Pierre Alessandrini

Is Hypospadias Associated with Prenatal Exposure to Endocrine Disruptors? A French Collaborative Controlled Study of a Cohort of 300 Consecutive Children Without Genetic Defect

BACKGROUND Numerous studies have focused on the association between endocrine-disrupting chemicals (EDCs) and hypospadias. Phenotype variability, the absence of representative comparison groups and concomitant genetic testing prevent any definitive conclusions. OBJECTIVE To identify the role of occupational and environmental exposures to EDCs in nongenetic isolated hypospadias. DESIGN, SETTING, AND PARTICIPANTS A total of 408 consecutive children with isolated hypospadias and 302 normal boys were prospectively included (2009-2014) in a multi-institutional study in the south of France, the area of the country with the highest prevalence of hypospadias surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS In patients without AR, SRD5A2, and MAMLD1 mutations, parental occupational and professional exposures to EDCs were evaluated based on European questionnaire QLK4-1999-01422 and a validated job-exposure matrix for EDCs. Environmental exposure was estimated using the zip code, the type of surrounding hazards, and distance from these hazards. Multivariate analysis was performed. RESULTS Fetal exposure to EDCs around the window of genital differentiation was more frequent in the case of hypospadias (40.00% vs 17.55%, odds ratio 3.13, 95% confidence interval 2.11-4.65). The substances were paints/solvents/adhesives (16.0%), detergents (11.0%), pesticides (9.0%), cosmetics (5.6%), and industrial chemicals (4.0%). Jobs with exposure were more frequent in mothers of hypospadiac boys (19.73% vs 10.26%, p=0.0019), especially cleaners, hairdressers, beauticians, and laboratory workers. Paternal job exposure was more frequent in the cases of hypospadias (40.13% vs 27.48%, p=0.02). Industrial areas, incinerators, and waste areas were more frequent within a 3-km radius for mothers of hypospadiac boys (13.29% vs. 6.64%, p<0.00005). Association of occupational and environmental exposures increases this risk. CONCLUSIONS This multicenter prospective controlled study with a homogeneous cohort of hypospadiac boys without genetic defects strongly suggests that EDCs are a risk factor for hypospadias through occupational and environmental exposure during fetal life. The association of various types of exposures may increase this risk. PATIENT SUMMARY Our multi-institutional study showed that parental professional, occupational, and environmental exposures to chemical products increase the risk of hypospadias in children.

Fetal bladder rupture due to anteriorurethral valves.

A rupture of the fetal bladder that resulted in urinary ascites has rarely been reported in published studies. We present the first case of a spontaneous rupture of the fetal bladder, due to an anterior urethral valve, in which the diagnosis was suspected prenatally by means of Doppler ultrasonography and was confirmed postnatally.

Small bowel obstruction caused by congenital mesocolic hernia: case report

Transmesocolic hernias are extremely rare. Their exact incidence is still unknown. A strangulated hernia through a mesocolic opening is a rare operative finding. Preoperative diagnosis still is difficult in spite of imaging techniques currently available. This is the case of a 4-month-old boy with transmesocolic internal hernia and coincident intestinal malrotation and volvulus of small bowel.

Prenatal urinoma related to ureteropelvic junction obstruction: poor prognosis of the affected kidney.

OBJECTIVES We evaluated functional outcome of kidneys with fetal urinoma associated to ureteropelvic junction obstruction. METHODS We retrospectively reviewed 5 cases of antenatally diagnosed urinoma associated to hydronephrosis. Prenatal imaging work-up consisted of ultrasound (US) and magnetic resonance (MR) examination. Differential renal function was assessed postnatally with renal scintigraphy. RESULTS Four male fetuses and 1 female fetuse presented with urinoma with hydronephrosis diagnosed by US at 24-25 weeks gestational age and confirmed by MRI examination at 28-29 weeks gestational age. On postnatal US, urinoma had disappeared in 4 cases. Parenchyma of the affected kidney was poorly differentiated in all cases. Ureteropelvic junction obstruction was confirmed in the 5 cases. Renal scintigraphy revealed poor functioning kidney (1%) in 2 cases, no function in 1 case, and impaired function in 2 cases (17%). CONCLUSIONS Association of upper urinary tract dilatation caused by ureteropelvic junction obstruction and prenatally diagnosed urinoma may suggest a poor ipsilateral functioning kidney.

