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1.
Surg Neurol Int ; 15: 270, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246780

RESUMO

Background: Hemorrhage originating from the intercavernous sinuses during transsphenoidal approaches for skull base injury is a common occurrence, but it can be easily controlled. However, in specific cases, it may necessitate suspending the surgery or result in hemodynamic instability. Case Description: We present the case of a 7-year-old female patient who underwent transsphenoidal endoscopic endonasal for craniopharyngioma resection. The patient's parents gave consent for the procedure. During the procedure, significant intraoperative bleeding occurred, which was necessary to stop the resection. After the surgery, cerebral angiography was performed, which identified a prominent anterior intercavernous venous sinus as the source of the bleeding. A successful embolization using onyx was performed, leading to a satisfactory postoperative recovery without any complications. The patient then underwent a second surgical intervention for the resection of the craniopharyngioma through an endoscopic endonasal transsphenoidal approach. This procedure achieved a complete resection of the lesion without complications, and the patient experienced an adequate postoperative recovery. Conclusion: The objective of this case is to describe a previously unreported technique involving onyx embolization for controlling prominent bleeding from the intercavernous sinus and as a presurgical embolization method to reduce the risk of bleeding during endoscopic endonasal surgery for resection of a craniopharyngioma.

2.
World Neurosurg ; 191: 138-148, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39233309

RESUMO

Cellular senescence in gliomas is a complex process that is induced by aging and replication, ionizing radiation, oncogenic stress, and the use of temozolomide. However, the escape routes that gliomas must evade senescence and achieve cellular immortality are much more complex, in which the expression of telomerase and the alternative lengthening of telomeres, as well as the mutation of some proto-oncogenes or tumor suppressor genes, are involved. In gliomas, these molecular mechanisms related to cellular senescence can have a tumor-suppressing or promoting effect and are directly involved in tumor recurrence and progression. From these cellular mechanisms related to cellular senescence, it is possible to generate targeted senostatic and senolytic therapies that improve the response to currently available treatments and improve survival rates. This review aims to summarize the mechanisms of induction and evasion of cellular senescence in gliomas, as well as review possible treatments with therapies targeting pathways related to cellular senescence.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39055532

RESUMO

Glioblastoma (GBM) is the most common malignant central nervous system tumor. The emerging field of epigenetics stands out as particularly promising. Notably, the discovery of micro RNAs (miRNAs) has paved the way for advancements in diagnosing, treating, and prognosticating patients with brain tumors. We aim to provide an overview of the emergence of miRNAs in GBM and their potential role in the multifaceted management of this disease. We discuss the current state of the art regarding miRNAs and GBM. We performed a narrative review using the MEDLINE/PUBMED database to retrieve peer-reviewed articles related to the use of miRNA approaches for the treatment of GBMs. MiRNAs are intrinsic non-coding RNA molecules that regulate gene expression mainly through post-transcriptional mechanisms. The deregulation of some of these molecules is related to the pathogenesis of GBM. The inclusion of molecular characterization for the diagnosis of brain tumors and the advent of less-invasive diagnostic methods such as liquid biopsies, highlights the potential of these molecules as biomarkers for guiding the management of brain tumors such as GBM. Importantly, there is a need for more studies to better examine the application of these novel molecules. The constantly changing characterization and approach to the diagnosis and management of brain tumors broaden the possibilities for the molecular inclusion of novel epigenetic molecules, such as miRNAs, for a better understanding of this disease.

