse probability of treatment weighted Cox proportional hazard regression. Analyses were conducted for LR disease under updated (size < 2 cm) and previous guidelines (size < 1 cm). RESULTS: Patients who were older, healthier, and treated at an academic facility had higher odds of receiving ET. In 851 identified patients with LR disease, RNU was associated with increased OS compared with ET (p = 0.006); however, there was no difference between ET and RNU (p = 0.79, n = 202) under the previous guidelines (size < 1 cm). In, otherwise, LR patients, the largest tumor size with no difference between ET and RNU was ≤ 1.5 cm (p = 0.07). CONCLUSIONS: RNU is associated with improved survival when compared with ET in the management of LR UTUC using current guidelines with a size threshold of < 2 cm. In appropriately selected LR patients, we find no difference between RNU and ET up to a tumor size of ≤ 1.5 cm. However, in the absence of prospective studies, the usage of ET is best left up to clinician discretion.

Adrenalectomy for benign and malignant disease: utilization and outcomes by surgeon specialty and surgical approach from 2003-2013.

INTRODUCTION: Data on the utilization of open, laparoscopic and robotic adrenalectomy on a national level is limited. MATERIALS AND METHODS: Data on patients who underwent open, laparoscopic, or robotic adrenalectomy for benign or malignant disease in the US from 2003-2013 were extracted using ICD-9 codes from the Premier Hospital Database. Surgeon specialty, patient demographics, hospital characteristics, and complications were compared. Data were analyzed using univariate and multivariable logistic regression analyses. RESULTS: A total of 8,831 adrenalectomies were performed for benign and malignant tumors. There was no significant difference in rate of adrenalectomy with regards to comorbidities, insurance status, or hospital characteristics. Non-urologists performed adrenalectomy more often for both benign (57% versus 43%; p = 0.011) and malignant disease (66% versus 34%; p = 0.011). Across all indications, non-urologists performed open surgery most often followed by laparoscopic and robotic approaches (56.3% versus 37.4% versus 6.4%, respectively), compared to urologists (48.8% versus 38.4% versus 12.9%, respectively). Overall, urologists were more likely to use laparoscopic or robotic approaches (p = 0.001). There was no difference in complication rates or operative times between surgical specialties or by surgeon/hospital case volume. On multivariable regression analysis, the best predictor of major complication was a Charlson Comorbidity Index (CCI) ≥ 2 (OR 3.9, 95%CI 2.1-7.1; p = < 0.001). Compared to open surgery, laparoscopy had significantly reduced odds of major complication (OR 0.6, 95%CI 0.3-0.9; p = 0.03). Patients undergoing robotic procedures had the shortest length of stay. CONCLUSION: In this retrospective study, adrenalectomy was more commonly performed by non-urologists via an open approach. Patients with CCI ≥ 2 were more likely to have postoperative complications while surgeon volume, hospital volume, and surgical approach did not influence complication rates.

Molecular effects of genistein on male urethral development.

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 <0.008). Among the most affected were hormonally regulated genes, including IGFBP-1, Kap and Rhox5. Differentially expressed genes were grouped into functional pathways of cell proliferation, adhesion, apoptosis and tube morphogenesis (p <0.0001), and were enriched for members of the MAPK (p <0.00001) and TGF-ß (p <0.01) signaling cascades. Differentially expressed genes preferentially contained ELK1, Myc/Max, FOXO, HOX and ER control elements. The MAPK pathway was active, and its upstream genistein affected tyrosine kinase receptors Ntrk1 and Ntrk2 were present in the developing male urethra. CONCLUSIONS: Gestational exposure to genistein contributes to hypospadias by altering pathways of tissue morphogenesis, cell proliferation and cell survival. In particular, genes in the MAPK and TGF-ß signaling pathways and those controlled by FOXO, HOX and ER transcription factors are disrupted.

Oligodendroglial and pan-neural crest expression of Cre recombinase directed by Sox10 enhancer.

