Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. METHODS: We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. RESULTS: We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. CONCLUSIONS: Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.

[Spinal pleomorphic xantoastrocytoma. Case report]. / Xantoastrocitoma pleomórfico espinal. Caso clínico.

INTRODUCTION: we report the clinical, radiological and pathological features of a spinal pleomorphic xanthoastrocytoma, an unusual neoplastic entity in a really rare location, establish an appropriated management of these lesions and review the short available english literature. CASE REPORT: a 60 years old woman consulted with doctor because she felt progressive clumsiness accompanied by occasional paresthesias on her left hand. Neurological examination showed up weakness and slight propioceptive disturbances. The differential imagine diagnosis was established between intramedullary astrocytoma and ependimoma. Patient underwent surgical gross total remove. Histopathological examination confirmed the diagnosis of pleomorfic xanthoastrocytoma. We performed MRI controls at 6, 12, 24 and 36 months that did not reveal recurrence. Nowadays, the patient has regained her previous quality of life. DISCUSSION AND CONCLUSION: comparing to published cases about intracranial pleomorphic xanthoastrocytomas, spinal pleomorphic xanthoastrocytomas (SPXA) present different epidemiological characteristics. The known SPXAs affected to cervical and/or high thoracic levels. The hypothesis about a more aggressive behaviour of PXA in spinal cord may be corroborated after literature review. Extension examination is mandatory since dissemination along the neuroaxis has been described. Removal extension is crucial in the prevention of tumour recurrence. Adyuvant radiotherapy should only be considered when there is postoperative residual tumour and/or anaplastic features. Randomized clinical trials or databases are necessary to know all the aspects of this pathological entity.

Superficial siderosis of the central nervous system in a patient with asymptomatic sacral paraganglioma as source of chronic bleeding. / Siderosis superficial del sistema nervioso central en una paciente con paraganglioma sacro asintomático como fuente de sangrado crónico.

INTRODUCTION: Superficial siderosis of the central nervous system is an infrequent pathology secondary to chronic bleeding into the cerebrospinal fluid. Spinal tumors are infrequent cause of superficial siderosis being ependymoma the most common etiology. CASE REPORT: We report the case of a woman with sensorineural hearing loss and cerebellar ataxia, diagnosed of superficial siderosis on brain MRI. She had no previous history of axial back pain or radicular leg pain or bowel or bladder incontinence. On spine MRI an intradural lesion was found at the S1 level. No signs of intratumoral hemorrhage were observed on MRI gradient-echo images. At surgery, an intradural soft mass with signs of chronic bleeding was completely resected. Based on microscopic examination and immunohistochemistry of the specimen, a diagnosis of paraganglioma World Health Organization grade I was made. CONCLUSIONS: Since the only proven treatment able to prevent further deterioration from superficial siderosis is to stop chronic bleeding into subarachnoid space, is of paramount importance to establish an early diagnosis of the source of bleeding. Cases of unexplained superficial siderosis of central nervous system should include routine spinal MRI to rule out bleeding of spinal tumor even in asymptomatic patients. Due to severity of potential deterioration caused by superficial siderosis, any tumoral lesion observed on spinal MRI even without documented sings of bleeding should be considered for resection.

TITLE: Siderosis superficial del sistema nervioso central en una paciente con paraganglioma sacro asintomático como fuente de sangrado crónico.Introducción. La siderosis superficial del sistema nervioso central es una patología poco frecuente secundaria al sangrado crónico en el líquido cefalorraquídeo. Los tumores medulares son causa poco habitual de siderosis superficial, y el ependimoma es la etiología más común. Caso clínico. Mujer con pérdida auditiva neurosensorial y ataxia cerebelosa, diagnosticada de siderosis superficial en la resonancia magnética cerebral. No tenía antecedentes de dolor raquídeo axial, dolor radicular ni incontinencia esfinteriana. En la resonancia magnética de la columna se encontró una lesión intradural en S1. No se observaron signos de hemorragia intratumoral en las secuencias de resonancia magnética en eco de gradiente. En la cirugía, se apreció una masa blanda intradural con signos de sangrado crónico que se resecó. Basado en el examen microscópico e inmunohistoquímico de la muestra, se alcanzó el diagnóstico de paraganglioma de grado I de la Organización Mundial de la Salud. Conclusiones. Dado que el único tratamiento probado capaz de prevenir un mayor deterioro por la siderosis superficial es detener el sangrado crónico en el espacio subaracnoideo, es importante establecer un diagnóstico temprano de la fuente de sangrado. Los casos no justificados de siderosis superficial del sistema nervioso central deben incluir una resonancia magnética de la columna rutinaria para descartar el sangrado de un tumor medular, incluso en pacientes asintomáticos. Debido a la gravedad del deterioro potencial causado por la siderosis superficial, cualquier lesión tumoral observada en una resonancia magnética del raquis, incluso sin presentar signos de sangrado, debería ser objeto de indicación quirúrgica.

