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Hemangioblastomas are rare lesions accounting for 1-5% of all spinal cord tumors and are mostly associated with von Hippel-Lindau syndrome. Localization in the cauda equina is uncommon. In this manuscript we aim to describe a rare case of sporadic intradural extramedullary hemangioblastoma of the cauda equina and present a literature review. A systematic research was performed on Pubmed, MEDLINE, and Google Scholar, using as keywords "spinal hemangioblastoma" and "cauda equina tumors". The previous literature is integrated by the description of the present case. A 49 year-old female, presented on August 2020 to our institution suffering from claudication neurogena, right sciatica and paraesthesia in right L5 radicular dermatome for more than 3 months. Neurological examination revealed hypoesthesia on right L5 dermatome and weakness of right anterior tibialis muscle. An MRI which showed an intradural mass at L1/2 level and an angiography that showing a nidus of serpiginous vessels inside the lesion. Microsurgical en bloc resection of lesion was performed with adjuvant neurophisological intra operative monitorings. Histological examination provided the diagnosis of hemangioblastoma. After surgery symptoms and neurological impairment gradually improved. A 10 months post-operative MRI showed no residual tumor. Although intradural extramedullary hemangioblastoma of the cauda equina without von Hippel-Lindau syndrome it is a rare pathological entity, this diagnosis must be taken in for cauda equina masses. Preoperative embolization is an option to minimize intraoperative bleeding. Radiosurgery seems to prevent recurrences when the tumor is not completely excised. Complete surgical removal of the lesion is usually possible and lead to a low likelihood of recurrence.
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Síndrome da Cauda Equina , Cauda Equina , Hemangioblastoma , Neoplasias da Medula Espinal , Doença de von Hippel-Lindau , Feminino , Humanos , Pessoa de Meia-Idade , Hemangioblastoma/complicações , Hemangioblastoma/diagnóstico por imagem , Hemangioblastoma/cirurgia , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/patologia , Cauda Equina/diagnóstico por imagem , Cauda Equina/cirurgia , Síndrome da Cauda Equina/patologia , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/diagnóstico por imagemRESUMO
The association of a meningioma and intratumoral aneurysm is extremely rare. The coexistence of both lesions may cause difficulties in diagnosis and treatment. We present the case of a 65 y.o. woman with a left temporal meningioma and an intralesional ruptured aneurysm of a terminal branch of the middle cerebral artery whose parental vessel fed the tumor. The tumor and the embedded aneurysm were removed safely with improvement of her symptoms.
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Aneurisma Roto , Aneurisma Intracraniano , Neoplasias Meníngeas , Meningioma , Humanos , Feminino , Meningioma/complicações , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Artéria Cerebral MédiaRESUMO
Background: Hemangioblastomas (HBs) are rare lesions accounting for 1%-5% of all spinal cord tumors, and are mostly associated with Von Hippel-Lindau (VHL) syndrome. Localization in the cauda equina is uncommon. Aim: In this manuscript, we aimed to describe a rare case of sporadic intradural extramedullary HB of the cauda equina and present a literature review. Mathods: A systematic research was performed on PubMed, MEDLINE, and Google Scholar, using the keywords "spinal HB" and "cauda equina tumors." The previous literature is integrated by the description of the present case. A 49-year-old female presented in August 2020 to our institution with a magnetic resonance imaging (MRI) which showed an intradural mass at L1/2 level and angiography that showing a nidus of serpiginous vessels inside the lesion. Symptoms were right sciatica and paresthesia in right L5 radicular dermatome for more than 3 months. Neurological examination revealed claudicatio spinalis and hypoesthesia on right L5 dermatome and weakness of right anterior tibialis muscle. Microsurgical en bloc resection of lesion was performed with adjuvant neurophysiological intraoperative monitoring. The histological examination provided the diagnosis of HB. Results: After surgery, symptoms and neurological impairment gradually improved. Postoperative MRI showed no residual tumor. Conclusions: Although intradural extramedullary HB of the cauda equina without VHL syndrome is a rare pathological entity, this diagnosis must be taken in consideration when a mass affects cauda equina. Preoperative embolization is an option to minimize intraoperative bleeding. Radiosurgery seems to prevent recurrences when the tumor is not completely excised. A complete surgical removal of the lesion is usually possible and it leads to a low likelihood of recurrence.
