Identification of CD114 Membrane Receptors as a Molecular Target in Medulloblastomas.

Medulloblastomas are the most common solid tumors in children, accounting for 8-30% of pediatric brain cancers. It is a high-grade tumor with aggressive behavior and a typically b poor prognosis. Its treatment includes surgery, chemotherapy, and radiotherapy, and presents high morbidity. Significant clinical, genetic, and prognostic differences exist between its four molecular subgroups: WNT, SHH, Group 3, and Group 4. Many studies seek to develop new chemotherapeutic agents for medulloblastomas through the identification of genes whose expressions are new molecular targets for drugs, such as membrane receptors associated with cell replication. This study aimed to assess the association of CD114 expression with mortality in patients with medulloblastoma. Databases from the Medulloblastoma Advanced Genomics International Consortium (MAGIC) were analyzed, focusing on the expression of the CD114 membrane receptor in different molecular types and its possible association with mortality. Our findings showed different CD114 expressions between Group 3 and other molecular groups, as well as between the molecular subtypes SHH γ and Group 3 α and Group 3 ß. There was no statistically significant difference between the other groups and subtypes. Regarding mortality, this study did not find statistical significance in the association between low and high CD114 expressions and mortality. Medulloblastoma is a heterogeneous disease with many subtype variations of its genetic and intracellular signaling pathways. Similarly to this study, which could not demonstrate different CD114 membrane receptor expression patterns between groups, others who sought to associate CD114 expression with mortality in other types of cancer failed to establish a direct association. Since many indications point to the relation of this gene with cancer stem cells (CSCs), it may be part of a more extensive cellular signaling pathway with an eventual association with tumor recurrence. This study found no direct relationship between CD114 expression and mortality in patients with medulloblastoma. Further studies are needed on the intracellular signaling pathways associated with this receptor and its gene (the CSF3R).

É possível prever a mortalidade molecular em meduloblastomas pela análise dos receptores de membrana CD114? / Is it possible to predict molecular mortality in meduloblastomas by analysis of CD114 membrane receptors?

Introdução: Os meduloblastomas são os tumores sólidos mais comuns da infância e classificados em 4 subgrupos moleculares: WNT, SHH, grupo 3 e grupo 4. Muitos estudos buscam desenvolvimento de novos quimioterápicos para os meduloblastomas através da identificação de genes cuja expressão sejam novos alvos moleculares para drogas, como receptores de membrana associados a replicação celular. Objetivo: Avaliar a associação da expressão de CD114 com a mortalidade de pacientes portadores de meduloblastoma. Métodos: Revisão feita colhendo informações publicadas em plataformas virtuais em português e inglês. Inicialmente foi realizada busca por descritores relacionados ao tema - neurocirurgia, oncologia cirúrgica, terapia de alvo molecular e meduloblastoma - e seus equivalentes em inglês - neurosurgery, surgical oncology, molecular targeted therapy e medulloblastoma - com busca AND ou OR, considerando o título e/ou resumo. Após, foram incluídos somente os que tinham maior relação ao tema, e realizada a leitura da íntegra dos textos. Finalmente foram referidos 2 artigos. Resultados: Há diferença na expressão do receptor de membrana CD114 entre o Grupo 3 e os demais grupos moleculares, além de diferença entre o subtipo molecular SHH γ e os subtipos moleculares Grupo 3 α e Grupo 3 ß. Não houve diferença estatisticamente significativa entre os demais grupos e subtipos. Em relação à mortalidade, esta revisão não demonstrou significância estatística na relação entre expressões baixas e elevadas desse gene e a mortalidade. Conclusão: Não há relação direta entre a expressão do receptor de membrana CD114 e a mortalidade em pacientes portadores de meduloblastoma. Entretanto, são necessários estudos adicionais sobre as vias de sinalização intracelulares associadas a esse receptor e ao seu gene, o CSF3R.