4.
Clin Neurol Neurosurg ; 241: 108305, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38713964

RESUMO

OBJECTIVE: Establish the evolution of the connectome before and after resection of motor area glioma using a comparison of connectome maps and high-definition differential tractography (DifT). METHODS: DifT was done using normalized quantitative anisotropy (NQA) with DSI Studio. The quantitative analysis involved obtaining mean NQA and fractional anisotropy (FA) values for the disrupted pathways tracing the corticospinal tract (CST), and white fiber network changes over time. RESULTS: We described the baseline tractography, DifT, and white matter network changes from two patients who underwent resection of an oligodendroglioma (Case 1) and an IDH mutant astrocytoma, grade 4 (Case 2). CASE 1: There was a slight decrease in the diffusion signal of the compromised CST in the immediate postop. The NQA and FA values increased at the 1-year follow-up (0.18 vs. 0.32 and 0.35 vs. 0.44, respectively). CASE 2: There was an important decrease in the immediate postop, followed by an increase in the follow-up. In the 1-year follow-up, the patient presented with radiation necrosis and tumor recurrence, increasing NQA from 0.18 in the preop to 0.29. Fiber network analysis: whole-brain connectome comparison demonstrated no significant changes in the immediate postop. However, in the 1-year follow up there was a notorious reorganization of the fibers in both cases, showing the decreased density of connections. CONCLUSIONS: Connectome studies and DifT constitute new potential tools to predict early reorganization changes in a patient's networks, showing the brain plasticity capacity, and helping to establish timelines for the progression of the tumor and treatment-induced changes.


Assuntos
Neoplasias Encefálicas , Conectoma , Imagem de Tensor de Difusão , Estudos de Viabilidade , Glioma , Humanos , Imagem de Tensor de Difusão/métodos , Conectoma/métodos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/cirurgia , Glioma/diagnóstico por imagem , Glioma/patologia , Masculino , Pessoa de Meia-Idade , Adulto , Córtex Motor/diagnóstico por imagem , Córtex Motor/cirurgia , Córtex Motor/fisiopatologia , Tratos Piramidais/diagnóstico por imagem , Feminino , Oligodendroglioma/cirurgia , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/patologia , Astrocitoma/cirurgia , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia
6.
Front Neurol ; 14: 1269014, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38020666

RESUMO

Augmented reality (AR) integrates computer-generated content and real-world scenarios. Artificial intelligence's continuous development has allowed AR to be integrated into medicine. Neurosurgery has progressively introduced image-guided technologies. Integration of AR into the operating room has permitted a new perception of neurosurgical diseases, not only for neurosurgical planning, patient positioning, and incision design but also for intraoperative maneuvering and identification of critical neurovascular structures and tumor boundaries. Implementing AR, virtual reality, and mixed reality has introduced neurosurgeons into a new era of artificial interfaces. Meningiomas are the most frequent primary benign tumors commonly related to paramount neurovascular structures and bone landmarks. Integration of preoperative 3D reconstructions used for surgical planning into AR can now be inserted into the microsurgical field, injecting information into head-up displays and microscopes with integrated head-up displays, aiming to guide neurosurgeons intraoperatively to prevent potential injuries. This manuscript aims to provide a mini-review of the usage of AR for intracranial meningioma resection.

7.
J Neurooncol ; 164(2): 287-298, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37698707

RESUMO

BACKGROUND AND OBJECTIVE: Awake craniotomy (AC) is a valuable technique for surgical interventions in eloquent areas, but its adoption in low- and middle-income countries faces challenges like limited infrastructure, trained personnel shortage, and inadequate funding. This scoping review explores AC techniques in Latin American countries, focusing on patient characteristics, tumor location, symptomatology, and outcomes. METHODS: A scoping review followed PRISMA guidelines, searching five databases in English, Spanish, and Portuguese. We included 28 studies with 258 patients (mean age: 43, range: 11-92). Patterns in AC use in Latin America were analyzed. RESULTS: Most studies were from Brazil and Mexico (53.6%) and public institutions (70%). Low-grade gliomas were the most common lesions (55%), most of them located in the left hemisphere (52.3%) and frontal lobe (52.3%). Gross-total resection was achieved in 34.3% of cases. 62.9% used an Asleep-Awake-Asleep protocol, and 14.8% used Awake-Awake-Awake. The main complication was seizures (14.6%). Mean post-surgery discharge time was 68 h. Challenges included limited training, infrastructure, and instrumentation availability. Strategies discussed involve training in specialized centers, seeking sponsorships, applying for awards, and multidisciplinary collaborations with neuropsychology. CONCLUSION: Improved accessibility to resources, infrastructure, and adequate instrumentation is crucial for wider AC availability in Latin America. Despite disparities, AC implementation with proper training and teamwork yields favorable outcomes in resource-limited centers. Efforts should focus on addressing challenges and promoting equitable access to this valuable surgical technique in the region.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Adulto , Neoplasias Encefálicas/cirurgia , América Latina , Vigília , Craniotomia/métodos , Glioma/cirurgia
8.
Neurooncol Pract ; 10(4): 381-390, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37457227

