Application of adaptive aperture in proton radiotherapy for brain tumors / 中华放射医学与防护杂志

Objective:To evaluate the clinical application value of the adaptive aperture by comparing intensity-modulated proton radiotherapy(IMPT) plans using and not using the aperture for brain tumors.Methods:A total of twenty patients treated with postoperative radiotherapy for brain tumors were enrolled in this study. IMPT plans were developed for each patient using and not using the adaptive aperture under the same optimization conditions. The target conformal index (CI) value, target homogeneity index (HI) value, and the dose to normal tissues of the two sets of plans were compared.Results:The IMPT plans designed using the adaptive aperture significantly increased the mean CI value from 0.58 to 0.66, while decreasing the mean 50% prescription dose volume from 797.70 cm 3 to 638.15 cm 3. These plans also reduced the irradiation doses to the cochlea, brainstem, optic chiasm, optic nerve, and lens ( t = 2.06, 3.02, 2.11, 2.58, 2.67, P < 0.05). Additionally, there was no significant difference in the HI value of the target volumes and the machine jumps (MU) between the two sets of plans ( P > 0.05). Conclusions:The adaptive aperture can significantly reduce the irradiation dose to normal tissues outside the target volumes, positively impacting the protection of organs at risk (OARs) around the target values. This demonstrates its great potential for clinical application.

LRAE-Unet:a lightweight network for fully automatic segmentation of brain tumor from MRI / 中国医学物理学杂志

A lightweight residual attention enhanced Unet(LRAE-Unet)is designed for the fully automatic brain tumor segmentation.LRAE-Unet uses lightweight residual module to solve the problems of gradient disappearance and network degradation when the network layers increases,lightweight self-attention module to suppress the irrelevant areas and highlight the significant features of specific local areas,and enhanced average pooling module with a larger field of perception to reduce the space of feature map,save computing resources and avoid over-fitting.The experiment on BraTS 2019 dataset shows that the proposed method has a Dice similarity coefficient of 91.24%,88.64%and 88.32%in the segmentations of the whole tumor,tumor core and enhanced tumor,which proves its feasibility and effectiveness for brain tumor segmentation.

Recent advance in cell membrane-modified nanoparticles for malignant brain tumor / 中华神经医学杂志

Cell membrane-modified nanoparticles (NPs) have attracted widespread attention as a new approach for malignant brain tumors in recent years. This method can enhance the targeting, biocompatibility, and circulation time of NPs by preserving the characteristics of source cell membrane, thereby ensuring efficient drug delivery to intracranial lesions. This paper focuses on the research progress in this field, especially advantages of NPs penetrating the blood-brain barrier, immune evasion and drug delivery, as well as modified effect of different cell membrane on NPs, in order to provide help for treatment of malignant brain tumors.

Association between intraoperative hypotension and postoperative acute kidney injury in patients un-dergoing brain tumor resection / 临床麻醉学杂志

Objective To investigate the association between intraoperative hypotension and post-operative acute kidney injury(AKI)in patients undergoing brain tumor resections.Methods A total of 428 patients undergoing elective craniotomy for tumor resection were selected,276 males and 152 females,aged≥18 years,BMI 15-36 kg/m2,ASA physical statusⅡ orⅢ.Based on postoperative occurrence of AKI,the patients were divided into two groups:the AKI group and the control group.This study defined three thresholds for hypotension,including MAP during surgery below 65 mmHg,60 mmHg,and 55 mmHg.Multivariate logistic regression was used to analyze the correlation between intraoperative hypotension and postoperative AKI under three thresholds.Results A total of 107 patients had postoperative AKI.The re-sults of multivariable regression analysis indicated that intraoperative MAP＜65 mmHg(OR = 1.11,95%CI 1.03-1.20,P = 0.010)and intraoperative MAP＜60 mmHg(OR = 1.12,95%CI 1.02-1.23,P = 0.017)were associated with postoperative AKI.Conclusion Intraoperative MAP＜65 mmHg or 60 mmHg is associated with postoperative AKI in patients undergoing brain tumor resection.

