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PURPOSE: Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients. METHODS: We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort). RESULTS: In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival. CONCLUSIONS: The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.
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Astrocitoma , Neoplasias Encefálicas , Feminino , Humanos , Masculino , Astrocitoma/patologia , Biomarcadores , Neoplasias Encefálicas/patologia , DNA/uso terapêutico , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Mutação , Prognóstico , Análise de Sequência de DNA , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.
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Angiotensinogênio/genética , Astrocitoma/genética , Neoplasias Encefálicas/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Variação Genética/genética , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética , Adulto , Astrocitoma/epidemiologia , Astrocitoma/patologia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has forced the modification of surgical practice worldwide. Medical centers have been adapted to provide an efficient arrangement of their economic and human resources. Although neurosurgeons are not in the first line of management and treatment of COVID-19 patients, they take care of patients with neurological pathology and potential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, the authors describe their institutional actions against the pandemic and compare these actions with those in peer-reviewed publications. METHODS: The authors conducted a search using the MEDLINE, PubMed, and Google Scholar databases from the beginning of the pandemic until July 11, 2020, using the following terms: "Neurosurgery," "COVID-19/SARS-CoV-2," "reconversion/modification," "practice," "academy," and "teaching." Then, they created operational guidelines tailored for their institution to maximize resource efficiency and minimize risk for the healthcare personnel. RESULTS: According to the reviewed literature, the authors defined the following three changes that have had the greatest impact in neurosurgical practice during the COVID-19 pandemic: 1) changes in clinical practices; 2) changes in the medical care setting, including modifications of perioperative care; and 3) changes in the academic teaching methodology. CONCLUSIONS: The Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez" is one of the major referral centers for treating highly complex neurosurgical pathologies in Mexico. Its clinical and neurosurgical practices have been modified with the implementation of specific interventions against the spread of COVID-19. These practical and simple actions are remarkably relevant in the context of the pandemic and can be adopted and suited by other healthcare centers according to their available resources to better prepare for the next event.
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COVID-19/epidemiologia , Procedimentos Neurocirúrgicos/normas , Equipamento de Proteção Individual/normas , Guias de Prática Clínica como Assunto/normas , Centros de Atenção Terciária/normas , COVID-19/prevenção & controle , Humanos , México/epidemiologia , Neurocirurgiões/normas , Neurocirurgiões/tendências , Procedimentos Neurocirúrgicos/tendências , Assistência Perioperatória/normas , Assistência Perioperatória/tendências , Equipamento de Proteção Individual/tendências , Centros de Atenção Terciária/tendênciasRESUMO
Gliomas are the most common primary intrinsic tumor in the brain and are classified as low- or high-grade according to the World Health Organization (WHO). Patients with high-grade gliomas (HGG) who undergo surgical resection with adjuvant therapy have a mean overall survival of 15 months and 100% recurrence. The renin-angiotensin system (RAS), the primary regulator of cardiovascular circulation, exhibits local action and works as a paracrine system. In the context of this local regulation, the expression of RAS peptides and receptors has been detected in different kinds of tumors, including gliomas. The dysregulation of RAS components plays a significant role in the proliferation, angiogenesis, and invasion of these tumors, and therefore in their outcomes. The study and potential application of RAS peptides and receptors as biomarkers in gliomas could bring advantages against the limitations of current tumoral markers and should be considered in the future. The targeting of RAS components by RAS blockers has shown potential of being protective against cancer and improving immunotherapy. In gliomas, RAS blockers have shown a broad spectrum for beneficial effects and are being considered for use in treatment protocols. This review aims to summarize the background behind how RAS plays a role in gliomagenesis and explore the evidence that could lead to their use as biomarkers and treatment adjuvants.
