[Child and adolescent: a challenge for society, a priority for health system]. / L'enfant et l'adolescent: un enjeu de société, une priorité du système de santé.

The objective of this article is to present the issue of the official report committed by the French Minister of Health, with the aim to improve the health care of children and adolescents, taking into account the present knowledge of their health status, the multiplicity and the compartmentalization of professionals and health structures. The statement speaks for the activation of a specific Commission in charge of a health care program (physical, mental, social health) designed for young people (0 to 18 years). Under the auspices of the Ministry of Health, it should get together all the professionals with practical experience, representative parents and associations, decision makers and financial raisers. Moreover, relationships have to be reinforced, if not established, with the other concerned ministries and between the national and regional levels.

Household exposure to pesticides and risk of childhood acute leukaemia.

OBJECTIVES: To investigate the relation between childhood acute leukaemia and household exposure to pesticides. METHODS: The study included 280 incident cases of acute leukaemia and 288 controls frequency matched on gender, age, hospital, and ethnic origin. The data were obtained from standardised face to face interviews of the mothers with detailed questions on parental occupational history, home and garden insecticide use, and insecticidal treatment of pediculosis. Odds ratios were estimated using unconditional regression models including the stratification variables parental socioeconomic status and housing characteristics. RESULTS: Acute leukaemia was observed to be significantly associated with maternal home insecticide use during pregnancy (OR = 1.8, 95% CI 1.2 to 2.8) and during childhood (OR = 1.7, 95% CI 1.1 to 2.4), with garden insecticide use (OR = 2.4, 95% CI 1.3 to 4.3), and fungicide use (OR = 2.5, 95% CI 1.0 to 6.2) during childhood. Insecticidal shampoo treatment of pediculosis was also associated with childhood acute leukaemia (OR = 1.9, 95% CI 1.2 to 3.3). CONCLUSION: The results reported herein support the hypothesis that various types of insecticide exposure may be a risk factor for childhood acute leukaemia. The observed association with insecticidal shampoo treatment of pediculosis, which has never been investigated before, requires further study.

A lack of neuroblastoma in Down syndrome: a study from 11 European countries.

An epidemiological investigation in 11 European countries comprising a total childhood population of 54.1 million children and using 8 separate data sources was conducted to evaluate the occurrence of neuroblastoma in Down syndrome (DS). No cases of DS were detected among 6724 infants and children with neuroblastoma, although more than five were expected. This highly significant result (P = 0.0045 according to the Poisson test) is consistent with data in the literature, which contains only two poorly detailed cases in epidemiological studies and one ganglioneuroma in a DS mosaic patient. Like other tumors, such as leukemias, testicular germ cell tumors and lymphomas are in excess in DS patients; the lack of neuroblastomas does not reflect a general decreased incidence of cancer but rather a specific underrepresentation of this precise tumor. S-100 b protein, the gene for which maps to the long arm of chromosome 21, (a) is overproduced in DS patients, (b) produces growth inhibition and differentiation of neural cells in vitro, (c) is abundant in good-prognosis neuroblastomas, and (d) has been shown to induce growth inhibition and differentiation and cell death in several human and murine neuroblastoma cell lines and could be responsible for this variation. Additional epidemiological and experimental studies are warranted to confirm our interpretation of these data.

Etoposide in relapsed or refractory Wilms' tumor: a phase II study by the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group.

