Helical CT angiography: dynamic cerebrovascular imaging in children.
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BACKGROUND AND PURPOSE: The purpose of this study was to assess the feasibility of helical CT cerebrovascular imaging (CTCVI) in children and to make initial comparisons with MR angiography and digital subtraction angiography (DSA). METHODS: Twenty-six patients, ages 3 days to 17 years, were examined with CTCVI. Patients were scanned with 1-mm collimation and 2:1 pitch 30 seconds after the initiation of a hand injection of 2 mL/kg nonionic contrast material (320 mg/dL iodine) with a maximum dose that did not exceed 80 mL (minimum volume, 5 mL in a 2.5-kg infant). Reconstructions were done using maximum intensity projection and integral rendering algorithms. Four patients had CTCVI, MR angiography, and DSA (42 vessels studied) and nine patients had CTCVI and DSA (136 vessels studied). Scores of 1 (not present) to 3 (present in continuity to the first bifurcation) were assigned independently by two radiologists to 32 vessels in each correlated case for each available technique. RESULTS: There were no technical failures. CTCVI depicted 18 thrombosed dural sinuses, three vascular malformations, one intracranial aneurysm, and four tumors. Ninety-five percent of the vessels seen with DSA were also seen with CTCVI. CTCVI identified all vessels seen on MR angiography. CONCLUSION: Helical CTCVI is an effective technique for assessing the intracranial circulation in children. In this initial comparison, CTCVI showed more vascular detail than MR angiography, and had fewer technical limitations. (+info)
Fas (APO-1/CD95) signaling pathway is intact in radioresistant human glioma cells.
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Radiation-induced apoptosis can be mediated through pathways initiated by either DNA damage or ceramide-induced Fas signaling. Glioblastoma multiforme is a primary brain tumor that is highly resistant to irradiation, and U-87 MG, SF126, and T98G are glioblastoma-derived cell lines that mimic this characteristic. We found that these radioresistant glioma cells are susceptible to Fas-mediated cell death induced by treatment with either anti-Fas antibody or exogenous ceramide. Fas-mediated cell death in these cell lines is p53-independent. These data demonstrate that apoptosis can be induced by ceramide and mediated through the Fas pathway in glioma cells, although high-dose ionizing radiation fails to trigger this pathway. (+info)
Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience. Societe Francaise d'Oncologie Pediatrique.
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Conventional therapy for intracranial germinomas is craniospinal irradiation. In 1990, the Societe Francaise d'Oncologie Pediatrique initiated a study combining chemotherapy (alternating courses of etoposide-carboplatin and etoposide-ifosfamide for a recommended total of four courses) with 40 Gy local irradiation for patients with localized germinomas. Metastatic patients were allocated to receive low-dose craniospinal radiotherapy. Fifty-seven patients were enrolled between 1990 and 1996. Forty-seven had biopsy-proven germinoma. Biopsy was not performed in ten patients (four had diagnostic tumour markers and in six the neurosurgeon felt biopsy was contraindicated). Fifty-one patients had localized disease, and six leptomeningeal dissemination. Seven patients had bifocal tumour. All but one patient received at least four courses of chemotherapy. Toxicity was mainly haematological. Patients with diabetus insipidus (n = 25) commonly developed electrolyte disturbances during chemotherapy. No patient developed tumour progression during chemotherapy. Fifty patients received local radiotherapy with a median dose of 40 Gy to the initial tumour volume. Six metastatic patients, and one patient with localized disease who stopped chemotherapy due to severe toxicity, received craniospinal radiotherapy. The median follow-up for the group was 42 months. Four patients relapsed 9, 10, 38 and 57 months after diagnosis. Three achieved second complete remission following salvage treatment with chemotherapy alone or chemo-radiotherapy. The estimated 3-year survival probability is 98% (CI: 86.6-99.7%) and the estimated 3-year event-free survival is 96.4% (CI: 86.2-99.1%). This study shows that excellent survival rates can be achieved by combining chemotherapy and local radiotherapy in patients with non-metastatic intracranial germinomas. (+info)
Gestational trophoblastic disease: does central nervous system chemoprophylaxis have a role?
