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Purpose Most children with spina bifida now survive into adulthood, although most have neuropathic bladder with potential complications of incontinence, infection, renal damage and diminished quality of life. In this study we sought to 1) describe contemporary bladder management and continence outcomes of adults with spina bifida, 2) describe differences from younger individuals and 3) assess for association with socioeconomic factors. Materials and Methods We analyzed data on bladder management and outcomes in adults with spina bifida from the National Spina Bifida Patient Registry. A strict definition of continence was used. Results were compared to young children (age 5 to 11 years) and adolescents (12 to 19). Statistical analysis compared cohorts by gender, ethnicity, spina bifida type, lesion level, insurance status, educational attainment, employment status and continence. Results A total of 5,250 patients with spina bifida were included, of whom 1,372 (26.1%) were adults. Of the adult patients 45.8% did not take medication, but 76.8% performed clean intermittent catheterization. Continence was decreased in adults with myelomeningocele (45.8%) vs those with nonmyelomeningocele spina bifida (63.1%, p <0.0001). Continence rates were higher in the older cohorts with myelomeningocele (p <0.0001) but not in those with nonmyelomeningocele spina bifida (p = 0.1192). Bladder management and history of urological surgery varied among age groups. On univariate analysis with spina bifida related or socioeconomic variables continence was significantly associated with educational level but on multivariable logistic regression analysis bladder continence was significantly associated with employment status only. Conclusions Bladder management techniques differ between adults and children with spina bifida. Bladder continence outcomes were better in adults, with nearly half reporting continence. Continence was significantly associated with employment status in patients age 25 years or older. [ABSTRACT FROM AUTHOR]

Purpose Urodynamic findings often guide treatment for neuropathic bladder and are reported as objective data points in multi-institutional trials. However, urodynamic interpretation can be variable. In a pilot study pediatric urologists interpreting videourodynamics exhibited only moderate agreement despite similar training and practice patterns. We hypothesized the pilot study variability would be replicated in a multi-institutional study. Materials and Methods We developed an anonymous electronic survey that contained 20 scenarios, each with a brief patient history, 1 urodynamic tracing and fluoroscopic imagery. All videourodynamics were completed during routine care of patients with neuropathic bladder at a single institution. Pediatric urologists from Centers for Disease Control and Prevention Urologic Protocol sites were invited to complete an interpretation instrument for each scenario. Fleiss kappa and 95% confidence limits were reported, with Fleiss kappa 1.00 corresponding to perfect agreement. Results The survey was completed by 14 pediatric urologists at 7 institutions. Substantial agreement was seen for assessment of fluoroscopic bladder shape (Fleiss kappa 0.73), while moderate agreement was observed for assessment of bladder safety, end filling detrusor pressure and bladder capacity (Fleiss kappa 0.50, 0.56 and 0.54, respectively). Fair agreement was seen for electromyographic synergy and presence of detrusor overactivity (Fleiss kappa 0.21 and 0.35, respectively). Conclusions Experienced pediatric urologists demonstrate variability during interpretation of videourodynamic tracings. Subjectivity of assessment of electromyographic activity and detrusor overactivity was confirmed in this expanded study. Future work to improve the reliability of videourodynamic interpretation would improve the quality of clinical care and the quality of multi-institutional studies that use urodynamic data points as outcomes. [ABSTRACT FROM AUTHOR]

Purpose Urodynamic studies are crucial to neuropathic bladder management and they often determine surgical intervention. However, current evidence indicates that interpretations show poor agreement across physicians. We sought to determine the interrater reliability of urodynamic interpretation in our practice. We hypothesized that there would be strong correlation among pediatric urologists of similar training in a single academic practice. Materials and Methods We retrospectively identified patients with neuropathic bladder who underwent urodynamics at our institution between 2014 and 2015. An anonymous electronic survey (phase I) was developed with 20 clinical scenarios, each containing a brief history, a single urodynamic tracing and an accompanying fluoroscopic image. Faculty members assessed each tracing by an online instrument developed using urodynamic reports and published literature. The primary outcome was statistical correlation across raters as measured by the Spearman correlation coefficient. In a followup study (phase II) we investigated the sources of variability in urodynamic interpretations. Results Six faculty members completed the study with a response rate of 100%. In comparing urodynamic interpretation across raters, the faculty demonstrated a weak to strong correlation (r s 0.39–0.61, p <0.001). A strong correlation was found for fluoroscopic and clinical decision making variables, while electromyography synergy and detrusor overactivity demonstrated weaker correlation across physicians. Conclusions Faculty interpretations of urodynamic tracings showed only moderate agreement despite a close working relationship and similar training at a single institution. Variability in interpretation can strongly impact patient treatment. Therefore, further work is needed to standardize the reporting and interpretation of urodynamic studies to optimize patient care. [ABSTRACT FROM AUTHOR]

Purpose We previously reported catheterizable channel associated outcomes and concluded that the incidence of postoperative complications was greatest in the first 2 years after surgery. At that time our followup was short. In this series we sought to determine whether complications continued to accumulate with longer followup in an updated cohort of patients. Materials and Methods We comprehensively reviewed the outcomes in 81 consecutive patients who underwent construction of a MACE (Malone antegrade continence enema) and/or a Mitrofanoff channel in association with complex genitourinary reconstruction. Mean followup was 80.1 months. Outcomes of these 119 stomas were classified by Clavien-Dindo grade and time to complication. Results The 48 unique, channel related events (40.3%) necessitated a total of 70 interventions with a mean 24.2 months to the first event. Difficult catheterization was the most common event, occurring in 20.1% of channels an average of 29.9 months after surgery. Stomal stenosis was also common, developing in 12.6% of channels at an average of 19.9 months after surgery. Unique complications clustered in the first 2 years, after which there was a statistically significant decline (p = 0.0013). High grade complications similarly clustered (p <0.0001). Channel composition was significantly associated with rates of difficult catheterization events. Conclusions Compared to our previous cohort of patients with similar volume but shorter followup, our assumption that channel associated complications cluster postoperatively and then decrease significantly was correct. Our current and more detailed series demonstrates that the rate of postoperative complications decreases with time. However, with longer followup patients continue to experience lower grade events requiring fewer interventions. [ABSTRACT FROM AUTHOR]