PURPOSE: Despite a high cure rate of approximately 85% in Wilms' tumor by multimodality therapy, to date only four drugs are known to be active against such tumors. There is a clear need for new active drugs. PATIENTS AND METHODS: Thirty-one patients with relapsed or refractory Wilms' tumor from three British and 14 French centers were treated with intravenous (IV) etoposide 200 mg/m2 daily for 5 days. Original stage was I (n = 3), II (n = 7), III (n = 9), IV (n = 10), and V (n = 2). Prior chemotherapy, administered initially or at relapse, included vincristine and dactinomycin in all cases, doxorubicin or epirubicin in 30, and ifosfamide in 20. Sites of relapse or resistant disease were lung in 13, abdomen or pelvis in six, liver in one, and multiple in 11. When entered onto the study, 12 patients were in first relapse, 10 in second relapse, and four in third or more relapse. Five had never obtained a complete remission. All but two (progressing) patients received two courses of etoposide, the second course being administered at day 21. RESULTS: A complete response (CR) was documented in two patients, partial response (PR) in 11, stable disease in 10, and progressive disease (PD) in eight. The duration of response could not be evaluated, because all responding patients were subsequently treated with multimodality therapy. The major toxicities observed were neutropenia and thrombocytopenia, but most patients had been heavily pretreated. No toxic death clearly associated with etoposide was noted. CONCLUSION: It is concluded that etoposide in this schedule is an active agent in Wilms' tumor and should be considered for inclusion in regimens for high-risk patients, such as those with metastatic disease at diagnosis and those who relapse after multiagent chemotherapy.

Conservative treatment for girls with nonmetastatic rhabdomyosarcoma of the genital tract: A report from the Study Committee of the International Society of Pediatric Oncology.

PURPOSE: To report the results of a conservative multimodal approach in girls with nonmetastatic rhabdomyosarcoma (RMS) of the genital tract, treated in International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumors 84 and 89 protocols. PATIENTS AND METHODS: From 1984 to 1994, 38 girls with RMS of the genital tract (vulva, vagina, uterus) were treated in SIOP protocols. With the exception of patients with rare small tumors, which were resected at the start of the studies, all patients received initial chemotherapy (CHT) (ifosfamide, vincristine, and actinomycin D). Local treatment including surgery, brachytherapy (BT), and external-beam radiotherapy (ERT) was given only to girls who did not achieve complete remission (CR) with CHT or who subsequently relapsed. RESULTS: The primary tumor originated in the vulva or vagina in 27 girls and in the uterus in 11. The overall survival rate (+/- SE) was 91% +/- 6% at 5 years, and the event-free survival rate was 78% +/- 7%. At a median follow-up of 5 years, 30 girls were alive and in first CR and five were alive and in second CR. Four patients treated with complete resection of the tumor at diagnosis received less CHT. Thirteen patients were treated with CHT alone. In 17 patients, local treatment was necessary to achieve complete local control, for a residual mass after initial CHT (10 patients), for viable tumor on biopsy (three patients), or for local relapse (four patients). The local treatment used was radiotherapy (RT) (ERT in three patients, BT in seven), radical surgery with uterine ablation (three patients), RT and radical surgery (three patients), and conservative surgery with RT (one patient). CONCLUSION: Girls with nonmetastatic RMS of the genital tract have an excellent prognosis. We found no difference in outcome between uterine and vulvovaginal RMS. Local treatment does not seem necessary in patients who have a complete response to CHT. When a local treatment is needed, BT may be an alternative to radical surgery or ERT.

N-Myc gene amplification is a major prognostic factor in localized neuroblastoma: results of the French NBL 90 study. Neuroblastoma Study Group of the Société Francaise d'Oncologie Pédiatrique.