Endocrine disorders in childhood brain tumour survivors: A single-centre study / Journal of the ASEAN Federation of Endocrine Societies

Objective@#The study aims to determine the prevalence and risk factors for endocrine disorders in childhood brain tumour survivors.@*Methodology@#124 childhood brain tumour survivors aged 18 years old or younger with either stable disease or in remission, and had survived for at least 2 years after diagnosis were included in the study. Demographic data (age at diagnosis, gender, ethnicity, socioeconomic status), clinical clues for endocrine disorders, anthropometrics (weight, height, midparental height), pubertal staging, tumour-related characteristics, treatment modalities and endocrine laboratory measurements at diagnosis and during follow up were obtained. Logistic regression was applied to evaluate risk factors for endocrine disorders in childhood brain tumour survivors.@*Results@#The prevalence of endocrine disorders in childhood brain tumour survivors was 62.1%. The risk factors were high BMI [adjusted odds ratio (OR) 1.29, 95% CI: 1.12 to 1.5], high-risk site [adjusted odds ratio (OR) 7.15, 95% CI: 1.41 to 36.3] and chemotherapy [adjusted odds ratio (OR) 0.18 , 95% CI: 0.05 to 0.62].@*Conclusion@#The prevalence of endocrine disorders in childhood brain tumour survivors in our centre was 62.1%. The significant risk factors were high BMI, tumour location (suprasellar and intrasellar) and chemotherapy.

Neurocognitive Dysfunction After Treatment for Pediatric Brain Tumors: Subtype-Specific Findings and Proposal for Brain Network-Informed Evaluations / 神经科学通报·英文版

The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment. As the lesion itself, as well as each treatment, can cause specific neural damage, the long-term neurocognitive outcomes are highly complex and challenging to assess. The number of neurocognitive studies in this population grows exponentially worldwide, motivating modern neuroscience to provide guidance in follow-up before, during and after treatment. In this review, we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor types. Based on this information, we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials.

Safety comparison of high-dose methotrexate via different intravenous infusion devices in pediatric patients with malignant brain tumors / 中国药房

OBJECTIVE To compare the safety of high-dose methotrexate （HD-MTX） via peripherally inserted central catheter （PICC） and totally implantable venous access port （TIVAP） in pediatric patients with malignant brain tumors. METHODS Patients with malignant brain tumors who received HD-MTX via PICCs or TIVAPs in our hospital from July 2018 to April 2022 were retrospectively analyzed. Clinical data were collected to compare differences in blood concentration of methotrexate （MTX），the incidence of adverse events （including adverse drug reactions and catheter-related complications） and length of stay in hospital. Multivariate linear regression was applied to analyze the factors that influenced the blood concentration of MTX. RESULTS A total of 107 patients were included in the study，with 65 patients in the PICC group and 42 patients in the TIVAP group. Blood concentration of MTX at 24 h （C24 h） in TIVAP group was significantly higher than PICC group （[ 126.87±61.99） μmol/L vs. （102.45±48.77） μmol/L，P＜0.05）. There was no significant difference in blood concentration of MTX at 42 h （C42 h），compared with PICC group （P＞0.05）. Results of multivariate linear regression analysis showed that TIVAP was associated with the increase of C24 h（P＜0.05）. No significant differences were observed in the incidence of adverse events and the length of stay in the hospital between 2 groups （P＞0.05）. CONCLUSIONS Risk of adverse events is not increased，although the MTX C24 h level is elevated after administration of TIVAP. TIVAP is a safe choice for HD-MTX therapy with implementing therapeutic drug monitoring.