Purpose Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. Materials and Methods In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. Results An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. Conclusions The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements. [ABSTRACT FROM AUTHOR]

Purpose Sacral neuromodulation has been demonstrated to improve refractory bowel bladder dysfunction in children. The purpose of the current study was to determine whether results are durable in children after longer followup, whether children with a lower body mass index are at risk for device failure and whether pretreatment urodynamic evaluation can predict posttreatment outcome. Materials and Methods Pediatric patients with refractory bowel bladder dysfunction were enrolled following informed consent and followed prospectively. All patients underwent preoperative videourodynamic evaluation and a 2-stage implantation procedure. Validated questionnaires were used to assess symptom severity and quality of life. Complications were analyzed with regard to treatment required and patient body mass index. Results During 45 months 30 patients were enrolled. Median age was 8.3 years at enrollment. Median followup was 14.8 months. Patients had significant improvement in quality of life and symptom scores, which persisted at the most recent followup. Patients who had uninhibited detrusor contractions on preoperative urodynamic assessment had significantly greater improvement in symptoms. Of the patients 23% had a complication requiring reoperation, most commonly neurostimulator lead breakage in those with a significantly lower body mass index. Conclusions Sacral neuromodulation significantly improves quality of life and symptom severity in children with refractory bowel bladder dysfunction. Children gain greater benefit if they show uninhibited bladder contractions on preoperative urodynamic evaluation. Children have a high rate of lead breakage requiring operative revision, which was seen after minor trauma in those with a lower body mass index. [ABSTRACT FROM AUTHOR]

Purpose Bullying has become a social plague associated with various deleterious outcomes. We hypothesized that pediatric lower urinary tract symptoms could be associated with exposure to bullying. Materials and Methods We assessed exposure to school bullying via the Setting the Record Straight bullying questionnaire in children 8 to 11 years old being evaluated for lower urinary tract symptoms at our pediatric urology clinic. Lower urinary tract symptoms were quantified with the Vancouver Symptom Score. Children 8 to 11 years old presenting for pediatric well visits also completed the questionnaires. Linear regression assessed the relationship between Vancouver Symptom Score and bullying score. Categorical variables were compared by chi-square test, while continuous variables were compared using the Student t-test. Results A total of 113 children at the urology clinic and 63 children in the primary care setting consented to participate. There were significant differences between the 2 populations, including gender and race, with significantly more perpetrators of bullying in the primary care group (7.9% vs 0.9%, p = 0.02). When looking specifically at the urology group, there was a significant association between Vancouver Symptom Score and self-perceived (p <0.001) and peer perceived (p <0.001) victimization scores. In the primary care group there was also a significant association between Vancouver Symptom Score and self-perceived (p = 0.01) and peer perceived (p = 0.001) bullying perpetrator scores. Of children seen at the primary care office 33% had a significant Vancouver Symptom Score. Conclusions Although bullying exposure is multifactorial, we found that Vancouver Symptom Score can be associated with bullying victimization and perpetrator scores. [ABSTRACT FROM AUTHOR]

Purpose: We theorized that progressive bladder dysfunction due to clinical diagnoses such as outlet obstruction occurs as a result of cyclical oxidative stress events. We hypothesized that measurement of F2-isoprostane, a marker of lipid peroxidation, could serve as a biomarker of oxidative stress in the murine bladder. Materials and Methods: At age 5 to 6 weeks oophorectomized female mice were subjected to 1 of 2 bladder injury models, that is partial bladder outlet obstruction or acute bladder distension. The time points studied after injury included 4, 8 and 16 weeks after obstruction, and 0 to 48 hours after acute bladder distension. In a separate group short-term repetitive acute bladder distension was performed every other day for 14 days. Bladder samples were analyzed for F2-isoprostane using gas chromatography and mass spectroscopy. Mean tissue F2-isoprostane levels were compared. Results: F2-isoprostane increased significantly after 4 weeks of partial bladder outlet obstruction from 1.46 ng/gm in controls to 2.31 ng/gm at 4 weeks (p = 0.01). Eight and 16 weeks after partial bladder outlet obstruction F2-isoprostane remained significantly elevated (2.39 and 2.48 ng/gm, respectively). Acute bladder distension resulted in a significant increase in F2-isoprostane immediately after distension compared to controls (1.6 vs 0.75 ng/gm, p = 0.04). In mice that underwent repetitive acute bladder distension F2-isoprostane did not change. Conclusions: Measurement of tissue F2-isoprostane in the bladder reflects the progression of oxidative stress, primarily in chronic injury models such as partial bladder outlet obstruction. The usefulness of F2-isoprostane measurements in shorter term injury models requires further study. [ABSTRACT FROM AUTHOR]

Purpose: Ileovesicostomy is a reconstructive option in complex urological cases but pediatric specific outcomes are lacking. We report our results with pediatric ileovesicostomy. Materials and Methods: We retrospectively evaluated patients younger than 18 years undergoing incontinent ileovesicostomy at Vanderbilt University. History, urinary tract management and operative course were reviewed in the electronic medical record. Particular attention was given to immediate and long-term postoperative complications. Results: Nine patients underwent incontinent ileovesicostomy between 2000 and 2013 at a mean age of 10.3 years (range 1.4 to 15.5). Surgical indication was sequelae of neurogenic or nonneurogenic neurogenic bladder (such as infection or worsening hydronephrosis) in 5 patients, reversal of vesicostomy in 3 and closure of cloacal exstrophy in 1. All 9 patients were thought incapable of reliable clean intermittent catheterization due to family unwillingness, poor social support or patient refusal. Median followup was 11.5 months (mean 48.2, range 1.3 to 144.8). Immediate postoperative complications included ileus requiring total parenteral nutrition and a wound infection in 1 patient. Long-term complications included urinary tract infection in 2 patients (febrile in 1 and positive culture for foul smelling urine in 1), stomal issues in 2 and temporary urethral leakage in 1. Constipation affected 3 children in long-term followup (all with neurogenic bowel preoperatively). Postoperative creatinine was stable or improved in all patients. Conclusions: Ileovesicostomy is a viable approach in children left with few other options, particularly those who are noncompliant or physically/socially unable to handle catheterization. This operation can help keep such patients out of diapers. [ABSTRACT FROM AUTHOR]

