[Prenatal path of care following the diagnosis of a malformation for which a novel prenatal therapy is available]. / Parcours prénatal devant une malformation pour laquelle un traitement in utero émergent est disponible.

OBJECTIVES: Fetal therapy is part of the available care offer for several severe malformations. The place of these emergent prenatal interventions in the prenatal path of care is poorly known. The objective of this study is to describe the decision-making process of patients facing the option of an emergent in utero intervention. METHODS: We have conducted a retrospective monocentric descriptive study in the department of maternal-fetal medicine of Necker Hospital. We collected data regarding eligibility or not for fetal surgery and the pregnancy outcomes of patients referred for myelomeningocele, diaphragmatic hernia, aortic stenosis and low obstructive uropathies. RESULTS: All indications combined, 70% of patients opted for fetal surgery. This rate was lower in the case of myelomeningocele with 21% consent, than in the other pathologies: 69% for diaphragmatic hernias, 90% for aortic stenoses and 76% for uropathy. When fetal intervention was declined, the vast majority of patients opted for termination of pregnancy: 86%. In 14% of the considering fetal surgery, the patient was referred too far. CONCLUSION: The acceptance rate for fetal surgeries depends on condition. It offers an additional option and is an alternative for couples for which termination of pregnancy (TOP) is not an option. Timely referral to an expert center allows to discuss the place of a fetal intervention and not to deprive couples of this possibility.

Biometric and morphological features on magnetic resonance imaging of fetal bladder in lower urinary tract obstruction: new perspectives for fetal cystoscopy.

OBJECTIVES: Incompatibility between currently available fetoscopes and the anatomical constraints of the distended fetal bladder, with the resulting curvature around the bladder neck, account for most technical difficulties during fetal cystoscopy in lower urinary tract obstruction (LUTO). The aim of this anatomical study was to assess by magnetic resonance imaging (MRI) the variation in three bladder angles (bladder-neck angle (BNA), vesicourethral angle (VUA) and angle between bladder dome and posterior urethra (DUA)), according to gestational age (GA), bladder volume and the presence of LUTO. METHODS: From our fetal medicine database, we retrieved for review 46 MRI examinations of male fetuses between 2015 and 2019, including 17 with LUTO, examined at a mean GA of 28.1 (range, 17.3-35.0) weeks and 29 age-matched controls, examined at 29.9 (range, 21.9-35.0) weeks. We measured bladder volume, bladder-wall thickness and the three bladder angles, and used the Mann-Whitney U-test to compare values between groups. Variations according to GA and bladder volume were determined using analysis of variance (ANOVA). A reliability study was performed using the Bland-Altman method and Lin's correlation coefficient was calculated. RESULTS: Both bladder volume and bladder-wall thickness were significantly greater in the LUTO group (P < 0.01). BNA was significantly larger in LUTO compared with control fetuses: the mean (range) was 127.1° (101.6-161.6°) vs 111.2° (88.5-157.3°) (P < 0.01). DUA averaged 117° and showed no difference between the groups (P = 0.92). No statistical comparison was performed on VUA since this was not measurable in most control fetuses. ANOVA showed no variation of any angle with bladder volume in both LUTO fetuses and control fetuses. BNA in LUTO fetuses was the only angle to vary with GA, being larger after, compared with at or before, 25 weeks (P = 0.04). The reliability study showed an acceptable bias for both intra- and interobserver reproducibility for all three angles. CONCLUSION: The findings that BNA is increased by approximately 15° in fetuses with LUTO and DUA averages 117° could aid in development of a customized fetal cystoscope and help to overcome the current technical challenges of fetal cystoscopy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Left lateral retroperitoneoscopic total nephrectomy of a horseshoe kidney in a 3-year-old boy.

The unilateral or bilateral approach for nephrectomy in horseshoe kidney by minimally invasive surgery has been described. A total binephrectomy by a unilateral retroperitoneoscopic approach was performed for congenital nephrotic syndrome. A unilateral retroperitoneoscopic approach was planned in a 3-year-old boy (13 kg) with congenital nephrotic syndrome resistant to steroids with massive protein loss. The operative time was 160 min. The postoperative course was uneventful with continued hemodialysis until renal transplant 18 months later. The unilateral retroperitoneal approach allows total nephrectomy to be completed safely in horseshoe kidney for benign disease. The retroperitoneal access preserves the abdominal cavity, should peritoneal dialysis be required.

