This Month in Pediatric Urology

Article Outline

• Candidate Urinary Biomarker Discovery in Ureteropelvic Junction Obstruction
• Proximal Hypospadias and the Risk of Acquired Cryptorchidism
• Transcutaneous Electrical Nerve Stimulation in Children With Overactive Bladder
• Sacral Neuromodulation for Urinary and Fecal Incontinence
• Lumbar to Sacral Nerve Rerouting for Spina Bifida
• Copyright

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Candidate Urinary Biomarker Discovery in Ureteropelvic Junction Obstruction 

Protocols have been established for the assessment of prenatal hydronephrosis with conservative management having a primary role. However even with established pathways, our evaluation, treatment and need for operative intervention can be subjective. Identifying an objective marker that consistently equates with an operative obstruction has significant value, potentially decreasing repeated studies and unnecessary family stress. Mesrobian et al (page 709) from Milwaukee, Wisconsin present a pilot analysis of urinary proteomes and their ability to stratify between patterns of hydronephrosis and a normal upper urinary tract. The authors compared 25 neonates with grade 4, unilateral, prenatal hydronephrosis to a normal control group, and followed them for at least 12 months.

In the 1 to 6-month age group 26 proteins were significantly increased and 5 were decreased compared to controls, with 13 proteins expressed only in the hydronephrotic group. In the 7 to 12-month age group 15 proteins were increased and 3 were decreased, with 14 expressed only in the hydronephrotic group. The 2 age groups shared 11 common proteins but those proteins were expressed differently with regard to up or down regulation. All proteins are believed to specifically relate to the kidney and changes in time are in response to different renal influences. The findings in this study are consistent with other reports showing that expression of urinary proteins is different between hydronephrotic and normal kidneys. Eventually 7 neonates underwent operative intervention, and studies are ongoing to determine if this subset has any characteristic proteomic differences. It will be interesting to see the results of the proposed clinical trial evaluating the value of these markers in a larger patient group.

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Proximal Hypospadias and the Risk of Acquired Cryptorchidism 

Acquired cryptorchidism has been reported in up to 7% of boys due to an unknown etiology. Tasian et al (page 715) from San Francisco, California propose reduced androgen activity as a cause of acquired cryptorchidism. They retrospectively compared 114 boys who underwent repair of significant proximal hypospadias to an age matched control group of 342 boys. The primary outcome was the development of acquired cryptorchidism using hypospadias as the primary predictor, and secondary variables of ethnicity, age and comorbidities. Separate analyses were conducted for the outcomes of acquired and primary cryptorchidism, and retractile testes.

Acquired cryptorchidism was noted in 16 boys in the hypospadias group and 1 control subject. Hypospadias and postnatal growth retardation correlated with development of acquired cryptorchidism on univariate analysis but growth retardation dropped out when assessed on multivariate analysis. Hypospadias was associated with retractile testes and contralateral retractile testes appeared to be associated with acquired cryptorchidism. A higher prevalence of retractile testes occurred in children with hypospadias compared to controls, leading the authors to postulate that retractile and acquired cryptorchidism are different points on the same spectrum. Bilateral cryptorchidism occurred more often in children with acquired cryptorchidism, indicating that a systemic process contributed to testicular ascent and supporting the hypothesis that disruption of normal androgen access occurs, which may be the unifying factor between acquired cryptorchidism and hypospadias. The authors note limitations in their study but conclude that there is an association between severe hypospadias and acquired cryptorchidism, suggesting that prenatal and postnatal androgen disruption should be explored further.

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Transcutaneous Electrical Nerve Stimulation in Children With Overactive Bladder 

Several articles have reported on the treatment of overactive bladder, the majority of which are retrospective and poorly controlled. Lordêlo et al (page 683) from Brazil present a prospective, randomized, sham controlled study of parasacral transcutaneous electrical nerve stimulation for the treatment of overactive bladder. Superficial electrodes were placed on each side of S2/S3 and in a scapular area. The sacral electrodes were activated in the test group (21 children) and the scapular electrodes in the sham group (16). The children underwent 20 minutes of stimulation 3 times a week for a total of 20 sessions. Those evaluating the outcome of the procedure were not involved with the stimulation and were blinded to the study participants. The results were based on subjective assessment of the parents determining if the child was improved as well as a visual analog improvement scale, nonvalidated adapted score of Toronto, and a diary indicating the number of voids per day, and average and maximal voided volume. Nonresponders in the sham group crossed over to stimulation for 20 treatments.