Incidence and prognosis of frontotemporal lobe glioma-related epilepsy / 中国医师进修杂志

Objective:To analyze the incidence and prognosis of epilepsy in frontotemporal lobe glioma.Methods:The clinical data of 208 patients with frontotemporal lobe gliomas in Sanbo Brain Hospital Capital Medical University from 2019 to 2021 were analyzed retrospectively. According to the 2016 World Health Organization (WHO) classification of tumors of the central nervous system, the incidence of epilepsy, Modified Rankin Scale (MRS) score, and Engel Outcome Scale of patients with different grades of tumors were calculated.Results:Among all the patients with frontotemporal lobe gliomas, there was more males than females, and it was more common in the 40 -59 age group. The incidence of epilepsy associated with WHO grade Ⅰand Ⅱ glioma was 100.0% (33/33) and 60.9% (14/23), respectively, while that of WHO grade Ⅳ glioma was 19.0%(19/100). The average follow-up time was (22 ± 9) months. During the follow-up period, the incidence of WHO grade Ⅰ, Ⅱ and Ⅲ glioma-related epilepsy decreased significantly. There was no significant difference in the incidence of glioma-related epilepsy between the total and subtotal resection groups ( P>0.05). There was no statistical correlation between the side of tumor occurrence and the occurrence of epilepsy ( P>0.05), also between the gene phenotype and the occurrence of epilepsy ( P>0.05). There was no significant difference in the Engel Outcome Scale among different grades of gliomas ( P>0.05). The prognosis of patients with Engel Outcome Scale Class 1 was significantly better than that of other grades. Conclusions:The incidence of glioma-related epilepsy is negatively correlated with tumor grade. Age and sex are risk factors for glioma-related epilepsy. The incidence of postoperative epilepsy in patients with low grade glioma is significantly lower than that in patients with high grade glioma, and the prognosis is better. However, there is no significant difference in the Engel Outcome Scale among different grades of gliomas.

Recent advance in role of cyclic GMP-AMP synthase-stimulator of interferon gene signal pathway in brain tumors / 中华神经医学杂志

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signal pathway is a classical pathway of STING activation, and in recent years, its role in stimulating innate immunity has gradually attracted wide attention. Besides, cGAS can recognize and combine endogenous or exogenous DNA, then catalyze ATP and GTP to synthesize cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), subsequently activate STING signal to promote type I interferon and inflammatory factors, finally induce natural and adaptive immunity. Existing studies have indicated that cGAS-STING signal pathway plays an important role in infections, inflammations and tumors, especially in high-grade gliomas with poor clinical treatment efficacy. Here, we briefly summarize the cGAS-STING signal pathway and its mechanism in brain tumors to provide new ideas for exploring therapeutic targets and drugs for brain tumors.

Recent advance in role of ubiquitin-specific protease 11 in central nervous system diseases / 中华神经医学杂志

Ubiquitin-specific protease 11 (USP11) is a family member of deubiquitylases (DUBs). It mediates substrates de-ubiquitination to inhibit their ubiquitin-proteasome degradation and participates in cell cycle process, DNA damage repair, cell death, autophagy, signal transduction, immune inflammatory response, cerebral cortex development, and other physiological processes. Studies show that USP11 also plays an important role in central nervous system diseases. This article starts with the structure and functions of USP11 to systematically review the mechanism of USP11 in central nervous system diseases and provide new ideas for USP11 as a therapeutic target.

Expression and role of deleted in malignant brain tumor protein 1 in acute respiratory distress syndrome rats induced by sepsis / 中华危重病急救医学