RESUMO

Background: DICER1 alterations are associated with intracranial tumors in the pediatric population, including pineoblastoma, pituitary blastoma, and the recently described "primary DICER1-associated CNS sarcoma" (DCS). DCS is an extremely aggressive tumor with a distinct methylation signature and a high frequency of co-occurring mutations. However, little is known about its treatment approach and the genomic changes occurring after exposure to chemoradiotherapy. Methods: We collected clinical, histological, and molecular data from eight young adults with DCS. Genomic analysis was performed by Next-generation Sequencing (NGS). Subsequently, an additional germline variants analysis was completed. In addition, an NGS analysis on post-progression tumor tissue or liquid biopsy was performed when available. Multiple clinicopathological characteristics, treatment variables, and survival outcomes were assessed. Results: Median age was 20 years. Most lesions were supratentorial. Histology was classified as fusiform cell sarcomas (50%), undifferentiated (unclassified) sarcoma (37.5%), and chondrosarcoma (12.5%). Germline pathogenic DICER1 variants were present in two patients, 75% of cases had more than one somatic alteration in DICER1, and the most frequent commutation was TP53. Seven patients were treated with surgery, Ifosfamide, Cisplatin, and Etoposide (ICE) chemotherapy and radiotherapy. The objective response was 75%, and the median time to progression (TTP) was 14.5 months. At progression, the most common mutations were in KRAS and NF1. Overall survival was 30.8 months. Conclusions: DCS is an aggressive tumor with limited therapeutic options that requires a comprehensive diagnostic approach, including molecular characterization. Most cases had mutations in TP53, NF1, and PTEN, and most alterations at progression were related to MAPK, RAS and PI3K signaling pathways.

9.
Surg Neurol Int ; 14: 225, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37404501

RESUMO

Background: Gliomas represent almost 30% of all primary brain tumors and account for 80% of malignant primary ones. In the last two decades, significant progress has been made in understanding gliomas' molecular origin and development. These advancements have demonstrated a remarkable improvement in classification systems based on mutational markers, which contribute paramount information in addition to traditional histology-based classification. Methods: We performed a narrative review of the literature including each molecular marker described for adult diffuse gliomas used in the World Health Organization (WHO) central nervous system 5. Results: The 2021 WHO classification of diffuse gliomas encompasses many molecular aspects considered in the latest proposed hallmarks of cancer. The outcome of patients with diffuse gliomas relies on their molecular behavior and consequently, to determine clinical outcomes for these patients, molecular profiling should be mandatory. At least, the following molecular markers are necessary for the current most accurate classification of these tumors: (1) isocitrate dehydrogenase (IDH) IDH-1 mutation, (2) 1p/19q codeletion, (3) cyclin-dependent kinase inhibitor 2A/B deletion, (4) telomerase reverse transcriptase promoter mutation, (5) α-thalassemia/ mental retardation syndrome X-linked loss, (6) epidermal growth factor receptor amplification, and (7) tumor protein P53 mutation. These molecular markers have allowed the differentiation of multiple variations of the same disease, including the differentiation of distinct molecular Grade 4 gliomas. This could imply different clinical outcomes and possibly impact targeted therapies in the years to come. Conclusion: Physicians face different challenging scenarios according to the clinical features of patients with gliomas. In addition to the current advances in clinical decision-making, including radiological and surgical techniques, understanding the disease's molecular pathogenesis is paramount to improving the benefits of its clinical treatments. This review aims to describe straightforwardly the most remarkable aspects of the molecular pathogenesis of diffuse gliomas.

