Henri Lottmann

OUTCOME OF POSTERIOR URETHRAL VALVES: TO WHAT EXTENT IS IT IMPROVED BY PRENATAL DIAGNOSIS?

PURPOSE To assess the impact of prenatal diagnosis and evaluation on the outcome of posterior urethral valves we studied all cases of valves detected prenatally, including cases of pregnancy termination due to posterior urethral valves. MATERIALS AND METHODS Between 1989 and 1996, 30 neonates with prenatally detected posterior urethral valves were treated at our hospital. The prenatal parameters analyzed were age of gestation at diagnosis, ultrasonographic appearance of renal parenchyma and amniotic fluid volume. Fetal urine was analyzed in 9 cases. We reviewed the outcome of 10 neonates treated for posterior urethral valves which were not diagnosed prenatally during the same period. RESULTS Of the 30 neonatal survivors 6 (20%) had renal failure, including end stage renal disease in 2, after a mean followup of 4 years. Renal failure developed in 2 of 5 cases detected before 24 weeks of gestation, in 1 of 6 with oligohydramnios and in 2 of 5 with abnormal parenchymal renal ultrasound. Normal parenchymal ultrasound and amniotic volume could not predict for good outcome. Renal failure developed in 2 of 7 cases predicted by fetal urinalysis as good prognosis and in 1 of 2 cases predicted as poor prognosis. Pregnancy was terminated for posterior urethral valves in 5 cases based on prenatal criteria of severe renal impairment. Considering these cases as poor outcome, the rate of poor prognosis increased from 20 to 31%. Among the 10 neonates without a prenatal diagnosis of posterior urethral valves renal failure developed in 2 (20%), including end stage renal disease in 1. CONCLUSIONS When negative parameters were absent and/or fetal urine predicted good outcome there were no cases of end stage renal disease in early infancy, which was a significant help in parent counseling. The predictive value of the currently available prenatal parameters needs to be updated with larger series specifically dealing with posterior urethral valves. According to the current data, the outcome of posterior urethral valves is not yet significantly improved by prenatal diagnosis.

Long-term effects of dextranomer endoscopic injections for the treatment of urinary incontinence : An update of a prospective study of 61 patients

PURPOSE A prospective study was initiated 7 years previously to assess the efficacy of endoscopic dextranomer based implants for pediatric structural incontinence. Preliminary results revealed that at 3 years 50% of the patients were either dry or significantly improved. We report long-term results in the same cohort of patients. MATERIALS AND METHODS A total of 33 children and adolescents 5 to 18 years old with severe incontinence due to sphincteric incompetence (exstrophy-epispadias complex in 13, neuropathic bladder in 16, bilateral ectopic ureter in 4) were enrolled. Of the patients 13 underwent 2 and 4 underwent 3 treatment sessions to achieve a definitive result. Mean injected volume was 3.9 ml (range 1.6 to 12) per session. At each evaluation patients were considered cured (dryness interval 4 hours), significantly improved (minimal incontinence requiring no more than 1 pad daily and no further treatment required) or treatment failures (no significant improvement). Videourodynamics were used to study the evolution of the bladder capacity, activity and compliance. A total of 31 patients were followed 3 to 7 years after the last injection. RESULTS At 3 years after treatment 15 of 30 patients (50%) were dry or improved. One patient who had leakage after 3 years of dryness due to bladder deterioration subsequently underwent ileocystoplasty. At 4 years 12 of 25 patients (48%) were dry or improved. At 5 years 9 of 21 patients (43%) were dry, as were 4 of 11 (36%) at 6 years and 2 of 5 (40%) at 7 years of followup. The success rate according to pathological evaluation was comparable in neuropathic bladders (7 of 14, or 50%), exstrophy (3 of 6, or 50%) and epispadias (3 of 7, or 43%). Of 12 patients who underwent bladder neck plasty before the injection of bulking agent 7 (58%) were either dry or improved. The success rate was higher in males (13 of 23, or 57%) than in females (3 of 8, or 38%). Also, at puberty 2 males who were improved became dry. Bladder capacity increased in 12 of 18 initially small bladders and remained normal and stable in 9, while 4 initially dry patients had development of recurrent leakage secondary to bladder deterioration and underwent augmentation. Otherwise, there were no long-term side effects observed related to the injection of the bulking agent. CONCLUSIONS Endoscopic treatment of severe organic urinary incontinence with dextranomer is durable for up to 7 years of followup in 40% of the patients.