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Background: Tentorial meningiomas account for only 3-6% of all intracranial meningiomas. Among them, tentorial incisura (notch) location must be considered as a subgroup with specific surgical anatomy and indications, morbidity, and mortality. In this study, we propose an update on preoperative management in order to reduce postoperative deficits. Methods: We retrospectively collected adult patients treated for incisural meningioma between January 1992 and December 2016 in two different neurosurgical departments. Demographic, clinical, and neuroradiological preoperative and postoperative data were analyzed. In the most recent subgroup of tumors, a preoperative digital simulation was performed to define a volumetric digital quantification of the tumor resection. A review of the pertinent literature has been also done. Results: We included 26 patients. The median age was 58.4 years. Onset neurological signs were cranial nerve deficit in 9 patients, hemiparesis in 7, gait disturbance in 3, and intracranial hypertension in 3 patients. Simpson grade I removal was achieved in 12 patients, II in 10, III in 3, and IV in 1 patient. An overall rate of 23% postoperative complications was observed. The average follow-up duration was 68.5 months. Residual tumor was reported in 8 patients. Five patients underwent gamma knife radiosurgery. In 34.6% of patients, the surgical approach was chosen with preoperative digital planning estimating the potential volume of postoperative residual tumor, the target for radiosurgical treatment. Conclusions: A multidisciplinary approach to plan incisural meningiomas management is important. To lower postoperative morbidity and mortality, a careful preoperative case analysis is useful. A planned residual tumor, supported by preoperative simulation imaging, could be safely treated with radiosurgery.
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BACKGROUND: The population ageing generates new challenges related to the treatment of chronic diseases. The course of the disease makes patients and caregivers (CGs) vulnerable and their ability to self-care is threatened. CGs can be supported by the Advanced Practice Nurse (APN). OBJECTIVE: The aim is to deepen the CGs' needs of people with chronic conditions in Insubrica region. METHOS: It's a qualitative descriptive survey, conducted between September 2019 and February 2020. The CGs' convenience sample of people with chronic illness was differentiated by age, gender, profession, chronic diseases and included 20 participants. Data were collected through short motivational interviews and the compilation of a socio-family genogram. The thematic analysis of the interviews' Verbatim transcription was carried out by 4 researchers. RESULTS: The thematic analysis has shown 26 themes collected in 6 macrothemes and in addition highlighted that the chronic condition and vulnerability are linked together; therapeutic adherence and self-care depend on disease awareness, and CGs make little use of the social support network; CONCLUSION: Based on the results, it can be said that the APN can meet the GCs' needs through the skills gained in training (CanMEDS and Hamric model); encourage inter-professional and integrated care, and promote the formal and informal network.
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Cuidadores , Apoio Social , Doença Crônica , Humanos , Pesquisa Qualitativa , AutocuidadoRESUMO
INTRODUCTION: Patients' needs and the change of health professionals' roles have led researchers to reflect about the involvement of nurses in care processes development, as well as health policies. Studies confirm how advanced nursing training promotes quality of care and reduces the costs of healthcare. The introduction of the Advanced Practice Nurses (APNs) could potentially be an added value also in the Swiss healthcare context, where this figure is positioning. The study aims to investigate how APNs can participate in building health policy projects. METHOD: This is a qualitative study. Four focus groups were conducted on nurses with managerial and clinical roles. A content analysis approach with three review phases was applied. RESULTS: The identified macro-themes are: APN: Advanced training provides the skills needed to exercise the role. However, it emerges that the recognition of nurses in the field of health policies originates from a cultural change. Interprofessional collaboration: Multidisciplinary work allows overall patient care. However, requests for advice from the APN is still marginal. Health policy: The emerged needs are: defining a target population, educating the population and encouraging organizations to obtain quality certifications. Proposals for improvement: adequate training and the involvement of specialized figures are required for suitable care. CONCLUSIONS: APNs have potential impact upon health policy discussions. The authors recommend investing on education and cultural change, in order to maximize the active involvement in discussions supporting progress in nursing practice.
