RESUMO
BACKGROUND: Leptomeningeal metastasis-related hydrocephalus causes distress to patients with end-stage cancer through headache and other symptoms by elevating intracranial pressure, thus reducing quality of life. Ventriculoperitoneal shunt has been used as a treatment option in palliative care. We review four cases of patients who underwent lumboperitoneal shunt for leptomeningeal metastasis-related hydrocephalus. CASES: All patients suffered from severe headache and nausea. The primary lesion was histologically diagnosed as lung adenocarcinoma in each case. The duration from diagnosis to onset of hydrocephalus symptoms ranged from 0 to 52 (mean 26) months. Cerebrospinal fluid pressure in every case was above the normal range due to high intracranial pressure. Case management: Conventional procedures for lumboperitoneal shunt were employed for all patients. Adjustable pressure valves were retrofitted into the shunt system. Case outcome: Three patients demonstrated significant improvement of clinical symptoms and quality of life after placement of lumboperitoneal shunts. In two cases, not only did performance status improve to independent daily activity but also comparatively long-term survival was achieved due to subsequent chemotherapies after surgery. No symptoms of peritoneal dissemination by floating cancer cells in cerebrospinal fluid were seen in any patients. CONCLUSION: Lumboperitoneal shunt appears to improve quality of life if the patient is suffering from symptoms of leptomeningeal metastasis-related hydrocephalus. Compared to ventriculoperitoneal shunt, lumboperitoneal shunt is less invasive and simpler, providing a suitable option for frail patients with end-stage cancer. Adjustable pressure shunt valves can cope with varying symptoms and ventricle sizes.
Assuntos
Derivações do Líquido Cefalorraquidiano , Hidrocefalia/terapia , Neoplasias Meníngeas/secundário , Cuidados Paliativos/métodos , Idoso , Feminino , Humanos , Hidrocefalia/etiologia , Masculino , Neoplasias Meníngeas/complicações , Pessoa de Meia-Idade , Qualidade de VidaRESUMO
OBJECTIVE: The aim of this work was to identify factors predictive of postoperative improvement of camptocormia in patients with Parkinson's disease (PD) treated by subthalamic nucleus (STN) stimulation. BACKGROUND: Camptocormia, one of the most disabling features of PD, often responds poorly to medical therapies. The reported effects of deep brain stimulation on PD-associated camptocormia vary, and preoperative characteristics affecting the surgical outcome remain unclear. METHODS: We evaluated 17 patients with camptocormia whose preoperative off-medication thoracolumbar angle exceeded 45°. We used photographs to measure their thoracolumbar angle preoperatively, 3â months after surgery, and at the last follow-up (mean 36.5â months postoperatively) in status on-medication and off-medication. The patient age, duration of PD and camptocormia, daily medications, Unified Parkinson's Disease Rating Scale (UPDRS) subscores and the Schwab-England activity of daily living scale (S-E) were also recorded. Univariate analysis was performed to identify factors predictive of the postoperative improvement of camptocormia. RESULTS: STN stimulation significantly improved the UPDRS subscores and S-E, and resulted in a reduction of daily medications 3â months post-treatment. The preoperative thoracolumbar angle (mean±SD) in status off-medication (84.0±29.5°) was significantly ameliorated 3â months postoperatively (49.8±29.3°) and at the last follow-up (54.8±28.3°). There was no correlation between the postoperative camptocormia improvement rate and preoperative parameters other than the duration and severity of camptocormia and the levodopa responsiveness of the thoracolumbar angle. Symptom duration negatively affected levodopa responsiveness. CONCLUSIONS: STN stimulation improves PD-associated camptocormia in parallel with preoperative levodopa responsiveness. Long symptom duration interferes with levodopa responsiveness.
