RESUMEN
BACKGROUND: Brain metastasis from breast cancer has a poor prognosis. For solitary cerebral metastases, surgical resection may contribute to the improvement of survival and QOL. We studied the prognosis and characteristics of solitary brain metastasis from breast cancer in patients undergoing surgical resection. METHODS: Seventeen patients had tumors metastatic to the brain at Kasukabe Municipal Hospital between June 2009 and May 2016, and 7 of them underwent craniotomy. Their treatment outcomes were analyzed retrospectively. RESULTS: The median age at diagnosis of brain metastasis was 56 years. The median survival duration was 19.6 months. With regard to radiation therapy after surgery, 3 patients received whole brain irradiation, 2 patients received stereotactic brain irradiation, and 2 patients received both. The site of brain metastasis was the cerebellum in 6 patients, and the occipital lobe in 1 patient. The number of HER2-positive breast cancer patients was 5, and lapatinib and capecitabine were administered to 4 out of these 5 patients. CONCLUSION: For solitary brain metastasis, the improvement in symptoms and the extension of the survival can be achieved using multidisciplinary treatment with surgery, radiation, and molecular targeting drugs.
Asunto(s)
Neoplasias Encefálicas/cirugía , Neoplasias de la Mama/patología , Adulto , Anciano , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Terapia Combinada , Craneotomía , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We report the first case of primary central nervous system lymphoma (PCNSL) developing in a patient with rheumatoid arthritis (RA) undergoing low-dose methotrexate therapy (LD-MTX). The characteristic clinical management and course in our experience of the present case illustrate the important points about PCNSL in methotrexate-associated lymphoproliferative disorders (MTX-LPD). The number of cases of MTX-LPD in RA patients may increase in the future, since current treatment strategies for RA recommend starting MTX use in early stage RA, and recent insights have tended to show an increase with higher doses.
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Antirreumáticos/efectos adversos , Artritis Reumatoide/complicaciones , Neoplasias del Sistema Nervioso Central/complicaciones , Linfoma/complicaciones , Metotrexato/efectos adversos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Biopsia , Neoplasias del Sistema Nervioso Central/patología , Femenino , Humanos , Inmunohistoquímica , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Linfoma/patología , Trastornos Linfoproliferativos/inducido químicamente , Trastornos Linfoproliferativos/patología , Metotrexato/uso terapéutico , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
It has occasionally been reported that mechanical trauma and posttraumatic inflammation may promote metastasis from a primary tumor to the site of the trauma. However, the etiologies that contribute to the metastasis formation at the trauma site remain unknown. We describe here the first case of skull metastasis from hepatocellular carcinoma (HCC) revealing a growing subcutaneous mass at the site of skull fracture. A 58-year-old man had undergone surgical resection of a primary tumor in the liver 2 years previously and was in clinical remission. The patient fell head first off his bicycle and suffered a skull fracture in the squamous portion of the left temporal bone without ostelysis. Three months after the head trauma, he presented at our department with a growing lump on the left side of his head, and magnetic resonance (MR) imaging revealed an osteolytic tumor extending into the adjacent subcutaneous and epidural space. The tumor was at the same location as the skull fracture sustained in the bicycle accident. The mass lesion was radically resected with surrounding normal bone. The tumor formed a well-demarcated mass with osteolysis of the inner and outer skull tables, and the inner layer of the dura mater was intact. The histological diagnosis for the surgical specimen from the skull tumor was a HCC identical to the primary tumor. Immunohistochemically, the tumor cells were diffusely and strongly positive for vascular endothelial growth factor (VEGF) and basic fibrous growth factor (bFGF). It is well known that the extracellular matrix and cytokines are involved in the processes of not only bone healing but also metastasis formation. The present case suggests that several processes involved in bone healing modified the microenvironment and represent a possible cause of skull metastasis from primary tumor.
Asunto(s)
Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/secundario , Curación de Fractura/fisiología , Neoplasias Hepáticas/patología , Fracturas Craneales/complicaciones , Neoplasias Craneales/etiología , Neoplasias Craneales/secundario , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/cirugía , Resultado Fatal , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Craneales/metabolismo , Neoplasias Craneales/cirugía , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: Both microglia and astrocytes respond immediately to traumatic brain injury (TBI). The present study was undertaken to examine whether or not excitatory amino acid (EAA) antagonists could attenuate such glial responses. METHODS: EAA antagonists, including the broad spectrum EAA antagonist, kynurenic acid (KYN), specific N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovalerate (AP-5), and AMPA-KA receptor blocker, 6,7-dinitroquinoxaline-2,3-dione (DNQX), as well as the voltage-dependent ion channel blocker, tetrodotoxin (TTX), were administered into the unilateral hippocampus of rats through a dialysis probe for 30 minutes before the induction of unilateral controlled cortical impact injury. The rats were killed 10 minutes after injury and their brains were processed immunohistochemically for OX42 (marker for microglia) and glial fibrillary acidic protein (GFAP; marker for astrocytes). RESULTS: Ten minutes after injury, microglial activation with increased OX42 immuno-reactivity was evident in the entire hemisphere including the hippocampus ipsilateral to the injury side. Similarly, swollen astrocytes with increased GFAP expression could be detected exclusively on the injury side. When KYN was administered in situ before injury, both the rapid microglial and astroglial responses in the hippocampus were significantly attenuated. However, AP-5, DNQX and TTX, the voltage-dependent ion channel blocker, at doses which can inhibit each channel activation, failed to attenuate these glial reactions. DISCUSSION: These findings indicate that massive ionic fluxes and/or concomitantly occurring EAA release may be closely related to the initiation of microglial and astroglial responses following TBI.
