RESUMEN
INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.
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Biomarcadores de Tumor/genética , Ensayos Clínicos como Asunto , Amplificación de Genes , Proteína Proto-Oncogénica N-Myc/genética , Neuroblastoma/mortalidad , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Estadificación de Neoplasias , Neuroblastoma/genética , Neuroblastoma/secundario , Neuroblastoma/terapia , Pronóstico , Tasa de SupervivenciaRESUMEN
The inflammatory reaction surrounding hemorrhagic and perihematomal brain parenchyma has been studied by means of light and transmission electron microscopy in 12 patients with severe traumatic head injuries complicated with subdural or extradural hematoma or hygroma. Perivascular cells, ameboid phagocytic microglial cells, and infiltrated macrophage/monocyte system were observed surrounding perivascular and intraparenchymal hemorrhagic foci. They showed phagocytic activity of degenerated nerve cell processes, and organized proteinaceous edema fluid present in the enlarged extracellular space. Endocytosis by means of clathrin coated vesicles also was observed. Facultative and professional phagocytes exhibited a full repertoire of lysosomes, phagosomes containing nerve cell debris, lipid droplets, and lipofucsin granules. Phagocytic pericytes remaining within the capillary basement membrane were also observed around perivascular hemorrhages. The inflammatory reaction was examined in young and old patients with an evolution time of brain injury ranging from 1 day to 2 years. The inflammatory process developed according to the intensity of traumatic insult, patient age, associated hematoma or hygroma, severity of vasogenic and cytotoxic oedema, and anoxic-ischemic conditions of brain parenchyma.
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Edema Encefálico/patología , Lesiones Encefálicas/patología , Corteza Cerebral/patología , Inflamación/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Edema Encefálico/etiología , Lesiones Encefálicas/complicaciones , Femenino , Humanos , Inflamación/etiología , Macrófagos/ultraestructura , Masculino , Microglía/ultraestructura , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Monocitos/ultraestructura , FagocitosisRESUMEN
The cortical biopsies of 31 patients with clinical diagnosis of congenital hydrocephalus, vascular anomalies, brain tumours and brain trauma were examined with the transmission electron microscope. A variety of swollen spine shapes were found: mushroom shaped, filopodic, lanceolated spines, and megaspines. The spines appeared axonless or making asymmetric synaptic contacts with swollen presynaptic axons. They exhibited a disrupted actin-like network, dilated endoplasmic reticulum profiles, oedematous clear or dense mitochondria, and clusters of free ribosomes. Some spines contained a hypertrophic cytoskeleton. The spine apparatus appeared generally swollen with clear and dilated cisterns. In severe brain trauma and tumours some spine apparatus appeared disorganised or atrophic. In complicated brain trauma with subdural haematoma or hygroma some degenerated spines displayed a high electron density. The ultrastructural findings suggest that alterations of the spines are responsible for the neurological symptoms exhibited by some patients, which imply a disturbance of cortical nerve circuits. The presence of axonless spines is symptomatic of a loss of nerve connectivity, and are expected to have a significant input on neurological and mental functions.
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Edema Encefálico/patología , Corteza Cerebral/patología , Espinas Dendríticas/ultraestructura , Microscopía Electrónica de Transmisión/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/irrigación sanguínea , Edema Encefálico/etiología , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/patología , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/patología , Malformaciones Vasculares del Sistema Nervioso Central/patología , Niño , Preescolar , Femenino , Humanos , Hidrocefalia/complicaciones , Hidrocefalia/patología , Lactante , Recién Nacido , Masculino , Persona de Mediana EdadRESUMEN
Purkinje dendritic spines (Pds) of mouse cerebellar cortex were examined by field emission scanning electron microscopy (FESEM) and by transmission electron microscopy (TEM) using ultrathin sections and freeze-etching replicas, to study their three-dimensional features and intramembrane morphology. FESEM showed unattached mushroom-type, elongated and lanceolate Pds separated by 100-500 nm on the dendritic shaft surface. High resolution FESEM showed 25-50 nm globular subunits at the spine postsynaptic density corresponding to the localization of postsynaptic proteins and/or postsynaptic receptors. TEM images of ultrathin sections showed gem-like, mushroom-shaped, lanceolate and neckless or stubby spines. Freeze etching replicas exposed postsynaptic intramembrane particles that can be correlated with the globular subunits observed at high resolution FESEM. Parallel and climbing fiber endings were observed making asymmetric synaptic contacts with the Pds heads. Simultaneous contacts with the necks and heads were also found. The variety of Pds shapes were interpreted as spine conformational changes related with spine dynamic, and spine plasticity.
