Long-term outcome of liver transplantation in childhood: A study of 20-year survivors.

We report the results of a study of survival, liver and kidney functions, and growth with a median follow-up of 24 years following liver transplantation in childhood. From 1988 to 1993, 128 children underwent deceased donor liver transplantation (median age: 2.5 years). Twenty-year patient and graft survival rates were 79% and 64%, respectively. Raised serum aminotransferase and/or γ-glutamyl transferase activities were present in 42% of survivors after a single transplantation. Graft histology (35 patients) showed signs of chronic rejection in 11 and biliary obstruction in 5. Mean total fibrosis scores were 4.5/9 and 3/9 in patients with abnormal and normal serum liver tests, respectively. Glomerular filtration rate was <90 mL·min-1 in 35 survivors, including 4 in end-stage renal disease who were undergoing dialysis or had undergone renal transplantation. Median final heights were 159 cm for women and 172 cm for men; final height was below the target height in 37 patients. Twenty-year survival after childhood liver transplantation may be close to 80%, and final height is within the normal range for most patients. However, chronic kidney disease or altered liver biochemistries are present in over one third of patients, which is a matter of concern for the future.

Ovarian tumors in children and adolescents: a series of 41 cases.

OBJECTIVE: Pictorial review with a detailed semiological analysis of ovarian tumors in children and adolescents to provide a relevant diagnostic approach. PATIENTS AND METHODS: Retrospective study (2001-2011) of 41 patients under the age of 15 who underwent surgery for an ovarian mass with a definite pathological diagnosis. RESULTS: Sixty-two percent of the lesions were benign, 33% were malignant and 5% were borderline. Germ cell tumors were most frequent (77.5%), followed by sex cord stromal tumors (12.5%) and epithelial tumors (7.5%). Malignant tumors were more frequent in children between 0 and 2 years old. On imaging, calcifications and fat were specific for germ cell tumors; the presence of a mural nodule was predictive of a mature teratoma (P<0.001). Predictive factors for malignancy were clinical, including abdominal distension (P<0.01) or a palpable mass (P=0.05), biological, including increased hCG and/or AFP levels (P<0.001) and radiological, including tumors larger than 12 cm (P<0.05), tumoral hypervascularity (P<0.01) and voluminous ascites (P<0.01). CONCLUSION: This semiological analysis confirms the role of imaging in diagnosing the etiology of ovarian lesions in children and adolescents and emphasizes the importance identifying tumoral hypervascularity, which, in addition to classic criteria, is highly predictive of malignancy.

The long-term outcome of hepatic artery thrombosis after liver transplantation in children: role of urgent revascularization.

Hepatic artery thrombosis (HAT), one of the most severe complications of pediatric orthotopic liver transplantation (OLT), often compromises graft and/or child survival. Of 590 OLT performed in 516 children over a 20-year period, 45 were complicated by early HAT, during the first 2 weeks after transplantation. Systematic Doppler ultrasonographic detection of HAT allowed successful surgical revascularization in 19 instances, resulting in a 20-year graft survival rate of 77% versus 24% of cases when revascularization was not attempted or failed. A combination of surgical emergency revascularization, biliary interventional radiology, biliary surgery and/or retransplantation resulted in an 80% 20-year patient survival rate, identical to that of transplanted children who did not experience early HAT. The majority of long-term survivors with their initial graft had normal liver tests, no biliary dilation on ultrasonography and minimal or moderate fibrosis on liver histology. A failed attempt at revascularization did not significantly alter patient survival. Despite these encouraging results, for the children and their parents to overcome the entire process in terms of reoperations, repeated radiological interventions, number of hospitalizations and emotional stress, remains an ordeal of such magnitude that it justifies renewed efforts to progress in the prevention of this complication.

Pancreatic resections for solid or cystic pancreatic masses in children.

