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High-risk neuroblastoma comprises nearly half of cases of neuroblastoma and the long-term survival is less than 50% despite complex and intensive treatments. Studies conducted in Europe and in North America in the last two decades have identified a strategy based on four therapeutic phases: an intensive induction therapy, a local control by surgery and radiation, a consolidation phase with single or tandem high dose chemotherapy and autologous transplant, and immunotherapy to eliminate residual disease. Future treatment improvements are based on progress at each of these therapeutic steps and ultimately a better stratification of the strategy adapted to the type of risk. A more extensive tumor molecular profiling at diagnosis and relapse will help to develop new therapeutics and to guide risk-based strategies. Earlier use of immunotherapy and identification of more effective combinations in induction or in maintenance treatment, identification of indications of more intense consolidations using high-dose chemotherapy combined or not with metabolic irradiation by 131I-MIBG and the introduction of other targeted treatments are tracks being explored., (Copyright © 2018. Published by Elsevier Masson SAS.)

Neuroblastoma, the most frequent solid extracranial tumor of childhood, is characterized by a wide variability of its clinical course. The most important clinical prognostic markers are stage and age at diagnosis, but these markers are insufficient to predict outcome reliably and to determine treatment intensity. Recent evidence indicates that neuroblastoma can be considered as a "genetic disease", firstly by the recent observation that certain alleles of specific genes significantly increase the relative risk to develop neuroblastoma, and the discovery of mutations in genes such as ALK or PHOX2B in rare familial cases. On the other hand, a large number of recurrent genetic somatic alterations have been described in neuroblastoma. Recent technological advances, such as array-CGH (comparative genomic hybridisation), now enable the analysis of these markers in a single step and allow the definition of genomic profiles associated with typical clinical features. Numerical chromosome alterations are observed more frequently in tumors of younger children with localised disease and a good prognosis, whereas segmental chromosome alterations are found more frequently in tumors of older children with advanced stages of disease and a poorer outcome. Future therapeutic stratification schemes can make use of the tumor genomic profile by proposing less intense treatment for infants with a neuroblastoma harboring a favorable tumor genomic profile, while intensifying treatment in case of a defavorable tumor genomic profile. Such approaches require standardisation of the molecular techniques and the interpretation of results for application in international trials.

The extension of a cancer is a major prognostic factor which determines the therapeutic strategy. The occurrence of metastatic relapses in patients with initially localized tumours, despite a good local control, gives evidence for the possibility of spreading of occult tumour cells. The recent improvements of immunohistochemistry and molecular biology methods enable to detect tumour cells in various sites such as lymph nodes, bone marrow and blood with a considerably increased sensitivity as compared to conventional approaches. The markers used to detect tumour cells by PCR or RT-PCR can be either "tissue-specific" or "tumour specific". The drawback of the first group of markers is linked to the observation that tissue-specificity is frequently a relative concept leading to a high rate of false positives. Tumour-specific markers include gene fusions observed in various sarcomas, point mutations and presence of viral genomes in tumour cells. They are available and can be easily monitored in only a limited set of cancers. This review focuses on the molecular biology approaches which are used to detect occult tumour cells and on their clinical applications. The large number of studies which have been published in that field show that such a detection can be performed in a variety of target sites. However, results of studies performed on larger series of patients together with a better standardization of technics are necessary before they can be used for individual staging of patients.

Background: Cyanosis associated to low oxygen saturation may reveal hemoglobin pathology., Case Report: A 3 year-old child had a nephroblastoma with pleural effusion. He suddenly developed persistent cyanosis despite pleural effusion drainage; transcutaneous and measured oxygen saturations were low and PaO2 on arterial blood gases was high. Methemoglobinemia was diagnosed, due to prilocaine-lignocaine cream used for local anesthesia, associated to partial G6PD deficiency. The methemoglobinemia disappeared after methylene blue treatment., Conclusion: Cyanosis with low oxygen saturation and high or normal PaO2 should lead to the search of a hemoglobin pathology, especially methemoglobinemia, by appropriate methods.