Utilizing a recently identified Sox10 distal enhancer directing Cre expression, we report S4F:Cre, a transgenic mouse line capable of inducing recombination in oligodendroglia and all examined neural crest derived tissues. Assayed using R26R:LacZ reporter mice expression was detected in neural crest derived tissues including the forming facial skeleton, dorsal root ganglia, sympathetic ganglia, enteric nervous system, aortae, and melanoblasts, consistent with Sox10 expression. LacZ reporter expression was also detected in non-neural crest derived tissues including the oligodendrocytes and the ventral neural tube. This line provides appreciable differences in Cre expression pattern from other transgenic mouse lines that mark neural crest populations, including additional populations defined by the expression of other SoxE proteins. The S4F:Cre transgenic line will thus serve as a powerful tool for lineage tracing, gene function characterization, and genome manipulation in these populations.

Trends in usage of cytoreductive partial nephrectomy and effect on overall survival in patients with metastatic renal cell carcinoma.

PURPOSE: Cytoreductive radical nephrectomy (cRN) improves survival in select patients with metastatic renal cell carcinoma (mRCC). It is unclear, however, whether cytoreductive partial nephrectomy (cPN) compromises oncologic efficacy. We evaluated trends in utilization of cPN and compared overall survival (OS) in patients who underwent cRN or cPN for mRCC. MATERIALS AND METHODS: We queried the National Cancer Database from 2006 to 2013 and identified patients who underwent cPN and cRN for mRCC. We analyzed rates of cPN over time. Logistic regression identified predictors of cPN. We matched patients based on propensity score for treatment. We used matched Kaplan-Meier survival analyses to compare OS, stratified by tumor size. We used multivariable Cox proportional hazards models to determine the effect of cPN and cRN on OS. RESULTS: A total of 10,144 patients met inclusion criteria, with 9,764 (96.2%) undergoing cRN and 381 (3.8%) undergoing cPN. Rates of cPN increased over time from 1.8% to 4.3% over the study period. Treatment at an academic/research facility, papillary and chromophobe histology, and more recent year of treatment were associated with increased odds of cPN. In a matched survival analysis, cPN was associated with improved OS compared with cRN (log rank, P = 0.001). This effect was limited to primary tumors<4cm. In a propensity-score adjusted multivariable Cox model, cPN was associated with improved OS (hazard ratio = 0.81; 95% CI: 0.71-0.93; P = 0.002). CONCLUSIONS: The use of cPN in patients with mRCC is increasing. cPN is associated with improved OS in patients with mRCC, although this effect is limited to patients with primary tumors<4cm.

Endoureterotomy for treatment of primary obstructive megaureter in children.

PURPOSE: To describe a new approach to the treatment of primary obstructive megaureter (POMU) using endoscopic endoureterotomy. The results obtained with this technique are reviewed with long-term follow-up. PATIENTS AND METHODS: A total of 47 children (mean age 3.7 years) with 52 POMU units and a history of failed conservative management underwent endoureterotomy of obstructed juxtavesical and intramural ureter. A 3F Double-J ureteral stent was introduced up to the obstructed segment of ureter. Then a zebra catheter was inserted into the affected ureter beside the stent, followed by a neonatal-size ureteroscope. Following delineation of the length of the narrowed portion of the ureter, a guidewire with a plastic sheath replaced the zebra catheter. A longitudinal incision was made through the detrusor muscle at the 6 o'clock position, leaving the bladder adventitia untouched. The Double-J stent was left in place, while its distal tip was fixed by long nylon suture and single knot to the external genitalia to permit easy removal 1 week after the procedure. RESULTS: With a mean follow-up of 39 months (range 14-62 months), no leakage, ureteral-orifice obstruction, or reflux was observed. The postoperative success rate was 90% (47 of 52 ureters), defined as resolution or decrease in hydroureteronephrosis and improvement or stability of renal function determined by renal scan. In 37 ureterorenal units (71%), there was complete resolution of hydroureteronephrosis. CONCLUSIONS: On the basis of previous studies demonstrating the value of endoureterotomy with stenting for the treatment of benign ureteral strictures in adults, we developed a modified endoscopic approach for the treatment of POMU and applied this technique in meticulously selected cases. Our results showed that this approach is a valid option for the treatment of children with POMU.

