A Single-Center, Observational Study of 607 Children and Young People Presenting With Differences of Sex Development (DSD).

Context: Differences of sex development (DSD) represent a wide range of conditions presenting at different ages to various health professionals. Establishing a diagnosis, supporting the family, and developing a management plan are important. Objective: We aimed to better understand the presentation and prevalence of pediatric DSD. Methods: A retrospective, observational cohort study was undertaken in a single tertiary pediatric center of all children and young people (CYP) referred to a DSD multidisciplinary team over 25 years (1995-2019). In total, 607 CYP (520 regional referrals) were included. Data were analyzed for diagnosis, sex-assignment, age and mode of presentation, additional phenotypic features, mortality, and approximate point prevalence. Results: Among the 3 major DSD categories, sex chromosome DSD was diagnosed in 11.2% (68/607) (most commonly 45,X/46,XY mosaicism), 46,XY DSD in 61.1% (371/607) (multiple diagnoses often with associated features), while 46,XX DSD occurred in 27.7% (168/607) (often 21-hydroxylase deficiency). Most children (80.1%) presented as neonates, usually with atypical genitalia, adrenal insufficiency, undescended testes or hernias. Those presenting later had diverse features. Rarely, the diagnosis was made antenatally (3.8%, n = 23) or following incidental karyotyping/family history (n = 14). Mortality was surprisingly high in 46,XY children, usually due to complex associated features (46,XY girls, 8.3%; 46,XY boys, 2.7%). The approximate point prevalence of neonatal referrals for investigation of DSD was 1 in 6347 births, and 1 in 5101 overall throughout childhood. Conclusion: DSD represent a diverse range of conditions that can present at different ages. Pathways for expert diagnosis and management are important to optimize care.

The predictive value of a repeat micturating cystourethrogram for remnant leaflets after primary endoscopic ablation of posterior urethral valves.

OBJECTIVE: We routinely perform a cystourethroscopy 3 months after initial ablation of posterior urethral valves. The aim of this study was to determine the predictive value of the urethral appearance on preoperative micturating cystourethrogram (MCUG) for further valve resection at check cystoscopy. PATIENTS AND METHODS: We retrospectively reviewed 31 consecutive boys (aged 4-18 months) who underwent check cystoscopy and repeat MCUG between 2006 and 2008. RESULTS: Repeat MCUG suggested remnant valves in 10, but no residual leaflets were identified cystoscopically in 4. In 20 boys, the valves appeared completely ablated on MCUG but valve leaflets received further resection in 10. One study was undiagnostic. Residual valves were resected in 83% (5/6) where valves and urethral dilatation were noted on MCUG. Where MCUG suggested either valves or persistent dilatation alone, further resection occurred in 40% (4/10). Remnant leaflets were also present in half of those (7/14) in whom the repeat MCUG had shown complete ablation and resolved/reduced posterior urethral dilatation. CONCLUSIONS: The positive predictive value of valve leaflets and/or posterior urethral dilatation on repeat MCUG for subsequent resection of valve remnants was 56%; the negative predictive value was 50%. We found repeat MCUG alone imprecise in excluding residual valve tissue and recommend check cystoscopy in all.

Further experience with the vascular hitch (laparoscopic transposition of lower pole crossing vessels): an alternate treatment for pediatric ureterovascular ureteropelvic junction obstruction.

