Hepatic Stem-like Phenotype and Interplay of Wnt/β-Catenin and Myc Signaling in Aggressive Childhood Liver Cancer

SummaryHepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/β-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. β-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy

Résultats et devenir 10 ans après une transplantation hépatique pour atrésie des voies biliaires (étude unicentrique concernant 280 enfants)

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Benign Hepatocellular Tumors in Children: Focal Nodular Hyperplasia and Hepatocellular Adenoma

Benign liver tumors are very rare in children. Most focal nodular hyperplasia (FNH) remain sporadic, but predisposing factors exist, as follows: long-term cancer survivor (with an increasing incidence), portal deprivation in congenital or surgical portosystemic shunt. The aspect is atypical on imaging in two-thirds of cases. Biopsy of the tumor and the nontumoral liver is then required. Surgical resection will be discussed in the case of large tumors with or without symptoms. In the case of associated vascular disorder with portal deprivation, restoration of the portal flow will be discussed in the hope of seeing the involution of FNH. HepatoCellular Adenoma (HCA) is frequently associated with predisposing factors such as GSD type I and III, Fanconi anemia especially if androgen therapy is administered, CPSS, and SPSS. Adenomatosis has been reported in germline mutation of HNF1-α. Management will depend on the presence of a predisposing factor and may include metabolic control, androgen therapy withdrawn, or closure of the shunt when appropriate. Surgery is usually performed on large lesions. In the case of adenomatosis or multiple lesions, surgery will be adapted. Close followup is required in all cases

Qualité de vie péri-opératoire des enfants (validation psychométrique des échelles de la douleur et de l'anxiété)

MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Does the sciatic nerve approach influence thigh tourniquet tolerance during below-knee surgery?

In this prospective, randomized, blinded study we assessed thigh tourniquet tolerance when a Labat's or a posterior popliteal approach of the sciatic nerve was used for below-knee surgery. One-hundred-twenty patients were divided into two groups of 60. A posterior popliteal (Group 1) or a Labat's (Group 2) sciatic nerve block was performed with 25 mL 1% mepivacaine + epinephrine 1:200,000. In both groups, a femoral nerve block was achieved. Patient comfort during block performance, sensory block, success rate, and thigh tourniquet tolerance were recorded. Performance of the block was significantly more comfortable in Group 1 than in Group 2 (P < 0.01). Completeness of the block at t(30 min.) and success rate were comparable in both groups. Thigh tourniquet pain increased with time in both groups. No statistically significant difference was observed between groups. We conclude that despite a complete sensory blockade of the posterior femoral cutaneous nerve in 91% of the patients, Labat's approach of the sciatic nerve provides no better thigh tourniquet tolerance than the popliteal approach. The popliteal approach is as efficient but more comfortable for the patient and is the preferred technique for below-knee surgery

A practical approach to pediatric liver transplantation in hepatoblastoma and hepatocellular carcinoma

Progressively, as chemotherapy has become more effective, more children with liver malignancies are amenable to liver transplantation, and indications have expanded from a limited range of cases (mostly hepatoblastoma) to a range of other unresectable malignant liver tumors; as a result, more children with hepatocellular carcinoma are also now proposed to transplantation, even and often outside the Milan criteria, for a cure. Recent series have highlighted that patient and graft survivals after transplantation for hepatoblastoma and hepatocellular carcinoma have improved in the last decade. Although consensus has not yet been reached about transplantation as a possible cure for other tumor types than hepatoblastoma and hepatocellular carcinoma, liver transplantation, generally speaking, has become an important pillar in the management of pediatric liver malignancies. Remaining limitations and inquiries relate to patient selection (in term of selection criteria considering the risk of recurrence), the role and usefulness of chemotherapy after transplantation, or the best immunosuppression strategy to both protect renal function and improve outcome. Although some prospective studies are on the way regarding these aspects, more studies are needed to explore this rapidly changing aspect of care