10.
Biomedica ; 42(4): 574-590, 2022 12 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36511679

RESUMO

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were tthe only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.


Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Bevacizumab , Sunitinibe , Everolimo , Estudos Retrospectivos , Neoplasias Meníngeas/genética
11.
Biomédica (Bogotá) ; 42(4): 574-590, oct.-dic. 2022. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1420307

RESUMO

Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.


Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were the only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.


Assuntos
Meningioma , Telomerase , Mutação com Ganho de Função
12.
Childs Nerv Syst ; 38(9): 1833-1835, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35141792

RESUMO

Central skull base osteomyelitis (CSBO) is a rare complication of infection in pediatric patients, especially when there are no comorbidities like immunosuppression or metabolic illness. The diagnosis of CSBO is a challenge in children, and imaging findings can mimic skull base tumor. We describe the clinical history and image diagnosis of a case in a 6-year-old girl with no relevant history who presented an extensive skull base lesion. She underwent tumor resection surgery. The intraoperative finding confirmed clivus osteomyelitis, and the histopathological studies discarded malignancy. After diagnosis, the patient completed 6-week antibiotic treatment with adequate evolution. In conclusion, CSBO should be considered within the differential diagnoses due to the fact that it can mimic skull base lesions and it may present without relevant history.


Assuntos
Osteomielite , Neoplasias da Base do Crânio , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Osteomielite/diagnóstico por imagem , Base do Crânio/diagnóstico por imagem , Base do Crânio/patologia , Neoplasias da Base do Crânio/complicações , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/cirurgia , Tomografia Computadorizada por Raios X
13.
Surg Neurol Int ; 12: 531, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754581

RESUMO

BACKGROUND: Normal pressure hydrocephalus (NPH) is a common neurodegenerative syndrome among the elderly characterized by ventriculomegaly and the classic triad of symmetric gait disturbance, cognitive decline and urinary incontinence. To date, the only effective treatment is a cerebrospinal fluid shunting procedure that can either be ventriculo-atrial, ventriculo-peritoneal, or lumbo-peritoneal shunt. The conventional ventriculo-atrial shunt uses venodissection, whereas the peel-away is a percutaneous ultrasound (US)-guided technique that shows some advantages over conventional technique. We sought to compare perioperative complication rates, mean operating time and clinical outcomes for both techniques in NPH patients at our institution. METHODS: A retrospective cohort-type analytical study was conducted, using clinical record data of patients diagnosed with NPH and treated at our center from January 2009 to September 2019. Parameters to be compared include: Perioperative complication rates, intraoperative bleeding, mortality, and mean operating time. Perioperative complication rates are those device-related such as shunt infection, dysfunction, and those associated with the procedure. Complications are further classified in immediate (occurring during the first inpatient stay), early (within the first 30 days of surgery), and late (after day 30 of surgery). RESULTS: A total of 123 patients underwent ventriculo-atrial shunt. Eighty-two patients (67%) underwent conventional venodissection technique and 41 patients (33%) underwent a peel-away technique. Immediate complications were 3 (3.6%) and 0 for conventional and peel-away groups, respectively. Early complications were 0 and 1 (2.4%) for conventional and peel-away groups, respectively. Late complications were 5 (6.1%) and 2 (4.9%) for conventional and peel-away groups, respectively. Mean operating time was lower in the peel-away group (P = 0.0000) and mortality was 0 for both groups. CONCLUSION: Ventriculo-atrial shunt is an effective procedure for patients with NPH. When comparing the conventional venodissection technique with a percutaneous US-guided peel-away technique, the latter offers advantages such as shorter operating time and lower perioperative complication rates.

