Search

Diffuse intrinsic pontine glioma is a pediatric oncologic disease with dismal prognosis and no effective treatment. Since 2007, our patients have been using valproic acid as prophylactic anticonvulsant. We have undertaken a retrospective study in order to evaluate the influence of valproate in the outcomes of children with this disease in our center. Patients were treated with weekly carboplatin and vincristine and received conformal radiotherapy, either concurrent or sequential. Event-free survival and overall survival of patients not treated with valproic acid were 6.5 and 7.8 months. Accelerated failure time model (a parametric multivariate regression test for time-to-failure data) showed a statistically significant superiority of the median event-free survival of treated patients (6.5 vs. 9.5 months in treated patients; HR 0.54-95 % CI 0.33-0.87; p < 0.05) and also of overall survival (7.8 vs. 13.4 months in treated patients; HR 0.60-95 % CI 0.37-0.98; p = 0.05).

Context and Objective: Hemangiomas are the commonest vascular tumors during childhood. In 2008, the effect of propranolol for treating capillary hemangiomas was demonstrated. Other similar results followed, showing that it rapidly reduces lesion volume. The objective here was to evaluate children and adolescents with hemangiomas that were treated with propranolol., Design and Setting: Retrospective study, conducted in a children's hospital., Methods: Patients aged 0-19 years with or without previous treatment, who were treated between January 2009 and December 2010, were included. The response was assessed by comparing the lesion appearance between the start of treatment and the last consultation. We considered partial or complete responses as the response to treatment., Results: Sixty-nine patients with a median follow-up of 11 months (mean age: 31 months) were included. Of these, 58 patients were recently diagnosed and 11 had had previous treatment. A response (partial or complete) was seen in 60 patients (87%). Among the capillary hemangioma cases, responses were seen in 50 out of 53 (94%), while in other lesion types, it was 10 out of 16 (63%) (P = 0.3; chi-square). Responses in patients less than one year of age were seen in 37 out of 38 (97%), whereas in those over one year of age, in 23 out of 31 (74%) (P = 0.4; chi-square). Side effects were uncommon and mild., Conclusions: Propranolol seemed to be effective for treatment of hemangiomas in children and adolescents, and not just in the proliferative stage, with responses in almost all the patients.

Purpose: The treatment of pediatric patients with malignant brain tumors has evolved considerably in the past decades. However, results are still unsatisfactory for some patients. Valproate has been shown to positively affect the survival of adult glioblastoma patients. We have been giving prophylactic antiepileptic drugs to newly diagnosed children with brain tumors. Since then, we noted a trend towards a better survival from our patients. In order to study this, we performed a retrospective evaluation in our institution., Methods: Standard survival analysis was used, calculating survival until death by all causes or censoring. Comparisons were made by Cox's proportional hazards model regression., Results: Between 2000 and 2010, 94 patients were treated (12 with high-grade gliomas, 56 medulloblastomas, and 26 ependymomas); median and mean ages were 7.7 and 7.8 years. Median follow-up was 60 months (35 for treated and 109 for untreated patients). Of these, 47 received valproate 10-15 mg/kg/day every 8-12 h and 47 did not. Patients who received valproate had a median survival of 34 months, whereas the other group had a median survival of 24 months (hazard ratios = 0.99, 0.57-1.75, p = 0.99)., Conclusions: These results do not prove that valproate prophylactic treatment in pediatric patients with malignant brain tumors had an influence on their survival. However, our cohort showed an effect of higher size than the recent European Organization for Research and Treatment of Cancer trial analysis, even though not significant. Clinical trials with valproate in pediatric malignant brain tumors should be carefully planned, in order to detect a possible effect of this drug in survival.

Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker) cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate). This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08 ± 6.7 mm(3) on the 7(th) day and 67.25 ± 19.8 mm(3) on 9(th) day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

Although substantial progress has been made in pediatric brain tumor management, patients with brainstem tumors and high-grade gliomas, as well as patients less than 3 years of age with high-risk malignant tumors, have a poorer prognosis. The authors have been treating these patients with radiotherapy and standard carboplatin and vincristine chemotherapy. Since January 2007 the authors have been using valproate as anticonvulsant for prophylaxis. The authors performed a retrospective cohort analysis of pediatric patients with high-risk brain tumors treated with chemotherapy, radiotherapy, and valproate prophylaxis, comparing this group with a historical control. The 2007-2008 group was comprised of 22 patients, 15 with brainstem tumors (7 diffuse intrinsic pontine glioma [DIPG], 3 focal, the remaining infiltrating with a solid portion), 4 with diencephalic tumors (2 thalamic), and 3 with supratentorial high-grade tumors (1 glioblastoma, 1 recurrent grade III ependymoma, 1 with gliomatosis). There were 15 patients alive (68%) after a mean follow-up time of 19 months. Survival function comparison by log rank test was highly significant (P = .004) with a hazard ratio of 0.31 (0.14-0.70). Radiological response showed 3 complete responses (14%), 8 partial responses (36%), 5 stable diseases (23%), and 5 progresssive diseases (23%). The authors hypothesize that valproate may have potentiated the antiangiogenic effect of vincristine, diminished expression of resistance to carboplatin, and sensitized tumor cells to radiotherapy. The authors suggest that clinical trials of carboplatin and vincristine associated with oral continuous low-dose valproate are indicated for pediatric patients with high-risk brain tumor.

