WT1 complete gonadal dysgenesis with membranoproliferative glomerulonephritis: case series and literature review.

BACKGROUND: Intronic WT1 mutations are usually causative of Frasier syndrome with focal segmental glomerulosclerosis as the characteristic nephropathy. Membranoproliferative glomerulonephritis is not commonly associated with disorders of sex development but has been recently identified as a WT1-associated nephropathy, but usually in cases of exonic mutations in either isolated Wilms tumor or Denys-Drash syndrome. METHODS: The clinical and genetic data from 3 individuals are reported. RESULTS: This report describes the kidney manifestations in 3 individuals from 2 unrelated families with Frasier syndrome intronic WT1 mutations, noting that 2 of the 3 individuals have histologically confirmed membranoproliferative glomerulonephritis. CONCLUSIONS: These case reports support expansion of the clinical spectrum of the kidney phenotypes associated with Frasier syndrome providing evidence of an association between WT1 mutation and an immune complex-related membranoproliferative glomerulonephritis. A higher resolution version of the Graphical abstract is available as Supplementary information.

Variation in ureteric re-implantation for Australian children.

BACKGROUND: Management options for vesicoureteric reflux are numerous, increasingly diversifying and debated. There is longstanding anecdotal opinion of inexplicable regional variation in vesicoureteric reflux management in Australia. This study investigates temporal trends in ureteric re-implantation for children, and variation between states and territories. METHODS: Ureteric re-implantation data for children aged 0-14 years were retrieved from the Medicare Benefits Scheme item reports database for the 20-year period from 1998-2017. Claims data were population adjusted for each state then standardized for age using Australian Bureau of Statistics records. National and regional trends were calculated using joinpoint regression. Comparison between eastern (New South Wales, Victoria, Queensland, Tasmania, Australian Capital Territory) and western or central (Western Australia, South Australia) states was performed using the Mann-Whitney U-test. RESULTS: There were 4919 procedure rebate claims during the study period. A national decrease in claim rates of 6.3% per 100 000 children was identified (P < 0.001). This was derived from significant decreases observed in eastern states. There was a threefold higher claim rate in Western Australia and South Australia per annum compared to the remainder of the country (4.0 versus 12.6 per 100 000; P < 0.001). For the most recent 5 years of the study period, this difference increased to a sevenfold higher rate (1.6 versus 11.1; P < 0.001). CONCLUSION: There has been a dramatic nationwide decline in the rate of ureteric re-implantation procedure claims. Regional disparity between each side of the country is widening. Further research is required to determine if this degree of variation is warranted or unwarranted. The observed regional variation facilitates opportunity for a nationwide pragmatic clinical trial.

Penile nerve block predicts higher revision surgery rate following distal hypospadias repair when compared with caudal epidural block: A consecutive cohort study.

INTRODUCTION: Recent literature has suggested caudal epidural blocks (CEB) may increase revision surgery rates following hypospadias repair. We sought to investigate this using a large, multi-surgeon series. OBJECTIVE: The primary objective of this study was to identify the impact of CEB or penile nerve blocks (PNB) on revision surgery rates following distal hypospadias repair at our centre. STUDY DESIGN: A prospectively maintained database of consecutive patients undergoing primary hypospadias repairs under the supervision of 8 different paediatric surgeons at our centre between January 2015 and December 2018 was queried for the following potential risk factors: Age at surgery, American Society of Anaesthesiologist's (ASA) grade, hypospadias type, type of surgery, CEB or PNB, and training level of primary surgeon. Revision surgery was defined as reoperation for fistulas, dehiscence, strictures or meatal stenosis. Univariate and Multivariate analysis was performed using logistic regression. RESULTS: 188 patients underwent primary distal hypospadias repair over the study time period. Patients were aged between 7 months and 15 years of age. Median age at surgery was 14 months. Revision surgery was performed for 31 patients (16.5%). Indications were urethrocutaneous fistula (n = 17, 9.0%), meatal stenosis or stricture (n = 9, 4.8%) and glans dehiscence (n = 5, 2.7%). 114 (60.6%) received a penile block and 74 (39.4%) a caudal block. On univariate analysis, PNB (HR 2.55 95% CI 1.04-6.27, p = 0.04) was statistically significant for revision surgery. This association remained significant on multivariate analysis (HR 2.74 95% CI 1.09-6.92, p = 0.03). All other prognostic factors examined were not statistically significant for revision surgery. DISCUSSION: Our findings suggest PNB are associated with higher revision surgery rates following distal hypospadias repair. This contrasts with the findings of other authors. CONCLUSION: Our study is the first to demonstrate an association between PNB and higher revision surgery rates following distal hypospadias repair.

Urethral syringocele: unseen but existing.

