John W. Brock

A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele

BACKGROUNDnPrenatal repair of myelomeningocele, the most common form of spina bifida, may result in better neurologic function than repair deferred until after delivery. We compared outcomes of in utero repair with standard postnatal repair.nnnMETHODSnWe randomly assigned eligible women to undergo either prenatal surgery before 26 weeks of gestation or standard postnatal repair. One primary outcome was a composite of fetal or neonatal death or the need for placement of a cerebrospinal fluid shunt by the age of 12 months. Another primary outcome at 30 months was a composite of mental development and motor function.nnnRESULTSnThe trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatal-surgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P=0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery.nnnCONCLUSIONSnPrenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606.).

THE ROLE OF HYPERCALCIURIA IN A SUBGROUP OF DYSFUNCTIONAL VOIDING SYNDROMES OF CHILDHOOD

PURPOSEnIdiopathic hypercalciuria is believed to be the cause of a variety of urinary tract complaints in clinical pediatrics, including urinary frequency, urgency, and/or dysuria, often associated with gross or microscopic hematuria. In children noncalculous manifestations of idiopathic hypercalciuria are reportedly more common than urolithiasis. We determine the use of the calcium-to-creatinine ratio for the evaluation of different subsets of functional voiding disorders.nnnMATERIALS AND METHODSnWe retrospectively evaluated 288 patients with functional voiding disorders during the last 8 years. Patients presenting with isolated urinary tract infection were not included in the study. A thorough history with emphasis on voiding patterns was elicited and a routine urinalysis was performed in all patients. Patients were divided into 5 groups of 22 with total gross hematuria and dysfunctional voiding pattern, 102 with microhematuria and dysfunctional voiding pattern, 66 with isolated childhood daytime frequency, 45 with the isolated dysuria syndrome and 53 with combined childhood frequency-urgency-dysuria syndrome. The season at presentation was noted to determine a seasonal pattern. In 149 patients urine was evaluated for a spot calcium-to-creatinine ratio.nnnRESULTSnMean age of the 95 (33%) males and 193 (67%) females was 6.1 years (range 2 to 14) and mean duration of symptoms was 10 months (1 week to 10 years). The incidence of idiopathic hypercalciuria was 28% in cases with gross hematuria and dysfunctional voiding, 30% with microscopic hematuria and dysfunctional voiding, 21% with pure childhood daytime frequency, 22% with pure dysuria, and 28% with frequency, urgency and dysuria. The patients were treated predominantly with behavioral therapy, correction of faulty voiding habits, anticholinergics and minor diet modification in some. Mean followup of 6.5 months (range 1 month to 10 years) was available for 153 patients (53%). Resolution of symptoms along with marked improvement in voiding habits was noted in 136 (89%) patients, moderate improvement in 10 (6.5%) and persistent symptoms with minimal improvement in 7 (4.5%). Treatment with thiazides was used in only 6 (2%) patients who had intractable symptoms and a markedly elevated urine calcium-to-creatinine ratio of whom 5 responded favorably.nnnCONCLUSIONSnIdiopathic hypercalciuria may have a significant role in cases of functional voiding disorders. It affects the different subsets of voiding disorders with remarkable consistency but the exact mechanism remains unknown. Although a significant number of patients with voiding dysfunction have an elevated calcium-to-creatinine ratio, the majority respond to standard behavioral therapy and pharmacotherapy in the form of anticholinergics, and treatment directed toward hypercalciuria is not required in most cases.

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.

PURPOSEnBetween 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.nnnMATERIALS AND METHODSnUsing 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.nnnRESULTSnWe 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.nnnCONCLUSIONSnNeurogenic 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.

Caudal Regression with Cake Kidney and a Single Ureter: A Case Report

We report the second case of a cake kidney with a single ureter accompanied by caudal regression. The embryology, presentation and management of this malformation are delineated.

Modulation of the Hypoxic Response Following Partial Bladder Outlet Obstruction

PURPOSEnTissue 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.nnnMATERIALS AND METHODSnA 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.nnnRESULTSnImmunostaining 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).nnnCONCLUSIONSnMurine 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.

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.

The Urologist's Role in the Management of Spina Bifida: A Continuum of Care

Caring for the child with spina bifida necessitates lifelong care by a coordinated team of health care providers, and the urologist plays a vital role in this team. The most important management goal of the urologist is the early establishment and consistent maintenance of a lower pressure urinary reservoir. Ensuring social continence along with its attendant social independence provides some of the greatest management challenges. In those patients who fail medical therapy, surgeons, caregivers, and patients must understand the scope of lower urinary tract reconstruction, the need for strict compliance, and the possibility of future surgery. In this article, we review the recent advances in spina bifida management.

SIU/ICUD Consultation on Urethral Strictures: Urethral strictures in children.

A literature search was made through PubMed from 1990 to the present for articles on strictures in children. There were 32 articles that provided the data for this review. The studies were rated according to the level of evidence and the grade of recommendation using the International Consultations in Urologic Disease standards.