Purpose: Bladder over distention secondary to anatomical or functional obstruction can eventually lead to pathological changes, including decreased elasticity and contractile dysfunction. We hypothesized that chronic bladder distention in a murine model would activate hypoxia dependent signaling pathways despite intermittent relief of distention. Materials and Methods: Female C57Bl/6 mice were oophorectomized at age 5 to 6 weeks and underwent urethral catheterization and 90-minute bladder distention. Acute and chronic time points were evaluated. Bladder tissue was harvested for hematoxylin and eosin, and immunohistochemical staining with the hypoxia markers Glut-1 (EMD Millipore, Merck, Darmstadt, Germany) and Hypoxyprobe™-1. Bladder tissue was also harvested for real-time polymerase chain reaction and oxidative stress measurement. Hypoxia polymerase chain reaction arrays were done to determine changes in gene expression. Oxidative stress was measured using F2-IsoP. Functional bladder changes were evaluated using voided urine blots. Results: After acute distention and 5 consecutive distentions, bladders showed marked inflammatory changes on hematoxylin and eosin staining, and evidence of tissue hypoxia on immunohistochemistry. Quantitative real-time polymerase chain reaction revealed up-regulation of hypoxia and oxidative stress related genes, including Hif1a, Arnt2, Ctgf, Gpx1 and Hmox1. Measurements of oxidative stress with F2-IsoP did not change. Voided urine blots before and after bladder distention showed marked changes with an overactive voiding pattern. Conclusions: Chronic bladder distention is possible in the female mouse. It generates hypoxic injury, as characterized functionally by increased voiding patterns. This bladder injury model might more closely replicate bladder dysfunction in patients with poor bladder emptying due to neurological disease, including those noncompliant with intermittent catheterization. [ABSTRACT FROM AUTHOR]

Purpose: Sacral neuromodulation for refractory urinary dysfunction in pediatrics shows promising results. We prospectively evaluated patients undergoing sacral neuromodulation using validated quality of life and bladder dysfunction questionnaires. Materials and Methods: All patients were prospectively enrolled in the study. Two validated questionnaires were completed preoperatively, after lead placement and at all followups. The PedsQL™ 4.0 Generic Core Scale, which assesses quality of life and bladder dysfunction, was quantified using the Vancouver Nonneurogenic Lower Urinary Tract Dysfunction/Dysfunctional Elimination Syndrome (NLUTD/DES) questionnaire. The Wilcoxon matched pairs test was used for statistical analysis with p <0.05 considered significant. Results: A total of 14 patients with a median age of 10 years were enrolled in the study. Median followup was 6 months. All patients underwent generator placement. No significant difference was seen in physical quality of life. Before and after lead placement mean ± SD psychosocial quality of life scores were 70.6 ± 17.4 and 81.43 ± 14.8 (p = 0.02), mean total quality of life scores were 75 ± 15.3 and 84.04 ± 13.2 (p = 0.006) and median NLUTD/DES scores were 23 ± 7.8 and 10.5 ± 7.0 (p <0.001), respectively. One month postoperatively a significant difference was seen in total quality of life and NLUTD/DES scores. Two patients required replacement of the temporary lead or generator. There were no infections. Conclusions: Patients undergoing sacral neuromodulation had significant improvement in NLUTD/DES scores, and psychosocial and overall total quality of life. Results were durable at 1 month. Continuing to follow these patients in a prospective manner with validated questionnaires will strengthen the current evidence supporting sacral neuromodulation in the pediatric population. [ABSTRACT FROM AUTHOR]

Purpose: The AAP (American Academy of Pediatrics) no longer recommends voiding cystourethrogram in children 2 to 24 months old who present with a first urinary tract infection if renal-bladder ultrasound is normal. We identified factors associated with abnormal imaging and recurrent pyelonephritis in this population. Materials and Methods: We retrospectively evaluated children diagnosed with a first episode of pyelonephritis at age 2 to 24 months using de-identified electronic medical record data from an institutional database. Data included age at first urinary tract infection, gender, race/ethnicity, need for hospitalization, intravenous antibiotic use, history of abnormal prenatal ultrasound, renal-bladder ultrasound and voiding cystourethrogram results, urinary tract infection recurrence and surgical intervention. Risk factors for abnormal imaging and urinary tract infection recurrence were analyzed by univariate logistic regression, the chi-square test and survival analysis. Results: We identified 174 patients. Of the 154 renal-bladder ultrasounds performed 59 (38%) were abnormal. Abnormal prenatal ultrasound (p = 0.01) and the need for hospitalization (p = 0.02) predicted abnormal renal-bladder ultrasound. Of the 95 patients with normal renal-bladder ultrasound 84 underwent voiding cystourethrogram. Vesicoureteral reflux was more likely in patients who were white (p = 0.003), female (p = 0.02) and older (p = 0.04). Despite normal renal-bladder ultrasound, 23 of 84 patients (24%) had dilating vesicoureteral reflux. Of the 95 patients with normal renal-bladder ultrasound 14 (15%) had recurrent pyelonephritis and 7 (7%) went on to surgical intervention. Conclusions: Despite normal renal-bladder ultrasound after a first pyelonephritis episode, a child may still have vesicoureteral reflux, recurrent pyelonephritis and the need for surgical intervention. If voiding cystourethrogram is deferred, parents should be counseled on these risks. [ABSTRACT FROM AUTHOR]

