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BACKGROUND: The transpetrosal approach is a complex skull base procedure with a high risk of complications, particularly caused by injury of the venous system. It is in part related to variability of blood outflow pathways and their distinctive patterns in each individual patient. OBJECTIVE: To evaluate outcomes and complications after skull base surgery with use of the petrosal approach modifications, which selection was based on the detailed preoperative assessment of venous drainage patterns. METHODS: Overall, 74 patients, who underwent surgery via the transpetrosal approach at our institution between 2000 and 2017, were included in this study. In all cases, the venous drainage pattern was assessed preoperatively and categorized according to the predominant blood outflow pathway into four types as previously suggested by Hacker: (1) sphenoparietal sinus (SpPrt), (2) sphenobasal vein (SpB), (3) sphenopetrosal sinus (SpPS), and (4) cortical. The blood outflow through the bridging petrosal vein and the vein of Labbé was also taken into consideration. In patients with SpPrt- and a cortical-type venous drainage, the transpetrosal approach was used in a standard way. In patients with SpB-type venous drainage, limited extradural anterior petrosectomy was combined with intradural anterior petrosectomy after dural opening, superior petrosal sinus transection, tentorial cutting, Meckel's cave opening, and trigeminal nerve mobilization. In patients with SpPS-type venous drainage, after standard petrosectomy, dural opening, and tentorial cutting, SpPS ligation was done followed by 2-week interval before staged definitive tumor resection. RESULTS: Gross total, near-total, and subtotal resection of the lesion (meningioma, 48 cases; retrochiasmatic craniopharyngioma, 11 cases; brain stem cavernoma, 7 cases; other tumors, 8 cases) was achieved in 30 (40.5%), 24 (32.4%), and 20 (27.0%) patients, respectively. Postoperative complications that were possibly related to venous compromise were noted in 18 patients (24.3%), but neither one was major. Of these 18 patients, 9 were symptomatic, but all symptoms-aphasia (4 cases), seizures (2 cases), and confusion (3 cases)-fully resolved after conservative treatment. Overall, 13 patients, including 4 symptomatic, had signal changes on T2-weighted brain MRI, which were permanent only in 3 cases (all asymptomatic). CONCLUSION: Our suggested surgical strategy can be applied to any type of the venous drainage pattern. Preoperative evaluation and intraoperative preservation of the blood outflow pathways are crucial means for safe and effective application of the transpetrosal approach.
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Neoplasias Meníngeas , Meningioma , Humanos , Base do Crânio/diagnóstico por imagem , Base do Crânio/cirurgia , Meningioma/irrigação sanguínea , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Craniotomia/métodos , Neoplasias Meníngeas/cirurgiaRESUMO
INTRODUCTION: This study investigates the current state of clinical practice and molecular analysis for elderly patients with diffuse gliomas and aims to elucidate treatment outcomes and prognostic factors of patients with glioblastomas. METHODS: We collected elderly cases (≥ 70 years) diagnosed with primary diffuse gliomas and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors. Clinical and pathological characteristics were analyzed retrospectively. Various factors were evaluated in univariate and multivariate models to examine their effects on overall survival. RESULTS: Included in the study were 140 elderly patients (WHO grade II: 7, III: 19, IV: 114), median age was 75 years. Sixty-seven patients (47.9%) had preoperative Karnofsky Performance Status score of ≥ 80. All patients underwent resection (gross-total: 20.0%, subtotal: 14.3%, partial: 39.3%, biopsy: 26.4%). Ninety-six of the patients (68.6%) received adjuvant treatment consisting of radiotherapy (RT) with temozolomide (TMZ). Seventy-eight of the patients (75.0%) received radiation dose of ≥ 50 Gy. MGMT promoter was methylated in 68 tumors (48.6%), IDH1/2 was wild-type in 129 tumors (92.1%), and TERT promoter was mutated in 78 of 128 tumors (60.9%). Median progression-free and overall survival of grade IV cases was 8.2 and 13.6 months, respectively. Higher age (≥ 80 years) and TERT promoter mutated were associated with shorter survival. Resection and adjuvant RT + TMZ were identified as independent factors for good prognosis. CONCLUSIONS: This community-based study reveals characteristics and outcomes of elderly glioma patients in a real-world setting. Elderly patients have several potential factors for poor prognosis, but resection followed by RT + TMZ could lengthen duration of survival.