OBJECTIVES: The aim of the study was to assess the diagnosis and management of solid pancreatic neoplasm in children and the type of surgical treatment, focusing on short- and long-term outcomes. METHODS: We retrospectively reviewed the charts of all children who had undergone pancreatic resection for suspicion of pancreatic tumor in Kremlin Bicêtre Hospital, Paris, between 1986 and 2008. We studied the symptoms at diagnosis, the type of surgery, and the short- and long-term morbidity and mortality. RESULTS: Of 18 patients identified, there were 7 pseudopapillary tumors, 3 neuroblastomas, 2 rhabdomyosarcomas, 1 acinar cell carcinoma, 1 endocrine cell carcinoma, 1 renal angiomyolipoma, and 3 pancreatic cysts. Symptoms at diagnosis were abdominal trauma, abdominal mass, and jaundice. Operative procedures were duodenopancreatectomy (11), mid-pancreatic resections (2), splenopancreatectomy (2), distal pancreatectomy (1), and tumorectomy (2). There were no deaths related to surgery. The postoperative morbidity rate was 45%, including 2 cases of fistula (11%) occurring after a mid-pancreatic resection and a pancreaticoduodenectomy. The median follow-up was 4.2 years (range 2-11). There was no diabetes mellitus, but there was 1 case of fat diet intolerance requiring pancreatic enzyme substitution. All of the children had a growth curve within normal limits. CONCLUSIONS: In this experience, pancreatic resections have proven to be a safe and efficient procedure, with low long-term morbidity, for the treatment of tumoral and selected nontumoral pancreatic masses.

Congenital portosystemic shunts in children: recognition, evaluation, and management.

Congenital portosystemic shunts are present in one in 30,000 children. Among the associated risks of severe complications are neonatal cholestasis, benign and malignant liver tumors, hepatopulmonary syndrome, portopulmonary hypertension, and encephalopathy. They can be detected on prenatal ultrasonograms, during the investigation of a positive galactosemia screening test in neonates or of a complication, or be found fortuitously on an abdominal ultrasound. Small intrahepatic shunts may resolve spontaneously within one year of age, but other shunts such as extrahepatic, persistent ductus venosus or persisting intrahepatic shunts, must be closed in one or two steps, by interventional radiology techniques or surgically. The plasticity of the intrahepatic portal system allows revascularization of the liver after shunt closure, even when no intrahepatic portal structures can be detected on imaging studies. This leaves little or no place for liver transplantation in the management of these children.

[Hereditary spherocytosis: guidelines for the diagnosis and management in children]. / Sphérocytose héréditaire: recommandations pour le diagnostic et la prise en charge chez l'enfant.

Hereditary spherocytosis (HS) is the commonest inherited disorder of the erythrocyte membrane in Northern Europe and North America. It is marked by a regenerative anemia which varies widely from asymptomatic patients to severe hemolysis. In 75% of HS patients, inheritance is autosomal dominant. The diagnosis of HS is easily made when there are a family history, hemolytic anemia, reticulocytosis, spherocytes and increased hyperdense cells. Specialized testing to clarify the nature of membrane disorder is required when the film appearance is atypical without a positive family history, in the absence of a family history, in the newborn and before the splenectomy, to rule out the stomatocytosis which is contraindicated. The indication for splenectomy is dependent on the degree of anemia and its clinical manifestation.

[Swallowing magnets: a dangerous game. A case report]. / Avaler des aimants : un jeu dangereux. A propos d'une observation.

Complications related to the ingestion of magnetic foreign bodies by children represents an affirmed health hazard in the United States. In France, an alert has been announced. We report the 1st case in France. Our aim is to alert pediatricians and emergency physicians and to draw attention to the particularities of this type of foreign body. Responsible for complications is the ingestion of at least 2 magnets, or 1 magnet and a metallic foreign body, with a time interval between ingestions. In these cases, it is strongly recommended to extract the foreign bodies with endoscopy if they have not yet passed the pylorus. For those further advanced in the intestinal tract, continuous observation is warranted and surgical extraction is indicated on apparition of 1st clinical symptoms.

Antenatal sonographic features of aneurysmal dilatation of a vitelline vein.

