Subclassification of B-acute lymphoblastic leukemia according to age, immunophenotype and microenvironment, predicts MRD risk in Mexican children from vulnerable regions.

Introduction: The decisive key to disease-free survival in B-cell precursor acute lymphoblastic leukemia in children, is the combination of diagnostic timeliness and treatment efficacy, guided by accurate patient risk stratification. Implementation of standardized and high-precision diagnostic/prognostic systems is particularly important in the most marginalized geographic areas in Mexico, where high numbers of the pediatric population resides and the highest relapse and early death rates due to acute leukemias are recorded even in those cases diagnosed as standard risk. Methods: By using a multidimensional and integrated analysis of the immunophenotype of leukemic cells, the immunological context and the tumor microenvironment, this study aim to capture the snapshot of acute leukemia at disease debut of a cohort of Mexican children from vulnerable regions in Puebla, Oaxaca and Tlaxcala and its potential use in risk stratification. Results and discussion: Our findings highlight the existence of a distinct profile of ProB-ALL in children older than 10 years, which is associated with a six-fold increase in the risk of developing measurable residual disease (MRD). Along with the absence of CD34+ seminal cells for normal hematopoiesis, this ProB-ALL subtype exhibited several characteristics related to poor prognosis, including the high expression level of myeloid lineage markers such as MPO and CD33, as well as upregulation of CD19, CD34, CD24, CD20 and nuTdT. In contrast, it showed a trend towards decreased expression of CD9, CD81, CD123, CD13, CD15 and CD21. Of note, the mesenchymal stromal cell compartment constituting their leukemic niche in the bone marrow, displayed characteristics of potential suppressive microenvironment, such as the expression of Gal9 and IDO1, and the absence of the chemokine CXCL11. Accordingly, adaptive immunity components were poorly represented. Taken together, our results suggest, for the first time, that a biologically distinct subtype of ProB-ALL emerges in vulnerable adolescents, with a high risk of developing MRD. Rigorous research on potential enhancing factors, environmental or lifestyle, is crucial for its detection and prevention. The use of the reported profile for early risk stratification is suggested.

Management experience of pediatric meningioma in a Mexican reference center.

OBJECTIVE: Determine the histopathological and clinical characteristics of patients diagnosed with meningiomas and to establish the frequency of these tumors in the pediatric population Mexican. Determine the NF1/2 frequency in meningioma pediatric. METHODS: Samples from the histopathology file were reviewed, and from the complete clinical file the following patient data was reviewed: age, gender, diagnosis, diagnosis year, surgical resection, location, tumor size, symptoms, and family background. The frequency of NF1/2 in pediatric meningioma was reviewed in literature. RESULTS: Forty-four de novo cases were collected from pediatric patients; 19 were female patients and 25 males. The most frequent histological subtype was transitional meningioma. Of all the cases, 75% had a supratentorial localization and 20% had an extramedullary intrarachidian localization. Some clinical manifestations included seizures, paresis, headache, and visual disturbances. CONCLUSION: There is a low incidence of meningiomas in the pediatric population, more than 70% are Grade I, and they have supratentorial localization.

Predictors of anthracycline-induced cardiotoxicity in a retro-prolective cohort of children surviving cancer.

INTRODUCTION: Cardiotoxicity is an adverse reaction associated with the use of anthracyclines. OBJECTIVE: To estimate the factors associated with the development of anthracycline cardiotoxicity in pediatric patients surviving cancer. METHOD: Retro-prolective cohort of children diagnosed with cancer and treated with anthracyclines. Baseline echocardiographic determination of ejection fraction (LVEF0) was carried out before the start of treatment and again at 12 months (LVEF1). Demographic characteristics and treatment were obtained from the medical record. A multiple logistic regression (MLR) model was constructed; LVEF1 < 50 % was the dependent variable, which was adjusted for the main confounding variables. RESULTS: Sixty-five patients were included, out of which 36.9 % were females and 56.8 % had a solid tumor. LVEF0 was 74.79 ± 7.3 % and LVEF1, 67.96 ± 6.7 % (p = 0.001); 60 % developed cardiotoxicity. In the MLR, only a cumulative dose > 430 mg was associated with cardiotoxicity (p = 0.001). CONCLUSIONS: In Mexican children, an anthracycline cumulative dose > 430 mg should be avoided in order to prevent cardiotoxicity.