Purpose: Questionnaires to quantify pediatric bladder/bowel dysfunction have recently been developed as research instruments. We evaluated our use of a bladder/bowel dysfunction questionnaire in a busy clinical setting. Materials and Methods: We distributed a validated bladder/bowel dysfunction questionnaire to all new pediatric urology outpatients older than age 4 years from May 1 to July 31, 2010. We instructed families to complete the questionnaire without assistance. Physicians were blinded to responses during the study period. We compared total scores between groups of patients with bladder/bowel dysfunction related and bladder/bowel dysfunction unrelated primary diagnoses. We also compared individual item scores pertaining to urinary incontinence, dysuria, nocturnal enuresis and constipation in patients with those specific primary ICD-9 diagnosis codes to those of other bladder/bowel dysfunction related diagnoses. Results: Of 358 questionnaires reviewed 91 (25%) could not be adequately scored. Of the remaining 267 patients 134 had bladder/bowel dysfunction related diagnoses and 133 had bladder/bowel dysfunction unrelated diagnoses. The patients with bladder/bowel dysfunction related diagnoses had a higher score on the validated questionnaire (p <0.001). Patients with primary ICD-9 diagnoses for urinary incontinence (p = 0.0026, p = 0.0164), dysuria (p = 0.008) and nocturnal enuresis (p <0.0001) had higher scores on corresponding items of the questionnaire than those with other bladder/bowel dysfunction related diagnoses. The ICD-9 diagnosis of constipation was not associated with higher scores for constipation related items. Conclusions: A validated bladder/bowel dysfunction questionnaire is a useful tool in the pediatric urology clinical setting that correlates well with physician assessment. The questionnaire can help patients and their families better define their bladder/bowel symptoms before their visit. Some families will not be able to fill out the questionnaire appropriately. [Copyright &y& Elsevier]

Purpose: Tissue level hypoxia has been noted in animal models of partial bladder outlet obstruction. The key mechanisms linking hypoxia and obstruction induced bladder dysfunction remain unknown. 2-Methoxyestradiol is a natural derivative of 17β-estradiol and is currently used as an oncologic agent for its ability to regulate the hypoxia pathway. We investigated the ability of 2-methoxyestradiol to modulate the hypoxia response in a mouse model of bladder obstruction. Materials and Methods: A group of 5 to 6-week-old female C57BL/6 mice underwent oophorectomy and partial bladder outlet obstruction. Obstructed animals received a subcutaneous pellet of cholesterol placebo (7) or 2-methoxyestradiol plus cholesterol (7). Age matched controls underwent oophorectomy only (8). After 4 weeks the bladders of mice with partial bladder outlet obstruction and of unobstructed animals were harvested. Bladder sections (5 μm) were immunostained for Hypoxyprobe™-1, glucose transporter 1 and hypoxia inducible factor-1α. Real-time polymerase chain reaction was performed for hypoxia inducible factor-1α and lysyl oxidase. Statistical analysis was performed using 1-way ANOVA and the Wilcoxon rank sum test. Results: Immunostaining for glucose transporter 1 and Hypoxyprobe-1 revealed the presence of tissue hypoxia after partial bladder outlet obstruction. Immunostaining and real-time polymerase chain reaction demonstrated the up-regulation of hypoxia inducible factor-1α in mice after partial bladder outlet obstruction compared to controls (p = 0.0394). Although not statistically significant, a trend toward lower gene expression of hypoxia inducible factor-1α was seen in mice receiving 2-methoxyestradiol compared to placebo (p = 0.0625). Compared to placebo, 2-methoxyestradiol treatment increased lysyl oxidase expression (p = 0.007). Conclusions: Murine partial bladder outlet obstruction resulted in hypoxia and up-regulation of the hypoxia inducible factor-1 pathway. Subcutaneous 2-methoxyestradiol administration attenuated this response and may be a viable tool to study the role of hypoxia after partial bladder outlet obstruction. [Copyright &y& Elsevier]

Purpose: Observation off continuous antibiotic prophylaxis is an option for vesicoureteral reflux. We evaluated the characteristics of patients observed off continuous antibiotic prophylaxis and risk factors for febrile urinary tract infection. Materials and Methods: We identified children 1 to 18 years old with primary vesicoureteral reflux between January 1, 2010 and December 31, 2010. We excluded patients with prior surgical correction from analysis. We recorded age, gender, race/ethnicity, primary language, insurance carrier, age at vesicoureteral reflux diagnosis, initial presentation and vesicoureteral reflux severity. We quantified bladder and bowel dysfunction with a validated questionnaire if toilet trained. We compared patients off vs on continuous antibiotic prophylaxis with the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. We used a univariate Cox proportional hazards model to assess predictors of febrile urinary tract infection during observation off continuous antibiotic prophylaxis. Results: Of 529 eligible patients 224 were observed off continuous antibiotic prophylaxis. Patients off continuous antibiotic prophylaxis tended to be older (p <0.001), to be older at diagnosis (p <0.001), to have an initial presentation other than febrile urinary tract infection (p = 0.05), to have nondilating vesicoureteral reflux on most recent cystogram (p <0.001) and to have lower bladder/bowel dysfunction scores if toilet trained (p <0.001). Of the patients off continuous antibiotic prophylaxis a febrile urinary tract infection developed in 19 (8.5%). Risk factors associated with febrile urinary tract infection included initial presentation of multiple febrile urinary tract infections (p = 0.03), older age at diagnosis (p = 0.03) and older age starting observation off continuous antibiotic prophylaxis (p = 0.0003). Conclusions: Criteria to select patients with vesicoureteral reflux for observation off continuous antibiotic prophylaxis remain poorly defined in the literature. Observation will fail in a subset of patients with vesicoureteral reflux. Physician biases regarding patient selection for observation off continuous antibiotic prophylaxis should be considered when interpreting studies that evaluate treatment strategies. [Copyright &y& Elsevier]