PURPOSE: Standard treatment for ureterovascular ureteropelvic junction obstruction has been dismembered pyeloplasty. We previously reported the alternative technique of laparoscopic transposition of lower pole vessels (the vascular hitch) in pediatric patients. This report is an update of this select group of pediatric patients with intermediate followup. MATERIALS AND METHODS: Patients underwent diagnostic renal sonography and (99m)technetium-mercaptoacetyltriglycine diuretic renography with additional magnetic resonance angiography in candidate patients. Radiographic criteria included moderate hydronephrosis with no caliceal dilatation and a well preserved cortex, poor renal drainage with preserved split function and lower pole crossing vessels. Intraoperative criteria included a normal ureter and ureteropelvic junction with peristalsis. Postoperatively patients were followed clinically, and with renal sonography and (99m)technetium-mercaptoacetyltriglycine renography at 1 and 2 months, respectively. Success was defined as symptom resolution with radiographic improvement in hydronephrosis and drainage with preserved renal function. RESULTS: Nine boys and 11 girls 7 to 16 years old (mean age 12.5) underwent laparoscopic transposition of crossing vessels, including 3 with da Vinci robot assistance. Mean operative time was 90 minutes (range 47 to 140). Median hospital stay was 24 hours. No ureteral stents or urethral catheters were placed intraoperatively. At a mean followup of 22 months (range 12 to 42) 19 of 20 patients (95%) had been successfully treated. One patient who had recurrent pain underwent successful laparoscopic pyeloplasty. CONCLUSIONS: At intermediate followup the laparoscopic vascular hitch procedure has been successful in treating patients with ureterovascular ureteropelvic junction obstruction. In these select patients this technique offers a feasible and durable alternative to standard dismembered pyeloplasty. Ongoing evaluation continues to ensure that the promising results endure.

Ureterocystoplasty: long-term functional results.

PURPOSE: Many institutions have reported varied levels of success with ureterocystoplasty. Recently, there have been concerns regarding the efficacy of ureterocystoplasty as a form of bladder augmentation. We report our long-term functional outcomes with the procedure based on the experience of a single surgeon. MATERIALS AND METHODS: A total of 17 procedures were performed during a 12-year period. Of the patients 10 had posterior urethral valves, 3 had bladder exstrophy, 2 had a neuropathic bladder, 1 had a cloacal anomaly and 1 had a left ectopic ureter. Mean patient age at operation was 5.9 years (range 0.3 to 14.2). All patients underwent preoperative ultrasound, urodynamic studies and radionuclide scanning. Postoperative urodynamics were performed at 6 months. RESULTS: Followup ranged from 0.5 to 11.5 years (mean 4.5). Nine patients underwent ureterocystoplasty with preservation of the ipsilateral kidney, and 1 underwent ureterocystoplasty alone and had a solitary right kidney. The remaining 7 patients underwent ureterocystoplasty with ipsilateral nephrectomy. Postoperatively, the mean bladder capacity improved from 125 to 292 ml, while the mean end filling pressure decreased from 72 to 22 cm H(2)O. Mean preoperative system compliance was 2.1 ml/cm H(2)O, which increased to 16.2 ml/cm H(2)O postoperatively. A total of 13 patients did not require further augmentation surgery. The remaining 4 patients had high pressure and poorly compliant bladders, and underwent ileocystoplasty. Subsequent postoperative nucleotide scans in these 4 patients demonstrated stable upper tracts with good drainage. CONCLUSIONS: Based on our results, ureterocystoplasty provides durable functional urodynamic improvement in patients with a megaureter.

Renal transplantation or bladder augmentation first? A comparison of complications and outcomes in children.

OBJECTIVE: To identify whether the order of performing transplant and bladder reconstruction operations in children who need both operations affects outcome of either operation. PATIENTS AND METHODS: A retrospective case note review was performed of children identified from our database, who had undergone both renal transplantation and bladder augmentation between 1990 and 2005. RESULTS: In all, 18 renal transplants (eight live-related) were performed in 16 children with 10 transplants done after bladder augmentation and eight transplants done before augmentation. The median age at transplantation was 7.5 years and at augmentation was 7.0 years. The median interval between the operations was 33.5 months and the median follow-up was 58.4 months after transplantation. Outcomes were compared between the two groups of patients: those who received their transplantation before bladder augmentation, and those who were transplanted after bladder augmentation. There was no difference between these groups in: the pre- transplant estimated glomerular filtration rate, inpatient stay after transplantation or after augmentation, and incidence of urinary tract infection in the 3 months after renal transplantation or after bladder augmentation. There was no statistical difference in renal allograft loss with one graft failure in the group who were augmented first, and four graft failures in the group who were transplanted first. However, it is of note that the single graft failure in the patient augmented first was due to renal artery thrombosis on the first day related to a double arterial anastomosis, whilst in the other group, three of the graft failures were in transplants that had initially been drained by ureterostomy. Three patients in the group transplanted first developed significant ureteric pathology, of which one developed graft failure. CONCLUSION: Bladder reconstruction can be performed safely before transplantation; it does not increase complications and might better protect the renal graft and specifically the transplant ureter.