Laparoscopic retroperitoneal nephrectomy in high risk children.

PURPOSE Nephrectomy may be indicated in children with end stage renal disease before transplantation. We studied the feasibility and results of nephrectomy performed via a retroperitoneal laparoscopic approach in these high risk children. MATERIALS AND METHODS We performed 12 nephrectomies in 9 children with end stage renal disease and a mean age of 7 years (range 7 months to 13 years) through a 3 trocar retroperitoneal laparoscopic approach. Cases were classified as American Society of Anesthesiologists grade III and presented with end stage renal disease, hypertension, thrombocytopenia and/or the nephrotic syndrome. The renal artery and vein were ligated separately with endocorporeal knots and clips. Mean size of the kidney was 8 cm. (range 5 to 12). Bilateral nephrectomy was performed simultaneously in 2 patients 7 and 12 months old, respectively. Cardiorespiratory changes related to retroperitoneal gas insufflation were assessed prospectively. To compare laparoscopic versus open nephrectomy we retrospectively analyzed the data of 12 open nephrectomies performed in 9 children with similar nephrological indications. RESULTS The procedure was feasible in all cases without conversion to open surgery, and no intraoperative incident occurred. Mean operative time of laparoscopic nephrectomy was 2 hours (range 1 hour 20 minutes to 3 hours 10 minutes). After retroperitoneal carbon dioxide insufflation systolic arterial pressure and end-tidal carbon dioxide were significantly increased without the need for specific measure to correct these modifications. Hemodialysis began 1 day postoperatively and feeding began 2 days postoperatively. Mean hospital stay was 5.2 days (range 3 to 7). The comparative study of the open nephrectomy group showed no significant difference in mean operating time (p = 0.07), and hospital stay was significantly shorter for the laparoscopic group (p <0.001). CONCLUSIONS Retroperitoneal laparoscopic nephrectomy is safe and feasible for high risk children. The relatively long operating time is necessary for hemostasis in these children at risk for hemorrhagic complications.

Mutation Analysis of NR5A1 Encoding Steroidogenic Factor 1 in 77 Patients with 46, XY Disorders of Sex Development (DSD) Including Hypospadias

Background Mutations of the NR5A1 gene encoding steroidogenic factor-1 have been reported in association with a wide spectrum of 46,XY DSD (Disorder of Sex Development) phenotypes including severe forms of hypospadias. Methodology/Principal Findings We evaluated the frequency of NR5A1 gene mutations in a large series of patients presenting with 46,XY DSD and hypospadias. Based on their clinical presentation 77 patients were classified either as complete or partial gonadal dysgenesis (uterus seen at genitography and/or surgery, n = 11), ambiguous external genitalia without uterus (n = 33) or hypospadias (n = 33). We identified heterozygous NR5A1 mutations in 4 cases of ambiguous external genitalia without uterus (12.1%; p.Trp279Arg, pArg39Pro, c.390delG, c140_141insCACG) and a de novo missense mutation in one case with distal hypospadias (3%; p.Arg313Cys). Mutant proteins showed reduced transactivation activity and mutants p.Arg39Pro and p.Arg313Cys did not synergize with the GATA4 cofactor to stimulate reporter gene activity, although they retained their ability to physically interact with the GATA4 protein. Conclusions/Significance Mutations in NR5A1 were observed in 5/77 (6.5%) cases of 46,XY DSD including hypospadias. Excluding the cases of 46,XY gonadal dysgenesis the incidence of NR5A1 mutations was 5/66 (7.6%). An individual with isolated distal hypopadias carried a de novo heterozygous missense mutation, thus extending the range of phenotypes associated with NR5A1 mutations and suggesting that this group of patients should be screened for NR5A1 mutations.