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Astrocitos/efectos de los fármacos , Lesiones Encefálicas/tratamiento farmacológico , Antagonistas de Aminoácidos Excitadores/farmacología , Gliosis/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Microglía/efectos de los fármacos , Animales , Astrocitos/citología , Astrocitos/metabolismo , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/fisiopatología , Antígeno CD11b/metabolismo , Modelos Animales de Enfermedad , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/fisiopatología , Gliosis/prevención & control , Hipocampo/metabolismo , Hipocampo/fisiopatología , Canales Iónicos/efectos de los fármacos , Canales Iónicos/metabolismo , Ácido Quinurénico/farmacología , Ácido Quinurénico/uso terapéutico , Masculino , Microglía/citología , Microglía/metabolismo , Quinoxalinas/farmacología , Quinoxalinas/uso terapéutico , Ratas , Ratas Wistar , Receptores de Glutamato/efectos de los fármacos , Receptores de Glutamato/metabolismo , Bloqueadores de los Canales de Sodio/farmacología , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiología , Valina/análogos & derivados , Valina/farmacología , Valina/uso terapéuticoRESUMEN
The metabolic fate of [1,2 13C]-labeled glucose was determined in male control and unilateral controlled cortical impact (CCI) injured rats at 3.5 and 24 h after surgery. The concentration of 13C-labeled glucose, lactate, glutamate and glutamine were measured in the injured and contralateral cortex. CCI animals showed a 145% increase in 13C lactate in the injured cortex at 3.5 h, but not at 24 h after injury, indicating increased glycolysis in neurons and/or astrocytes ipsilateral to CCI. Total levels of 13C glutamate in cortical tissue extracts did not differ between groups. However, 13C glutamine increased by 40% in the left and 98% in the right cortex at 3.5 h after injury, most likely resulting from an increase in astrocytic metabolism of glutamate. Levels of 13C incorporation into the glutamine isotopomers had returned to control levels by 24 h after CCI. The singlet to doublet ratio of the lactate C3 resonances was calculated to estimate the flux of glucose through the pentose phosphate pathway (PPP). CCI resulted in bilateral increases (9-12%) in the oxidation of glucose via the PPP, with the largest increase occurring at 24 h. Since an increase in PPP activity is associated with NADPH generation, the data suggest that there was an increasing need for reducing equivalents after CCI. Furthermore, 13C was incorporated into glutamate and glutamine isotopomers associated with multiple turns of the tricarboxylic acid (TCA) cycle, indicating that oxidative phosphorylation of glucose was maintained in the injured cortex at 3.5 and 24 h after a moderate to severe CCI injury.
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Lesiones Encefálicas/metabolismo , Ciclo del Ácido Cítrico/fisiología , Glucosa/metabolismo , Vía de Pentosa Fosfato/fisiología , Animales , Modelos Animales de Enfermedad , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Ácido Láctico/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Ratas , Regulación hacia ArribaRESUMEN
To clarify the role of vascular endothelial growth factor (VEGF) in the formation of contusion edema and necrosis after traumatic brain injury, we examined the time course of changes in the VEGF expression (enzyme-linked immunosorbent assay), cerebrovascular permeability (extravasation of Evans blue), and water content (dry-wet weight method) of the contused brain tissue in a cortical impact injury model using rats. In addition, we tested the effects of administration of bevacizumab (VEGF monoclonal antibody) on changes in the cerebrovascular permeability and water content of the contused brain tissue, as well as the neurological deficits (rota rod test) and volume of contusion necrosis. Increased VEGF expression was maximal at 72 h after injury (p<0.003). Increases in cerebrovascular permeability and water content, however, became maximal within 24 h (p<0.001) after injury (p<0.01), respectively. Administration of bevacizumab did not influence these changes in cerebrovascular permeability and water content, but led to a significant rise in the neurological deficits at 72 h-14 days (p<0.05 or 0.01) and the volume of contusion necrosis at 21 days (p<0.001) after injury. These findings suggest that increased expression of VEGF after injury does not contribute to the formation of contusion edema, but attenuates the formation of contusion necrosis. This is probably because of an increased angiogenesis and improved microcirculation in the areas surrounding the core of contusion.