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Angiotensinas/uso terapêutico , Biomarcadores/metabolismo , Neoplasias Encefálicas/terapia , Glioma/terapia , Sistema Renina-Angiotensina/fisiologia , Angiotensinas/química , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Humanos , Fragmentos de Peptídeos/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacosRESUMO
Women have always had a hard time in the history of medicine; Dr. Isabel Blackwell was the first woman in history to practice medicine. Dr. Diana Beck became the world´s first female neurosurgeon. The first Latin American female neurosurgeon was Dr. María Cristina García Sancho y Álvarez-Tostado. All of these women had to face a large number of social, cultural, and economic obstacles in their path; however, this situation has changed gradually. Dr. Ana Lilia Siordia Karam was the first neurosurgeon to graduate from INNN. Nineteen years later the second female neurosurgeon at this institute was Dr. María Petra Herrera Guerrero. During their time at this institute they endured a lot of difficulties, especially with most of their coworkers; however, some coworkers treated them with respect and no gender distinction. Nowadays, four of the 25 total neurosurgery residents at INNN are women, and even though some of them have had to endure acts of gender discrimination, the general situation has changed. With work and respect, women have managed to have a larger role in the surgical field. We hope that in the near future a gender discrimination-free environment will be achieved in medicine and its specialties.
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Academias e Institutos/história , Neurologia/história , Neurocirurgia/história , Médicas/história , Feminino , História do Século XX , História do Século XXI , Humanos , MéxicoRESUMO
This research aims to propose a neurological surgery care protocol for the lesbian, gay, bisexual, transgender, queer, questioning, intersex, or asexual (LGBTQIA+) community. In recent years, people belonging to the LGBTQIA+ community have started to come out and express their identity due to growing awareness and various factors like the implementation of legal protections and rights in several countries; it is well documented in the literature that this community faces unique health needs as well as barriers and inequalities in healthcare. The lack of tailored training for medical specialists affects the level of quality and access to medical care for these individuals, and neurosurgical care is no exception. This literature review included studies in scientific journals and articles discussing problems, best practices, and gaps in the existing neurological surgical care protocols for LGBTQIA+ people. Accordingly, it highlights shared challenges such as healthcare-related difficulties, communication barriers, discrimination, and stigmatization. The primary aim is to create a safe and respectful care environment that ensures fair medical treatment to all patients regardless of their sexual orientation or gender identity. The review sheds light on the need for inclusive and sensitive neurosurgical care to improve clinical outcomes and the experience of patients belonging to the LGBTQIA+ community, thereby ensuring an environment of dignified treatment and satisfactory recovery from neurosurgical events.
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Background: Glioblastoma multiforme represents approximately 60% of all brain tumors in adults. This malignancy shows a high level of biological and genetic heterogeneity associated with exceptional aggressiveness, leading to poor patient survival. One of the less common presentations is the appearance of primary multifocal lesions, which are linked with a worse prognosis. Among the multiple triggering factors in glioma progression, the administration of sex steroids and their analogs has been studied, but their role remains unclear to date. Case Description: A 43-year-old transgender woman who has a personal pathological history of receiving intramuscular (IM) hormone treatment for 27 years based on algestone/estradiol 150 mg/10 mg/mL. Three months ago, the patient suddenly experienced hemiplegia and hemiparesis in her right lower extremity, followed by a myoclonic focal epileptic seizure, vertigo, and a right frontal headache with a visual analog scale of 10/10. Magnetic resonance imaging images revealed an intra-axial mass with poorly defined, heterogeneous borders, and thick borders with perilesional edema in the left parietal lobe, as well as a rounded hypodense image with well-defined walls in the right internal capsule. The tumor was resected, and samples were sent to the pathology department, which confirmed the diagnosis of wild-type glioblastoma. Conclusion: This report identifies prolonged use of steroid-based hormone replacement therapy as the only predisposing factor in the oncogenesis of multifocal glioblastoma. It is an example that highlights the importance for physicians not to consider pathologies related to the human immunodeficiency virus rather than neoplasms in transgender patients in view of progressive neurological deterioration.