Objective:To observe the expression of deleted in malignant brain tumor protein 1 (DMBT1) in rat acute respiratory distress syndrome (ARDS) model induced by sepsis and its relationship with ARDS related biomarkers.Methods:Forty-eight healthy male rats were randomly divided into sham operation group (Sham group) and ARDS model group, and the rats in each group were further divided into three subgroups at 6, 12 and 24 hours after operation, with 8 rats in each subgroup. The rats in the Sham group were exposed to the cecum only, and sepsis induced ARDS model was reproduced by cecal ligation and puncture (CLP) in the ARDS model group. The general performance was observed at 6, 12, 24 hours after operation. Abdominal aortic blood of rats was collected, and the levels of DMBT1, surfactant-associated protein D (SP-D), vascular endothelial growth factor (VEGF), interleukins (IL-6, IL-10) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The lung tissues were collected, and the lung wet/dry weight (W/D) ratio was determined. The lung tissue pathological changes were observed under light microscope after hematoxylin-eosin (HE) staining, and the lung tissue injury score was evaluated. The expression of DMBT1 protein in lung tissue was determined by Western blotting. The relationship between the serum DMBT1 and SP-D, VEGF, IL-6, IL-10, lung tissue injury score were analyzed by Pearson correlation analysis.Results:Rats in the ARDS model group showed obvious pathological manifestations after operation. The alveolar structure destruction, inflammatory cell infiltration, and alveolar hemorrhage were observed under microscope. Compared with the Sham group, the lung tissue injury score and the lung W/D ratio at 12 hours after operation in the ARDS model group were significantly increased (lung tissue injury score: 3.35±0.13 vs. 1.16±0.07, lung W/D ratio: 5.36±0.44 vs. 4.38±0.35, both P < 0.05), and pulmonary edema was present, which suggested that the ARDS model caused by CLP was successfully reproduced. The results of ELISA and Western blotting showed that the levels of serum DMBT1, SP-D, VEGF and IL-6 in the ARDS model group increased gradually with time, while the level of IL-10 increased first and then decreased. Compared with the Sham group, the levels of DMBT1 in serum and the expressions of DMBT1 protein in lung tissue in the ARDS model group were significantly increased from 6 hours after operation [serum (ng/L) : 231.96±19.17 vs. 187.44±10.19, lung tissue (DMBT1/β-actin): 2.05±0.19 vs. 0.93±0.25, both P < 0.05], and the levels of SP-D, VEGF, IL-6 and IL-10 in serum were significantly increased from 12 hours after operation [SP-D (ng/L): 73.35±8.05 vs. 43.28±5.77, VEGF (ng/L): 89.85±8.47 vs. 43.19±5.11, IL-6 (ng/L): 36.01±2.48 vs. 17.49±1.77, IL-10 (ng/L): 84.55±8.41 vs. 39.83±5.02, all P < 0.05]. Pearson correlation analysis showed that serum DMBT1 was positively correlated with serum SP-D, VEGF, IL-6, IL-10 and lung injury score at 12 hours and 24 hours in the ARDS model group (12 hours: r values were 0.946, 0.942, 0.931, 0.936, 0.748, respectively; 24 hours: r values were 0.892, 0.945, 0.951, 0.918, 0.973, respectively; all P < 0.05). Conclusion:DMBT1 is a novel early biomarker of ARDS by affecting alveolar epithelial cell, alveolar capillary permeability and inflammatory response.

Factores pronósticos asociados a la supervivencia de pacientes con tumores astrocíticos / Prognostic factors associated with the survival of patients with astrocytic tumors / Fatores prognósticos associados à sobrevida de pacientes com tumores astrocíticos

RESUMEN Introducción: Los tumores cerebrales son un grupo heterogéneo dada las diferentes líneas celulares que los originan. Los tumores cerebrales más frecuentes son los que se derivan de la glía, siendo los astrocitomas los más comunes. Objetivo: Sistematizar los hallazgos de los estudios que examinaron múltiples factores pronósticos de supervivencia en pacientes con tumores cerebrales tipo astrocitoma. Método: Se realizó una revisión sistemática de estudios observacionales, analíticos, prospectivos. La búsqueda bibliográfica se efectuó en las bases de datos electrónicas Medline, SciELO, LILACS, PubMed y Google Académico, con los siguientes términos descriptores: edad, sexo, factores pronósticos, cáncer cerebral, astrocitoma. Resultados: En la búsqueda se hallaron 136 452 artículos que estaban distribuidos en diferentes bases de datos. Al aplicar los criterios de elegibilidad quedaron para el análisis 13 artículos. En el caso de los factores pronósticos dependientes de la lesión, tumor o enfermedad, en la mayoría de las investigaciones se mostró una tendencia a evaluar el grado histológico y la histología de la lesión. En el caso de los pronósticos dependientes del paciente existió una mayor inclinación hacia la edad, el sexo y la sintomatología presentada, mientras que en los dependientes del tratamiento se mostraron indistintamente las modalidades de tratamiento sugeridas a los pacientes: cirugía, quimioterapia y radioterapia. Conclusiones: En esta investigación se presentaron los principales factores pronósticos en pacientes con tumores astrocíticos contenidos en las literaturas referentes al tema, que se agrupan en factores pronósticos dependientes del tumor, el paciente y el tratamiento. Estos deben ser tenidos en cuenta para evaluar al paciente con estas lesiones tumorales cerebrales.