INTRODUCCIÓN: La cardiotoxicidad es una reacción adversa asociada al uso de antraciclinas. OBJETIVO: Estimar los factores asociados al desarrollo de cardiotoxicidad por antraciclinas en pacientes pediátricos supervivientes de cáncer. MÉTODO: Cohorte retroprolectiva de niños con diagnóstico de cáncer tratados con antraciclinas. Se realizó determinación ecocardiográfica basal de la fracción de expulsión (FEVi0) antes del inicio del tratamiento y a los 12 meses (FEVi1). Del expediente se obtuvieron las características demográficas y el tratamiento. Se realizó un modelo de regresión logística múltiple (RLM); la FEVi1 < 50 % fue la variable dependiente, que se ajustó por las principales variables confusoras. RESULTADOS: Se incluyeron 65 pacientes, 36.9 % fue del sexo femenino y 56.8 % presentó un tumor sólido. La FEVi0 fue de 74.79 ± 7.3 % y la FEVi1, de 67.96 ± 6.7 % (p = 0.001); 60 % desarrolló cardiotoxicidad. En la RLM solo la dosis acumulada > 430 mg se asoció a cardiotoxicidad (p = 0.001). CONCLUSIONES: En los niños mexicanos se debe evitar una dosis acumulada > 430 mg de antraciclinas para evitar la cardiotoxicidad.

Factores predictivos de cardiotoxicidad inducida por antraciclinas en una cohorte retroprolectiva de niños supervivientes de cáncer / Predictors of anthracycline-induced cardiotoxicity in a retro-prolective cohort of children surviving cancer

Resumen Introducción: La cardiotoxicidad es una reacción adversa asociada al uso de antraciclinas. Objetivo: Estimar los factores asociados al desarrollo de cardiotoxicidad por antraciclinas en pacientes pediátricos supervivientes de cáncer. Método: Cohorte retroprolectiva de niños con diagnóstico de cáncer tratados con antraciclinas. Se realizó determinación ecocardiográfica basal de la fracción de expulsión (FEVi0) antes del inicio del tratamiento y a los 12 meses (FEVi1). Del expediente se obtuvieron las características demográficas y el tratamiento. Se realizó un modelo de regresión logística múltiple (RLM); la FEVi1 < 50 % fue la variable dependiente, que se ajustó por las principales variables confusoras. Resultados: Se incluyeron 65 pacientes, 36.9 % fue del sexo femenino y 56.8 % presentó un tumor sólido. La FEVi0 fue de 74.79 ± 7.3 % y la FEVi1, de 67.96 ± 6.7 % (p = 0.001); 60 % desarrolló cardiotoxicidad. En la RLM solo la dosis acumulada > 430 mg se asoció a cardiotoxicidad (p = 0.001). Conclusiones: En los niños mexicanos se debe evitar una dosis acumulada > 430 mg de antraciclinas para evitar la cardiotoxicidad.

Abstract Introduction Cardiotoxicity is an adverse reaction associated with the use of anthracyclines. Objective: To estimate the factors associated with the development of anthracycline cardiotoxicity in pediatric patients surviving cancer. Method: Retro-prolective cohort of children diagnosed with cancer and treated with anthracyclines. Baseline echocardiographic determination of ejection fraction (LVEF0) was carried out before the start of treatment and again at 12 months (LVEF1). Demographic characteristics and treatment were obtained from the medical record. A multiple logistic regression (MLR) model was constructed; LVEF1 < 50 % was the dependent variable, which was adjusted for the main confounding variables. Results: Sixty-five patients were included, out of which 36.9 % were females and 56.8 % had a solid tumor. LVEF0 was 74.79 ± 7.3 % and LVEF1, 67.96 ± 6.7 % (p = 0.001); 60 % developed cardiotoxicity. In the MLR, only a cumulative dose > 430 mg was associated with cardiotoxicity (p = 0.001). Conclusions: In Mexican children, an anthracycline cumulative dose > 430 mg should be avoided in order to prevent cardiotoxicity.

Nutritional status and cytokine concentration during chemotherapy in Mexican children: A longitudinal analysis.

OBJECTIVE: The aim of this study was to assess whether the nutritional status of children with cancer is influenced by variations in cytokine concentrations observed during chemotherapy. We also evaluated whether this relationship could be modified by nutritional status at diagnosis and type of cancer. METHODS: Mexican children with lymphoma or solid tumors were evaluated at diagnosis and at 2- and 6-mo follow-up visits. Blood samples were obtained to determine serum prealbumin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, leptin concentrations, and hemoglobin. Children were classified as undernourished (UN) or well nourished (WN), according to prealbumin concentration. The influence of each cytokine on prealbumin concentration was analyzed by time-series regression model. RESULTS: Fifty patients (ages 2-17 y) were enrolled. There were 17 children with lymphomas and 33 with solid tumors. At baseline, 56% were UN and 26% presented anemia; the frequencies of UN children were higher for those with lymphoma than for those with a solid tumor (P = 0.003). By nutritional status, UN children presented lower leptin (P = 0.002) but higher IL-6 concentrations (P = 0.009) than the WN group. Children with lymphoma presented lower prealbumin (P = 0.003), but higher TNF-α (P = 0.001) and IL-6 (P = 0.011) concentrations than those with solid tumors. At follow-up, the concentration of prealbumin increased and IL-6 decreased in children with lymphoma. Multivariate analysis demonstrated that decreases in prealbumin concentration at the end of follow-up were associated with increases in IL-6 and TNF-α concentration during chemotherapy. CONCLUSIONS: These results suggest that the cytokine responses during chemotherapy are related to nutritional status at the end of 6 mo of treatment regardless of the initial nutritional status and the type of cancer.

