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Although the prognosis of CHARGE syndrome can be highly variable from mild until severe, final diagnosis is difficult to establish in utero. The aim of our study is to compare antenatal and postnatal findings in a retrospective cohort of 10 successive patients with a positive CHD7 gene variant in order to identify the specific prenatal features for CHARGE syndrome diagnosis. Fetal ultrasound, follow-up and supplementary investigations are collected and compared to postnatal findings. Congenital heart defect (7/10), choanal atresia (7/10) and tracheoesophageal atresia (4/10) are the most frequent fetal anomalies found. Inner and external ear anomalies appear as the keystone (constant features) for prenatal diagnosis of CHARGE syndrome in fetuses with multiple anomalies and normal microarray karyotype. External ear malformations are identified in all cases by 3D ultrasound when carefully evaluated. MRI and temporal bone CT-Scan are second line useful tools to assess the diagnosis when looking for semicircular canal agenesis, arhinencephaly and/or choanal atresia. Before availability of prenatal exome sequencing in clinical routine, present findings lead to the recommendation that fetuses, with congenital heart defect (mainly septal and conotruncal), cleft lip/palate or unexplained polyhydramnios should carefully be screened for clues suggesting CHARGE syndrome using 2D and 3D ultrasound, MRI and temporal bone CT-Scan. When CHARGE syndrome is suspected with normal molecular karyotype, CHD7 gene sequencing must be offered.

Cirrhosis in adults is associated with modifications of systemic and liver hemodynamics, whereas little is known about the pediatric population. The aim of this work was to investigate whether alterations of hepatic and systemic hemodynamics were correlated with cirrhosis severity in children. The impact of hemodynamic findings on surgical management in pediatric living donor liver transplantation (LT) was evaluated. Liver and systemic hemodynamics were studied prospectively in 52 children (median age, 1 year; 33 with biliary atresia [BA]). The hemodynamics of native liver were studied preoperatively by Doppler ultrasound and intraoperatively using invasive flowmetry. Portosystemic gradient was invasively measured. Systemic hemodynamics were studied preoperatively by Doppler transthoracic echocardiography and intraoperatively by using transpulmonary thermodilution. Hemodynamic parameters were correlated with Pediatric End-Stage Liver Disease (PELD) score and the histological degree of fibrosis (collagen proportionate area [CPA]). Cirrhosis was associated with a 60% reduction of pretransplant total liver flow (n = 46; median, 36 mL/minute/100 g of liver) compared with noncirrhotic livers (n = 6; median, 86 mL/minute/100 g; P = 0.002). Total blood flow into the native liver was negatively correlated with PELD (P

“Serpentine-like syndrome” is a severe and rare association of multiple congenital malformations, characterised by brachioesophagus, secondary intrathoracic stomach, and vertebral anomalies. Other associated anomalies have been described, such as malposition and herniation of abdominal organs. We report the natural history of a baby girl born at 29 weeks of gestation with intra uterine growth restriction, short neck, large rachischisis from cervical to thoracic spine, a very short oesophagus, thoracic stomach associated with a midline diaphragmatic hernia, malrotated gut and median cleft lip. Most of these anomalies were detected antenatally. Molecular karyotype was normal. She died at age 12 days. To our knowledge, the present patient represents the 8th report of a case of “Serpentine-like syndrome”. Brachioesophagus and congenital vertebral anomalies, in particular rachischisis, are the cardinal features of this condition. All reported cases have been sporadic and the cause is still unknown. We believe that the specificity of the presentation as well as the similarities between available descriptions of patients suggests a common, yet to identify, molecular cause, possibly involving a developmental “toolkit”/homeobox gene or related pathways.

Malformations of cortical development (MCD) represent a large group of brain cortical anomalies characterized by distinctive MRI findings. This 'radiologically-based' classification required re evaluation over time on identified underlying mechanisms (cytogenetic and/or molecular). The understanding of genotype findings (nature of cytogenetic/molecular mutation, cellular pathways consequences, timing, …) draw line of evidence on these distinctive group of conditions whereas sometimes precise and constant recurrent genotype/phenotype correlation may not be present. The clinical diagnosis of MCD is often difficult due to variability and rarity of individual types of malformations. Recent studies have established a relationship between lissencephaly and pathogenic variants in genes involved in the kinesin/tubulin pathways, as the KIF5C gene. Pathogenic variants in the KIF5C gene are a more recently discovered cause of severe developmental delay with epilepsy, characterized by specific malformation of cortical development such as pachygyria. Only seven children have been described to date. We report the natural history of a sixteen years old patient identified carrier of a KIF5C gene mutation who developed infantile epilepsy. We then gather phenotype description and molecular results of all reported patients so far in order to better define this entity.

Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited, Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. Objective. This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Methods. Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti– human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. Results. The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. Conclusions. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.

Vascular anomalies, which are broadly identified as "angiomas", are rare entities and often unknown by the medical sphere. They are divided in two different categories which carry different prognosis and management: "vascular tumors" and "vascular malformations". Their precise identification is crucial and involves a good knowledge of the biological classification published by Mulliken and Glowacki and that has recently been updated by the International Society for the Study of Vascular Anomalies (ISSVA). Vascular tumors are benign, common, inborn or not and most of the time disappear with growth. Vascular malformations are always congenital and growth with the child. They can involve type of vessels solely or combined with others. A rheologic differentiation between slow and fast flow malformations is essential in order to characterize the seriousness of the lesion. Frequently, their diagnosis is clinically established and the anamnesis is conducted to answer three questions that are the time of revelation of the lesion ("When?"), its aspect ("What?") and its evolution ("How?"). Further investigations are usually not required but a non-invasive imaging technique such as Doppler ultrasound could be useful if a doubt exists. Surgery is not mandatory and must always be well thought because its consequences might be disastrous. It must be left to cosmetic sequelae of these lesions or to lesions that are totally resectable without causing any unacceptable deformation.

OBJECTIVES: Cirrhotic children wait-listed for liver transplant are prone to bleeding from gastrointestinal varices. Grade 2-3 esophageal varices, red signs, and gastric varices are well-known risk factors. However, the involvement of hemostatic factors remains controversial because of the rebalanced state of coagulation during cirrhosis. METHODS: Children suffering from decompensated cirrhosis were prospectively included while being on waitlist. Portal hypertension was assessed by ultrasound and endoscopy. Coagulopathy was evaluated through conventional tests, thromboelastometry, and platelet function testing. The included children were followed up until liver transplantation, and all bleeding episodes were recorded. Children with or without bleeding were compared according to clinical, radiological, endoscopic, and biological parameters. In addition, validation of a predictive model for risk of variceal bleeding comprising of grade 2-3 esophageal varices, red spots, and fibrinogen level

Background Extensive and complex vascular malformations often cause chronic pain and severe functional restraint. Conventional treatments, such as surgery and/or sclerotherapy, are rarely curative, underscoring the great need for new therapeutic modalities. Recent preclinical and clinical data demonstrated that sirolimus could offset the progression of vascular malformations and significantly improve quality of life of patients through inhibition of the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathway. The purpose of this prospective study was to assess the efficacy and safety of this treatment in patients with extensive or complex slow-flow vascular malformations. Methods Sirolimus was administered orally on a continuous dosing schedule with pharmacokinetic-guided target serum concentration level of 10 to 15 ng/ml. Patients were seen every month for the first three months and subsequently every three months. The primary endpoints were safety and efficacy, based on clinical, biological and radiological evaluations, as well as a quality of life questionnaire. Results Nineteen patients, from 3 to 64 years old, with lymphatic (LM), venous (VM) or complex slow-flow malformations, refractory to standard care, were enrolled and received sirolimus continuously. After 12 months of follow-up, 16 patients were available for assessment of efficacy and safety: all had a significant and rapid improvement of their symptoms and quality of life. In two patients, sirolimus treatment permitted sclerotherapy and surgery, initially evaluated unfeasible. Sirolimus was well tolerated, with mucositis as the most common (10% of patients) grade 3 adverse event. Conclusions Sirolimus was efficient in extensive LM, VM and/or complex malformations that were refractory to conventional treatments and was well tolerated.

International audience; Mutations in the oligophrenin 1 gene (OPHN1) have been identified in patients with X-linked intellectual disability (XLID) associated with cerebellar hypoplasia and ventriculomegaly, suggesting it could be a recognizable syndromic intellectual disability (ID). Affected individuals share additional clinical features including speech delay, seizures, strabismus, behavioral difficulties, and slight facial dysmorphism. OPHN1 is located in Xq12 and encodes a Rho-GTPase-activating protein involved in the regulation of the G-protein cycle. Rho protein members play an important role in dendritic growth and in plasticity of excitatory synapses. Here we report on 17 individuals from four unrelated families affected by mild to severe intellectual disability due to OPHN1 mutations without cerebellar anomaly on brain MRI. We describe clinical, genetic and neuroimaging data of affected patients. Among the identified OPHN1 mutations, we report for the first time a missense mutation occurring in a mosaic state. We discuss the intrafamilial clinical variability of the disease and compare our patients with those previously reported. We emphasize the power of next generation techniques (X-exome sequencing, whole-exome sequencing and targeted multi-gene panel) to expand the phenotypic and mutational spectrum of OPHN1-related ID.