BACKGROUND: Bulbourethral syringocele is an uncommon and under-diagnosed condition most commonly seen in the paediatric population, although there is increasing recognition in adults. Due to the difficulty in diagnosis, we report our experience of urethral syringocele in a quaternary paediatric hospital, with differing presentations, diagnosis and treatment. METHODS: This is a retrospective review of seven cases of children over a period of 14 years, including their presentations, diagnosis, treatment and follow-up. A review of the current literature is presented. RESULTS: The median age of these seven cases at presentation was 11 years (6 days to 16 years). Clinical features varied with age, with obstructive uropathy in a neonate, urinary tract infection in an infant, scrotal abscess in two children and lower urinary tract obstructive symptoms in three teenagers. Diagnostic voiding cystogram diagnosed the majority of syringoceles and two were seen on magnetic resonance imaging. Five boys underwent endoscopic transurethral deroofing and two children required transperineal marsupialization. Long-term follow-up showed all had complete resolution of symptoms. CONCLUSION: Urethral syringocele presents from the neonatal period to late adolescence, with the presenting features reflective of age. Surgical management can be performed endoscopically or by open approach. Awareness of this condition and inclusion in the differential diagnosis, particularly in the setting of an atypical or recurrent scrotal abscess, could avoid a prolonged therapeutic course.

Retroperitoneoscopic partial nephrectomy in children: a multicentric international comparative study between lateral versus prone approach.

BACKGROUND: Very limited informations are currently available about the best approach to perform retroperitoneoscopic surgery. This multicentric international study aimed to compare the outcome of lateral versus prone approach for retroperitoneoscopic partial nephrectomy (RPN) in children. METHODS: The records of 164 patients underwent RPN in 7 international centers of pediatric surgery over the last 5 years were retrospectively reviewed. Sixty-one patients (42 girls and 19 boys, average age 3.8 years) were operated using lateral approach (G1), whereas 103 patients (66 girls and 37 boys, average age 3.0 years) underwent prone RPN (G2). The two groups were compared in regard to operative time, postoperative outcome, postoperative complications, and re-operations. RESULTS: The average operative time was significantly shorter in G2 (99 min) compared to G1 (160 min) (p = 0.001). Only 2 lateral RPN required conversion to open surgery. There was no significant difference between the two groups as for intraoperative complications (G1:2/61, 3.3%; G2:6/103, 5.8%; p = 0.48), postoperative complications (G1:9/61, 14.7%; G2:17/103, 16.5%; p = 0.80), and re-operations (G1:2/61, 3.3%; G2:4/103, 3.8%; p = 0.85). Regarding postoperative complications, the incidence of symptomatic residual distal ureteric stumps (RDUS) was significantly higher in G2 (7/103, 6.8%) compared to G1 (1/61, 1.6%) (p = 0.001). Most re-operations (4/6, 66.6%) were performed to remove a RDUS . CONCLUSIONS: Both lateral and prone approach are feasible and reasonably safe to perform RPN in children but the superiority of one approach over another is not still confirmed. Although prone technique resulted faster compared to lateral approach, the choice of the technique remains dependent on the surgeon's personal preference and experience. Our results would suggest that the lateral approach should be preferred to the prone technique when a longer ureterectomy is required, for example in cases of vesico-ureteral reflux into the affected kidney moiety, in order to avoid to leave a long ureteric stump that could become symptomatic and require a re-intervention.

Spontaneous bladder rupture in non-augmented bladder exstrophy.

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 (<10) bladders. Both had high leak point pressures: 60 cmH2O at 100 mL. The mean age at rupture was 11 years, with a range of 5-20 years. Patients presented with abdominal pain, associated with signs of intestinal obstruction in seven and fever in two. Eight patients underwent laparotomy and one prolonged drainage via SPC. Simple closure was performed in seven and bladder neck closure in one, because of extension of the rupture inferiorly. All patients recovered well. Following rupture, five underwent augmentation and Mitrofanoff. One of these suffered a recurrent rupture. Two other patients refused augmentation and Mitrofanoff and one of these has since had a subsequent rupture. 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.

Dual genetic diagnoses: Atypical hand-foot-genital syndrome and developmental delay due to de novo mutations in HOXA13 and NRXN1.

We describe a male patient with dual genetic diagnoses of atypical hand-foot-genital syndrome (HFGS) and developmental delay. The proband had features of HFGS that included bilateral vesicoureteric junction obstruction with ectopic ureters, brachydactyly of various fingers and toes, hypoplastic thenar eminences, and absent nails on both 4th toes and right 5th toe. The atypical features of HFGS present were bilateral hallux valgus malformations and bilateral preaxial polydactyly of the hands. Chromosomal microarray analysis identified a de novo 0.5 Mb deletion at 2p16.3, including the first four exons of the NRXN1 gene. Whole exome sequencing and subsequent Sanger sequencing identified a de novo missense mutation (c.1123G>T, p.Val375Phe) in exon 2 of the HOXA13 gene, predicted to be damaging and located in the homeobox domain. The intragenic NRXN1 deletion is thought to explain his developmental delay via a separate genetic mechanism.