Assuntos
Estimulação Encefálica Profunda , Levodopa/uso terapêutico , Atrofia Muscular Espinal/fisiopatologia , Atrofia Muscular Espinal/terapia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Curvaturas da Coluna Vertebral/fisiopatologia , Curvaturas da Coluna Vertebral/terapia , Núcleo Subtalâmico/fisiopatologia , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico/efeitos dos fármacos , Postura/fisiologia , Período Pré-Operatório , Prognóstico , Estatística como AssuntoRESUMO
BACKGROUND: Evaluating cerebrovascular reserve (CVR) is important for patients with moyamoya disease (MMD). 123I-iodoamphetamine single-photon emission CT (SPECT) with acetazolamide (ACZ) challenge is widely carried out, but using ACZ becomes problematic owing to its off-label use and its adverse effects. Here, we report the efficacy of dynamic susceptibility contrast MRI (DSC-MRI) for the evaluation of CVR in MMD patients. METHODS: All 33 MMD patients underwent both SPECT and DSC-MRI at an interval of <10 days from each other (mean age 38.3 years). The region of interest (ROI) was the anterior cerebral artery (ACA) territory, middle cerebral artery (MCA) territory, basal ganglia and cerebellum hemisphere for cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) images. The ratios of the ROIs to the ipsilateral cerebellum were calculated for each parameter and evaluated. The CVR was calculated using images acquired by SPECT before and after ACZ administration. The ratios of DSC-MRI parameters and CVR were compared and evaluated for each ROI. RESULTS: The MTT of the ACA and MCA territories significantly correlated with CVR (p < 0.0001). However, CBF and CBV had no correlation with CVR. The MTT ratio had a threshold of 1.966, with a sensitivity of 68.4% and a specificity of 91.5% for predicting decreased CVR (<10%). CONCLUSION: MTT had a negative correlation with CVR. DSC-MRI is easy, safe and useful for detecting decreased CVR and can be used as a standard examination in MMD patient's care.
Assuntos
Circulação Cerebrovascular , Meios de Contraste/administração & dosagem , Gadolínio DTPA/administração & dosagem , Imageamento por Ressonância Magnética , Doença de Moyamoya/diagnóstico por imagem , Imagem de Perfusão/métodos , Adolescente , Adulto , Área Sob a Curva , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Tomografia Computadorizada de Emissão de Fóton Único , Adulto JovemRESUMO
Epithelioid glioblastomas are one of the rarest histological variants of glioblastomas, which are not formally recognized by the World Health Organization (WHO) classification. Epithelioid glioblastomas usually occur as primary lesions, but there have been several reports of secondary epithelioid glioblastomas or epithelioid glioblastomas with pre- or co-existing lesions to date. The serine/threonine-protein kinase B-Raf (BRAF) V600E mutation has been found at a high frequency of 54% in epithelioid glioblastomas. We present a case of a 26-year-old female patient with an epithelioid glioblastoma with the BRAF V600E mutation in her right frontal lobe. In the present case, a low-grade diffuse astrocytoma component had colocalized with the epithelioid glioblastoma. The component presented prominent calcification on neuroimages as well as by histology, and low-grade diffuse astrocytoma was considered to be a precursor lesion of an epithelioid glioblastoma. However, the BRAF V600E mutation was detected only in epithelioid glioblastoma but not in low-grade diffuse astrocytoma. To the best of our knowledge, this is the first report demonstrating a discrepancy in the BRAF V600E mutation states between epithelioid glioblastoma and colocalized low-grade astrocytoma.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Glioblastoma/genética , Mutação , Neoplasias Primárias Múltiplas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Astrocitoma/patologia , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/patologia , Humanos , Imuno-Histoquímica , Gradação de Tumores , Neoplasias Primárias Múltiplas/patologiaRESUMO
BACKGROUND: Whether a difference in morphology of the infratentorial space is associated with hemifacial spasm is not well understood. The aim of this study was to analyze the three-dimensional conformation of the infratentorial space and evaluate any possible contribution of morphological characteristics to the development of neurovascular compression leading to hemifacial spasm. METHODS: We enrolled 25 patients with hemifacial spasm and matched them by age and sex to controls. The extent of the three-dimensional axes and the volume of the infratentorial space were measured using image analysis software for three-dimensional MRI. We evaluated the correlation between a morphological difference in the infratentorial space and changes in vascular configuration in the brain stem. RESULTS: We found no statistical difference in volumetric analyses. The mean aspect ratio on the coronal plane (the ratio of the Z to X extent) of the infratentorial space in patients with hemifacial spasm was significantly lower (p < 0.01) than that in controls, as was the mean aspect ratio on the sagittal plane (the ratio of Z to Y extent, p < 0.01). A smaller sagittal aspect ratio was correlated (p < 0.05) with greater lateral deviation of the basilar artery. CONCLUSIONS: Our results suggest that flatness of the superior-inferior dimension of the infratentorial space is an anatomical feature that characterizes patients with hemifacial spasm. We hypothesize that this unique structural variation may exaggerate the lateral deviation of the vertebrobasilar arteries due to arteriosclerosis and exacerbate the space competition among vessels and cranial nerves.
