Tom P.V.M. de Jong

Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux

Congenital anomalies of the kidney and urinary tract (CAKUT) include vesicoureteral reflux (VUR). VUR is a complex, genetically heterogeneous developmental disorder characterized by the retrograde flow of urine from the bladder into the ureter and is associated with reflux nephropathy, the cause of 15% of end-stage renal disease in children and young adults. We investigated a man with a de novo translocation, 46,X,t(Y;3)(p11;p12)dn, who exhibits multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. This translocation disrupts ROBO2, which encodes a transmembrane receptor for SLIT ligand, and produces dominant-negative ROBO2 proteins that abrogate SLIT-ROBO signaling in vitro. In addition, we identified two novel ROBO2 intracellular missense variants that segregate with CAKUT and VUR in two unrelated families. Adult heterozygous and mosaic mutant mice with reduced Robo2 gene dosage also exhibit striking CAKUT-VUR phenotypes. Collectively, these results implicate the SLIT-ROBO signaling pathway in the pathogenesis of a subset of human VUR.

Treatment of the neurogenic bladder in spina bifida

Renal damage and renal failure are among the most severe complications of spina bifida. Over the past decades, a comprehensive treatment strategy has been applied that results in minimal renal scaring. In addition, the majority of patients can be dry for urine by the time they go to primary school. To obtain such results, it is mandatory to treat detrusor overactivity from birth onward, as upper urinary tract changes predominantly start in the first months of life. This means that new patients with spina bifida should be treated from birth by clean intermittent catheterization and pharmacological suppression of detrusor overactivity. Urinary tract infections, when present, need aggressive treatment, and in many patients, permanent prophylaxis is indicated. Later in life, therapy can be tailored to urodynamic findings. Children with paralyzed pelvic floor and hence urinary incontinence are routinely offered surgery around the age of 5 years to become dry. Rectus abdominis sling suspension of the bladder neck is the first-choice procedure, with good to excellent results in both male and female patients. In children with detrusor hyperactivity, detrusorectomy can be performed as an alternative for ileocystoplasty provided there is adequate bladder capacity. Wheelchair-bound patients can manage their bladder more easily with a continent catheterizable stoma on top of the bladder. This stoma provides them extra privacy and diminishes parental burden. Bowel management is done by retrograde or antegrade enema therapy. Concerning sexuality, special attention is needed to address expectations of adolescent patients. Sensibility of the glans penis can be restored by surgery in the majority of patients.

Bladder-sphincter dysfunction in myelomeningocele

Abstract Pediatric urodynamics taught us that detrusor-sphincter dyssynergia creates a bladder outlet obstruction in about 50% of any population of children with myelomeningocele. This functional obstruction causes renal damage due to obstructive uropathy, exactly the same way as a congenital anatomical urethral obstruction does. Pediatric urodynamics also taught us that in children with myelomeningocele pelvic floor activity and detrusor activity can be abnormal (hyperactive or inactive) completely independent from each other. These insights have changed the management of myelomeningocele. Children with overactivity of the pelvic floor can be singled out at infant age, and started on clean intermittent catherization, to prevent obstructive uropathy and preserve renal function. Children with detrusor overactivity can be singled out too at very early age, and treated with anticholinergics, to prevent irreversible structural damage to the detrusor and preserve normal bladder capacity and compliance.

Cultural Bias in the AAP’s 2012 Technical Report and Policy Statement on Male Circumcision

The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report’s conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non–US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.

Urologic problems in anorectal malformations. Part 1: Urodynamic findings and significance of sacral anomalies.

A series of 90 children with anorectal malformations received a total of 163 urodynamic studies. The mean number of studies per patient was 1.8 (range, 1 to 7), and the mean age at the time of initial evaluation was 17 months (range, 1 to 128). Sacral anomalies were found in 38 children (42%); 30 of them had partial sacral agenesis and eight had sacral dysplasia without bony defect. Normal lower urinary tract function was found in 98% of the children who had a normal sacrum, in all children who had sacral dysplasia, and in a small number of those who had partial sacral agenesis that affected smaller parts of the S-4 and S-5 pedicles. Severe lower urinary tract dysfunction was observed in 22 patients (24%), all but one of whom had partial sacral agenesis. There was no correlation between the type of sacral agenesis and a specific urodynamic pattern. It is concluded that virtually all children with an anorectal malformation and associated sacral agenesis have neurological bladder-sphincter dysfunction and therefore should receive early urodynamic assessment and appropriate urological treatment.

The surgical correction of buried penis : a new technique

AbstractPurpose: We report a new surgical technique for the correction of buried penis.Materials and Methods: The study comprised 10 boys with buried penis. The technique consisted of resection of abnormal dartos attachments, unfurling of the prepuce and correction of the deficient shaft skin by reapproximation of the preputial skin flaps in a defined way to obtain sufficient penile skin coverage.Results: Outcome was excellent in 6 cases, good in 3 and unsatisfactory in 1.Conclusions: Perfect cosmetic results were obtained and no serious complications developed.

