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Abstract: Background: In children older than 1year with localised unresectable neuroblastoma (NB), treatment strategies are heterogeneous according to the national groups. The objective of this phase III non-randomised study was to evaluate the efficacy of conventional chemotherapy followed by surgery. Patients and methods: In the presence of surgical risk factors (SRF), six courses of chemotherapy alternating Carboplatin–Etoposide and Vincristin–Cyclophosphamide–Doxorubicin were given, and surgical resection was attempted after four. Survival analyses were performed using an intention-to-treat approach. The main objective was to achieve a 5-year survival over 80%. Results: Out of 191 registered children, 160 were evaluable. There were 62.5% older than 18months and 52.5% had unfavourable histology according to International Neuroblastoma Pathology Classification (INPC). Chemotherapy reduced the number of SRFs by one third. Delayed surgery was attempted in 86.3% of patients and was complete or nearly complete in 74%. The 5-year EFS and OS were 76.4% and 87.6% respectively, with significant better results for patients younger than 18months or with favourable histology. Conclusion: This strategy provides encouraging results in children older than 1year or 12months with localised unresectable NB without MYCN amplification. However, in children older than 18months and with unfavourable histology, additional treatment is recommended. [Copyright &y& Elsevier]

Neuroblastoma is the most frequent tumor observed in the newborn. The aim of this study was to review clinical features, treatment and outcome of newborns diagnosed with a localized neuroblastoma.Population and methods. – Data from 52 cases treated according to the NBL 90 and 94 protocols between 1990 and 1999 in 18 French centers of pediatric oncology were analyzed.Results. – The median age at diagnosis was 12 days (range 0–28) with antenatal detection in 14 patients (27%). Tumor location was abdominal in 40 patients (adrenal in 20 of the 40), thoracic in eight, pelvic in three, and cervical in one. N-myc amplification was observed in one out of 40 evaluable cases. The size of the primary tumor was less than 5 cm in 25 cases, between 5 and 10 cm in 25 and more than 10 cm in two. Dumbbell tumor was observed in seven, of whom five had neurological deficit. One child died from hemorrhage after fine needle biopsy during diagnostic procedure. Primary surgical resection was attempted in 37 infants, of whom two died of surgery related complications and three had nephrectomy. Tumor was deemed as unresectable in 14 patients, and primary chemotherapy was given followed by surgical excision in 12. One of them died a few days after the beginning of chemotherapy. As a whole, continuous complete remission was achieved in 48 children, four of them after relapse. Overall survival was 92% with a median follow-up of 46 months (0–113 months).Conclusion. – The excellent prognosis of localized NB in neonates needs very restrictive surgical indications, with well-established anatomic and imaging criteria. Indeed, chemotherapy based on weight and managed by expert teams should allow to perform surgical excision in safer conditions for unresectable tumors. [Copyright &y& Elsevier]

The purpose of this study was to evaluate the efficacy of low-dose chemotherapy in infants with localised and unresectable neuroblastoma (NB). All consecutive infants with localised NB and no N-myc amplification were eligible in the SFOP-NBL 94 study. Primary tumour was deemed as unresectable according to imaging data showing any risk of immediate resection. Diagnostic procedures and staging were conducted according to INSS recommendations. For children, provided that they had no threatening symptom (i.e. vital risk or dumb-bell NB with neurologic deficit), chemotherapy consisted in low-dose cyclophosphamide (5 mg(-1)kg day(-1) x 5 days) and vincristine (0.05 mg kg(-1) at day 1)-CV and repeated one to three times every 2 weeks until surgical excision can be safely performed. No postoperative treatment was given. Between January 1995 and December 1999, 134 consecutive infants with localised NB were registered in the study, of whom 39 had an unresectable NB without N-myc amplification. Among them 28 had no threatening symptom and received CV according to the protocol. Objective response was observed in 14 (50%) and the other 14 were given second-line chemotherapy because of no response. Surgery was attempted in 38 patients including 14 after CV alone, leading to complete resection in 23. Relapses occurred in four patients all local. Survival and event-free survival were 100 and 90+/-5% with a median follow-up of 55 months (range 33-93). In conclusion primary low-dose chemotherapy without anthracyclines is efficient in about half of the infants presenting with an unresectable NB and no N-myc amplification, allowing excellent survival rates without jeopardising their long-term outcome even for nonresponding patients who received standard regimen. [ABSTRACT FROM AUTHOR]