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TREX1 is a gene that encodes an exonuclease on the C-terminal strand at the 3 Ì end for DNA repair. Multiple syndromes associated with the alteration of this gene have been described, focusing in this case on retinal vasculopathy with cerebral leukodystrophy (RVCL). We present the case of a 44-year-old female patient with a familial history of cerebral pseudotumors. At the time of diagnosis, the patient presented weakness in the lower limbs and dysesthesias of the right body at the beginning of the clinical picture, without visual alterations or retinal changes at fundus examination. A cranial magnetic resonance imaging (MRI) study showed a pseudotumoral lesion at the inferior frontal gyrus with a report of a choline peak in spectroscopy, ring enhancement in contrasted T1 sequence, and apparent central necrosis. A molecular study shows a mutation in c2136G>A, c.799dup, and c.5312A>G related to genes expressing PDE6A, TREX1, and VCAN proteins, respectively, mutations that have not been previously reported.
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Gangliogliomas are central nervous system (CNS) tumors with a neuronal and glial component considered grade 1 according to the World Health Organization (WHO) classification. On the other hand, oligodendrogliomas are diffuse infiltrating gliomas (CNS WHO grade 2 or 3) characterized by both an isocitrate dehydrogenase mutation and 1p/19q co-deletion. There have been some cases with the coexistence of these two tumors. Here, we present the case of a low-growing left frontoparietal brain tumor with a definite diagnosis of ganglioglioma (CNS WHO grade 1) and oligodendroglioma (CNS WHO grade 2) with areas of anaplastic oligodendroglioma (CNS WHO grade 3) in a patient with long-standing epilepsy.
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Psychiatric symptoms caused by brain lesions are not uncommon nowadays, caused by several different pathologies such as Alzheimer's, dementia, vascular and oncological diseases, etc. and they are known as neuropsychiatric or neurobehavioral symptoms, overlapping as mental health disorders. The most common primary brain tumors are gliomas, and the most common neuropsychiatric symptoms caused by them are depression, anxiety disorder, schizophrenia-like psychosis, anorexia nervosa, or cognitive dysfunction. We present a case of a 46-year-old male with no psychiatric familial history who started with a schizophrenia-like psychosis with hallucinations and, in consequence, killed his mother, symptoms which, after almost eight years, were known to be caused by a brain tumor.
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Background: The aim of the study was to describe the origin, course, and termination of frontal aslant tract (FAT) in the Mexican population of neurosurgical referral centers. Methods: From January 2018 to May 2019, we analyzed 50 magnetic resonance imaging (MRI) studies in diffusion tensor imaging sequences of patients of the National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez." Five brains were fixed by the Klingler method and dissected in the neurosurgery laboratory of the Hospital Civil de Guadalajara to identify the origin, trajectory, and ending of the FAT. Results: FAT was identified in 100% of the MRI and brain dissections. The origin of the FAT was observed in 63% from the supplementary premotor area, 24% from the supplementary motor area, and 13% in both areas. Its ending was observed in the pars opercularis in 81%, pars triangularis in 9%, and in both pars opercularis and ventral premotor area in 10% in the magnetic resonance images, with a left side predominance. In the hemispheres dissections, the origin of FAT was identified in 60% from the supplementary premotor area, 20% from the supplementary motor area, and 20% in both areas. Its ending was observed in the pars opercularis in 80% and the pars triangularis in 20%. It was not identified as an individual fascicle connected with the contralateral FAT. Conclusion: In the Mexican population, FAT has a left predominance; it is originated more frequently in the supplementary premotor area, passes dorsal to the superior longitudinal fascicle II and the superior periinsular sulcus, and ends more commonly in the pars opercularis.