Long-Term Followup of Hypospadias: Functional and Cosmetic Results

PURPOSE We assessed long-term results after hypospadias surgery with respect to urinary and sexual function, cosmetic appearance and intimate relationships. MATERIALS AND METHODS We contacted 116 patients who are now adults and who underwent surgery between 1987 and 1992. Participation included mailed questionnaires containing the International Prostate Symptom Score, International Index of Erectile Function and the Dutch Survey of Intimate Relations (Nederlandse Relatie Vragenlijst) as well as uroflowmetry and cosmesis assessment using the Pediatric Penile Perception Score. A control group of 151 male students completed the International Prostate Symptom Score and International Index of Erectile Function, and underwent uroflowmetry. RESULTS A total of 91 patients (78%) were traceable, 57% returned the questionnaires and 27% visited the clinic. Hypospadias was distal, mid shaft and proximal in 47, 8 and 11 patients, respectively. International Prostate Symptom Score was greater than 7 in 9 of 64 patients (14%) compared to 10 of 151 controls (7%). Patients with distal hypospadias complained more about micturition. Patients with proximal hypospadias had lower maximum urine flow than other patients and controls. For sexuality the total International Index of Erectile Function did not differ between patients and controls. Patients with proximal hypospadias reported less satisfaction with penile length and objectively penile length was less than the average of all patients (10.8 vs 12.1 cm). Cosmetic outcome was considered satisfactory. Outcomes in the 33 patients who returned the Dutch Survey of Intimate Relations correctly were above average, especially for sexuality and independence. CONCLUSIONS Patients with distal hypospadias have a higher International Prostate Symptom Score and patients with proximal hypospadias have lower maximum urine flow than controls. Sexual function and cosmesis are rated good. The quality of intimate relationships is above average.

The relevance of urodynamic studies for urge syndrome and dysfunctional voiding: A multicenter controlled trial in children

PURPOSE The objective of this study was to compare prospectively, in urge syndrome and dysfunctional voiding, clinical patterns with urodynamic patterns, to assess changes in urodynamic patterns after treatment, and to correlate urodynamic patterns and parameters with treatment outcome. MATERIALS AND METHODS In the European Bladder Dysfunction Study 97 children with clinically diagnosed urge syndrome received standard treatment, to which was randomly added placebo, oxybutynin or bladder training with online feedback. In a separate branch 105 children with clinically diagnosed dysfunctional voiding were randomly allocated to standard treatment or standard treatment plus pelvic floor training with online feedback. In all children urodynamic studies were performed before and immediately after treatment. RESULTS In urge syndrome detrusor overactivity was present in 33% of cases before and 27% after treatment (of which 65% were de novo). Detrusor overactivity did not correlate with treatment outcome. In dysfunctional voiding increased pelvic floor activity during voiding, which was present in 67% of cases before and 56% after treatment (of which 45% were de novo), did not correlate with treatment outcome. In urge syndrome as well as in dysfunctional voiding neither maximum detrusor pressure during voiding, cystometric bladder capacity, bladder compliance nor free flow patterns correlated with treatment outcome. CONCLUSIONS Neither detrusor overactivity nor increased pelvic floor activity during voiding correlated with treatment outcome. Standard treatment could be the first choice in urge syndrome as well as in dysfunctional voiding, reserving urodynamic studies for patients in whom this first approach fails.

Home uroflowmetry biofeedback in behavioral training for dysfunctional voiding in school-age children: a randomized controlled study.

PURPOSE We studied the added value of home uroflowmetry for biofeedback training compared to added attention and standard therapy in a multicomponent behavioral training program for voiding disorders in school-age children. Little is known about the role of biofeedback by home uroflowmetry for dysfunctional voiding due to NNBSD in children. MATERIALS AND METHODS A randomized controlled study was conducted at an outpatient pediatric incontinence university clinic from January 2000 to June 2003. A total of 192 children 6 to 16 years old who were suffering from recurrent urinary tract infections with or without urge incontinence were screened for NNBSD. Of 143 eligible patients 44 were randomly allocated to receive 8 weeks of standard therapy (outpatient behavioral therapy), 46 to receive 8 weeks of home video instructions together with standard therapy and 53 to receive 8 weeks of home uroflowmetry biofeedback together with standard therapy. After 8 weeks all treatment groups proceeded with standard therapy for 16 weeks, after which prophylaxis with antibiotics was stopped and patients were followed for another 6 months. Main outcome measurement was total relief of complaints, namely urinary tract infections and, if present, incontinence, at 12 months after randomization. RESULTS At baseline there was no reason to predict major incomparabilities between the groups. In an intent to treat analysis there was no difference in total relief between standard treatment (44%) and added video instruction (42%, RR 0.96, 95% CI 0.59 to 1.56). Total relief in the added home uroflowmetry group (55%) was higher than with standard therapy (RR 1.24, 95% CI 0.80 to 1.93), although the difference was not statistically significant. A per protocol analysis suggested that the groups with added home uroflowmetry showed better total relief than the pooled groups with standard therapy and those with added video (RR 1.40, 95% CI 0.98 to 2.00). CONCLUSIONS Home uroflowmetry appears to be a useful adjunctive treatment for the reduction of complaints in children with dysfunctional voiding due to nonneurogenic bladder-sphincter dyssynergia.

Lower Urinary Tract Dysfunction in Children with Benign Sacrococcygeal Teratoma

We evaluated 8 girls and 3 boys with benign sacrococcygeal teratoma for lower urinary tract dysfunction. All children underwent ultrasonography of the urinary tract, voiding cystourethrography and at least 2 standard urodynamic evaluations. Mean patient age at first urodynamic study was 59 months (range 1 to 136). Nine of the 11 children had abnormal studies, including detrusor instability and associated pelvic floor overactivity during micturition in 2, an anatomical infravesical obstruction in 2 and neurogenic bladder-sphincter dysfunction in 5 (2 detrusor hyperreflexia with sphincter dyssynergia, 2 hyporeflexic bladder-sphincter function and 1 detrusor hyporeflexia with normal sphincter function). Although the major cause of neurogenic lower urinary tract dysfunction seems to be related to surgical trauma of the pelvic plexus and sacral nerves, we observed tethered spinal cord as a primary cause in 2 patients. The incidence of voiding dysfunction in children with sacrococcygeal teratoma is high and is usually neurogenic in origin.