ABSTRACT Introduction: Brain tumors are a heterogeneous group given the different cells that originate them. The most frequent brain tumors are those derived from the glia, with astrocytomas being the most common. Objective: To systematize the findings of studies that examined multiple prognostic factors for survival in patients with astrocytoma-type brain tumors. Method: a systematic review of observational, analytical, prospective studies was carried out. The bibliographic search was carried out in the electronic databases Medline, SciELO, LILACS, PubMed and Google Scholar, with the following descriptive terms: age, sex, prognostic factors, brain cancer, astrocytoma. Results: The search found 136,452 articles that were distributed in different databases. When applying the eligibility criteria, 13 articles remained for analysis. In the case of prognostic factors dependent on the lesion, tumor or disease, most researches showed a tendency to evaluate the histologic grade and the histology of the lesion. In the case of the patient-dependent prognoses, there was a greater inclination towards age, sex and the symptoms presented, while in those dependent on the treatment, the treatment modalities suggested to the patients were shown indistinctly: surgery, chemotherapy and radiotherapy. Conclusions: In this research, the main prognostic factors contained in the literature about patients with astrocytic tumors were presented, which are grouped into prognostic factors depending on the tumor, the patient and the treatment. These must be taken into account to evaluate the patient with these brain tumor lesions.

RESUMO Introdução: Os tumores cerebrais são um grupo heterogêneo devido às diferentes linhagens celulares que os originam. Os tumores cerebrais mais frequentes são os derivados da glia, sendo os astrocitomas os mais comuns. Objetivo: Sistematizar os achados de estudos que examinaram múltiplos fatores prognósticos de sobrevida em pacientes com tumores cerebrais do tipo astrocitoma. Método: Foi realizada uma revisão sistemática de estudos observacionais, analíticos e prospectivos. A busca bibliográfica foi realizada nas bases de dados eletrônicas Medline, SciELO, LILACS, PubMed e Google Acadêmico, com os seguintes termos descritivos: idade, sexo, fatores prognósticos, câncer cerebral, astrocitoma. Resultados: A busca encontrou 136.452 artigos que foram distribuídos em diferentes bases de dados. Ao aplicar os critérios de elegibilidade, restaram 13 artigos para análise. No caso de fatores prognósticos dependentes da lesão, tumor ou doença, a maioria das investigações mostrou uma tendência a avaliar o grau histológico e a histologia da lesão. No caso dos prognósticos paciente-dependentes, houve maior inclinação para a idade, sexo e os sintomas apresentados, enquanto nos dependentes do tratamento, as modalidades de tratamento sugeridas aos pacientes foram mostradas indistintamente: cirurgia, quimioterapia e radioterapia. Conclusões: Nesta pesquisa foram apresentados os principais fatores prognósticos em pacientes com tumores astrocíticos contidos na literatura sobre o assunto, os quais são agrupados em fatores prognósticos dependendo do tumor, do paciente e do tratamento. Estes devem ser levados em consideração para avaliar o paciente com essas lesões tumorais cerebrais.