Predicting clinically significant prostate cancer based on pre-operative patient profile and serum biomarkers.

Previous studies have reported association of multiple preoperative factors predicting clinically significant prostate cancer with varying results. We assessed the predictive model using a combination of hormone profile, serum biomarkers, and patient characteristics in order to improve the accuracy of risk stratification of patients with prostate cancer. Data on 224 patients from our prostatectomy database were queried. Demographic characteristics, including age, body mass index (BMI), clinical stage, clinical Gleason score (GS) as well as serum biomarkers, such as prostate-specific antigen (PSA), parathyroid hormone (PTH), calcium (Ca), prostate acid phosphatase (PAP), testosterone, and chromogranin A (CgA), were used to build a predictive model of clinically significant prostate cancer using logistic regression methods. We assessed the utility and validity of prediction models using multiple 10-fold cross-validation. Bias-corrected area under the receiver operating characteristics (ROC) curve (bAUC) over 200 runs was reported as the predictive performance of the models. On univariate analyses, covariates most predictive of clinically significant prostate cancer were clinical GS (OR 5.8, 95% CI 3.1-10.8; P < 0.0001; bAUC = 0.635), total PSA (OR 1.1, 95% CI 1.06-1.2; P = 0.0003; bAUC = 0.656), PAP (OR 1.5, 95% CI 1.1-2.1; P = 0.016; bAUC = 0.583), and BMI (OR 1.064, 95% C.I. 0.998, 1.134; P < 0.056; bAUC = 0.575). On multivariate analyses, the most predictive model included the combination of preoperative PSA, prostate weight, clinical GS, BMI and PAP with bAUC 0.771 ([2.5, 97.5] percentiles = [0.76, 0.78]). Our model using preoperative PSA, clinical GS, BMI, PAP, and prostate weight may be a tool to identify individuals with adverse oncologic characteristics and classify patients according to their risk profiles.

Paradoxical dose- and time-dependent regulation of superoxide dismutase and antioxidant capacity by vitamin E in rat.

BACKGROUND: Previous data about the regulation of SOD activity as the key part of the endogenous antioxidant system by vitamin E is conflicting. METHODS: 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. RESULTS: We observed a linear increase in SOD activity in the first dosing group, which was significant (p<0.05) 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. CONCLUSIONS: 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.

Effect of Uncontrolled Diabetes on Outcomes After Cystectomy in Patients With Bladder Cancer: A Population-Based Study.

BACKGROUND: We evaluated the complications, mortality, hospital length of stay (LOS), and cost for patients with diabetes undergoing radical cystectomy (RC). MATERIALS AND METHODS: Data were extracted from the National (Nationwide) Inpatient Sample for 2001 to 2012 using the "International Classification of Diseases, Ninth Revision, Clinical Modification" codes for patients with uncontrolled diabetes (UD) (patients with diabetes receiving treatment that did not keep the blood glucose at acceptable levels) and controlled diabetes (CD) (patients with diabetes not otherwise stated as uncontrolled) who had undergone RC. χ2 and Wilcoxon rank sum tests and multivariable regression analysis were used for statistics. The LOS and cost are presented as the median and interquartile range. RESULTS: In the present study, 989 patients had UD, 15,693 CD, and 73,603 had no diabetes (ND). Postoperative complications were significantly more common in the UD group (73%) than in the CD (51%) and ND (52%) groups (P < .0001). On multivariable analysis, the UD group were more likely than the CD group to have any complication (odds ratio [OR], 2.3; 95% confidence interval [CI], 2.0-2.7), including renal (OR, 2.1; 95% CI, 1.8-2.4) and infectious (OR, 2.7; 95% CI, 2.3-3.1) complications. Patients with UD were also 4.3 times (95% CI, 3.1-5.8) more likely to die after surgery than were patients with CD. The ND group was slightly more likely than the CD group to experience any complication (OR, 1.13; 95% CI, 1.09-1.17) and death (OR, 1.6; 95% CI, 1.4-1.8). The LOS and cost for UD patients were greater than for CD patients. On multivariable analysis, UD patients had a 30% increase in LOS and 23% increase in cost (P < .0001). CONCLUSION: The findings from the present study have demonstrated an increase in post-RC complications rates, hospital mortality, and hospital resource usage for patients with UD undergoing RC. UD might be a modifiable preoperative risk factor for post-RC morbidity and mortality. Further studies are needed to validate this association.