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Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Glioma/metabolismo , Glioma/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Metilação de DNA , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Feminino , Glioma/genética , Glioma/mortalidade , Humanos , Isocitrato Desidrogenase/genética , Japão , Masculino , Mutação , Gradação de Tumores , Prognóstico , Estudos Retrospectivos , Telomerase/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Schwannoma arising from the olfactory system, often called olfactory groove schwannoma (OGS), is rare, as the olfactory bulb and tract, belonging to the central nervous system, should lack Schwann cells. Another rare entity called olfactory ensheathing cell tumor (OECT) has been reported, which mimics clinical and radiological characteristics of OGS. Here, we report two rare cases of schwannoma-like tumor in the anterior cranial fossa that showed negative staining for Leu7, but positive staining for Schwann/2E, and discuss their origin. Two cases of mass lesions in the anterior cranial fossa in a 26-year-old man and a 24-year-old woman were successfully removed. Morphological examination of these tumors was compatible with a diagnosis of schwannoma. Immunohistochemically, both cases were negative for Leu7, yielding a diagnosis of OECT, but were positive for the schwannoma-specific marker, Schwann/2E. Immunohistochemical staining results in our two cases question the current assumption that OGS and OECT can be distinguished only by Leu7 staining pattern. In conclusion, the origins of OGS and OECT remain to be determined, and further studies in larger numbers of cases are needed to characterize these rare tumors in the anterior cranial fossa.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Antígenos CD57/imunologia , Fossa Craniana Anterior/patologia , Neurilemoma/diagnóstico , Neurilemoma/patologia , Neoplasias da Base do Crânio/diagnóstico , Neoplasias da Base do Crânio/patologia , Adulto , Anticorpos Monoclonais , Neoplasias Encefálicas/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Neurilemoma/imunologia , Bulbo Olfatório/imunologia , Bulbo Olfatório/patologia , Neoplasias da Base do Crânio/imunologia , Adulto JovemRESUMO
Optic canal invasion by tuberculum sellae meningiomas (TSMs) has been reported, but the characteristics of invasion remain unclear. This study was performed to clarify the incidence and characteristics of optic canal invasion by TSM and to determine whether optic canal invasion could be predicted preoperatively by magnetic resonance imaging (MRI). Between February 2002 and August 2014, 31 patients with TSM underwent tumor resection in our institute. In all cases, the optic canal was explored to identify any tumor invasion. We classified the characteristics of optic canal invasion from intraoperative findings. Invasion was classified into four types: type 1: no invasion; type 2: secondary invasion; type 3: partial wall invasion (two subtypes); and type 4: invasion into the supero-medial-inferior walls of the optic canal. Thirty of 31 cases showed optic canal invasion. Of these 30 cases, 9 (30 %) showed bilateral optic canal invasion. The most common finding was type 1 (23 sides). Among cases with optic canal invasion (39 sides), type 4 was the most common pattern (17 sides), followed by type 3-infero-medial (13 sides), type 2 (5 sides), and type 3-supero-medial (4 sides). Blinded prediction of tumor invasion was accurate in 61 % of cases, but characteristics of tumor invasion were undeterminable from preoperative MRI. In conclusion, optic canal invasion was frequently seen in our consecutive series of TSM, characteristics of which were unpredictable preoperatively. Neurosurgeons should be aware of the high incidence and variety of optic canal invasion in planning strategies for TSM treatment.
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Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos , Sela Túrcica/cirurgia , Neoplasias Cranianas/cirurgia , Neoplasias Supratentoriais/cirurgia , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Nervo Óptico/cirurgia , Neoplasias Cranianas/diagnóstico , Osso Esfenoide/cirurgia , Adulto JovemRESUMO
Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. Second neoplasms as late effects of therapy for ALL have been recognized as a significant clinical issue given the increasing number of long-term survivors of ALL, because they can be the cause of death in such cases. In contrast, glioblastoma (GBM) is the most common primary brain tumor in adults. It is a malignant brain tumor that most often occurs in elderly patients, and GBM in young adults or adolescents appears to be rare. Here, we describe our experience of two cases of GBM in young long-term survivors of ALL, and emphasize the necessity of careful follow up of patients treated for ALL for the potential occurrence of central nervous system second neoplasms, especially when the patients have previously undergone cranial radiotherapy.