Cognitive evaluation following the evolution of brain myofibroblastic tumor in the adolescence: a case study report / Avaliação cognitiva após a evolução do tumor miofibroblástico cerebral na adolescência: relato de estudo de caso

ABSTRACT Objective To report the case of a teenager (12 years old) diagnosed with a brain tumor in the right frontal-parietal region emphasizing the main characteristics observed in neuropsychological examinations. Methods In the pre-surgical evaluation, the patient presented behavioral alterations, including deficits in verbal comprehension, perceptual organization, working memory, processing speed, and slight alterations regarding constructive praxis. Results A reevaluation after two years surgery revealed significant improvement in verbal and perceptual comprehension and constructive praxis while remaining a slight change in processing speed. These results suggest that the tumor's surgical resection produced significant improvements in the patient's neurocognitive context, especially in executive functions. This study also indicates that Neuropsychological evaluation are useful for pre- and post- surgical evaluation of cognitive functioning and its evolution. Conclusion Brain tumor causes cognitive and behavioral changes and its resection can result in improvements in the patient's quality of life.

RESUMO Objetivo Relatar o caso de uma adolescente (12 anos de idade) diagnosticada com tumor cerebral na região frontoparietal direita, enfatizando as principais características observadas em exames neuropsicológicos. Métodos Na avaliação pré-cirúrgica, a paciente apresentou alterações comportamentais, incluindo déficits na compreensão verbal, organização perceptual, memória de trabalho, velocidade de processamento e pequenas alterações na praxia construtiva. Resultados Uma reavaliação dois anos após a cirurgia revelou melhora significativa na compreensão verbal e perceptiva e na práxis construtiva, permanecendo uma ligeira alteração na velocidade de processamento. Esses resultados sugerem que a ressecção cirúrgica do tumor produziu melhoras significativas no contexto neurocognitivo da paciente, sobretudo nas funções executivas. Este estudo também indica que a avaliação neuropsicológica é útil para avaliação pré e pós-cirúrgica do funcionamento cognitivo e sua evolução. Conclusão O tumor cerebral causa alterações cognitivas e comportamentais e a sua ressecção pode resultar em melhorias na qualidade de vida do paciente.

Abordaje perioperatorio en cirugía neurológica con el paciente despierto / Perioperative approach in neurological surgery with the patient awake

Resumen: La craneotomía con el paciente despierto se refiere a aquellos procedimientos en los que el paciente conserva su estado de consciencia durante toda la cirugía o en parte de ésta con el objetivo de explorar la integridad de sus funciones cerebrales superiores en tiempo real. Estas técnicas neuroanestésicas son útiles para ayudar al neurocirujano a preservar la integridad del tejido cerebral, o bien, no causar mayor daño del que la propia enfermedad ha causado.

Abstract: Awake craniotomy refers to those procedures in which the patient remains conscious for all or part the time, with the aim of explore in real time the integrity of their higher brain functions. This kind of neuroanesthetic techniques are useful in assisting the neurosurgeon to preserve the integrity of the brain or not to damage more than what the disease has caused.

Medulloblastoma outcomes in tertiary care set?up in India using contemporary treatment protocols ? A retrospective study

Background: Medulloblastoma is the commonest embryonal brain tumor in children. It has shown improved outcomes with combined modality treatment. We aimed to study patient characteristics and survival outcomes of patients with this disease across two tertiary care centers in India. Methods: We analyzed data of patients with histological diagnosis of medulloblastoma treated from January 2010 to January 2016. Patient characteristics and follow-up data were retrieved from hospital records. Descriptive statistics were used to describe clinical and pathological characteristics. Overall survival (OS) was calculated from date of diagnosis to death due to any cause. Relapse-free survival (RFS) was calculated from date of diagnosis to occurrence of relapse or death. Result: Out of 26 patients treated, 24 were children and 2 were adults. Median age was 10 years (range = 0.8–22 years). Twenty (76.9%) patients were male. Fifteen (57.7%) patients were stratified as high-risk (HR), rest 11 (42.3%) were categorized as average risk (AR). Histopathology showed classical variety in majority of patients except for 4 (15%) cases, 3 with desmoplastic and 1 with anaplastic subtype. Median follow-up was 49.7 months (range= 4.2–102.5 months). Overall, eight (30.8%) patients relapsed and six (23%) deaths occurred. Five (33.3%) patients in HR category and 3 (27.3%) patients in AR group showed relapse. Median RFS and OS were not yet reached. Five-year RFS was 69.2% whereas five-year OS was 76.9%. Conclusion: This study highlighted patient characteristics and treatment outcomes in Indian patients. With adherence to standard treatment, high remission rates and improvement in mortality rates were achieved.

