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Summary Introduction Infants with myelomeningocele are at risk for chronic kidney disease caused by neurogenic bladder dysfunction. Urodynamic evaluation plays a key role to risk stratify individuals for renal deterioration. Objective To present baseline urodynamic findings from the Urologic Management to Preserve Initial Renal function for young children with spina bifida (UMPIRE) protocol, to present the process that showed inadequacies of our original classification scheme, and to propose a refined definition of bladder hostility and categorization. Study design The UMPIRE protocol follows a cohort of newborns with myelomeningocele at nine children's hospitals in the United States. Infants are started on clean intermittent catheterization shortly after birth. If residual volumes are low and there is no or mild hydronephrosis, catheterization is discontinued. Baseline urodynamics are obtained at or before 3 months of age to determine further management. Based on protocol-specific definitions, urodynamic studies were reviewed by the clinical site in addition to a central review team; and if necessary, by all site urologists to achieve 100% concurrence. Results We reviewed 157 newborn urodynamic studies performed between May 2015 and September 2017. Of these 157 infants, 54.8% were boys (86/157). Myelomeningocele closure was performed in-utero in 18.4% (29/157) and postnatally in 81.5% (128/157) of newborns. After primary review, reviewers agreed on overall bladder categorization in 50% (79/157) of studies. Concurrence ultimately reached 100% with further standardization of interpretation. We found that it was not possible to reliably differentiate a bladder contraction due to detrusor overactivity from a volitional voiding contraction in an infant. We revised our categorization system to group the “normal” and “safe” categories together as “low risk”. Additionally, diagnosis of detrusor sphincter dyssynergia (DSD) with surface patch electrodes could not be supported by other elements of the urodynamics study. We excluded DSD from our revised high risk category. The final categorizations were high risk in 15% (23/157); intermediate risk in 61% (96/157); and low risk in 24% (38/157). Conclusion We found pitfalls with our original categorization for bladder hostility. Notably, DSD could not be reliably measured with surface patch of electrodes. The effect of this change on future renal outcomes remains to be defined. Download : Download high-res image (392KB) Download : Download full-size image summary figure . Change in urodynamic bladder categorization.

Relative value units (RVUs) are the measure of value used in United States Medicare and Medicaid reimbursement. The Relative Update Committee (RUC) determines physician work RVU (wRVUs) based on operative time, technical skill and effort, mental effort and judgment, and stress. The primary aim of this study was to assess whether operative time is adequately accounted for in the wRVU system in pediatric urology.The American College of Surgeons National Surgical Quality Improvement Program Pediatric Participant User File (ACS-NSQIPP-PUF) was reviewed from 2012 to 2017. Most common single pediatric urology current procedural terminology (CPT) codes were included. The primary variable was wRVU per hour of operative time (wRVU/h). Linear regression analysis was used to assess the relative influence that operative time had on wRVU/h.25,432 cases were included in the final study population from 45 unique CPT codes. The median operative time was 79 min, and the median RVU/h was 12.2. Procedures with operative time less than 79 min had higher wRVU/h compared with procedures longer than 79 min (14.5 vs 10.5, p 0.001). Procedures with higher than average incidence of any complications had a lower wRVU/h (9.0 vs. 14.6 p 0.001). Linear regression analysis revealed that each additional hour of operative time was expected to decrease wRVU/h by 4.2 (-0.70 per 10 min, 95% CI: -0.71 to -0.69, p 0.001; RThis analysis of contemporary large pediatric population national-level data suggests that the wRVU system significantly favors shorter and less complex procedures in Pediatric Urology. Pediatric urologists performing longer and more complex procedures are not adequately compensated for the increase in complexity.Retrospective comparative study.

The Mirena intrauterine device (IUD) is a hormone-secreting contraceptive device. Pregnancy with the Mirena is rare and effects to the fetus are unknown. Here we present four females with genital virilization after pregnancy with persistent Mirena IUD. All patients had a 46, XX karyotype and normal hormone evaluation. All underwent exam under anesthesia, demonstrating posterior labial fusion and short urogenital sinus with normal bladder, urethra, vagina, and cervix. Three of four patients underwent flap vaginoplasty without complications and good cosmetic outcomes. This series suggests that persistent levonorgestrel-secreting IUD during pregnancy is associated with genital virilization in female fetuses.

Summary Introduction Excision of the prostatic utricle has been a challenging surgical problem due to the location deep in the pelvis between the rectum and bladder. Robotic-assisted laparoscopic surgery allows minimally invasive access to this location. Objective To describe the robotic surgical outcomes and important techniques associated with robotic excision of the prostatic utricle and explain how these techniques apply to similar pediatric pelvic pathology. Study design Retrospective chart evaluation of patients treated at a single institution with robotic excision of a prostatic utricle as well as two other patients in which the similar approach was employed. Results 4 patients underwent robotic excision of a prostatic utricle. A fifth patient underwent excision of urethral diverticulum that was the remnant of an ectopic ureter. The sixth patient had a high urogenital sinus that required laparoscopic assisted vaginoplasty approached in a similar manner to the above listed cases. Mean age at surgery was 35.5 months for the utricle patients. Mean follow-up duration for the utricle patients was 30.75 months. Average hospital stay for the utricle patients was one day. In the utricle patients one patient developed transient urinary retention and one had a postoperative urinary tract infection. Concomitant cystoscopy used in the two non-utricle patients was a key step in defining the proper location of dissection. Discussion Robotic-assisted laparoscopic retrovesical excision of the prostatic utricle is a safe operation that requires a skill set that can be readily applied to other complex pelvic pathology such as the ectopic ureter, urethral diverticulum, and urogenital sinus. Concomitant cystoscopy can aid significantly in defining the location and limits of dissection.

Pediatric patients present unique challenges in the performance and interpretation of urodynamic studies. Interpretation of urodynamics to guide clinical management at an institutional level is accepted as reliable. Challenges arise however when multi-site collaborations incorporate urodynamics into study design to determine primary or secondary outcomes or to direct decision-making. Although standardized terminology has been established by ICCS, the application of this shared language to performance and interpretation of pediatric urodynamics to across multiple sites may not be intuitive or reliable. With a primary goal of defining the care necessary to protect future renal function, the UMPIRE protocol (Urologic Management to Preserve Initial REnal function) utilizes a urodynamics-based risk stratification to determine medical management for infants with myelomeningocele. Iterative changes in the protocol are based upon the clinical progress of the enrolled children. Despite a team experienced in subtleties of urodynamics and despite efforts to minimize variability across sites, the UMPIRE study group identified several areas in which the language of urodynamics required additional clarification or creation of more explicit definitions to standardize performance and interpretation across sites. This article reviews the foundations of current urodynamics practice, describes limitations and challenges unique to pediatric studies, and the shares the humble lessons learned by the UMPIRE study group on their journey toward standardized urodynamic language for management of infants and children with myelomeningocele.