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Background Cardioembolic stroke (CE) is usually associated with a larger ischemic area leading to higher morbidity and mortality rates. No biomarkers for CE are available, which causes difficulty in differential diagnosis of CE from other subtypes of acute ischemic stroke. Methods: We prospectively evaluated consecutive patients with acute ischemic stroke to identify biomarkers that could distinguish between CE and other subtypes of acute ischemic stroke. Etiological diagnoses were identified according to the National Institute of Neurological Disorders and Stroke (NINDS) 111 classification using clinical examinations, computed tomography (CT), magnetic resonance imaging (MRI), cardiac evaluations, and other tests. The biomarkers N-terminal pro-brain natriuretic peptide (NT-pro-BNP), Thrombin-Antithrombin III Complex (TAT), and D-dimer were determined in blood samples collected within 48 hours of onset and compared between groups with and without CE. Non- CE consisted of atherothrombotic brain infarction (ATBI), lacunar infarction (LI), and other stroke subtypes of unknown cause (other). Results: This study included 279 patients diagnosed with acute ischemic stroke. Serum levels of NT-pro- BNP were significantly higher in those with than in those without CE stroke (p<0.0001). Analysis of receiver operating characteristics (ROC) curves indicated that an NT-pro-BNP cutoff of 332 pg/mL provided optimal sensitivity (98.3%) and specificity (75.8%) for distinguishing CE from non-CE. Conclusions: Serum levels of NT-pro-BNP may help in diagnosis of CE during the acute phase and thus allow appropriate therapy t6 prevent subsequent cardiogenic stroke.
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Cardiopatias , Embolia Intracraniana , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Acidente Vascular Cerebral , Idoso , Biomarcadores/sangue , Diagnóstico Diferencial , Feminino , Cardiopatias/sangue , Cardiopatias/complicações , Cardiopatias/diagnóstico , Humanos , Embolia Intracraniana/sangue , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/etiologia , Japão , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Tomografia Computadorizada por Raios X/métodosRESUMO
INTRODUCTION: Although cavernous sinus (CS) dural arteriovenous fistulas (d-AVFs) are usually treated with transvenous embolization (TVE) via the inferior petrosal sinus (IPS), IPSs are sometimes thrombosed and angiographically invisible. In such cases, the first obstacle to TVE is detecting the entry to the IPS. We report a new technique for TVE via IPS using intravascular ultrasonography (IVUS). METHODS: Three consecutive cases of CS d-AVF with ipsilateral or bilateral IPS occlusion were involved in this study. On TVE, the orifice of the IPS was investigated with IVUS placed in the jugular vein or jugular bulb. RESULTS: This technique has been successfully adapted in all three cases. In two of these cases, IPS was well visualized with the help of IVUS, and TVE was successfully performed. CONCLUSION: To our knowledge, this is the first report to mention the usefulness of IVUS for detecting angiographically occult IPS.
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Fístula Arteriovenosa/diagnóstico por imagem , Seio Cavernoso/diagnóstico por imagem , Embolização Terapêutica/métodos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Ultrassonografia de Intervenção/métodos , Insuficiência Venosa/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/terapia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento , Insuficiência Venosa/terapiaRESUMO
Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite current advances in therapy consisting of surgery followed by chemotherapy and radiation, the overall survival rate still remains poor. Therapeutic failures are partly attributable to the highly infiltrative nature of tumor adjacent to normal brain parenchyma. Recently, evidence is mounting to suggest that actin cytoskeleton dynamics are critical components of the cell invasion process. Drebrin is an actin-binding protein involved in the regulation of actin filament organization, and plays a significant role in cell motility; however, the role of drebrin in glioma cell invasiveness has not yet been fully elucidated. Therefore, this study was aimed to clarify the role of drebrin in glioma cell morphology and cell motility. Here we show that drebrin is expressed in glioma cell lines and in operative specimens of GBM. We demonstrate that stable overexpression of drebrin in U87 cells leads to alterations in cell morphology, and induces increased invasiveness in vitro while knockdown of drebrin in U87 cells by small interfering RNA (siRNA) decreases invasion and migration. In addition, we show that depletion of drebrin by siRNA alters glioma cell morphology in A172 GBM cell line. Our results suggest that drebrin contributes to the maintenance of cell shape, and may play an important role in glioma cell motility.