Asunto(s)
Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Animales , Barrera Hematoencefálica/patología , Edema Encefálico/etiología , Edema Encefálico/metabolismo , Edema Encefálico/patología , Permeabilidad Capilar , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Masculino , Necrosis/etiología , Necrosis/metabolismo , Necrosis/patología , Ratas , Ratas Sprague-DawleyRESUMEN
A 64-year-old male presented with an extremely unusual case of solitary clivus metastasis from gastric cancer manifesting as mild headache and diplopia 10 years after radical excision of the primary tumor. The patient underwent surgical resection using an endoscopic transsphenoidal approach. Histological examination revealed typical signet ring cell carcinoma (SRC) which was identical to that of the previous gastric cancer. Why the late recurrence occurred such a long time after the first surgery and how it spread to the clivus remain unclear. The characteristics of SRC and the process of "tumor dormancy" may have been involved in the mechanism underlying late metastasis.
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Carcinoma de Células en Anillo de Sello/secundario , Carcinoma de Células en Anillo de Sello/cirugía , Fosa Craneal Posterior/patología , Neoplasias de la Base del Cráneo/secundario , Neoplasias de la Base del Cráneo/cirugía , Neoplasias Gástricas/cirugía , Anciano , Carcinoma de Células en Anillo de Sello/diagnóstico , Quimioterapia Adyuvante , Terapia Combinada , Supervivencia sin Enfermedad , Estudios de Seguimiento , Gastrectomía , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroendoscopía , Radiocirugia , Reoperación , Neoplasias de la Base del Cráneo/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
A 63-year-old man presented with an unusual supracallosal epidermoid cyst with repetitive hemorrhages that initially manifested as severe headache in 2003. Physical examination found no neurological deficit. Computed tomography demonstrated a homogeneously high density mass lesion measuring 3 x 3 cm in the supracallosal area, and the clinical diagnosis was cavernous malformation. No change occurred in neurological findings except for headache, but the lesion underwent hemorrhages several times over a 4-year period and increased in size to 4 x 5 cm. Surgery revealed a pearly cyst filled with old blood and debris. Histological examination disclosed keratinizing, stratified squamous epithelium without hair follicles or sebaceous glands, consistent with the diagnosis of epidermoid cyst. Surgery was successfully performed without complications such as akinetic mutism, motor weakness, or chemical meningitis. The present case suggests that epidermoid cyst should be considered in the differential diagnosis of suspected cavernous malformation in any location.
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Neoplasias Encefálicas/patología , Hemorragia Cerebral/patología , Quiste Epidérmico/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/cirugía , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/cirugía , Hemorragia Cerebral/etiología , Hemorragia Cerebral/fisiopatología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Descompresión Quirúrgica , Quiste Epidérmico/complicaciones , Quiste Epidérmico/cirugía , Epitelio/patología , Cefalea/etiología , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
This study determined the effects of intraperitoneal sodium pyruvate (SP) treatment on the levels of circulating fuels and on cerebral microdialysis levels of glucose (MD(glc)), lactate (MD(lac)), and pyruvate (MD(pyr)), and the effects of SP treatment on neuropathology after left cortical contusion injury (CCI) in rats. SP injection (1000 mg/kg) 5 min after sham injury (Sham-SP) or CCI (CCI-SP) significantly increased arterial pyruvate (p < 0.005) and lactate (p < 0.001) compared to that of saline-treated rats with CCI (CCI-Sal). Serum glucose also increased significantly in CCI-SP compared to that in CCI-Sal rats (p < 0.05), but not in Sham-SP rats. MD(pyr) was not altered after CCI-Sal, whereas MD(lac) levels within the cerebral cortex significantly increased bilaterally (p < 0.05) and those for MD(glc) decreased bilaterally (p < 0.05). MD(pyr) levels increased significantly in both Sham-SP and CCI-SP rats (p < 0.05 vs. CCI-Sal) and were higher in left/injured cortex of the CCI-SP group (p < 0.05 vs. sham-SP). In CCI-SP rats the contralateral MD(lac) decreased below CCI-Sal levels (p < 0.05) and the ipsilateral MD(glc) levels exceeded those of CCI-Sal rats (p < 0.05). Rats with a single low (500 mg/kg) or high dose (1000 mg/kg) SP treatment had fewer damaged cortical cells 6 h post-CCI than did saline-treated rats (p < 0.05), but three hourly injections of SP (1000 mg/kg) were needed to significantly reduce contusion volume 2 weeks after CCI. Thus, a single intraperitoneal SP treatment increases circulating levels of three potential brain fuels, attenuates a CCI-induced reduction in extracellular glucose while increasing extracellular levels of pyruvate, but not lactate, and can attenuate cortical cell damage occurring within 6 h of injury. Enduring (2 week) neuronal protection was achieved only with multiple SP treatments within the first 2 h post-CCI, perhaps reflecting the need for additional fuel throughout the acute period of increased metabolic demands induced by CCI.