Assuntos
Aterosclerose/complicações , Artéria Basilar/diagnóstico por imagem , Espasmo Hemifacial/diagnóstico por imagem , Adulto , Idoso , Artéria Basilar/patologia , Tronco Encefálico/irrigação sanguínea , Tronco Encefálico/diagnóstico por imagem , Feminino , Espasmo Hemifacial/etiologia , Espasmo Hemifacial/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Previously we have reported a metal chelating histidine-pyridine-histidine system possessing a trityl group on the histidine imidazole, namely HPH-2Trt, which induces apoptosis in human pancreatic adenocarcinoma AsPC-1 cells. Herein the influence of the imidazole substitution of HPH-2Trt was examined. Five related compounds, HPH-1Trt, HPH-2Bzl, HPH-1Bzl, HPH-2Me, and HPH-1Me were newly synthesized and screened for their activity against AsPC-1 and brain tumor cells U87 and U251. HPH-1Trt and HPH-2Trt were highly active among the tested HPH compounds. In vitro DNA cleavage assay showed both HPH-1Trt and HPH-2Trt completely disintegrate pUC19 DNA. The introduction of trityl group decisively potentiated the activity.
Assuntos
DNA/química , Histidina/química , Imidazóis/química , Piridinas/química , Quelantes/química , HumanosRESUMO
BACKGROUND: This retrospective single-center study assessed the feasibility, outcomes, and side-effects of high-dose methotrexate (HD-MTX) plus procarbazine in the treatment of immunocompetent patients with primary central nervous system lymphoma (PCNSL). METHODS: Ninety-one patients diagnosed with PCNSL between January 2001 and December 2011 were treated with HD-MTX plus procarbazine. To reduce neurotoxicity in patients aged ≥60 years, only those not responding to chemotherapy and patients with relapse underwent whole-brain irradiation. RESULTS: All 91 consecutive patients were scheduled to receive HD-MTX. Their median age was 66 years (range 32-88 years) and their median Karnofsky performance score was 40 (range 20-100). While 56 patients (61.5 %) completed 3 cycles of HD-MTX chemotherapy and 48 (52.7 %) showed a complete response, treatment was stopped in 11 patients (12.1 %) due to toxicity. The median overall survival and progression-free survival were 40.6 and 11.7 months, respectively. Overall survival was significantly improved in patients who completed 3 cycles of chemotherapy compared with those did not (56.4 vs 24.0 months; p = 0.013 by univariate and p = 0.022 by multivariate analysis). CONCLUSIONS: Initial treatment with HD-MTX plus procarbazine was effective in patients with PCNSL. Completion of 3 cycles of HD-MTX chemotherapy was a significant independent prognostic factor for patient survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Procarbazina/administração & dosagem , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Glioblastoma multiforme (GBM) is the most frequent and aggressive brain tumor, and which harbors not only rapidly dividing cells but also small populations of slowly dividing and dormant cells with tumorigenesity-, self-renewal-, and multi-lineage differentiation capabilities. GBM stem cells (GSCs), which are resistant to conventional chemo -radiotherapy and may be a cause of local recurrence and dissemination. Additionally, heterogeneity of GSCs in the same tumor had been shown by the innovation of microarray and sequencing technology. However, outcome in patients with GBM remains unsatisfactory. Accumulation of the clinical evidence and basic research findings targeting for GSCs and their specific microenvironments (GSC niches) raise the possibility of new treatments to overcome GBM.
Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma , Células-Tronco Neoplásicas , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/terapia , Humanos , Mutação , Células-Tronco Neoplásicas/metabolismo , Recidiva , Nicho de Células-TroncoRESUMO
Temozolomide (TMZ), used to treat glioblastoma and malignant glioma, induces autophagy, apoptosis and senescence in cancer cells. We investigated fibrin glue (FG) as a drug delivery system for the local administration of high-concentration TMZ aimed at preventing glioma recurrence. Our high-power liquid chromatography studies indicated that FG containing TMZ (TMZ-FG) manifested a sustained drug release potential. We prepared a subcutaneous tumor model by injecting groups of mice with three malignant glioma cell lines and examined the antitumor effect of TMZ-FG. We estimated the tumor volume and performed immunostaining and immunoblotting using antibodies to Ki-67, cleaved caspase 3, LC3 and p16. When FG sheets containing TMZ (TMZ-FGS) were inserted beneath the tumors, their growth was significantly suppressed. In mice treated with peroral TMZ plus TMZ-FGS the tumors tended to be smaller than in mice whose tumors were treated with TMZ-FGS or peroral TMZ alone. The TMZ-FGS induced autophagy, apoptosis and senescence in subcutaneous glioma tumor cells. To assess the safety of TMZ-FG for normal brain, we placed it directly on the brain of living mice and stained tissue sections obtained in the acute and chronic phase immunohistochemically. In both phases, TMZ-FG failed to severely damage normal brain tissue. TMZ-FG may represent a safe new drug delivery system with sustained drug release potential to treat malignant glioma.
Assuntos
Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Adesivo Tecidual de Fibrina/administração & dosagem , Glioma/tratamento farmacológico , Animais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/química , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Dacarbazina/administração & dosagem , Dacarbazina/química , Dacarbazina/farmacocinética , Preparações de Ação Retardada/farmacologia , Feminino , Adesivo Tecidual de Fibrina/química , Camundongos , Camundongos Endogâmicos ICR , Camundongos Nus , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Transplante de Neoplasias , TemozolomidaRESUMO
BACKGROUND: Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been suggested to possess pleiotropic effects, including antioxidant and anti-inflammatory properties. We investigated the protective effects of pretreatment with rosuvastatin, a relatively hydrophilic statin, on early brain injury (EBI) after a subarachnoid hemorrhage (SAH), using the endovascular perforation SAH model. METHODS: Eighty-six male Sprague-Dawley rats were randomly divided into 3 groups: (1) sham operation, (2) SAH+vehicle, and (3) SAH+10 mg/kg rosuvastatin. Rosuvastatin or vehicle was orally administered to rats once daily from 7 days before to 1 day after the SAH operation. After SAH, we examined the effects of rosuvastatin on the neurologic score, brain water content, neuronal cell death estimated by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate nick end labeling staining, blood-brain barrier disruption by immunoglobulin G (IgG) extravasation, oxidative stress, and proinflammatory molecules. RESULTS: Compared with the vehicle group, rosuvastatin significantly improved the neurologic score and reduced the brain water content, neuronal cell death, and IgG extravasation. Rosuvastatin inhibited brain superoxide production, nuclear factor-kappa B (NF-κB) activation, and the increase in activated microglial cells after SAH. The increased expressions of tumor necrosis factor-alpha, endothelial matrix metalloproteinase-9, and neuronal cyclooxygenase-2 induced by SAH were prevented by rosuvastatin pretreatment. CONCLUSIONS: The present study demonstrates that rosuvastatin pretreatment ameliorates EBI after SAH through the attenuation of oxidative stress and NF-κB-mediated inflammation.
