Abstract: A male infant showed a humeral diaphysis fracture at 5 months of age and a distal tibial physis fracture at 2 years of age. A specialized consultant ruled out child abuse. This child had the characteristic features of type I osteogenesis imperfecta: blue sclerae, osseous fragility, and presumably autosomal dominant inheritance, as his father suffered from similar disorders. Later on, multiple painful osteochondromas were also found and some of these were surgically treated. The child's mother showed several peripheral osteochondromas. We describe the follow-up of this patient up to the age of 18 years. To our knowledge, the fortuitous association of these two inherited conditions has not been reported in medical literature.
Abstract: Cancer stem cells that display tumor-initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective therapeutic strategies. However, evidence of such cells in sarcomas, which include some of the most aggressive and therapy-resistant tumors, has not been shown to date. Here, we identify and characterize cancer stem cells in Ewing's sarcoma family tumors (ESFT), a highly aggressive pediatric malignancy believed to be of mesenchymal stem cell (MSC) origin. Using magnetic bead cell separation of primary ESFT, we have isolated a subpopulation of CD133+ tumor cells that display the capacity to initiate and sustain tumor growth through serial transplantation in nonobese diabetic/severe combined immunodeficiency mice, re-establishing at each in vivo passage the parental tumor phenotype and hierarchical cell organization. Consistent with the plasticity of MSCs, in vitro differentiation assays showed that the CD133+ cell population retained the ability to differentiate along adipogenic, osteogenic, and chondrogenic lineages. Quantitative real-time PCR analysis of genes implicated in stem cell maintenance revealed that CD133+ ESFT cells express significantly higher levels of OCT4 and NANOG than their CD133- counterparts. Taken together, our observations provide the first identification of ESFT cancer stem cells and demonstration of their MSC properties, a critical step towards a better biological understanding and rational therapeutic targeting of these tumors. [Cancer Res 2009;69(5):OF1-6].
Abstract: Central venous occlusion in children is a challenging problem that can occur after a central venous catheter insertion. Long-term catheter-related complications include sepsis and venous thrombosis with consequent loss of central access. We describe 2 cases of children younger than 1 year who were dependent on a central venous catheter for total parenteral nutrition. They developed a chronic extensive obstruction of the right and left brachiocephalic veins with a superior vena cava syndrome. The patients' survival was dependent on the restoration of central venous access until the planned intestinal transplantation could be performed. Retrograde recanalization of the superior vena cava was successfully achieved using a pathway created under general anesthesia from the femoral vein to, respectively, the right thyroid vein and the right subclavian vein.
Abstract: Ewing's sarcoma family tumors (ESFT) express the EWS-FLI-1 fusion gene generated by the chromosomal translocation t(11;22)(q24;q12). Expression of the EWS-FLI-1 fusion protein in a permissive cellular environment is believed to play a key role in ESFT pathogenesis. However, EWS-FLI-1 induces growth arrest or apoptosis in differentiated primary cells, and the identity of permissive primary human cells that can support its expression and function has until now remained elusive. Here we show that expression of EWS-FLI-1 in human mesenchymal stem cells (hMSC) is not only stably maintained without inhibiting proliferation but also induces a gene expression profile bearing striking similarity to that of ESFT, including genes that are among the highest ESFT discriminators. Expression of EWS-FLI-1 in hMSCs may recapitulate the initial steps of Ewing's sarcoma development, allowing identification of genes that play an important role early in its pathogenesis. Among relevant candidate transcripts induced by EWS-FLI-1 in hMSCs, we found the polycomb group gene EZH2, which we show to play a critical role in Ewing's sarcoma growth. These observations are consistent with our recent findings using mouse mesenchymal progenitor cells and provide compelling evidence that hMSCs are candidate cells of origin of ESFT.