Relative value units (RVU) are the measure of value used in United States Medicare and Medicaid reimbursement. The Relative Update Committee (RUC) determine physician work RVU (wRVU) based on operative time, technical skill and effort, mental effort and judgement, and stress. In theory, wRVU should account for the complexity and operative time involved in a procedure.The primary aim of this study is to assess if operative time and complexity of hypospadias surgery is adequately accounted for by the current wRVU assignments.The American College of Surgeons National Surgical Quality Improvement Program Participant User File (ACS-NSQIP PUF) database was utilized from 2012 to 2017. Single stage hypospadias current procedural terminology (CPT) codes (including acceptable secondary CPT codes) were extracted. Using total wRVU and total operative time, the primary variable of wRVU per hour was calculated (wRVU/hr). Multivariable linear regression analysis was used to assess the relative influence that wRVU and operative time had on the wRVU/hr variable.9810 cases were included in the final study population divided into four categories: simple distal (eg. MAGPI, V-Flap), single stage distal, single stage mid, single stage proximal. On analysis of variance, there was statistically significant different wRVU/hr for the four different types of hypospadias repairs with simple distal having the highest mean wRVU/hr of 19.5 and the lowest being proximal hypospadias repairs at 13.2. Simple distal, distal and midshaft hypospadias had statistically significantly higher wRVU/hr compared to proximal hypospadias (16.2, 95% CI: 15.8-16.5 vs. 13.2, 95% CI 10.9-15.5; p0.001). Multivariable linear regression revealed that each additional hour of operative time was expected to decrease wRVU/hr by 10.5 (-10.5, 95% CI: -11.0 to -10.1, p 0.001); total work wRVU had a statistically significant independent association with wRVU/hr (0.6, 95%CI: 0.5-0.7, p0.001).This the first objective assessment of the current wRVU assignments with regards to one stage hypospadias repairs. More complex and longer hypospadias procedures are not adequately compensated by wRVU. Most notably, simple distal procedures are reimbursed at a mean of 19.5 wRVU/hr compared to 13.2 wRVU/hr for one stage proximal repairs.This analysis of national-level data suggests that the current wRVU assignments significantly favor shorter and simpler procedures in hypospadias surgery.

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.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.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.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.

Summary Introduction There are no large multi-institutional studies reporting on perioperative complications of hypospadias repairs. We sought to determine perioperative complications of hypospadias repairs from the National Surgical Quality Improvement Program Pediatrics (NSQIP-P) to aid in patient counseling. Study design This cohort study from 2012 to 2017 was conducted using NSQIP-P database. Pediatric patients undergoing hypospadias surgery were identified and compared based on 4 major categories: distal/midshaft repair, one-stage repair proximal, stage one repair, and stage two repair. Baseline demographics between the four groups and perioperative parameters were compared. Multivariable logistic regression analysis models including type of repair was used to determine associations with overall complications, infectious complications, and dehiscence. Discussion There were 11,292 patients identified in the study population. Overall, 78% underwent distal/midshaft hypospadias repair, 12% underwent one-stage proximal repair, 1.4% underwent proximal first stage repair and 9% underwent proximal second stage repair. Multivariable logistic regression analysis revealed that proximal first stage procedures had similar overall complications to distal/mid repairs but proximal one-stage and proximal second stage procedures were associated with significantly more overall complications, local infectious complications, and dehiscence. Age, race, operative time, prematurity were also independently associated with increased overall complications. As expected, complication rates are higher in those with proximal hypospadias. In staged hypospadias, first stage has a lower complication rate compared to second stage. All complications, especially of infectious and dehiscence are the highest in the one-stage proximal and proximal second stage repairs. Conclusion We report large multi-institutional analysis of 30-day peri-operative hypospadias repair complications; this information is useful for patient counseling and education. Summary Table . Parameter All Distal/mid hypospadias One-stage Proximal Proximal First Stage Proximal Second Stage P-value SSI 58 (0.5%) 28 (0.3%) 13 (1.0%) 0 17 (1.8%) UTI 78 (0.7%) 45 (0.5%) 13 (1.0%) 0 20 (2.1%) Dehiscence 293 (2.6%) 149 (1.7%) 59 (4.3%) 4 (2.5%) 81 (8.4%) PNA 8 (0.1%) 3 (0.03%) 2 (0.2%) 1 (0.6%) 2 (0.2%) Return to OR 88 (0.8%) 49 (0.6%) 22 (1.6%) 2 (1.2%) 15 (1.6%) Readmission 157 (1.4%) 96 (1.1%) 28 (2.1%) 3 (1.9%) 30 (3.1%) Infectious comp 127 (1.1%) 67 (0.8%) 25 (1.8%) 0 (0%) 35 (3.6%) Any complication 467 (4.1%) 250 (2.8%) 93 (6.8%) 7 (4.3%) 117 (12.1%)

We present an unusual pediatric case of invasive upper tract urothelial carcinoma with an associated genetic predisposition. A 14-year-old female presented with intermittent right flank pain, and was found to have a poorly functioning hydronephrotic right kidney. Laparoscopic nephrectomy was performed. Pathology demonstrated upper tract urothelial carcinoma, and she subsequently underwent completion ureterectomy. Genetic studies demonstrated a double-hit constitutional deletion of a DNA mismatch repair protein, revealing a rare Lynch syndrome variant known as Constitutional Mismatch Repair Deficiency Syndrome. This disease places her at high risk for multiple malignancies, including upper tract urothelial carcinoma.

Objectives Pelvic immobilization constitutes a necessary component of successful bladder exstrophy closure. The efficacy of spica cast immobilization has been reported as markedly inferior to external fixation, with success rates below 25%. We reviewed our experience with spica cast immobilization following bladder closure. Patients and methods We retrospectively reviewed classic bladder exstrophy patients undergoing bladder closure with spica cast immobilization. Success of bladder closure and complications related to immobilization were noted, as were age, type of closure, use of osteotomy, duration of immobilization, and number of cast changes. Results Fifteen patients underwent bladder closure (10 staged, 5 complete repair) at a median age of 4 days (range 1–6) and 14 were immobilized with spica casts. Initial closures were successful in 11 (73%). Success rates were higher in patients undergoing osteotomies (6/7, 86%) compared to those without osteotomies (5/8, 63%). No patients immobilized with spica casts developed serious complications related to their immobilization. Minor skin breakdown occurred in 3/14 patients (21%). Median time of immobilization was 39 days (range 22–48). Conclusions Spica casts are a safe, effective method of postoperative immobilization and are associated with a low risk of cast-related complications.