Giant occipital intradiploic epidermoid cyst associated with iatrogenic puncture.

The origin of cranial epidermoid cysts (EC) remains controversial, and although generally considered to be congenital, acquired origin has been reported. EC represent 0.2 to 1.8% of all brain tumours, and only one fourth are intradiploic in location. We report of a 44-year-old woman with a giant intradiploic EC of the occipital bone with intracranial extension confirmed on brain MRI. Three years previously, in the same location, she underwent resection of an intradermal melanocytic naevus of the skin under local anaesthesia with lidocaine infiltration of skin and periosteum. Brain CT scan performed at the time of naevus surgery because of associated headache did not show a lesion of the cranial vault. Iatrogenic epidermoid tumours are extremely rare, and although seeding of epidermal cells has been classically described only after lumbar puncture, the same mechanism may be involved after head injury, cranial surgery or cranial periosteal iatrogenic puncture.

[Fibrinolytic treatment of cerebral intraventricular hemorrhage]. / Tratamiento fibrinolítico de la hemorragia intraventricular cerebral.

INTRODUCTION: Spontaneous cerebral intraventricular hemorrhage (SCIVH) is associated with hydrocephaly which requires ventricular drainage as treatment. Maintenance of adequate debit through the drainage system contributes to reduce morbid mortality. When the drain becomes obstructed, intermittent irrigation is necessary. This causes increased intracranial pressure and risk of infection. We propose the use of recombinant plasminogen tissue activator (r-tPA) in the treatment of SCIVH and associated hydrocephaly. CLINICAL CASES: We gave two patients with SCIVH 4 cc/day of r-tPA intraventricularly, at a concentration of 1 mg/ml over 4 consecutive days. Daily computerized tomography (CT) series were done. In both cases there was complete resolution of the SCIVH, with no complications related to the treatment. The ventricular drainage systems maintained a constant debit, did not become obstructed and required no revision. The patients did not subsequently require permanent ventricular shunts. One patient died of an unrelated septic condition. The other patient, a year later, could walk unaided, had motor dysphasia and on CT had neither intraventricular blood nor hydrocephaly. CONCLUSIONS: The intraventricular administration of r-tPA is a valid therapeutic tool in selected cases. It contributes to lysis of the intraventricular clot, permits permeability of the drainage, and may reduce the incidence of chronic hydrocephaly requiring a permanent ventricular shunt.

[Histological prediction of cerebral tumors using SPECT with 201T1]. / Predicción histológica de los tumores cerebrales mediante SPECT con 201T1.

INTRODUCTION AND OBJECTIVE: SPECT with 201Tl provides information regarding the degree of malignancy of cerebral tumours, their possible relapses, the differentiation of necrotic tissue in the tumours following chemotherapy or radiotherapy and permits differentiation into zones of various grades of histological malignancy. MATERIAL AND METHODS: We carried out a prospective analysis of the usefulness of SPECT with 201Tl for the histological prognosis of cerebral tumours. For one year 68 patients diagnosed (on CT and/or MR) as having an expansive cerebral lesion were studied. The early uptake (ICP) and retention (R) indices were calculated, and these results correlated with the morbid anatomy (AP) findings and the results obtained with surgery and stereotactic biopsy. Four patients were excluded due to lack of AP results. RESULTS: Significant differences were found between the ICP of grade I-II astrocytomas (1.34 +/- 0.52) and glioblastomas multiformes (2.56 +/- 0.57), between the ICP of meningiomas (4.53 +/- 1.68) and metastases (2.45 +/- 0.58) and between those of meningiomas and all glial tumours. With regard to IR, we saw significant differences between the figures for meningiomas (0.63 +/- 0.13) and meningiomas with malignant relapses (0.94 +/- 0.17) and between metastases (0.8 +/- 0.03) and all glial tumours. CONCLUSIONS: From our study, it may be concluded that rapid, high captation of 201Tl (high ICP) with a slow fall (high IR), is associated with a process showing malignancy on histological study (malignant relapse of meningioma, glioblastoma multiforme, metastasis), whilst high take-up (high ICP) with rapid elimination (low IR) corresponds to a benign hypervascularized tumour (meningioma).