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BACKGROUND: Surgical resection plays a pivotal role in the management of glial tumors and a greater extent of resection (EOR) should be the goal in most surgeries to improve overall survival. Many factors may limit the EOR. A potential role for preoperative chemotherapy to decrease the volume and/or infiltration of gliomas, thereby facilitating a safe radical resection, has been recently suggested. This review aims to provide an overview of the current state of neoadjuvant therapy in the field of glioma surgery. METHODS: A systematic review was conducted according to PRISMA guidelines to identify articles of low- and high-grade gliomas that received neoadjuvant chemotherapy prior to surgery to improve the EOR from 2000 to 2020. Full-text articles that addressed this subject were included for evaluation. RESULTS: Case reports and clinical trials have been published for the use of chemotherapy as a neoadjuvant therapy to improve surgical resection in low-grade gliomas. More scarce information exists regarding this strategy for high-grade glioma surgery. CONCLUSIONS: Neoadjuvant chemotherapy has played a role in overcoming obstacles that limit the EOR in patients with complex gliomas, especially low-grade gliomas.
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Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Quimioterapia Adjuvante/métodos , Glioma/terapia , Terapia Neoadjuvante/métodos , HumanosRESUMO
BACKGROUND: Decompressive craniectomy (DC) has been used for the treatment of refractory increased intracranial pressure (ICP) in patients with brain trauma and stroke; its beneficial role is still a matter of debate. Little has been written on the role of DC in the setting of patients with intracranial tumors. METHODS: We retrospectively reviewed our institutional tumor registry for all adult patients treated with a DC as an emergency treatment between January 2012 and June 2019. RESULTS: A total of 61 patients were taken into surgery for a DC secondary to raised ICP related to a central nervous system tumor. The Kaplan-Meier curves in the study showed that 18.9 months was the mean survival time (MST) of the global population, 40 patients died (65.5%) during the follow-up period. Patients in the group of over 60 years had a worst survival time than younger patients (p = 0.01). Patients with intracerebral hemorrhage had the worst MST compared with the patients with other etiologies (p = 0.04). CONCLUSION: Our data show that in some selected cases DC is a viable option as a salvage treatment for patients with intracranial tumors.
ANTECEDENTES: la craniectomía Descompresiva (CD) se ha utilizado para el tratamiento del aumento de la presión intracraneal en pacientes con traumatismo cerebral y accidente cerebrovascular; su papel beneficioso sigue siendo un tema de debate. Poco se ha escrito sobre el papel de la CD en el contexto de pacientes con tumores intracraneales. MÉTODOS: Revisamos retrospectivamente nuestro registro institucional de tumores para todos los pacientes adultos tratados con craniectomía descompresiva como tratamiento de emergencia entre enero de 2012 y junio de 2019. RESULTADOS: Un total de 61 pacientes fueron llevados a cirugía por una CD secundaria a elevación de ICP secundario a un tumor del sistema nervioso central. Las curvas de Kaplan-Meyer mostraron que 18.9 meses fue el tiempo medio de supervivencia de la población global, 40 pacientes murieron (65.5%) durante el período de seguimiento. Los pacientes del grupo de más de 60 años tuvieron un peor tiempo de supervivencia que los pacientes menores (p = 0,01). Los pacientes con hemorragia intracerebral tuvieron la peor sobrevida en comparación con los pacientes con otras etiologías (p = 0,04). CONCLUSIÓN: Nuestros datos muestran que en algunos casos seleccionados, la CD es una opción viable como tratamiento de rescate para pacientes con tumores intracraneales.