There has been an emergence of a therapeutic nihilistic attitude about the surgical treatment of vesicoureteral reflux (VUR). Evidence-based reviews have questioned whether surgical treatment is beneficial for children with VUR. Even the use of prophylactic antibiotics, which have traditionally been the first-line therapy recommended for virtually all patients with VUR, has come under scrutiny after several randomized controlled trials found them to have no effect on decreasing the risk of urinary tract infections (UTIs) in children with VUR. Grade is the strongest predictor of VUR resolution, with high-grade VUR being much less likely to resolve. Other factors that negatively influence resolution include lower bladder volume or pressure at onset of reflux, older age, female sex, bilateral VUR, ureteral duplication, abnormal or scarred kidneys, and bladder dysfunction. These factors can be used, along with grade, in computer models or nomograms to improve the ability to predict spontaneous resolution.

We previously developed a computational model to predict vesicoureteral reflux resolution 1 and 2 years after diagnosis. Previous studies suggest that an abnormal renal scan may be a predictor of the failure of vesicoureteral reflux to resolve. We investigated whether the addition of renal scan data would improve the accuracy of our computational model.Medical records and renal scans were reviewed on 161 children, including 127 girls and 34 boys, with primary reflux between 1988 and 2004. In addition to the 9 input variables from our prior model, we added renal scan data on decreased relative renal function (40% or less in the refluxing kidney) and renal scars. Resolution outcome was evaluated 1 and 2 years after diagnosis. Data sets were prepared for 1 and 2-year outcomes, and randomized into a modeling set of 111 and a cross-validation set of 50. The model was constructed using neUROn++.A logistic regression model had the best fit with an ROC area of 0.945 for predicting reflux resolution in the 2-year model. This was improved compared to our previous model without renal scan data. A prognostic calculator using this model can be deployed for availability on the Internet, allowing input variables to be entered and calculating the odds of resolution.This computational model uses multiple variables, including renal scan data, to improve individualized prediction of early reflux resolution with almost 95% accuracy. The prognostic calculator is a useful tool for predicting individualized vesicoureteral reflux resolution.

Objectives To examine the outcome of transcutaneous electrical nerve stimulation (TENS) use in children with overactive bladder refractory to behavioral and anticholinergic therapy. Methods We reviewed the data of 18 children (13 girls and 5 boys; mean age 9 years) with overactive bladder refractory to standard therapy who underwent at-home TENS treatment twice daily for 20 minutes. Symptoms and objective measures (noninvasive uroflowmetry and postvoid residual urine volume) were noted at baseline and after treatment. Results Of the 18 children, 15 had pretreatment incontinence and 3 had only increased urgency/frequency. The incontinence group averaged 3.2 ± 2.1 daytime accidents. The mean length of TENS use was 8 ± 7 months, and the mean follow-up after starting TENS was 13 ± 9 months. Of the 15 patients with incontinence, 2 became dry (13%), 9 were significantly improved (60%), and 4 reported no improvement (27%). Of 12 children with marked urinary frequency, 8 had significant symptom improvement. Noninvasive uroflow and postvoid residual urine volume measurements were not significantly different statistically before and after treatment. Pretreatment patient sex, age, and frequency of wetting were not predictive of the outcome. A post-TENS parabolic uroflow curve showed a statistically significant correlation with patients who became dry or improved ( P = 0.018). Conclusions The results of our study have indicated that TENS use in children with incontinence refractory to pharmacotherapy is safe and well tolerated. The encouraging results of this treatment modality in the refractory patient population warrant additional study of the pediatric overactive bladder.

Questions regarding the efficacy and safety of long-term prophylactic antibiotics and the option of minimally invasive therapy have increased clinical emphasis on predicting early resolution in patients with vesicoureteral reflux. We reviewed multiple potential prognostic factors in addition to grade to enhance predictive ability regarding early vesicoureteral reflux resolution.Medical records and cystograms from 324 children (257 girls and 67 boys) with primary vesicoureteral reflux were reviewed. Multiple factors were analyzed with respect to outcome and multivariable dependent tables were constructed to enhance the prediction of vesicoureteral reflux resolution.Mean +/- SD age at diagnosis was 2.3 +/- 2.1 years and followup was 1.7 +/- 2.8 years. Reflux grade was significantly associated with resolution (p0.001). Multivariate analysis stratifying by grade demonstrated that a bladder volume at reflux onset on the initial cystogram of greater than 50% of predicted bladder capacity (p0.001), age younger than 2 years at diagnosis (p = 0.003) and history of prenatal hydronephrosis (p0.001) were significant factors predicting resolution within 2 years. Multivariable tables using age, bladder volume at reflux onset and grade demonstrated that children younger than 2 years at diagnosis and volume at onset greater than 50% of predicted bladder capacity had a higher early resolution rate for grades 2 (p = 0.012) and 3 (p0.001) reflux.Initial reflux grade, bladder volume at reflux onset, age at diagnosis and history of prenatal hydronephrosis were shown to be independent factors affecting the resolution rates of vesicoureteral reflux. The multivariable tables permit improved individualized prediction of resolution in patients with grades 2 and 3 reflux.

Minimally invasive treatment options and concern regarding long-term antibiotics have increased emphasis on predicting the chance of early vesicoureteral reflux resolution. Computational models, such as artificial neural networks, have been used to assist decision making in the clinical setting using complex numeric constructs to solve multivariable problems. We investigated various computational models to enhance the prediction of vesicoureteral reflux resolution.We reviewed the records of 205 children with vesicoureteral reflux, including 163 females and 42 males. In addition to reflux grade, several clinical variables were recorded from the diagnostic visit. Outcome was noted as resolved or unresolved at 1 and 2 years after diagnosis. Two separate data sets were prepared for the 1 and 2-year outcomes, sharing the same input features. The data sets were randomized into a modeling set of 155 and a cross-validation set of 50. The model was constructed with several constructs using neUROn++, a set of C++ programs that we developed, to best fit the data.A linear support vector machine was found to have the highest accuracy with a test set ROC curve area of 0.819 and 0.86 for the 1 and 2-year models, respectively. The model was deployed in JavaScript for ready availability on the Internet, allowing all input variables to be entered and calculating the odds of 1 and 2-year resolution.This computational model allowed the use of multiple variables to improve the individualized prediction of early reflux resolution. This is a potentially useful clinical tool regarding treatment decisions for vesicoureteral reflux.

