Neuroblastoma intracraneal en una niña / Intracranial neuroblastoma in a girl I: en

Se describe el caso clínico de una niña de 13 meses de edad, quien fue asistida en el Servicio de Neurocirugía del Hospital Infantil Sur Dr. Antonio María Béguez César de Santiago de Cuba, y posteriormente en el Servicio de Oncología de la institución, remitida del área de salud por presentar proptosis, exoftalmos del ojo derecho y aumento del perímetro craneal. Luego de realizados el examen clínico y los estudios complementarios pertinentes, incluidos resonancia magnética simple y contrastada de cráneo, estudio histopatológico, así como aspiración y biopsia bilateral de médula ósea, se confirmó que se trataba de un neuroblastoma parameníngeo con infiltración medular (estadio IV), sin evidencia de tumor primario. La evolución luego de la quimioterapia fue satisfactoria.

The case report of a 13 months girl is described who was assisted in the Neurosurgery Service of Antonio María Béguez Cesar Southern Children Hospital in Santiago de Cuba, and later on in the Oncology Service of the institution, referred from the health area due to proptosis, exophthalmos of the right eye and increase of the cranial perimeter. After the clinical exam and the pertinent complementary studies, including simple and contrasted magnetic resonance of skull, histopatologic study, as well as aspiration and bilateral biopsy of bone marrow, the presence of a parameningeal neuroblastoma with medullary infiltration (stage IV), without evidence of primary tumor was confirmed. The evolution after the chemotherapeutic treatment was satisfactory.

Effectiveness of autologous hematopoietic stem cell transplantation in the treatment of high-risk neuroblastoma in children: a single-center clinical study / 中国当代儿科杂志

OBJECTIVES@#To investigate the effectiveness of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) in the treatment of children with high-risk neuroblastoma (NB).@*METHODS@#A retrospective analysis was performed on 29 children with high-risk NB who were admitted to Shanghai Children's Hospital and were treated with high-dose chemotherapy combined with ASCT from January 2013 to December 2021, and their clinical features and prognosis were analyzed.@*RESULTS@#Among the 29 children treated by high-dose chemotherapy combined with ASCT, there were 18 boys (62%) and 11 girls (38%), with a median age of onset of 36 (27, 59) months. According to the International Neuroblastoma Staging System, 6 children (21%) had stage III NB and 23 children (79%) had stage IV NB, and the common metastatic sites at initial diagnosis were bone in 22 children (76%), bone marrow in 21 children (72%), and intracalvarium in 4 children (14%). All 29 children achieved reconstruction of hematopoietic function after ASCT. After being followed up for a median time of 25 (17, 45) months, 21 children (72%) had continuous complete remission and 8 (28%) experienced recurrence. The 3-year overall survival rate and event-free survival rate were 68.9%±16.1% and 61.4%±14.4%, respectively. Presence of bone marrow metastasis, neuron-specific enolase ≥370 ng/mL and positive bone marrow immunophenotyping might reduce the 3-year event-free survival rate (P<0.05).@*CONCLUSIONS@#Children with high-risk NB who have bone marrow metastasis at initial diagnosis tend to have a poor prognosis. ASCT combined with high-dose chemotherapy can effectively improve the prognosis of children with NB with a favorable safety profile.

Meroterpenoids from Rhododendron nivale / 中国中药杂志

To elucidate the chemical material basis of Rhododendron nivale, this study comprehensively used various chromatographic techniques to isolate and obtain five new meroterpenoid enantiomers(1a/1b-5a/5b) from the ethyl acetate extract of R. nivale. A variety of spectral analytical methods, such as high-resolution mass spectrometry(HRMS), nuclear magnetic resonance spectroscopy(NMR), and infrared(IR) spectrum, were used to evaluate the structure, combined with the measurement and calculation of electronic circular dichroism(ECD). The new compounds 1a/1b-4a/4b were named as(±)-nivalones A-B(1a/1b-2a/2b) and(±)-nivalnoids C-D(3a/3b-4a/4b), along with one known enantiomer(±)-anthoponoid G(5a/5b). Human neuroblastoma cells(SH-SY5Y cells) induced by hydrogen peroxide(H_2O_2) were used as oxidative stress models to evaluate the protective activity of the isolated compounds against oxidative damage to nerve cells. It was found that compounds 2a and 3a had a certain protective effect on nerve cells against H_2O_2-induced oxidative damage at concentrations of 50 μmol·L~(-1), which increased the cell survival rate from 44.02%±2.30% to 67.82%±1.12% and 62.20%±1.87%, respectively. Other compounds did not show a significant ability to protect cells from oxidative damage. These findings enrich the chemical constituents of R. nivale and provide valuable information for identifying the structure of its meroterpenoids.