We herein report the case of a 3-year-old girl with atypical congenital right upper limb lymphedema who developed an angiosarcoma. Only a few cases have been reported following congenital form of lymphedema and only 4 in such a young child. We also summarize all cases of angiosarcoma associated with congenital lymphedema reported in the literature., info:eu-repo/semantics/published

Biliary complications (BCs) still remain the Achilles heel of liver transplantation (LT) with an overall incidence of 10% to 35% in pediatric series. We hypothesized that (1) the use of alternative techniques (reduced size, split, and living donor grafts) in pediatric LT may contribute to an increased incidence of BCs, and (2) surgery as a first treatment option for anastomotic BCs could allow a definitive cure for the majority of these patients. Four hundred twenty-nine primary pediatric LT procedures, including 88, 91, 47, and 203 whole, reduced size, split, and living donor grafts, respectively, that were performed between July 1993 and November 2010 were retrospectively reviewed. Demographic and surgical variables were analyzed, and their respective impact on BCs was studied with univariate and multivariate analyses. The modalities of BC management were also reviewed. The 1- and 5-year patient survival rates were 94% and 90%, 89% and 85%, 94% and 89%, and 98% and 94% for whole, reduced size, split, and living donor liver grafts, respectively. The overall incidence of BCs was 23% (n = 98). Sixty were anastomotic complications [47 strictures (78%) and 13 fistulas (22%)]. The graft type was not found to be an independent risk factor for the development of BCs. According to a multivariate analysis, only hepatic artery thrombosis and acute rejection increased the risk of anastomotic BCs (P

Intramural duodenal hematomas have most frequently been reported in children in a traumatic setting. We present two cases of duodenal hematoma that occurred after upper gastrointestinal tract endoscopy with biopsy in children without significant prior medical history. The diagnosis was made by ultrasound, in correlation with the clinical presentation. Because the patients were hemodynamically stable, they were treated conservatively and the regression of the hematoma was followed up with ultrasound until its complete resolution. These cases demonstrate the risks of endoscopy, which are not to be neglected even in children without impaired coagulation, and the manner in which ultrasound can provide the correct diagnosis and follow-up.

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n=100), common CM(s) (port-wine stain; n=100), Sturge-Weber syndrome (n=37), or isolated AVM(s) (n=24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the second-hit hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up. (C) 2013 Wiley Periodicals, Inc.

WOS: 000372165300007 PubMed ID: 26951490 Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases. We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations. We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy. Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia. Academy of Medical Sciences (AMS) [AMS-SGCL11-Briggs]

Background : Cerebral folate transporter deficiency caused by FOLR-1 mutations has been described in 2009. This condition is characterized by a 5MTHF level

The diagnosis of intestinal malrotation is based on an upper gastrointestinal contrast series (UGI), which is considered the imaging reference standard. It may however be challenging even for experienced paediatric radiologists. The purpose of this study was to demonstrate the agreement between UGI and US in assessing the position of the third portion of the duodenum (D3) and to show that a retroperitoneal duodenum indicates normal forgut rotation. In a prospective study, US assessment of the duodenum and the superior mesenteric vessels was performed in consecutive children who were referred for clinically indicated UGI at a single institution. Eighty-five children, 5 months to 14 years old, were studied. In 82/85 (96%), both US and UGI suggested normal forgut rotation. In three children, US demonstrated a normal position of the D3 whereas UGI showed an abnormal position of the duodeno-jejunal junction. US is a non-invasive, easily performed technique for excluding malrotation. UGI may be reserved for situations where US does not demonstrate a normal position of the D3.

Hepatic involvement is frequent in patients with cystic fibrosis (CF), with focal biliary cirrhosis being the pathognomonic hepatic manifestation. In around one-quarter of CF patients, it results in CF-associated liver disease (CFLD). This occurs as a relatively early complication with the majority of patients presenting in childhood or their early teens. However, a normal US does not preclude significant liver fibrosis and liver biopsy is an invasive procedure that is hampered by potential sampling errors. Transient elastography (TE) (Fibroscan) is a non-invasive, user-friendly and quick technique that provides an objective and reproducible measure of liver stiffness. This is accomplished with a device using an US probe mounted in the axis of a vibrator. Vibrations are transmitted by the transducer, inducing an electronic shear wave that propagates through the underlying tissue.We aimed to prospectively compare TE and transabdominal US scanning in children and adults attending a CF clinic.A total of 134 consecutive patients with documented CF were prospectively studied. In each case, transient elastography measurement was performed immediately after the routine annual US evaluation of the liver. Sonographic appearance of the liver was classified from 1 to 5. Ten validated TE measurements were performed in each patient with the result expressed in kilopascals (kPa). The median value was considered representative of the elastic modulus of the liver.Measurements were performed in 59 CF adults, 75 CF children and 31 control children. There was no relationship between age and liver stiffness in either the control group or CF patients. Elasticity values of controls, CF pancreatic sufficient (PS) patients and pancreatic insufficient (PI) CF patients with a US score3 were comparable and significantly lower than in CF patients with a US scoreor = 3 (all PI) (P0.002). Median elasticity in CF patients was significantly higher in males (4.7 kPa) than in females (3.9 kPa) (P = 0.0013).Considering the limitations of US and the low risk-benefit rate of liver biopsy in most CF patients, this preliminary study suggests that TE is an attractive non-invasive way to assess and follow-up liver disease in these patients.