Assuntos
Lesões Encefálicas/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Fluorbenzenos/uso terapêutico , NF-kappa B/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Pirimidinas/uso terapêutico , Hemorragia Subaracnóidea/tratamento farmacológico , Sulfonamidas/uso terapêutico , Superóxidos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Fluorbenzenos/farmacologia , Masculino , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Pirimidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Rosuvastatina Cálcica , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/metabolismo , Sulfonamidas/farmacologiaRESUMO
BACKGROUND: To determine the prognostic value of isocitrate dehydrogenase 1 (IDH1) mutation, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and 1p/19q co-deletion in Japanese patients with malignant gliomas. METHODS: We studied 267 malignant gliomas, which included 171 glioblastomas (GBMs), 40 anaplastic astrocytomas (AAs), 30 anaplastic oligodendrogliomas (AOs), and 26 anaplastic oligoastrocytomas (AOAs). These malignant gliomas were divided into 2 groups (Group 1: GBM + AA, Group 2: AO + AOA) according to the presence of the oligodendroglioma component. We examined IDH1 mutation and MGMT promoter methylation in each group by direct sequencing and methylation-specific PCR, respectively. We further examined 1p/19q co-deletion in Group 2 by fluorescence in situ hybridization. Survival between groups was compared by Kaplan-Meier analysis. RESULTS: In Group 1, patients with IDH1 mutations exhibited a significantly longer survival time than patients with wild-type IDH1. However, no significant difference was observed in Group 2, although patients with IDH1 mutations tended to show prolonged survival. For both Group 1 and Group 2, patients with MGMT methylation survived longer than those without this methylation. Further, patients with 1p/19q co-deletion showed significantly better outcome in Group 2. CONCLUSIONS: Our study confirms the utility of IDH1 mutations and MGMT methylation in predicting the prognosis of Group 1 patients (GBM + AA) and demonstrated that IDH1 mutations may serve as a more reliable prognostic factor for such patients. We also showed that MGMT methylation and 1p/19q co-deletion rather than IDH1 mutations were prognostic factors for Group 2 patients (AOA + AO). Our study suggests that patients survive longer if they have IDH1 mutations and undergo total resection. Further, irrespective of MGMT promoter methylation status, the prognosis of glioma patients can be improved if total resection is performed. Moreover, our study includes the largest number of Japanese patients with malignant gliomas that has been analyzed for these three markers. We believe that our findings will increase the awareness of oncologists in Japan of the value of these markers for predicting prognosis and designing appropriate therapeutic strategies for treating this highly fatal disease.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Mutação/genética , Regiões Promotoras Genéticas/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , DNA de Neoplasias/genética , Feminino , Seguimentos , Glioma/mortalidade , Glioma/cirurgia , Humanos , Hibridização in Situ Fluorescente , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Central nervous system (CNS) hemangioblastoma (HB) is one of the most common manifestations in von Hippel-Lindau disease (VHL), but large-scale studies on clinical features of CNS HB in VHL are scarce. METHODS: On the basis of the results of a questionnaire, we collected data of VHL patients with CNS HB. RESULTS: The total number of CNS HBs in 111 VHL patients (male 59, female 52) was 264 with the following distributions: cerebellar, 65.4 %; brainstem, 9.9 %; spinal cord, 23.9 %; and pituitary, 1. 1 %. The follow-up period was 0.6 to 39.2 years, with the mean 12.5 years. Patients bearing brainstem or spinal cord HB also had another HB significantly more frequently than those bearing cerebellar HBs (P < 0.05). The mean onset age of CNS HB was 29.1 years, and that of patients bearing a single HB (mean 34.4 years) was significantly greater than that of multiple HBs (mean 25.7 years). Patients with multiple HBs under 40 years are more dominant than those with a single HB. The distribution rate of brainstem HB is significantly smaller in patients below 30 years than patients above 29 years. Although ECOG PS score increased along with number of operations, the onset age decreased with increasing number of operations. The mean ECOG PS score of patients below 20 years is significantly smaller than patients above 19 years. CONCLUSIONS: When the onset age of CNS HB is under 40 years, and CNS HB is located at the brainstem or spinal cord HB, the probability of multiple occurrence can be predicted. Since patients with an onset age under 20 years old preserve a high performance status, early detection of CNS HB would be important. In addition, since a multiple operations aggravate performance status, number of operations should be reduced.