14.
J Neurooncol ; 154(3): 353-364, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34498213

RESUMO

BACKGROUND: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer. METHODS: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial next-generation sequencing panel in liquid biopsy. RESULTS: There were ten males (66.7%), and the median patient's age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR. CONCLUSIONS: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glioblastoma , Acrilamidas , Adulto , Idoso , Compostos de Anilina , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB/genética , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Humanos , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases , Estudos Retrospectivos
15.
PLoS One ; 14(6): e0217340, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220093

RESUMO

PURPOSE: To compare the effectiveness of octreotide/everolimus vs. sunitinib for the systemic treatment of recurrent aggressive meningiomas. METHODS: 31 patients with recurrent or refractory WHO II or WHO III meningiomas were examined in two reference centers in Colombia. Patients who had systemic treatment (sunitinib, everolimus/octreotide) and a complete follow-up were included. Overall survival (OS), progression-free survival (PFS) and toxicities were evaluated. Additionally, tissue samples were examined for PDGFRß and VEGFR2, their expression was correlated with outcomes. RESULTS: Twenty-two patients (72%) were female with a median age of 55 years (SD±15.3). The most prevalent histology was anaplastic meningioma in 20 patients (65%) with 48% of patients suffering from three previous relapses before the start of systemic treatment. A total of 14 patients received combination therapy with octreotide/everolimus, 11 received sunitinib and the remaining 6 received other second-line agents. Median OS was 37.3 months (95%CI 28.5-42.1) and the PFS during the treatment with everolimus/octreotide (EO) and sunitinib (Su) was 12.1 months (95%CI 9.2-21.1) and 9.1 months (95%CI 6.8-16.8); p = 0.43), respectively. The OS of the group treated with the EO→Su→Bev sequence (1st/2nd/3rd line) was 6.5 months longer than the Su→EO→Bev sequence (36.0 vs. 29.5 months) (p = 0.0001). When analyzing molecular markers, the positive PDGFRß and negative VEGFR2 expression were associated with longer survival both in OS and PFS. CONCLUSION: Sunitinib and octreotide/everolimus have similar efficacy and safety in the systemic management of refractory meningioma. VEGFR2 and PDGFRß expression are associated with better outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/sangue , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Meníngeas , Meningioma , Proteínas de Neoplasias/sangue , Receptor beta de Fator de Crescimento Derivado de Plaquetas/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Everolimo/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/sangue , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/mortalidade , Meningioma/sangue , Meningioma/tratamento farmacológico , Meningioma/mortalidade , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Estudos Retrospectivos , Sunitinibe/administração & dosagem , Taxa de Sobrevida
16.
Acta neurol. colomb ; 34(4): 239-244, oct.-dic. 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-973530

RESUMO

RESUMEN Se expone el caso de una mujer de 19 años a quien se le realizó el diagnóstico de un xantoastrocitoma pleomórfico anaplásico parietooccipital izquierdo, neoplasia poco frecuente que suele presentarse en la población pediátrica y en los adultos jóvenes. Dicho tumor debuta generalmente con crisis convulsivas y sus características histológicas patognomónicas son el pleomorfismo celular, la vacuolización lipídica de su citoplasma y la reactividad a la proteína ácida fibrilar glial (PAFG) y S100. El estudio de nuevos marcadores que puedan brindar otras oportunidades terapéuticas ha permitido encontrar mutaciones en el oncogén BRAF. Este tumor presenta una variante anaplásica más agresiva que se trata con cirugía y quimiorradiación. En nuestro caso, después de varias progresiones a otras intervenciones, se utilizó bevacizumab y carmustine como tratamiento de segunda línea con respuesta completa.