Stage 4s neuroblastoma (NB) is usually associated with a favourable outcome, despite a large tumour burden, as spontaneous regression frequently occurs. However, in some infants rapid disease progression can be observed with severe functional impairment. Thus, for all patients the potential risks of cytotoxic therapy must be weighed against the benefits of early medical intervention. We have retrospectively reviewed the charts of 94 infants treated for stage 4s NB in centres of the French Society of Paediatric Oncology between 1990 and 2000, and describe the different first-line treatment approaches that were, successively, liver irradiation, chemotherapy using a cyclophosphamide-vincristine regimen, and chemotherapy using a carboplatin-etoposide regimen. The overall survival was 88% (+/-7.6%), with a mean follow-up of 64 months. Elevated serum neuron-specific enolase (>100 nmol ml(-1)), ferritin (>280 ng ml(-1)) and urinary dopamine levels (>2500 nmol mmol(-1) creatinine) were associated with a poor outcome, as were the genetic markers N-myc amplification and chromosome 1p deletion (P<0.0005 and P=0.0016, respectively). Patients who required medical intervention at diagnosis fared worse than those who received supportive treatment only (P<0.005). The clinical evolution observed with the different successive treatment approaches suggests that if infants do require therapy, the prompt initiation of a more intensive regimen such as carboplatin-etoposide may be more beneficial. [ABSTRACT FROM AUTHOR]

Individual dosing of carboplatin based on drug monitoring was performed within a multi-centric phase I study based on high AUC-levels in children. Twelve patients (aged 3–17 years old) have been included: 3, 5, and 4 patients at the overall target ultrafilterable carboplatin AUC of 20, 25, or 30 mg/ml×min, respectively. Carboplatin was administered as a daily 60-min infusion, repeated on five consecutive days. The initial daily dose corresponding to the three first days was calculated according to the carboplatin clearance (CL) predicted from patients’ characteristics (body weight, serum creatinine and nephrectomy status). Three blood samples were taken per patient. The individual CL were estimated by MAP (maximum a posteriori approach) Bayesian method implemented in the MP-K program. The doses for day 4 and 5 was adjusted in order to obtain the overall target AUC. Drug monitoring led to a change in the carboplatin dose (overall administered dose versus overall dose planned) ranging from −41% to +45%. Pharmacokinetics were performed at day 5 for 7/12 children: mean relative change between day 1 and day 5 was −11% showing a statistically significant, but limited, decrease of CL from day 1 to day 5. The percentage of difference between the observed and target overall AUC ranged between −7% and +14%. Three patients (one at each AUC level) who were previously treated with cisplatin experienced dose-limiting hearing loss. In conclusion, drug monitoring and dose adjustment is needed for the control of carboplatin plasma exposure when administering high doses of carboplatin in children. [Copyright &y& Elsevier]

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse. [ABSTRACT FROM AUTHOR]

Material and methods. – This retrospective study reports 15 cases of hemophagocytic syndrome in children treated in our department during a eight-year period.Results. – Underlying diseases were acute lymphoblastic leukemia (n=8) acute myeloblastic leukemia (n=6) and Burkitt lymphoma (n=1). Hemophagocytic syndrome was suspected after chemotherapy, in case of an unusual prolonged febrile neutropenia (n=14) or isolated thrombocytopenia (n=1). That fever was associated with cutaneous, pulmonary, hematologic, digestive and cardiac signs. Biological disorders included hypoprotidemia, hyponatremia, increased liver enzymes and fibrinopenia. Thrombocytopenia was observed in all patients and was associated with neutropenia for 14 of them. Diagnosis of hemophagocytic syndrome was always confirmed by bone marrow aspiration (infiltration with activated macrophages). Infection was documented in eight children. The treatment of hemophagocytic syndrome relied on steroids and resolution of symptoms occurred within three days of therapy. No recurrence of hemophagocytic syndrome was observed with a median follow up of two years and a half.Conclusion. – Such complication should be suspected in cases of prolonged febrile neutropenia and/or thrombocytopenia, and confirmed by bone marrow aspiration. Indeed, steroid therapy is effective and chemotherapy can be then pursued. [Copyright &y& Elsevier]

