Douglass B. Clayton

Urologic management of spina bifida.

The urologist plays an important role in the multidisciplinary team of physicians who provide care for patients with spina bifida. We review common strategies for managing the urinary tract in these patients. The primary objective in all phases of life is protecting kidney function by minimizing bladder hostility and establishing a good capacity, low-pressure urinary reservoir. Ensuring adequate bladder and bowel continence is also paramount for enhancing self-esteem and independence. Medical therapy incorporating clean intermittent catheterization and antimuscarinic medication is the cornerstone of neurogenic bladder management and often the only intervention required to achieve the above goals. Others may require formal lower urinary tract reconstruction to prevent urinary tract deterioration. As will be shown, current management, while effective, is not supported by strong evidence-based protocols; and the impact of any intervention upon quality of life, while subjectively seen as positive, does not have objective validation. These limitations are recognized and currently the subject of urologic investigation.

Long-term urological impact of fetal myelomeningocele closure.

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.

Incidence of abnormal imaging and recurrent pyelonephritis after first febrile urinary tract infection in children 2 to 24 months old.

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.

The increasing pediatric stone disease problem

While once thought to be relatively rare in developed nations, the prevalence of pediatric urolithiasis appears to be increasing, and a number of factors may be contributing to this increase. Many theories are plausible and such theories include the increasing childhood obesity epidemic, a changing sex predilection, climate change, alterations in dietary habits and improving diagnostic modalities. Yet, unlike adult patients, rigorous epidemiologic studies do not exist in pediatric populations. Thus, in the setting of an increasing prevalence of childhood stone disease, improved research is critical to the development of uniform strategies for pediatric urolithiasis management.

Lower Urinary Tract Obstruction in the Fetus and Neonate

This article summarizes the most recent literature regarding congenital lower urinary tract obstruction in the fetus and newborn. Lower urinary tract obstruction is a heterogeneous group of rare diagnoses that have significant potential for in utero mortality and long-term morbidity in survivors. The diagnosis and management of the most common causes are reviewed. In addition, the current state of prenatal intervention for congenital lower urinary tract obstruction is discussed.

Prospective Evaluation of Sacral Nerve Modulation in Children with Validated Questionnaires

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.

Modulation of the Hypoxic Response Following Partial Bladder Outlet Obstruction

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.

Prospective Evaluation of Sacral Neuromodulation in Children: Outcomes and Urodynamic Predictors of Success

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.

Bullying and Lower Urinary Tract Symptoms: Why the Pediatric Urologist Should Care about School Bullying

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.

Prenatal Ultrasound and Urological Anomalies

Prenatal ultrasound is an integral part of caring for pregnant women in the United States. Although surprisingly few data exist to support the clinical benefit of screening ultrasound during pregnancy, its use continues to rise. Urologic anomalies are among the most commonly identified, with overall detection sensitivity approaching 90%. Prenatal hydronephrosis is the most frequently identified finding and predicting postnatal pathology based on its presence can be difficult. As the degree of fetal hydronephrosis increases so does the risk of true urinary tract pathology. Diagnoses that require more urgent care include causes of lower urinary tract obstruction and bladder and cloacal exstrophy.