SUMMARY The case of a young woman of 19-years-old is presented; whom the diagnosis was made of a left parietal-occipital xanthoastrocytoma pleomorphic anaplastic; this neoplasia is rare and usually affects the pediatric and young adult population. This generally debuts with seizures and their pathognomonic histologic characteristics are the pleomorphic cells with cytoplasmatic lipid vacuolation and the reactivity of glial fibrillary acidic protein (GFAP) and S100. The study of new markers that may provide other therapeutic opportunities has allowed finding mutations in the BRAF oncogene. This tumor has a more aggressive anaplastic variant that is treated with surgery and chemoradation. In our case after several progressions to other interventions, we used bevacizumab and carmustine as second-line treatment obtaining complete response.


Assuntos
Radioterapia , Carmustina , Bevacizumab , Glioma , Antineoplásicos
17.
J Neurooncol ; 136(2): 363-371, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29177594

RESUMO

Epilepsy is a common symptom in patients with glioblastoma (GB). 213 patients with GB from RedLANO follow-up registry were included. All patients underwent surgery, if feasible, followed by chemoradiation based on temozolomide (Stupp platform). Information was recorded regarding demographics, seizure timing, anti-epileptic drugs (AEDs), dosage, time to next seizure, total seizures in 6 months, and main side effects of AEDs. The relationship between epilepsy treatment and overall survival (OS) was evaluated. Mean age was 53 years old and 56.8% were male. Seventy-eight patients (37%) were treated with levetiracetam (LEV), 27% were given another AED and 36% did not require any AED. Choice of AED was not associated with age (p = 0.67), performance status (p = 0.24) or anatomic tumor site (p = 0.34). Seizures and AED requirement were greater in those having primary GB (p = 0.04). After starting an AED, the mean time until next crisis was 9.9 days (SD ± 6.3), which was shorter in those receiving LEV (p = 0.03); mean number of seizures during the first 3 and 6 months were 2.9 and 4, respectively. Most patients treated with LEV (n = 46) required less than two medication adjustments compared to those treated with other AEDs (p = 0.02). Likewise, less patients exposed to LEV required a coadjuvant drug (p = 0.04). Additionally, patients receiving LEV had significantly less adverse effects compared to patients treated with another AED. OS was significantly higher in the group treated with LEV compared to other AEDs (25.5 vs. 17.9 months; p = 0.047). Patients treated with LEV had better seizure control and longer OS compared to other AEDs.


Assuntos
Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/complicações , Epilepsia/tratamento farmacológico , Glioblastoma/complicações , Levetiracetam/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Epilepsia/complicações , Feminino , Hispânico ou Latino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
18.
Neurooncol Pract ; 3(3): 164-172, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386063

RESUMO

BACKGROUND: Low-grade gliomas (LGGs) are classified by the World Health Organization as astrocytoma (DA), oligodendroglioma (OD), and mixed oligoastrocytoma (OA). TP53 mutation and 1p19q codeletion are the most-commonly documented molecular abnormalities. Isocitrate dehydrogenase (IDH) 1/2 mutations are frequent in LGGs; however, IDH-negative gliomas can also occur. Recent research suggests that ATRX plays a significant role in gliomagenesis. METHODS: We investigated p53 and Olig2 protein expression, and MGMT promoter methylation, 1p19q codeletion, IDH, and ATRX status in 63 Colombian patients with LGG. The overall survival (OS) rate was estimated and compared according to genotype. RESULTS: The most common histology was DA, followed by OD and OA. IDH1/2 mutations were found in 57.1% and MGMT+ (positive status of MGMT promoter methylation methyl-guanyl-methyl-transferase gene) in 65.1% of patients, while overexpression of p53 and Olig2 was present in 30.2% and 44.4%, respectively, and 1p19q codeletion in 34.9% of the patients. Overexpression of ATRX was analyzed in 25 patients, 16% tested positive and were also mutations in isocitrate dehydrogenase and negative 1p19q-codelition. The median follow-up was 15.8 months (95% CI, 7.6-42.0) and OS was 39.2 months (95% CI, 1.3-114). OS was positively and significantly affected by MGMT+, 1p19q codeletion, surgical intervention extent, and number of lobes involved. Multivariate analysis confirmed that MGMT methylation status and 1p19q codeletion affected OS. CONCLUSIONS: This is the first study evaluating the molecular profile of Hispanic LGG patients. Findings confirmed the prognostic relevance of MGMT methylation and 1p19q codeletion, but do not support IDH1/2 mutation as a relevant marker. The latter may be explained by sample size and selection bias. ATRX alterations were limited to patients with DA and were mutations in isocitrate dehydrogenase and negative 1p19q-codelition.