Unsuspected Lung Pathology in Autopsies of Children with Cancer.

BACKGROUND: Although pulmonary involvement is common in patients with cancer, its frequency and nature is seldom reported in the medical literature. OBJECTIVE: To determine the frequency and type of lung pathological conditions revealed by autopsy in children with cancer. METHODS: All reports from autopsies performed in children with cancer from 1989 to 2012 in a pediatric hospital were reviewed. RESULTS: In the analyzed period, 118 autopsies (10.2% of all autopsies) corresponded to children who died with cancer; 76 had complete information and were included in the analysis. Children were seen in the Hematology (41 cases) or the Oncology (35 cases) services. Their median age at decease was 7 years (range, 15 days to 16.1 years) and 46.1% were females. Main diagnoses were acute lymphoblastic (31 patients) or myeloblastic (10 patients) leukemias and tumors of the central nervous system (12 patients). A pathological respiratory condition was diagnosed antemortem in 31 (40.8%) patients, and at autopsy in 62 (81.6%) cases. Omitted diagnoses occurred in 58 (76.3%) children, being pneumonia (24 cases) and pulmonary hemorrhage (23 cases) the most frequent omissions. Nine patients had clinically unsuspected tumor infiltration or metastases. CONCLUSIONS: In these children with cancer, more than 80% of autopsies revealed some lung pathology, mainly of infectious or hemorrhagic nature. Thus, pulmonary involvement should be investigated in all children with cancer in a timely and intentional manner.

[Pineal region tumors in children: is gross-total resection necessary? A single-center experience]. / Tumores de región pineal en niños: ¿es la resección total necesaria? Experiencia en un centro de referencia.

BACKGROUND: Survival of children with pineal region tumors has increased significantly in the last decade; these tumors have an insidious outcome associated with endocrine disorders with high morbidity and mortality, especially after gross resection. The objective was to report the survival, outcome, morbidity and mortality according to type of surgery, histology and treatment in children with pineal region tumors. METHODS: This retrospective study included all patients of 17 years or less with diagnosis of pineal region tumor, who went over a period of 10 years to a children's hospital. A histopathological review was made, and the extent of resection was determined. The survival was also estimated. RESULTS: Forty-six patients were included, out of which 36 had complete medical records and adequate pathologic material. Gross resection was performed in 24 (66.6 %), and biopsy in 12 (33.3 %); 23 (88 %) patients died; hydroelectrolytic imbalance was the cause of 14 deaths (60 %) and the other nine (39.1 %) were secondary to tumor progression. Ten-years survivals among patients treated with gross resection and biopsy were 52 and 75 %, respectively (p = 0.7). Endocrine alterations were observed in 13 patients (36.1 %); in 10 of these (76.9 %) the total resection was performed. CONCLUSIONS: Pineal region tumors in children can be treated with diagnostic biopsy, followed by adjuvant treatment consisting of chemotherapy and radiotherapy.

Introducción: la supervivencia de los niños con tumores de la región pineal se ha incrementado en la última década; estos tienen una evolución insidiosa asociada con los desórdenes endocrinológicos y una alta morbilidad y mortalidad, sobre todo después de la resección. El objetivo es reportar la supervivencia, la morbilidad y mortalidad según el tipo de cirugía, la histología y el tratamiento en un grupo de niños con tumores de la región pineal. Métodos: estudio retrospectivo que incluyó a todos los pacientes con diagnóstico de tumor de la región pineal menores de 17 años de edad que acudieron en un periodo de 10 años a un hospital de pediatría. Se realizó una revisión histopatológica, se determinó la extensión de la resección y se estimó la supervivencia. Resultados: se incluyeron 46 pacientes, 36 de los cuales tenían expediente completo y material de patología adecuado. La resección total se realizó en 24 (66.6 %) y biopsia en 12 (33.3 %); fallecieron 23 pacientes (88 %) y fue el desequilibrio hidroelectrolítico la causa de 14 defunciones (60 %) y la progresión tumoral la causa de las 9 defunciones restantes (39.1 %). La sobrevida a 10 años de los pacientes tratados con resección total y biopsia fue del 52 y 75 %, respectivamente, con una p = 0.7; se presentaron alteraciones endocrinológicas en 13 (36.1%) pacientes de los cuales a 10 (76.9 %) se les realizó la resección de la tumoración. Conclusión: los tumores de la región pineal en niños se pueden tratar con biopsia diagnóstica seguida de tratamiento adyuvante con quimioterapia y radioterapia.

