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Background: Mutations of the NR5A1 gene encoding steroidogenic factor-1 have been reported in association with a wide spectrum of 46,XY DSD (Disorder of Sex Development) phenotypes including severe forms of hypospadias., Methodology/principal Findings: We evaluated the frequency of NR5A1 gene mutations in a large series of patients presenting with 46,XY DSD and hypospadias. Based on their clinical presentation 77 patients were classified either as complete or partial gonadal dysgenesis (uterus seen at genitography and/or surgery, n = 11), ambiguous external genitalia without uterus (n = 33) or hypospadias (n = 33). We identified heterozygous NR5A1 mutations in 4 cases of ambiguous external genitalia without uterus (12.1%; p.Trp279Arg, pArg39Pro, c.390delG, c140_141insCACG) and a de novo missense mutation in one case with distal hypospadias (3%; p.Arg313Cys). Mutant proteins showed reduced transactivation activity and mutants p.Arg39Pro and p.Arg313Cys did not synergize with the GATA4 cofactor to stimulate reporter gene activity, although they retained their ability to physically interact with the GATA4 protein., Conclusions/significance: Mutations in NR5A1 were observed in 5/77 (6.5%) cases of 46,XY DSD including hypospadias. Excluding the cases of 46,XY gonadal dysgenesis the incidence of NR5A1 mutations was 5/66 (7.6%). An individual with isolated distal hypopadias carried a de novo heterozygous missense mutation, thus extending the range of phenotypes associated with NR5A1 mutations and suggesting that this group of patients should be screened for NR5A1 mutations.

Unlabelled: This study evaluates the results of paediatric liver transplantation (PLT) with split liver grafts at Bicêtre hospital., Patients and Methods: Between January 1, 1988 and December 31, 1995, 205 PLT were performed in 180 children. One auxiliary PLT was excluded from the study. The graft was a whole (WLG), reduced (RLG) and split liver graft (SLG) in 76, 112 and 16 cases respectively. The SLG consisted of segments II + III in 14 cases, and II + III + IV in 2 cases. Results of PLT with SLT, RLT and WLG were retrospectively compared. Minimal follow-up was 12 months., Results: In elective PLT, actual 1 year patient (graft) survival were 93.3% (84.4%) with WLG (n = 64), 84.1% (76.4%) with RLG (n = 72), 81.8% (81.8%) with SLG (n = 11). In urgent LT, actual patient (graft) survival were 100% (83.3%) with WLG (n = 6), 58.6% (52.5%) with RLG (n = 40), 25% (20%) with SLG (n = 5). Specific complications of the splitting technique were: 2 Budd-Chiari syndromes in 2 early patients, without any new case after modification of the technique of left hepatic vein to inferior vena cava anastomosis; 4 bile leaks (25%) from the left hepatic duct to Roux-en-Y loop anastomosis., Discussion: In our experience, the results of PLT with SLG were satisfactory in the elective situation, but disappointing in urgent cases. In the current context of liver graft shortage, appropriate use of this sophisticated and demanding technique depends on the experience of the team, recipient's condition, and logistic considerations.

The objective of this report is to review portal complications (PC) after pediatric liver transplantation (LT) for biliary atresia (BA) in the Bicêtre surgical series. From January 1, 1988, to February 28, 1995, 96 children with BA underwent 115 LTs Portal anastomosis was done on either the recipient portal vein (n = 85) or superior mesenteric vein (n = 11). No antiaggregative agents were administered postoperatively. Median follow-up was 50 months (range, 12 to 97). Nineteen PC (16.5%) occurred in 17 recipients: 16 portal thrombosis (PT) and 3 portal stenosis (PS). Fifteen instances of early PT occurred between days 0 and 17 (median, day 2). Emergency thrombectomy was performed in 9 cases (successful in 5). Three children underwent a secondary portosystemic shunt (successful in 2). Three PS were cured by either surgery or balloon dilatation. Four children died, 3 are alive with portal hypertension (PHT), and 10 are alive without PHT. Three-year patient actuarial survival is 82.4% in PC cases and 82% in others (NS). Significant risk factors of PC are young age and weight at the time of LT, small portal vein, and emergency LT. Analysis of our own results and review of the literature suggest that prevention of PC depends primarily on appropriate surgical technique. Reduction of postoperative hypercoagulability may also play an important role: a meta-analysis of 1,257 published pediatric LT show an overall risk of PT of 2.2% in teams using aspirin with or without dipyridamole compared with 7.8% when no antiaggregative agents are given (P = .0001).