Diterpenoid constituents in Pseudolarix amabilis and their antitumor activities in vitro / 中国中药杂志

By various chromatographic techniques and extensive spectroscopic methods, 17 abietane diterpenoids were isolated from the dichloromethane fraction of the 95% ethanol cold-soak extracts of the seeds of Pseudolarix amabilis, namely pseudoamaol A(1), 12α-hydroxyabietic acid(2), 12-methoxy-7,13-abietadien-18-oic acid(3), 13-hydroxy-8,11,13-podocarpatrien-18-oic acid(4), 15-hydroxy-7,13-abietadien-12-on-18-oic acid(5), 8(14)-podocarpen-13-on-18-oic acid(6), holophyllin K(7), metaglyptin B(8), 7α-hydroxydehydroabietinsaure-methylester(9), 7-oxodehydroabietic acid(10), 15-hydroxy-7-oxodehydroabietinsaure-methy-lester(11), 15-methoxydidehydroabietic acid(12), 7-oxo-15-hydroxy-dehydroabietic acid(13), 15-hydroxydehydroabietic acid(14), 8,11,13-abietatriene-15,18-diol(15), 8,11,13-abietatriene-15-hydroxy-18-succinic acid(16), and 7β-hydroxydehydroabie-tic acid(17). Compound 1 was a new compound. The isolated compounds were evaluated for their antitumor activities(HepG2, SH-SY5Y, K562), and compounds 8 and 17 showed potential cytotoxic activity against K562 cells, with IC_(50) values of 26.77 and 37.35 μmol·L~(-1), respectively.

Treatment and outcomes of high-risk neuroblastoma in Southeast Asia: a single-institution experience and review of the literature

INTRODUCTION@#In Europe and North America, the majority of children with high-risk neuroblastoma survive the disease. Elsewhere, the treatment outcomes are poor.@*METHODS@#A retrospective review of children treated for high-risk neuroblastoma in a single institution in Singapore from 2007 to 2019 was carried out. Treatment consisted of intensive chemotherapy, surgery aimed at gross total resection of residual disease after chemotherapy, consolidation with high-dose therapy followed by autologous stem cell rescue, and radiotherapy to the primary and metastatic sites followed by maintenance treatment with either cis-retinoic acid or anti-disialoganglioside monoclonal antibody therapy. Survival data were examined on certain clinical and laboratory factors.@*RESULTS@#There were 57 children (32 male) treated for high-risk neuroblastoma. Their mean age was 3.9 (range 0.7-14.9) years. The median follow-up time was 5.5 (range 1.8-13.0) years for the surviving patients. There were 31 survivors, with 27 patients surviving in first remission, and the five-year overall survival and event-free survival rates were 52.5% and 47.4%, respectively. On log-rank testing, only the group of 17 patients who were exclusively treated at our centre had a survival advantage. Their five-year overall survival rate compared to patients whose initial chemotherapy was done elsewhere was 81.6% versus 41.1% (P = 0.011), and that of event-free survival was 69.7% versus 36.1% (P = 0.032). Published treatment results were obtained from four countries in Southeast Asia with five-year overall survival rates from 13.5% to 28.2%.@*CONCLUSION@#Intensified medical and surgical treatment for high-risk neuroblastoma proved to be effective, with superior survival rates compared to previous data from Southeast Asia.

Anestesia e Manejo da Dor Pós-Operatória Associada à Técnica de Monitorização Neurofisiológica em Oncopediatria: Relato de Caso / Anesthesia and Postoperative Pain Management Associated with the Neurophysiological Monitoring Technique in Pediatric Oncology: Case Repor / Anestesia y Manejo del Dolor Postoperatorio Asociado a la Técnica de Monitoreo Neurofisiológico en Oncología Pediátrica: Informe de Caso

neuroblastoma é o tumor maligno sólido extracraniano mais comum na infância. Entre seis e dez milhões de crianças são identificadas com essa doença por ano. O tratamento cirúrgico, que envolve a ressecabilidade tumoral, é fator decisivo na estratégia terapêutica desses pacientes, com evidente influência no prognóstico da doença. Relato do caso: Lactente submetido à anestesia geral e a bloqueio de nervo periférico para ressecção de neuroblastoma com monitorização neurofisiológica intraoperatória (MNIO). Como estratégia anestésica, foi realizado o bloqueio do plano do eretor da espinha (ESP Block) associado à técnica de analgesia multimodal visando ao controle da dor. A dor pós-operatória foi avaliada por meio da Children's and Infants' Postoperative Pain Scale (CHIPPS). Conclusão:A MNIO, apesar de restringir as técnicas anestésicas, tem se firmado como uma importante ferramenta para monitorar as funções neurológicas durante as abordagens cirúrgicas com envolvimento do sistema nervoso central, com a finalidade de evitar danos permanentes de importantes estruturas. A interação e a comunicação de toda a equipe são de suma importância nos resultados pós-operatórios