Purpose: Between 1997 and 2002 a large number of fetal myelomeningocele closures were performed at our institution. Previously early reports showed little improvement in neonatal bladder function after fetal back closure. We evaluated the long-term urological impact of this procedure. Materials and Methods: Using a combination of retrospective review and survey questionnaire we reviewed the records of 28 patients in whom fetal myelomeningocele closure was done at our institution between 1997 and 2002. The areas addressed included medical management for neurogenic bladder and bowel, need for lower urinary tract reconstruction and functional bladder assessment by videourodynamics. Parameters after fetal myelomeningocele closure were compared to those of 33 age and sex matched patients with myelomeningocele who underwent standard postnatal closure. Results: We reviewed the records of 28 patients after fetal myelomeningocele closure. At a mean age of 9.6 years 23 used clean intermittent catheterization to manage the bladder, 24 required a bowel regimen to manage constipation and 6 underwent lower urinary tract reconstruction with enterocystoplasty and a catheterizable bladder channel. Videourodynamics performed in 14 patients at a mean age of 7.4 years revealed decreased bladder capacity in 71%, detrusor overactivity in 35% and increased detrusor pressure in 25%. Compared to age and sex matched children who underwent postnatal closure we noted no significant differences in bladder management, urinary tract surgery or urodynamics. Conclusions: Neurogenic bowel and bladder management continues to be a significant issue for patients after fetal myelomeningocele closure. After fetal surgery patients should be followed closely, similar to patients who undergo postnatal closure. [Copyright &y& Elsevier]

Purpose: Magnetic resonance imaging is sometimes used to rule out spinal pathology in patients with dysfunctional elimination, although its usefulness in this setting is unclear. We determined the usefulness of magnetic resonance imaging in children with isolated dysfunctional elimination, and normal cutaneous, neurological and orthopedic examinations. Materials and Methods: We reviewed the records of children with dysfunctional elimination who underwent lumbosacral magnetic resonance imaging and identified those who were neurologically normal and who had normal cutaneous back examinations. Our primary goal was to determine the rate at which magnetic resonance imaging identified a spinal abnormality in this population. Univariate analysis was performed to assess the association of several clinical variables with a radiographic abnormality on magnetic resonance imaging. Results: Between 2000 and 2009 a total of 49 lumbosacral magnetic resonance imaging studies were performed in 29 females and 18 males with a mean age of 8.5 years (range 2.1 to 17). Four of the 49 imaging studies (8%) revealed a radiographic abnormality but in only 1 (2%) was clinically significant spinal pathology identified, that is filum lipoma causing cord tethering. Findings on the 3 remaining abnormal imaging studies were considered unrelated to bladder dysfunction. No clinical, demographic or videourodynamic findings were associated with a radiographic abnormality on magnetic resonance imaging. Conclusions: In children with isolated dysfunctional elimination complaints, and normal neurological, orthopedic and back examinations the diagnostic yield of lumbosacral magnetic resonance imaging is low but not zero. We suggest that spinal magnetic resonance imaging be used judiciously and as a test of last resort in these children. [Copyright &y& Elsevier]

Purpose: Postnatal diagnosis of posterior urethral valves continues despite the prevalence of prenatal ultrasound. We identified risk factors associated with chronic kidney disease in these children. Materials and Methods: We retrospectively reviewed the medical records of boys with posterior urethral valves with clinical presentations other than prenatal hydronephrosis. We recorded presenting symptoms, age at presentation, and preoperative hydronephrosis and/or vesicoureteral reflux. Chronic kidney disease was defined as previous renal transplantation, dialysis dependence or glomerular filtration rate less than 60 ml per minute/1.73 m2 at last followup. We used univariate survival analysis with the log rank test of equality for categorical variables and Cox proportional hazard regression for continuous variables to identify risk factors associated with progression to chronic kidney disease. Results: We identified 141 boys with posterior urethral valves with a postnatal presentation. Median age at presentation was 46 months (range 0.3 to 174). Febrile urinary tract infection in 28% of patients and voiding complaints in 50% were the most common presentations. A total of 12 patients (9%) progressed to chronic kidney disease up to 23 years after initial presentation. Preoperative bilateral hydronephrosis, increased hydronephrosis severity and bilateral vesicoureteral reflux were associated with progression to chronic kidney disease. Conclusions: Approximately 10% of cases with postnatal presentation of posterior urethral valves progress to chronic kidney disease, sometimes decades after the initial presentations. Although all patients with posterior urethral valves should be counseled on the potential loss of renal function, children with risk factors warrant close followup into adulthood. [ABSTRACT FROM AUTHOR]

Purpose: Mesenchymal stem cells have various therapeutic benefits in various organ injury models. Bladder outlet obstruction causes smooth muscle hypertrophy and fibrosis, leading to lowered compliance, increased storage pressures and renal injury. Decreased blood flow and hypoxia may contribute to obstruction related bladder decompensation. We used a mouse model to determine whether mesenchymal stem cell recruitment occurred after bladder outlet obstruction and whether this was associated with changes in bladder hypoxia, histology and function. We also identified potential chemokines involved in mesenchymal stem cell recruitment. Materials and Methods: A total of 20 female mice underwent bladder outlet obstruction. Three days later 2 million green fluorescent protein labeled mesenchymal stem cells were intravenously administered. After 4 weeks urodynamic and histological evaluation was performed. Quantitative reverse transcriptase-polymerase chain reaction was done to determine relative expression of the chemokines CCL2, CCL20, CCL25, CXCL9 and CXCL16. We simultaneously studied mice with bladder outlet obstruction only without mesenchymal stem cell injection and a control group. Results: In 10 of 15 surviving mesenchymal stem cell injected mice mesenchymal stem cells were identified in the detrusor, and decreased hypoxia, hypertrophy and fibrosis was seen. Nine of 10 mice with mesenchymal stem cell engraftment had improved compliance compared to those without engraftment (mean ± SD 9.6 ± 5.1 vs 3.9 ± 2.6 μl/cm H2O, p = 0.012). Polymerase chain reaction revealed a 2-fold increase in CCL2 expression but there were no significant changes in other chemokine levels. Conclusions: Mesenchymal stem cell recruitment to the bladder after bladder outlet obstruction appears to be associated with increased blood flow and decreased tissue hypoxia, which may contribute to improvement in histopathological and functional parameters. Mesenchymal stem cell recruitment may be related to CCL2 over expression. Additional studies in larger samples are needed but these initial results suggest a potential role for mesenchymal stem cell based therapy for bladder outlet obstruction related bladder injury. [Copyright &y& Elsevier]