[Imaging strategy for children after a first episode of pyelonephritis]. / Explorations morphologiques après un premier épisode de pyélonéphrite chez l'enfant.

Pyelonephritis is a common bacterial disease in young children and is a serious infection because of its potential to produce renal scarring. One of the concerns of physicians is therefore the diagnosis of uropathy at risk for recurrence of pyelonephritis, especially high-grade reflux. There are no French recommendations on imaging evaluation after a first episode of pyelonephritis. Voiding cystography was systematically proposed years ago and recommended by the American Academy of Pediatrics until 1999. This systematic strategy exposed all children to a painful, irradiating exam, and exposed them to urinary tract infection. The American recommendations changed in 2011 and cystography is now only proposed to children with recurrence of pyelonephritis or with ultrasound abnormalities. A collaborative review of the literature involving the Pediatric Emergency, Nephrology and Surgery Departments at Necker-Enfants-Malades Hospital led us to propose an algorithm for imaging after the first episode of pyelonephritis in children. This algorithm was based on data from the past medical history (results of prenatal ultrasonography or recurrence of pyelonephritis), the results of the ultrasound exam at the time of diagnosis, and the procalcitonin concentration, to limit the indications for voiding cystography, limiting risk for delaying high-grade reflux diagnosis. Children with low risk for high-grade reflux can be followed up with an ultrasound exam 6 months after acute infection.

[Anorectal malformations]. / Malformations ano-rectales.

Anorectal malformations (ARM) are the result of an abnormal development of the terminal part of the digestive tract interesting anus and/or rectum that occur early between the sixth and tenth week of embryonic development. They carry a malformation spectrum of severity depending on the level of disruption of the anorectal canal and of the associated caudal malformations (sacrum and spine). ARM are associated in over half the cases with other malformations that can be integrated in some cases in known syndromes. If surgical treatment to restore anatomy as normal as possible is indispensable, post-operative care is essential for these patients whose defecation mechanisms are altered, to reach if not continence, at least a socially acceptable cleanliness.

Renal transplantation in 4 patients with methylmalonic aciduria: a cell therapy for metabolic disease.

INTRODUCTION: Patients with methylmalonic acidemia (MMA) may develop many complications despite medical treatment, in particular, severe central nervous system damage and chronic kidney disease (CKD). A kidney transplant may partially correct the metabolic dysfunctions. Liver, kidney and combined liver-kidney transplantations have been advocated but no guidelines are available to identify the most suitable organ to transplant. PATIENTS AND METHODS: Four patients with MMA (mut° phenotype) received a kidney graft because of repeated metabolic decompensations, with progression to CKD in 3 patients (end-stage kidney disease in two patients and CKD stage III in one patient with an estimated glomerular filtration rate [eGFR] of 40ml/min/1.73m(2)) but normal renal function in one (eGFR of 93ml/min/1.73m(2)) before transplantation. RESULTS: The medium age at transplantation was 7.9y (5-10.2) and the median follow-up was 2.8years (1.8-4.6). Renal transplantation improved the relevant metabolic parameters in 4/4 patients and renal function in the patients with CKD. Plasma and urinary MMA levels immediately decreased and remained normal or subnormal (mean values of plasma MMA before transplantation 1530µmol/L versus 240µmol/L after transplantation, and mean values of urine MMA before transplantation 4700mmol/mol creatinine versus 2300mmol/mol creatinine after transplantation). No further acute metabolic decompensation was observed and protein-intake was increased from 0.60 to 0.83g/Kg/day. One patient transplanted at age 9.7years developed a hepatoblastoma at age 11years with subsequent neurological complications and eventually died. The three other patients are alive. Two of them remained neurologically stable. The 3rd patient who displayed choreoathetosis transiently improved his neurological condition immediately after transplantation and then remained stable. CONCLUSION: Kidney transplantation represents an interesting alternative therapeutic option in methylmalonic aciduria, for renal complications but also as a "cellular therapy" that may significantly reduce metabolic decompensations and hospitalizations. However, further neurological impairment remains possible.