Mesenchymal hamartoma or embryonal sarcoma of the liver in childhood: a difficult diagnosis before complete surgical excision

Clinical experience shows that the primary diagnosis of mesenchymal hamartoma (MHL) and embryonal sarcoma of the liver (ESL) recurrently is mistaken, leading to inadequate managements. We evaluated the accuracy of the primary diagnosis of those liver tumors, compared with the final histological diagnosis

The Use of Cavitron Ultrasonic Surgical Aspirator for High-Risk Neuroblastoma with Image-Defined Risk Factors in Children

Aim of the study: The cavitron ultrasonic surgical aspirator (CUSA) has gained popularity in adult surgical oncology, but its application in children is limited to liver surgery and neurosurgical procedures. The complete resection of neuroblastoma with image-defined risk factors (IDRFs) is still considered one of the most difficult procedures to achieve in pediatric surgical oncology, with a high morbidity rate and potential risk of intraoperative mortality. The aim of our study is to describe the application of ultrasonic dissection in neuroblastoma with IDRFs. Methods: A retrospective study was performed, analyzing patients operated on from 2000 to 2018. Patient characteristics, resection completeness, and postoperative surgical and oncology outcomes were analyzed. Main results: Twenty-six patients with high-risk neuroblastoma and IDRFs were operated on in the study period with a CUSA. A complete macroscopic resection was performed in 50% of patients, while the other half was operated on with minimal residual (Conclusions: The application of the CUSA in neuroblastoma with IDRFs can be considered an effective and safe alternative technique to achieve a radical resection

Contrast-enhanced ultrasound in fibro-lamellar hepatocellular carcinoma: a case report.

International audienceA case of fibrolamellar hepatocellular carcinoma, occurring in a 13 year-old girl with the characteristics of the dynamic enhancement observed during contrast-enhanced ultrasound within the tumour and within vascular extension into the portal vein is reported. The lesion showed marked hypervascularity in the early arterial and arterial phases with irregular, tortuous vessels. During the early portal phase, centripetal filling of the tumour was observed, except in an irregular area and adjacent hypo-enhancing bands, related to a central scar, on subsequent CT and MRI images. Centrifugal wash-out led to the absence of sustained enhancement during the late phase. Similar enhancement patterns were observed within the portal tumoural thrombosis, and evaluation of its extension was easy on delayed images. Contrast-enhanced ultrasound is a useful diagnostic tool for the characterisation and evaluation of extension of such a rare malignant hepatic tumour

Activation of β-catenin in epithelial and mesenchymal hepatoblastomas

International audienceWnt/β-catenin signaling is frequently activated in cancer cells by stabilizing mutations of β-catenin or loss-of-function mutations of the APC tumor suppressor gene. We have analysed the role of β-catenin in the pathogenesis of hepatoblastoma (HB), an embryonic liver tumor occurring mainly in children under 2 years of age. Sequence analysis of the β-catenin NH2-terminal domain in 18 epithelial and mixed HBs revealed missense mutations in the GSK3β phosphorylation motif or interstitial deletions in 12 tumors (67%). In the remaining cases, no truncating mutation of APC could be evidenced. Immunohistochemical analysis of β-catenin in 11 HBs demonstrated nuclear/cytoplasmic accumulation of the protein in all tumors analysed, with predominant nuclear β-catenin immunostaining in undifferentiated cells. Membranous β-catenin localization was preserved only in fetal-type tumoral hepatocytes and was associated with E-cadherin expression. Moreover, we show that β-catenin is aberrantly overexpressed in a large spectrum of tumor components, including hepatocyte-like cells at various differentiation stages and heterologous elements such as squamous, osteoid and chrondroid tissues, and in occasional other mesenchymally-derived cells. These data strongly suggest that activation of β-catenin signaling is an obligatory step in HB pathogenesis, and raise the possibility that it interferes with developmental signals that specify different tissue types at early stages of hepatic differentiation