Résumé Introduction Les enfants et adolescents atteints de cancer sont pris en charge en France par des équipes pluri-professionnelles au sein de centres spécialisés d’onco-hématologie pédiatrique, labellisés par l’Institut national du cancer, qui travaillent en réseau avec des centres de pédiatrie de proximité. Le diplôme inter-universitaire d’oncologie pédiatrique (DIUOP) propose une formation à l’onco-hématologie maligne pédiatrique comprenant un enseignement théorique, un stage dans un service validant et un projet de recherche soutenu devant un jury. Méthode Nous avons adressé un questionnaire aux diplômés pour connaître leur situation professionnelle actuelle et avons recherché sur PubMed tous les articles publiés. Résultats De 2000 à 2011, le DIUOP a formé 290 médecins spécialistes : 242 pédiatres, 21 chirurgiens et 19 radiothérapeutes, 8 ayant une autre spécialité telle que l’imagerie, l’hématologie ou l’anatomo-pathologie. Quatre-vingt-douze étaient titulaires d’un diplôme obtenu à l’étranger : en Europe (50 %), en Afrique et au Proche-Orient (42 %) et en Amérique du Sud (8 %). Cent quatre-vingt-dix-sept des 266 diplômés (74 %) ont répondu au questionnaire. Quatre-vingt-dix pour cent prenaient en charge des enfants et adolescents atteints de cancer. Pour ceux exerçant en France, ils travaillaient principalement dans les établissements impliqués dans l’organisation des soins définie par la circulaire DHOS (Direction de l’hospitalisation et de l’organisation des soins) de 2004. Soixante-neuf articles, soit un mémoire sur 4, avaient été publiés dans une revue avec un facteur d’impact médian de 3,5 (0–22,6) dont 85 % en langue anglaise. Conclusion Le DIUOP est la seule formation européenne en langue française offrant une formation professionnalisante, multidisciplinaire, de qualité et complète aux spécialistes impliqués dans la prise en charge des cancers de l’enfant et de l’adolescent. Summary Introduction According to the European Society of Pediatric Oncology (SIOPE) standard of care guidelines, high-quality care of children and adolescents with cancer needs to be delivered by well-trained multidisciplinary teams in specialist centers working with designated shared-care local centers in a so-called hub-and-spoke model. The Diplôme Inter-Universitaire d’Oncologie Pédiatrique (DIUOP) is the only European training program in pediatric oncology in French for all physicians involved in care of patients with pediatric malignancies. In agreement with the SIOPE syllabus, the DIUOP is composed of training courses (120 h), on-site practical training in a specialist center, and a research project to be defended before an examining board. Method All graduates received a questionnaire to describe their current professional position. A comprehensive PubMed analysis retrieved all papers published form DIUOP research projects. Results From 2000 to 2011, 290 physicians were trained: 242 pediatricians, 21 surgeons, and 19 radiation therapists. Eight had another specialty including imaging, hematology, and pathology. Ninety-two were initially trained outside of France: 50% in Europe (mainly in Italy, Belgium, and Switzerland), 42% in Africa and the Middle East, and 8% in South America. Of the 266 graduates, 74% answered the questionnaire, and 90% of them take care of children and adolescents with cancer. Sixty-nine articles, i.e., one out of four research projects, were published in 34 journals with a median impact factor of 3.5 (0–22.6), 85% in English. Conclusion DIUOP is the only French-speaking European education program providing a high-quality, professionalizing, and comprehensive multidisciplinary training program for French and international specialists taking care of children and adolescents with cancer. [ABSTRACT FROM AUTHOR]