Neuroblastoma is the most common non-central nervous system in childhood. From six to ten million children are identified with this disease annually. Surgical treatment, which involves tumor resectability, is a decisive factor in the therapeutic strategy of these patients, with clear influence on disease's prognosis. Case report: Nursling submitted to general anesthesia and peripheral nerve block for neuroblastoma surgical resection with intraoperative neurophysiological monitoring (IONM) and spinal erector plane block(ESP), associated with the multimodal analgesia technique for pain control. The postoperative pain was evaluated using the Children's and Infants' Postoperative Pain Scale (CHIPPS). Conclusion: IONM has established itself as an important tool to monitor neurological functions during surgical approaches with involvement of the central nervous system, in order to avoid permanent damage to important structures. The interaction and communication of the entire team are of paramount importance in the postoperative results.

Neuroblastoma es el tumor maligno sólido extracraneano más común en la infancia. Entre seis y diez millones de niños son identificados con esta enfermedad por año. El tratamiento quirúrgico, que implica la resecabilidad tumoral, es un factor decisivo en la estrategia terapéutica de estos pacientes, con una influencia evidente en el pronóstico. Informe del caso: Lactante sometido a anestesia general y bloqueo nervioso periférico para resección de neuroblastoma con monitoreo neurofisiológico intraoperatorio (MNIO). Como estrategia anestésica, para resección del neuroblastoma, se realizó bloqueo del plano erector espinal (Bloqueo ESP), asociado a la técnica de analgesia multimodal para controlar el dolor. El dolor postoperatorio se evaluó mediante la Children's and Infants' Postoperative Pain Scale (CHIPPS). Conclusión: La MNIO, a pesar de restringir las técnicas anestésicas, se ha posicionado como una importante herramienta para monitorear las funciones neurológicas durante los abordajes quirúrgicos que involucran al sistema nervioso central, con el fin de evitar daños permanentes a estructuras importantes. La interacción y la comunicación de todo el equipo son de suma importancia en los resultados posoperatorios

Collection, cryopreservation and thawing of stem cells for children weighing less than 25 Kg with high-risk neuroblastoma: A single center results in Morocco

ABSTRACT Introduction: An important component of the advances made in neuroblastoma treatment has been the use of peripheral blood stem cells to support high-dose chemotherapy. In this study, we report our experience on a series of small children who have undergone standard and large volume leukaphersis (LVL) procedures, provide an update on a single institution's experience with cryopreservation of autologous peripheral blood stem cells (PBSCs), using 10% dimethyl sulfoxide (DMSO) and applying post-thaw DMSO depletion and analyze a number of variables that may affect viability. Methods: A total of 36 aphereses were performed on 29 children weighing less than 25 kg between July 2016 and October 2019 at the Ibn Sina university hospital. Results: Seven females and twenty-two males, median bodyweight 14 kg (9 - 22). A single apheresis was sufficient to obtain at least 3 × 106/kg body weight (BW) of CD34+ cells in 82.8% of the cases. The LVL was performed in 22 aphereses. A median number of 5.9 × 106/ kg CD34 cells were collected per apheresis. A total of 60 PBSC samples were cryopreserved and 46 samples were infused. The mean cell viability percentage decreased from 94.75 ± 1.14% before freezing to 70.84 ± 8.6% after thawing (p < 0.001). No correlation was found between post-thaw viability and storage time (r = -0.233; p = 0.234) or number of total nucleated cells (r = 0.344; p = 0.073). Conclusion: Leukapheresis is safe and feasible in small pediatric patients if the appropriate measures are used. Cryopreservation poses numerous challenges, especially a decrease in cell viability after thawing.

Artichoke extracts with potential application in chemoprevention and inflammatory processes

Abstract The aim of this work is to study three cultivars of artichoke (Cynara cardunculus var. scolymus): Gauchito, Guri and Oro Verde in terms of their in vitro chemoprevention and anti-inflammatory properties. These cultivars show good productive performance. The phenolic composition of their fresh leaves and edible bracts was analyzed by high performance liquid chromatography and high resolution mass spectrometry (HPLC-HRMS), showing mainly caffeoylquinic acids and flavonoids. Caffeoylquinic acids were quantified and the highest content was found in Gauchito cultivar. In this cultivar, the content of dicaffeoylquinic acids in fresh bracts was six times higher than that in fresh leaves (10064.5 ± 378.3 mg/kg versus 1451.0 ± 209.3 mg/kg respectively). Luteolin flavonoids were detected in leaves. The extracts from fresh bracts and leaves were assessed in their in vitro bioactivity against human neuroblastoma cells (SH-SY5Y). Inhibition of SH-SY5Y cells proliferation by Gauchito and Guri leaf extracts (8 µg/mL) was higher than 50 %. The leaf extracts of the same cultivars showed an inhibitory effect on human interferon IFN-I, decreasing its activity 50% at 40 µg/mL. Interestingly, the bract extracts did not show in vitro bioactivity at these concentrations, nor did the pure compounds chlorogenic acid, cynarin, apigenin and luteolin (at 2 µg/mL). These results suggest that Gauchito and Guri leaf extracts have potential for human neuroblastoma chemoprevention and treatment of inflammatory processes.