Purpose: Febrile urinary tract infection represents significant morbidity in patients with vesicoureteral reflux, especially following open surgical or endoscopic treatment. The reported incidence of febrile urinary tract infection after ureteroneocystostomy varies from 10% to 24%. We investigated the incidence of febrile urinary tract infection following ureteroneocystostomy in a contemporary, single institution series. Materials and Methods: We retrospectively reviewed medical records of 395 consecutive patients undergoing ureteroneocystostomy for primary vesicoureteral reflux at our institution between 2002 and 2007. We examined demographic, diagnostic and operative data, including presence of postoperative febrile urinary tract infection. A Cox proportional hazards model was performed to assess predictors of febrile urinary tract infection following ureteroneocystostomy. Results: Ureteroneocystostomy was performed in 395 patients (673 ureters) at a mean age of 58 months. The most common reflux grade was III (41%). The incidence of postoperative febrile urinary tract infection was 4.6% at a mean followup of 15 months. Postoperative dysfunctional elimination syndrome was a significant predictor of febrile urinary tract infection (HR 3.8, 95% CI 1.2–12, p = 0.02), and was identified in 58 of 340 toilet trained children (15% overall). Age at diagnosis, initial presentation, age at surgery, indication for surgery, reflux grade, laterality, surgical technique and preoperative dysfunctional elimination syndrome were not predictive of postoperative febrile urinary tract infection. Conclusions: The incidence of febrile urinary tract infection following ureteroneocystostomy may be lower than previously reported. The presence of postoperative dysfunctional elimination syndrome is a significant predictor of postoperative febrile urinary tract infection. [Copyright &y& Elsevier]

Purpose: In the classic view of bladder development the trigone originates from the mesoderm derived wolffian ducts while the remainder of the bladder originates from the endoderm derived urogenital sinus. Recent molecular developmental studies have questioned the veracity of this received wisdom, suggesting an endodermal origin for the trigone. To shed further light on this issue we observed mesenchymal-epithelial interactions between trigone epithelium and fetal urogenital sinus mesenchyma to infer the trigonal germ layer of origin. Materials and Methods: Mouse trigone epithelium was recombined with fetal rat urogenital sinus mesenchyma in tissue recombinant grafts that were placed beneath the renal capsule of athymic mouse hosts. Grafts were harvested at 4 weeks. Control grafts with bladder dome and ureteral epithelium were also examined. Tissues were evaluated with hematoxylin and eosin, and Hoechst dye 33258 to confirm cell species origin. Immunohistochemistry was done with androgen receptor, broad spectrum uroplakin, dorsolateral prostate secretions and seminal vesicle secretions to differentiate prostatic and seminal vesicle differentiation. Results: Grafts of mouse trigone epithelium with fetal rat urogenital sinus mesenchyma yielded epithelial tissue that stained for dorsolateral prostate secretions but not for seminal vesicle secretions. Control grafts of bladder dome epithelium yielded the expected endodermal prostate differentiation. Control grafts of ureteral epithelium yielded the expected mesodermal seminal vesicle differentiation. Conclusions: The consistent finding of prostatic epithelium in tissue recombinants of trigone epithelium and fetal urogenital sinus mesenchyma reinforces the hypothesis that the trigone is derived from the endoderm and not from the mesoderm, as commonly accepted. [Copyright &y& Elsevier]

Purpose: Intra-abdominal testes can be treated with several surgical procedures. We evaluated factors influencing the outcome of orchiopexy for intra-abdominal testis. Materials and Methods: We retrospectively reviewed 156 consecutive orchiopexies performed for intra-abdominal testis, defined as a nonpalpable testis on examination and located in the abdomen at surgery. All surgical approaches were included in the study. Primary outcome was the overall success rate and secondary outcomes were success based on surgical approach, age and a patent processus vaginalis. Success was considered a testis with normal texture and size compared to the contralateral testis at followup. Multivariate analysis was performed to determine factors predictive of success. Results: The overall success rate of all orchiopexies was 79.5%. Median patient age at orchiopexy was 12 months and mean followup was 16 months. Of the patients 117 had a patent processus vaginalis at surgery. One-stage abdominal orchiopexy was performed in 92 testes with 89.1% success. Of these cases 32 were performed laparoscopically with 96.9% success. One-stage Fowler-Stephens orchiopexy was performed in 27 testes and 2-stage Fowler-Stephens orchiopexy was performed in 37 with success in 63.0% and 67.6%, respectively. Multivariate analysis revealed that 1-stage orchiopexy without vessel division had more successful outcomes than 1 and 2-stage Fowler-Stephens orchiopexy (OR 0.24, p = 0.007 and 0.29, p = 0.19, respectively). Neither age at surgery nor an open internal ring was significant (p = 0.49 and 0.12, respectively). Conclusions: The overall success of orchiopexy for intra-abdominal testis is 79.5%. While patient selection remains a critical factor, 1-stage orchiopexy without vessel division was significantly more successful and a laparoscopic approach was associated with the fewest failures for intra-abdominal testes. [Copyright &y& Elsevier]