Simultaneous determination of LY3214996,abemaciclib,and M2 and M20 metabolites in human plasma,cerebrospinal fluid,and brain tumor by LC-MS/MS / 药物分析学报

A sensitive and rapid liquid chromatography tandem mass spectrometry(LC-MS/MS)method was established for the quantification of total and unbound concentrations of LY3214996,an extracellular signal-regulated kinase inhibitor;abemaciclib,a cyclin-dependent kinase 4/6 inhibitor;and abemaciclib active metabolites,M2 and M20,in human plasma,brain tumor,and cerebrospinal fluid samples.The method was validated over a concentration range of 0.2-500 nM within a total run time of 3.8 min using isocratic elution on a Kinetex? Fs column.Detection was performed on a Sciex QTRAP 6500+mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization.The intra-and inter-batch accuracy as well as the precision of the method for all matrices was within±20％and≤20％at the lower limit of quantification,and within±15％and≤15％for other quality control levels for all analytes.The unbound fractions of drugs and metabolites in spiked and patient samples were determined using an optimized equilibrium dialysis.The validated method was successfully applied in a phase 0/2 clinical trial to assess the central nervous system penetration of LY3214996 and abemaciclib.

Progress in Multidisciplinary Diagnosis and Treatment of Familial Brain Tumors / 肿瘤防治研究

The tumors of central nervous system refer to a group of benign and malignant diseases originating from tissues or structures within the central nervous system. Common tumors of central nervous system are sporadic, but a few have familial onset. Compared with sporadic brain tumors, the clinical symptoms, diagnostic ideas and follow-up review plans of familial brain tumors are more complicated. The multidisciplinary diagnosis and treatment (MDT) mode usually refers to a treatment mode in which a case involving multiple organs and systems is discussed, and the best treatment plan is formulated for the patient based on the comprehensive opinions of various disciplines. Because familial brain tumors often involve multiple organs, multiple disciplines and multiple systems, and their low incidence leads to less clinical experience for neurosurgeons, the MDT model is more conducive to efficient diagnosis, treatment and management of familial brain tumors. This review elaborates on the neurosurgeon-led MDT model, and introduces the latest research on the epidemiology, genetic characteristics, clinical manifestations, diagnostic ideas and multidisciplinary management of familial brain tumors.

Glioblastoma multiforme con presentación seudovascular / Glioblastoma multiforme with pseudovascular presentation

Introducción: El glioblastoma multiforme es el tumor cerebral primario más frecuente y agresivo en adultos, representa cerca de 25 por ciento de los tumores intracraneales. Las principales manifestaciones clínicas están dadas por cefalea, convulsiones, cambios de conducta y un síndrome focal más definido (frontal, temporal, parietooccipital o del cuerpo calloso). En algunos pacientes, el comienzo es brusco por hemorragia o crecimiento rápido de un quiste intratumoral. El diagnóstico se realiza por resonancia magnética y se confirma con biopsia cerebral. El tratamiento es multidisciplinario e incluye resección quirúrgica, quimioterapia y radioterapia. No obstante, el pronóstico es desfavorable en la mayor parte de los pacientes. Objetivo: Describir el caso de un paciente con glioblastoma multiforme que se presentó en forma seudovascular. Caso clínico: Se presenta el caso de un paciente masculino de 60 años de edad con antecedentes de hipertensión arterial y enfermedad cerebrovascular. Tres días antes de su ingreso comenzó a manifestar dificultad para hablar y alteración en la marcha por pérdida de la fuerza muscular en el hemicuerpo derecho. Por lo anteriormente expuesto fue llevado al Hospital Clínico Quirúrgico Julio Trigo López donde fue ingresado y se diagnosticó un tumor cerebral. El paciente evolucionó tórpidamente y falleció. El estudio anatomopatológico arrojó la presencia de un glioblastoma multiforme. Conclusiones: El caso presentado de glioblastoma multiforme forma de defecto motor ofrece información sobre esta afección que en nuestro centro no es habitual(AU)