A influência de macrófagos M1, M2 e TAM, e do receptor P2X7 na invasividade e resistência de neuroblastoma / The influence of different macrophages' phenotypes, and of the P2X7 receptor, on the invasiveness and chemoresistance of neuroblastoma

O neuroblastoma é um tumor sólido muito comum em crianças. O estágio mais avançado da doença é altamente agressivo e invasivo, além de pouco responsivo à terapia, que é limitada por mecanismos de resistência e reincidência relacionados à metástase. Muitos estudos tem sido feitos para identificar mecanismos de invasão e quimioresistência de células tumorais, afim de aumentar a sobrevida dos pacientes com câncer. Nesse trabalho, nós estudamos o efeito dos macrófagos, as células imunes mais abundantes no microambiente tumoral, os TAMs (do inglês tumor-associated macrophage) e do receptor P2X7, um purinoreceptor acionado por ATP, nesses processos. Os TAMs respondem e atuam de acordo com a miríade de fatores que encontram, podendo gerar populações heterogêneas e com funções distintas, tanto antitumorais, como pró-tumorais. Altos níveis de ATP extracelular são encontrados no microambiente tumoral, podendo então ativar o receptor P2X7. Este receptor tem sido relacionado tanto a funções inflamatórias como funções na resolução da inflamação de macrófagos. Além disso, o receptor P2X7 está envolvido em uma variedade de eventos celulares, incluindo a secreção de mediadores pró-inflamatórios, a proliferação celular e a apoptose de células tumorais. Primeiramente, foi avaliado o papel do receptor P2X7 na polarização de macrófagos da derivados medula óssea de camundongos wild-type e nocaute para o P2X7 na presença e ausência de fatores secretados por células de neuroblastoma, e então foi estudada a influência desses diferentes macrófagos polarizados em eventos celulares de grande relevância clínica para o neuroblastoma: a invasividade e quimiorresistência. Os resultados demonstraram que, apesar do reconhecido envolvimento do receptor P2X7 na inflamação, a ausência deste receptor não atenua a expressão de marcadores característicos do fenótipo inflamatório, M1. O aumento da expressão do receptor P2Y2, também envolvido na inflamação, nessas células, sugere um mecanismo genético de compensação para não atenuação da inflamação em macrófagos que não expressam o receptor P2X7. Contudo, a ausência do receptor P2X7 levou a alterações no fenótipo alternativo, M2, de modo que a expressão de Tnf, marcador de M2, não foi reprimido. TAMs noucates para P2X7 tiveram a expressão de arg1, marcador de M2, suprimida, reforçando a importância do receptor P2X7 no estabelecimento de fenótipos ativados alternativamente. Nossos dados também sugerem que ausência do receptor P2X7 em TAMs permite a aquisição de um fenótipo capaz de tornar as células de neuroblastoma que expressam P2X7 mais invasivas e mais quimioresistentes à vincristina. Por outro lado, TAMs, independentemente da presença ou ausência do receptor P2X7, induziram a proliferação e quimioresistência das células de neuroblastoma silenciadas para o receptor P2X7, o que nos leva a concluir que o receptor P2X7 em TAMs é desfavorável à progressão de tumores expressando P2X7

