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Summary Introduction Germline-inactivating DICER1 mutations are responsible of a familial tumour susceptibility syndrome with an increased risk of tumours, mainly pleuropulmonary blastoma (PPB). DICER1 mutations also cause a range of other tumours, some of them in urogenital organs (cystic nephroma [CN], ovarian sex cord-stromal tumours, bladder and cervix embryonal rhabdomyosarcoma [ERMS]). Objective The aim was to clarify the range of urogenital phenotypes associated with DICER1 mutations and to give practical course of action to paediatric urologist that are exposed to DICER1-related conditions. Study design A literature review was performed. Pertinent papers focused on urogenital diseases associated with DICER1 mutations were reviewed. Results Seventy per cent of CN have a DICER1 germline mutation. The majority of them (80%) have PPB. Like PPB, CN could undergo a malignant progression to a primitive sarcoma. Some rare cases of Wilms tumours were reported. Regarding gonadal manifestations, sex-cord stromal neoplasia of the ovary, especially Sertoli–Leydig cell tumour (SLCT), is the most frequent tumour associated with DICER1 germline mutation. Germline DICER1 mutations also predispose to uterine cervix and bladder ERMS. Discussion The presence of unusual tumours suggesting DICER1 mutations may alert clinicians. The first step is to obtain a complete familial history. The variable clinical presentation and the modest penetrance raise concerns about the appropriateness of genetic testing to patients and their relatives. The education of DICER1 mutations carriers about tumour-related symptoms is consensual. In the first 5 years of life, a yearly chest X-ray and abdominal ultrasound are recommended. Conclusion The presence of a CN, ovarian SLCT or urogenital ERMS in a child should alert the clinician to the possibility of DICER1 mutation and the associated risk of PPB. Individuals with one of the typical DICER1 conditions should be offered DICER1 analysis. Despite the low penetrance, a genetic counselling and testing should be offered to the family of the affected child.

Summary Objectives Peritoneal dialysis (PD) is the modality of choice for children with end-stage renal disease (ESRD) awaiting renal transplant; however, this option is sometimes avoided for those with previous laparotomy. The goal of this study was to compare the outcomes of PD in patients with and without previous laparotomy. Patients and methods Twenty-four patients who had been started on peritoneal dialysis were retrospectively analysed. Group LAP consisted of six patients with previous laparotomy, and Group NO-LAP of 18 controls with either retroperitoneal or no abdominal surgery. The percentage of theoretical maximum volume of infusion, time to reach it, complications (infection and drainage difficulties), and number of catheters needed to finish therapy were analysed. Results The characteristics of patients and technique of insertion are presented in Table. The percentage of maximum theoretical volume of infusion was similar in both groups. Median of catheter survival was similar in both groups. Complications were divided into malfunction (slow drainage, obstruction or leak) and infection. Incidence of complications per catheter and per month of dialysis was ten times lower in Group NO-LAP. Peritoneal dialysis failed in one patient with recurrent intraperitoneal adhesions after adhesiolysis in Group LAP. Conclusion Despite a higher incidence of complications (malfunction and infections), PD remains an acceptable option after laparotomy. In this series, it was sufficient in achieving adequate filtration in five patients. Table . Characteristics of patients, details of catheter use and complications, and overall efficacy of PD in both groups. Total 24 patients Median age (m) at insertion Median weight (kg) at insertion Technique of insertion: laparoscopic Median delay before 1st use (d) Median percentage of maximum theoretical volume Complications Median of catheter survival (m Efficacy 1400 ml/m2 if >2 y 40 ml/kg Malfunction Infection 800 ml/m2 if LAP (n = 6) 114 (5.5 m–15 y) 24.6 (3.8–37.5) 4 patients 1.5 (1–3) 86% 83% 1 per 23 months of dialysis 0.01 per catheter per month 1 per 17 months of dialysis 0.01 per catheter per month 12 m (1 w–2 y) 5 of 6 patients NO-LAP (n = 18) 133.5 (1 w–16.5 y) 33.1 (4–41.8) 14 patients 1 (1–45) 77% 86% 1 per 31 months of dialysis 0.001 per catheter per month 1 per 27 months of dialysis 0.001 per catheter per month 11.5 m (2 w–3 y) 18 of 18 patients