[Chromosomal imbalances and survival in patients with astrocytomas]. / Alteraciones cromosómicas y supervivencia en pacientes con astrocitomas.

BACKGROUND: Cytogenetics has revealed that the development of brain tumors might be induced by molecular alterations. The association of chromosomal imbalances with survival will allow for the prognosis and treatment of these tumors to be assessed. The objective of this study was to determine chromosomal imbalances and overall and disease-free survival in pediatric patients with astrocytoma and the association between chromosomal imbalances and survival. METHODS: Medical charts of patients diagnosed with astrocytoma according to records from 1995 to 2005 were reviewed. Paraffin blocks were retrieved in order to extract tumor material and a comparative genomic hybridization technique was used to search for chromosomal gains and losses. RESULTS: Out of 35 patients, 31 had at least some alteration in chromosomes 1, 5, 9 or 18, the latter with gains or losses in 65.7 % of the patients. By histology, 7/9 pilocytic astrocytomas had alteration of chromosome 9, and in 5/6 anaplastic astrocytomas, of chromosome 18. Patients with alterations in these chromosomes had a worse survival. CONCLUSIONS: The results of this study suggest that there is an association between the anaplastic histology and chromosome 18 alterations, as well as between diffuse astrocytoma and alterations in chromosome 5, which could be relevant in the Latin American population.

INTRODUCCIÓN: la citogenética ha revelado que el desarrollo de los tumores cerebrales pudiera estar inducido por alteraciones moleculares. La asociación de las alteraciones cromosómicas con la supervivencia permitirá valorar el pronóstico y tratamiento de estos tumores. El objetivo de este estudio fue determinar las alteraciones cromosómicas, la supervivencia global y libre de enfermedad en pacientes pediátricos con astrocitomas, y la asociación entre ellas. MÉTODOS: se revisaron los expedientes clínicos de los pacientes con diagnóstico de astrocitoma de acuerdo con los registros de 1995 a 2005. Se buscaron los bloques de parafina para extraer el material tumoral y se realizó técnica de hibridación genómica comparativa para buscar ganancias y pérdidas cromosómicas. RESULTADOS: de 35 pacientes, 31 presentaron al menos alguna alteración en los cromosomas 1, 5, 9 o 18, este último presentó ganancias o pérdidas en 65.7 % de los pacientes. Al analizarlas según la estirpe histológicas de los tumores, en 7/9 astrocitomas pilocíticos se observó alteración del cromosoma 9, y en 5/6 astrocitomas anaplásicos, del cromosoma 18. Los pacientes con alteraciones en estos cromosomas tuvieron una menor supervivencia. CONCLUSIONES: los resultados de este estudio sugieren que existe asociación entre la histología anaplásica y las alteraciones del cromosoma 18, así como entre el astrocitoma difuso y las alteraciones en el cromosoma 5, lo cual podría ser relevante en la población latinoamericana.

Onychomycosis in immunosuppressed children receiving chemotherapy.

Onychomycosis in children has a low incidence worldwide; certain conditions such as immunosuppression have been described as risk factors for it. We studied 72 children receiving chemotherapy for different neoplasms to determine the frequency of onychomycosis. Only one patient had white superficial onychomycosis from Trichophyton rubrum, a frequency of 1.3%, not different from that reported in healthy patients.

A proteomic approach of pediatric astrocytomas: MiRNAs and network insight.

Pediatric astrocytomas, a leading cause of death associated with cancer, are the most common primary central nervous system tumors found in children. Most studies of these tumors focus on adults, not on children. We examined the global protein and microRNA expression pattern by 2D SDS-PAGE, mass spectrometry (MALDI-TOF), and RT(2) miRNA PCR Array System. Proteomic studies revealed 49 proteins with changes on the expression. Interactome showed that vimentin, calreticulin, and 14-3-3 epsilon protein are hub proteins in these neoplasms. MicroRNA analyses demonstrated for the first time novel microRNAs involved in the astrocytoma biology. In conclusion, our results show that novel proteins and microRNAs with expression changes on pediatric astrocytoma could serve as biomarkers of tumor progression. BIOLOGICAL SIGNIFICANCE: Astrocytomas are tumors that progress rapidly and that invade surrounding tissues. Although some drugs have been developed to treat these neoplasms, the mortality of patients is still very high. In this study, we describe for the first time, to our knowledge, some proteins and miRNAs associated with the biology of astrocytic tumors that could be postulated as possible diagnostic or prognostic biomarkers. Altogether, our results indicate that large-scale analyses allow making a fairly accurate prediction of different cellular processes altered in astrocytic tumors.