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In the UK there are standardized surveillance procedures for gestational trophoblastic disease. However, there are differences in practice between the two treatment centres in terms of definition of persistent gestational trophoblastic disease, prognostic risk assessment and chemotherapeutic regimens. The role of prophylactic chemotherapy for cerebral micrometastatic disease in persistent gestational trophoblastic disease is unclear. We have analysed the outcome of 69 patients with lung metastases who elsewhere might have received prophylactic intrathecal chemotherapy. Of the 69 patients, 67 received intravenous chemotherapy only. The other two patients had cerebral metastases at presentation. One patient who received only intravenous chemotherapy subsequently developed a cerebral metastasis, but this patient's initial treatment was compromised by non-compliance. This experience supports our current policy of not treating patients with pulmonary metastases, without clinical evidence of central nervous system (CNS) involvement, with prophylactic intrathecal therapy. (+info)
Effective T cell regeneration following high-dose chemotherapy rescued with CD34+ cell enriched peripheral blood progenitor cells in children.
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The ex vivo enrichment for the CD34+ cell fraction of PBPC, while it retains the capacity to restore haematopoiesis and potentially reduces a contamination by tumour cells, implements a depletion of T cells. To test whether such a setting adversely affects T cell reconstitution, we monitored T cells in four paediatric patients after CD34+ selected PBPC transplantation. The dose of CD34+ cells, which were enriched to 74%, median, was 7.1 x 10(6)/kg, median, that of T cells was 0.071 x 10(6)/kg, median. The patients were homogenous with respect to features with a potential to effect T cell reconstitution (low median age, (35 years); stage IV malignant tumours in first CR, uncomplicated post-treatment course). The results of sequential FACS analyses showed that by 9 months after treatment all four patients had recovered (1) a normal T cell count (CD3+ cells 1434/microl, median); (2) a normal CD4+ cell count (816/microl, median), while CD8+ cells were recovered (>330/microl) already by 3 months; (3) a normal CD4/CD8 ratio (1.8, median), as a result of an augmented growth of CD4+ cells between 3 and 6 months (increase of CD4+ cells 4.9-fold, median, CD8+ cells 1.1-fold, median). Expansion of cells with a CD45RA+ phenotype (thymus-derived T cells) predominated; from 3 to 6 months the increase of CD4+/CD45RA+ T cells was 130-fold, that of CD4+/CD45RO+ cells was 1.7-fold; CD8+/CD45RA+ cells increased 9-fold, CD8+/CD45RO+ cells increased 2.1-fold, indicating effective thymopoiesis. The findings demonstrate that in paediatric patients the setting of HD-CTX rescued with autologous CD34+ selected PBPC per se is not predictive of an impaired T cell recovery. High thymic activity may be a key factor for the rapid restoration of T cells. (+info)
Acute encephalopathy: a new toxicity associated with high-dose paclitaxel.
