Neuroblastoma: validation of the INRG classification system in a small series.

PURPOSE: In 2009, the International Neuroblastoma Risk Group (INRG) published a new classification system of the childhood neuroblastic tumors. In this work, we present the results of the application of this new classification system in our patients. METHODS/PATIENTS: We conducted a retrospective analysis of the patients diagnosed with a neuroblastic tumor in our center in the last 20 years. We classified them according to the new classification and performed a survival analysis based on the Kaplan-Meier method and Mantel-Cox test. RESULTS: The five-year event-free survival (5-year EFS) was 95.8, 80.8, 50 and 45.9% for the very low, low, intermediate and high-risk groups. Mantel-Cox test showed statistically significant differences between these risk groups (p = 0.002). CONCLUSION: The 5-year EFS for the different risk groups was similar to the expected by the INRG. Therefore, this classification allows us to predict the evolution of this tumor and apply the correct intensity of treatment.

[Analysis of small areas of pediatric cancer in the municipality of Murcia (Spain)]. / Análisis en áreas pequeñas del cáncer pediátrico en el municipio de Murcia.

INTRODUCTION: Occasionally, primary care pediatricians notice the presence of small clusters of pediatric cancer (PC), but are often frustrated by the findings after statistical analysis. The study of small areas in spatial epidemiology has led to advances in identifying clusters and the environmental risk factors involved. The purpose of this study was to describe the PC incidence and the spatial distribution at the minimum level of disaggregation possible in Murcia, presenting the first urban municipality map of PC in Spain. MATERIALS AND METHODS: A population-based descriptive study was conducted on the PC cases diagnosed in children younger than 15 years, between 1998 and 2013 in the municipality of Murcia. Cases were classified by sex, age group, and tumor type. Coordinates of home addresses at the time of diagnosis were assigned to each case, and spatial and spatio-temporal analyses were carried out at the level of census tracts, using FleXScan and SatScan. RESULTS: A total of 155 cases of PC were diagnosed during this period. The overall incidence of PC (138/10(6) of children under the age of 15) and the incidence for individual tumor types were within the expected ranges for Europe. A spatio-temporal cluster of Hodgkin lymphoma was identified. CONCLUSIONS: Small area analysis of PC cases may be a useful tool for the identification of PC clusters, which would allow for the generation of hypotheses regarding disease etiology, as well as developing urban models for environmental surveillance of PC.

[Long-term follow up of childhood cancer survivors in the Murcia Region: preferences and attitudes of Primary Care professionals]. / Programa de largo seguimiento de supervivientes de cáncer pediátrico en la Región de Murcia: preferencias y actitudes de los profesionales de Atención Primaria.

OBJECTIVE: To assess attitudes, beliefs and knowledge of primary medical care professionals as regards the follow-up of Childhood Cancer Survivors (CCS) and the introduction of a Long-Term Follow-Up Program for Childhood Cancer Survivors in the Region of Murcia (PLASESCAP-MUR). MATERIAL AND METHODS: Descriptive cross-sectional study using a structured, self-administered questionnaire. These questionnaires were sent to all primary medical care professionals in Murcia Health District 1. RESULTS: Response rate of 58% (100/172), with 71% and 22% being family physicians and pediatricians, respectively, of whom 49% provided medical care to a CCS in the last 5 years, with 84% reporting that they never or rarely received a detailed report of overall assessment of the survivor. More than 75% found that access to detailed follow-up information was quite or very useful; 95% prefer to consult experts when providing medical care to survivors, and 80% believe that improving the quality of the environment may decrease the morbidity and mortality of the survivors. A statistically significant relationship was found between the length of practicing medicine and the perception of the importance of environmental factors. CONCLUSIONS: It seems to be important to increase the training of primary care professionals for the long-term follow-up of CCS, as well as having the detailed information through a personalized long-term follow-up of each survivor. PLASESCAP-MUR offers an integrated follow-up to CCS in a model of shared care between Long Term Monitoring Units and Primary Care Units.

[Update on L-asparaginase treatment in paediatrics]. / Actualización del tratamiento con L-asparraginasa en Pediatría.

L-asparaginase (L-ASP) is one of the cornerstones of the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma. It is an enzyme of bacterial origin capable of transforming L-asparagine to aspartic acid. The extracellular depletion of L-asparagine inhibits protein synthesis in lymphoblasts, inducing their apoptosis. Numerous studies have demonstrated that treatment with L-ASP improves survival of patients, but there are clear differences in the characteristics of the three currently available formulations. This article reviews the dosage, activity and side effects of the two L-ASP derived from Escherichia coli (native and pegylated), and the one derived from Erwinia chrysanthemi (Erwinia ASP). Despite its indisputable indication over the past50 years, there are still many points of contention, and its use is still marked by the side effects of the inhibition of protein synthesis. The short half-life of native forms, and the most frequently used parenteral administration by intramuscular injections, affects the quality of life of the patients. Therefore, recent studies claim to evaluate alternatives, such as the formulation of longer half-life pegylated L-ASP, and the use of intravenous formulations. There are encouraging results to date with both preparations. Still, further studies are needed to establish which should be the formulation and frontline indicated route of administration, optimal dosing, and management of adverse effects.