Artificial urinary sphincter in children: voiding or emptying? an evaluation of functional results in 44 patients

PURPOSE We evaluated functional results with an artificial urinary sphincter in children and adolescents in terms of complications, continence and voiding ability through followup. MATERIALS AND METHODS A total of 44 patients (39 males and 5 females, age 8.6 to 29.5 years, median 14) underwent implantation of a pericervical AMS 800trade mark artificial urinary sphincter, primarily for severe urinary incontinence of neuropathic origin, between 1986 and 2005. Of the patients 25 had undergone augmentation cystoplasty previously (8), simultaneously (7) or after implantation (10). Median followup was 5.5 years (range 1 to 18). Complications included dysuria and/or urinary retention (24 cases), worsening of bladder function (13), urethral erosion (2), scrotal erosion (5), mechanical dysfunction (7), infection of the artificial urinary sphincter (2) and accidental puncture of the tubes (2). These complications resulted in 9 removals, 5 deactivations, 6 revisions and 5 total replacements. RESULTS Of 44 patients 9 (20%) were incontinent after removal of the artificial urinary sphincter. Among the remaining patients 32 (73%) were dry and 3 (7%) were incontinent with a deactivated device. Of the 35 patients with an artificial urinary sphincter in place 17 (48.6%) voided to completion with spontaneous voiding, 9 (25.7%) performed post-void clean intermittent catheterization and 9 (25.7%) emptied exclusively with clean intermittent catheterization. The ability to maintain voiding to completion after implantation was significantly decreased when the artificial urinary sphincter was implanted before puberty (p = 0.0025) or in conjunction with an augmented bladder (p = 0.01). CONCLUSIONS The artificial urinary sphincter provides a good rate of continence. However, complications are frequent, leading to removal in 20% of the cases. In time only a limited number of patients can empty the bladder without clean intermittent catheterization.

Clinical, Biological and Genetic Analysis of Anorchia in 26 Boys

Background Anorchia is defined as the absence of testes in a 46,XY individual with a male phenotype. The cause is unknown. Methods We evaluated the clinical and biological presentation, and family histories of 26 boys with anorchia, and sequenced their SRY, NR5A1, INSL3, MAMLD1 genes and the T222P variant for LGR8. Results No patient had any associated congenital anomaly. At birth, testes were palpable bilaterally or unilaterally in 13 cases and not in 7; one patient presented with bilateral testicular torsion immediately after birth. The basal plasma concentrations of anti-Müllerian hormone (AMH, n = 15), inhibin B (n = 7) and testosterone (n = 19) were very low or undetectable in all the patients evaluated, as were the increases in testosterone after human chorionic gonadotropin (hCG, n = 12). The basal plasma concentrations of follicle stimulating hormone (FSH) were increased in 20/25, as was that of luteinising hormone in 10/22 cases. Family members of 7/26 cases had histories of primary ovarian failure in the mother (n = 2), or sister 46,XX, together with fetal malformations of the only boy with microphallus and secondary foot edema (n = 1), secondary infertility in the father (n = 2), or cryptorchidism in first cousins (n = 2). The sequences of all the genes studied were normal. Conclusion Undetectable plasma concentrations of AMH and inhibin B and an elevated plasma FSH, together with 46,XY complement are sufficient for diagnosis of anorchia. The hCG test is unnecessary. NR5A1 and other genes implicated in gonadal development and testicle descent were not mutated, which suggests that other genes involved in these developments contribute to the phenotypes.

CYSTOGRAPHY AFTER THE COHEN URETEROVESICAL REIMPLANTATION: IS IT NECESSARY AT A TRAINING CENTER?