Neuroblastoma is a highly common childhood solid tumor. The most advanced stage of the disease is highly aggressive and invasive, besides from being poorly responsive to therapies, which are limited by resistance and recurrence mechanisms related to metastasis. Several studies attempt to identify invasion and resistance mechanisms of the tumor cells in order to increase overall survival of the patients. On the present work, we investigated the effect of macrophages, the most abundant immune cells on the tumor microenvironment, called TAMs (tumor-associated macrophages), and of the P2X7 receptor, an ATP-gated purinoceptor, on these processes. TAMs and cancer cells crosstalk, and behave accordingly to a miriad of factors present at the TME, generating heterogeneous populations with distinct functionalities, either pro- or antitumor. High extracellular levels of ATP are found in the TME, being able to activate the P2X7 receptor. This receptor mediates both pro- and anti-inflammatory functions in macrophages. In addition, it is involved in several cellular events, including the secretion of pro-inflammatory mediators, cell proliferation and tumor cell apoptosis. At first, we evaluated the role of the P2X7 receptor on the polarization of bone marrow-derived macrophages (BMDM), either wild-type or knockout for the P2X7 receptor, in presence or absence or factors secreted by neuroblastoma cells. Next, we investigated the influence of the polarized macrophages in highly relevant cellular events for neuroblastoma, such as invasiveness and chemoresistance. Our results showed that, despite the known involvement of P2X7 receptor on inflammation, its absence did not decrease the expression if inflammatory markers of M1 macrophage populations. An increase in the expression of the P2Y2 receptor, also involved in inflammation, on these cells suggest a genetic compensation mechanism for preventing attenuation of inflammation when P2X7 is lacking. However, P2X7 receptor absence did compromise the M2 phenotype, driving the expression of Tnf. TAMs knockout for the P2X7 receptor were not able to express arg1, also an M2 marker, reinforcing a role of the P2X7 receptor on establishing alternative macrophage phenotypes. Our data also suggest that TAMs lacking the P2X7 receptor acquire a phenotype capable of turning P2X7R-expressing neuroblastoma cells more invasive and chemoresistant to vincristine. On the other hand, TAMs, independently on the presence of the P2X7 receptor, induced proliferation and resistance of neuroblastoma cells silenced for P2X7 receptor expression, leading us to the conclusion that the P2X7 receptor in TAMs is unfavorable for the progression of P2X7R-expressing tumors

Clinical efficacy of combined therapy in children with stage 4 neuroblastoma / 中国当代儿科杂志

OBJECTIVES@#To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma.@*METHODS@#A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021.@*RESULTS@#The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years.@*CONCLUSIONS@#Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.

Recent clinical research on the application of liquid biopsy in neuroblastoma / 中国当代儿科杂志

Neuroblastoma (NB) is the most common extracranial solid tumor in children and has the features of high recurrence rate and low survival rate, and therefore, early diagnosis, treatment response evaluation, and recurrence monitoring are of great significance for NB patients. Liquid biopsy refers to the detection of cells and nucleic acids in fluid specimens, mainly blood. It is noninvasive and can overcome tumor heterogeneity, thus making it possible to achieve the early diagnosis and dynamic detection of NB. This review introduces the latest advances in clinical research on the application of liquid biopsy in NB.

Presentación atípica de un neuroblastoma congénito metastásico con efecto renal grave: informe de caso / Atypical presentation of a congenital metastatic neuroblastoma with severe renal impact: case report

El neuroblastoma es un tumor derivado de la cresta neural. Se trata del tumor maligno más frecuente en recién nacidos y existe una amplia variabilidad en su forma de presentación. En algunos casos, el diagnóstico se realiza mediante un hallazgo ecográfico, mientras que en otros se manifiesta como enfermedad metastásica agresiva. Se presenta el caso de una paciente prematura con diagnóstico posnatal de neuroblastoma congénito metastásico con manifestaciones clínicas graves y evolución atípica. Asimismo, se destaca una lesión renal grave que requirió terapia dialítica.

Neuroblastoma is a neural crest-derived tumor and the most common malignant tumor in neonates. Its clinical presentation can be quite variable. In some cases, it presents as an aggressive metastatic disease whilst in others it is a finding in scans performed for other reasons. The following report presents the case of a premature newborn, diagnosed postnatally with metastatic congenital neuroblastoma, with an atypical and torpid course, including severe renal injury and dialysis requirement.

Epignatus con extensión intracraneana: autopsia, reporte de un caso, y revisión bibliográfica / Epignatus with intracranial extension: autopsy, case report, and literature review

Metodología y descripción: se reporta el caso de una paciente de 31 años de edad, primigesta, que consulta a las 20 semanas por hallazgo ecográfico de tumoración orofaríngea fetalAutopsia y resultados: se obtuvo un feto femenino de 950 grs con teratoma maduro de 10x6x5 cm que protruye a través de la boca. Discusión: en la actualidad, se aplica el término epignatus a cualquier teratoma de la cavidad orofaríngea sin especificar el sitio de origen. La pesquisa es por ecografía(3) pero es necesaria una resonancia obstétrica para descartar algunos diagnósticos diferenciales (meningo encefalocele, neuroblastoma, glioma nasal, teratoma cervical) y malformaciones en otras localizaciones que puedan asociarse(2). Pueden tener un crecimiento unidireccional o bidireccional. La mayoría de las publicaciones de epignatus con tumor intracraneano se limitan a reportes de casos. Conclusión: actualmente, el tratamiento quirúrgico agresivo del epignatus con extensión intracraneana no está recomendado. Creemos que correlacionando los estudios pre-natales con los hallazgos post-natales, se podría establecer una clasificación que determine la viabilidad fetal y los casos que serían candidatos a beneficiarse con un tratamiento quirúrgico.