Objectives To analyze the utility of assessing degree of constipation by abdominal radiograph (KUB) in relation to symptoms and urodynamic data in children with dysfunctional elimination. Methods A retrospective review of children with concomitant constipation and daytime incontinence was performed. Inclusion required at least two consecutive visits with KUB and noninvasive uroflowmetry. Patients were excluded for anticholinergic medication use or neurogenic or anatomic abnormalities. Rectal fecal quantification and presence of stool throughout the colon was assessed on KUB and categorized as “empty,” “normal amount of stool,” or “fecal distention of rectum (FDR).” Results Twenty-six patients met inclusion requirements (6 boys, 20 girls; average age, 7.7 ± 2.2 years). The average time between the initial and subsequent visit was 12.5 ± 7.8 weeks. Initial KUB revealed FDR in 17. No statistical significance was found between FDR on initial or final KUB and outcome of wetting symptoms, nor could a relationship between FDR uroflow parameters at either visit be demonstrated. Conclusions No correlation between any uroflowmetry parameter and the presence of FDR at the initial or final visits could be demonstrated. Similarly, no statistical significance between FDR on final or initial KUB and outcome of wetting symptoms was established.

OBJECTIVES The bladder pressure at the onset of reflux may reflect the competence of the ureterovesical junction. The predictive value of the bladder pressure at the onset of vesicoureteral reflux, as measured by nuclear cystometrography, was assessed relative to subsequent reflux resolution. METHODS Nuclear cystometrograms of 67 children were reviewed to determine the presence of reflux, bladder pressure at the onset of reflux, and bladder volume at the onset of reflux. The data were analyzed for significant relationships between the nuclear cystometrogram results and patient outcomes using a Cox proportional hazards regression model, controlling for the duration of follow-up and for patients with bilateral reflux. RESULTS Data were gathered for reflux occurring in 85 ureters. As expected, reflux of a greater grade was less likely to resolve spontaneously (P = 0.005). The pressure at the onset of reflux was also highly predictive of spontaneous resolution (P = 0.0005). Reflux occurring at greater pressures was more likely to resolve spontaneously, independent of the reflux grade or bladder volume at the onset of reflux. Patient age (P = 0.45), normalized volume of urine refluxed (P = 0.97), and normalized bladder volume at the onset of reflux (P = 0.18) were not significant predictors of reflux resolution. CONCLUSIONS The findings of this report have demonstrated for the first time, to our knowledge, that the bladder pressure at the onset of vesicoureteral reflux, as determined by nuclear cystometrography, is a significant independent predictor of vesicoureteral reflux resolution in children.

The treatment of vesicoureteral reflux has evolved over the past half-century from primarily surgical to nonoperative treatments. Although the benefits of surgical correction versus medical management are debated, the surgical techniques that have evolved are highly effective in correcting vesicoureteral reflux. Recently, the US Food and Drug Administration has approved an injectable implant of dextranomer/hyaluronic acid copolymer for use in children, making the endoscopic treatment of reflux a potential alternative to open surgical correction. This article reviews the different surgical techniques,postoperative management, and complications, as well as the various implants used in the endoscopic correction of vesicoureteral reflux and their outcomes.

Increased recognition of the association between urinary tract infections and reflux, sibling screening, and the evaluation of antenatal hydronephrosis have resulted in an increase in the diagnosis of reflux early in life. Although many children would sustain no untoward affects of their condition if reflux were left untreated, the disease can be severe and even life threatening. Although antireflux operations have been refined and improved, it remains difficult to determine which individuals truly benefit from these operations. A large prospective randomized placebo-antibiotic-operation study with long-term follow-up is needed, as is the development of nomograms, to assess the individual child's risk of adverse outcomes.

Reflux grade predicts resolution and influences followup and treatment. Bladder pressure at the onset of reflux may reflect the ureterovesical junction competence. By combining simultaneous cystometry with nuclear cystography (nuclear cystometrogram) we determined bladder pressure at the onset of reflux.Nuclear cystometrograms were performed in 40 children to determine bladder pressure at the onset of reflux, reflux volume and bladder capacity at the onset of reflux. The effect of bladder pressure and capacity at the onset of reflux was assessed with a reflux pressure volume index.A weak inverse correlation existed between bladder pressure at the onset of reflux and a normalized volume of reflux (r = -0.32, p = 0.018). A stronger correlation existed between reflux pressure and bladder volume at reflux (r = 0.47, p = 0.0002). An inverse correlation of the reflux pressure-volume index and reflux volume was significant (r = -0.49, p = 0.0002) as was the correlation between bladder volume at reflux and amount of reflux (r = -0.47, p = 0.0003). The reflux pressure-volume index for patients with persistent reflux at followup (median 1.89) was significantly smaller than that for those without reflux (median = 8.71, p = 0.02). A difference existed in normalized bladder volume at reflux between resolved and persistent reflux (p = 0.003). No difference was detected with respect to reflux volume and resolution (p = 0.738).A nuclear cystometrogram is no more invasive than a standard cystogram and permits determination of bladder pressure at the onset of reflux. Factors such as reflux pressure and bladder volume at reflux provide additional characterization of the ureterovesical junction and may help determine the prognosis for reflux resolution.

A duplex kidney associated with a poorly functioning upper-pole segment is commonly associated with incontinence, voiding dysfunction, and urinary tract infections. A standard treatment option for this condition is upper-pole heminephrectomy. With the continued development of minimally invasive urology, this technique can now be safely performed laparoscopically. This report details step by step our technique of laparoscopic upper-pole heminephrectomy. Key points include placement of a catheter in the normal ureter at the start of the case, full mobilization of the upper-pole ureter away from the renal hilum, and precise identification of the vasculature supplying the upper pole. Laparoscopic upper-pole heminephrectomy for ectopic ureter is safe and reproducible and offers the patient the typical postoperative benefits of laparoscopic surgery.