Objectives: To estimate survival and evaluate prognostic factors of pediatric patients with central nervous system (CNS) tumors treated in a single center., Methods: Retrospective analysis of survival of 103 children with primary brain tumors diagnosed consecutively from January 2000 to December 2006. Cox regression was used for multivariate analysis of factors that affect overall survival to define possible prognostic factors., Results: Median and mean ages were 7.2 and 7.6 years. There was a male predominance (1.22:1). Most patients had medulloblastomas or primitive neuroectodermal tumors (PNET, 38%), or low-grade astrocytomas (18%). The anatomic site of most tumors was the cerebellum (49%) and the brain stem (21%). Five-year survival after diagnosis was 84% for low-grade astrocytomas and 51% for medulloblastomas and PNET. Prognostic factors for overall survival were histopathological type (high-grade astrocytomas and ependymomas; hazard ratio = 3.7 to 3.9), surgery (hazard ratio of 0.5 for completely resected tumors) and radiotherapy (hazard ratio of 0.5 for patients who underwent radiotherapy)., Conclusions: Overall survival of pediatric patients with brain tumors in this study was similar to that found in populations of the United States and Europe. The prognostic factors defined for overall survival are also similar to those published in previous studies.

Objectives: Piplartine (piperlongumine; 5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl]-2(1H) pyridinone) is an alkaloid amide isolated from Piper species (Piperaceae). It has been reported to show multiple pharmacological activities in vitro and in vivo., Methods: We evaluated the in-vitro antiplatelet effect of piplartine isolated from the roots of P. tuberculatum, on human platelet aggregation induced in platelet-rich plasma by the agonists collagen, adenosine 5'-diphosphate (ADP), arachidonic acid (AA) and thrombin., Key Findings: Piplartine (100 mug/ml) caused a 30% inhibition in platelet aggregation when collagen was the agonist. At 200 mug/ml, piplartine significantly inhibited the aggregation induced by arachidonic acid (100%), collagen (59%) or ADP (52%) but not that induced by thrombin. The highest concentration of piplartine (300 mug/ml) inhibited thrombin- (37%), ADP- (71%) and collagen- (98%) induced aggregation. The inhibitory effect of piplartine on ADP-induced platelet aggregation was not modified by pretreatment with pentoxifylline (a phosphodiesterase inhibitor), L-arginine (a substrate for nitric oxide synthase) or ticlopidine (a P2Y(12) purinoceptor antagonist). However, aspirin, a well-known inhibitor of cyclooxygenase, greatly increased the inhibitory effect of piplartine on arachidonic-acid-induced platelet aggregation., Conclusions: The mechanism underlying the piplartine antiplatelet action is not totally clarified. It could be related to the inhibition of cyclooxgenase activity and a decrease in thromboxane A(2) formation, similar to that occurring with aspirin. This and other possible mechanisms require further study.

The acute anti-inflammatory properties of a fraction rich in the chalcones lonchocarpin and derricin, from the roots of Lonchocarpus sericeus (HFLS), were studied for the first time, using a paw oedema model induced in rats by various stimuli. Results showed that HFLS (100 and 200 mg kg(-1), i.p.) was ineffective in inhibiting dextran-induced paw oedema. The HFLS (200 mg kg(-1), p.o. or i.p.) also failed to inhibit the bradykinin-induced oedema. In the yeast-elicited oedema, the HFLS (200 mg kg(-1), i.p.) caused inhibitions ranging from 42 to 59% in the first to fourth hours. Orally administered HFLS (200 mg kg(-1)) was active only in the second (27%) and fourth (32%) hours after yeast injection. It was observed that HFLS (50, 100 and 200 mg kg(-1), i.p.) showed inhibitions of 34, 57 and 74%, respectively, in the third hour for the carrageenan-induced oedema. The inhibition was smaller when the HFLS (100 and 200 mg kg(-1)) was administered orally. The effect of the HFLS (20 mg kg(-1), i.p.) in the carrageenan-induced oedema was not modified by the L-NAME, but the association of pentoxifylline and HFLS increased its effect, suggesting an involvement of the PDE enzyme.

Acute promyelocytic leukemia (APL) is an uncommon form of pediatric acute nonlymphocytic leukemia. It is characterized by clinical (refractory coagulopathy), morphologic (promyelocytic differentiation arrest), and cytogenetic t(15;17) hallmarks. The introduction of all-transretinoic acid (ATRA) or tretinoin, a biologic response modifier, in its therapy was followed by dramatic improvement in its outcome. To show the results of APL treatment in our hospital, we reviewed the information about 15 patients less than 18 years old, newly diagnosed with APL between November 2002 and November 2006. The diagnosis was made upon examination of bone marrow aspirates. The clinical charts were searched for data regarding clinical presentation, diagnosis, initial response with induction therapy, toxicity of ATRA, and antracyclic drug (daunorubicin). The median age was 10 years; the male-to-female ratio was 2:1. Fourteen patients received induction chemotherapy. Thirteen achieved complete remission. Six patients showed signs of coagulopathy. Only 1 patient was diagnosed with ATRA syndrome. There was a death owing to sepsis before the beginning of the therapy and 2 relapses with death associated with the therapy discontinuation. Preliminary results are encouraging and confirm that ATRA is safe and efficacious as first choice therapy for APL.