Infantile myofibromatosis is a rare disorder characterized by the formation of tumors in the skin, soft tissues, bone, and viscera. We report the case of a 3-week-old girl who presented with severe hypertension due to generalized infantile myofibromatosis including renal involvement. The infant was treated by chemotherapy and showed progressive regression of the tumors. However, her evolution was marked by the development of aneurismal dilations of the renal and iliac arteries as observed in fibromuscular dysplasia. We discuss the possibility of a link between these two mesenchymal disorders.

Context: Obesity in childhood is associated with an increased mortality due to cardiovascular (CV) diseases in adulthood, independent of adult weight. Recent studies in children indicate that the atherosclerosis process starts at an early age and is linked to obesity. Objective: The aim of the study was to investigate determinants of increased carotid intima-media thickness (IMT), an early marker of atherosclerosis, in obese children. Design: A total of 104 obese children [age, 12.7 ± 0.2 yr; body mass index (BMI)-z-score, 2.8 ± 0.7] underwent an oral glucose tolerance test. Fasting levels of glucose, insulin, C-reactive protein and adhesion molecules (sICAM, sVCAM, sE-selectin), lipid profile, adiponectin, and resistin were determined. IMT was measured by ultrasound. Insulin resistance was estimated by the homeostatic model assessment index. Baseline measurements of blood parameters were obtained from 93 nonobese children (age, 13.0 ± 0.2 yr; BMI-z-score, −0.2 ± 0.9), and IMT was measured in 23 other control children with similar characteristics. Results: Univariate analysis showed a significant positive correlation between IMT and relative BMI, the degree of systolic hypertension, fasting insulin levels, homeostatic model assessment-R index, and resistin concentrations, whereas an inverse correlation with adiponectin levels was found. No correlation was obtained between IMT and classical CV risk factors such as positive familial history of type 2 diabetes or precocious CV disease, visceral obesity, or the lipid profile. C-reactive protein and adhesion molecule levels were not associated with IMT in our obese population. When controlled for sex, Tanner stage, and relative BMI, only adiponectin levels remained an independent determinant of IMT. Conclusion: Adiponectin more than conventional CV risk factors and inflammation status may be related to early atherosclerosis in obese children.

Over the last 15 years, various oncology groups throughout the world have used the PRETEXT system for staging malignant primary liver tumours of childhood. This paper, written by members of the radiology and surgery committees of the International Childhood Liver Tumor Strategy Group (SIOPEL), presents various clarifications and revisions to the original PRETEXT system.

The understanding of vascular anomalies (vascular tumours and vascular malformations) was obscured, for a long time, by confusion and uncertainties in nosology and terminology. The International Society for the Study of Vascular Anomalies (ISSVA) recently adopted a classification scheme, clearly separating vascular tumours (hemangiomas of different types) which result from active cell proliferation, from vascular malformations, which are inborn defects in vascular morphogenesis. These two types of lesions have different clinical behaviour and require different diagnostic and therapeutic strategies. The most frequent vascular tumour is infantile hemangioma. Its clinical aspects and evolution are well-known. New data have been recently obtained concerning the phenotype of tumour cells and its histogenesis. Of the numerous new vascular tumours, which have been recently described, only the congenital hemangiomas, the vascular tumours associated with the Maffucci syndrome and the tumours that may be complicated by a profound thrombocytopenia (Kasabach and Merritt phenomenon) will be considered. Vascular malformations can be classified according to the vessel(s) types they are composed of. A classification table is presented, separating the malformations of vascular trunks from tissular malformations which are more intimately embedded in the surrounding tissues. The different syndromes associated with vascular anomalies take also place in this table. The clinical, imaging and histological aspects of the most frequent malformations (capillary, venous, lymphatic and arteriovenous) are presented. This classification intend to clarify the nosology and terminology of the complex field of vascular tumours and malformation and to offer a common language to the different physicians and specialists contributing, preferably with a interdisciplinary approach, to the diagnosis and treatment of these difficult lesions.