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Prática Avançada de Enfermagem , Enfermeiras e Enfermeiros , Grupos Focais , Política de Saúde , Humanos , Pesquisa QualitativaRESUMO
INTRODUCTION: Bullying in health care setting has a globally prevalence between 1% and 87% and it's in constant increase described by "WHO" as: "Bullying is a major public health problem". It is defined as a repeated ill-treatment, harmful for the health of one or more individuals by one or more people. There are different types of behaviours and they vary from verbal abuse, offensive conduct, humiliating and intimidating attitudes. Those attitudes won't help you doing your job. Different are the outcomes that those actions have on victims: anxiety, sleep disturbances, generalized pain and reduced attention. The objective of the study was to investigate the presence of the phenomenon within the Ticino (Swiss Canton) on healthcare contexts and to explain its experiences. METHODS: A qualitative study was conducted on a sample of healthcare professionals who are active in the Ticino (Switzerland) healthcare context through 18 semi-structured interviews and their thematic analysis. RESULTS: The results that emerged shows how the problem is also relevant in Ticino`s healthcare contexts, sometimes with different modalities and outcomes, moreover, experiencing these situations during one's working career leads to re-proposing such behaviours, as it is considered a rite of passage. What emerges in a predominant way is the lack of programs or structures aimed to prevent and support the victim and the perpetrator.
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Bullying , Ansiedade , Bullying/prevenção & controle , Atenção à Saúde , Pessoal de Saúde , Humanos , Pesquisa QualitativaRESUMO
INTRODUCTION: According to the theory of Self-Regulation, the individual develops self-regulation processes that guide the course of pathology through mental representations of disease. These should be an essential part of nursing in developing the patient's motivation and self-efficacy, and the Illness Perception Questionnaire allows us to understand the construction processes. AIM: The aim is to analyze the mental representations of illness of a group of chronically ill patients, to evaluate the implications in therapeutic adherence and clinical practice. METHODS: Pilot study conducted on a sample of 89 chronically ill patients through the Illness Perception Questionnaire. RESULTS: By correlating the illness dimensions of the Self-Regulation, the significant relationship between emotional representations and the other dimensions emerges. Negative emotions lead the individual to perceive more the cyclical duration of the disease, the severity of its consequences, have a lower perception of coherence and understanding of the disease. A greater opinion of personal control corresponds to a lower perception of serious consequences and a greater perception of control of treatment. The prevalence of negative emotions and a lower disease consistency score are highlighted in patients with low educational level. CONCLUSION: The study demonstrated the adequacy of IPQ-r in detecting disease representations, which can affect outcomes in treatment. Above all, the importance of the emotional dimension related to the perception of the disease. The application of IPQ-r can be a valid tool for nurses in detecting the perception of illness of their patients resulting in a useful strategy to promote the educational process and promote adequate therapeutic adherence.
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Emoções , Percepção , Humanos , Projetos Piloto , Psicometria , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Cervical pial arteriovenous malformation (AVM) is an extremely rare condition that can present with progressive myelopathy or acute hemorrhage (subarachnoid or intramedullary). The classification process is still a topic of discussion, given the limited number of cases described, as well as correct therapeutic management. Here, we present a case of a young female with anterior cervical pial AVM associated with spinal aneurysm. CASE DESCRIPTION: A 31-year-old female in the fifth month of pregnancy presented to the emergency department for tetraparesis, sphincter disturbances, and burning dysesthesia. Through magnetic resonance angiography, a cervical pial arteriovenous malformation (AVM) with a spinal aneurysm has been diagnosed. After a multidisciplinary consult, a neurosurgical approach has been proposed to minimize the hemorrhagic risk. A laminectomy C2-C4 level was performed, followed by identification of the AVM on the anterior-lateral left-sided surface of the spinal cord. The lesion was associated with a thrombosed aneurysm at the C2 level. Using neurophysiologic monitoring, we performed a temporary clipping of afferent vessels to the AVM. The thrombosed aneurysm was removed. Indocyanine green fluorescein and intraoperative Doppler confirmed complete resolution of AVM. The postoperative course has been regular with no complications recorded. CONCLUSIONS: Surgical procedure with perioperative neuromonitoring is an effective way to treat anterior cervical pial AVM associated with spinal aneurysm. A multidisciplinary approach is always suggested.