Objectif Evaluer les résultats fonctionnels et oncologiques à long terme après traitement d’un tératome sacro-coccygien (TSC) chez le nouveau-né et le nourrisson Matériel et méthode Etude rétrospective monocentrique des patients traités pour un TSC avant l’âge d’un an entre 2000 et 2013. Résultats 14 patients consécutifs ont été inclus dont 8 cas diagnostiqués en anténatal. Le terme de naissance était de 37.3 semaines (30.5-40.0) et le poids moyen opératoire de 4.1 kg (1.4-6.2). L’exérèse chirurgicale a été effectuée dans le premier mois de vie pour 8 patients. La voie d’abord était périnéale (n=10) pour les TSC exopelviens et associée à un abord rachidien (n=3) ou pelvien (n=1) en cas de TSC intracanalaire ou endopelvien. Un contingent immature était présent dans 3 cas. Le suivi post-opératoire moyen était de 47 mois (7-122). La survie globale et sans récidive étaient respectivement de 86% et 83%. Deux patients ont eu une récidive locale (n=1) et métastatique pulmonaire (n=1) traitée chirurgicalement après chimiothérapie. Deux patients (17%) ont eu des complications fonctionnelles à type de vessie neurologique. Conclusion Le traitement du TSC néonatal s’inscrit dans une démarche pluridisciplinaire afin d’augmenter la survie globale et limiter les séquelles fonctionnelles. [ABSTRACT FROM AUTHOR]

Lors d’une bactériémie à Staphylococcus aureus (S. aureus) sur cathéter veineux central (CVC), le retrait du cathéter est recommandé mais une conservation est parfois considérée. Objectif Evaluer le devenir clinique des enfants porteurs de maladies malignes hospitalisés pour neutropénie fébrile avec une bactériémie à S. aureus chez qui une conservation du CVC avait été proposée. Matériels et Méthodes Analyse rétrospective des bactériémies à S. aureus chez des enfants neutropéniques fébriles porteurs de CVC entre 2007 et 2012 dans l’unité d’oncologie pédiatrique (CHU Toulouse). Résultats 27 épisodes ont été observés chez 19 patients. Onze CVC ont été conservés notamment chez tous ceux ayant une tumeur solide (n=4). Tous les CVC avec signes inflammatoires locaux ont été retirés (n=5). Sept patients ont eu une deuxième bactériémie, trois des complications graves. Aucun facteur prédictif de récidive infectieuse n’a été identifié. Aucun décès ni séquelle fonctionnelle n’ont été observés. Conclusion 58% des CVC ont été conservés après une première bactériémie à S. aureus . En l’absence de facteurs prédictifs infectieux (récurrence, complication), le retrait est recommandé mais la conservation peut être discutée dans certains cas après appréciation de la situation clinique. [ABSTRACT FROM AUTHOR]

Background: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse.Methods: In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials.Results: Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival.Conclusion: In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate the efficacy and safety of irinotecan in paediatric recurrent or refractory neuroblastoma. PATIENTS AND METHODS: Thirty seven patients aged between 6 months and < or = 20 years, with relapsed or refractory neuroblastoma, received irinotecan at 600 mg/m(2) administered as a 60-min infusion, every 3 weeks. Tumour response was evaluated by conventional radiological and mIBG scans every two cycles. RESULTS: No objective response was observed during the study. Stable disease was observed in 13% of evaluable patients. Median times to progression and survival were 1.4 months (range, 1.2-1.5 months) and 8.8 months (range, 6.7-11.3 months), respectively. One forty two cycles were administered, with a median of two cycles per patient (range, 1-17 cycles). The most common grade 3-4 toxicities were neutropenia (65% of patients), anaemia (43%), thrombocytopenia (38%), vomiting (14%), abdominal pain or cramping (8%), and nausea (5%). CONCLUSION: Irinotecan administered intravenously as a single agent every 3 weeks induced no objective response in relapsed or refractory neuroblastoma. [ABSTRACT FROM AUTHOR]