Hidden danger of button batteries.

This case highlights a rare but important presentation of aorto-oesophageal fistula caused by a concealed foreign body. Primary prevention strategies are needed to address the danger associated with button batteries.

Reninoma: an uncommon cause of Renin-mediated hypertension.

Reninoma (juxtaglomerular cell tumor) is a rare cause of renin-mediated hypertension. Reninomas are usually diagnosed in adolescents and young adults with occasional reports in younger children. Patients typically present with a long history of headaches leading to a diagnosis of severe hypertension that responds well to antihypertensive treatment targeting the renin-angiotensin-aldosterone system. The clue to clinical diagnosis is the presence of hypokalemia and metabolic alkalosis on the first blood sample drawn before any treatment is instituted. Elevated blood levels of renin and aldosterone confirm the clinical suspicion of renin-mediated hypertension. Diagnostic imaging is employed to identify the source of excessive renin production. While renal ultrasound can miss reninoma, contrast CT or magnetic resonance imaging of the kidneys are diagnostic modalities of choice leading to the correct diagnosis. Renal vein renin sampling with lateralization might help to identify the site of excessive renin production. Nephron-sparing surgery is curative with maintenance of normal blood pressure after discontinuation of antihypertensive medications in the majority of patients. In this paper, we present the case of reninoma in an adolescent girl emphasizing clinical presentation, diagnostic evaluation, and medical and surgical treatment of this rare tumor. We also discuss important points in the management of children presenting with renin-mediated hypertension.

Long-term review of sutureless ward reduction in neonates with gastroschisis in the neonatal unit.

BACKGROUND: A sutureless ward reduction (SWR) protocol was implemented in the neonatal intensive care unit of a tertiary level hospital in 1999. Although the short-term outcomes associated with SWR have been documented, the long-term outcomes are unknown. METHODS: Retrospective data were collected from the medical records of all neonates with gastroschisis from September 1999 to December 2010. Data on their growth and development and the prevalence of any health problems were collected. RESULTS: Eighty-eight patients with gastroschisis were managed over an 11 year period. Forty-four of these patients received SWR, with 2 deaths in the neonatal period. In the 42 survivors, 35 patients were reviewed at a median age of 7 years and 10 months (range, 6-134 months; interquartile range, 37-124 months). One patient experienced failure to thrive and developmental delay, and later died of a medical complication. Thirty-two patients (91.4%) developed an umbilical hernia, only 2 of whom required umbilical herniotomy. Four patients (11.4%) developed small bowel obstruction, all within the first year. CONCLUSION: Most patients with SWR exhibited normal growth with minimal bowel complications. Despite the high incidence of umbilical hernia, the majority resolved spontaneously and did not require subsequent herniotomy.

Urethral duplication: cases of ventral and dorsal complete duplication and review of the literature.

Urethral duplication is a rare congenital anomaly, with multiple described anatomical variants. Duplications in the sagittal plane can be complete or partial, dorsal or ventral, and may be associated with other congenital urogenital anomalies. The anatomy of the duplication should be defined, and the functional urethra identified prior to any corrective surgical intervention. Correction aims to restore normal cosmesis, provide functional voiding and maintain continence. We describe two cases of urethral duplication in the sagittal plane, outline our approach to surgical correction, and review the literature.

Laparoscopic versus open appendectomy in children: a retrospective comparative study of 2,332 cases.

AIM: The laparoscopic treatment of paediatric appendicitis remains controversial, especially in the presence of complications. This study evaluated the outcomes of open appendectomy (OA) and laparoscopic appendectomy (LA) by analysing the data from a multicentre study. METHODS: The authors retrospectively reviewed a series of 2,332 appendectomies (1,506 LA and 826 OA) performed in children and adolescents (median age 8 years) in 9 different centres of paediatric surgery. For the patients operated using laparoscopy, an IN procedure was employed in 921 (61.2%), an OUT procedure in 571 (37.9%) and a MIXED procedure in 14 (0.9%). In the open surgery, a McBurney incision was adopted in 795 patients (96.4%). RESULTS: Median duration of surgery was 40 minutes for LA and 45 minutes for OA. Median hospital stay was 3 days (LA) and 4.3 days (OA) in case of simple appendicitis and 5.2 days (LA) and 8.3 days (OA) in case of peritonitis. Complications were recorded in 124 LA cases (8.2%) and 65 OA cases (7.9%). The conversion rate in laparoscopy was only 1.6% (25 cases). The statistical analysis was performed using the Mann-Whitney test, and the main significant difference that emerged was the length of hospital stay, which was in favour of laparoscopy compared with open surgery (P < 0.0001). CONCLUSIONS: We conclude that in clinical settings where laparoscopic surgical expertise and equipment are available and affordable, LA seems to be an effective and safe alternative to OA. Three out 9 centres participating in our survey perform LA in all patients with a suspicion of appendicitis. Our study shows that laparoscopy significantly reduces hospital stay in case of appendicitis and peritonitis and presents an extremely low conversion rate (1.6%) to open surgery. Laparoscopic transumbilical appendectomy (37.9%) in our series seems to be a simple option, even for less-skilled laparoscopic surgeons.