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The purpose of this study was to describe acute encephalopathy as a new toxicity associated with paclitaxel, when it is delivered at high doses (> or =600 mg/m2) with stem cell support. A total of 129 patients, included in clinical trials of paclitaxel-containing high-dose chemotherapy, were analyzed. A total of 114 patients received paclitaxel at a dose of > or =600 mg/m2. Six patients presented acute encephalopathy starting between 7 and 23 days after paclitaxel treatment; two of them had received prior whole-brain irradiation. Paclitaxel was given alone (one patient), with cyclophosphamide and cisplatin (two patients), and with cyclophosphamide and cisplatin plus 1,3-bis(2-chloroethyl)-1-nitrosourea (three patients). Central nervous system toxicity consisted of rapid obtundation and coma (five patients) and severe confusional picture with paranoid ideations (one patient). Brain magnetic resonance imaging showed diffuse white matter atrophy (one patient) or multiple small infarcts (one patient), or it was normal (four patients). Other complementary tests, including cerebrospinal fluid analysis and electroencephalography, were nondiagnostic. An effect from concomitant psychotropic medications or from other organ toxicities was excluded in all patients. Three patients recovered after 8-15 days, either spontaneously (two patients) or after high-dose steroids (one patient). Three patients died of irreversible coma. Necropsy, performed in two patients, showed generalized white matter atrophy and multiple brain parenchymal infarcts, respectively. No pharmacodynamic correlation between the occurrence of encephalopathy and a pharmacokinetic parameter of paclitaxel could be identified. Paclitaxel-containing high-dose chemotherapy can cause severe acute encephalopathy. An aggravating effect from prior brain irradiation or concurrent 1,3-bis(2-chloroethyl)-1-nitrosourea seems possible. (+info)
Expression of cell cycle regulator p27Kip1 is correlated with survival of patients with astrocytoma.
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p27Kip1 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation by mediating cell cycle arrest in G1. This study was undertaken to assess the prognostic value of p27Kip1 for astrocytomas. Tissue samples from 130 astrocytomas (WHO grade 1, 5 cases; grade 2, 23 cases; grade 3, 64 cases; grade 4, 38 cases), including 92 primary and 38 recurrent tumors, were examined immunohistochemically for Ki-67 and p27Kip1 expression. Patient charts were reviewed for clinical presentation, and survival was followed. The p27Kip1 labeling index (LI) ranged from 2.3 to 98.4%, with a mean value of 47.5% (+/-23.4%). The p27Kip1 LI decreased with increasing tumor grade but did not correlate with other parameters. There was no correlation between Ki-67 LI and p27Kip1 LI. For patients with primary astrocytomas, the 50% survival times of those with low p27Kip1 LI (<50%) and those with high p27Kip1 LI (> or =50%) were 17.1 and 69.6 months, respectively. For patients with high-grade tumors, the 50% survival times were 13.1 months for those with low p27Kip1 LI and 33.7 months for those with high LI. On multivariate analysis, p27Kip1 was one of the most significant prognostic factors, indicating that low p27Kip1 LI was associated with poor prognosis (primary, risk ratio = 2.5, P = 0.0023; high-grade, risk ratio = 2.2; P = 0.0139). The expression of p27Kip1 was inversely related to tumor grade and positively related to favorable outcome of patients with astrocytoma, suggesting that p27Kip1 may be a candidate for prognostic factor for this tumor. (+info)
Cathepsin B immunohistochemical staining in tumor and endothelial cells is a new prognostic factor for survival in patients with brain tumors.
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The cysteine endopeptidase, cathepsin (Cat) B, and its endogenous inhibitor, stefin A, were found relevant for cancer progression of many neoplasms, including human brain tumors. Histological sections of 100 primary brain tumors, 27 benign and 73 malignant, were stained immunohistochemically for Cat B and stefin A. The immunohistochemical staining of Cat B in tumor cells, endothelial cells, and macrophages was scored separately from 0-12. The score in tumor and endothelial cells was significantly higher in malignant tumors compared with benign tumors (P<0.000). A significant correlation between immunostaining of Cat B (scored together for tumor and endothelial cells) and clinical parameters, such as duration of symptoms, Karnofsky score, psycho-organic symptoms, and histological score was demonstrated. Univariate survival analysis indicated that total Cat B score above 8 was a significant predictor for shorter overall survival (P = 0.003). In glioblastoma multiforme, intense Cat B staining of endothelial cells was a significant predictor for shorter survival (P = 0.003). Stefin A immunostaining was weak and detected only in a few benign and some malignant tumors, suggesting that this inhibitor alone is not sufficient in balancing proteolytic activity of Cat B. We conclude that specific immunostaining of Cat B in tumor and endothelial cells can be used to predict the risk of death in patients with primary tumors of the central nervous system. (+info)