PURPOSE Reimplantation by the Cohen procedure has a low rate of recurrent reflux, although postoperative cystography is done routinely at most centers. According to the French training program for pediatric surgery and urology residents, reimplantation is the main pediatric urology procedure performed during residency. We determine whether it is necessary to perform postoperative cystography routinely and whether the fact that the procedure is done by a junior surgeon modifies management. MATERIALS AND METHODS A total of 268 children with primary vesicoureteral reflux underwent ureteral reimplantation by the Cohen transtrigonal technique. Bilateral reimplantation was done in 97% of the cases. Reimplantation was performed by a surgery resident assisted by a clinical fellow or senior consultant surgeon in 37% of the cases. Routine cystography and renal ultrasound were done in all patients postoperatively. Followup ranged from 6 months to 5 years (mean 10 months). RESULTS In 2 children (0.7%) with recurrent reflux surgery was not performed by a resident. One of the 2 children had asymptomatic persistent reflux and no further surgery was done. In the other child postoperative cystography was normal at 6 months. One year later she had acute pyelonephritis with recurrent unilateral reflux and underwent repeat reimplantation. CONCLUSIONS Routine cystography is not necessary after bilateral Cohen reimplantation. Reflux recurrence is low even at a training center where surgery may be performed by junior surgeons.

Poor compliance with primary nocturnal enuresis therapy may contribute to insufficient desmopressin response.

PURPOSE Studies of desmopressin in children with primary nocturnal enuresis show a greater than 90% decrease in wet nights in 20% to 30%, a 50% to less than 90% decrease in 20% to 40% and less than a 50% decrease in up to 60%. Insufficient response to desmopressin is attributable to various factors, including differences in the primary nocturnal enuresis definition, underlying bladder dysfunction and/or desmopressin pharmacokinetic characteristics. However, little attention has been given to poor compliance with therapy as a possible explanatory factor. For a drug with an effect duration limited to the night after administration a high degree of compliance is essential to ensure consistent therapeutic effects. MATERIALS AND METHODS This was a substudy of an international investigation of treatment for 6 months or less with desmopressin tablets in children with primary nocturnal enuresis. Medication was dispensed at each visit as required and collected at each subsequent visit. Compliance was determined by pill counts by study staff. RESULTS Compliance data were available on 723 patients. Of the patients 81% to 91% ingested all medication as instructed during the initial run-in phases. However, this decreased to 77% and 71% during the first and second 3-month treatment periods, respectively. CONCLUSIONS Patient motivation and compliance are generally stronger in clinical trials than in clinical practice. However, this study shows that some patients were poorly compliant with medication even at study initiation and only 71% were fully compliant with long-term treatment. Decreased compliance was associated with a lower response rate. Patients should be encouraged to comply fully with treatment to achieve an optimal outcome.

Original Koyanagi urethroplasty versus modified Hayashi technique: Outcome in 57 patients

OBJECTIVE To compare outcomes of the original Koyanagi technique with the Hayashi modification in severe hypospadias, i.e. hypospadias with a division of the corpus spongiosum located behind the penile midshaft associated with marked hypoplasia of the ventral aspect of the penis and a non-preservable urethral plate. Choice of technique for treating severe hypospadias is discussed. PATIENTS AND METHODS Twenty-six patients (group I) were operated in Lyon using the original Koyanagi procedure and 31 (group II) underwent a modified Hayashi procedure in Paris. Most patients received preoperative androgenic stimulation. Mean follow up was 25 months (group I) and 34 months (group II). RESULTS Sixteen patients (61.5%) in group I and 19 (61.3%) in group II developed complications leading to 21 additional procedures in each group. Urethral dehiscence was found in 11/26 patients in group I (42.3%), and in 6/31 patients in group II (19.3%); fistulae were respectively found in 5/26 (19.2%) and 12/31 (38.7%), and stenosis in 9/26 (34.6%) and 5/31 (16.1%) patients. Urethrocele was found in 7/26 (26.9%) and 5/31 (16%) patients, respectively. Twelve (group I) and 7 (group II) patients are awaiting re-operation. CONCLUSION Although the complication rate is quite similar between the original and the modified Koyanagi procedure, the Hayashi technique seems to provide a better distal blood supply to the reconstructed urethra.

Long‐term desmopressin response in primary nocturnal enuresis: open‐label, multinational study

Background:  Primary nocturnal enuresis (PNE) is a distressing condition, particularly in severe cases (≥ 3 wet nights/week). A prevalent pathophysiological mechanism, especially in monosymptomatic PNE (PMNE), is commonly believed to be an insufficient increase in night‐time release of antidiuretic hormone. Desmopressin, a synthetic analogue of antidiuretic hormone, has been shown to reduce the number of wet nights experienced by PMNE patients in several controlled trials.