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Neoplasias Encefálicas/patologia , Movimento Celular/genética , Glioma/patologia , Neuropeptídeos/fisiologia , Neoplasias Encefálicas/genética , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Forma Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/genética , Humanos , Invasividade Neoplásica , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/farmacologia , Análise Serial de Tecidos , TransfecçãoRESUMO
BACKGROUND: The venous drainage of the temporal lobe, through bridging veins to the middle cranial fossa, is pivotal in determining the surgical corridor for skull base lesions. In dealing with select cases, where venous drainage was an obstacle in the surgical approach, we hypothesized that staged 'intentional' ligation of the dominant pathway of venous drainage would provide a safer and wider access to skull base tumors. We study the indications and safety of this surgical strategy in the management of skull base lesions. MATERIALS AND METHODS: From 1995 to 2012, 318 patients with skull base tumors were treated at our institute by the fronto-orbito-zygomatic (FOZ) or transpetrosal approaches, eight of whom we planned for staged 'intentional' bridging vein ligation. Seven patients underwent planned ligation of the bridging veins from the temporal lobe to the middle cranial fossa floor in the first stage, followed by definitive surgery through the desired skull base approach, in the second stage, while in one patient the strategy was abandoned. These patients were evaluated with respect to their clinical presentation, pre- and post-operative radiology including venogram, intra-operative findings and post-operative course. RESULTS: Seven patients, four males and three females, with ages ranging from 16 to 63 years, underwent staged 'intentional' bridging vein ligation. The diagnoses were recurrent craniopharyngioma in four, and petroclival meningioma, sphenopetroclival meningioma and spheno-orbital meningioma in one each. Six of these lesions were approached from the dominant (left) side, while one lesion was on the right side. Venograms done after the first-stage procedure showed obliteration of the dominant venous drainage with opening up of anastomotic venous channels in all patients. All patients tolerated the first-stage procedure well; only one patient showed asymptomatic mild temporal lobe edema on MRI, which resolved in 3 weeks. None of the patients had venous complications after definitive surgery. One patient with recurrent chordoma, who was planned for staged ligation, did not undergo ligation as, intra-operatively, the draining channel turned out to be a cortical vein, which could be mobilized without ligation. CONCLUSION: In an attempt to detether the temporal lobe, the disconnection of the bridging veins from the temporal lobe to the middle cranial fossa floor in the first stage may lead to re-direction of the venous outflow over time. This may allow skull base surgeons a better surgical corridor and ensure safety of venous structures during the definitive surgery.
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Veias Cerebrais/cirurgia , Craniofaringioma/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Base do Crânio/cirurgia , Adolescente , Adulto , Fossa Craniana Média/irrigação sanguínea , Fossa Craniana Média/cirurgia , Craniofaringioma/irrigação sanguínea , Drenagem/métodos , Feminino , Humanos , Ligadura/métodos , Masculino , Meningioma/irrigação sanguínea , Pessoa de Meia-Idade , Estudos Retrospectivos , Base do Crânio/irrigação sanguínea , Base do Crânio/cirurgia , Neoplasias da Base do Crânio/irrigação sanguínea , Lobo Temporal/irrigação sanguínea , Lobo Temporal/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
The hepatocyte growth factor (HGF)/MET pathway plays a critical role in the development of the nervous system and has been implicated in medulloblastoma pathogenesis. Recent studies have shown a role for gene amplification of activators of this pathway, as well as silencing of its inhibitors in medulloblastoma pathogenesis. We analyzed exon array data from a cohort of 103 primary medulloblastomas to show that HGF/MET pathway elements are dysregulated in tumors compared to normal cerebellum. To determine if mutation of HGF/MET pathway genes is a mechanism for pathway dysregulation, we conducted a mutational analysis by exon resequencing of three key components of this pathway, including serine protease inhibitor Kunitz-type 1 (SPINT1), serine protease inhibitor Kunitz-type 2 (SPINT2), and MET, in 32 primary human medulloblastoma specimens. From this analysis, we identified multiple coding synonymous and nonsynonymous single nucleotide polymorphisms in these genes among the 32 tumor samples. Interestingly, we also discovered two unreported sequence variants in SPINT1 and SPINT2 in two tumors that resulted in Arginine to Histidine amino acid substitutions at codons 418 and 233, respectively. However, conservation assessment and functional assays of these two variants indicate that they involve nonconserved residues and that they do not affect the function of SPINT1 and SPINT2 as tumor suppressor genes. In conclusion, our data suggest that mutation alone plays a minor role in causing aberrancies of the HGF/MET pathway in medulloblastoma in comparison with other malignancies such as breast, hepatocellular, renal, and lung carcinomas.