Assuntos
Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/patologia , Hemangioblastoma/epidemiologia , Hemangioblastoma/patologia , Doença de von Hippel-Lindau/complicações , Adolescente , Adulto , Idade de Início , Idoso , Neoplasias do Sistema Nervoso Central/terapia , Criança , Estudos de Coortes , Feminino , Indicadores Básicos de Saúde , Hemangioblastoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Adulto Jovem , Doença de von Hippel-Lindau/patologia , Doença de von Hippel-Lindau/terapiaRESUMO
BACKGROUND/AIMS: Central nervous system germ cell tumors (CNS-GCTs) are relatively rare. While their incidence was thought to be higher in East Asia than the USA, recent evidence suggests the difference between Japan and the USA is not statistically significant. The aim of this study was to determine the rate of pediatric primary CNS-GCTs in Kumamoto prefecture, Japan. METHODS: We surveyed 6,615 new cases of primary intracranial tumors diagnosed in Kumamoto prefecture between 1989 and 2011. Among these, 251 (3.8%) occurred in patients younger than 15 years. The age-adjusted incidence rates were calculated by the direct method using 5-year age groupings; the incidence in the total Japanese population in the year 2000 was the standard. RESULTS: During the 23-year period, 70 cases of primary GCT were diagnosed. Of these tumors, 31 (44.3%) arose in patients aged between 0 and 14 years (22 boys, 9 girls). Their tumor location was pineal in 45.2%; the other sites were nonpineal. There were more germinomas (64.5%) than nongerminomas (35.5%) in this group. The age-adjusted annual incidence rate was 0.45 cases (boys: 0.64, girls: 0.28) per 10(5) children. At 2.29, the ratio of CNS-GCTs was higher in these boys than girls. Our data showed higher rates than data from CBTRUS 2012 (0.18/10(5)), SEER 2008 (0.15/10(5)) and Germany (0.10/10(5)). CONCLUSIONS: Our survey showed that the incidence of primary CNS-GCTs in children was higher in Kumamoto prefecture than in the USA and other Western countries, suggesting that racial backgrounds play a role.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Sistema de RegistrosRESUMO
OBJECTIVES: We retrospectively investigated the correlation between disease duration and the therapeutic effect of globus pallidus internus (GPi) stimulation in patients with primary cervical dystonia (CD). MATERIALS AND METHODS: Eight patients with CD unresponsive to medical treatments underwent bilateral GPi deep brain stimulation (DBS). They were followed for 63.5 ± 38.2 months (mean ± standard deviation) and were assessed before and at 1, 12, 24, and 36 months after surgery and at their final visit to our outpatient clinic using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Univariate analysis was performed to identify factors that affected their postoperative TWSTRS score. RESULTS: At last follow-up, disease severity and the degree of disability and pain on the TWSTRS were significantly improved by 70.2%, 76.1%, and 87.1%, respectively (p < 0.05, Wilcoxon signed-rank test). Neither age nor preoperative CD severity was predictive of postoperative improvement; however, the disease duration affected their reduction rate of TWSTRS severity score at each time point investigated (p < 0.05). CONCLUSIONS: Bilateral GPi-DBS is an effective long-term therapy in patients with CD. The delivery of GPi stimulation in the earlier course of CD may yield greater postoperative improvement.
Assuntos
Estimulação Encefálica Profunda/métodos , Globo Pálido/fisiologia , Torcicolo/congênito , Adulto , Idoso , Avaliação da Deficiência , Distonia/congênito , Feminino , Humanos , Estudos Longitudinais , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Torcicolo/terapia , Resultado do TratamentoRESUMO
The management of medication overuse headache (MOH) is sometimes challenging, particularly for patients with a long disease duration. We observed that patients who used goshuyuto, a traditional Japanese medicine, exhibited a favorable clinical course. Two women who had a history of MOH for over 20 years were treated using 5.0-7.5 g/day goshuyuto in an outpatient setting. The treatment reduced their use of habitual drugs, including triptan (33-55%) and non-steroidal anti-inflammatory drugs (75-82%), as well as the headache impact test score-6 (16-23%) over 24 weeks. As goshuyuto has a protective effect on chronic headache and is reported not to lead to MOH, it is a good candidate for the treatment of patients with MOH in an outpatient setting, even for those with an over 20-year history of MOH.