Utilidad de la proteína C reactiva para el diagnóstico de infección bacteriana en el paciente pediátrico con cáncer, fiebre y neutropenia / Usefulness of C-reactive protein in the diagnosis of bacterial infection in the pediatric patient with cancer, fever and neutropenia

Introducción. El diagnóstico de infección bacteriana en el paciente con cáncer, fiebre y neutropenia se dificulta debido a una pobre respuesta inflamatoria. Se han realizado evaluaciones con reactantes de fase aguda, como la proteína C reactiva, con resultados variables. El objetivo de este trabajo fue calcular la sensibilidad, especificidad, valores predictivos positivos y negativos y razones de verosimilitud de la proteína C reactiva para el diagnóstico de infección bacteriana en pacientes con cáncer y neutropenia febril. Métodos. Se realizó el estudio de la prueba diagnóstica. Se incluyeron pacientes pediátricos con cáncer, y neutropenia (<500 NA/mm³). La proteína C reactiva se cuantificó por nefelometría. Los episodios se clasificaron en cuatro grupos: grupo I, infección microbiológicamente documentada; grupo II, infección clínicamente documentada; grupo III, fiebre por otras causas; y grupo IV, pacientes con neutropenia sin fiebre. Se realizó el cálculo de sensibilidad, especificidad, valores predictivos positivos y negativos, curvas operantes del receptor y razones de verosimilitud. Para la comparación de variables cuantitativas se emplearon la U de Mann-Whitney y Kruskal-Wallis y para variables cualitativas, χ². Resultados. Se incluyeron 127 episodios que se distribuyeron en: 29, 47, 20 y 31 episodios para los grupos I, II, III y IV, respectivamente. Las medianas de la proteína C reactiva fueron 282 mg/L para el grupo I, 205 mg/L grupo II, 27.3 mg/L grupo III y 5.1 mg/L para el grupo IV (p < 0.001). Con la proteína C reactiva de 60 mg/L se obtuvo una sensibilidad de 94%, especificidad de 94%, valor predictivo positivo 96% y valor predictivo negativo 92%; razón de verosimilitud para un resultado positivo 15.6 y de 0.06 para resultado negativo. Conclusiones. La proteína C reactiva es una prueba útil y económica para el diagnóstico de infección bacteriana en el paciente con cáncer, fiebre y neutropenia.

Background. Diagnosis of bacterial infection in the patient with cancer, fever and neutropenia is difficult due to the poor inflammatory response. Several evaluations of acute phase reactants such as C-reactive protein (C-RP) have been performed with diverse results. The aim of this study was to calculate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and likelihood ratios (LR) for C-RP in the diagnosis of bacterial infection of patients with cancer, neutropenia and fever. Methods. We carried out a diagnostic test study. Pediatric patients with cancer and neutropenia (<500 NA/mm³) were selected. C-RP was determined by nephelometry. Episodes were classified into the following groups: group I: microbiologically documented infection; group II: clinically documented infection; group III: fever of unknown origin; group IV: patients with neutropenia without fever. Sensitivity, specificity, PPV, NPV, receiving operating curves (ROC) and LR were calculated. Mann-Whitney U test and Kruskal-Wallis test were used for comparison of quantitative variables. For qualitative variables, χ2 test was used. Results. There were 127 episodes distributed as follows: 29, 47, 20 and 31 for groups I, II, III and IV, respectively. Median of C-RP values were 282 mg/L for group I, 205 mg/L group II, 27.3 mg/L group III and 5.1 mg/L group IV (p <0.001). With a C-RP value of 60 mg/L, we obtained a sensitivity of 94%, specificity 94%, PPV 6% and NPV 92%. LR for a positive test was 15.6 and LR for a negative test was 0.06. Conclusions. C-RP is a useful and economically feasible test for diagnosis of bacterial infection in patients with cancer, neutropenia and fever.

[Survival of patients with malignant astrocytomas according to the expression of Ki67 antigen in a pediatric hospital]. / Sobrevida de los pacientes con astrocitoma de alto grado que expresan el antígeno Ki67, atendidos en un hospital de pediatría.