Summary Objective To report a case of juxtaglomerular cell tumour of the kidney (reninoma) in a child treated with laparoscopic nephron-sparing surgery. Patients and results A 14-year-old girl was incidentally found to have hypertension (180/114 mmHg) at the time of adenotonsillectomy. Pre-operative investigations revealed a plasma renin level of 225.9 ng/dl (4.4–46), normal aldosterone, cortisol and urinary catecholamine. Abdominal ultrasound detected a 1.9 × 1.5-cm hypoechoic lesion in the right kidney lower pole; CT scan confirmed the presence of a 1.5-cm, circumscribed, solid, hypoenhancing cortical lesion in the right lower pole. Laparoscopic nephron-sparing surgery was accomplished by clamping the renal artery for 30 min; after excision, the tumour bed was closed using barbed V-loc sutures. The procedure was completed laparoscopically in 150 min with no peri-operative complications. The patient was discharged home on day 4 postoperatively. Histology confirmed the diagnosis of a juxtaglomerular cell tumour that was completely excised. The J-J stent was removed 1 month later. At follow-up, the patient's blood pressure was normalized and medications were stopped. A DMSA scan confirmed 36% residual right kidney function. Conclusion Laparoscopic nephron-sparing surgery should be considered in children with juxtaglomerular tumours. This technique allows prompt recovery with preservation of significant renal function.

Summary Introduction Prader–Willi syndrome (PWS) is a rare (1:20.000) genetic condition affecting both males and females. Among other features, in boys, the syndrome is characterized by cryptorchidism in 86–100% of cases, hypogonadism, delayed puberty and infertility. The aim of the present study is to appraise the results of orchidopexy in this selected population of children. Study design A follow-up study of children with PWS treated for undescended testes at a single institution over a 20-year period was performed. Patients were identified from a National PWS registry and reviewed at a special follow-up clinic. Data were collected from electronic and hard copies records and reported as median (range). Results Thirty-three children (1–17 years) were identified. Co-morbidities were present in 22 (66%) and 15 (45%) were on growth-hormone therapy. Six patients (19%) had normal testes palpable in the scrotum; twenty-seven (81%) had undescended testes and required orchidopexy. Thirteen (48%) underwent a bilateral procedure for a total of 40 procedures. A 2-stage Fowler-Stephens orchidopexy was required in 2 (7%) testes. At surgery hypotrophic testes were documented in 6 (22%) patients. Age at orchidopexy was 1.4 years (0.5–5.5). Age at F U was 7.2 years (1.7–17). Length of follow-up is 3.5 years (0.4–14). At follow-up 16 (40%) testes were of normal size and palpable in the scrotum; 7 (17.5%) testes required redo-orchidopexy. All patients (6/33) over 16 years of age that had testosterone levels tested had values below normal limits after successful orchidopexy. Conclusions This study evaluates the results of orchidopexy in a large population of children with PWS. At follow-up, only 40% of testes were of normal size and in the scrotum. This information should be taken into consideration for patients' management and pre-operative parents' counseling. Findings at follow-up (40 testes) Number (%) Normal testes in scrotum 16 (40) Hypotrophic testes in scrotum 8 (20) Testes in inguinal canal 10 (25) Non-palpable testes 4 (10) Atrophic testes in scrotum 2 (5) Redo-orchidopexy 7 (17.5)