A 15-months-old girl presented an excentration of the hip associated with a defect image of the acetabulum. Arthrography revealed a communication between the hip joint and the acetabular defect. Bacteriological specimens of the articular fluid were negative. The radiographic images were compatible with subacute osteomyelitis. Relative immobilization using an Atlanta abduction devise was undertaken. No medical treatment was prescribed for this adolescent who had received antibiotics for polymicrobial urinary tract infections and for pharyngitis prior to detection of the orthopedic disorder. Outcome was satisfactory with progressive filling of the acetabular defect but also with development of a subluxating coxa valga which required varus osteotomy of the femur. This case appears to illustrate a particular form of subacute osteomyelitis which is not described in earlier classifications.

Rivera J, Fusaro F, de Magnee C, Clapuyt P, Reding R. Meso-Rex shunt for immediate portal revascularization in pediatric liver transplantation: First report. Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S. Abstract: We describe the case of a 13-month-old girl transplanted for biliary atresia with PV hypoplasia. She received the left liver lobe of her mother and presented intraoperative portal thrombosis. Because of technical reasons, the opportunity to have conventional PV reconstruction using the donor left PV stump was lost. Immediate conversion to a meso-Rex shunt, using the recipient jugular vein as a bridge between the superior mesenteric vein and the graft Rex recessus, allowed excellent portal revascularization of the transplant. We suggest that synchronous meso-Rex shunt may constitute a valid alternative to truncal PV anastomosis during pediatric LT.

Post-transplant children are regularly followed by colour Doppler US exam. Liver parenchyma, biliary tract and portal, subhepatic and arterial vascularisation are checked. We observed a post-transplant child with spontaneous meso-portal bypass after portal vein thrombosis (PVT). After orthotopic liver transplantation (OLT), PVT is frequently observed. When it occurs early (before 3 weeks), it has been identified as a cause of graft failure. On the other hand, late PVT (after 3 weeks) can be extremely well-tolerated, with cavernous transformation of the portal vein and formation of hepatopetal collaterals that deliver blood to the liver. However, extrahepatic portal hypertension (EHPH) and its related complications can develop. Cavernoma transformation is usually seen, but spontaneous shunt is not yet described in transplant patients. Distinction from the classic cavernoma can be achieved by the depiction of a single transcapsular vessel. This bypass partially corrects the EHPH. However it was decided to completely prevent shunt development by performing a surgical mesenterico-left portal vein bypass.

A case of liver transplantation for HCC complicating BA in an eight-month old infant is reported. HCC in BA is extremely rare. Screening of AFP and ultrasonographic examination should be performed regularly in patients with secondary biliary cirrhosis for early detection of HCC.

The purpose of this study was to evaluate the diagnostic value of the “whirlpool sign” detected at color Doppler sonography in adults complaining of acute abdominal pain. During a 2-year period, the whirlpool sign was systematically looked for with color Doppler sonography in all patients admitted in the emergency room for acute abdominal pain. The whirlpool sign was observed in 13 patients: 2 cases of surgically proven primary volvulus of the small bowel, 10 cases of proven or suspected small bowel obstruction secondary to adhesions, and 1 case of acute leukemia with enlarged mesenteric lymph nodes. In the first 12 cases, the whirlpool sign was associated with radiologic (N=9) and sonographic (N=12) signs of small bowel obstruction. In the last case, no sign of obstruction was observed. In patients who had the whirlpool sign and who underwent operations (N=6), primary or secondary volvulus was present in 3 cases but was absent in the other 3 cases. The whirlpool configuration detected with color Doppler sonography has to be considered as a sign of limited value, because it may be observed in various conditions, including primary or secondary volvulus, postsurgical adhesions without volvulus, and acute abdominal diseases without obstruction.