Whereas neuroblastoma (NB) with MYCN amplification presents a poor prognosis, no single marker allows to reliably predict outcome in tumours without MYCN amplification. We report here an extensive analysis of 147 NB samples at diagnosis, without MYCN amplification, by chromosomal comparative genomic hybridisation (CGH), providing a comprehensive overview of their genomic imbalances. Comparative genomic hybridisation profiles showed gains or losses of entire chromosomes (type 1) in 71 cases, whereas partial chromosome gains or losses (type 2), including gain involving 17q were observed in 68 cases. Atypical profiles were present in eight cases. A type 1 profile was observed more frequently in localised disease (P<0.0001), and in patients of less than 12 months at diagnosis (P<0.0001). A type 2 genomic profile was associated with a higher risk of relapse in the overall population (log-rank test; P<0.0001), but also in the subgroup of patients with localised disease (log-rank test, P=0.007). In multivariate analysis, the genomic profile was the strongest independent prognostic factor. In conclusion, the genomic profile is of prognostic impact in patients without MYCN amplification, making it a help in the management of low-stage NB. Further studies using higher-resolution CGH are needed to better characterise atypical genomic alterations. [ABSTRACT FROM AUTHOR]

A new mutation of the CD40LG gene that encodes the CD40 ligand molecule was characterized in a young patient harboring a hyper-IgM with immunodeficiency syndrome. Inactivation of CD40LG gene resulted from the insertion of an AluYb8 element in exon 1 responsible for a total deficiency of CD40 ligand expression by T lymphocytes. Maternal transmission of the X-linked mutation was confirmed by gene-specific polymerase chain reaction. This is the 17th case report concerning a human genetic disease caused by an Alu element insertion in a coding sequence. [ABSTRACT FROM AUTHOR]

Abstract: Background. – The feasibility and complication rate of central venous totally implantable access ports (TIAP), used for delivering high-dose chemotherapy (HDC) with autologous stem cell transplantation, have not been fully investigated to date, due to the almost exclusive use of external catheters (EC) in this clinical setting. Patients and methods. – We retrospectively studied infectious and mechanical complications of 45 TIAP and 19 EC, in 64 children receiving HDC and autologous stem cell transplantation at the Centre Leon-Berard (Lyon) or at the oncology unit of Toulouse children hospital between January 1999 and December 2003. Results. – From the beginning of intensification to 60 days after bone marrow transplantation, 7 catheter-related bloodstream infections (3/19 EC or 15.8% corresponding to 2.69 infections for 1000 days of observation; 4/45 TIAP or 8.9% corresponding to 1.38 infections for 1000 days of observation) and 2 local infections (1/45 TIAP; 1/19 EC) were reported. Seven cases of reversible obstruction (6/7 with TIAP) and no deep venous thrombosis were detected. In 7 cases, another venous access was required either for accidental removal (2 EC), catheter infection (2 TIAP), or admission to intensive care (2 TIAP, 1 EC). TIAP complication rate does not seem to be influenced by factors such as low weight, massive blood product transfusion or prolonged parenteral nutrition. In 8 children, TIAP were used for collection of hematopoietic progenitor cells. Conclusions. – The use of TIAPs appears as a safe and effective option for HDC. We found more mechanical complications but less infectious complications with TIAP than with EC. Nevertheless, results need to be validated prospectively in a larger study cohort. [Copyright &y& Elsevier]