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Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/cirurgia , Veias Cerebrais/anormalidades , Vértebras Cervicais/anormalidades , Vértebras Cervicais/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Aneurisma/etiologia , Veias Cerebrais/cirurgia , Embolização Terapêutica , Feminino , Humanos , Laminectomia , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Gravidez , Doenças da Coluna Vertebral/etiologia , Resultado do TratamentoRESUMO
INTRODUCTION: Brainstem cavernous malformations (BSCMs) are clusters of dilated sinusoidal channels. Clinical presentation is characterized by focal neurological deficits and/or hemorrhage. The goal of this study is to analyze surgical indications and approaches in a series of patients with BSCM and review pertinent literature and suggest prognostic factors related to the anatomical, clinical, and surgical data collected. METHODS: We retrospectively reviewed the clinical data of 55 patients with BSCM, treated at three centers, from January 2006 to March 2016. We collected anagraphic data, pre and postoperative neurological status, pre and postradiological images, surgical procedures, and follow-up results. We summarized the anatomical, clinical, and surgical aspects of the lesions and identified two large groups based on the chosen approach: lateral and medial. Clinical and radiological results were then compared. RESULTS: The series comprised 55 patients. Hemorrhagic onset was observed in all patients. Suboccipital, retrosigmoid, anterior, subtentorial, subtemporal, transvermian, telovelar, far lateral and trans, and infratentorial approaches were performed. Neurological status improved postoperatively in 34 cases at last follow-up. Five patients showed clinical neurological worsening. Total resection was achieved in 46 cases and, during a mean follow-up of 63.4 months, no recurrence or re-bleeding occurred in those patients. The mean follow-up was 63.9 months. The mean modified Rankin Scale at final follow-up was used to analyze the results and draw our conclusions. CONCLUSIONS: A reasonable surgical approach, selection, and gentle handling of the surrounding structures are required to prevent impairment of neurologic function and avoid partial resection.
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Cerebral cavernous malformation (CCM) is a capillary malformation arising in the central nervous system. CCM may occur sporadically or cluster in families with autosomal dominant transmission, incomplete penetrance, and variable expressivity. Three genes are associated with CCM KRIT1, CCM2, and PDCD10. This work is a retrospective single-center molecular study on samples from multiple Italian clinical providers. From a pool of 317 CCM index patients, we found germline variants in either of the three genes in 80 (25.2%) probands, for a total of 55 different variants. In available families, extended molecular analysis found segregation in 60 additional subjects, for a total of 140 mutated individuals. From the 55 variants, 39 occurred in KRIT1 (20 novel), 8 in CCM2 (4 novel), and 8 in PDCD10 (4 novel). Effects of the three novel KRIT1 missense variants were characterized in silico. We also investigated a novel PDCD10 deletion spanning exon 4-10, on patient's fibroblasts, which showed significant reduction of interactions between KRIT1 and CCM2 encoded proteins and impaired autophagy process. This is the largest study in Italian CCM patients and expands the known mutational spectrum of KRIT1, CCM2, and PDCD10. Our approach highlights the relevance of seeking supporting information to pathogenicity of new variants for the improvement of management of CCM.
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Proteínas Reguladoras de Apoptose/genética , Proteínas de Transporte/genética , Neoplasias do Sistema Nervoso Central/genética , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Proteína KRIT1/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas/genética , Deleção de Sequência , Adulto , Idoso , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia , Proteínas de Transporte/metabolismo , Células Cultivadas , Neoplasias do Sistema Nervoso Central/metabolismo , Criança , Pré-Escolar , Simulação por Computador , Éxons , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Hemangioma Cavernoso do Sistema Nervoso Central/metabolismo , Humanos , Itália , Proteína KRIT1/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Proteínas Proto-Oncogênicas/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The transnasal approach to lesions involving the craniovertebral junction represents a technical challenge because of limited inferior exposure. The endoscopic transseptal approach (EtsA) with posterior nasal spine (PNS) removal is described. This technique can create a wide exposure of the craniovertebral junction, thereby increasing the caudal exposure. METHODS: On patients undergoing anterior craniovertebral junction decompression, we calculated the degree of exposure on the sagittal plan through a paraseptal route, an EtsA without and with PNS removal. The horizontal exposure and working area with the latter approach were also evaluated. RESULTS: Five patients underwent the transnasal procedure. The age of patients ranged from 34-71 years. All patients harbored basilar impression. The mean postoperative Nurick grade (1, 8) was improved versus the average preoperative grade (3). The average follow-up duration was 16 months. All patients underwent occipitocervical fixation. The mean vertical distances, from the clinoid recess to the inferior most limit with the paraseptal approach, EtsA without and with PNS removal were 38.52, 44.12, and 51.16 mm, respectively. The difference between our approach and a standard paraseptal route was statistically significant (P = 0.041; P< 0.05). The mean horizontal distances were 31.68 mm (mononostril entry) and 35.37 mm (binostril entry). The mean working area was 1795.53 mm2. CONCLUSIONS: Endoscopic endonasal approaches to the craniovertebral junction are increasing, but the downward extension on the anterior cervical spine represents a limit. Therefore, many surgeons prefer transoral or transcervical approaches. The EtsA with PNS removal allows for a more caudal exposure than the standard paraseptal approach, with reduced nasal trauma.