Gene transfer efficiency and specific cell targeting of vectors is a major obstacle in preclinical studies of gene therapy for malignant disease. Previous attempts at gene transfer in bladder cancer models have resulted in variable urothelial and tumor transgene expression after intravesical administration of recombinant viral vectors. In the current study we compared the gene transfer efficiencies of different viral vectors.We compared the gene transfer efficiencies of the viral vectors replication-deficient adenovirus, attenuated vaccinia virus (NYVAC) and canarypox virus (ALVAC) in vitro and in an orthotopic murine bladder cancer model. We used beta-galactosidase and firefly luciferase reporter gene expression to compare gene transfer efficiency.Significantly higher transgene expression was observed in vitro when these cells were infected with NYVAC or ALVAC compared with adenovirus vectors. Similarly the efficiency of adenovirus vectors to transfer genetic material into bladder urothelium and orthotopic bladder tumors was inferior to that of ALVAC and NYVAC vectors, which interestingly appeared to have a predilection to infect the orthotopic tumor. Analysis of the expression of coxsackie-adenovirus receptor using reverse transcriptase-polymerase chain reaction revealed the bladder tumor cell lines were lacking this adenovirus receptor. While adenovirus transferred genes poorly to normal bladder, coxsackie-adenovirus receptor expression was high in bladder tissue.The viral vectors examined in these experiments resulted in significantly different gene transfer in the orthotopic bladder cancer model, underscoring the importance of vector selection in gene therapy protocols.

In pre-clinical gene therapy studies of bladder cancer there is tremendous variation in the ability of viral vectors to deliver genetic material to bladder epithelium. Possible explanations for this variability may involve the physical parameters of delivering vectors in these experimental models. We examined the effects of intravesical volume and pressure during instillation as well as chemical modification of the bladder epithelium on subsequent gene expression in the bladder in mice.Female C57B1/6 mice underwent intravesical instillation of the replication restricted canarypox virus (ALVAC) recombinant for the reporter genes luciferase or beta-galactosidase. Similar viral titers were instilled at different volumes and a pressure transducer measured intravesical pressure when the vector was instilled. Also, various agents, including 0.6 N hydrochloric acid, 0.4% oxychlorosene, poly-L-lysine and 0.25 M. ammonium chloride, were used to modify the bladder surface before vector instillation and then assayed for transgene expression.As expected, maximum intravesical pressure measured during instillation was significantly greater in mice instilled with a higher volume (33.1 versus 9.8 mm. Hg). Significantly more gene expression was detected in bladders instilled with a higher volume of viral vectors (p0.05). Likewise, higher instillation pressures resulted in higher transgene expression in distant organs. Modification of the bladder epithelium with agents such as oxychlorosene and poly-L-lysine resulted in elevated gene expression with only minimal increases in systemic activity.Significant differences in gene expression are achieved by varying physical parameters during intravesical instillation. Increased gene expression associated with larger volume instillation may be responsible for some reported variability of gene transfer to the bladder. Alternate manipulations, such as modifying the bladder surface, may be done to enhance gene transfer to the urothelium without increasing systemic distribution.

Background: Although there are increasingly more clinical trials involving gene therapy, efficient gene transfer remains a major hurdle to success. To enhance the efficiency of delivery of viral vectors in gene therapy protocols, we evaluated the effect of various matrices to act as a vehicle for recombinant virus during intratumoral injection. Methods: The ability of several vehicles (catgut spacer, polyglycolic acid, chromic catgut, and gelatin sponge matrix) to deliver the canarypox virus ALVAC to the cells of the murine prostate cancer cell line RM-1 was studied in vitro and in vivo. ALVAC recombinants encoding the murine cytokines interleukin 2 (IL-2), interleukin 12 (IL-12), and tumor necrosis factor-a (TNF-a) were used to assess enhancement of antitumor activity after intratumoral inoculation. Confirmatory experiments were conducted by use of another mouse prostate cancer cell line, RM-11, and a mouse bladder cancer cell line, MB-49. All statistical tests were two-sided. Results: The gelatin sponge matrix proved to be the most effective solidstate vehicle for delivering viral vectors to cells in culture. In addition, this matrix statistically significantly enhanced expression of ALVAC-delivered reporter genes in tumor models when compared with fluid-phase delivery of virus (P = .037 for the RM-1 model and P = .03 for the MB-49 model). Statistically significant growth inhibition of established tumors was observed when a combination of the three recombinant ALVAC viruses expressing IL-2, IL-12, and TNF-a was delivered with the matrix in comparison with 1) fluidphase intratumoral injection of the ALVAC recombinants, 2) no treatment, or 3) treatment with parental ALVAC (all P

In children with severe unilateral reflux nephropathy and diminished relative renal function (RRF) a dilemma exists between the choice of treatment with ureteral reimplantation or nephrectomy. Limited followup data are available regarding relative renal function or postoperative complications after ureteral reimplantation in kidneys with significant unilateral reflux nephropathy.We retrospectively reviewed the records of 460 patients who underwent ureteral reimplantation between 1980 and 2002, and identified children with primary vesicoureteral reflux and severe unilateral reflux nephropathy (RRF 30% or less on renal scintigraphy). The postoperative outcomes were assessed for relative renal function and complications including hypertension, pyelonephritis or persistent reflux.A total of 18 girls and 14 boys with a mean preoperative relative renal function of 20.1 +/- 7.8% (range 2% to 30%) met the inclusion criteria. Reflux grade in the poorly functioning kidney was II in 4 children (13%), III in 14 (44%), IV in 11 (34%) and V in 3 (9%). Reflux was unilateral in 15 children (47%) and bilateral in 17 (53%). Mean followup from surgery was 3.7 years (range 0.3 to 12.9). In 28 children with both preoperative and postoperative renal scans, mean preoperative RRF was 20.3 +/- 7.4% and mean postoperative RRF was 20.5 +/- 8.6% with a mean time between renal scans of 2.3 years. No statistically significant change was noted from preoperative to postoperative relative renal function with a mean change of +0.2 +/- 3.7% (range -6.5% to +10%, p=0.82). Postoperative complications occurred in 7 of the 32 children (22%), including hypertension (1), pyelonephritis (3) and persistent reflux (4). Pyelonephritis occurred in 1 child with persistent reflux. No statistically significant difference existed in mean preoperative relative renal function between those with and without complications (24.6 +/- 8.9% vs 18.8 +/- 7.2%, p = 0.09).Children who underwent ureteral reimplantation in association with unilateral reflux nephropathy maintained stable relative renal function.