PURPOSE: To assess the relevance of N-Myc gene amplification (NMA) as a prognostic factor in localized neuroblastoma (NB) and to evaluate whether less intensive adjuvant treatment is advisable in infants without NMA. PATIENTS AND METHODS: Assessment of NBs included clinical and imaging data to allow tumor-node-metastasis (TNM) staging, biologic determinations (N-Myc gene analysis), and standard histology and work-up to eliminate metastatic spread (metaiodobenzylguanidine [MIBG] scintigraphy and extensive bone marrow staging). Resectability was defined according to imaging findings. Chemotherapy was indicated in children older than 1 year at diagnosis who had postoperative residual disease or lymph node (LN) involvement, in infants with NMA, or as primary treatment in children with an unresectable NB, including dumbbell tumors. Radiotherapy was recommended in children older than 1 who presented with persistent gross residual disease at the end of therapy. RESULTS: Between 1990 and 1994, 316 consecutive children who presented with a localized NB were registered in the NBL 90 study. The median age was 12 months, and 42 patients had dumbbell tumors (13%). NMA was found in 22 of 225 assessable children (10%) and correlated with adverse prognostic indicators such as age older than 1 year, an abdominal primary tumor, a large tumor (T3), and unresectability. Among 186 children who had primary excision, five died of surgery-related complications. Primary chemotherapy was given to 130 patients, which allowed removal of the tumor in all but four. The 5-year overall survival (OS) and event-free survival (EFS) rates were, respectively, 91% and 84% with a median follow-up time of 36 months. The outcome of infants and older children was similar (P = .2). EFS of patients with resectable tumors was slightly better than with unresectable primary tumors (EFS, 89% v 78%; P = .02). In dumbbell NBs, neurologic recovery was achieved in 74% of cases that presented with symptoms, and initial laminectomy was avoided in 75% of children. In a univariate analysis, large tumors, high neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels, positive LNs, macroscopic residue, and NMA adversely influenced outcome. In the multivariate analysis, NMA was the most powerful unfavorable predictive indicator: OS and EFS rates for these children were 36% and 32%, compared with 98% and 90% in nonamplified tumors (P < .001). CONCLUSION: Our data confirm the overall good prognosis of localized NBs, even when unresectable. NMA is the most relevant adverse prognostic factor in localized NBs, and more intensive treatment should be investigated in these patients. Prospective studies of other biologic factors are warranted to tailor therapy more accurately. The EFS of children who underwent primary surgery was excellent, and further justifies elimination of adjuvant treatment provided they have no NMA. Despite the elimination of postoperative therapy, infants with non-NMA tumors have an excellent outcome, which suggests that initial chemotherapy can be further reduced in case of unresectable NBs.

[Lorraine childhood cancer registry: incidence, survival 1983-1999]. / Le registre lorrain des cancers de l'enfant: incidence, survie 1983-1999.

BACKGROUND: Cancer in childhood account for less than 1% of all cancers and for the second most important cause of death for children aged less than 15 years in France, injuries being the leading cause. Compared to adult cancers, childhood cancers' particularities justify to create pediatric registries. The first French population-based registry was created in Lorraine in 1983. The incidence and survival results from a 17 year-period are presented. METHODS: In Lorraine region, all children (0-14 years) with cancer diagnosed between 1983 and 1999 were included. Crude, age-standardized (world population) and cumulative incidence rates were calculated just as overall, specific-disease and event-free survival rates, using Kaplan-Meier methods. RESULTS: With 1086 registered cases, the crude incidence rate per million children is 132.4, the age-standardized incidence rate per million is 137.5; 1 out of every 500 children will develop cancer before the age of 15 years. The incidence of all cancers combined is slightly higher in males than in females with a M/F ratio of 1.13. For this 17 years-period, no trend in childhood cancer incidence is observed. The main cancer groups are leukemia (30.7%), brain and spinal tumors (23.2%) and lymphomas (12.9%), sympathetic nervous system tumors (7.4%), soft-tissue sarcomas (6.1%), renal tumors (5.2%), and bone tumors (5.0%). Five-year specific survival rates for all cancers combined is 71.4% [95% CI: 68.5-74.3]. The prognosis is significatively worse for the<1 year age group (55%) and for some histologic types: brain stem gliomas (27%), hepatic tumors (43%), osteosarcomas (57%), neuroblastomas (65%), rhabdomyosarcomas (55%). DISCUSSION: Relative distribution of histologic groups, incidence and survival rates observed in Lorraine registry are compatible with the general pattern in the European Union cancer registries. The lack of significative trend in incidence unlike others country may be explained by too small numbers. CONCLUSION: The acquired experience in developping this regional registry allowed us to create a national registry of childhood solid tumors and contribute to valid national data.

European experience in the treatment of hyperuricemia.