Introduction: Medulloblastomas are the most common solid tumors of childhood and classified into 4 molecular subgroups: WNT, SHH, Group 3 and Group 4. Many studies seek to develop new chemotherapy drugs for medulloblastomas by identifying genes whose expression is new molecular targets for drugs, such as membrane receptors associated with cell replication. Objective: To evaluate the association of CD114 expression with mortality in patients with medulloblastoma. Methods: Review carried out collecting information published on virtual platforms in Portuguese and English. Initially, a search was carried out for descriptors related to the topic - neurosurgery, surgical oncology, molecular targeted therapy and medulloblastoma, with AND or OR search, considering the title and/or summary. Afterwards, only those that were most related to the topic were included, and the texts read in full. Finally, 23 articles were referred. Results: There is a difference in the expression of the CD114 membrane receptor between Group 3 and the other molecular groups, in addition to a difference between the SHH γ molecular subtype and the Group 3 α and Group 3 ß molecular subtypes. There was no statistically significant difference between the other groups and subtypes. Regarding mortality, this review did not demonstrate statistical significance in the relationship between low and high expressions of this gene and mortality. Conclusion: There is no direct relationship between the expression of the CD114 membrane receptor and mortality in patients with medulloblastoma. However, additional studies are needed on the intracellular signaling pathways associated with this receptor and its gene, CSF3R.

[Surgical approaches to petroclival meningiomas Part 2: narrative review of what we learned with 30 cases]. / Abordajes quirúrgicos de los meningiomas petroclivales Parte 2: revisión narrativa y lo que aprendimos con 30 casos.

Background: The surgical ressection of petroclival meningiomas is challenging due to its deep location and relationship with vital neurovascular structures. Usually they are benign injuries, but they can involve or infiltrate skull base bones, dura mater and brainstem. This makes the total removing very difficult or impossible without causing neurological deficits. The objective of this study is to review the surgical approaches used on the treatment of petroclival meningiomas and the knowledge which we achieved upon the surgical management of 30 cases. Methods: Series of 30 petroclival meningioma-cases. In the beginning of our series we used petrous approach for all the cases, however, with the acquiring of experience, we are indicating the retrosigmoid approach, leaving the petrous and skull-orbito-zigomatics approaches for selected cases. Results: Owing to the difficulty of the access, the petroclival meningiomas usually require different surgical approaches and have distint surgical difficulties. There are three main approaches: fronto-orbito-zigomatics and variants; petrous and variants and retrosigmoid, and they can be combined. The choice for a surgical approach is usually on the location and size of the tumor, on the skull shape, the involvement of venous structures and according to the surgeon´s experience. Conclusion: Petroclival meningiomas are rare and complex on the skull base. The adequate choice is crucial to achieve the good surgical result.

Avoiding vascular complications in insular glioma surgery - A microsurgical anatomy study and critical reflections regarding intraoperative findings.

Introduction: Vascular lesions in insular glioma surgery can severely impact patients' quality of life. This study aims to present the results of our dissections and authors' reflections on the insular vascular anatomy. Matherials and Methods: The insular vascularization was examined using ×3 to ×40 magnification in 20 cadaveric cerebral hemispheres in which the arteries and veins had been perfused with colored silicone. Results: In insular gliomas, this individualization of the anatomical structures is rarely possible, as the gyri are swollen by the tumor and lose their individuality. In the transsylvian approaches, the anatomical parameters for delimiting the insula in tumors are best provided by the superior and inferior circular sulci. The branches of the MCA are easily identified in the transcortical approach, but only at the end of the surgery after the tumor is resected.). One of the factors under-discussed in the literature is the involvement of the lenticulostriate arteries by the medial part of the tumor. In our experience of 52 patients (article submitted to publishing), LSTa were founded to be involved by the tumor in 13 cases. In 39 patients, there was no involvement of the LSTa, which allowed a more aggressive resection. Early preoperative identification of the anterior perforated substance on the MRI and its proximity to the tumor may help determine the route of the LSTa over the medial tumor boundaries. Discussion: Our reflections introduced our imaging and anatomical concept regarding LSTa in insular glioma surgery. Accurate identification of origin, route, and distribution of the LSTa is pivotal to surgical success, especially in the lateral group. The anatomical knowledge of their path directly impacts the extent of tumor resection and functional preservation. Conclusion: Knowledge of microsurgical anatomy, brain mapping, and surgical experience counts a lot in this type of surgery, creating a reasonable procedure flowchart to be taken intraoperatively.