We report a case of aneurysmal dilatation of a vitelline vein observed antenatally. Intra-abdominal vascular dilatation was diagnosed on ultrasound examination at 24 weeks' gestation. The relationship with the umbilicus and portal vein suggested the diagnosis of umbilical vein varix. Fetal tolerance remained excellent in spite of a gradual increase in the size of the dilated vein. Postnatal ultrasound examination revealed thrombosis of the aneurysm with gradual extension to the portal vein and the onset of serious coagulation problems. Operative findings on postnatal day 9 included the absence of intra-abdominal umbilical vein, and the presence of an abnormal, dilated and thrombosed vein connecting the umbilicus to the portal vein and following the trajectory of the right vitelline vein. Corrective surgery was attempted by resection of the aneurysm and portal thrombectomy, but this did not prevent the development of portal obstruction syndrome with cavernous hemangioma. This anomaly, in which the fetal venous return uses the vitelline vein in the absence of the umbilical vein, does not appear to have been described before. The mechanism in question could be anastomosis between the right vitelline vein and umbilical vein. Antenatal diagnosis should enable early surgical management before the formation of a portal thrombosis.

Identification and specificity of a 38 kDa Loa loa antigenic fraction in sera from high-microfilaraemic Gabonese patients.

Circulating antigens isolated from sera of three high-microfilaraemic ( Loa loa) Gabonese patients were fractionated by gel filtration. A major component (38 kDa) was identified after SDS-PAGE and immunoblotting using sera of amicrofilaraemic patients with high level of antimicrofilariae Loa loa antibodies. The 38 kDa fraction was not found in the sera of parasitised patients or healthy controls. We looked for the 38 kDa antigen in the various stages of the filarial life cycle and found it in extracts of Loa loa microfilariae but not in somatic extracts of Loa loa male and female adult worms. This fraction could be used as a diagnostic marker in loiasis for amicrofilaraemic patients.

Localized cervical neuroblastoma: prevention of surgical complications.

OBJECTIVES: The purpose of this study focused on cervical neuroblastoma (NB) was to assess the prognosis, define the most suitable methods of investigation, and evaluate risk factors for complications following primary surgery. METHODS: Between 1990 and 1999, we conducted two consecutive prospective multicentric studies (NBL90 and NBL94) on localized NB. Because the first study (1990-1994) found surgery-related morbidity and mortality, several surgical risk factors (i.e. adhesion to major vessels, size, friability, and dumb bell tumor) were defined and used prospectively as criteria of resectability in the second study (1994-1999). RESULTS: Of 617 cases included in the two studies, 43 involved cervical NB including 17 cervicothoracic tumors. With a median follow-up of 4 years, overall survival and event-free survival rates were 91 and 81%, respectively with no significant difference between cervical or cervicothoracic NB. Seventeen patients were included in the second study; surgery was used as the first line treatment in 11. Full pre-operative work-up was performed in eight patients, demonstrating one or more risk factors in three. The remaining three patients underwent emergency surgery with no pre-operative work-up or only ultrasound: two developed serious complications. All three patients presenting documented risk factors developed post-operative complications versus only two of the eight patients who presented no risk factor (n = 5) or were inadequately evaluated (n = 3) (P = 0.06). None of the five patients in whom full work-up demonstrated no risk factor had post-operative complications (P = 0.02). CONCLUSIONS: Cervical neuroblastoma has a favorable prognosis. Surgery is the treatment of choice but there is a risk of complications. Appropriate pre-operative work-up is mandatory to evaluate resectability. The surgical risk factors defined for our second study seem to be significant predictors of post-operative complications.

Characteristics of EPI-hNE4 aerosol: a new elastase inhibitor for treatment of cystic fibrosis.

The purpose of this study was to define nebulization conditions providing delivery of aerosols of EPI-hNE4, an inhibitor of human neutrophil elastase (HNE). EPI-hNE4 was nebulized with Pari LC Star and tested at three concentrations (2.5, 5, and 10 mg/mL). The inhaled mass was measured over 15 min. Particle size distribution was measured by cascade impaction. The effect was also tested of mixing EPI-hNE4 with a (99m)Tc human serum albumin (HSA) tracer on the aerodynamic properties of the aerosol. The inhibitory activity of EPI-hNE4 after nebulization was assessed on purified HNE. The inhaled mass was 32.3 +/- 3.5% (mean +/- SD) after 10 min and 44.2 +/- 3.8% (mean +/- SD) after 15 min. Mass median aerodynamic diameter ranged between 1.2 and 1.8 microm. The (99m)Tc HSA EPI-hNE4 aerosol was similar in terms of particle size distribution (y = 1.0338x - 0.003, r = 0.83). (99m)Tc activity was predictive of EPI-hNE4 mass distribution (y = 1.0278x - 1.6991, r = 0.89). The inhibitory capacity of aerosolized samples remained unchanged after up to 10 min of nebulization. EPI-hNE4 can be nebulized efficiently without decrease in its activity. Mixing this inhibitor with (99m)Tc HSA should allow quantification of its deposition in CF patients.