Purpose: Transforming growth factor-β is a potent stimulator of extracellular matrix production. Several studies show that loss of transforming growth factor-β signaling decreases kidney, liver and lung fibrosis. However, the role of transforming growth factor-β signaling in bladder fibrosis is not entirely understood. We investigated the effect of stromal loss of such signaling in mice after partial bladder outlet obstruction. Materials and Methods: We performed partial bladder outlet obstruction by urethral ligation in 5-week-old female Tgfbr2colTKO mice. These mice were compared to WT mice with partial bladder outlet obstruction and to WT nonobstructed controls. After 4 weeks and before sacrifice urodynamics were performed. Bladder tissue was harvested, and p-Smad2 and collagen (Masson''s trichrome) staining were performed. Results: Bladder compliance was increased in partially obstructed Tgfbr2colTKO mice and decreased in partially obstructed WT mice. The latter had increased smooth muscle hypertrophy and increased collagen deposition between smooth muscle bundles compared to those in Tgfbr2colTKO mice and nonobstructed controls. Transforming growth factor-β responsive collagen promoter activity was significantly decreased in Tgfbr2 knockout bladder stromal cells vs WT stromal cells. Conclusions: Stromal loss of transforming growth factor-β signaling decreased collagen deposition after partial bladder outlet obstruction. In contrast to collagen production by recruited macrophages, stromal transforming growth factor-β signaling appears to be the primary source of fibrosis after partial bladder outlet obstruction. These findings further support the hypothesis that manipulating transforming growth factor-β signaling in bladder stromal cells would provide a future avenue for neuropathic bladder and bladder fibrosis treatment. [Copyright &y& Elsevier]

Purpose: Bladder fibrosis is an undesired end point of partial bladder outlet obstruction. In fibrotic disease of the lung, kidney, skin and heart chemokines recruit bone marrow derived cells to injured tissue. Blockade of chemokines like CCL2 results in decreased fibrosis in other organs. To our knowledge we present the first report of bone marrow derived cell recruitment to the bladder in a murine bladder outlet obstruction model. Materials and Methods: We lethally irradiated WT female mice and reconstituted their bone marrow using fetal liver cells from transgenic mice ubiquitously expressing green fluorescent protein. Periurethral collagen injection was used for bladder outlet obstruction. Obstruction was assessed by urodynamics, and bladder and kidney histological changes. Bladders were harvested 1 to 12 weeks after bladder outlet obstruction and compared to those in nonobstructed controls. The chemokine CCL2 was compared between obstructed and nonobstructed mice with reverse transcriptase-polymerase chain reaction. Green fluorescent protein expressing bone marrow derived cells were identified with immunohistochemistry and fluorescence activated cell sorting. Results: Bladders showed histological and urodynamic changes consistent with obstruction. CCL2 induction increased after obstruction compared to that in controls. After obstruction bone marrow derived cells were present in the urothelial and stromal layers. Activated epidermal growth factor receptor was found in cells associated with bone marrow derived cells. Conclusions: Bone marrow derived cells are recruited to the bladder by bladder outlet obstruction and are present in the urothelial and stromal layers. Stromal bone marrow derived cells may have a role in hypertrophy and fibrosis. Further study of the recruitment and function of bone marrow derived cells in the bladder may provide potential targets for antifibrotic therapy. [Copyright &y& Elsevier]

Purpose: Data addressing ureteroscopic management of intrarenal calculi in prepubertal children are limited. We reviewed our experience from January 2002 through December 2007. Materials and Methods: We retrospectively reviewed ureteroscopic procedures for intrarenal calculi in children younger than 14 years. Stone-free status was determined with postoperative imaging. Multiple logistic regression analysis was used to assess the influence of preoperative factors on initial stone-free status and the need for additional procedures. Results: Intrarenal calculi were managed ureteroscopically in 52 kidneys in 50 children with a mean age of 7.9 years (range 1.2 to 13.6). Mean stone size was 8 mm (range 1 to 16). Stone-free rate after a single ureteroscopic procedure was 50% (25 of 50 patients) on initial postoperative imaging and 58% (29 of 50) with extended followup. Initial stone-free status was dependent on preoperative stone size (p = 0.005) but not stone location. Additional stone procedures were required in 18 upper tracts. Younger patient age (p = 0.04) and larger preoperative stone size (p = 0.002) were associated with the need for additional procedures. Additional procedures were required in more than half of the stones 6 mm or larger but in no stone smaller than 6 mm. Conclusions: Ureteroscopy is a safe method for the treatment of intrarenal calculi in the prepubertal population. Our ureteroscopic stone-free rate for intrarenal stones is lower than that reported for ureteral stones. Parents should be informed that additional procedures will likely be required, especially in younger patients and those with stones larger than 6 mm. [Copyright &y& Elsevier]

Purpose: Fecal incontinence and constipation in children with spina bifida are recognized to impact quality of life. Most disease specific quality of life instruments on fecal incontinence target adults and/or children without neuropathic bowel. We developed an instrument to evaluate bowel function and its impact on quality of life in children with spina bifida and their caregivers. Materials and Methods: A 51-item questionnaire termed the FIC QOL (Fecal Incontinence and Constipation Quality of Life) survey was developed from expert opinion, patient interviews, and modification of previously published adult and pediatric studies for nonneuropathic bowel dysfunction. The items are divided into 7 quality of life factor groupings, including bowel program, dietary management, symptoms, travel and socialization, family relationships, caregiver emotional impact and financial impact. The questionnaire was given to caregivers of children with and without spina bifida. Discriminant validity was evaluated by comparing the spina bifida and control groups. Test-retest reliability was evaluated by having 41 patients complete 2 surveys within 4 to 6 weeks. Results: Comparing questionnaires from 92 index patients and 52 controls showed a statistically significant difference for all 7 quality of life factor groupings. The FIC QOL instrument objectively demonstrated the negative impact of fecal incontinence and constipation on quality of life in these families. Comparing 82 questionnaires at 2 time points demonstrated the reliability of all FIC QOL questions. Conclusions: The FIC QOL instrument provides a valid and reliable measure of the effect of fecal incontinence and constipation on the quality of life of caregivers and their children with spina bifida. [Copyright &y& Elsevier]