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Articulação Atlantoaxial/cirurgia , Articulação Atlantoccipital/cirurgia , Doenças Neurodegenerativas/cirurgia , Processo Odontoide/cirurgia , Cirurgia Endoscópica Transanal/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoccipital/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Boca/cirurgia , Doenças Neurodegenerativas/diagnóstico por imagem , Nariz/cirurgia , Processo Odontoide/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Optimal vision and ergonomics are important factors contributing to achievement of good results during neurosurgical interventions. The operating microscope and the endoscope have partially filled the gap between the need for good surgical vision and maintenance of a comfortable posture during surgery. Recently, a new technology called video-assisted telescope operating monitor or exoscope has been used in cranial surgery. The main drawback with previous prototypes was lack of stereopsis. We present the first case report of cranial surgery performed using the VITOM 3D, an exoscope conjugating 4K resolution view and three-dimensional technology, and discuss advantages and disadvantages compared with the operating microscope. CASE DESCRIPTION: A 50-year-old patient with vertigo and headache linked to a petrous ridge meningioma underwent surgery using the VITOM 3D. Complete removal of the tumor and resolution of symptoms were achieved. The telescope was maintained over the surgical field for the duration of the procedure; a video monitor was placed at 2 m from the surgeons; and a control unit allowed focusing, magnification, and repositioning of the camera. CONCLUSIONS: VITOM 3D is a video system that has overcome the lack of stereopsis, a major drawback of previous exoscope models. It has many advantages regarding ergonomics, versatility, and depth of field compared with the operating microscope, but the holder arm and the mechanism of repositioning, refocusing, and magnification need to be ameliorated. Surgeons should continue to use the technology they feel confident with, unless a distinct advantage with newer technologies can be demonstrated.
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Procedimentos Neurocirúrgicos/instrumentação , Cirurgia Vídeoassistida/instrumentação , Craniotomia/instrumentação , Transtornos da Cefaleia/etiologia , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Pessoa de Meia-Idade , Telescópios , Vertigem/etiologiaRESUMO
BACKGROUND: Human gliomas are a heterogeneous group of primary malignant brain tumors whose molecular pathogenesis is not yet solved. In this regard, a major research effort has been directed at identifying novel specific glioma-associated genes. Here, we investigated the effect of TRIM8 gene in glioma. METHODS: TRIM8 transcriptional level was profiled in our own glioma cases collection by qPCR and confirmed in the independent TCGA glioma cohort. The association between TRIM8 expression and Overall Survival and Progression-free Survival in TCGA cohort was determined by using uni-multivariable Cox regression analysis. The effect of TRIM8 on patient glioma cell proliferation was evaluated by performing MTT and clonogenic assays. The mechanisms causing the reduction of TRIM8 expression were explored by using qPCR and in vitro assays. RESULTS: We showed that TRIM8 expression correlates with unfavorable clinical outcome in glioma patients. We found that a restored TRIM8 expression induced a significant reduction of clonogenic potential in U87MG and patient's glioblastoma cells. Finally we provide experimental evidences showing that miR-17 directly targets the 3' UTR of TRIM8 and post-transcriptionally represses the expression of TRIM8. CONCLUSIONS: Our study provides evidences that TRIM8 may participate in the carcinogenesis and progression of glioma and that the transcriptional repression of TRIM8 might have potential value for predicting poor prognosis in glioma patients.
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Neoplasias Encefálicas/genética , Proteínas de Transporte/biossíntese , Glioma/genética , Proteínas do Tecido Nervoso/biossíntese , Prognóstico , Neoplasias Encefálicas/patologia , Proteínas de Transporte/genética , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Proteínas do Tecido Nervoso/genéticaRESUMO
Gliomas represent a disparate group of tumours for which there are to date no cure. Thus, there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA (miRNA) profile of 8 WHO grade II gliomas and 24 higher grade tumours (2 WHO grade III and 22 glioblastomas) by using the Affymetrix GeneChip miRNA Array v. 1.0. A relative quantification method (RT-qPCR) with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas (TCGA) datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade tumours. RT-qPCR confirmed the differential expression in the two patients' groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme (GBM) and Lower Grade Glioma (LGG) datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. Moreover, in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses (HR 1.19, pâ=â0.04, and HR 1.18, pâ=â0.029 respectively). Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas.