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Corteza Cerebelosa/citología , Dendritas/ultraestructura , Microscopía Electrónica de Rastreo/métodos , Microscopía Electrónica de Transmisión/métodos , Células de Purkinje/ultraestructura , Animales , Grabado por Congelación/métodos , RatonesRESUMEN
We have studied by means of transmission electron microscopy the umbilical cord endothelial cells in 11 preeclamptic women. Endothelial cells exhibited oval, round, elongated, flattened, triangular or polygonal shapes. The nuclei displayed shallow and deep invaginations of nuclear envelope. The endoplasmic reticulum appeared highly dilated and vacuolated. The swollen mitochondria showed cristae fragmentation. Areas of focal necrosis were appreciated throughout the cytoplasm. A marked enlargement of subendothelial space and the presence of an electron dense granular material were also found. The findings reveal activation and injury of endothelial cells and disruption of endothelial cell layer.
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Endotelio Vascular/ultraestructura , Preeclampsia/patología , Cordón Umbilical/irrigación sanguínea , Adulto , Núcleo Celular/ultraestructura , Femenino , Humanos , Edad Materna , Microscopía Electrónica , Preeclampsia/fisiopatología , Embarazo , Segundo Trimestre del Embarazo , Embarazo de Alto Riesgo , Cordón Umbilical/patologíaRESUMEN
The hydropic changes of oligodendroglial cells have been examined by means of transmission electron microscopy in seventeen cases of human, mostly infant hydrocephalus and associated pathology. Hydropic oligodendrocytes exhibited dilated endoplasmic reticulum and nuclear envelope, edematous mitochondria, enlarged and fragmented Golgi complexes, dense bodies and nuclear chromatin homogenization. A process of nuclear pore disassembly, extrusion of nuclear heterochromatin and an apoptotic-like process were observed in some swollen oligodendrocytes. Some resting or quiescent oligodendrocytes were also observed in the edematous neuropil. Oligodendrocyte cell processes appeared atrophic, degenerated and isolated in the enlarged extracellular spaces. They did not show any association with neighbouring axons, and myelinated axons were not observed in the neuropil. These observations suggest demyelination in infant hydrocephalus.
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Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/patología , Hidrocefalia/patología , Oligodendroglía/ultraestructura , Niño , Preescolar , Femenino , Humanos , Hidrocefalia/etiología , Lactante , Recién Nacido , Masculino , Vaina de Mielina/ultraestructuraRESUMEN
Cortical biopsies of 11 patients with traumatic brain oedema were consecutively studied by light microscopy (LM) using thick plastic sections, scanning-transmission electron microscopy ((S)TEM) using semithin plastic sections and transmission electron microscopy (TEM) using ultrathin sections. Samples were glutaraldehyde-osmium fixed and embedded in Araldite or Epon. Thick sections were stained with toluidine-blue for light microscopy. Semithin sections were examined unstained and uncoated for (S)TEM. Ultrathin sections were stained with uranyl and lead. Perivascular haemorrhages and perivascular extravasation of proteinaceous oedema fluid were observed in both moderate and severe oedema. Ischaemic pyramidal and non-pyramidal nerve cells appeared shrunken, electron dense and with enlargement of intracytoplasmic membrane compartment. Notably swollen astrocytes were observed in all samples examined. Glycogen-rich and glycogen-depleted astrocytes were identified in anoxic-ischaemic regions. Dark and hydropic satellite, interfascicular and perivascular oligodendrocytes were also found. The status spongiosus of severely oedematous brain parenchyma observed by LM and (S)TEM was correlated with the enlarged extracellular space and disrupted neuropil observed by TEM. The (S)TEM is recommended as a suitable technique for studying pathological processes in the central nervous system and as an informative adjunct to LM and TEM.