Cisplatin may have additive activity with temozolomide due to ablation of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (MGMT). This phase I/II study determined recommended combination doses using the Continual Reassessment Method, toxicities and antitumour activity in paediatric patients, and evaluated MGMT in peripheral blood mononuclear cells (PBMCs) in order to correlate with haematological toxicity. In total, 39 patients with refractory or recurrent solid tumours (median age approximately 13 years; 14 pretreated with high-dose chemotherapy, craniospinal irradiation, or having bone marrow involvement) were treated with cisplatin, followed the next day by oral temozolomide for 5 days every 4 weeks at dose levels 80 mg m(-2)/150 mg m(-2) day(-1), 80/200, and 100/200, respectively. A total of 38 patients receiving 113 cycles (median 2, range 1-7) were evaluable for toxicity. Dose-limiting toxicity was haematological in all but one case. Treatment-related toxicities were thrombocytopenia, neutropenia, nausea-vomiting, asthenia. Hearing loss was experienced in five patients with prior irradiation to the brain stem or posterior fossa. Partial responses were observed in two malignant glioma, one brain stem glioma, and two neuroblastoma. Median MGMT activity in PBMCs decreased after 5 days of temozolomide treatment: low MGMT activity correlated with increased severity of thrombocytopenia. Cisplatin-temozolomide combinations are well tolerated without additional toxicity to single-agent treatments; the recommended phase II dosage is 80 mg m(-2) cisplatin and 150 mg m(-2) x 5 temozolomide in heavily treated, and 200 mg m(-2) x 5 temozolomide in less-heavily pretreated children. [ABSTRACT FROM AUTHOR]

Neuroblastoma and its benign counterpart, ganglioneuroma, are pediatric neuroblastic tumors arising in the sympathetic nervous system from neural-crest cells. Neuroblastoma, the most common extra-cranial solid tumour during childhood, is unique for its broad spectrum of clinical virulence from spontaneous remission to rapid and fatal progression despite intensive multimodality therapy. To a large extent, outcome could be predicted by the stage of disease and the age at diagnosis. However, a number of molecular events in neuroblastoma tumors, accounting for the variability of outcome and response to therapy, have been identified over the past decades. Among these, MYCN amplification is the most relevant prognostic factor and was the first genetic marker, in paediatric oncology, to be included in clinical strategies as a guide for therapeutic decision. This has allowed the most suitable intensity of therapy to be delivered according to a risk-stratified strategy, from observation to megadose chemotherapy with stem cell transplantation. Recent advances in understanding the biology and genetics of neuroblastoma will ultimately allow to select poor-risk patients for appropriate future biologically based therapies. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

The aim of this study was to analyse the outcome of optic pathway gliomas in 30 children with neurofibromatosis type 1, the indications of treatment, and the follow-up and screening protocol.Patients and methods. – All patients with a minimal two years follow-up (median six years, range two to 19 years), in two multidisciplinary consultations of Saint-Vincent-de-Paul (Paris) and Purpan (Toulouse) hospitals, were included in the study. In our series, we practiced systematic screening MRI in children under six years’ of age or with neuropsychological deficiency that may imply an unreliable ophthalmological examination.Results. – Thirty-seven percent (11 patients) had progressive ophthalmological signs and were treated, and 63 % (19 patients) were not progressive. Our study confirmed that most of optic pathway gliomas were stable during evolution, but rare cases may have bad prognosis.Conclusion. – Our study supported the importance of close ophthalmological follow-up during child-hood for which screening methods are discussed. There is a consensus to limit treatment for patients with progressive ophthalmological symptoms. [ABSTRACT FROM AUTHOR]

Objectifs: Appréhender le vécu de parents et adolescents lors de la fin des traitements oncologiques. Sujets: 15 adolescents âgés de 12 à 18 ans en fin de traitements pour hémopathie maligne et leur parent accompagnateur. Matériel: Nous avons procédé à deux entretiens semi-directifs enregistrés: un auprès de l’adolescent et un auprès du parent. Méthode: Ces dyades ont été rencontrées au sein des services d’oncohématologie pédiatriques de Toulouse, Montpellier et Bordeaux lors du bilan de fin de traitements. Résultats: La perception du risque de récidive est moins manifeste chez l’adolescent que son parent, mais elle reste présente en testant les limites des pédiatres face à leurs demandes d’activités. Demandes qui génèrent par ailleurs des conflits avec les parents très anxieux qui maintiennent une surprotection vis-à-vis de leur adolescent. Une usure physique et psychique est présente chez les parents. Près de la moitié des dyades rencontrées n’est pas rassurée par une prise en charge médicale en ville mais le retour à l’hôpital semble difficile pour l’adolescent. Conclusions: Un accompagnement psychologique auprès des familles en rémission semble nécessaire. Travail soutenu par la SFCe et La Ligue Nationale contre le Cancer. [ABSTRACT FROM AUTHOR]