The aim of this work is to determine the influence of age, extrahepatic biliary lesions pattern (EHBP) and association to polysplenia syndrome (PS) on 10 years outcome of 164 patients with biliary atresia (BA) treated from 1984 to 1992 by initial Kasai operation (KO) and secondary liver transplantation (LT) when necessary. Actuarial crude survival without or after LT (CS), actuarial survival with native liver (NLS) and jaundice-free actuarial survival with native liver (JFS) were calculated from 1 to 10 years versus age (under/over 45 days), EHBP (favorable/ unfavorable) and PS (no/yes). Overall 10-year CS is 70%, overall 10-year NLS and JFS are 14%. In univariate analysis, age at KO under 46 days, favorable EHBP (BA with patent gallbladder, and/or cystic dilatation of extrahepatic bile duct, or BA restricted to choledocus), and absence of PS are significant determinants of a better outcome regarding CS, NLS and JFS. EHBP is more discriminant than age. Influence of PS in this series is redundant with that of EHBP since 11/11 patients with PS had unfavorable EHBP.

According to French rules for cadaver organ sharing, children with biliary atresia (BA) complicated with acute necrosis (ALN) can be registered on the waiting list for liver transplantation (LT) in a special intermediate grade urgent code. Over a 7 years period, 100 children have been submitted to elective LT for BA and 15 to urgent LT. Urgent procedures accounted for 25% of LT for BA in patients aged 0-2 years and 67% (8/12) in patients under 1 year of age. Children actuarial survival at 1, 12 and 48 months was respectively 66%, 60% and 60% versus 92%, 86% and 85%, deaths occurring earlier in the urgent group. Graft actuarial survival at 1, 12 and 48 months were 60%, 53% and 53% versus 85%, 77% and 76% (p < 0.05), respectively. Outcome of children and grafts after LT is not significantly different in BA cases and in other urgent indications, excluding retransplantations. In a LT program based on cadaver organ donation, allocation of in an urgent registration code to children with BA and ALN offers them more than 50% chance to escape death and does not result in wasting of grafts.

An abdominal or pelvic tumor in very seldom detected in a prenatal ultrasound examination. The most commonly detected tumors are, in order of decreasing frequency, sacrococcygeal teratomas, neuroblastomas and kidney tumors. According to the present state of the art, diagnosis of a sacrococcygeal teratoma only leads to specific monitoring of the pregnancy, because an early delivery or delivery by cesarean section will be necessary in some cases to improve the prognosis of child and/or mother. For other types of tumors investigations and actions should be delayed until after birth.

Eleven patients presenting with spontaneous perforation of the biliary tract were treated at Bicêtre Hospital between 1971 and 1993. Three groups were individualised, each with a different pattern of local presentation: generalised biliary peritonitis (n = 2), localised biliary peritonitis (n = 4), secondary biliary stenosis (n = 5). In each case, cholestatic jaundice developed after a postnatal symptom-free interval. Ten patients were operated on. Perforation was located in the cystic duct (n = 2), at the junction of the cystic and hepatic ducts (n = 4), in the common hepatic duct (n = 1) or common bile duct (n = 1). The site of perforation was no longer identifiable in two cases with stenosis. A cholecystectomy was performed in the 2 cases with cystic duct perforation; in the cases of lesions of the main duct, either simple external biliary drainage (n = 3) or biliary reconstruction (n = 5) was carried out. Postoperative complications included bile leak (n = 2), ascending cholangitis (n = 1), portal vein thrombosis (n = 2). Five patients were submitted to further surgery including biliary revision (n = 3), porto-systemic shunt (n = 1), and other procedures (n = 2). One infant died from postoperative sepsis; 2 were lost to follow-up, one of which probably did not survive; 4 are alive and well. Late sequelae are present in 4 children: portal hypertension (n = 1), mild residual bile duct dilatation without cholestasis (n = 1), and mild to moderate liver fibrosis (n = 2). Prompt diagnosis and appropriate treatment should improve the prognosis of this rare condition.

From 1981 to 1987, 86 children aged 16 months to 16 years underwent a portosystemic shunt procedure using an autologous venous graft (internal jugular vein in 80 cases). Fifty-five mesocaval, 20 splenorenal, 4 portacaval, and 7 makeshift shunts were constructed. The indication for shunting was an extrahepatic portal obstruction in 59 cases, intrahepatic portal obstruction in 23 cases (including 6 cases of congenital hepatic fibrosis), and Budd-Chiari syndrome in 4 cases. One patient of the latter group died early from intractable ascites with a nonfunctioning shunt, and a second child died 2 months after operation from unknown reasons with a patent shunt. With a follow-up over 1 year for 58 of the 84 survivors, 78 successes and 6 failures were recorded according to the clinical outcome and the findings of ultrasonic and endoscopic examinations. Three of the six children with a failed shunt have been submitted to a second successful H-type shunt operation. No case of encephalopathy was recorded in this series. Thus, with an approximate success rate of 95%, the H-type shunt with a venous graft should be recommended for treatment of portal hypertension of extrahepatic origin, especially in young children.