BACKGROUND: Pediatric patients with malignant gliomas and same histological diagnosis respond distinctly to treatment. It is thus necessary to determine other factors that may influence the response to treatment and survival. Over expression of the Ki67 protein has been associated with poor treatment response. The aim of this study was to determine if the expression of this antigen influences survival of patients treated for malignant gliomas in the CMN SXXI Pediatrics Hospital. METHODS: We included patients with anaplasic astrocitoma or glioblastoma multiforme seen at our hospital between 1995 and 2005. We determined the expression of Ki67 by immunohistochemistry and correlated the findings with tumor histology and patient survival. RESULTS: Of the 21 patients studied, 12 overexpressed antigen Ki67. There was no significant association between over expression of Ki67 and survival, although we observed a clinical association. Over expression of Ki67 correlated with more aggressive histology. Being under the age of 11 was a poor prognostic factor. Overall survival was 49% at 120 months. CONCLUSIONS: Being young (under 11 years) is a marker of poor prognosis among pediatric patients with anaplasic astrocytoma or glioblastoma multiforme. Overexpression expression of antigen Ki67 is associated with histology and may be associated with poor survival among patients treated in our hospital.

Sobrevida de los pacientes con astrocitoma de alto grado que expresan el antígeno Ki67, atendidos en un hospital de pediatría / Survival of patients with malignant astrocytomas according to the expression of Ki67 antigen in a pediatric hospital

Antecedentes: Los pacientes pediátricos con astrocitomas de alto grado con mismas histologías presentan respuestas diferentes a idéntico tratamiento. Es necesario identificar los factores que influyen en el pronóstico y respuesta al mismo. La sobreexpresión de la proteína Ki67 se ha asociado con respuestas poco favorables. El objetivo fue determinar si la expresión de este antígeno influye en la sobrevida de los pacientes con astrocitoma de alto grado del Hospital de Pediatría del Centro Médico Nacional Siglo XXI. Métodos: Se incluyeron pacientes con astrocitoma anaplásico o glioblastoma multiforme atendidos entre 1995 y 2005. Por inmunohistoquímica se determinó la expresión del antígeno Ki67 en las muestras de tejido tumoral y se correlacionó con la histología tumoral y la sobrevida de los pacientes. Resultados: De 21 pacientes, 12 sobreexpresaron el antígeno Ki67. No se encontró asociación estadísticamente significativa entre la sobreexpresión del antígeno Ki67 y la sobrevida, aunque sí clínica. Se encontró asociación estadísticamente significativa entre la sobreexpresión del Ag Ki67 y el grado de malignidad del tumor. La edad menor de 11 años resultó un factor de mal pronóstico. La sobrevida global fue de 49 % a 120 meses. Conclusiones: La edad menor de 11 años fue un factor de mal pronóstico en los pacientes estudiados con astrocitoma o glioblastoma multiforme. La sobreexpresión del antígeno Ki67 está asociada con la histología y pareciera tener relación con la sobrevida de los pacientes pediátricos con astrocitoma.

BACKGROUND: Pediatric patients with malignant gliomas and same histological diagnosis respond distinctly to treatment. It is thus necessary to determine other factors that may influence the response to treatment and survival. Over expression of the Ki67 protein has been associated with poor treatment response. The aim of this study was to determine if the expression of this antigen influences survival of patients treated for malignant gliomas in the CMN SXXI Pediatrics Hospital. METHODS: We included patients with anaplasic astrocitoma or glioblastoma multiforme seen at our hospital between 1995 and 2005. We determined the expression of Ki67 by immunohistochemistry and correlated the findings with tumor histology and patient survival. RESULTS: Of the 21 patients studied, 12 overexpressed antigen Ki67. There was no significant association between over expression of Ki67 and survival, although we observed a clinical association. Over expression of Ki67 correlated with more aggressive histology. Being under the age of 11 was a poor prognostic factor. Overall survival was 49% at 120 months. CONCLUSIONS: Being young (under 11 years) is a marker of poor prognosis among pediatric patients with anaplasic astrocytoma or glioblastoma multiforme. Overexpression expression of antigen Ki67 is associated with histology and may be associated with poor survival among patients treated in our hospital.

Epidemiological and some clinical characteristics of neuroblastoma in Mexican children (1996-2005).