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Neoplasias do Sistema Nervoso Central , Craniectomia Descompressiva , Hipertensão Intracraniana , Adulto , Humanos , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/cirurgia , Pressão Intracraniana , Estudos Retrospectivos , Terapia de Salvação , Resultado do TratamentoRESUMO
The incidence of primary brain tumors during pregnancy is uncommon. The etiology of these can range from different genetic syndromes such as Li Fraumeni, neurofibromatosis type I, and hormonal associated tumors. The number of meningiomas gradually tends to increase during pregnancy, suggesting a relationship between non-malignant meningiomas and hormonal changes. Clinical features are non specific or can be misinterpreted with pregnancy symptoms such as headache, vomiting and dizziness. It is worth mentioning that the symptoms due to intracranial tumors are no different in pregnant compared with non pregnant patients. However, retrospective studies in glioma behavior suggested that both tumor volume and growth, increased during pregnancy. These changes were correlated with clinical worsening and increased frequency of seizures. The diagnosis requires a proper neurologic exploration and the support of imaging studies. Treatment of tumors is very controversial since we look for the preservation of both mother and fetus. In theory, the best therapy for the mother will also be the best therapy for the fetus. During pregnancy, ideally the treatment is symptomatic, to preserve the fetus, and definite treatment may be performed after birth; the latter is not always accomplished since patients may present with impending herniation or a malignant tumor for which immediate management is necessary. We intend to give an updated review in the literature on the adequate treatment of brain tumors during pregnancy and the anesthetic management during the definite treatment. Literature data was obtained from Pubmed using the search terms: "Pregnancy", "Brain", "Tumors". A total of forty-three articles were selected.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Complicações Neoplásicas na Gravidez/terapia , Feminino , Feto/diagnóstico por imagem , Feto/fisiologia , Glioma/complicações , Glioma/diagnóstico por imagem , Glioma/terapia , Cefaleia/diagnóstico por imagem , Cefaleia/etiologia , Cefaleia/terapia , Humanos , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/terapia , Meningioma/complicações , Meningioma/diagnóstico por imagem , Meningioma/terapia , Gravidez , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/etiologia , Convulsões/terapia , Vômito/diagnóstico por imagem , Vômito/etiologia , Vômito/terapiaRESUMO
INTRODUCTION: Astrocytomas are the most common and aggressive primary brain tumors, and they are classified according to the degree of malignancy on a scale of I to IV, in which grade I is the least malignant and grade IV the highest. Many factors are related to astrocytomas progression as progesterone receptor (PR), whose transcriptional activity could be regulated by phosphorylation by protein kinase C alpha (PKCα) at the residue Ser400. Our aim was to investigate if PR phosphorylation together with PKCα expression could be used as a prognostic factor for astrocytomas malignancy. METHODS: By immunofluorescence, we detected the content of PKCα, PR and its phosphorylation at Ser400 in 46 biopsies from Mexican patients with different astrocytoma malignancy grades; by bioinformatic tools using TCGA data, we evaluated the expression of PR and PKCα mRNA according to astrocytoma malignancy grades. For all statistical analyses, significance was p<0.05. RESULTS: We detected a positive correlation between the tumor grade and the content of PKCα, PR and its phosphorylation at Ser400, as well as the intracellular colocalization of these proteins. Interestingly, using an in silico assay, we found that the PR and PKCα expression at mRNA level has an inverse ratio with astrocytomas tumor grade. DISCUSSION: These results indicate that PR and its phosphorylation at Ser400 site, as well as PKCα and their colocalization, could be considered as possible malignancy biomarkers for astrocytomas grades I-IV.
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BACKGROUND: Recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents an important negative impact on global training of neurosurgery residents. Even before the pandemic, discrimination is a challenge that neurosurgical residents have consistently faced. In the present study, we evaluated discriminatory conditions experienced by residents during their neurosurgical training in Mexico before the SARS-CoV-2 pandemic. METHODS: An electronic survey of 18 questions was sent among residents registered in the Mexican Society of Neurological Surgery (MSNS), between October 2019 and July 2020. Statistical analysis was made in IBM SPSS Statistics 25. The survey focused on demographic characteristics, discrimination, personal satisfaction, and expectations of residents. RESULTS: A response rate of 50% (132 of 264 residents' members of MSNS) was obtained and considered for analysis. Median age was 30.06 ± 2.48 years, 5.3% (n = 7) were female and 16.7% (n = 22) were foreigners undergoing neurosurgical training in Mexico. Approximately 27% of respondents suffered any form of discrimination, mainly by place of origin (9.1%), by gender (8.3%) or by physical appearance (6.1%). About 42.9% (n = 3) of female residents were discriminated by gender versus 6.4% (n = 8) of male residents (P = 0.001); while foreign residents mentioned having suffered 10 times more an event of discrimination by place of origin compared to native Mexican residents (36.4% vs. 3.6%, P < 0.001). CONCLUSION: This manuscript represents the first approximation to determine the impact of discrimination suffered by residents undergoing neurosurgical training in Mexico before the SARS-CoV-2 pandemic.