19.
Rev. argent. radiol ; 76(3): 211-215, set. 2012. ilus
Artigo em Espanhol | LILACS | ID: lil-740623

RESUMO

Se presentan dos pacientes sometidos a derivación ventricular por hidrocefalia idiopática y cisticercosis del cuarto ventrículo, respectivamente. En la resonancia magnética (RM) de control se encontró un aumento en el tamaño del cuerpo calloso con zonas de prolongación de los tiempos de relajación sin restricción en la secuencia de difusión. Las teorías fisiopatológicas mencionan: efectos mecánicos directos tras la colocación de la derivación, efecto compresivo crónico sobre el cuerpo calloso contra la hoz cerebral por la hidrocefalia, tracción de ramas perforantes de las arterias pericallosas que conduce a isquemia (probablemente ausente en estudios prequirúrgicos por el adelgazamiento del cuerpo calloso) y descompresión, luego de la derivación, que produce reexpansión del cuerpo calloso y edema intersticial del mismo. Los hallazgos pueden explicarse por el antecedente de derivación e hidrocefalia sin repercusión clínica aparente...


Assuntos
Humanos , Feminino , Adulto , Hidrocefalia , Imageamento por Ressonância Magnética , Corpo Caloso , Derivação Ventriculoperitoneal
20.
Acta neurol. colomb ; 26(3): 149-154, jul.-sept. 2010. ilus
Artigo em Espanhol | LILACS | ID: lil-569700

RESUMO

La nocardiosis es una infección localizada o diseminada causada por un microorganismo aeróbico. En el sistema nervioso central (SNC) es poco común, sólo 2% de todos los abscesos cerebrales. Usualmente afecta a los pacientes inmunocomprometidos y es muy rara en los inmunocompetentes. En ambos causa una morbimortalidad significativa. No hay un tratamiento ideal; la cirugía desempeña un papel importante, ya que facilita el diagnóstico bacteriológico y en ocasiones alivia la presión intracraneana. Se presenta un paciente de 58 años con cefalea intensa y hemiparesia. El estudio de resonancia magnética demostró múltiples lesiones cerebrales. Se hicieron estudios de extensión para metástasis cerebrales, pero todos fueron negativos. Se efectuó una biopsia cerebral esterotáxica, negativa para malignidad en los cultivos creció una Nocardia spp. El manejo antibiótico ocasionó mejoría clínica significativa y a los 18 meses post-tratamiento el paciente está asintomático.


Nocardiosis can be a localized or disseminated infection caused by an aerobic microorganism. In the centralnervous system (CNS) is rare, only 2% of all brain abscesses. It usually affects immunocompromised patients and is uncommon in immunocompetent, but cause significant morbidity and mortality in both. There is no idealtreatment, surgery plays an important role because it facilitates the bacteriological diagnosis and sometimes relieve intracranial pressure. This paper reports a patient of 58 years with severe headache and hemiparesis. The MRI showed multiple brain lesions. Studies to rule out brain metastases were done, but all were negative. One stereotactic brain biopsy, negative for malignancy was positive for Nocardia spp. The antibiotic treatment gave a significant clinical improvement and18 months after treatment, patient is asymptomatic.


Assuntos
Humanos , Biópsia , Neurologia , Nocardia
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