BACKGROUND: Neuroblastoma (NB) is the principal tumor of the sympathetic nervous system in children under one year of age. The incidence in developed countries is greater than that in developing countries. The aim of this article is to present the epidemiological and some clinical characteristics of Mexican children with NB. METHODS: A population-based, prolective study, with data obtained from the Childhood Cancer Registry of the Instituto Mexicano de Seguro Social. STATISTICAL ANALYSIS: The simple frequencies of the variables of the study and the annual average incidence (per 1,000,000 children/years) by age and sex were obtained. The trend was evaluated by calculating the annual percentage of change. The curves of Kaplan-Meyer were employed for the survival rate and the log-rank test was used to compare the curves. RESULTS: Of a total of 2,758 children with cancer registered during the period from 1996-2005, 72 (2.6%) were identified as having Group IV, defined according to the International Classification of Childhood Cancer. The incidence for NB was 3.8 per 1,000,000 children/year; NB was highest in the group of children under one year of age, followed by the group of children between the ages 1-4 years (18.5 and 5.4 per 1,000,000 children/years, respectively). The male/female ratio was 1.1 and there was no trend toward an increase. The time of diagnosis was 26 days (median), but varied according to the stage at diagnosis. Stages III and IV were presented in 88% of the cases. There was no association between the stage, the age at time of diagnosis, or the histological pattern. The overall five-year survival rate was 64%; the patients with stage I, II, III, or IVs did not die; and the five-year survival rate of cases in Stage IV was 40%. CONCLUSION: It is possible that the low incidence of neuroblastoma in Mexican children is due to the difficulty in diagnosing the cases with the best prognosis, some of which could have had spontaneous regression. There was no trend to an increase; the majority of the cases were diagnosed in the advanced stages; and the overall five-years survival rate was similar to that for developed countries.

[Prognostic and survival factors among pediatric patients with ependymomas]. / Factores pronósticos y sobrevida de pacientes pediátricos con ependimomas.

BACKGROUND: Ependymomas constitute the third most common intracranial tumors in children. Risk factors include age, location, extent of surgical excision, and radiation therapy. Recently, chromosomal imbalances have been described. OBJECTIVE: Determine global survival of patients with ependymomas according to different prognostic factors. METHODS: We reviewed the medical charts of every pediatric patient with ependymoma from 1996 to 2005. Genomic imbalances were determined using comparative genomic hybridization (CGH). Survival was calculated using the Kaplan and Meier method. We used the Log Rank test for each risk factor. Death risk was calculated by odds ratio (OR). RESULTS: We included 24 patients. Global survival was 58.04%. The presence of chromosomal imbalances, particularly in chromosome 21, significantly affected survival Being under 5 years of age, anaplastic histology, chemotherapy other than ICE (ifosfamida-carboplatin-etoposide) and partial resection increased the risk of death. CONCLUSIONS: Known risk factors were confirmed in our study, including chromosomal imbalances. We describe a new chromosomal imbalance in chromosome 21 among 30% of study participants.

Factores pronósticos y sobrevida de pacientes pediátricos con ependimomas / Prognostic and survival factors among pediatric patients with ependymomas

Antecedentes: El ependimoma es el tercer tumor intracraneano más frecuente en pediatría. Los factores que influyen en el pronóstico son la localización, la edad del paciente, la resección quirúrgica y el tratamiento con radioterapia. Recientemente se ha descrito la presencia de alteraciones cromosómicas en el tumor como factor de mal pronóstico. El objetivo de esta investigación fue determinar la sobrevida de pacientes pediátricos con ependimoma de acuerdo con los diferentes factores pronósticos. Métodos: Se revisaron los expedientes de pacientes pediátricos con ependimoma de 1996 a 2005. Se determinaron las alteraciones cromosómicas mediante hibridación genómica comparativa. Se calculó la sobrevida de acuerdo con el método Kaplan-Meier y prueba de log rank de acuerdo a cada factor pronóstico. Se calculó el riesgo de morir para cada factor de acuerdo con la razón de momios. Resultados: Se incluyeron 24 pacientes. La sobrevida global fue de 58.04%. La presencia de alteraciones cromosómicas, particularmente en el cromosoma 21, afectó significativamente la sobrevida. La edad menor a cinco años, la histología anaplásica, la quimioterapia diferente a ifosfamida-carboplatino-etopósido y la resección parcial aumentaron el riesgo de morir. Conclusiones: Se confirman los factores descritos anteriormente en la literatura, incluyendo alteraciones cromosómicas. Se describe un nuevo desbalance en el cromosoma 21 en 30% de los pacientes.

BACKGROUND: Ependymomas constitute the third most common intracranial tumors in children. Risk factors include age, location, extent of surgical excision, and radiation therapy. Recently, chromosomal imbalances have been described. OBJECTIVE: Determine global survival of patients with ependymomas according to different prognostic factors. METHODS: We reviewed the medical charts of every pediatric patient with ependymoma from 1996 to 2005. Genomic imbalances were determined using comparative genomic hybridization (CGH). Survival was calculated using the Kaplan and Meier method. We used the Log Rank test for each risk factor. Death risk was calculated by odds ratio (OR). RESULTS: We included 24 patients. Global survival was 58.04%. The presence of chromosomal imbalances, particularly in chromosome 21, significantly affected survival Being under 5 years of age, anaplastic histology, chemotherapy other than ICE (ifosfamida-carboplatin-etoposide) and partial resection increased the risk of death. CONCLUSIONS: Known risk factors were confirmed in our study, including chromosomal imbalances. We describe a new chromosomal imbalance in chromosome 21 among 30% of study participants.