Neuroblastoma ­ revisão da literatura com caso ilustrativo / Neuroblastoma ­ literature review with illustrative case

RESUMO Neoplasias na infância são incomuns, mas ainda são a principal doença relacionada a morte em crianças. Os tumores sólidos representam cerca de 30% de todas as neoplasias malignas pediátricas, sendo o tumor de Wilms e o neuroblastoma duas das malignidades abdominais mais comuns. O neuroblastoma acomete principalmente a faixa etária entre 2 meses e 2 anos, sendo ligeiramente mais comum em meninos caucasianos. O neuroblastoma é a neoplasia maligna sólida extracraniana pediátrica mais comum e, de todas as malignidades, a segunda - 10% de todas as neoplasias. Apresenta associação com as Síndromes de Klippel-Feil, alcoólica fetal, fenil- -hidantoínicas, doença de Hirschsprung e, também, com a de Beckwith-Wiedemann. Quanto mais jovem o paciente ao diagnóstico, maior sua chance de sobrevivência. Os exames de imagem - ultrassonografia, tomografia computadorizada e ressonância magnética - apresentam alta acurácia. Os exames de imagem, em conjunto com a clínica do paciente e dados epidemiológicos, permitem o diagnóstico dos tumores renais pediátricos, mas o exame anatomopatológico ainda é indispensável. PALAVRAS-CHAVE: Neuroblastoma, ultrassonografia, tomografia computadorizada por raios X

ABSTRACT Although uncommon, childhood neoplasms are still the main death-related illness in children. Solid tumors represent about 30% of all pediatric malignancies, with Wilms' tumor and neuroblastoma being two of the most common abdominal malignancies. Neuroblastoma mainly affects the age group between 2 months and 2 years, being slightly more common in Caucasian boys. Neuroblastoma is the most common pediatric extracranial solid malignancy and, of all malignancies, the second ­ 10% of all neoplasms. It is associated with Klippel-Feil, fetal alcoholic, phenytoin/hydantoin and Beckwith-Wiedemann's syndromes, as well as with Hirschsprung's disease. The younger the patients at diagnosis, the greater their chance of survival. Imaging exams ­ ultrasound, computed tomography and magnetic resonance ­ are highly accurate. Imaging exams, together with the patient's clinic and epidemiological data, allow the diagnosis of pediatric kidney tumors, but the anatomopathological exam is still indispensable. KEYWORDS: Neuroblastoma, ultrasonography, X-ray computed tomography

Short-term effect of intensity-modulated radiotherapy for children with high-risk neuroblastoma: an analysis of 24 cases / 中国当代儿科杂志

OBJECTIVE@#To study the efficacy and safety of intensity-modulated radiotherapy (IMRT) in children with high-risk neuroblastoma (NB).@*METHODS@#A retrospective analysis was performed on the medical data of 24 children with high-risk NB who were diagnosed and treated with IMRT in the Department of Hematology and Oncology, Hunan Provincial People's Hospital, from April 2018 to December 2020. The medical data included age, radiotherapy dose, times of radiotherapy, laboratory examination results, adverse reactions, and survival.@*RESULTS@#All 24 children (14 boys and 10 girls) received IMRT, with a mean age of (65±23) months and a median age of 59 months. The primary tumor was located in the abdomen in 23 children and 1 child had primary tumor in the mediastinum. The median age was 41.5 months at the time of radiotherapy. The radiation dose of radiotherapy ranged from 14.4 to 36.0 Gy, with a mean dose of (22±3) Gy and a daily dose of 1.8-2.0 Gy. The radiotherapy was performed for a total number of 8-20 times, with a mean number of 11.9 times. Among these children, 6 received radiotherapy for the residual or metastatic lesion. Of all the 23 children, 3 experienced cough, 2 experienced diarrhea, and 1 experienced vomiting during radiotherapy. At 2 weeks after radiotherapy, serum creatinine ranged from 2.3 to 70.1 μmol/L and alanine aminotransferase ranged from 9.1 to 65.3 μ/L. Ten children experienced grade Ⅲ bone marrow suppression and 2 experienced grade Ⅳ bone marrow suppression 1 to 2 weeks after radiotherapy. Four children experienced grade Ⅲ bone marrow suppression and 1 experienced grade Ⅳ bone marrow suppression 3 to 4 weeks after radiotherapy. During a median follow-up time of 13.5 months, 23 children (96%) achieved stable disease and 1 died. Up to the follow-up date, second malignant tumor or abnormal organ function was not observed.@*CONCLUSIONS@#IMRT can improve the local control rate of NB. IMRT appears to be safe in the treatment of children with NB.