Successful management of lymphangiomatosis and chylothorax in a 7-month-old infant.

A 7-month old infant presented with an effusion and multiple lesions in his spleen. A diagnosis of lymphangiomatosis was made based on chylous effusion and an MRI demonstrating numerous enhancing lesions within the spleen on T2-weighed images. Conservative measures, including the withdrawal of feeds and octreotide, did not significantly reduce the rate of chyle production and increasing requirement for respiratory support. Resection of the patient's spleen and partial pleurectomy were associated with a dramatic improvement in his condition. At 27 months the patient was well with no evidence of further lymphangiomas or a recurrence of his chylothoraces.

Retroperitoneoscopic resection of retroperitoneal bronchogenic cysts.

Two children aged 8 and 15 years underwent excision of retroperitoneal bronchogenic cysts (RBC) via a posterior retroperitoneoscopic approach (RPA). The operative technique and efficacy of this approach are reviewed. One lesion was symptomatic, while the other was an incidental finding on abdominal ultrasound. Operating times were 45 and 55 min. One patient was discharged on the day of surgery, the other on the 1st postoperative day. Both returned to normal physical activities within 1 week of surgery. No complication occurred in either case. To our knowledge, this is the first description in the literature of excision of this rare lesion via a RPA. We conclude that this is a safe method for resection of RBCs that offers several potential advantages compared with the open technique.

Limb constriction as a complication of intra-uterine vesico-amniotic shunt: fetoscopic release.

Complete fetal bladder outlet obstruction was first diagnosed in a fetus at 13.5 weeks. After sequential vesicocentesis had shown good renal function, a vesico-amniotic shunt was inserted at 17 weeks with a Rodeck catheter. The procedure was successful and amniotic fluid volume re-accumulated to normal levels. A detailed scan at 20 weeks showed that the distal free end of the catheter was wound round the left fetal thigh. As the fetus grew, there was progressive constriction of the fetal thigh by the catheter. By 29 weeks, Doppler blood flow changes to the left leg were apparent. Fetoscopic surgery was performed at 30 weeks to release the constriction. The catheter was divided successfully, but the divided end of the shunt subsequently retracted into the fetal abdomen, producing urinary ascites, bilateral hydroureter and hydronephrosis. The baby was delivered at 31.5 weeks in good condition. Endoscopic resection of anterior and posterior urethral valves was performed at 6 months of age. At 2 years, the child has normal renal function, growth parameters and developmental milestones. Mild indentation of the left thigh was still apparent, although there was no functional impairment.

Sertoli-Leydig cell tumor of the ovary, a rare cause of precocious puberty in a 12-month-old infant.

We report a 12-month-old infant who presented with a 4-month history of isosexual precocious puberty secondary to an estrogenizing Sertoli-Leydig cell tumor of the ovary. Total serum immunoreactive inhibin and subunits A and B were markedly elevated before surgical resection and subsequently decreased 7 wk later into the normal prepubertal range. Twenty weeks following surgical removal, the patient presented again with central precocious puberty; inhibin B levels were raised on this occasion, a luteinizing releasing hormone stimulation test confirmed central precocious puberty. This is the youngest reported occurrence of this rare sex cord stromal neoplasm. The prognosis of this extremely rare tumor presenting at this early juvenile stage is uncertain. This report illustrates the usefulness of serum inhibin as a tumor marker during therapeutic suppression with leuprorelin acetate for central precocious puberty. Analysis of genomic and tumor DNA revealed a normal nucleotide sequence for the LH receptor and the Galpha(s) gene. To understand the molecular pathogenesis of this tumor we analyzed mRNA levels for the inhibin A and B subunits, FSH receptor, LH receptor aromatase, steroidogenic factor-1 and the ER beta genes. Molecular characterization reveals the presence of genes specific for granulosa and Leydig cells; the relative expression of these genes, in addition to its histologic characteristics, suggests that this tumor may result from a dysdifferentiation of a primordial follicle.