Abstract: ABSTRACT: BACKGROUND: Totally implanted vascular access devices are frequently used in children for repeated blood samples or intravenous treatments. This prospective study aims at identifying the risk factors associated with infections, obstructions and surgical complications of these devices in pediatric patients. METHODS: From January 2006 to January 2008, all children older than one year of age with a diagnosis of solid or blood cell malignancy were included in the study. Insertion was performed by the surgeon according to a standardized protocol after landmark-guided puncture of the subclavian or internal jugular vein by a senior anesthesiologist. Dressing and post-operative care were standardized. Every manipulation was prospectively recorded by specialized dedicated nurses, and all patients were screened for complications one month post-surgery. RESULTS: 45 consecutive patients 1 to 16 years old were enrolled in the study. Mean age at the time of procedure was 8.5 years (range 1.3-15.6; SD +/- 4.88). There were 12 peroperative adverse events in 45 procedures (27%), detailed as follows: 3 pneumothoraces (7%), 3 hematomas (7%), 6 arterial punctures (13%). Among these events, intervention was necessary for two pneumothorax and one arterial puncture. There was no air embolism. At one month, we recorded 5 post-operative complications (11%): 2 thrombotic obstructions, one unsightly scar, and one scapular pain of unknown etiology. One patient needed repositioning of the catheter. There was no catheter-related infection. CONCLUSION: Prospective recording of TIVA insertion in children reveals a significant number of early incidents and complications, mainly associated with the percutaneous puncture technique. We found no infection in this series. Results of a longer follow-up in the same population are pending.
Abstract: OBJECTIVE: To determine whether specific steps taken after a critical quality control of our results in hypospadias surgery lead to a decrease in fistula rate. PATIENTS AND METHODS: Retrospective review of prospectively collected data. Between 1994 and 2001, our series of 85 tubularized plate urethroplasties (modified Duplay or Duplay-Snodgrass procedure) had a fistula rate of 25.9%. In 2001, we modified our approach by systematically padding the urethral suture with a layer of vascularized subcutaneous preputial tissue, as described by Snodgrass. Scrotal hypospadias were excluded. Surgical outcome was assessed at 1 and 12months. In both groups, all repairs were performed by or under direct supervision of the senior author (BJM). RESULTS: After 2001, 57 hypospadias repairs were performed in 57 patients aged 8months to 14years (median 1.4years). Fistula occurred in two cases, one of which closed spontaneously within 6months. Our fistula rate had dropped to 3.5%, with a minimum follow up of 12months. CONCLUSION: Covering the urethral suture with a padding flap of vascularized preputial tissue helps avoid fistula formation. Technique modification after critical appraisal of our own series led to a much better outcome in this demanding surgery.
Abstract: A 4-year-old boy underwent pulmonary testing for diagnosis of exercise-induced dyspnea and subsequent cyanosis. Findings demonstrated the presence of multiple pulmonary arteriovenous fistulas resulting in oxygen desaturation owing to shunting (PaO2, 44 mm Hg). Abdominal ultrasound, abdominal computer tomography, and mesenteric angiography revealed an extrahepatic portocaval fistula (PCF), absence of a patent portal vein, and no evidence of portal hypertension. Because these findings were consistent with hepatopulmonary syndrome (HPS), liver transplantation was initially considered. However, subsequent workup using cavofistulography revealed the presence of a hypoplastic portal vein that selective catheterization showed to be threadlike but patent. Based on this finding, a definitive diagnosis of a congenital PCF with hypoplasia of the portal vein (type 2 Abernethy malformation) was made and surgical ligation with transection of the fistula was performed at the age of 5. Treatment was successful without subsequent development of portal hypertension and pulmonary symptoms disappeared. Follow-up examination 4 years later showed that the boy was asymptomatic and that the intrahepatic portal system was patent with normal hepatopetal flow. This is the first reported case of HPS because of portal type 2 Abernethy malformation. Anatomical types of PCF and corresponding therapeutic options in case of HPS are discussed.