During the period from 1972 to 1992, 59 children received surgical treatment at the University of Louvain Medical School for biopsy-proven Hirschsprung's disease (HD). The extent of aganglionosis was as follows: short segment restricted to the rectosigmoid or descending colon (n = 44, 75%); long segment (n = 9,15%); ultra-short segment (n = 3, 5%); unknown length because of death without autopsy (n = 3, 5%). The median age at operation was 7 months for short-segment disease compared with 14 months for those with long-segment disease. Surgical procedures used for short-segment disease were Swenson with colostomy (n = 16), Swenson-Pellerin without colostomy (n = 27), Duhamel (n = 1), and for long-segment disease were Martin (n = 3), Swenson-Deloyers (n = 2), Swenson-Boley (n = 2) and ileostomy only in = 2). Lynn's sphincteromyotomy was performed in the three ultra-short cases. There were six deaths (10%) at a median age of 86 days (range, 28 to 1545 days), three had long-segment disease, and the others were not classified because of death before curative surgery. Enterocolitis (EC) was the most common cause of death (five cases) and was also the major source of morbidity after curative surgery (12 of 44, 27%) in short-segment patients, three of seven (43%) in long-segment patients. The functional success of the procedure was evaluated in 70% of the surviving patients (37 of 53; mean follow-up, 8.7 years; range, 1.2 to 21.5), using a novel semiquantitative scoring system, specifically designed for children who have HD. This system assesses normal stool evacuation, abdominal distention, soiling, and severe incontinence. The results were compared with those from a population of 39 healthy children and adolescents and demonstrated progressive improvement in function during childhood and adolescence (P = .04) for patients treated for short-segment disease. However, function was found to be consistently poorer in all age groups when compared with healthy controls (5 to 10 years, P.01; 10 to 15 years, P.05;15 years, P.01).

Congenital limb anomalies occur in Europe with a prevalence of 3.81/1,000 births and can have a major impact on patients and their families. The present study concerned a female fetus aborted at 23 weeks of gestation because she was affected by non-syndromic bilateral absence of the zeugopod (leg) and autopod (foot). Autopsy of the aborted fetus, X-ray imaging, MRI, and histochemical analysis showed that the distal extremity of both femurs was continued by a cartilage-like mass, without joint cavitation. Karyotype was normal. Moreover, no damaging variant was detected by exome sequencing. The limb characteristics of the fetus, which to our knowledge have not yet been reported in humans, suggest a developmental arrest similar to anomalies described in chicks following surgical experiments on the apical ectodermal ridge of the lower limbs.

A 3-year-old girl suffering from ornithine carbamoyltransferase (OTC) deficiency was poorly equilibrated under conventional diet and scavenger treatment. Following unsuccessful cryopreserved hepatocyte transplantation, she received two infusions of Adult Derived Human Liver Stem/Progenitor Cells (ADHLSCs) expanded in vitro under GMP settings, the quantity being equivalent to 0.75% of her calculated liver mass. Using FISH immunostaining for the Y chromosome, the initial biopsy did not detect any male nuclei in the recipient liver. Two liver biopsies taken 100 days after ADHLSC transplantation showed 3% and 5% of male donor cells in the recipient liver, thus suggesting repopulation by donor cells. Although limited follow-up did not allow us to draw conclusions on long-term improvement, these results provide a promising proof of concept that this therapy is feasible in an OTC patient.

BACKGROUND: In most cases of total hepatectomy (TH) required for hepatoblastoma (HB), the retrohepatic inferior vena cava (IVC) has to be removed with the native liver for complete tumor excision. Because the liver graft procured by living donation has no IVC, a reconstruction of the recipient IVC is needed. We report our experience with living-related liver transplantation (LRLT) and IVC replacement in such cases. METHODS: Between May 1998 and December 1999, four children underwent TH, including IVC and LRLT with IVC replacement for otherwise irresectable HB after chemotherapy (SIOPEL 2 and 3 protocols). IVC reconstruction used an allogenic iliac vein procured from a cadaveric donor (bank graft) in two cases and an internal jugular vein procured from the donor parent in two cases. Median age and weight at surgery were 17 months (range 10-60) and 9.6 kg (range 8.3-17.9). RESULTS: In the living donors, there were two complications of the procurement: one intra-abdominal biliary collection and one subcutaneous abscess. In all four children, complete excision of the tumor could be achieved without any intra-operative complication. One patient died 5 months after LRLT due to lung metastases. Three patients were alive and well with no evidence of tumor recurrence 13-24 months after surgery. Reconstructed IVC was patent in two patients, and asymptomatic thrombosis occurred 2 years after operation in one patient. CONCLUSION: Total hepatectomy including the retrohepatic IVC is not a technical obstacle to LRLT. Therefore, scheduled surgery, at the best time after chemotherapy, can be considered in all patients with otherwise irresectable HBs.

A 15-year-old female had been followed in our department of pediatric radiology since the age of 11, in order to control a solitary osteochondroma (exostosis) of the right distal femur.

We report the case of a young girl who had hemihypertrophy and developed Wilms' tumor in both kidneys and clear-cell adenocarcinoma of the uterine cervix with no maternal history of stilbestrol ingestion during pregnancy. Karyotype on the second Wilms' tumor showed monosomy 22. The link between hemihypertrophy and Wilms' tumor is well known, but their association with clear-cell carcinoma of the cervix has not been previously described. (C) 1993 Wiley-Liss, Inc.