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Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Glioma/genética , MicroRNAs/genética , Invasividade Neoplásica/genética , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Fenótipo , PrognósticoRESUMO
Capillary hemangioblastomas (HGBs) of the CNS occur either sporadically or as part of the von Hippel-Lindau (VHL) syndrome. Molecular characterizations of the VHL gene in sporadic HGBs at the somatic level have been limited to date. We investigated the VHL gene in 57 patients most of whom (55 [96%] of 57) had a solitary CNS HGB at the time of surgery. Tissues from 23 HGBs of these patients (2 VHL related and 21 unrelated) were also investigated at genetic and epigenetic levels. Two of the 51 patients with apparently sporadic HGBs and no additional evidence of VHL (â¼4%) were found to have a germline VHL gene mutation; both of these patients subsequently developed evidence of VHL syndrome. Somatic VHL gene mutations were found in 11 (52%) of the 21 non-VHL-related cases. A germline mutation was identified in 5 (84%) of 6 VHL-associated HGBs; double gene inactivation was observed in tumor tissue from VHL syndrome patients. Seven different previously unreported VHL gene alterations (6 somatic and 1 germline) were identified; double hits were identified in 7 (12%) of 57 cases. Our findings confirm the usefulness of VHL gene analysis at the germline level in patients who present with apparently solitary HGB. Moreover, the genetic and epigenetic VHL gene investigations performed support a key role for functional alterations of the VHL gene in sporadic neuraxial HGB.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Capilares/patologia , Hemangioblastoma/diagnóstico , Hemangioblastoma/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adulto , Estudos de Coortes , Feminino , Seguimentos , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Análise de Sequência de DNA/métodos , Adulto JovemRESUMO
Glioblastoma multiforme (World Health Organization, grade IV astrocytoma) is the most common and most aggressive malignant primary brain tumor. We report a novel cell line, designated as ANGM-CSS, which was established from a 56-year-old male patient with a surgically removed glioblastoma multiforme. The ANGM-CSS cell line was established in vitro and characterized using histological and immunohistochemical staining, classical and molecular cytogenetic analyses, molecular studies and functional assays using a xenograft model in immunodeficient animals. ANGM-CSS was positive for CD133, nestin and vimentin proteins, whereas GFAP showed staining only in a fraction of the cells. Cytogenetic and molecular cytogenetic analysis revealed a near-tetraploid karyotype, with a modal chromosome number from 88 to 91, and additional cytogenetic abnormalities, such as the t(6;14)(p12;q11.2), t(8;10)(q24.2;q21.1) and t(5;9)(q34;p21) unbalanced translocations. Moreover, ANGM-CSS showed amplification of the MET and EGFR genes whose overexpression was observed at the mRNA level. Interestingly, ANGM-CSS is tumorigenic when implanted in immunodeficient mice, and the cells obtained from the xenografts showed the same morphology and karyotype in vitro as the original cell line. ANGM-CSS represents a biologically relevant cell line to be used to investigate the molecular pathology of glioblastoma multiforme, also to evaluate the efficacy of novel therapeutic drugs in vitro.
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Neoplasias Encefálicas/patologia , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral , Glioblastoma/patologia , Animais , Neoplasias Encefálicas/genética , Glioblastoma/genética , Humanos , Cariotipagem , CamundongosRESUMO
Solitary fibrous tumor (SFT) of the central nervous system was first described in 1996. A number of cases have been reported since. The authors present 5 new cases: 4 intracranial and 1 intraspinal. All patients were adults (age range, 47 to 75 years); 4 were male and 1 female; 4 cases were primary tumors; and 1 was a second tumor recurrence. All patients were surgically treated with gross total removal. All cases were histologically examined with immunohistochemical confirmation; 2 tumors exhibited diffuse classic histology, 1 tumor was a cellular variant, 1 tumor was myxoid, and 1 was predominantly classic with focal myxoid features and focally pleomorphic. The postoperative course was uneventful in all. The patient with the cellular variant experienced 2 local recurrences and eventually died of disease 10 years after the initial diagnosis. The patient with the myxoid variant--the tumor studied--which was the second recurrence of a previously misdiagnosed fibrous meningioma surgically treated 15 years earlier, had a recurrence after 2 years for the third time and eventually died of disease. Three patients are alive and well 11.6, 6, and 4 years after surgery. SFT is a rare tumor that needs to be differentiated from some mimickers, mainly fibrous meningioma, hemangiopericytoma, and with regard to the myxoid variant, also adult-onset myxochordoid meningioma and myxoid peripheral nerve sheath tumor. Immunohistochemistry is crucial for the correct diagnosis of SFT. The authors also performed a review of the literature and found a little more than 200 cases on record.