Objectifs: L’étude de phase II MIITOP évalue l’efficacité d’une double infusion de MIBG I131 associée au topotécan dans le traitement des neuroblastomes réfractaires ou en rechute. Nous rapportons la tolérance de ce traitement chez les 5 premiers patients inclus. Méthode: Une dose de 444 MBq/kg de MIBG I131 est injectée à J1 associée au topotécan de J1 à J5. La dose d’irradiation corporelle (ICT) reçue est mesurée. Une deuxième cure est effectuée à J21 pour obtenir une ICT de 4 Gy. Une réinjection de cellules souches périphériques est réalisée à J31. Résultats: 5 patients ont été traités : 1 neuroblastome métastatique réfractaire et 4 en rechute. La durée médiane d’hospitalisation par cure était de 7 jours. L’ICT médiane totale était de 4,5 Gy. La toxicité hématologique était acceptable (durée médiane de neutropénie grade 4 : 15 jours, de thrombopénie grade 4 : 8 jours). Une élévation isolée de la TSH était observée chez 2 patients. Aucune autre toxicité extra-hématologique n’était observée. 1 CR, 2 SD et 2 PD étaient obtenues. Conclusion: Cette approche permet l’augmentation des doses de MIBGI131 avec une toxicité minimale. La poursuite des inclusions est nécessaire pour en évaluer l’efficacité notamment pour les neuroblastomes métastatiques réfractaires en fin d’induction. [ABSTRACT FROM AUTHOR]

Objectifs: Le neuroblastome (NB) est un cancer pédiatrique avec une grande hétérogénéité clinique. Des nombreuses altérations génétiques récurrentes ont été décrites : une amplification de MYCN associée à un pronostic pauvre, ainsi que des variations de la ploïdie ou des altérations chromosomiques segmentaires (délétions du chromosome 1p, 3p, 4p, 11q ; gain du chromosome 2p, 17q) dont l’importance pronostique reste à être déterminée. Afin d’étudier l’association de ces altérations génétiques entre elles et leur impact pronostique, nous avons entrepris une analyse en CGH-array d’une grande série de NB. Méthodes: 389 échantillons de NB ont été analysés en hybridation génomique comparative (CGH), sur une puce d’ADN à BAC/PAC avec une résolution moyenne de 1Mb. Résultats: L’analyse du profil génomique permet de distinguer 2 différents types d’instabilité génétique : une instabilité numérique et une instabilité segmentaire. L’instabilité numérique est caractérisée par une variation en nombre de chromosomes entiers sans altérations segmentaires (n = 162). Elle est associée à une survie sans progression et une survie globale excellente. L’instabilité segmentaire se caractérise par des translocations chromosomiques déséquilibrées. Elle a été observée dans des tumeurs sans (n = 45) ou avec (n = 97) variations numériques, ou en association avec une amplification de MYCN (n = 67). Ce type génomique est associé à un risque élevé de rechute (p < 0.0001, log-rank test), quel que soit le type de l’altération segmentaire. En analyse multivariée, après prise en compte du type génomique, des altérations génétiques individuelles et des caractéristiques cliniques, un profil génomique de type segmentaire est le marqueur pronostique le plus fort (p < 0.0002). Les autres marqueurs retenus sont l’age (p = 0.022) et le stade (p = 0.06). Conclusion: Dans le NB, un profil génomique de type segmentaire est le marqueur pronostique le plus fort. Ceci souligne l’importance du mécanisme à l’origine des translocations déséquilibrées dans l’oncogenèse du NB. Le typage génomique devra donc être pris en compte pour l’attribution à un groupe de risque et la stratification thérapeutique. Le NB est le premier modèle de l’utilité d’une classification génomique pour une meilleure prise en charge thérapeutique. [Copyright &y& Elsevier]