The nonrecombinant form of urate oxidase has been routinely used in France since 1975 as standard practice in the initial management of non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL), and for prevention of tumor lysis syndrome (TLS). A retrospective study was performed to evaluate the frequency of metabolic complications and dialysis in 410 patients with B-cell stage III and IV NHL and L-3 ALL treated in France according to the LMB89 protocol, and to compare these results to those of other series of patients treated without urate oxidase. Of the 57 patients treated at Institut Gustave-Roussy, only five had metabolic complications occurring in the first cycle of chemotherapy. Two patients (3.5%) underwent dialysis: one because of oliguria, the second for preventive reasons. In all the other cases, metabolic problems were successfully resolved or prevented, using nonrecombinant urate oxidase (Uricozyme, Sanofi-Sythélabo, Inc, Paris, France) in combination with hyperhydration. Nonrecombinant urate oxidase is generally well tolerated. However, allergic reactions may occur, with rates varying from 0% to 4.5%. In addition, the extraction technology used to produce the product is limited by a low yield. A recombinant form of urate oxidase (rasburicase) was therefore developed. European clinical development results indicate that this agent produces a sharp and consistent decrease in uric acid levels in patients undergoing cytoreductive therapy. Additionally, there is a very low incidence of anaphylaxis. Studies have demonstrated the efficacy of urate oxidase in lowering uric acid levels, preventing hyperuricemia after the initiation of cytoreductive therapy, and preserving renal function in patients with B-cell advanced stage NHL and ALL.

Loss of chromosome 1p may have a prognostic value in localised neuroblastoma: results of the French NBL 90 Study. Neuroblastoma Study Group of the Société Française d'Oncologie Pédiatrique (SFOP).

Between March 1990 and December 1994, 316 consecutive children with localised neuroblastoma were registered in the French NBL 90 study. In addition to the assessment of a new chemotherapy regimen in unresectable neuroblastoma, we evaluated the prognostic significance of MYCN amplification and loss of the short arm of chromosome 1 (LOH1p). MYCN was found in 22/225 children (10%) and associated with unfavourable clinical features such as age at diagnosis > 1 year and large and unresectable tumours. LOH1p was observed in 9/91 patients (10%), of whom some had favourable prognostic factors such as age at diagnosis < 1 year (n = 4), INSS stage 1 or 2 (n = 3) and no MYCN amplification (n = 4). Overall survival (OS) and event-free survival (EFS) were, respectively, 56% and 22% (median follow-up: 36 months) for children with LOH1p compared with 97% and 94% for those without (log-rank = 10(-8)). All except 1 of the 5 children with MYCN amplification and LOH1p relapsed and ultimately died of the disease. Among the 4 with LOH1p and no MYCN amplification, recurrence occurred in 3 (2 local, 1 metastatic), all alive in second remission after salvage therapy (12-19 months after the relapse). In multivariate analysis, LOH1p was the strongest prognostic indicator for subsequent relapse. LOH1p appears more discriminant than MYCN amplification for predicting the risk of recurrence in children with localised neuroblastoma. However, its analysis was possible in only 30% of our patients and its final impact on survival should be confirmed in larger, prospective studies in order to stratify subsequent treatment.

Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology: MMT84.