Abstract: BACKGROUND: The aim of this study was to analyse different clinical aspects and embryologic hypotheses of duodenal duplications. METHODS: Duodenal duplications occurring since 1995 were recorded. The age of the children at the time of diagnosis, the sex, location of the duplication, type of mucosa, clinical signs, associated lesions, and the type of surgical intervention were defined. RESULTS: We identified 5 patients (3 girls and 2 boys) who presented with histological or intraoperative findings of duodenal duplication. Their ages ranged from 4 days to 9 years, with the exception of two prenatal diagnoses. Three children were symptomatic: high intestinal obstruction (1 case), digestive bleeding (2 cases). In 1 case we found a palpable abdominal mass and 1 case was completely asymptomatic (prenatal detection). The abnormality was located on the duodenal concavity, originating from the third part in 2 cases and from the second part in 3 cases. All cases were non communicating types, 4 of which were cystic duplications and 1 was a tube-like variety. The epithelial lining was duodenal mucosa in all patients, but gastric heterotopies were identified in 2 cases. We performed two complete resections and 3 intraduodenal derivations. The outcome was uneventful in 5 cases with an average follow-up of 2 years. CONCLUSION: Duodenal duplications are rare malformations with several anatomical varieties. The preferred treatment for duodenal duplications is complete removal when the location allows it without endangering nearby anatomical structures.
Abstract: OBJECTIVES: To investigate the incidence, nature, and management of associated ipsilateral genitourinary malformations in children with multicystic dysplastic kidney (MCDK). METHODS: In this retrospective study, we analyzed the medical records and imaging studies of 93 patients with MCDK. Patients underwent ultrasonography, voiding cystourethrography, intravenous urography, and radionuclide renal imaging studies during their first month of age. RESULTS: A diagnosis of MCDK associated with malformation of the ipsilateral internal genitalia was confirmed in 11 patients after birth investigations of prenatal MCDK. Three were diagnosed at 1, 12, and 14 years of age because of epididymitis, pelvic pain associated with amenorrhea, and accidentally during lumbar pain assessment, respectively. The male/female sex ratio was 10:4. The left side was involved in 9 patients. We had 3 cases of Gartner duct persistence, 6 of cystic retrovesical and laterovesical masses with vanishing MCDK, 4 of cystic retrovesical or laterovesical masses with compressive MCDK, and 1 of a blind-ending hemivagina. Nine patients were periodically observed, and four underwent nephroureterectomy. All patients underwent 6-month follow-up examinations with ultrasonography (mean follow-up 6.54 years, range 36 months to 14 years). CONCLUSIONS: Of the 93 patients with MCDK, 14 (15%) had malformations of the ipsilateral internal genitalia. Persistence of seminal cysts in boys and Gartner ducts were encountered even if the MCDK had involuted. These results suggest that follow-up of patients with MCDK should be performed until the end of puberty to detect genitourinary malformations.
Abstract: Duodenal cystic dystrophy due to ectopic pancreas deposit is an uncommon pathology. Diagnosis is made by modern imaging techniques, mainly endoscopic ultrasound which localizes precisely cysts in duodenal wall. The most frequent clinical symptoms are pain, duodenal obstruction, and weight loss. We report the case of a 40 year-old man with cystic dystrophy of the 2nd part of the duodenum, without chronic pancreatitis, treated by a conservative surgical procedure including segmental duodenal resection. This original approach is an alternative to the Whipple procedure.
Abstract: OBJECT: An increasing number of asymptomatic children are diagnosed with occult spinal dysraphism, raising the question of their optimal management. Urodynamic study (UDS) is the most reliable method of detecting neuro-urological abnormalities in these children. The rate of postoperative retethering ranges from 10 to 20% and is not always immediately clinically significant. The aim of this prospective study was to develop a reliable method that could be used in the preoperative assessment and postoperative follow-up of children with a tethered cord syndrome (TCS). METHODS: From 1989 to 1997, 15 children underwent spinal cord untethering for TCS. Preoperatively, patients were assessed with MRI and UDS. Postoperative UDS were repeated at 6- to 12-month intervals. Four UDS parameters were identified, graded, and added to obtain a UDS score. A group of 38 children without dysraphic condition was used as control and allowed the calculation of a normal score. CONCLUSIONS: There was a statistically significant difference in the preoperative UDS scores between the control group and the study group ( p<0.001). Postoperatively, there was a statistically significant improvement ( p<0.001) in UDS scores. UDS score is a reliable tool for identifying and quantifying neuro-urological disorders in patients with TCS. Postoperatively, this score was useful in the early diagnosis of spinal cord retethering.