Summary Objective Bladder perforation is not commonly described in bladder exstrophy patients without bladder augmentation. The goal of this study was to identify the risk factors of spontaneous perforation in non-augmented exstrophy bladders. Methods The study was a retrospective multi-institutional review of bladder perforation in seven male and two female patients with classic bladder exstrophy–epispadias (E–E). Results Correction of E–E was performed using Kelly repair in two and staged repair in seven (Table). Bladder neck repair was performed in eight patients at a mean age of 6 years. Three patients had additional urethral surgery. Before rupture, six patients were voiding only per urethra. Two patients were voiding urethrally but were also performing occasional CIC via a Mitrofanoff. One patient was performing CIC 3 hourly per urethra. Six were dry during the day. Six of the patients had lower urinary tract symptoms: five had frequency and four were straining to void. Two had suffered episodes of urinary retention. Pre-rupture ultrasound showed that the upper urinary tract was dilated in four patients. Micturating cystourethrogram was performed in six showing vesico-ureteral reflux in five. Two had urethral stenosis. Nuclear medicine was done in three patients with two abnormal differential function. Urodynamics was performed in two patients with low capacity (100 mL) and hypocompliant ( Conclusions The limitations of this series include the small number of patients and its retrospective nature, without knowledge of the incidence. Bladder rupture is a risk even in non-augmented bladder exstrophy. It is potentially life-threatening and most often requires laparotomy. Rupture occurs because of poor bladder emptying and/or high pressure. Urodynamics may identify those at risk. CIC with or without augmentation should not be delayed once poor bladder emptying and/or high pressure are identified. Table . Patients with bladder perforation. Pt Pre-rupture imaging Pre-rupture continence Age, years Management Outcome 1 Small right kidney with high-grade VUR and high PVR 90 min voiding with episodes of retention 13 Laparotomy IDC 3 weeks Refused augmentation and Mitrofanoff. Recurrent bladder rupture 2 Small left kidney (15% df) with high-grade VUR and high PVR. Poorly compliant bladder on urodynamics Straining to void with frequency 8 Laparotomy and bladder neck closure with SPC Augmentation and Mitrofanoff 3 Trabeculated bladder Straining to void. High PVR. Incontinent 5 Laparotomy SPC 3 weeks Refused Mitrofanoff. Ongoing straining and lost to f/u 4 Trabeculated bladder, low-grade VUR bilaterally and urethral stenosis 2–3 hourly voiding with straining. High PVR 20 SPC with prolonged drainage No further surgery or recurrences known 5 Bilateral HUN 3 hourly voiding with high PVR 15 Laparotomy IDC 3 weeks No further surgery or recurrences known 6 Normal USS Voiding and dry on desmopressin and oxybutynin 11 Laparotomy IDC 3 weeks Augmentation with Mitrofanoff 7 Bilateral HUN with high-grade VUR. Poorly compliant bladder on urodynamics CIC 3 hourly 9 Laparotomy SPC Augmentation with Mitrofanoff. Bladder stone post augment 8 Bilateral HUN with high-grade VUR and reduced function on left Voiding with day and night wetting. Occasional CIC via Mitrofanoff 8 Laparotomy. Drainage via Mitrofanoff Augmentation. Recurrent rupture near the anastomosis of the augment 9 Normal USS. Bladder capacity 100 mL. Low compliance Voiding with day and night leaking. Occasional CIC via Mitrofanoff 10 Laparotomy. Drainage via Mitrofanoff Augmentation, redo Mitrofanoff (Monti) CIC, clean intermittent catheterization; HUN, hydroureteronephrosis; IDC, indwelling catheter; Pt, patient; PVR, post void residual; R, rupture; SPC, suprapubic catheter; USS, ultrasound; VUR, vesicoureteric reflux.

Summary Introduction Although two-stage graft urethroplasty is widely used, the literature regarding the complication rates and functional characteristics of reconstructed neourethra is relatively modest. Objectives The aim was to analyze the complication rates and uroflow data of boys who have previously undergone a two-stage graft urethroplasty procedure for proximal and complicated hypospadias. Patients and methods We retrospectively reviewed the clinical outcomes of 52 boys with proximal (n = 44) and complicated (n = 8) hypospadias who underwent two-stage graft urethroplasty repair (median age of 15 months and 3 years respectively) between 2004 and 2015. Fifteen toilet-trained boys without fistulas underwent uroflowmetry. The uroflow data were plotted on age–volume-dependent normograms with normal controls. The median follow-up was 34 months (8 months–8 years). Results and complications Complications were identified in three patients (6%) after the first stage (i.e. contracture of the graft) and in 20 patients (38.4%) after the second stage, including meatal stenosis (n = 8, 15.3%), urethral stricture (n = 4, 7.6%), urethrocutaneous fistula (n = 8, 15.3%), glandular dehiscence (n = 1, 1.9%), and diverticulum (n = 1, 1.9%). The patients with failed hypospadias experienced fewer complications than those who underwent the two-stage procedure for primary repair (25% and 45%, respectively). The reoperation rate was 36.8%. Eleven of the 15 toilet-trained boys were asymptomatic but exhibited flow rates below the normal range (median Qmax = 7 mL/s, range 3.5–16.7). Only one of the boys with a low flow rate was confirmed to have urethral stenosis under general anesthesia. Discussion In our study, primary hypospadias repair requiring urethral plate transection elicited worse outcomes than those observed in the prior failed hypospadias cases. However, because of our study's retrospective design, we were unable to accurately assess the initial position of the meatus in the redo hypospadias cases. Our data also demonstrated that the majority of cases without any voiding symptoms exhibited flow rates that were below the normal range despite no urethral stricture under general anesthesia. These findings indicate that urethras reconstructed via two-stage graft urethroplasty repair are not functionally equivalent to normal urethras, at least prior to puberty. Conclusion Two-stage graft urethroplasty repair was successful in 62% of cases after the second-stage procedure, but one-third of the boys required a reoperation after the two-stage planned repair. We demonstrated that although we used a urethral tissue substitute, the urine flow patterns of the patients without strictures were abnormal. Table . Two-stage graft urethroplasty repair for proximal or complicated hypospadias. Two-stage graft urethroplasty repair (n = 52), proximal hypospadias (n = 44), or complicated hypospadias (n = 8) Complications (n = 23) Contraction of the graft 3 (6%) Meatal stenosis 8 (15.3%) Urethral stricture 4 (7.6%) Urethrocutaneous fistula 8 (15.3%) Glanular dehiscence 1 (1.9%) Diverticulum 1 (1.9%) Follow-up 34 months (range 8 months to 8 years) Uroflow data (n = 15) Qmax (mL/s) 9.3 ± 0.7 Voided volume (mL) 109.8 ± 4.5 Flow rate (s) 25.4 ± 2.9 Plateau sharped curve 11 (73%)