The second International Society of Paediatric Oncology (SIOP) study for rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; and (2) to reduce the late effects from therapy by restricting the indications for surgery and/or radiotherapy after good response to initial chemotherapy. A further aim was to investigate the role of high-dose chemotherapy in young patients with parameningeal primary tumours. 186 previously untreated eligible patients entered the study. Patients with completely resected primary tumour received three courses of IVA (ifosfamide, vincristine and actinomycin D). Patients with incompletely resected tumour received six to 10 courses of IVA according to stage. Patients achieving complete remission with chemotherapy alone did not usually receive radiotherapy or undergo extensive surgery, but patients remaining in partial remission received local therapy with surgery and/or radiotherapy. Only patients over 5 years of age with parameningeal disease and patients over 12 years with tumours at any site were given systematic irradiation. Complete remission was achieved in 91% (170/186) of all patients. With a median follow-up of 8 years, the 5-year overall survival was 68% (+/- 3% standard error of the mean (SEM) and the 5-year event-free survival 53% (+/- 4% SEM). These results show an improvement over previous SIOP study (RMS75) in which survival was 52% and event-free survival was 47%. Among the 54 patients who exhibited isolated local relapse, 35% (19/54) survived in further remission longer than 2 years after retreatment, including local therapy (surgery +/- radiotherapy). Analysis of the overall burden of therapy received by all surviving children (including primary treatment and treatment for relapse if required) showed that 24% (28/116) were treated by limited surgery followed by three courses of IVA, 29% (34/116) were treated by chemotherapy alone (after initial biopsy) and 13% (15/116) received chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensive local therapy defined as radical wide field radiotherapy or radical surgery or both. Compared with the results obtained in the previous SIOP study, treatment in MMT84 was based on response to initial chemotherapy and, despite an overall reduction of the use of local therapy, significantly improved survival for patients with non-metastatic disease. This trial, also for the first time, provides evidence that retreatment after local relapse can achieve long-term second remissions.

A tumor profile in Down syndrome.

We conducted a review of cancers in Down syndrome (DS), because solid tumors are poorly understood in DS. Cancers are in excess in this condition because of the 20-fold excess of leukemias, whereas malignant solid tumors seem to be globally underrepresented as compared with those in the general population. However, among these tumors, some tumors are in excess: lymphomas, gonadal and extragonadal germ cell tumors, and possibly retinoblastomas and pancreatic and bone tumors. Neoplasms in excess are seen earlier, sometimes in fetal life (leukemias and testicular germ cell tumors) or neonatally (leukemias and lymphoma) and affect mainly male subjects. There seems to exist an excess of rare karyotypes. Other tumors are underrepresented, particularly neuroblastomas and nephroblastomas, in young children, and perhaps common epithelial tumors in adults. These observations suggest that DS has a particular tumor profile, with some tissues more affected by malignant diseases (hematopoietic tissue and germ cells) and others that seem to be protected (central and peripheral nervous system, renal tissue, and epithelial tissues). The mechanism is mainly genetic, but differences in exposure to exogenous agents compared with the general population must be kept in mind. These findings are of interest for the management of these patients and early detection of cancers. Better knowledge of this tumor profile could help us to understand the mechanisms of carcinogenesis and should be compared to the current knowledge of genes on chromosome 21.

Serum beta-carotene and antioxidant micronutrients in children with cancer. The 'Cancer in Children and Antioxidant Micronutrients' French Study Group.

Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and selenium for 418 children with newly diagnosed malignancy were compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited in 1986-1989. Age- and sex-adjusted serum concentrations of retinol, beta-carotene and alpha-tocopherol were significantly inversely associated with cancer. In similar models, the odds ratio (OR) comparing the highest with the lowest quintile was 2.06 (95% confidence interval [CI] 1.40-3.02) for retinol, 3.87 (95% CI: 2.54-5.90) for beta-carotene, 2.15 (95% CI: 1.48-3.10) for alpha-tocopherol, 1.29 (95% CI: 0.75-2.23) for selenium, and 1.94 (95% CI: 1.17-2.23) for zinc. The cancer sites that were associated with serum beta-carotene were, in general, leukaemia, lymphoma, central nervous system, bone and renal tumours. Moreover, leukaemia was associated with low mean serum levels of retinol, selenium and zinc. Subjects with lymphoma, bone and renal tumours also had lower mean retinol and alpha-tocopherol levels than controls. Brain tumour patients had low vitamin E levels. Low serum values of antioxidant vitamins were associated with childhood neoplasm occurrence. Some site-specific effect was reported. Low peripheral nutrient levels are not considered as cancer promoters but rather as an impairment of the body's defence mechanism occurring during the cancer-related metabolic and nutritional disturbances and inflammation processes.

Prophylactic use of ganciclovir for allogeneic bone marrow transplant recipients.