Minor Hypospadias: The “Tip of the Iceberg” of the Partial Androgen Insensitivity Syndrome

Background Androgens are critical in male external genital development. Alterations in the androgen sensitivity pathway have been identified in severely undermasculinized boys, and mutations of the androgen receptor gene (AR) are usually found in partial or complete androgen insensitivity syndrome (AIS). Objective The aim of this study was to determine whether even the most minor forms of isolated hypospadias are associated with AR mutations and thus whether all types of hypospadias warrant molecular analysis of the AR. Materials and Methods Two hundred and ninety-two Caucasian children presenting with isolated hypospadias without micropenis or cryptorchidism and 345 controls were included prospectively. Mutational analysis of the AR through direct sequencing (exons 1–8) was performed. In silico and luciferase functional assays were performed for unreported variants. Results Five missense mutations of the AR were identified in 9 patients with glandular or penile anterior (n = 5), penile midshaft (n = 2) and penile posterior (n = 2) hypospadias, i.e., 3%: p.Q58L (c.173A>T), 4 cases of p.P392S (c.1174C>T), 2 cases of p.A475V (c.1424C>T), p.D551H (c.1651G>C) and p.Q799E (c.2395C>G). None of these mutations was present in the control group. One mutation has never been reported to date (p.D551H). It was predicted to be damaging based on 6 in silico models, and in vitro functional studies confirmed the lowered transactivation function of the mutated protein. Three mutations have never been reported in patients with genital malformation but only in isolated infertility: p.Q58L, p.P392S, and p.A475V. It is notable that micropenis, a cardinal sign of AIS, was not present in any patient. Conclusion AR mutations may play a role in the cause of isolated hypospadias, even in the most minor forms. Identification of this underlying genetic alteration may be important for proper diagnosis and longer follow-up is necessary to find out if the mutations cause differences in sexual function and fertility later in life.

Pyélonéphrite xanthogranulomateuse diffuse du nourrisson

We report a case of a renal mass in a 4-month boy, which occured during the assessment of a pelvi-calyceal dilatation diagnosed at 23 weeks of gestational age. There was no history of urinary infection, fever or weight loss. Physical examination revealed a mass of the left flank with significant flank tenderness. Laboratory test showed a biological inflammatory syndrome and urine culture was negative. Investigations including ultrasound and computed tomography scan were suggestive of diffuse xanthogranulomatous pyelonephritis with a non-functioning left kidney. Left total nephrectomy was performed through a lumbar incision with an extraperitoneal approach. The kidney was enlarged with a dilated pelvis containing pus upstream of a proximal ureteral atretic segment. Pathological examination of the kidney confirmed the diagnosis of diffuse xanthogranulomatous pyelonephritis. The boy remains well at 1 year follow-up. Xanthogranulomatous pyelonephritis is very rare in infants. It is an uncommon severe progressive renal infection resulting in destruction of renal parenchyma, histologically replaced by xanthomatous cells and granulomatous reaction. Pathogenesis of xanthogranulomatous pyelonephritis remains unclear. But it is well known that urinary tract obstruction and renal lithiasis are determining factors. It can occur in variant clinical forms but its symptoms remain non-specific. Curative treatment consists in nephrectomy and definitive diagnosis is made on histological examination of the kidney. This diagnosis should be discussed when a renal mass occurs in a context of malformative uropathy and xanthogranulomatous pyelonephritis have to be included in the differential diagnosis of renal mass in infants and children.

Agénésie déférentielle bilatérale et hernie inguinale chez un enfant. Une présentation précoce rare de la mucoviscidose

Epididymal and ductal anomalies can be discovered incidentally during inguinal herniorraphy in children. The congenital bilateral absence of vas deferens is frequently associated with cystic fibrosis. Case report. – This agenesia of vas deferens was detected in a 5-month-old boy who underwent an inguinal herniorraphy. Although the child did not present any symptoms, he actually presented cystic fibrosis: the sudoral test showed high levels of chloride (95 mmol/L) and an isolated homozygous delta F 508 deletion on the gene CFTR was evidenced on genetic investigations. Conclusion. – The congenital bilateral absence of vas deferens is the most frequent anomaly of the male genital tract discovered in adults investigated for azoospermia. Relations with cystic fibrosis are well established but congenital bilateral absence of vas deferens discovered during infancy is an exceptional situation that requires genetic investigations to show evidence of a likely underlying cystic fibrosis.

Value of diagnosis imaging in the evaluation of the severity of histological lesions in duplex systems.