Purpose: We compared 2 treatment modalities (sling cystourethropexy and periurethral collagen injection) in patients with intrinsic sphincter deficiency alone or with urethral hypermobility (combined stress urinary incontinence).Materials and Methods: We retrospectively reviewed a series of 50 consecutive patients treated surgically for intrinsic sphincter deficiency during a 2-year period. All patients were evaluated by history and physical examination to assess urethral hypermobility and urodynamic testing. Intrinsic sphincter deficiency was assessed by abdominal leak point pressure and video urodynamics. Of the 50 patients 28 underwent a pubovaginal sling operation and 22 received a periurethral injection of collagen.Results: Of the patients studied 40 percent had combined stress urinary incontinence. A pubovaginal sling procedure resulted in a cure rate of 81 percent in this group, compared to 25 percent for periurethral injection of collagen.Conclusions: A subgroup of women exists with combin...

Children with daytime wetting often have constipation, and treatment of constipation helps children become dry. Polyethylene glycol 3350 (Miralax, Braintree Laboratories, Braintree, Massachusetts) is a nonaddictive, tasteless powder that can be mixed with any liquid for treatment of constipation.We review our use of polyethylene glycol 3350 in 35 girls and 11 boys with dysfunctional elimination. Noninvasive urodynamic studies and post-void residual measurement were performed before and during treatment.A significant increase in frequency of bowel movements occurred while taking polyethylene glycol 3350 (p = 0.0001). Average final dose was 0.63 gm/kg. The only reported adverse effect was diarrhea (9 patients). Of the children 18 became dry, 26 had decreased wetting and 2 had no improvement. Voided volume increased (146 vs 210 ml, p0.0001) and post-void residual decreased significantly (92 vs 48 ml, p0.0001) while on polyethylene glycol 3350. Ten children were still considered constipated including both patients who experienced no change in wetting. Average final dose in this group (0.69 gm/kg) did not differ significantly from those in whom constipation resolved (0.61 gm/kg). Patients in whom constipation resolved had a significantly lower post-void residual than those who remained constipated (11.8% vs 30.6%, p0.01) and were significantly more likely to become dry or improved (p = 0.045).The efficacy, compliance and lack of significant side effects make polyethylene glycol 3350 an ideal substance for treatment of constipation in children with dysfunctional elimination. Persistent constipation was associated with decreased resolution of voiding symptoms and significantly increased post-void residuals.

Vesicoureteral reflux (VUR) grading may be difficult when discrepancies exist between the degree of dilation of the pyelocalyceal system and the ureter. Resolution may be more accurately predicted by the appearance of the distal ureter. We analyzed a novel, objective method of evaluating VUR based on the diameter of the distal ureter.Seventy-nine voiding cystourethrograms were reviewed (18 boys; 61 girls; aged 1 month to 7.5 years). The largest ureteral diameter within the false pelvis was measured and normalized by dividing by the distance from the L1-L3 vertebral body to give the distal ureteral diameter: L1-L3 ratio (UDR). Clinical outcome was defined as spontaneous resolution or surgical correction.A significant association between grade and UDR existed (p0.0001). Mean UDR was significantly greater in those who underwent surgical correction (0.34 ± 0.02 vs 0.18 ± 0.02; p0.0001). Logistic regression analysis demonstrated a significant association of UDR with outcome controlling for grade (p = 0.001). Grade effect on outcome when controlling for UDR was not significant (p = 0.76). Odds ratio for surgical correction corresponding to a 0.1 increase in UDR equaled 2.25 (95% CI: 1.39, 3.64).UDR provides an objective measurement of VUR and appears more predictive of clinical outcome than grade in this series.

Constipation is commonly seen in pediatric patients. It is a frequent complaint seen by pediatric gastroenterologists as well as primary care providers. Constipation is very relevant to pediatric urology patients as it is seen frequently in patients presenting with urinary tract infections and/or voiding dysfunction. Dysfunctional elimination is the combination of bowel and bladder dysfunction that was initially described in patients with recurrent urinary tract infections and vesicoureteral reflux. It is important to seek out symptoms of bowel dysfunction in patients seen with urinary complaints and vice versa. The treatment of constipation is an integral part of the treatment regimen in children with voiding dysfunction. Encopresis, or fecal incontinence associated with constipation and chronic fecal impaction may also be present in patients with voiding dysfunction and recurrent urinary tract infections. In children with constipation an organic cause should be sought out during the evaluation including neurologic, endocrine, or anatomic causes. In 95% of patients no etiology is found and they are classified as having functional constipation.

Objective In a group of children diagnosed with vesicoureteral reflux (VUR) we evaluated renal ultrasound findings, associated findings on renal scan, and prognostic impact on VUR resolution. Methods Medical records were reviewed for children with primary reflux and no history of antenatal hydronephrosis who underwent an initial renal ultrasound. Abnormal renal ultrasound was defined as hydronephrosis or relative difference in renal size ≥1 cm. Reflux resolution was evaluated at 2 years post diagnosis. Results In 129 children with VUR (111 girls, 18 boys), 39 (30%) had an abnormal renal ultrasound. Two-year VUR resolution in the abnormal renal ultrasound group was 21% versus 46% in the group with normal renal ultrasound (P = 0.01). Combining grade II and III reflux, an abnormal ultrasound was associated with a statistically significantly lower resolution rate (grade II–III 23% vs 47%, P = 0.049). For children with moderate hydronephrosis, 8/9 (89%) had abnormal initial renal scans and all failed to achieve resolution of reflux at 2 years. Conclusions In this cohort of children with VUR, 30% had abnormalities on renal ultrasound. The presence of moderate hydronephrosis on ultrasound may indicate a high likelihood of abnormality on renal scan and failure to achieve early resolution of VUR.

Supernumerary kidney and cloacal exstrophy are rare anomalies of the genitourinary tract. We present an exceedingly rare case of a supernumerary third kidney discovered by antegrade nephrostography of a 6-month-old child with OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects).

Bladder augmentation is still a commonly performed reconstructive procedure for pediatric patients with severe bladder dysfunction. Recent developments in the long-term risks associated with this procedure are reviewed.There are metabolic changes in these patients after incorporation of bowel into the urinary tract. Linear growth and bone mineral density are more affected by the primary disorder rather than bladder augmentation. There is a high rate of reoperation in patients after bladder augmentation for perforation, bladder stones, and bowel obstruction. Bladder cancer has been reported in patients after bladder augmentation but also in patients without augmentation.Bladder augmentation is associated with a number of potential long-term risks, including a high risk of needing further surgery and development of serious complications such as bowel obstruction or bladder perforation. Bladder stones continue to be common in patients after bladder augmentation. Multiple cases of bladder cancer have been reported recently in young adults with a history of bladder augmentation in childhood and reinforce the need for lifelong follow up for these patients. Future studies will hopefully define the benefits and role of cancer surveillance for these patients.