Association between Wegener´s granulomatosis and severe lumbar pain

Introducción: La granulomatosis de Wegener (GW) es una enfermedad autoinmune sistémica caracterizada por vasculitis granulomatosa necrotizante que afecta principalmente a las vías respiratorias superiores, pulmones y riñones. Sin embargo, con menos frecuencia puede afectar a los músculos, las articulaciones, la piel, los ojos, el sistema cardiovascular y el sistema nervioso. La presencia de dolor lumbar consiste en una manifestación clínica inusual debido a la afectación del sistema nervioso. Objetivo: El objetivo de este estudio es alertar a los profesionales de la salud acerca de la posibilidad de cortar el dolor lumbar estar relacionado con la granulomatosis de Wegener, su impacto en la vida diaria del paciente, así como los signos clínicos y las formas de diagnóstico. Materiales y Métodos: Revisión de la literatura utilizando PubMed, MEDLINE, Google Scholar, SciELO, EBSCO. Los trabajos seleccionados entre 1995 y 2013 por un total de 48 obras de las cuales se seleccionaron 21 de acuerdo con sus informes de afectación neurológica, diagnóstico y tratamiento. Discusión: Los síntomas neurológicos pueden ocurrir en 22-50 por ciento de los pacientes durante el curso de la GW. sistema nervioso (SNC) central es poco frecuente (sólo 2-8 por ciento de los pacientes) dolor lumbar .Severe es una manifestación clínica poco frecuente y puede estar asociada con la participación de sistema nervioso central y periférico. CNS debido a la compresión de la médula espinal a nivel lumbar. sistema nervioso periférico debido a la compresión de las raíces nerviosas. Conclusión: La granulomatosis de Wegener es ser una enfermedad sistémica puede presentar diferentes manifestaciones clínicas De acuerdo con el sitio involucrado. Es asociaciones con el dolor lumbar es rara y la refleja la afectación neurológica. Por lo tanto, en pacientes con dolor lumbar grave sin diagnóstico confirmado, granulomatosis de Wegener no debería ser considerado.

Introduction: Wegener’s granulomatosis (WG) is a systemic autoimmune disease characterized by necrotizing granulomatousvasculitis which primarily affects upper respiratory tract, lungs and kidneys. However, less frequently can affect muscles,joints, skin, eyes, cardiovascular system and nervous system. The presence of lumbar pain consists in an unusual clinicalmanifestation due to the involvement of the nervous system. Objective: The objective of this study is to alert health professionalsabout the possibility that severe lumbar pain be related to Wegener’s granulomatosis, it’s impact on the patient’s dailylife as well as clinical signs and diagnosis forms. Materials and Methods: Literature review using PubMed, MEDLINE, GoogleScholar, SciELO, EBSCO. Selected works from 1995 to 2013 totaling 48 works of which 21 were selected according to theirreports of neurological involvement, diagnosis and treatment. Discussion: Neurological symptoms may occur in 22-50 percent of patients during the course of WG. Central nervous system (CNS) involvement is uncommon (only 2-8 percent of patients).Severelumbar pain is a rare clinic manifestation and it can be associated with the involvement of central and peripheral nervous system.CNS due to compression of the spinal cord at the lumbar level. Peripheral nervous system due to compression of nerveroots. Conclusion: Wegener’s granulomatosis for being a systemic disease can present different clinical manifestations accordingto the involved site. It’s associations with lumbar pain is rare and reflects it’s neurological involvement. Therefore, inpatients with severe lumbar pain without confirmed diagnosis, Wegener’s granulomatosis should be considered.