Regional Cost Variations of Robot-Assisted Radical Prostatectomy Compared With Open Radical Prostatectomy.

INTRODUCTION: The purpose of the study was to evaluate the cost differences between robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) in various census regions of the United States because RARP has been reported to be more expensive than ORP with significant regional cost variations in radical prostatectomy (RP) cost across the United States. PATIENTS AND METHODS: International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with prostate cancer who underwent RARP or ORP from the Nationwide Inpatient Sample (NIS) database from 2009 to 2011. Hospital costs were compared using the Wilcoxon rank sum test and multivariable linear regression analysis adjusting for age, sex, race, comorbidities, and hospital characteristics. RESULTS: From the NIS database, 24,636 RARP and 13,590 ORP procedures were identified and evaluated. The lowest cost overall was in the South; the highest cost RARP was in the West and for ORP in the Northeast. In multivariable analysis, adjusted according to patient and hospital characteristics, RARP was 43.3% more costly in the Midwest, 37.2% more costly in the South, and 39.1% more costly in the West (P < .0001 for all). In contrast, the cost for RARP in the Northeast was 12.8% less than for ORP (P < .0001). CONCLUSION: Cost for RP significantly varies within the nation and in most regions it is significantly greater for RARP than for ORP. ORP in the Northeast is more costly than RARP. Further research is needed to delineate the reason for these differences and to optimize the cost of RP.

Urological outcomes in the omphalocele exstrophy imperforate anus spinal defects (OEIS) complex: experience with 80 patients.

OBJECTIVE: To review the urological management and outcomes of patients with the OEIS (omphalocele, exstrophy of the bladder, imperforate anus, spinal abnormalities) complex. PATIENTS AND METHODS: 80 patients with the OEIS complex managed at a single institution between 1974 and 2009 were reviewed. RESULTS: 37 had initial closure at our institution (2 failed - 5%); 22 with successful closure were referred for incontinence; 15 failed closure at an outside institution (2 of whom are awaiting closure); 6 are skin-covered variants. Osteotomy was performed in 39/43 (91%) with successful closure versus 8/17 (47%) who failed initial bladder closure. 40 were dry (56%), but most needed additional urinary reconstruction: 2 had small bowel neobladders; 32 (84%) had augmentation cystoplasty; 30 (79%) had a continent catheterizable channel; only 9 (24%) were continent with an intact urethra. Bladder neck reconstruction allowed dryness in 7 (18%). 45 patients had XY genotype--19 had female gender assignment at birth. All patients with XX genotype had female gender assignment. CONCLUSIONS: Osteotomy improves success of initial bladder closure. A bladder neck procedure, catheterizable channel, and augmentation cystoplasty will be required in the majority of patients to attain urinary dryness.

Infantile bladder rupture during voiding cystourethrography.

Bladder rupture is rare during infancy and most of reported cases had urethral obstruction or neurogenic bladder. We report two cases of infantile bladder rupture during voiding cystourethrography (VCUG). This report reinforces the criteria for proper VCUG imaging procedure. Consideration of expected bladder volume for body weight, and close monitoring of bladder pressure and injection speed could prevent such complications.

Intravesical injection of botulinum toxin type A: management of neuropathic bladder and bowel dysfunction in children with myelomeningocele.

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.

Infantile bladder rupture during voiding cystourethrography

Bladder rupture is rare during infancy and most of reported cases had urethral obstruction or neurogenic bladder. We report two cases of infantile bladder rupture during voiding cystourethrography (VCUG). This report reinforces the criteria for proper VCUG imaging procedure. Consideration of expected bladder volume for body weight, and close monitoring of bladder pressure and injection speed could prevent such complications.