[Environment and paediatric cancer in the Region of Murcia (Spain): integrating clinical and environmental history in a geographic information system]. / Medio ambiente y cáncer pediátrico en la Región de Murcia (España): integrando la historia clínica medioambiental en un sistema de información geográfica.

INTRODUCTION: Environment and Paediatric Cancer (PC) in the Region of Murcia (RM) is an on-going research project that has the following aims: to collect a careful paediatric environmental history (PEH) and to use geographical information systems (GIS) to map the incidence and analyze the geographic distribution of the PC incidence in the RM. The objectives are to present the methodology used for the collection and processing of data and disseminate initial results on the spatial and temporal incidence of PC in the RM (Spain). MATERIAL AND METHODS: A descriptive and georeference study of all PC cases under 15 years, diagnosed from 1 January 1998 to December 31, 2009. Three postal addresses were assigned to each case, residence during pregnancy, postnatal, and at the time of diagnosis. Other variables such as sex, date of birth, date of diagnosis, and histopathology classification were collected. RESULTS: No increase was observed in the trend of incidence of PC. The crude annual incidence rate was 14.3 cases per 100,000 children under 15 years. The standardised incidence ratio was higher in the north-west of the RM. Before diagnosis, 30% of cases had a different postal address than during the pregnancy. CONCLUSIONS: Integrating the spatial and temporal information through the PEH in a GIS should allow the identification and study of space-time clusters through an environmental monitoring system in order to know the importance of associated risk factors.

[GATA1 analysis in myeloproliferative disorders associated to trisomy 21]. / Análisis de GATA1 en los trastornos mieloproliferativos asociados a la trisomía 21.

INTRODUCTION: Neonatal transient myeloproliferative disorder and acute megakaryoblastic leukaemia of Down syndrome are considered different manifestations of the same disease. In most cases, transient myeloproliferative disorders require no treatment, while acute megakaryoblastic leukaemia of Down's syndrome is characterised by an increased sensitivity to chemotherapy and its treatment should be adapted with a reduction in dose intensity. Both entities share specific mutations at exón 2 of the transcription factor GATA1. PATIENTS AND METHODS: We analysed biological features and GATA1 mutations in 4 patients with transient abnormal myelopoiesis (2) and acute megakaryoblastic leukaemia (2) including one phenotypically normal trisomy 21 mosaicism. We found abnormal GATA1 mutated clones in each case, and a specific point mutation at exón 2 was detected in three cases. Given the heterogeneous phenotype of megakaryoblastic blasts and the low percentage of blasts at presentation, the recognition of GATA1 mutations was helpful for diagnosis. In addition, molecular remission was established in 2 patients after subsequent normal mutational GATA1 analysis. CONCLUSIONS: We conclude that GATA1 mutational study is a useful tool for the diagnosis and management of trisomy 21 associated myeloproliferative disorders.

[Neonatal tumours and congenital malformations]. / Tumores neonatales y malformaciones congénitas.

INTRODUCTION: The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. OBJECTIVES: First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. MATERIALS AND METHOD: Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". RESULTS: 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data exist on the neonatal period and the majority are from medical institutions registers. The prevalence varies from 15 to 31.6%. To explain this association, the hypotheses are based on prenatal exposures (preconceptional and transplacental exposure), to mutagenic and carcinogenic risk factors. CONCLUSIONS: Neonatal tumours are more often associated to congenital abnormalities than other pediatric cancers. The inclusion and classification criteria needs to be unified to better understand the association between the neonatal tumours and congenital abnormalities. The environmental history in all neonatal tumours associated to congenital abnormalities, including the constitutional and environmental risk factors, will help to improve our knowledge of the underlying prenatal mechanisms and to an advance in its prevention.

[Testicular and paratesticular prepuberal tumors: our experience and update on the topic]. / Tumores testiculares y paratesticulares prepuberales. Experiencia en nuestro centro y revisión de la literatura.

OBJECTIVES: To evaluate the importance of testicular and paratesticular prepubertal tumors in our center and to make an update on the topic. METHODS AND PATIENTS: Data from all patients diagnosed of testicular and paratesticular prepubertal tumors and treated in our pediatric oncology unit from January 1st 1998 to December 31st 2003 have been revised. RESULTS: Seven cases are reported among one hundred and ninety patients (represents 3,68 percent of all treated tumors): five tumors affecting the testis and two cases of paratesticular tumors. Pathology classification was as follows: one yolk sack tumor, one mature teratoma, two nongerminomatous testicular tumors (one Sertoli cell tumor and one unclassifiable), one Burkitt's lymphoma and two paratesticular rhabdomyosarcomas. Primary approach was inguinal radical orchiectomy in all cases except neoadjuvant chemotherapy in the case of lymphoma and partial escrotectomy in one patient previously managed with transcrotal orchiectomy. Rhabdomyosarcoma cases received adjuvant chemotherapy. All patients are alive and well after a follow-up period ranging from 17 to 74 months. CONCLUSIONS: Testicular and paratesticular prepubertal tumors are rare. Except for one patient affected of lymphoma, surgical primary approach have been essential for treatment. The prognoses in this series has been excellent.