Neuroblastoma cervical: presentación de casos y revisión actualizada del tema / Cervical neuroblastoma: presentation of cases and updated review of the topic

El neuroblastoma es uno de los tumores sólidos extracraneales más comunes en la edad pediátrica, y se origina en células precursoras del sistema nervioso simpático. La ubicación cervical corresponde a un 2-5% del total de los neuroblastomas y puede tener distintas manifestaciones clínicas, tales como masa cervical, disnea, estridor, síndrome de Horner o disfagia. Esta entidad debe ser considerada dentro del diagnóstico diferencial de una masa cervical pediátrica, especialmente ante la presencia de masas sólidas, laterales o paramedianas, palpables o no al examen físico. El tratamiento específico del neuroblastoma depende de la clasificación de riesgo del paciente, pudiendo ser expectante en casos específicos, exclusivamente quirúrgico, o bien requerir complementarse con otras terapias. En este artículo se presentan 2 casos clínicos de pacientes pediátricos con neuroblastoma cervical tratados de forma exclusiva y exitosa con cirugía, y una revisión del tema.

Neuroblastoma is one of the commonest extracranial solid tumors at pediatric age, originating from sympathetic nervous system precursor cells. Cervical position stands for 2-5% of all neuroblastomas, with variable clinical expression that includes cervical mass, dyspnea, stridor, Horner syndrome and dysphagia. This condition must be considered in the differential diagnosis of a pediatric cervical mass, specially in those solid, lateral/paramedian masses that could be palpable or not at physical examination. The specific treatment in neuroblastoma depends on patient´s risk group, including conservative follow-up in selected cases, surgery alone, or complementary perioperative therapy with chemotherapy and others. In this article, the group report two cases of cervical neuroblastoma exclusively treated with surgery with good results, and a literature review.

Crisis adrenérgica como forma de debut de un neuroblastoma / Adrenergic crisis as a debut form of a neuroblastoma

INTRODUCCIÓN: La forma clínica de presentación más común del neuroblastoma es el de una masa abdominal, pero puede presentarse con sintomatología menos habitual, como es la crisis adrenérgica por liberación de catecolaminas. OBJETIVO: Describir una forma de presentación inusual de neuroblastoma y el amplio diagnóstico diferencial que existe en un lactante con síntomas adrenérgicos. CASO CLÍNICO: Lactante femenina de 7 semanas de vida, consultó por historia de tres semanas de sudoración e irritabilidad a lo que se asoció fiebre de 24 h de evolución y dificultad respiratoria. Al ingreso presentaba mal esta do general, irritabilidad, sudoración, enrojecimiento facial, taquipnea y palidez cutánea, taquicardia sinusal extrema e hipertensión arterial (HTA), interpretadas como sintomatología adrenérgica. Se completó el estudio con una ecografía abdominal y resonancia magnética que mostraron una gran masa retroperitoneal compatible con neuroblastoma. Las catecolaminas en sangre y en orina mostraron altos niveles de dopamina, adrenalina y noradrenalina, probablemente de origen tumoral. Se inició tratamiento antihipertensivo con fármacos alfa bloqueantes con buen control de la tensión arterial. Se resecó quirúrgicamente el tumor sin incidencias y con una adecuada recuperación posterior. La paciente presentó evolución favorable a tres años de seguimiento. CONCLUSIONES: en un lactante con sintomatología adrenérgica como irritabilidad, enrojecimiento, sudoración asociada a HTA, se debe descartar patología cardiaca, metabólica (hipoglucemia), intoxicaciones y/o patología suprarrenal. Dentro de esta última, el neuroblastoma es la primera posibilidad diagnóstica, por ser uno de los principales tumores en la infancia y aunque esta presentación no es habitual puede producir estos síntomas.