Le diagnostic de neuroblastome repose souvent sur un syndrome de masse. Plus rarement, un syndrome paranéoplasique constitue le symptôme principal : opsomyoclonie ou diarrhée sécrétoire liée à la synthèse de Vaso-Intestinal Peptide (VIP). Les tumeurs sécrétant du VIP sont considérées d’excellent pronostic. L’évolution occasionnellement défavorable interroge toutefois sur l’homogénéité clinique de ces tumeurs. Nous avons mené une analyse rétrospective des tumeurs neuroblastiques (TN) sécrétant du VIP diagnostiquées en France. Les critères diagnostiques étaient i) une histologie de TN ii) une diarrhée sécrétoire iii) une expression anormale de VIP. Les données cliniques, biochimiques et histologiques ont été analysées. 21 patients répondaient aux critères, sur une période de 1988 à 2006. La diarrhée, fréquemment associée à une hypokaliémie (15/21 patients), précédait le diagnostic tumoral dans 16 cas (vipomes primaires) et apparaissait 1 à 4 mois après le début du traitement chez 5 patients (vipomes secondaires). Tous les vipomes primaires étaient différenciés, 15/16 étaient localisés dont un avec amplification de N-myc. Aucun patient n’a rechuté. Tous les vipomes secondaires étaient de haut risque (4 métastatiques, 2 avec amplification de N-myc). L’histologie mettait en évidence une différenciation tumorale sous chimiothérapie pour 2 tumeurs. Deux tumeurs ont rechuté, dont une conduisant au décès. Pour les 21 vipomes, seule l’exérèse a permis d’arrêter la diarrhée. Les neuroblastomes sécrétant du VIP sont exceptionnels. Les troubles métaboliques associés peuvent mettre en jeu le pronostic vital et doivent encourager à une exérèse tumorale précoce. Deux entités distinctes peuvent être discutées. Les vipomes primaires, localisés, d’emblée différenciant et de pronostic favorable, se distinguent des vipomes secondaires, formes évolutives sous chimiothérapie de certains neuroblastomes plus agressifs. Cette seconde présentation pourrait refléter une modification sous traitement de la biologie tumorale vers la différenciation, dont l’impact pronostique reste à évaluer. [Copyright &y& Elsevier]

Objectifs: La fascéite nécrosante (FN) est une infection grave des tissus mous caractérisée par la nécrose du fascia et de la graisse sous-cutanée dont la mortalité reste importante puisqu’évaluée à plus de 25% par certains auteurs. Entité clinique rare chez l’enfant, sa prise en charge est bien codifiée chez l’adulte. Le but de ce travail est de discuter des différents aspects cliniques, bactériologiques, radiologiques et thérapeutiques de cette pathologie chez l’enfant. Matériel: Il s’agit d’une étude rétrospective de 4 cas de FN pris en charge à l’Hôpital des Enfants de Toulouse. A partir du dossier des malades, nous avons étudié les données démographiques, cliniques, radiologiques et bactériologiques de ces 4 cas de FN. Résultats: Il s’agit de 2 filles et 2 garçons d’âge moyen de 5ans (6 mois à 8 ans). Dans 3 des 4 cas, il existait une pathologie hématologique sous-jacente ; pour le dernier cas, aucune cause générale n’a été retrouvée. Les lésions sont réparties au niveau du tronc pour 3 enfants et au niveau du membre pelvien pour le dernier. Les résultats bactériologiques retrouvaient un Pseudomonas Aeruginosa dans 2 cas sur 4 associé à un Clostridium Perfringens dans un cas, un Streptocoque A dans un cas. La prise en charge médico-chirurgicale, dans tous les cas, a consisté en un parage chirurgical large et précoce associé à une antibiothérapie par voie générale. Aucun décès n’est survenu. Le recul moyen est de 6,5 ans. Conclusion: L’analyse de ces cas nous permet de confirmer l’importance de la prise en charge chirurgicale et médicale précoces ainsi que de la recherche d’une pathologie hématologique sous-jacente. L’analyse de la littérature indique l’intérêt de l’IRM, ou à défaut du scanner, qui permettent d’apprécier l’extension en profondeur. [Copyright &y& Elsevier]