Part II: Treatment of primary malignant non-Wilms' renal tumours in children.

Renal-cell carcinoma, clear-cell sarcoma, (congenital) mesoblastic nephroma, rhabdoid tumour, and renal medullary carcinoma form a heterogeneous group of childhood renal malignancies known as non-Wilms' tumours. Progress has been slow in improving the management of these tumours to decrease morbidity and increase survival. However, greater cooperation between national and international centres should engender specialisation, and an increased knowledge of the molecular biology of these tumours will inevitably lead to substantial progress over the next decade. This review is the second of two parts: the first part provided an updated review of the clinical presentation, imaging, and pathology of non-Wilms' tumours and this second part provides an updated review of the treatment of these tumours.

Part I: Primary malignant non-Wilms' renal tumours in children.

Non-Wilms' tumours form a small heterogeneous group of clinically significant renal malignancies in children, including renal-cell carcinoma, clear-cell sarcoma, (congenital) mesoblastic nephroma, rhabdoid tumour, and renal medullary carcinoma. Good progress has been made in the assessment of these tumours, which has led to a greater understanding of the molecular changes that occur in their development. This review is the first of two parts, and provides an updated review of the clinical presentation, imaging, and pathology of these tumours.

An initial experience of 100 paediatric laparoscopic nephrectomies with transperitoneal or posterior prone retroperitoneoscopic approach.

The objective of this study was to evaluate the outcome of the initial 100 consecutive laparoscopic nephrectomies using a transperitoneal or a posterior prone retroperitoneoscopic approach. The medical records of 97 consecutive children who underwent laparoscopic nephrectomy between January 2000 and December 2003 were reviewed. Children having concomitant operative procedures were excluded from the study. Laparoscopy was performed by a transperitoneal (TP) or a posterior prone retroperitoneoscopic (PPR) approach based on the preference of the operating surgeon. A total of 100 procedures were successfully completed laparoscopically. Two children required conversion to open surgery. The median operating time was 112 min for the TP approach and 96 min for the PPR approach (P = 0.002). There was no significant difference in the analgesic requirements between the two groups. The rate of complications was similar, as was the length of hospital stay. This was despite the fact that the children in the TP group were somewhat older in age. In children having bilateral native kidney nephrectomy, peritoneal dialysis was successfully established within 48 h after surgery in the PPR group. Taking into account the heterogeneous nature of our group of patients, a reliable conclusion in regard to the difference in operative time, analgesic requirement or approach could not be ascertained. There is the suggestion however, that both the TP and PPR approaches for nephrectomy are equally applicable in children. The posterior prone retroperitoneoscopic approach may have an advantage in children who require peritoneal dialysis.

Long-term outcome of vaginal reconstruction: comparing techniques and timing.