Purpose: The potential benefits of laparoscopic pyeloplasty may recede in younger age groups. We used a multi-institutional database to address the effect of laparoscopic approach on length of stay and postoperative parenteral narcotic use in specific pediatric age groups. Materials and Methods: We performed a retrospective study of 5,261 children with an ICD-9 procedure code for correction of ureteropelvic junction obstruction from the Pediatric Health Information System, a database of freestanding pediatric hospitals. Discharge dates from January 1, 2002 to June 30, 2007 were included. Laparoscopic cases were identified by ICD-9 procedure codes and hospital equipment charges. We used multivariate linear regression to investigate the effect of laparoscopic approach on length of stay and parenteral narcotic use in several age categories, including infant (1 month to less than 2 years old), preschool (2 to less than 6 years), grade school (6 to less than 10 years), preadolescent (10 to less than 13 years) and adolescent (13 to less than 19 years). Results: Laparoscopic approach decreased length of stay and number of parenteral narcotic pharmacy charges in the preadolescent (p = 0.03 and p = 0.005, respectively) and adolescent (p = 0.03 and p = 0.006, respectively) groups but not in any of the younger groups. Conclusions: Laparoscopic approach was associated with a shorter hospital stay and decreased parenteral narcotic use in patients older than 10 years. Evolving technique may reveal less morbidity in younger patients. Future comparisons to open pyeloplasty should address specific pediatric age groups and outpatient convalescence. [Copyright &y& Elsevier]

Purpose: Pyeloplasty is increasingly performed on a short stay basis. We sought to determine what patient and treatment variables affect postoperative pain and length of stay, and whether an open approach could be considered “minimally invasive.” Materials and Methods: We performed a retrospective review of patients younger than 10 years who underwent open pyeloplasty between 2001 and 2007. All patients received ketorolac every 6 hours and acetaminophen with codeine as needed. Data extracted from the medical records included morphine and codeine usage, patient age and gender, incision type, operative time, stent usage and outcome data (pain scores and length of stay). Multiple regression analyses were used to determine the association between variables and outcomes. Results: A total of 51 patients met the inclusion criteria. Patient age and gender, operative time and stent usage had no significant correlation with mean or median pain scores. Children who received morphine had significantly higher mean, median and maximum pain scores and length of stay (33 vs 23 hours) than those who did not receive morphine. Multiple regression analyses revealed that morphine usage and dorsal lumbotomy incision were independently associated with higher mean, median and maximum pain scores, and a nephroureteral catheter was correlated with a higher maximum pain score. The only variable associated with length of stay was morphine usage. Conclusions: Morphine usage was the most significant variable associated with increased pain scores and increased length of stay. Ketorolac and acetaminophen/codeine provide better pain control, and allow children to return home within 24 hours. With mean pain scores less than 1 this series demonstrates that open pyeloplasty can be “minimally invasive.” [Copyright &y& Elsevier]

Purpose: Hypospadias repair is a complex and seminal procedure that has defined the subspecialty of pediatric urology. We sought to determine the degree of training and opinions regarding the need for fellowship training to achieve necessary competence in hypospadias repair. Materials and Methods: An electronic survey was sent to 518 urology residents and recent graduates, and to 168 practicing pediatric urologists. Nonresponders were resent the survey 2 additional times. The survey consisted of basic questions on level of training or years in practice. Residents and practicing pediatric urologists were asked about the level of resident participation for each step of the hypospadias procedure, and opinions on the necessity of fellowship training. Data were analyzed for statistical differences with Wilcoxon rank sum and multiple and logistic regression tests. Results: Surveys were completed by 89 pediatric urologists and 208 urology residents or recent graduates (response rate 53% and 40%, respectively). Approximately 70% of residents and attending physicians report that less than 50% of the overall hypospadias procedure is performed by the resident. There appears to be agreement between residents and attending physicians regarding the perceived amount of resident participation for all steps of the procedure except glanular mobilization. Additionally, 71% of residents and 86% of attending physicians believe that a pediatric fellowship is necessary to perform hypospadias surgery. Conclusions: The majority of residents and attending physicians report limited resident participation in hypospadias surgery. Residents and attending physicians have significant agreement on perceived participation. Our data do not corroborate the program data regarding the role of urology residents in hypospadias repair. The majority of residents and pediatric urologists believe specialized training is required to perform hypospadias surgery. [Copyright &y& Elsevier]

Purpose: Urological complications are well documented in patients with traumatic spinal cord injury. We examined the long-term urological outcomes in a large population of children affected by transverse myelitis. Materials and Methods: We retrospectively reviewed the medical history, imaging studies and urodynamic findings in 22 children with transverse myelitis. Age at disease onset ranged from 3 months to 18 years (average 8.8 years). Results: At a mean followup of 7.1 years 19 patients (86%) had persistent bladder dysfunction and 17 (77%) had persistent bowel dysfunction. Initial evaluation at least 1 month after disease onset revealed detrusor overactivity in 59% of patients, detrusor external sphincter dyssynergia in 41%, low compliance in 47% and detrusor leak point pressure greater than 40 cm water in 12%. Functional motor recovery and absence of lower extremity spasticity did not reflect normal urodynamic findings. Of the 19 patients with imaging available for review 5 (26%) had upper tract changes. One patient had development of chronic renal insufficiency. Low compliance (p = 0.02) and upper tract changes (p = 0.1) were more frequent in patients who started clean intermittent catheterization more than 2 years after disease onset. Conclusions: Persistent bowel and bladder dysfunction is common in transverse myelitis. Urodynamic abnormalities may be present despite normal neurological examination and absence of urinary symptoms. All pediatric patients with transverse myelitis require baseline renal ultrasound and urodynamic evaluation to guide treatment. Early institution of clean intermittent catheterization appears to preserve bladder compliance and decrease upper tract disease, and should be instituted at disease onset. [Copyright &y& Elsevier]