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Neoplasias Cerebelares/genética , Fator de Crescimento de Hepatócito/genética , Meduloblastoma/genética , Proteínas Proto-Oncogênicas c-met/genética , Adolescente , Adulto , Sequência de Aminoácidos , Movimento Celular , Proliferação de Células , Neoplasias Cerebelares/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Éxons , Feminino , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Lactente , Masculino , Meduloblastoma/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Dados de Sequência Molecular , Mutação , Polimorfismo de Nucleotídeo Único , Proteínas Secretadas Inibidoras de Proteinases/genética , Proteínas Secretadas Inibidoras de Proteinases/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de SinaisRESUMO
This study aimed whether the uptake of amino tracer positron emission tomography (PET) can be used as an additional imaging biomarker to estimate the prognosis of glioma. Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) grade II-IV astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution. Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10-0.41, p < 0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95% CI 1.23-22.8, p = 0.025; glioblastoma: HR 11.52, 95% CI 2.27-58.47, p = 0.0032), preoperative KPS ≥ 80 (HR 0.23, 95% CI 0.09-0.62, p = 0.004), maximum lesion-to-contralateral normal brain tissue (LN max) ≥ 4.03 (HR 0.24, 95% CI 0.08-0.71, p = 0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95% CI 1.81-109.2, p = 0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max ≥ 4.03 (29.3 months) than in patients with LN max < 4.03 (not reached; p = 0.03). OS differed significantly between patients with IDH mutant/LN max < 4.03 and patients with IDH mutant/LN max ≥ 4.03. LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO grade II-IV astrocytic glioma.
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Tomografia por Emissão de PósitronsRESUMO
BACKGROUND: The relationship between uptake of amino acid tracer with positron emission tomography (PET) and glioma subtypes/gene status is still unclear. OBJECTIVE: To assess the relationship between uptake of [11C]methionine using PET and pathology, IDH (isocitrate dehydrogenase) mutation, 1p/19q codeletion, and TERT (telomerase reverse transcriptase) promoter status in gliomas. METHODS: The participants were 68 patients with newly diagnosed and untreated glioma who underwent surgical excision and preoperative [11C]methionine PET examination at Osaka City University Hospital between July 2011 and March 2018. Clinical and imaging studies were reviewed retrospectively based on the medical records at our institution. RESULTS: The mean lesion/contralateral normal brain tissue (L/N) ratio of diffuse astrocytomas was significantly lower than that of anaplastic astrocytomas (P = 0.00155), glioblastoma (P < 0.001), and oligodendrogliomas (P = 0.0157). The mean L/N ratio of IDH mutant gliomas was significantly lower than that of IDH wild-type gliomas (median 1.75 vs. 2.61; P = 0.00162). A mean L/N ratio of 2.05 provided the best sensitivity and specificity for distinguishing between IDH mutant and IDH wild-type gliomas (69.2% and 76.2%, respectively). The mean L/N ratio of TERT promoter mutant gliomas was significantly higher than that of TERT promoter wild-type gliomas (P = 0.0147). Multiple regression analysis showed that pathologic diagnosis was the only influential factor on L/N ratio. CONCLUSIONS: Distinguishing glioma subtypes based on the revised 2016 World Health Organization classification of the central nervous system tumors on the basis of [11C]methionine PET alone seems to be difficult. However, [11C]methionine PET might be useful for predicting the IDH mutation status in newly diagnosed and untreated gliomas noninvasively before tumor resection.