OBJECTIVE: In a retrospective review, to analyse the long-term outcomes of vaginal reconstruction, comparing techniques and timing. PATIENTS AND METHODS: We identified 63 patients who underwent a total of 71 vaginoplasties in 1985-2000. The techniques used were posterior skin flap (42), intestinal replacement (21) and pull through (8). The majority of operations were performed before puberty (63%) and as primary procedures (79%). Presenting diagnoses were congenital adrenal hyperplasia (23), cloacal exstrophy (8), true persistent cloaca (12), androgen insensitivity (8), urogenital sinus anomaly (6), mixed gonadal dysgenesis (3), true hermaphroditism (2) and sacrococcygeal teratoma (1). RESULTS: The mean age at operation was 83.9 (2-235) and mean follow up was 116.8 (48-232) months. Strictures and discharge were the most common problems. Nine patients underwent revision surgery and a fistula repair was required in two patients. Mucosal prolapse was observed in one ileo- and one colovaginoplasty patient, and diversion colitis occurred after colovaginoplasty in one patient. More complications occurred in operations performed prior to than following puberty. CONCLUSION: If vaginoplasty is the only indicated operation, delaying until puberty may minimize complications. When other genital surgery is indicated or in the presence of symptoms pre-pubertal vaginoplasty should be performed, since the second procedure usually involves simple dilatations and is associated with good results.

Injectable polydimethylsiloxane for treating incontinence in children with the exstrophy-epispadias complex: long-term results.

OBJECTIVE: To present our experience with the use of injectable polydimethylsiloxane (Macroplastique, Uroplasty, Minneapolis, MI, USA) for treating incontinence in children with the exstrophy-epispadias complex (EEC), as incontinence continues to be a challenging problem in such children, and although the primary management of EEC has developed over the last few decades, with early closure and reconstruction of the penis, achieving satisfactory continence status remains elusive. PATIENTS AND METHODS: We retrospectively reviewed the hospital records of 52 patients (41 boys and 11 girls, mean age at first injection 6.6 years, range 3.6-16.7) with EEC who had injections with Macroplastique between January 1991 and February 2004; 34 had bladder exstrophy and 18 primary epispadias. For this study we defined success as complete dryness with no use of pads or nappies. Improvement was defined as being occasionally wet but with dry intervals lasting >or= 4 h. RESULTS: The mean (range) follow-up was 4.6 (0.5-9) years. Twenty patients had one injection, 10 had two, 13 had three, six had four, two had six and one had seven injections. In most patients a maximum of three injections predicted the outcome. The injection of Macroplastique was successful in nine patients (17%; with an annual follow-up, two at 1-2 years, three at 2-5 years and four at >5 years), whilst 17 (33%) improved significantly (one at <1 year, two at 1-2 years, eight at 2-5 years and six at >5 years). Those patients comprised five of 18 (27%) with epispadias and four of 34 (12%) with exstrophy. A history of previous surgery and gender had no significant effect on the outcome. Overall half the patients benefited from the procedure. CONCLUSIONS: This series confirms that injection with Macroplastique is minimally invasive, durable in significantly many patients and has a reasonable success rate. A history of previous surgery and gender had no significant effect on the outcome. Patients with epispadias are more likely to benefit from an injection with Macroplastique than those with bladder exstrophy. A maximum of three injections is predictive with reasonable certainty of any benefit from the procedure.

Single-centre experience of genitourinary complications of epidermolysis bullosa.

Epidermolysis bullosa (EB) is a heterogeneous skin disorder that is sometimes associated with genitourinary involvement. We report our experience with the urological problems seen in these patients. Dermatology and nephro-urology databases were used to identify EB patients with urological problems, between 1980 and 2004. In total, five patients, all male, were identified, and the hospital records were reviewed. Genitourinary complications of EB present difficult challenges. The disorder can lead to urothelial blistering and strictures that can result in obstruction throughout the urinary tract. In addition, urethral instrumentation and surgical reconstruction in patients with EB has a high complication rate and should be avoided whenever possible.

Renal function and outcome following salvage surgery for bilateral Wilms' tumor.