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INTRODUCTION: Diffuse gliomas are brain neoplasms with an infiltrative growing pattern to cortical and subcortical structures, frequently adjacent to eloquent areas; direct cortical and subcortical stimulation in awake craniotomy is a useful tool to achieve a gross total resection with the least neurological deficit. PRESENTATION OF CASES: A 24 years old male presented with tonic-clonic seizures. The magnetic resonance imaging (MRI) showed a left parietal glioma. Awake craniotomy was performed using neuronavigation system and brain mapping with cortical and subcortical stimulation. Functional areas were found at the rostral margin of the tumor; however, the rest of the tumor was almost totally resected. Patient was discharged without neurological deficit. A 29 years old male presented in two occasions generalized tonic-clonic seizures, with right hemiparesis. The MRI showed a left parietal glioma. Awake craniotomy was performed using neuronavigation system and brain mapping with cortical and subcortical stimulation, achieving a gross total resection. Patient was discharged without neurological deficit. CONCLUSIONS: Awake craniotomy with brain mapping by cortical and subcortical stimulation and neuronavigation, are the best assets to treat diffuse gliomas and achieve a gross total resection, ensuring the major disease-free interval and preserving the function of eloquent areas.
INTRODUCCIÓN: Los gliomas difusos son neoplasias cerebrales con un patrón de crecimiento infiltrativo, frecuentemente adyacentes a áreas elocuentes. El mapeo cerebral con estimulación cortico-subcortical con el paciente despierto es una herramienta útil para lograr la mayor resección con el menor déficit posoperatorio. PRESENTACIÓN DE CASOS: Varón de 24 años con crisis tónico-clónicas. La resonancia magnética (RM) mostró un glioma parietal izquierdo. Se realizó cirugía con el paciente despierto y mapeo cerebral por estimulación cortical y subcortical directa. Se obtuvo una resección casi total, ya que se encontraron áreas fucionales en el borde rostral del tumor. El paciente egresó sin déficit neurológico. Varón de 29 años que presenta crisis tónico-clónicas generalizadas, acompañadas de hemiparesia derecha. La RM reportó un glioma parietal izquierdo. Se realizó cirugía con el paciente despierto y mapeo cerebral por estimulación cortical y subcortical directa. Se logró una resección total y el paciente egresó sin déficit. CONCLUSIONES: La cirugía con el paciente despierto con mapeo por estimulación directa y neuronavegación es la mejor opción en el tratamiento de los gliomas difusos, para lograr una resección máxima tumoral asegurando un mayor tiempo libre de enfermedad y la conservación de la función de áreas elocuentes.