Phase II study of metronomic chemotherapy with thalidomide, carboplatin-vincristine-fluvastatin in the treatment of brain stem tumors in children.

BACKGROUND: Brain stem tumors (BST) constitute 20% of all intracranial tumors. Survival for these patients has been very poor worldwide. Four different treatment schemes have been evaluated at our institution, with only a discrete increment in survival when treated with carboplatin-vincristine and fluvastatin (CVF). Low-dose, continuous antiangiogenic treatment has been recently introduced in the treatment of cancer. Our objective was to determine tumor response to metronomic chemotherapy combined with an antiangiogenic drug and fluvastatin and to calculate the survival of pediatric patients with brain stem tumors. METHODS: This was a phase II study. A magnetic resonance (MRI) study was made at inclusion and after the fourth course. Routine laboratory analyses were performed prior to each treatment scheme. Patients received four courses of chemotherapy every 28 days consisting of thalidomide alternating with fluvastatin every 14 days and combined with carboplatin and vincristine every 14 days followed by radiotherapy (56 cGy) and four more courses of the same chemotherapy. Toxicity was evaluated according to Miller criteria. RESULTS: Nine recently diagnosed BST patients were included. Five patients had low-grade astrocytomas, three patients had glioblastoma multiforme, and one patient presented high-grade astrocytoma. There was a significant reduction in tumor volume and a significant increase in survival at 24 months. Two patients died. Toxicity included carboplatin allergy in one patient, grades 1 and 3 neutropenia in two patients, and grade 4 thrombocytopenia in two patients. CONCLUSIONS: Metronomic treatment with carboplatin and vincristine associated with fluvastatin and thalidomide significantly increased survival of pediatric brain stem tumor patients. Tumor volume showed a significant reduction. Quality of life was also increased. Sample size must be increased in order to make final conclusions.

Palonosetron hydrochloride is an effective and safe option to prevent chemotherapy-induced nausea and vomiting in children.

BACKGROUND: Emesis and nausea are common adverse effects of chemotherapy. Consequences include dehydration, acute renal failure, esophageal rupture, electrolyte imbalance and undernutrition, among others. First-generation 5-HT3 antagonists significantly reduce these symptoms but are expensive and require administration every 8-12h. Palonosetron, a second generation 5-HT3 antagonist has proven better results in adult populations. Other benefits include a one-dose administration with effect for up to 7 days and a lower treatment cost. No clinical studies have evaluated the safety and efficacy of palonosetron in children. METHODS: Prior to every course, patients were randomized to receive palonosetron or ondansetron. Patients or guardians recorded the number of emetic events and the intensity of nausea over a 7-day period. They also reported any possible adverse effects. Statistical analysis included chi(2) test, relative risk, and Student's t test. RESULTS: Fifty courses were analyzed for each group. There was a significant reduction in emesis on the first 3 days and in the intensity of nausea in the first four days in the palonosetron group. There was an increased risk of presenting emesis and nausea in the acute phase when treated with ondansetron. No adverse effects were reported. The cost of treatment was also reduced when using palonosetron. CONCLUSIONS: Palonosetron is a safe and effective antiemetic treatment in children, as well as being cost effective.

Clinical and molecular parameters for risk stratification in Mexican children with medulloblastoma.

BACKGROUND: Clinical, histological, and more recently, molecular factors have been described as important in survival of the patient with medulloblastoma. Best survival results include aggressive chemotherapeutic protocols. More exact risk analysis may differentiate patients who require aggressive treatments from those with low risk who may respond adequately to less aggressive protocols. METHODS: Twenty six patients were included over a 10-year period and were followed for at least 5 years. Personal variables were obtained from their clinical records. Immunochemistry studies were performed on their formalin-fixed paraffin-embedded tissues. Statistical analysis included chi(2) test, odds risk, linear regression models, and Kaplan-Meier survival analysis. RESULTS: Metastatic disease and chemotherapy with VP16-carboplatin reduce the patient's probability of survival, whereas anaplastic histology increases the probability of death. Global survival and disease-free survival were 66.6 and 45.02%, respectively. Only two patients overexpressed the ERBB2 protein, and no significant difference was found in survival in terms of ERBB2 overexpression. CONCLUSIONS: Risk stratification has become very important in medulloblastoma. We found an increased hazard of death when metastatic disease was present. Gene expression in Mexican children requires a larger sample in order to be analyzed.