Limited studies suggest a relationship between scarring on renal scan and failure to resolve vesicoureteral reflux. We evaluated the impact of abnormal renal scans on early vesicoureteral reflux resolution.The medical records and renal scans were reviewed of children diagnosed with primary reflux between 1988 and 2004. We defined an abnormal renal scan as renal scarring or relative renal function 40% or less. Reflux resolution was noted 1 and 2 years after diagnosis.Renal scan data were available on 161 children with vesicoureteral reflux, including 127 girls and 34 boys. Relative renal function was 15% or less in 7 children, 16% to 35% in 14, 36% to 40% in 18 and greater than 40% in 122. Of the 161 patients 79 (43%) had an abnormal renal scan, including 37% with grades 1 to 3 reflux. The rate of 2-year reflux resolution in the abnormal and normal renal scan groups was 13% vs 53%. Of children with grades II and III reflux those with an abnormal renal scan were less likely to have reflux resolution compared to those with normal renal scans (23% vs 55% and 4% vs 41, respectively, p0.05). The same relationship was present at 1 year for grades 2 and 3 (18% vs 49% and 4% vs 30, respectively, p0.05).Abnormal renal scans are an important independent predictor of early failure to resolve vesicoureteral reflux. An abnormal renal scan should be considered when counseling families about the likelihood of early reflux resolution. Performing a renal scan may be indicated in select patients.

Patients with neurogenic bladder dysfunction due to spina bifida have been reported to be at increased risk for bladder cancer. Recent publications suggest that bladder augmentation is also a significant risk factor. We reviewed our experience with treating patients with spina bifida and bladder cancer.Patients with spina bifida treated for bladder cancer between 1995 and 2005 were identified. Patient demographics, mode of bladder management, risk factors and presenting symptoms were recorded along with therapy, pathological findings and outcome. This patient cohort was combined with all prior known published studies for analysis.Eight patients with a median age of 41 years were treated. Only 1 patient (13%) had undergone bladder augmentation. Locally advanced stage (T3 or greater) or lymph node metastases were present in 88% of cases. Median survival was 6 months with only 1 patient alive with no evidence of recurrence at 20 months. A total of 11 prior published cases were identified and combined with this series. Transitional cell carcinoma was present in 58% of patients. Median survival was 6 months. Only 37% of patients had undergone bladder augmentation.Patients with spina bifida and bladder cancer present at a young age with variable tumor histology and advanced stage, and they have poor survival. Presenting symptoms are often atypical and bladder cancer should be a consideration in this patient population, even in young adults. Due to poor survival further study is warranted in this population to determine whether screening would be beneficial for earlier detection and improved outcomes.

Objective To describe a unique vaginal outlet obstruction and its ultrasound-assisted surgical correction. Design Case report. Setting An academic medical center. Patient(s) A 12-year-old girl was seen with cyclic abdominal pain, nausea, and an abdominal mass. External genital examination revealed no vaginal opening or dimple. Transabdominal ultrasound revealed a large hematometrocolpos 5 cm proximal to the perineum, with an otherwise normal-appearing uterus and ovaries. Intervention(s) Surgical treatment included perineal incision, creation of a 5-cm passage through connective tissue, drainage of the hematometrocolpos, and mobilization of the proximal vagina, allowing for pull-through vaginoplasty. Ultrasound guidance was used throughout the surgery and allowed for a safe transperineal approach. A vaginal form was placed in the neovagina. Main Outcome Measure(s) Follow-up clinical evaluation and pelvic ultrasonography. Result(s) A well-healed perineum and patent 5-cm–long vagina were observed at 4-month follow-up. The patient reported three regular menses. Postoperative pelvic ultrasound scan was normal. Conclusion(s) We describe a unique case of isolated distal vaginal agenesis of significant length that was successfully treated via a perineal approach with the intra-operative assistance of ultrasound guidance.

To examine the response to conversion from regular oxybutynin (Ditropan) to an extended-release form (Ditropan XL) in children with persistent daytime urinary incontinence.A retrospective review of patients with daytime wetting who switched from Ditropan to Ditropan XL included patient age, sex, reason for the change in medication, uroflowmetry findings before and after the change, side effects, and duration and dosage of the medication. The data were analyzed using a paired, two-tailed t test, with P0.05 considered significant.Twenty-seven patients were followed up for an average of 35.8 months. A lack of improvement (n = 11), convenience (n = 6), side effects (n = 2), and a dislike of the taste (n = 2) were identified as reasons for changing to the extended release form. The mean dosage of Ditropan and Ditropan XL did not differ significantly (0.40 and 0.38 mg/kg/day, respectively). After the change to Ditropan XL, 6 patients had a resolution of side effects and 7 developed new side effects. Of the 27 patients, 13 became dry or had significant improvement by the first visit after the change to Ditropan XL. Significant increases in voided volume (38% versus 53%; P0.01) and total bladder capacity (55% versus 70%; P = 0.03), normalized for age-expected bladder capacity, occurred by the first clinic visit after beginning Ditropan XL. No significant changes in the postvoid residual urine volume occurred.The frequency of wetting decreased and the voided volume and bladder capacity increased after a change to Ditropan XL in children with persistent wetting when taking Ditropan.

We report the incidence of calcifications developing at the bladder neck/urethra in pediatric patients treated with glutaraldehyde cross-linked collagen for urinary incontinence.We reviewed charts of patients treated with glutaraldehyde cross-linked collagen injections for urinary incontinence between 1994 and 1999. Etiology of incontinence, pertinent medical history, operative details and postoperative imaging were examined.Of 31 patients 4 (13%) had development of submucosal calcifications in the bladder neck/urethra. All 4 patients had received multiple injections of glutaraldehyde cross-linked collagen for incontinence secondary to neurogenic bladder. The calcifications were confirmed surgically. Pathology reports available for 2 of 4 patients showed chronic inflammation without dysplasia or malignant changes. Mean followup was significantly different between calcified and noncalcified cases (10.3 vs 7.2 years, p = 0.009), as was total volume of collagen injected (21 vs 12 cc, p = 0.012). Mean time to diagnosis of calcifications was 8.8 years (range 7 to 11) after first injection. A total of 24 patients without calcification underwent bladder imaging at a mean of 6.8 years (+/-2.2) after glutaraldehyde cross-linked collagen injection, which was not significantly different than the time to diagnosis (p = 0.089). The number of injections was not significantly different between the 2 groups (p = 0.426).Of our patients 13% had development of calcifications at the site of prior glutaraldehyde cross-linked collagen injections for incontinence. These calcifications were surrounded by chronic inflammation. Patients who have undergone glutaraldehyde cross-linked collagen injections may benefit from long-term followup with bladder imaging to detect and follow calcifications at prior injection sites.