OBJECTIVE In order to determine the effectiveness of imagery in the assessment of the severity of histological lesions in duplex systems in children we compared histology results from heminephrectomies with diagnosis imaging findings [renal ultrasound (US), scintigraphy, unenhanced and contrast-enhanced magnetic resonance imagery (MRI)]. MATERIALS AND METHODS Between 2007 and 2013, 34 children with duplex system underwent surgery. The results from US (n = 34), dimer captosuccinic acid scintigraphy (n = 23) and MRI (n = 16) were compared with histological data. Five histological lesions were found (chronic interstitial inflammation, interstitial fibrosis, tubular atrophy, glomerulosclerosis and dysplasia) and categorized as severe (>25%) or moderate (≤ 25%). RESULTS Severe histological lesions were found in 76.5% and moderate lesions in 23.5%. Radiological features were compared with histological results. In US, severe parenchymal thinning was associated with chronic interstitial inflammatory. The absence of parenchymal enhancement and/or severe cortical thinning in MR urography (MRU) was significantly associated with interstitial fibrosis. All poorly functioning poles were associated with severe histological lesions (p = 0.091), but not to a specific category of lesions. CONCLUSIONS MRI sensibility was excellent (90%) in the diagnosis of poorly functioning pole. Severe thinning on US and minimal pole function on MRU can be used to predict the severity of histological lesions.

Antegrade Percutaneous Balloon Dilation of Ureteral Strictures After Failed Pelviureteric or Ureterovesical Reimplantation in Children

OBJECTIVES To assess the morbidity and success rate of percutaneous treatment of the postoperative ureteric strictures in children. MATERIALS AND METHODS Between January 1994 and December 2003, 12 children were treated by antegrade percutaneous balloon dilation for postoperative ureteric strictures. Stenosis occurred at the pelviureteric junction in 5 cases and ureterovesical junction in 7 cases. The 10 boys and 2 girls were between 3 months and 14 years old (mean, 5 years ± 4.7 years). General anesthesia was used in 10 cases for nephrostomy catheter placement. Five ureteral stents were used additionally for nephrostomy drainage with a 6-F catheter. Both nephrostomy and ureteric stents were in place for 28.5 ± 12 days, then removed after control antegrade pyelography. RESULTS Dilation was technically successful in 9 of our patients. Two peroperative complications occurred. Postoperative results were evaluated by ultrasonography, intravenous urography, antegrade pyelography, and diethylene triamine pentaacetic acid renography that confirmed no obstacle in all 5 cases of pelviureteric stricture with a follow-up of 4 ± 2.9 years and in 4 cases of ureterovesical junction with a follow-up of 4.7 ± 2.8 years. Three unsuccessful results were reported: in 2 cases, the guide wire could not be advanced over the stenotic ureterovesical junction and in 1 case an early restenosis occurred that eventually required surgery. CONCLUSIONS Although the main treatment of the postoperative ureteral strictures is surgical, the percutaneous antegrade balloon dilation seems to be an alternative to surgery with a low morbidity rate and short hospitalization period.

Cas cliniquePyélonéphrite xanthogranulomateuse diffuse du nourrissonDiffuse xanthogranulomatous pyelonephritis in infant

We report a case of a renal mass in a 4-month boy, which occured during the assessment of a pelvi-calyceal dilatation diagnosed at 23 weeks of gestational age. There was no history of urinary infection, fever or weight loss. Physical examination revealed a mass of the left flank with significant flank tenderness. Laboratory test showed a biological inflammatory syndrome and urine culture was negative. Investigations including ultrasound and computed tomography scan were suggestive of diffuse xanthogranulomatous pyelonephritis with a non-functioning left kidney. Left total nephrectomy was performed through a lumbar incision with an extraperitoneal approach. The kidney was enlarged with a dilated pelvis containing pus upstream of a proximal ureteral atretic segment. Pathological examination of the kidney confirmed the diagnosis of diffuse xanthogranulomatous pyelonephritis. The boy remains well at 1 year follow-up. Xanthogranulomatous pyelonephritis is very rare in infants. It is an uncommon severe progressive renal infection resulting in destruction of renal parenchyma, histologically replaced by xanthomatous cells and granulomatous reaction. Pathogenesis of xanthogranulomatous pyelonephritis remains unclear. But it is well known that urinary tract obstruction and renal lithiasis are determining factors. It can occur in variant clinical forms but its symptoms remain non-specific. Curative treatment consists in nephrectomy and definitive diagnosis is made on histological examination of the kidney. This diagnosis should be discussed when a renal mass occurs in a context of malformative uropathy and xanthogranulomatous pyelonephritis have to be included in the differential diagnosis of renal mass in infants and children.