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Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Metionina , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/diagnóstico por imagem , Astrocitoma/cirurgia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Criança , DNA de Neoplasias/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Glioma/cirurgia , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Mutação , Procedimentos Neurocirúrgicos , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/cirurgia , Regiões Promotoras Genéticas/genética , Estudos Retrospectivos , Sensibilidade e Especificidade , Telomerase/genética , Adulto JovemRESUMO
To image cerebral neural activity in ischemic areas, we proposed a novel technique to analyze spontaneous neuromagnetic fields based on standardized low-resolution brain electromagnetic tomography modified for a quantifiable method (sLORETA-qm). Using a 160-channel whole-head-type magnetoencephalographic system, cerebral magnetic fields were obtained pre- and postoperatively from 5 patients with unilateral internal carotid artery occlusive disease and 16 age-matched healthy volunteers. For quantitative imaging, voxel-based time-averaged intensities of slow waves in 4 frequency bands (0.3-2 Hz, 2-4 Hz, 4-6 Hz and 6-8 Hz) were obtained by the proposed technique based on sLORETA-qm. Positron emission tomography with (15)O gas inhalation ((15)O-PET) was also performed in these patients to evaluate cerebral blood flow and metabolism. In all 5 patients, slow waves in every frequency band were distributed in the area of cerebrovascular insufficiency, as confirmed by (15)O-PET preoperatively. In 4 patients, slow-wave intensities in theta bands (4-6 Hz, 6-8 Hz) decreased postoperatively along with improvements in cerebral blood flow and metabolism, whereas delta bands (0.3-2 Hz, 2-4 Hz) showed no significant differences between pre- and postoperatively. One patient with deterioration of cerebral infarction after surgery showed marked increases in slow-wave intensities in delta bands (0.3-2 Hz, 2-4 Hz) postoperatively, with distribution close to the infarct region. The proposed quantitative imaging of spontaneous neuromagnetic fields enabled clear visualization and alternations of cerebral neural conditions in the ischemic area. This technique may offer a novel, non-invasive method for identifying cerebral ischemia, although further studies in a larger number of patients are warranted.
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Isquemia Encefálica/patologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Isquemia Encefálica/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Disartria/patologia , Eletroencefalografia , Humanos , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Paresia/patologia , Tomografia por Emissão de PósitronsRESUMO
The authors report two cases of hypoglycemic coma in which both diffusion-weighted imaging (DWI) and single photon emission computed tomography (SPECT) were used. A 74-year-old woman (case 1) presented with deep coma associated with hypoglycemia (blood glucose level: 20 mg/dl), and DWI on admission revealed extensive hyperintensity lesions. SPECT obtained on the second hospital day revealed diffuse hyperperfusion and a follow-up SPECT on the eighth hospital day showed relative hypoperfusion. An 89- year- old woman (case 2) presented with coma associated with hypoglycemia (blood glucose level: 45 mg/dl), and DWI showed diffuse hyperintensity lesions in both hemispheres. SPECT obtained on the ninth hospital day showed relative hypoperfusion compared to the first scan obtained on the third hospital day. Although the blood glucose level was rapidly corrected, the level of consciousness remained unchanged in both cases. Our results suggest that cerebral blood flow may increase even after glucose correction and that relative hypoperfusion could occur in the subacute stage of hypoglycemic coma.
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Circulação Cerebrovascular/fisiologia , Coma/etiologia , Coma/fisiopatologia , Hipoglicemia/complicações , Hipoglicemia/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Coma/patologia , Imagem de Difusão por Ressonância Magnética , Feminino , Escala de Coma de Glasgow , Humanos , Hipoglicemia/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
AIM: To investigate clinicopathological significance of autophagy and its association with genetic alterations in gliomas. MATERIALS AND METHODS: The expression of three autophagy-related proteins, light chain-3 (LC3), beclin 1, and p62 was immunohistochemically analyzed in 32 low-grade gliomas and 65 high-grade gliomas. RESULTS: LC3, beclin 1, and p62 expression was positive in 70/94 (74%), 51/94 (54%) and 55/96 (57%) gliomas, respectively. High expression of LC3, beclin 1 and p62 was significantly more frequent in high-grade gliomas than in low-grade. Positive expression of LC3, beclin 1 and p62 were significantly positively correlated with overall survival, methylation of O6-methylyguanine-DNA methyltransferase (MGMT) promoter, mutations of isocitrate dehydrogenase 1 (IDH1) and telomerase reverse transcriptase (TERT) promoter, and 1p/19q co-deletion. Kaplan-Meier analyses revealed that LC3, p62 and autophagy status (positivity for at least two of the three proteins) were significantly associated with poorer survival. CONCLUSION: Autophagy might be associated with the progression of glioma, particularly high-grade, and thus might be a useful prognostic factor in patients with glioma.