Ganciclovir which has proved effective in the treatment of cytomegalovirus (CMV) infection was given prophylactically to 40 bone marrow transplant (BMT) patients pre and post-transplant in seropositive patients and post-transplant in seronegative patients with a seropositive donor. All patients were transfused with screened blood products and 33 received CMV hyperimmune globulin. They were compared with an historical control group consisting of 39 patients who had received significantly more unscreened blood products (p = 0.01) and less HLA-mismatched marrow transplants (p = 0.05). Toxicity of ganciclovir was hematological-neutropenia was responsible for cessation of the drug in seven patients and transfusion requirements were significantly higher in the ganciclovir group. Non-hematological toxicity did not occur in any patient. Only one patient (2.5%) experienced symptomatic CMV infection and no patient developed CMV pneumonitis. In contrast, in the control group, 23 (59%) patients had clinical symptoms of CMV infection (p < 0.0001) and 4 (10%) experienced CMV pneumonitis (p < 0.01). Ganciclovir significantly reduced the incidence of positive CMV antigenemia (7.5% in the treated group vs 72% in the control group; p < 0.01). However, ganciclovir delivery did not result in an improved overall survival due to a higher rate of regimen-related deaths and chronic GVHD mostly in patients transplanted from an HLA-mismatched donor. The prophylactic administration of ganciclovir abrogates CMV pneumonitis and considerably reduces the incidence of CMV infection in BM recipients at high risk of developing this disease after transplantation.

Bone marrow transplantation as treatment for X-linked immunodeficiency with hyper-IgM.

We report a 10-year-old boy with a severe form of immunodeficiency with hyper-IgM who underwent successful bone marrow transplantation with his HLA-matched sister as donor. Busulfan (20 mg/kg) and cyclophosphamide (200 mg/kg) were used as conditioning. The post-transplant course was uneventful. He is alive 25 months later with full hematological and immunological reconstitution.

Incidence of childhood leukaemia and non-Hodgkin's lymphoma in France: National Registry of Childhood Leukaemia and Lymphoma, 1990-1999.

The French National Registry of Childhood Leukaemia and Lymphoma (NRCL) covers the whole French mainland population aged less than 15 years (approximately 11 million children) for all childhood haematopoietic tumours since 1 January 1990, except Hodgkin's disease, which has been registered since 1 January 1999. During the period from 1990 to 1999, 5757 cases of leukaemia, lymphoma and myelodysplastic syndrome were registered in the NRCL, with an average of 2.5 sources per case. The age-standardized incidence rates per million per year were 43.1 for leukaemia (34.3 for acute lymphoblastic leukaemia, 7.1 for acute myeloblastic leukaemia, 0.6 for chronic myeloid leukaemia and 0.5 for chronic myelomonocytic leukaemia), 8.9 for non-Hodgkin's lymphomas and 6.7 for Hodgkin's disease. Down's syndrome was present in 110 cases of acute leukaemia (2.5%) and three cases of non-Hodgkin's lymphoma (0.3%). The incidence of acute lymphoblastic leukaemia showed a typical peak at age 2 years for girls and 3 years for boys. The incidence rates of leukaemia and non-Hodgkin's lymphoma did not show any temporal trends over the 10 year period.

The French version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.

Treatment of Langerhans-cell histiocytosis in children. Experience at the Children's Hospital of Nancy.

Forty children who had Langerhans-cell histiocytosis were followed for an average of six years (range, excluding patients who died of the disease, two to fifteen years). The patients were divided into two diagnostic groups: those who had localized disease (involving one bone or more only) and those who had multifocal disease (an osseous lesion and a soft-tissue mass, a skin rash, diabetes insipidus, or generalized disease). Methods of treatment included curettage, bone-grafting, chemotherapy, local or systemic corticosteroids, and radiotherapy. Nineteen of the thirty patients who had localized disease had a complete response to the therapy, four had a partial response, and seven had no response. Twenty-one of these thirty patients had not had a recurrence by the time of the latest follow-up examination; nine had a local recurrence within four years after the initial therapy but had no additional recurrences after treatment of the local recurrence. No recurrence occurred more than four years after the time that the initial diagnosis had been made. Five of the ten patients who had multifocal disease had a complete response to the therapy, two had a partial response, and three had no response. Six patients had a recurrence; four did not. Two patients died of the disease. As a result of this study, we recommend the avoidance of intensive measures of treatment, if possible, and we advise long-term follow-up of these patients.