Assuntos
Analgésicos , Transtornos da Cefaleia Secundários , Humanos , Feminino , Analgésicos/efeitos adversos , Pacientes Ambulatoriais , Transtornos da Cefaleia Secundários/induzido quimicamente , Dor/induzido quimicamenteRESUMO
We previously showed tumor-associated macrophages/microglia (TAMs) polarized to the M2 phenotype were significantly involved in tumor cell proliferation and poor clinical prognosis in patients with high grade gliomas. However, the detailed molecular mechanisms involved in the interaction between TAMs and tumor cells have been unclear. Current results reveal that, in coculture with human macrophages, BrdU incorporation was significantly elevated in glioma cells, and signal transducer and activator of transcription-3 (Stat3) activation was found in both cell types. Direct mixed coculture led to stronger Stat3 activation in tumor cells than did indirect separate coculture in Transwell chamber dishes. Screening with an array kit for phospho-receptor tyrosine kinases revealed that phosphorylation of macrophage-colony stimulating factor receptor (M-CSFR, CD115, or c-fms) is possibly involved in this cell-cell interaction; M-CSFR activation was detected in both cell types. Coculture-induced tumor cell activation was suppressed by siRNA-mediated downregulation of the M-CSFR in macrophages and by an inhibitor of M-CSFR (GW2580). Immunohistochemical analysis of phosphorylated (p)M-CSFR, pStat3, M-CSF, M2 ratio, and MIB-1(%) in high grade gliomas revealed that higher staining of pM-CSFR in tumor cells was significantly associated with higher M-CSF expression and higher MIB-1(%). Higher staining of pStat3 was associated with higher MIB-1(%). High M2 ratios were closely correlated with high MIB-1(%) and poor clinical prognosis. Targeting these molecules or deactivating M2 macrophages might be useful therapeutic strategies for high grade glioma patients.
Assuntos
Glioma/metabolismo , Glioma/patologia , Macrófagos/citologia , Adulto , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Cocultura , Regulação para Baixo , Feminino , Glioma/genética , Humanos , Imuno-Histoquímica , Macrófagos/metabolismo , Masculino , Microglia/metabolismo , Microglia/patologia , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Receptor de Fator Estimulador de Colônias de Macrófagos/genética , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismoRESUMO
Recent findings have demonstrated that malignant tumors, including glioblastoma multiforme (GBM), contain cancer-initiating cells (CICs; also known as cancer stem cells), which self-renew and are malignant. However, it remains controversial whether such CICs arise from tissue-specific stem cells, committed precursor cells, or differentiated cells. Here, we sought to examine the origin of the CICs in GBM. We first showed that the overexpression of oncogenic HRas(L61) transformed p53-deficient oligodendrocyte precursor cells (OPCs) and neural stem cells (NSCs) into glioma-initiating cell (GIC)-like cells in mice. When as few as 10 of these GIC-like cells were transplanted in vivo, they formed a transplantable GBM with features of human GBM, suggesting that these GIC-like cells were enriched in CICs. DNA microarray analysis showed that widespread genetic reprogramming occurred during the OPCs' transformation: they largely lost their OPC characteristics and acquired NSC ones, including the expression of prominin1, hmga2, ptgs2, and epiregulin. In addition, the combination of a Ptgs2 inhibitor and an epidermal growth factor receptor (EGFR)-signaling inhibitor prevented the tumorigenesis of transformed OPCs and human GICs (hGICs) obtained from anaplastic oligodendroglioma, but not of transformed NSCs or hGICs obtained from GBM. Together, these findings suggest that GBM can arise from either OPCs or NSCs and that the therapeutic targets for GBM might be different, depending on each GIC's cell-of-origin.