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Mapeamento Encefálico , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Glioma/fisiopatologia , Glioma/cirurgia , Vigília , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Craniotomia/métodos , Intervalo Livre de Doença , Glioma/diagnóstico por imagem , Glioma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuronavegação/métodos , Convulsões/etiologia , Adulto JovemRESUMO
INTRODUCTION: Renin-angiotensin system (RAS) in brain cancer represents a scarcely explored field in neuro-oncology. Recently, some pre- and clinical studies have reported that RAS components play a relevant role in the development and behavior of gliomas. The angiotensinogen (AGT) rs5050 genetic variant has been identified as a crucial regulator of the transcription of AGT mRNA, which makes it a logical and promising target of research. The aim of this study was to determine the relationship between the AGT rs5050 genetic variant in blood with prognosis in astrocytoma. METHODS: A prospective pilot study was performed on forty-eight astrocytoma patients, who received the standard-of-care treatment. Blood samples were taken prior to surgery and DNA was sequenced using Ion Torrent next-generation sequencing and analyzed by Ion Reporter software. Descriptive, bivariate, multivariate, and survival analyses were performed using SPSS v21, STATA 12 and GraphPad Prism 7. RESULTS: Median follow-up was 41 months (range 1-48). Survival analysis showed a significant difference between the rs5050 genotypes (p = .05). We found lower survival rates in individuals with the GG-genotype of rs5050 AGT compared to patients with the TT- and TG-genotype (2 months vs. 11.5 months, respectively [p = .01]). In bivariate and multivariate analyses, GG-genotype was negatively associated with survival. CONCLUSIONS: In patients with astrocytoma, AGT rs5050 GG-genotype was associated with poor prognosis. We propose this germline genetic variant as a complementary biomarker, which can be detected practically and safely in blood samples or saliva.
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Angiotensinogênio/genética , Astrocitoma/diagnóstico , Astrocitoma/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Mutação em Linhagem Germinativa , Adulto , Idoso , Angiotensinogênio/sangue , Astrocitoma/mortalidade , Astrocitoma/terapia , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Feminino , Seguimentos , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Adulto JovemRESUMO
Object: Leptomeningeal Carcinomatosis (LCM) represents a state of systemic malignant disease with poor prognosis. The purpose of this study is to compare overall survival (OS) between intraventricular chemotherapy through Ommaya reservoir (OR) and chemotherapy through lumbar puncture (LP) in LCM. Patients and Methods: Forty adult patients with LCM were included. All patients underwent lumbar puncture and Magnetic resonance imaging (MRI). Thirty patients received chemotherapy through LP and 10 undergone colocation of Ommaya reservoir for intraventricular chemotherapy. Results: The most common symptom was headache (Present in 50%). The cranial nerves most affected were VI and VII. Leptomeningeal enhancement was the most frequent finding in MRI. The OS in the LP group was 4 months and Ommaya group was 9.2 months (p = 0.0006; CI:1.8-3), with statistical differences in favor to Intraventricular treatment. Proportional hazard regression showed that receiving chemotherapy through Ommaya reservoir was a protective factor (Hazard ratio = 0.258, Standard Error = 0.112, p = 0.002 and 95% CI 0.110-0.606). Using KPS as a factor did not affect the hazard ratio of Ommaya reservoir itself. Conclusions: OS was significantly higher in patients with Ommaya reservoir in spite of Karnofsky Performance Status (KPS) previous to chemotherapy. Therefore, intraventricular chemotherapy should be preferred over lumbar puncture chemotherapy administration if there are resources available.
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Intracellular progesterone receptors (PRs) and protein kinases C (PKCs) are known regulators of cancer cell proliferation and metastasis. Both PRs and PKCs are found overexpressed in grade IV human astrocytomas, also known as glioblastomas, which are the most frequent and aggressive brain tumors. In the present study, we investigated whether PR activation by PKC induces the migration and invasion of glioblastoma derived cell lines and if PKCα and δ isoforms are involved in PR activation. We observed that PKC activation with tetradecanoylphorbol acetate (TPA) increases the migration and invasion capacity of two human glioblastoma derived human cell lines (U251 MG and U87) and that the treatment with the PR receptor antagonist RU486 blocks these processes. Interestingly, the pharmacological inhibition of the isoenzymes PKCα and PKCδ also resulted in a blocked PR transcriptional activity. Also, TPA-dependent PR activation increases the expression of progesterone-induced blocking factor (PIBF), a known PR target gene. These results hint to an existing cross-talk between PKCs and PRs in regulating the infiltration process of human glioblastomas.