J. Christopher Austin

Long-term risks of bladder augmentation in pediatric patients

Purpose of review 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. Recent findings 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. Summary 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.

Treatment of stress urinary incontinence in women with urethral hypermobility and intrinsic sphincter deficiency.

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% had combined stress urinary incontinence. A pubovaginal sling procedure resulted in a cure rate of 81% in this group, compared to 25% for periurethral injection of collagen. CONCLUSIONS A subgroup of women exists with combined stress urinary incontinence due to urethral hypermobility and intrinsic sphincter deficiency. When treated with sling cystourethropexy women with combined stress urinary incontinence do as well or better than those with intrinsic sphincter deficiency alone and those treated with periurethral collagen injection do worse.

Bladder Volume at Onset of Reflux on Initial Cystogram Predicts Spontaneous Resolution

PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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 (p <0.0001). CONCLUSIONS 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.

Abnormal Renal Scans and Decreased Early Resolution of Low Grade Vesicoureteral Reflux

PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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, p <0.05). The same relationship was present at 1 year for grades 2 and 3 (18% vs 49% and 4% vs 30, respectively, p <0.05). CONCLUSIONS 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.

Evaluation of gene transfer efficiency by viral vectors to murine bladder epithelium

PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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 (p <0.05). 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. CONCLUSIONS 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.

DMSA renal scans and the top-down approach to urinary tract infection.

Assessment of first febrile urinary tract infection in young children has usually involved 2 imaging techniques: renal ultrasonogram and voiding cystourethrography. Currently, there is growing interest in using the dimercaptosuccinic acid (DMSA) scan labeled with technetium-99m as an alternative initial study, in the evaluation of UTI. DMSA renal scanning is the most sensitive radiologic study to detect acute pyelonephritis. Early DMSA renal scanning has been called the top-down approach, because the focus is the identification of kidney injury rather than reflux. Positive and negative aspects of DMSA renal scans are discussed by a pediatric urologist.

Cystic dysplasia of the testis associated with ipsilateral renal agenesis and contralateral crossed ectopia

Cystic dysplasia is a benign congenital lesion of the rete testis often associated with ipsilateral wolffian duct and ureteral abnormalities. We present a case of cystic dysplasia and associated anomalies in a 12-year-old boy. The workup revealed right testicular cystic dysplasia, ipsilateral renal agenesis, contralateral crossed renal ectopia, and vesicoureteral reflux. We performed right testicular-preserving cyst enucleation and ureteroneocystostomy. No testicular atrophy or new cyst formation was evident at 1 year of follow-up. This is the first reported case of cystic dysplasia associated with ipsilateral renal agenesis and contralateral crossed renal ectopia.

Adding Renal Scan Data Improves the Accuracy of a Computational Model to Predict Vesicoureteral Reflux Resolution

PURPOSE 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. MATERIALS AND METHODS 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++. RESULTS 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. CONCLUSIONS 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.

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida

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.

Safety and efficacy of spica casts for immobilization following initial bladder closure in classic bladder exstrophy.

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.