Assuntos
Proteína Beclina-1/genética , Neoplasias Encefálicas/genética , Glioma/genética , Proteínas Associadas aos Microtúbulos/genética , Proteína Sequestossoma-1/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autofagia , Proteína Beclina-1/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Feminino , Glioma/metabolismo , Glioma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Proteína Sequestossoma-1/metabolismo , Adulto JovemRESUMO
BACKGROUND/AIM: Glioblastoma (GBM) is one of the most lethal solid cancers due to its highly invasive nature. The malignant potential of GBM cells might be partially regulated by surrounding normal cells, such as oligodendrocytes or fibroblasts. The aim of this study was to examine the interaction between stromal cells and GBM cells. MATERIALS AND METHODS: Two GBM cell lines were used. The effect of stromal cells, oligodendrocytes or fibroblasts, on the invasive ability of GBM cells was examined by wound-healing assay and invasion assay. RESULTS: Oligodendrocytes, in contrast to fibroblasts, significantly increased the migration and invasive ability of GBM cells. Angiopoietin-2 levels were high in the conditioned medium obtained from oligodendrocytes. Angiopoietin-2 significantly increased the motility of GBM, and the motility-stimulating activity of the oligodendrocytes-derived conditioned medium was significantly decreased by anti-angiopoietin-2-neutralizing antibody. CONCLUSION: Glioma stromal cells, oligodendrocytes, might up-regulate the invasiveness of GBM cells via angiopoietin-2 signaling.
Assuntos
Angiopoietina-2/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Oligodendroglia/citologia , Transdução de Sinais , Anticorpos Neutralizantes/química , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Meios de Cultivo Condicionados , Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Glioma/metabolismo , Humanos , Invasividade Neoplásica , Proteoma , Células Estromais/metabolismo , Regulação para CimaRESUMO
Identification of genotypes is crucial for treatment of glioma. Here, we developed a method to predict tumor genotypes using a pretrained convolutional neural network (CNN) from magnetic resonance (MR) images and compared the accuracy to that of a diagnosis based on conventional radiomic features and patient age. Multisite preoperative MR images of 164 patients with grade II/III glioma were grouped by IDH and TERT promoter (pTERT) mutations as follows: (1) IDH wild type, (2) IDH and pTERT co-mutations, (3) IDH mutant and pTERT wild type. We applied a CNN (AlexNet) to four types of MR sequence and obtained the CNN texture features to classify the groups with a linear support vector machine. The classification was also performed using conventional radiomic features and/or patient age. Using all features, we succeeded in classifying patients with an accuracy of 63.1%, which was significantly higher than the accuracy obtained from using either the radiomic features or patient age alone. In particular, prediction of the pTERT mutation was significantly improved by the CNN texture features. In conclusion, the pretrained CNN texture features capture the information of IDH and TERT genotypes in grade II/III gliomas better than the conventional radiomic features.