Introduction: Glioblastoma multiforme is the most frequent and aggressive primary brain tumor in adults, representing about 25percent of intracranial tumors. The main clinical manifestations are given by headache, seizures, behavior changes and a more defined focal syndrome (frontal, temporal, parieto-occipital or corpus callosum). In some patients, the onset is abrupt due to bleeding or rapid growth of an intratumoral cyst. The diagnosis is made by magnetic resonance imaging and confirmed with brain biopsy. Treatment is multidisciplinary and it includes surgical resection, chemotherapy, and radiation therapy. However, the prognosis is poor in most patients. Objective: To describe the case of a patient with glioblastoma multiforme that presented in a pseudovascular form. Clinical report: The case of a 60-year-old male patient with a history of arterial hypertension and cerebrovascular disease is report. Three days before his admission, he began to show difficulty speaking and gait disturbance due to loss of muscle strength in the right half of his body. For the foregoing, he was taken to Julio Trigo López Surgical Clinical Hospital where he was admitted and diagnosed with a brain tumor. The patient evolved torpidly and died. The pathological study revealed the presence of a glioblastoma multiforme. Conclusions: The reported case of glioblastoma multiforme in the form of a motor defect provides information on this condition that is not common in our center(AU)

Brain Tumor Heterogeneity

Tumor heterogeneity is the concept that different tumor cells provide distinct biomorphological lesions, gene expressions, proliferation, microenvironment and graduated capacity of metastatic lesions. Brain tumor heterogeneity has been recently discussed about the interesting interaction of chronic inflammation, microenvironment, epigenetics and glioma steam cells. Brain tumors remain a challenge with regards to medication and disease, due to the lack of treatment options and unsatisfactory results. These results might be the result of the brain tumor heterogeneity and its multiple resistance mechanisms to chemo and radiotherapy.

Utility of Intraoperative Ultrasound in Neurosurgery

Objective The purpose of the present study is to demonstrate the usefulness of intraoperative ultrasound guidance as a technique for the assessment, in real time, of tumor resection and as a navigation aid during intra-axial brain lesion removal on patients admitted in the Neurosurgical Department at the Hospital Universitario de Caracas, Caracas, Venezuela, in 2018. Methods A total of 10 patients were enrolled, each with intra-axial brain lesions with no previous neurosurgical procedures and a mean age of 49 years old, ranging from 29 to 59 years old. Results A male predominance was observed with 7 cases (70%) over 3 female cases (30%). Six patients had lesions in the dominant hemisphere. The frontal lobe was the most commonly affected,with 5 cases, followed by the parietal lobe,with 4 cases. After craniotomy, ultrasound evaluation was performed previously to dural opening, during tumor resection and after tumor removal. The mean tumor size in axial, coronal and sagittal views was 3.72 cm, 3.08 cm and 3.00 cm, respectively, previously to dural opening with intraoperative ultrasound. The average tumor depth was 1.73 cm from the cerebral cortex. The location and removal duration from the beginning of the approach (ultrasound usage time) was 83.60 minutes, and the average surgery duration was 201 minutes. Navigation with intraoperative ultrasound served to resect intra-axial tumors more precisely and safely. There was no postoperative complication associated with the surgery in this series of cases. Conclusions Intraoperative ultrasound guidance for intra-axial subcortical tumor resection is a technique that serves as a surgical and anatomical orientation tool.