Primary angiitis of the central nervous system (PACNS) is an idiopathic, usually recurrent vasculitis confined to the brain. PACNS has been reported rarely in children, although the disease is probably underdiagnosed.: We report the clinical history of a 3-year-old girl who presented subacute neurological deterioration characterised by headache, speech regression, and altered level of consciousness. Brain MRI revealed severe inflammatory lesions involving both grey and white matters. All blood and cerebrospinal fluid (CSF) tests for inflammatory or infectious processes were negative. Over the next 10 years, the patient relapsed eight times. Brain biopsy confirmed lesions suggestive of cerebral vasculitis. Based on histopathological features and due to the absence of systemic vasculitis, the patient was considered to have PACNS. She developed partial epilepsy, and clinical stabilisation was finally achieved via continuous oral corticosteroids and immunosuppressive agents.PACNS may be the cause of subacute and relapsing inflammatory encephalopathy in children after excluding other diagnoses, such as multiple sclerosis, sarcoidosis, recurrent acute disseminated encephalomyelitis (ADEM), and primary central nervous system lymphoma. Brain biopsy is necessary to confirm the diagnosis of PACNS and exclude diseases with similar symptoms. Neurological outcome remains poor.

Cellular (or atypical) congenital mesoblastic nephroma (CMN) is a potentially aggressive form of the benign classical congenital mesoblastic nephroma. We report here a case of cellular CMN in a 5-month-old boy treated preoperatively with chemotherapy with an excellent response allowing a complete surgical resection.

Objective: To evaluate if elevated D-dimer level is specific for venous malformations (VMs) and thus useful for differential diagnosis, which can be problematic even in specialized interdisciplinary centers. Localized intravascular coagulopathy, characterized by elevated D-dimer levels, has been observed in approximately 40% of patients with VMs. Design: Prospective convenience sample accrued from 2 interdisciplinary sites. Setting: Two interdisciplinary centers for vascular anomalies in Brussels, Belgium, and Caen, France Participants: The study population comprised 280 patients with clinical data, Doppler ultrasonograms (for 251 patients), and coagulation parameter measurements. Main Outcome Measure: Measurement of D-dimer levels. Results: A VM was diagnosed in 195 of 280 patients (69.6%), and 83 of them had elevated D-dimer levels; the sensitivity of D-dimer dosage was 42.6% (95% confidence interval, 35.6%-49.5%). Among the 85 patients without VM, D-dimer levels were elevated only in 3 patients; the specificity of the dosage was 96.5% (95% confidence interval, 92.5%-100%). Conclusions: Elevated D-dimer level is highly specific for VMs (pure, combined, or syndromic), and therefore this easy and inexpensive biomarker test should become part of the clinical evaluation of vascular anomalies. It can detect hidden VMs and help differentiate glomuvenous malformation (normal D-dimer levels) from other multifocal venous lesions. Elevated D-dimer level also differentiates a VM from a lymphatic malformation. Moreover, slow-flow Klippel-Trenaunay syndrome (capillaro-lymphatico-venous malformation with limb hypertrophy) can be distinguished from fast-flow Parkes Weber syndrome (capillary malformation with underlying multiple microfistulas and limb hypertrophy). For these reasons, D-dimer level measurement is a useful complementary tool for diagnosing vascular anomalies in everyday practice.

Capillary malformation-arteriovenous malformation (CM-AVM) is a newly recognized autosomal dominant disorder, caused by mutations in the RASA1 gene in six families. Here we report 42 novel RASA1 mutations and the associated phenotype in 44 families. The penetrance and de novo occurrence were high. All affected individuals presented multifocal capillary malformations (CMs), which represent the hallmark of the disorder. Importantly, one-third had fast-flow vascular lesions. Among them, we observed severe intracranial AVMs, including vein of Galen aneurysmal malformation, which were symptomatic at birth or during infancy, extracranial AVM of the face and extremities, and Parkes Weber syndrome (PKWS), previously considered sporadic and nongenetic. These fast-flow lesions can be differed from the other two genetic AVMs seen in hereditary hemorrhagic telangiectasia (HHT) and in phosphatase and tensin homolog (PTEN) hamartomatous tumor syndrome. Finally, some CM-AVM patients had neural tumors reminiscent of neurofibromatosis type 1 or 2. This is the first extensive study on the phenotypes associated with RASA1 mutations, and unravels their wide heterogeneity.

We describe a neurologically symptom-free adolescent with aggressive vertebral body haemangiomas at two sites.