Complete improvement was reported by the parents in the treatment group only, although significant improvement was reported by parents in both groups. Higher results were recorded in the treatment arm compared to the sham group when using the visual analog scale, and the modified Toronto score showed a statistically significant difference in both groups. The treatment group had an increase in mean and average voided volumes with a decrease in the number of voids per day not seen in the sham group. All 16 children in the sham group crossed over to the treatment group. Followup at 16.2 months revealed symptom recurrence in 4 children. The authors note that the mechanism of action of electrical stimulation and its effect on overactive bladder are unknown. They appreciate limitations of their study and plan further studies on the effectiveness of decreasing the number of weekly sessions, and altering the pulse width and frequency.

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Sacral Neuromodulation for Urinary and Fecal Incontinence 

Sacral neuromodulation (SNM) has been shown to be effective in adults with sphincter disorders secondary to neurogenic causes but only small pediatric series have been reported. Haddad et al (page 696) from Marseille, France describe the results of a large pediatric, prospective, randomized, crossover study stimulating S3 nerve roots with a neuromodulator at multiple centers throughout France. Study inclusion criteria were urinary incontinence, post-void residual greater than 50% of functional bladder capacity, poor bladder compliance, overactive bladder contractions and/or fecal incontinence. Children were randomized to group A (stimulation on for 6 months then off for 6 months or group B (sequence opposite that of group A). A primary end point was disappearance of urinary leakage and/or fecal soiling with no need for pads, or a decrease of more than 50% in the number of leaks and/or soiling. Neuromodulation was considered effective if urinary or fecal response occurred. Secondary end points were urodynamic and rectal anal manometric parameters.

Clinical response, and urinary and fecal continence were significantly better when SNM was on than off. Clinical improvement in urinary or fecal continence did not correlate with improvement in urodynamic parameters or manometric measurements, respectively. The authors report that the physiological mechanism of the action of SNM on fecal and urinary incontinence is not understood. However, they conclude that SNM is effective in treating neurogenic incontinence and should be considered before proceeding with other irreversible operative interventions.

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Lumbar to Sacral Nerve Rerouting for Spina Bifida 

Creation of a skin-central nervous system-bladder reflex arc is one of the most innovative operations used to treat neurogenic bladder, which has gained a great deal of attention because of the success reported in the Chinese population. The reflex begins with cutaneous stimulation of a specific dermatome that sends a sensory signal from the dorsal somatic nerve root of L4-L6 with return of a motor signal to the ventral aspect of the nerve root that has been anastomosed to S2 or 3, resulting in a reflex contraction of the bladder. To investigate the safety and efficacy of this procedure Peters et al (page 702) from Royal Oak, Michigan established the first North American pilot study in 9 children with spina bifida in whom this reflex arc was created. An active donor nerve root was required for anastomosis and, therefore, all children were ambulatory. An attempt was made to sacrifice only half of the motor nerve to preserve lower extremity function.

As expected, weakness was noted postoperatively in 1 or more of the lower extremity muscle groups that corresponded to the dermatome distribution of the sacrificed nerve. At 6 and 9 months postoperatively patients reported worsening of bladder and bowel continence which subsequently improved. At 1 year all but 1 child experienced return to baseline function, 7 patients had a reproducible bladder reflex with cutaneous stimulation, 7 could initiate a spontaneous void with a satisfactory voided volume but with a persistent post-void residual, bladder compliance improved from a baseline of 16.1 to 21.8 ml/cm H₂O and all patients had been taken off antimuscarinic medication. While improvements are documented, no child achieved urinary continence. At the completion of the study improvement in bladder function was continuing without plateau and the maximal benefit has not yet been achieved.

The results are encouraging but the authors note the problems of objectively determining the true benefit of the procedure balanced by the potential risk of decreased lower extremity motor function. They clearly demonstrate that somatic to visceral nerve rerouting is possible in children with spina bifida with some changes in bladder and bowel function. Further investigation is required to determine whether these changes can be reproduced on a large scale with limited morbidity and a positive impact on quality of life.