Acute childhood leukaemia and environmental exposure to potential sources of benzene and other hydrocarbons; a case-control study.

AIM: To analyse the association between potential environmental exposure to hydrocarbons and the risk of acute childhood leukaemia. METHODS: A hospital based multicentre case control study, stratified on centre, age, and sex, with 280 leukaemia cases and 285 controls was carried out. Data were collected by a standardised interview of the mothers. RESULTS: No clear association was seen between maternal occupational exposure to hydrocarbons during pregnancy and leukaemia, or between residential traffic density and leukaemia. There was an association between dwellings neighbouring a petrol station or a repair garage during childhood and the risk of childhood leukaemia (OR 4.0, 95% CI 1.5 to 10.3), with a duration trend. The association, which appeared particularly strong for acute non-lymphocytic leukaemia (OR 7.7, 95% CI 1.7 to 34.3), was not altered by adjustment for potential confounding factors. CONCLUSIONS: Results showed an association between acute childhood leukaemia and dwellings neighbouring auto repair garages and petrol stations, which are benzene emitting sources. These findings could be due to chance, although the strength of the association and the duration trend are arguments for a causal association.

[Systemic chemotherapy with conventional doses for brain tumors in children: phase II trials]. / Chimiothérapie systémique à dose conventionnelle des tumeurs cérébrales de l'enfant: les essais de phase II.

The analysis of Phase II trials with regard to brain tumors in children, aiming to test the activity of 1 drug or a combination of drugs is not easy, due to the following reasons: poor selection of patients (clinical and pathological heterogeneity), not always rational choice of the drugs and mostly, variability of the criteria and the methods used to assess the tumor response. When using a single drug, the current most efficient agents seem to be: cisplatinum, carboplatin, cyclophosphamide and etoposide, while nitroso-ureas have not been strictly studied. When using polychemotherapy, the best results have been obtained with the "8 drugs in 1 d" regimen. The most chemo-sensitive tumors are: medulloblastomas, primitive neurectodermal tumors, pinealoblastomas; high grade ependymomas and astrocytomas have been studied less in children than in adults. Present and future strict organisation of Phase II trials in brain tumors is compulsory in order to select the active agents, and to establish the best modalities of administration. The need to assess chemotherapy not only in refractory or relapsing patients, but also at diagnosis in high-risk patients is emphasized (after incomplete surgery and before radiotherapy).

[Histological and immunohistochemical diagnosis of bone marrow metastases of neuroblastomas]. / Diagnostic histologique et immunohistochimique des métastases ostéomédullaires des neuroblastomes.

A retrospective, morphological and immunochemical study was performed on 60 bone marrow biopsies (BOM) and 12 tumor specimens surgically excised, from 9 patients with neuroblastoma (NB). Immunochemistry concerned "neuron-specific enolase" (NSE), chromogranin A (CGA) and synaptophysin (SP). The results of immunochemical stains and the study of reticulin network on the argentic stain were compared to the results of morphological evaluation on the routine stain. NSE, CGA and SP staining of tumor cells (part or all of them) was obtained from all surgical specimens. 17/75 BOM (20%) were discarded because of poor material. NB cells were observed in 24 BOM from 3 patients. Tumor cells formed large strands (1 patient) or nests (2 patients) associated with segregated cells. Diagnosis of metastatic BM involvement was negative or doubtful for 6 BOM (3 obtained at the same time, 2 patients), in which NB cells were clearly demonstrated by immunochemical staining of NSE and/or CGA. Reticulin and/or collagen myelofibrosis was present in 32/35 BOM from the 3 patients metastatic in bone marrow (BM+) even if NB cells could not be demonstrated in these samples.