Two cases of gastroduodenal outlet obstruction caused by arteriomesenteric compression in children who have cerebral palsy are reported. Clinical symptoms of gastrointestinal obstruction include recurrent postprandial nausea and vomiting, upper abdominal distension, and pain. In such patients, multiple predisposing factors can contribute to the development of arteriomesenteric compression, including marked weight loss, supine position, and severe scoliosis. Upper gastrointestinal x-rays using barium contrast allow diagnostic confirmation. In our experience, this cause of acute gastroduodenal outlet obstruction may usually resolve after conservative treatment using a jejunal feeding tube passed beyond the compression, left lateral positioning, and renutrition.

OBJECTIVE. We sought to investigate whether the outer diameter of the vermiform appendix on cross-sectional sonography is as reliable a criterion with which to confirm acute appendicitis in patients with cystic fibrosis as in those without cystic fibrosis. CONCLUSION. The outer appendiceal diameter of 6 mm or more cannot be considered a reliable criterion for the diagnosis of acute appendicitis in patients with cystic fibrosis.

We present a case of spinal cord injury due to birth trauma and assess the value of sonography for diagnosis, lesion characterization, and follow-up. Sonography is a non-invasive and easily reproducible imaging method for examining a ventilated child, and its initial sensitivity is comparable to that of MRI. Sonography is the method of choice for guiding diagnosis in this type of traumatic lesion to the newborn.

A 1-yr-old child presented with intractable right sided pleural effusion and progressive clinical deterioration 3 weeks after liver transplantation for Alagille Syndrome. He had been treated successfully for severe acute rejection before. Ultrasound and Doppler mode studies repeatedly demonstrated air in the portal vein. Intra-abdominal and intra-thoracic lymphoproliferation was detected, and EBV virus load and serology were suggestive of primary EBV infection. Liver biopsy revealed blast-like infiltrates of B-cells, considered diagnostic for post-transplant lymphoproliferative disease. The disease resolved upon reduction of immunosuppression. We suggest that the detection of portal vein gas in pediatric liver transplant recipients beyond the early post-operative period may be a sign of intra-abdominal post-transplant lymphoproliferative disease.

We report the case of a child who developed, 2 yr after orthotopic liver transplantation (OLTx) for biliary atresia, a multi-focal hepatic tumor with lymphonodular metastases, identified as an Epstein-Barr virus (EBV)-associated leiomyosarcoma. Chemotherapy was given without tumor response. Subsequently, slow growth of the tumor was observed. Immunosuppression was tapered and stopped 9 yr after transplantation. At the present time, 12 yr after the discovery of the first hepatic lesions, the patient is alive and completely symptom-free, the abdominal masses are stable, and liver function tests are completely normal. Smooth muscle tumors are increasingly recognized in children with various immunodeficiencies occurring after organ transplantation. This unusual evolution of a clinically aggressive tumor into a stable disease after restoration of immunity confirms that the immune status of the patient is a crucial factor.

BACKGROUND: Lymphatic malformations (LM) are rare benign congenital tumors appearing mainly in the head and neck with a considerably variable outcome. A need exists to validate a staging system, taking into account the prognosis of the malformation, including preoperative and postoperative complications, long-term sequelae, and persistence of the disease to improve parental counseling and evaluate the outcome of a surgical treatment of such tumors. METHODS: Twenty-two patients treated for LM were selected from a series of 129 patients operated on for congenital malformations of the head and neck between 1986 and 1997 at St-Luc University Hospital, Brussels, Belgium. Their charts were reviewed retrospectively, with a special focus on the anatomic location of the lesions and all the complications reported. According to de Serres et al, LM up to now have been divided into six possible categories according to their unilateral or bilateral infrahyoid and/or suprahyoid locations. RESULTS: Stage I (unilateral infrahyoid): nine patients, 11% of complications (without mediastinal extension: 0%, with mediastinal extension: 50%); stage II (unilateral suprahyoid): three patients, 33% of complications; stage III (unilateral suprahyoid and infrahyoid): eight patients, 75% of complications; stage V (bilateral suprahyoid and infrahyoid): two patients, 100% of complications. None of the children was initially seen with stage IV (bilateral suprahyoid) or stage VI (bilateral infrahyoid) LM. Overall complications, preoperative complications, postoperative com- plications, and long-term morbidity showed a significant in- crease from stage I to V (p

Article abstract The authors describe the clinical, radiologic, and pathologic features of a neonatal spinal neurenteric cyst (NC) presenting with long-lasting fever and acute myelopathy, and compare this observation with other infants reported in the literature. This observation shows that NC must be considered in the differential diagnosis of acute myelopathy with persistent fever in infancy. Fever is attributed to degenerative changes in the NC, triggering inflammatory cell infiltration and tumor necrosis factor alpha secretion.