Assuntos
Linhagem da Célula , Transformação Celular Neoplásica/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Receptores ErbB/antagonistas & inibidores , Glioblastoma/metabolismo , Oligodendroglia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Diferenciação Celular , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Citometria de Fluxo , Genes ras/genética , Glioblastoma/patologia , Humanos , Camundongos , Camundongos Knockout , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Oligodendroglia/citologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Deleção de Sequência , Proteína Supressora de Tumor p53/genéticaRESUMO
High-dose methotrexate (HD-MTX) is effective in the initial treatment of primary central nervous system lymphoma (PCNSL). Because treatment options in patients with progressive or recurrent PCNSL are limited, prognosis is poor. Temozolomide, a well-tolerated oral alkylating agent that permeates the blood brain barrier (BBB), is effective against malignant glioma and recurrent PCNSL. The gene for the deoxyribonucleic acid (DNA) repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT), which is closely related to cellular sensitivity to alkylating agents, is inactivated by promoter hypermethylation. We evaluated the results of temozolomide treatment and the methylation status of the promoter region of the MGMT gene in 17 patients (median age 68 years) with refractory or relapsed PCNSL. They were immunocompetent and had received initial treatment with HD-MTX (3.5 g/m(2)) with or without irradiation. All were treated with temozolomide 150-200 mg/m(2), for 5 days in the course of 28 days; treatment was continued until disease progression. We observed five complete remissions, five partial responses (PRs) with stable disease (SD), and seven with disease progression. Median overall survival after the temozolomide treatment was 6.7 months. One patient manifested grade 3 neutropenia and thrombocytopenia. Eleven tumor specimens were available for MGMT analysis. MGMT promoter methylation (mMGMT) in the tumor tissue was found in 4 (36.4%), the other seven harbored a non-methylated MGMT promoter (nmMGMT). There was no statistically significant difference in median overall survival between patients with mMGMT (11.1 months) and nmMGMT (6.7 months) (P = 0.63). Although some patients were elderly and had been heavily pre-treated, temozolomide resulted in a complete response (CR) in 29% and was well tolerated without any major toxicity.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Dacarbazina/análogos & derivados , Linfoma/tratamento farmacológico , Terapia de Salvação/métodos , Proteínas Supressoras de Tumor/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias do Sistema Nervoso Central/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma/genética , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Temozolomida , Proteínas Supressoras de Tumor/genéticaRESUMO
High-grade (World Health Organization grades II and III) meningiomas grow aggressively and recur frequently, resulting in a poor prognosis. Assessment of tumor malignancy before treatment initiation is important. We attempted to determine predictive factors for high-grade meningioma on magnetic resonance (MR) imaging before surgery. We reviewed 65 meningiomas (39 cases, benign; 26 cases, high-grade) and assessed four factors: (1) tumor-brain interface (TBI) on T1-weighted imaging (T1WI), (2) capsular enhancement (CapE), i.e., the layer of the tumor-brain interface on gadolinium-enhanced T1WI (T1Gd), (3) heterogeneity on T1Gd, and (4) tumoral margin on T1Gd. All four factors were useful in distinguishing high-grade from benign meningiomas, according to univariate analysis. On multivariate regression analysis, unclear TBI and heterogeneous enhancement were independent predictive factors for high-grade meningioma. In meningiomas with an unclear TBI and heterogeneous enhancement, the probability of high-grade meningioma was 98%. Our data suggest that this combination of factors obtained from conventional sequences on MR imaging may be useful to predict high-grade meningioma.
Assuntos
Imageamento por Ressonância Magnética , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gadolínio , Humanos , Processamento de Imagem Assistida por Computador , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Adulto JovemRESUMO
Meningiomas are the most frequent intracranial tumors. Although most are benign WHO grade I tumors, grade II and III tumors are aggressive and survival is poor. Treatment options for grade II and III meningiomas are limited, and molecular targets are few. The re-programming of metabolic pathways including glycolysis, lipogenesis, and nucleotide synthesis is a hallmark of the physiological changes in cancer cells. Because fatty acid synthase (FAS), the enzyme responsible for the de-novo synthesis of fatty acids, has emerged as a potential therapeutic target for several cancers, we investigated its involvement in meningiomas. We subjected 92 paraffin-embedded samples from 57 patients with grade I, 18 with grade II and III, and six with radiation-induced tumors to immunohistochemical study of FAS. Whereas its expression was increased in grade II and III meningiomas (62.9 %) compared with grade I tumors (29.8 %) (chi-squared test: p < 0.001), FAS was expressed in grade I tumors with a high MIB-1 index and infiltration into surrounded tissues. All radiation-induced meningiomas expressed FAS and its expression was positively correlated with the MIB-1 index (p < 0.005). Our findings suggest that increased FAS expression reflects the aggressiveness of meningiomas and that it may be a novel therapeutic target for treatment of unresectable or malignant tumors.