[Age for testicular torsion?]. / Un âge pour la torsion testiculaire ?

UNLABELLED: Classically, testicular torsion occurs in neonates or during puberty. Between these two ages, is it really an exception? METHOD AND PATIENTS: In order to answer the question, we reviewed the charts of the patients referred to the department of pediatric surgery of Bicêtre hospital between 1992 and 2001. We studied the preoperative examinations, the operative data and the long term evolution. Cases of torsion occurring during neonatal or pubertal periods were excluded. RESULTS: During nine years, 86 patients with "acute scrotum symptoms" underwent surgery. The ages of patients ranged from one month to 11 years (average age: five years) in 26 patients, among which 12 had true testicular torsion. Consultation at the emergency room occurred after one to 72 hours (average of 17). The localization of the pain was on the left in eight cases and on ectopic testicle in two. The testicular volume was increased in 11 cases. Cremasteric reflex was absent in four cases. The doppler flow was normal in four cases and absent in four. During surgery, the testis appearance was considered as normal in six testicles, as necrotized in three (and an orchidectomy was performed) and as ischemic in three. In seven cases, a peroperative contralateral testicle fixation was performed and later one in two. The postoperative course was simple, without infection and with a normal testicular volume in eight cases, increased in one ischemic testis. Testicular atrophy was noted in an ischemic testis, after several months. CONCLUSION: Whatever the age, testicular torsion remains a surgical emergency even with a normal doppler flow.

Acute liver failure in infancy: a 14-year experience of a pediatric liver transplantation center.

Clinical charts of 80 infants younger than 1 year who presented over a 14-year period (1986 to 2000) with acute liver failure (ALF), defined as prolonged prothrombin time greater than 17 seconds and decrease of clotting factor V plasma level below 50% of normal, were reviewed retrospectively. The main causes of ALF were inherited metabolic disorders in 42.5% of cases, including mitochondrial respiratory chain disorders in 17, type I hereditary tyrosinemia in 12, and urea cycle disorders in 2; neonatal hemochromatosis in 16% of cases; and acute viral hepatitis in 15% of cases (hepatitis B in 6, herpes virus type 6 in 4, and herpes simplex virus type 1 in 2). The cause of ALF remained undetermined in 16% of cases. A total of 19 (24%) infants survived without orthotopic liver transplantation; 38 (47%) infants died from sepsis, multiple organ failure, or because the underlying disease contraindicated orthotopic liver transplantation (12 [15%] infants), and 23 (29%) infants underwent orthotopic liver transplantation within 12 months from onset, 12 of whom are alive with a mean follow-up period of 5.2 years from orthotopic liver transplantation. We conclude that ALF during the first year of life is a severe condition with poor prognosis, despite the advent of liver transplantation.

Reversible inhibition of cathepsin L-like proteases by 4-mer pseudopeptides.

A library of 121 pseudopeptides was designed to develop reversible inhibitors of trypanosomal enzymes (cruzain from Trypanosoma cruzi and congopain from Trypanosoma congolense). The peptides share the framework: Cha-X1-X2-Pro (Cha=cyclohexyl-alanine, X1 and X2 were phenylalanyl analogs), based on a previous report [Lecaille, F., Authié, E., Moreau, T., Serveau, C., Gauthier, F. and Lalmanach, G. (2001) Eur. J. Biochem. 268, 2733-2741]. Five peptides containing a nitro-substituted aromatic residue (Tyr/Phe) and one a 4-chloro-phenylalanine at the X1 position, and 3-(2-naphthyl)-alanine, homocyclohexylalanine or 3-nitro-tyrosine (3-NO(2)-Tyr) at the X2 position, were selected. They inhibited congopain more effectively than cruzain, except Cha-4-NO(2)-Phe-3-NO(2)-Tyr-Pro which bound the two parasitic enzymes similarly. Among this series, Cha-3-NO(2)-Tyr-HoCha-Pro and Cha-4-NO(2)-Phe-3-NO(2)-Tyr-Pro are the most selective for congopain relative to host cathepsins. No hydrolysis occurred upon prolonged incubation time with purified enzymes. In addition introduction of non-proteogenic residues in the peptidyl backbone greatly enhanced resistance to proteolysis by mammalian sera.