PURPOSE: Maintaining adequate renal function without compromising cure in children with bilateral Wilms' tumor is surgically demanding and challenging. The aim of this study was to assess renal function and outcome in children treated in one institution for bilateral Wilms' disease by renal salvage procedures. METHODS: This study is a retrospective review of all patients with histologically proven bilateral nephroblastoma who underwent a renal salvage procedure between November 1973 and June 2002. The median follow-up time was 52 months (range, 8 to 326 months). RESULTS: Twenty-three patients were included in the study. The median age at diagnosis was 19 months (range, 5 to 65 months). Patients who presented before 1982 (n = 5) were treated surgically first followed by chemotherapy. The remainder (n = 18) received initial chemotherapy before the operation. Of the 46 kidneys, 18 had a nephrectomy. The remaining 28 underwent a renal salvage procedure. At follow-up, 19 patients had good renal function, 2 had satisfactory function, and 2 had renal failure. Seventeen of the 23 children are alive and tumor free at follow-up (74%). Four children died of distant metastases and 2 of renal failure. Local recurrence in the salvaged kidney was detected in 1 patient 12 years after surgery after the commencement of immunosuppression for renal transplantation. CONCLUSIONS: These results confirm that renal salvage procedures, in combination with chemotherapy, are a safe and effective way of treating children with bilateral Wilms' disease. In addition, renal salvage surgery can maintain satisfactory renal function in the majority of these patients without an increased risk of local recurrence. When transplantation is required, the remaining native kidney should be removed to prevent tumor recurrence.

A novel, inexpensive, double lumen suprapubic catheter for urodynamics.

PURPOSE: We describe a novel, double lumen, intravesical, suprapubic catheter designed to meet the requirements of pediatric urodynamics that is easy to use and has minimal complications. MATERIALS AND METHODS: A commercially available 10Fr pediatric suprapubic pigtail catheter forms the outer lumen for instilling filling media. A 16 gauge epidural catheter is inserted through the outer catheter providing an inner lumen for measuring intravesical pressures. The resultant double-lumen catheter is inserted suprapubically using a peel away needle supplied with the 10Fr catheter, with the patient under general anesthetic. RESULTS: The catheter has been used for 15 years in more than 700 patients with good reliability and few complications. The concentric construction of the double lumens and the rigidity of the inner intravesical pressure channel ensure there is no transmission of pressure from the filling channel to the inner lumen. The catheter has a circular cross section and a pigtail distal end which help to retain it within the bladder. There is low resistance to filling that allows adequate filling rates to be achieved by gravity rather than necessitating a pump. The catheter is easily made from readily available components and is less expensive than other double-lumen catheters suitable for suprapubic use. CONCLUSIONS: A reliable, double lumen catheter that fulfills criteria not found in commercially available alternatives can be inexpensively made for urodynamics.

Tethering of the spinal cord in mouse fetuses and neonates with spina bifida.

OBJECT: Tethering of the spinal cord is a well-known complication in humans with spina bifida aperta or occulta. Its pathogenesis consists of a pathological fixation of the spinal cord resulting in traction on the neural tissue which, in turn, leads to ischemia and progressive neurological deterioration. Although well established in humans, this phenomenon has not been described in animal models of spina bifida. METHODS: A fetal mouse model with naturally occurring, genetically determined spina bifida was produced by generating double mutants between the curly tail and loop-tail mutant strains. Microdissection, labeling with 1,1'-dioctadecyl-3,3,3,',3'-tetramethylindocarbocyanine perchlorate, immunohistochemistry for neurofilaments, H & E staining of histological sections, and whole-mount skeletal preparations were performed and comparisons made among mutant and normal fetuses. Normal fetuses exhibited the onset of progressive physiological ascent of the spinal cord from embryonic Day 15.5. Spinal cord ascent resulted, by embryonic Day 18.5, in spinal nerve roots that pass caudolaterally from the spinal cord toward the periphery. In contrast, fetuses with spina bifida exhibited spinal cord tethering that resulted, at embryonic Day 18.5, in nerve roots that run in a craniolateral direction from the spinal cord. The region of closed spinal cord immediately cranial to the spina bifida lesion exhibited marked narrowing, late in gestation, suggesting that a potentially damaging stretch force is applied to the spinal cord by the tethered spina bifida lesion. CONCLUSIONS: This mouse model provides an opportunity to study the onset and early sequelae of spinal cord tethering in spina bifida.