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Neoplasias Encefálicas/patologia , Tumores Fibrosos Solitários/patologia , Neoplasias da Medula Espinal/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We reviewed the world literature on solitary fibrous tumors of the central nervous system from August 1996 to July 2011, focusing on both clinicopathological features and diagnostic findings. The anatomical distribution of the 220 cases reported so far reveals that most are intracranial and just over one-fifth are intraspinal. In decreasing frequency, intracranial tumors involve the supratentorial and infratentorial compartments, the pontocerebellar angle, the sellar and parasellar regions, and the cranial nerves. Intraspinal tumors are mainly located in the thoracic and cervical segments. Although most solitary fibrous tumors of the central nervous system are dural based, a small subset presents as subpial, intraparenchymal, intraventricular, or as tumors involving the nerve rootlets with no dural connection. Preoperative imaging and intraoperative findings suggest meningioma, schwannoma or neurofibroma, hemangiopericytoma, or pituitary tumors. Immunohistochemistry is critical to establish a definitive histopathological diagnosis. Vimentin, CD34, BCL2, and CD99 are the most consistently positive markers. The usual histologic type generally behaves in a benign manner if complete removal is achieved. Recurrence is anticipated when resection is subtotal or when the tumor exhibits atypical histology. The proliferative index as assessed by MIB1 labeling is of prognostic significance. Occasionally, tumors featuring conventional morphology may recur, perhaps because of minimal residual disease left behind during surgical extirpation. Rare extracranial metastases and tumor-related deaths are on record. Surgery is the treatment of choice. Stereotactic and external beam radiation therapy may be indicated for postsurgical tumor remnants and for unresectable recurrences. Long-term active surveillance of the patients is mandatory.
Assuntos
Neoplasias Encefálicas/diagnóstico , Tumores Fibrosos Solitários/diagnóstico , Neoplasias da Medula Espinal/diagnóstico , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirurgia , Proliferação de Células , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Radioterapia Adjuvante , Tumores Fibrosos Solitários/metabolismo , Tumores Fibrosos Solitários/cirurgia , Neoplasias da Medula Espinal/metabolismo , Neoplasias da Medula Espinal/cirurgiaRESUMO
In light with the view that KEAP1 loss of function may impact tumour behavior and modify response to chemotherapeutical agents, we sought to determine whether KEAP1 gene is epigenetically regulated in malignant gliomas. We developed a Quantitative Methylation Specific PCR (QMSP) assay to analyze 86 malignant gliomas and 20 normal brain tissues. The discriminatory power of the assay was assessed by Receiving Operating Characteristics (ROC) curve analysis. The AUC value of the curve was 0.823 (95%CI: 0.764-0.883) with an optimal cut off value of 0.133 yielding a 74% sensitivity (95%CI: 63%-82%) and an 85% specificity (95%CI: 64%-95%). Bisulfite sequencing analysis confirmed QMSP results and demonstrated a direct correlation between percentage of methylated CpGs and methylation levels (Spearman's Rho 0.929, P=0.003). Remarkably, a strong inverse correlation was observed between methylation levels and KEAP1 mRNA transcript in tumour tissue (Spearman's Rho -0.656 P=0.0001) and in a cell line before and after treatment with 5-azacytidine (P=0.003). RECPAM multivariate statistical analysis studying the interaction between MGMT and KEAP1 methylation in subjects treated with radiotherapy and temozolomide (n=70), identified three prognostic classes of glioma patients at different risk to progress. While simultaneous methylation of MGMT and KEAP1 promoters was associated with the lowest risk to progress, patients showing only MGMT methylation were the subgroup at the higher risk (HR 5.54, 95% CI 1.35-22.74). Our results further suggest that KEAP1 expression is epigenetically regulated. In addition we demonstrated that KEAP1 is frequently methylated in malignant gliomas and a predictor of patient's outcome.