Immunisation of cattle with cysteine proteinases of Trypanosoma congolense: targetting the disease rather than the parasite.

In order to test the hypothesis that trypanosome cysteine proteinases (CPs) contribute to pathology of trypanosomosis, cattle were immunised with CP1 and/or CP2, the major CPs of Trypanosoma congolense, and subsequently challenged with T. congolense. Immunisation had no effect on the establishment of infection and the development of acute anaemia. However, immunised cattle, unlike control cattle, maintained or gained weight during infection. Their haematocrit and leukocyte counts showed a tendency to recovery after 2-3 months of infection. Cattle immunised with CP2 mounted early and prominent IgG responses to CPs and to the variable surface glycoprotein following challenge. Thus trypanosome CPs may play a role in anaemia and immunosuppression; conversely, anti-CP antibody may modulate the trypanosome-induced pathology.

Functional expression of the catalytic domains of two cysteine proteinases from Trypanosoma congolense.

The catalytic domains of two closely related cysteine proteinases (CP1 and CP2) from Trypanosoma congolense, referred to as C1 and C2, were expressed as proforms in Escherichia coli (C1) and in the baculovirus system (C1 and C2). While the bacterial expression system did not allow recovery of active C1, the baculovirus system led to secretion of inactive zymogens which could be processed at acidic pH into mature enzymes. Active C1 and C2 were purified from serum-free culture supernatants by anion-exchange chromatography and characterised. Their kinetic parameters and pH activity profiles confirmed the relatedness between C2 and native CP2 (congopain). These properties also underline major functional differences between C1 and C2, that appear to relate to discrete but essential sequence differences. It is likely that these two enzymes perform distinct roles in vivo, in the parasite and/or in the host-parasite relationships.

Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation.

Heterozygous, de novo mutations in the glial fibrillary acidic protein (GFAP) gene have recently been reported in 12 patients affected by neuropathologically proved Alexander disease. We searched for GFAP mutations in a series of patients who had heterogeneous clinical symptoms but were candidates for Alexander disease on the basis of suggestive neuroimaging abnormalities. Missense, heterozygous, de novo GFAP mutations were found in exons 1 or 4 for 14 of the 15 patients analyzed, including patients without macrocephaly. Nine patients carried arginine mutations (four had R79H; four had R239C; and one had R239H) that have been described elsewhere, whereas the other five had one of four novel mutations, of which two affect arginine (2R88C and 1R88S) and two affect nonarginine residues (1L76F and 1N77Y). All mutations were located in the rod domain of GFAP, and there is a correlation between clinical severity and the affected amino acid. These results confirm that GFAP mutations are a reliable molecular marker for the diagnosis of infantile Alexander disease, and they also form a basis for the recommendation of GFAP analysis for prenatal diagnosis to detect potential cases of germinal mosaicism.

Characterization of PSA-RP2, a protein related to prostate-specific antigen and encoded by alternative hKLK3 transcripts.

Despite the wide use of prostate-specific antigen (PSA) as a marker of prostate cancer, analysis of its gene products has not yet been completed. The structure of two alternative mRNAs (0.9 and 1.65 kb) of the hKLK3 gene that retain the third intron is reported here. These partially spliced transcripts were detected by hybridization or RT-PCR in normal prostate tissue, benign prostate hyperplasia (BPH) and cancerous prostate tissues, and also in the prostate LNCaP cell line. Insertion of the unspliced intron creates an in-frame stop codon and results in a truncated prepro PSA variant of 180 amino-acid residues. This novel variant, designated PSA-RP2, has an alternate C-terminal tail and lacks the serine residue essential for the catalytic activity of PSA. Prepro PSA-RP2 was transiently produced in COS-7 cells and detected in the spent medium using an anti-PSA serum. Secreted PSA-RP2 was glycosylated with an apparent molecular mass of 25 kDa. Our findings suggest that PSA-RP2 contributes to the molecular heterogeneity of free-PSA in the serum of patients with benign or malignant prostate tumors.