Summary Introduction Posterior urethral valves (PUV) are among the most common urological causes of chronic kidney disease (CKD) in childhood. Recently, genomic imbalances have been cited as potential risk factors for altered kidney function and have been associated with CKD. The phenotypic effects of a copy number variant (CNV) in boys with PUV are unknown. Here, it was hypothesised that the progression to early renal failure in PUV patients may be influenced by genetic aberrations. Objective To assess the relationship between CNVs and renal outcomes. Patients and methods Between September 2012 and July 2015, 45 children with PUV were recruited to evaluate the presence of CNVs in their DNA. The patients' medical records were retrospectively reviewed. The criteria for outcomes of renal function included: assessments of the nadir serum creatinine in the first year of life, the estimated glomerular filtration rate at 1 and 5 years, and the requirement for renal replacement. Results Thirteen CNVs were identified in 12 boys (29% of the cohort). Microarray analysis revealed two pathogenic CNVs (well-established CNVs known to be associated with genetic disease) and 11 of unknown significance (CNVs with insufficient current available evidence for unequivocal determination of clinical significance), including genes that have been previously implicated in kidney diseases and urogenital disorders. The median follow-up was 10.2 years (range 3–17.5) in the group of patients with CNV compared with 5.8 years (range 1–16.6) in those CNV−. The nadir creatinine values were significantly higher in boys with CNVs than in those without CNVs (57.5 μmol/L (range 23–215) and 28 μmol/L (range 18–155), respectively (P = 0.05) (Figure). Boys CNV+ had a worse prognosis, with a higher incidence of Stage-V CKD compared with the control group (33% with CNVs vs. 9% in CNV−, P = 0.06) at a median age of 22 months (range 8 months–16 years). Four (33%) patients CNV+ underwent renal transplantation. Discussion The role of CNVs in the deterioration of renal function remains unknown. It can be hypothesised that CNVs could be a contributing factor or may serve as an accelerant for the progression to renal failure. Conclusion The CNVs >100 Kb were significantly associated with early onset renal failure in children with PUV. Prenatal detection of CNV could help to identify foetuses at high risk of severe renal impairment in cases of suspected PUV, especially in cases without oligohydramnios or severe pulmonary hypoplasia. These preliminary results should be confirmed in a larger cohort of patients. Download : Download high-res image (121KB) Download : Download full-size image Summary Figure . Box plot graphic representation of nadir of creatinine value during the first year of life according to the presence of CNV (CNV+) or the absence of CNV (CNV−).

Purpose The management of exstrophy-epispadias has changed markedly over the past thirty years, and long-term outcomes for different approaches of closure are not known. We have evaluated the outcomes and complications seen in all patients with exstrophy-epispadias complex managed at our institution over the past thirty years. Material and methods A retrospective notes review of all patients treated for exstrophy-epispadias complex was carried out. Basic patient demographics were recorded, as were details of all operations, complications, continence and renal function. Continence rates for patients with classic bladder exstrophy were calculated. Patients were divided into three groups on the basis of their date of birth (1975-1985, 1985-1995 and 1995-2005). Results A total of 62 patients with exstrophy-epispadias complex were treated at RCH from 1975-2005. The majority of these patients were treated from 1985-2005 (53), using the Kelly soft tissue mobilisation principle. The majority of patients had classic bladder exstrophy (42). Patients typically undergo a large number of operations in the management of classic bladder exstrophy and for complications of surgery. Complications remain commonplace, but a small number of patients had no complications. Most patients have normal renal function, but with attempts to achieve continence, more patients have some degree of renal impairment (25% of patients born 1995-2005). Continence without catheterisation is uncommon in patients with classic bladder exstrophy aged under 10 (25%), but continence improves dramatically in patients aged between 10 and 20 with 53% of patients in this age range being continent without catheterisation and a further 25% continent with catheterisation. Conclusions Bladder exstrophy remains a challenging condition to treat effectively. Complications are common, and continence is uncommon in the first decade of life. Secondary operations to improve bladder capacity and reconstruct the bladder neck have allowed the majority of patients to achieve continence in adolescence and early adult life.