INTRODUCTION: The most common clinical presentation of neuroblastoma is an abdominal mass, but it can present with uncommon symptoms, such as adrenergic storm due to catecholamine release. OBJECTIVE: To describe an unusual presentation of neuroblastoma and the wide differential diagnosis that exists in an infant with adrenergic symptoms. CLINICAL CASE: A 7-week old female infant was evaluated due to a 3-week history of sweating and irritability associated with a 24-hour fever and respiratory distress. At admission, she presented poor general condition, irritability, sweating, facial redness, tachypnea and skin paleness, extreme sinus tachycardia, and high blood pressure (HBP), interpreted as adrenergic symptoms. The study was completed with abdominal ultrasound and magnetic reso nance imaging that showed a large retroperitoneal mass compatible with neuroblastoma. Plasma and urinary catecholamines tests showed high levels of dopamine, adrenaline, and noradrenaline, probably of tumor origin. We started antihypertensive treatment with alpha-blocker drugs, showing a good blood pressure control. The tumor was surgically resected without incidents and adequate subsequent recovery. The patient presented a favorable evolution after three years of follow-up. CONCLUSIONS: In an infant with adrenergic symptoms such as irritability, redness, sweating associated with HBP, it should be ruled out pathology heart or metabolic (hypoglycemia) pathology, intoxications, and/or adrenal pathology. Within this last one, neuroblastoma is the first diagnostic possibility, since it is one of the main tumors in childhood and, although this presentation is not usual, it can produce these symptoms.

Disfunción tiroidea por I131-Metayodo Benzilguanidina en pacientes con neuroblastoma / Thyroid dysfunction due to 131I-metaiodobenzylguanidine in patients with neuroblastoma

Resumen: Introducción: El tratamiento del neuroblastoma en estadios avanzados incluye quimioterapia, cirugía y terapia con I131-Metayodo benzilguanidina (I131-MIBG). La disfunción tiroidea se reporta entre 12 y 85% a pesar de la protección tiroidea. Objetivo: Identificar la frecuencia de disfunción tiroidea en casos de neu roblastoma tratados con I131-MIBG. Pacientes y Método: Estudio transversal. Se incluyeron todos los casos con diagnóstico de neuroblastoma que recibieron I131-MIBG en el periodo de 2002-2015, a los cuales se les realizó antropometría completa, perfil de tiroides: hormona estimulante de tiroides (TSH), Triyodotironina total y libre (T3t y T3l), tiroxina total y libre (T4t, T4l), y anticuerpos antitiroglobulina y antiperoxidasa. Resultados: Se identificaron un total de 27 pacientes; once fallecieron (40%). De los 16 casos sobrevivientes, 9 (56%) presentaron disfunción tiroidea: 2 (13%) casos con hipotiroidismo subclínico y 7 (44%) casos con hipotiroidismo clínico (3 casos por retraso en el desa rrollo psicomotor y 4 por desaceleración del crecimiento). Los pacientes presentaron manifestaciones clínicas a los 16,1 meses (1,2-66,3 meses) de recibir el radiofármaco a una dosis acumulada de 142 mCi (96-391.5 mCi). No se logró evidenciar diferencias en la edad al diagnóstico, la edad al inicio del tratamiento con el I131-MIBG, la dosis acumulada del I131-MIBG y el tiempo trascurrido entre la dosis y el perfil tiroideo entre los casos con o sin disfunción tiroidea. Conclusiones: El 56% de los pacientes con neuroblastoma presentaron disfunción tiroidea. La mayoría de los casos con hipotiroidismo fue ron referidos cuando los datos de disfunción tiroidea eran clínicamente evidentes. Se propone en esta poblacion realizar perfil tiroideo semestral y valoración anual por un endocrinólogo pediatra durante los primeros 5 años posteriores al diagnóstico oncológico.

Abstract: Introduction: The treatment of advanced neuroblastoma includes chemotherapy, surgery, and radiotherapy with 131-I-Metaiodobenzylguanidine (131-I-MIBG). Despite strategies to protect thyroid function, its dysfunction is reported between 12 and 85%. Objective: To identify the frequency of thyroid dys function in cases of neuroblastoma treated with 131-I-MIBG. Patients and Method: Cross-sectional study. We included all the cases with neuroblastoma treated with 131-I-MIBG between 2002 and 2015, with complete somatometry, and complete thyroid profile (TSH, free and total T3 and T4, and anti-thyroglobulin and antiperoxidase antibodies). Results: 27 patients were identified out of which eleven died (40%). Out of the 16 surviving cases, 9 (56%) presented thyroid dysfunction: 2 (13%) cases with subclinical hypothyroidism and 7 (44%) cases with clinical hypothyroidism (3 cases due to psychomotor developmental delay and 4 due to growth deceleration). The patients presented cli nical manifestations at 16.1 months (1.2-66.3 months) after receiving the radiopharmaceutical at acumulative dose of 142 mCi (96-391.5 mCi). No differences were found in the age at diagnosis, age at the start of treatment with 131-I-MIBG, the cumulative dose of 131-I-MIBG, and the time elapsed between the dose and the thyroid profile among the cases with or without thyroid dysfunction. Con clusions: 56% of patients with neuroblastoma had thyroid dysfunction. Most of the cases with hypothyroidism were referred when thyroid dysfunction was clinically evident. A thyroid profile should be performed every 6 months, along with an annual endocrinological evaluation during the next 5 years in these patients.

Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.