Despite the acute onset, partial bladder outlet obstruction in the rabbit induces detrusor remodeling similar to that in men with benign prostatic hyperplasia in terms of its impact on structural and functional alterations in smooth muscle. We determined if partial bladder outlet obstruction induced remodeling alters the protein kinase C signaling pathway that leads to contraction.Smooth muscle from control animals and those subjected to 2 weeks of partial bladder outlet obstruction were mounted for isometric force recording, measurement of myosin light chain phosphorylation and levels of adducin phosphorylation. Bladder muscle strips were stimulated by phorbol dibutyrate or carbachol in the presence and absence of bisindolylmaleimide-1.Smooth muscle strips from animals subjected to partial bladder outlet obstruction showed little to no increase in stress in response to phorbol dibutyrate and no increase in myosin light chain phosphorylation levels. Muscle strips from control animals produced a robust contraction with concomitant increases in myosin light chain phosphorylation. Inhibition of protein kinase C by bisindolylmaleimide-1 significantly depressed carbachol induced contractions of muscle strips from control animals but it had no effect on carbachol induced contractions of muscle strips from outlet obstructed animals. Phorbol dibutyrate increased phospho-adducin levels in muscle strips from the 2 animal sources, suggesting that protein kinase C could be activated.We propose that partial bladder outlet obstruction does not alter protein kinase C activation, but rather abolishes or uncouples the pathway(s) downstream of protein kinase C, leading to contraction. Loss of this pathway may contribute to the loss of normal voiding behavior and the resultant decompensated state.

Reflux grade is the factor most commonly used to predict spontaneous reflux resolution. We evaluated other potential predictive factors aside from reflux grade relative to spontaneous resolution.We reviewed the records of 20 males and 98 females who were diagnosed with primary vesicoureteral reflux between ages 0 and 7 years between 1990 and 2000. Age, sex, height, weight, reflux grade, bladder volume at onset of reflux and laterality were recorded for the first, second and most recent voiding cystourethrogram or nuclear cystogram before spontaneous resolution or operative intervention.Of 118 patients 75 (64%) had spontaneous resolution, 27 (23%) underwent corrective surgery and 16 (13%) are still being followed. Average age at diagnosis was 2.3 years (range 1 day to 7.7 years) and average followup was 4.3 years (range 0.2 to 14). Average time to spontaneous resolution was 2.2 years (range 0.5 to 10.3) vs a time to operative treatment of 3.6 years (range 0.2 to 11.2). There was a significantly higher spontaneous resolution rate for lower reflux grades (p = 0.0004). Reflux occurring at greater than 75% of predicted bladder capacity had a significantly higher resolution rate (p = 0.0005). The initial height and weight percentile was not significant for predicting spontaneous resolution. Breakthrough urinary tract infections were negative predictors of spontaneous resolution (p0.0001).In addition to grade, bladder volume relative to predicted bladder capacity at the onset of reflux appears to provide additional prognostic information regarding the likelihood of spontaneous resolution of primary vesicoureteral reflux.

We hypothesized that the calcineurin pathway mediated some of the complex remodeling process that allows a bladder subjected to partial outlet obstruction to adapt to its new workload. Atrial natriuretic factor mRNA expression served as a marker of calcineurin activation.A total of 16 New Zealand White rabbits underwent surgical creation of partial outlet obstruction, followed by randomization to receive cyclosporin A (20 mg/kg intramuscularly twice daily) or no additional treatment for 14 days. Three animals underwent 2 weeks of partial bladder outlet obstruction followed by bladder biopsy and the reversal of obstruction.Atrial natriuretic factor expression was seen only in bladders with severe hypertrophy and it disappeared with the reversal of outlet obstruction. Cyclosporin A treatment resulted in a decrease in atrial natriuretic factor mRNA expression (p0.05) and a marked shift in myosin heavy chain A-to-B ratios toward normal (p0.01) and an increase in smooth muscle cross sectional area (p0.05). Bladder mass decreased 40% but did not attain statistical significance (p = 0.08).The calcineurin pathway has a significant role in bladder wall hypertrophy following partial outlet obstruction. Bladder hypertrophy could not be fully prevented by cyclosporin A, suggesting that multiple signaling pathways are involved in this pathophysiology. The expression of myosin heavy chain AB isoforms is regulated in part by the calcineurin pathway.

Objectives To examine the variables relative to the response of oxybutynin treatment in children with daytime urinary incontinence. Methods The records of patients seen for voiding problems between 1999 and 2003 were reviewed. Patients taking oxybutynin for 3 months or longer were included in the study. Patients with structural or neurologic bladder abnormalities and those taking oxybutynin at the initial visit were excluded. Age, sex, uroflowmetry findings, postvoid residual urine volume, duration and severity of symptoms before oxybutynin, urinary tract infection history, constipation, and the duration, dosage, and adverse effects of oxybutynin treatment were evaluated. Data were analyzed using Fisher’s exact test for categorical variables, the two-sample t test or Wilcoxon rank-sum test for continuous and ordinal variables, and the linear mixed model analysis for uroflow data. Results Eighty-one patients met the inclusion criteria. After an average follow-up of 1.2 years, 31 (38.3%) were dry, 25 (30.9%) had experienced significant improvement, 19 (23.5%) had experienced slight improvement, and 6 (7.4%) were unchanged. No significant differences were detected between those who became dry and those with little to no improvement with respect to age, sex, duration of symptoms, follow-up, uroflow pattern, postvoid residual urine volume, or bladder capacity. Those children presenting with decreased frequency of wetting episodes were significantly more likely to obtain daytime continence. The most common side effects were constipation (18.5%), dry mouth (17.3%), and flushing (13.6%). Conclusions Children with daytime incontinence presenting with the lowest frequency of wetting were most likely to achieve continence. The frequency of wetting should be considered a significant prognostic variable when assessing the results of therapeutic intervention trials.