[The use of SPECT with 201Tl in the evaluation of brain tumors]. / Utilidad de la SPECT con 201Tl en la evaluación de los tumores cerebrales.

There is increasing interest in the literature regarding the use of SPECT (single photon emission computed tomography) with 201Tl in the evaluation of cerebral tumours. Thallium (201Tl) is one of the isotopes most commonly used in studies of the myocardium and in the diagnosis of various tumours. Normal brain takes up very little 201Tl, but in viable tumour tissue the 201Tl becomes intracellular and is rapidly cleared from the blood stream. Such cerebral tumour uptake is related to changes in the permeability of the blood-brain barrier, regional blood flow and transport by means of the Na(+)-K+ adenosine triphosphate pump. Once the SPECT images have been obtained following administration of the radioisotope, one can calculate the indices of early and of late uptake together with the retention index. The usefulness of SPECT in the preoperative detection of malignant expansive pathology, choice of tumour region during stereotaxic biopsy, control of tumour reproduction and their differentiation from post-radiotherapy necrotic tissue, and evaluation of chemotherapy in treatment of cerebral tumours are analyzed. Finally the application of SPECT in metastatic conditions and the differential diagnosis of expansive lesions is considered.

Xantoastrocitoma pleomórfico espinal. Caso clínico / Spinal pleomorphic xantoastrocytoma. Case report

Introducción. Presentamos los aspectos clinicopatológicos y radiológicos de uno de los escasos casos dexantoastrocitoma pleomórfico espinal publicado, una entidad neoplásica infrecuente en una realmente rara localización. Revisamos la breve literatura inglesa disponible y establecemos un apropiado manejo en función de ésta.Caso clínico. Mujer de 60 años de edad que consultó por acorchamiento progresivo de su mano izquierda, acompañado de ocasionales parestesias de dos meses de evolución. La exploración neurológica mostró debilidad y un leve trastorno de la sensibilidad propioceptiva de la extremidad superior derecha. El diagnóstico diferencial tras las pruebas de imagen se estableció entre astrocitoma y ependimoma. La paciente recibió tratamiento quirúrgico obteniéndose una resección completa y el diagnóstico de xantoastrocitoma pleomórfico. En los controles de imagen realizados a los 6, 12, 24 y 36 meses no seo bjetivó recidiva tumoral. Actualmente la paciente ha recuperado su calidad de vida previa.Discusión y conclusión. Comparando con los xantoastrocitomas pleomórficos intracraneales, aquellos con localización espinal (XAPE) presentan diferentes características epidemiológicas, con afectación predominante de niveles cervical y dorsal alto. La hipótesis de comportamiento más agresivo de los XAPE podría ser corroborada tras la revisión de la literatura. El estudio de extensión es fundamental para descartar la descrita diseminación a través del neuroeje. El grado de extensión de la resección quirúrgica es crucial en la prevención de la recurrencia tumoral. La radioterapia adyuvante debería únicamente considerarse cuando aparece tumor residual y/o anaplasia. Ensayos clínicos randomizados y bases de datos multicéntricas son necesariaspara conocer todos los aspectos de esta entidad neoplásica (AU)

Summary Introduction. We report the clinical, radiological and pathological features of a spinal pleomorphic xanthoastrocytoma,an unusual neoplastic entity in a really rare location, establish an appropriated management of these lesions and review the short available english literature.Case report. A 60 years old woman consulted with doctor because she felt progressive clumsiness accompanied by occasional paresthesias on her left hand.Neurological examination showed up weakness and slight propioceptive disturbances. The differential imagine diagnosis was established between intramedullary astrocytoma and ependimoma. Patient under went surgicalgross total remove. Histopathological examination confirmed the diagnosis of pleomorfic xanthoastrocytoma.We performed MRI controls at 6, 12, 24 and 36 months that did not reveal recurrence. Nowadays, the patient has regained her previous quality of life.Discussion and conclusion. Comparing to published cases about intracranial pleomorphic xanthoastrocytomas, spinal pleomorphic xanthoastrocytomas (SPXA)present different epidemiological characteristics. The known SPXAs affected to cervical and/or high thoraciclevels. The hypothesis about a more aggressive behaviour of PXA in spinal cord may be corroborated after literature review. Extension examination is mandatory since dissemination along the neuroaxis has been described.Removal extension is crucial in the prevention of tumour recurrence. Adyuvant radiotherapy should only be considered when there is postoperative residualtumour and/or anaplastic features. Randomized clinical trials or databases are necessary to know all the aspects of this pathological entity (AU)