Morphological mosaicism of the pancreatic islets: a novel anatomopathological form of persistent hyperinsulinemic hypoglycemia of infancy.

BACKGROUND: Morphological studies of the pancreas in persistent hyperinsulinemic hypoglycemia of infancy (PHHI) have focused on the diagnosis of focal vs. diffuse forms, a distinction that determines the optimal surgical management. ABCC8 or KCNJ11 genomic mutations are present in most of them. AIM: Our aim was to report a new form of PHHI with peculiar morphological and clinical characteristics. RESEARCH DESIGN AND METHODS: Histopathological review of 217 pancreatic PHHI specimens revealed 16 cases morphologically different from diffuse and focal forms. They were analyzed by conventional microscopy, quantitative morphometry, immunohistochemistry, and in situ hybridization. RESULTS: Their morphological peculiarity was the coexistence of two types of islet: large islets with cytoplasm-rich ß-cells and occasional enlarged nuclei and shrunken islets with ß-cells exhibiting little cytoplasm and small nuclei. In small islets, ß-cells had abundant insulin content but limited amount of Golgi proinsulin. Large islets had low insulin storage and high proinsulin production and were mostly confined to a few lobules. No evidence for K(ATP) channels involvement or 11p15 deletion was found. Genomic mutations for ABCC8, KCNJ11, and GCK were absent. Patients had normal birth weight and late hypoglycemia onset and improved with diazoxide. Ten were cured by limited pancreatectomy. Six recurred after surgery and were medically controlled. CONCLUSION: This new form of PHHI is characterized by a morphological mosaicism. Pathologists should recognize this mosaicism on intraoperative frozen sections because it is often curable by partial pancreatectomy. The currently unknown genetic background does not involve the classical genomic mutations responsible for diffuse and focal PHHI.

ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.

BACKGROUND: Congenital hyperinsulinism (CHI) is characterised by an over secretion of insulin by the pancreatic ß-cells. This condition is mostly caused by mutations in ABCC8 or KCNJ11 genes encoding the SUR1 and KIR6.2 subunits of the ATP-sensitive potassium (K(ATP)) channel. CHI patients are classified according to their responsiveness to diazoxide and to their histopathological diagnosis (either focal, diffuse or atypical forms). Here, we raise the benefits/limits of the genetic diagnosis in the clinical management of CHI patients. METHODS: ABCC8/KCNJ11 mutational spectrum was established in 109 diazoxide-unresponsive CHI patients for whom an appropriate clinical management is essential to prevent brain damage. Relationships between genotype and radiopathological diagnosis were analysed. RESULTS: ABCC8 or KCNJ11 defects were found in 82% of the CHI cases. All patients with a focal form were associated with a single K(ATP) channel molecular event. In contrast, patients with diffuse forms were genetically more heterogeneous: 47% were associated with recessively inherited mutations, 34% carried a single heterozygous mutation and 19% had no mutation. There appeared to be a predominance of paternally inherited mutations in patients diagnosed with a diffuse form and carrying a sole K(ATP) channel mutation. CONCLUSIONS: The identification of recessively inherited mutations related to severe and diffuse forms of CHI provides an informative genetic diagnosis and allows prenatal diagnosis. In contrast, in patients carrying a single K(ATP) channel mutation, genetic analysis should be confronted with the PET imaging to categorise patients as focal or diffuse forms in order to get the appropriate therapeutic management.

Hypospadias: surgery and complications.

The aim of this review is to summarize the various steps of the surgical procedures to treat a hypospadias. Hundreds of procedures have been described but most of them follow the same principles. They include correction of a ventral curvature, the urethroplasty itself and penile skin reconstruction. Most of the affected children may be treated with a one-stage procedure. Each hypospadias surgeon has to know a variety of techniques and tailor the procedure used for each individual child. Complications are frequent after the hypospadias correction. Fistulas are the more frequent of these complications occurring in less than 5% of anterior cases, but up to 50% in posterior cases. Long-term follow-up is mandatory to evaluate the sexual outcome of the adults operated on during childhood for a posterior hypospadias, even if the available data seem reassuring.