Assuntos
Glioma/diagnóstico , Glioma/genética , Isocitrato Desidrogenase/genética , Imageamento por Ressonância Magnética , Mutação , Redes Neurais de Computação , Regiões Promotoras Genéticas , Telomerase/genética , Biomarcadores Tumorais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Reprodutibilidade dos TestesRESUMO
UNLABELLED: We evaluated the diagnostic accuracy of PET with l-methyl-(11)C-methionine ((11)C-MET) for the differentiation of recurrent brain tumors from radiation necrosis. METHODS: Seventy-seven patients who had been previously treated with radiotherapy after primary treatment for metastatic brain tumor (n=51) or glioma (n=26) were studied to clarify the diagnostic performance of (11)C-MET PET in differentiating between recurrent brain tumors and radiation necrosis. A total of 88 PET scans with (11)C-MET were obtained; sometimes more than one scan was obtained when there was an indication of recurrent brain tumor or radiation necrosis. A definitive diagnosis was made on the basis of pathologic examination for recurrent brain tumors and on the basis of pathologic examination or clinical course for radiation necrosis. Several indices characterizing the lesions were determined; these included mean and maximum standardized uptake values (SUV(mean) and SUV(max), respectively) and the ratios of lesion uptake to contralateral normal frontal-lobe gray matter uptake corresponding to the SUV(mean) and the SUV(max) (L/N(mean) and L/N(max), respectively). Receiver-operating-characteristic (ROC) curve analysis was used to determine the optimal index of (11)C-MET PET and cutoff values for the differential diagnosis of tumor recurrence and radiation necrosis. RESULTS: The values of each index of (11)C-MET PET tended to be higher for tumor recurrence than for radiation necrosis. There were significant differences between tumor recurrence and radiation necrosis in all of the indices except for the L/N(max) for glioma. ROC analysis indicated that the L/N(mean) was the most informative index for differentiating between tumor recurrence and radiation necrosis. An L/N(mean) of greater than 1.41 provided the best sensitivity and specificity for metastatic brain tumor (79% and 75%, respectively), and an L/N(mean) of greater than 1.58 provided the best sensitivity and specificity for glioma (75% and 75%, respectively). CONCLUSION: (11)C-MET PET can provide quantitative values to aid in the differentiation of tumor recurrence from radiation necrosis, although these values do not appear to be absolute indicators. Quantitative analysis of (11)C-MET PET data may be helpful in managing irradiated brain tumors.
Assuntos
Neoplasias Encefálicas/diagnóstico , Metionina , Necrose/diagnóstico , Necrose/etiologia , Tomografia por Emissão de Pósitrons/métodos , Radioterapia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Radioisótopos de Carbono , Diagnóstico Diferencial , Feminino , Glioma/diagnóstico , Glioma/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e EspecificidadeRESUMO
Molecular biological characterization of tumors has become a pivotal procedure for glioma patient care. The aim of this study is to build conventional MRI-based radiomics model to predict genetic alterations within grade II/III gliomas attempting to implement lesion location information in the model to improve diagnostic accuracy. One-hundred and ninety-nine grade II/III gliomas patients were enrolled. Three molecular subtypes were identified: IDH1/2-mutant, IDH1/2-mutant with TERT promoter mutation, and IDH-wild type. A total of 109 radiomics features from 169 MRI datasets and location information from 199 datasets were extracted. Prediction modeling for genetic alteration was trained via LASSO regression for 111 datasets and validated by the remaining 58 datasets. IDH mutation was detected with an accuracy of 0.82 for the training set and 0.83 for the validation set without lesion location information. Diagnostic accuracy improved to 0.85 for the training set and 0.87 for the validation set when lesion location information was implemented. Diagnostic accuracy for predicting 3 molecular subtypes of grade II/III gliomas was 0.74 for the training set and 0.56 for the validation set with lesion location information implemented. Conventional MRI-based radiomics is one of the most promising strategies that may lead to a non-invasive diagnostic technique for molecular characterization of grade II/III gliomas.
Assuntos
Glioma/diagnóstico por imagem , Glioma/genética , Isocitrato Desidrogenase/genética , Imageamento por Ressonância Magnética/métodos , Regiões Promotoras Genéticas/genética , Telomerase/genética , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Feminino , Glioma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Mutação/genética , Adulto JovemRESUMO
A 68-year-old woman presented with an extremely rare brain abscess associated with old and acute hemorrhages manifesting as gradual onset of symptoms of headache and fever. Magnetic resonance imaging clearly visualized the hemorrhage as heterogeneously hyperintense on diffusion-weighted imaging, concentric hypo-isointense on T(1)-weighted imaging, and homogeneously hyperintense with a hypointense rim on T(2)(*)-weighted imaging. T(1)-weighted imaging with contrast medium revealed a well-enhanced cyst wall. In spite of treatment with antibiotics, the neurological status of the patient deteriorated due to expansion of the abscess and perifocal edema. Needle aspiration of the cyst yielded bloody purulent fluid. The magnetic resonance imaging findings indicate that neovascularization of the cyst wall is involved in the mechanism of hemorrhage in brain abscess. Careful follow-up examinations are recommended in patients with brain abscess to detect warning signs of neurological deterioration.