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Journal of Neuro-oncology Aug 2016Sporadic optic pathway gliomas (OPGs) have been reported to cause more vision loss than OPGs associated with neurofibromatosis type-1, but long-term visual outcome data...
Sporadic optic pathway gliomas (OPGs) have been reported to cause more vision loss than OPGs associated with neurofibromatosis type-1, but long-term visual outcome data are limited. The purpose of this study was to report the visual outcomes of a cohort of pediatric patients with sporadic OPGs. This was a retrospective, cohort study at a tertiary care pediatric hospital and cancer institute. The study included all patients with sporadic OPGs evaluated from 1990 to 2014. The primary outcome was visual acuity at final follow-up. Secondary outcomes were risk factors for a poor visual outcome and the rate of progression. There were 59 pediatric patients included in the study. Median age at presentation was 2.5 years old and median follow-up was 5.2 years. In the worse eye at final follow-up, 16 patients (27 %) were 20/30 or better, 9 patients (15 %) were between 20/40 and 20/80, and 34 patients (58 %) were 20/100 or worse. In the better eye at final follow-up, 33 patients (56 %) were 20/30 or better, 11 patients (19 %) were between 20/40 and 20/80, and 15 patients (25 %) were 20/100 or worse. Risk factors for a poor visual outcome included younger age at presentation, optic nerve pallor, and tumor extent. Of the 54 patients (92 %) who received treatment, 40 (74 %) experienced disease progression during or after treatment. A majority of pediatric patients with sporadic OPGs had significant long-term visual impairment. In spite of treatment, tumor progression is common. Serial ophthalmic examinations with quantitative vision measurements are essential in the management of sporadic OPGs.
Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Disease-Free Survival; Female; Humans; Male; Neurofibromatosis 1; Optic Nerve Glioma; Optic Nerve Neoplasms; Retrospective Studies; Risk Factors; Vision Disorders; Visual Acuity; Visual Pathways
PubMed: 27311725
DOI: 10.1007/s11060-016-2163-4 -
Journal of Clinical Oncology : Official... Apr 2016Patients treated with cranial radiation therapy (RT) are at risk for sensorineural hearing loss (SNHL). Although SNHL is often characterized as a delayed consequence of...
PURPOSE
Patients treated with cranial radiation therapy (RT) are at risk for sensorineural hearing loss (SNHL). Although SNHL is often characterized as a delayed consequence of anticancer therapy, longitudinal reports of SNHL in childhood cancer survivors treated with contemporary RT are limited. We report the incidence, onset, severity, and long-term trajectory of SNHL among children receiving RT. Potential risk factors for SNHL were also identified.
PATIENTS AND METHODS
Serial audiologic testing was conducted on 235 pediatric patients who were treated with conformal or intensity-modulated RT as part of an institutional phase II trial for localized primary brain tumors, including craniopharyngioma, ependymoma, and juvenile pilocytic astrocytoma. All but one patient had measurable cochlear radiation dose (CRD) greater than 0 Gy. The median follow-up from RT initiation to latest audiogram was 9 years with a median of 11 post-RT audiograms per patient. Audiograms were classified by the Chang Ototoxicity Grading Scale. Progression was defined by an increase in Chang grade from SNHL onset to the most recent evaluation.
RESULTS
At last evaluation, SNHL was prevalent in 14% of patients: 2.1% had mild and 11.9% had significant SNHL requiring hearing aids. Median time from RT to SNHL onset was 3.6 years (range, 0.4 to 13.2 years). Among 29 patients with follow-up evaluations after SNHL onset, 65.5% experienced continued decline in hearing sensitivity in either ear and 34.5% had no change. Younger age at RT initiation (hazard ratio [HR], 2.32; 95% CI, 1.21 to 4.46), higher CRD (HR, 1.07; 95% CI, 1.03 to 1.11), and cerebrospinal fluid shunting (HR, 2.02; 95% CI, 1.07 to 3.78) were associated with SNHL.
CONCLUSION
SNHL is a late effect of RT that likely worsens over time. Long-term audiologic follow-up for a minimum of 10 years post-RT is recommended.
Topics: Acoustic Impedance Tests; Adolescent; Age Factors; Astrocytoma; Audiometry; Brain Neoplasms; Child; Child, Preschool; Cranial Irradiation; Craniopharyngioma; Ependymoma; Female; Follow-Up Studies; Hearing Loss, Sensorineural; Humans; Incidence; Infant; Kaplan-Meier Estimate; Longitudinal Studies; Male; Proportional Hazards Models; Prospective Studies; Radiotherapy Dosage; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Risk Factors; Severity of Illness Index; United States; Young Adult
PubMed: 26811531
DOI: 10.1200/JCO.2015.63.6738 -
World Neurosurgery Apr 2016The posterior fossa is the site of many types of tumors, and brain metastases are the most common malignancies in that location among adults. Other brain tumors, such as... (Review)
Review
BACKGROUND
The posterior fossa is the site of many types of tumors, and brain metastases are the most common malignancies in that location among adults. Other brain tumors, such as ependymomas, medulloblastomas, and juvenile pilocytic astrocytomas, mostly occur during childhood and are relatively rare in adults. Most primary malignant brain tumors, such as gliomas and lymphomas, tend to be located in the supratentorial compartment.
METHODS
This review summarizes prognostic factors, therapeutic management, and molecular data of intra-axial posterior fossa tumors in adults, including ependymomas, medulloblastomas, and pilocytic astrocytomas.
RESULTS
The literature on intra-axial posterior fossa tumors in adults relies mainly on limited retrospective clinical studies, and such studies employ a wide range of treatment approaches that are usually based on therapies developed specifically for children or for supratentorial brain tumors.
CONCLUSIONS
The clinical course and surgical outcome of adult patients with intra-axial brain tumors in the posterior fossa are summarized in this review. The prognostic factors and therapeutic management of patients with these tumors are controversial because of their rarity, their heterogeneity, and the lack of sufficient data in the literature.
Topics: Biomarkers, Tumor; Evidence-Based Medicine; Female; Humans; Infratentorial Neoplasms; Male; Treatment Outcome
PubMed: 26743385
DOI: 10.1016/j.wneu.2015.12.066 -
Cell and Tissue Research Jun 2016Mutation of the Parkin gene causes an autosomal recessive juvenile-onset form of Parkinson's disease. However, recently, it has been also linked to a wide variety of...
Mutation of the Parkin gene causes an autosomal recessive juvenile-onset form of Parkinson's disease. However, recently, it has been also linked to a wide variety of malignancies, including glioblastoma multiforme (GBM). In this pathology, Parkin exhibits a tumor suppressor role by mitigating the proliferation rate in both in vitro and in vivo models. However, Parkin involvement in the hypoxic process has not as yet been investigated. GBM is the most common and aggressive primary brain tumor in adults and is characterized by hypoxic areas. The low oxygen supply causes the expression of hypoxia-inducible factors (HIFs) leading to an accumulation of pro-angiogenic factors and tumoral invasiveness. We assess the relationship between Parkin and two HIFs expressed during hypoxic conditions, namely HIF-1α and HIF-3α. Our data show that Parkin is downregulated under hypoxia and that it interferes with HIF expression based on cellular oxygen tension. These results suggest a role for the involvement of Parkin in GBM, although further studies will be needed to understand the mechanism by which it modulates HIF-1α and HIF-3α expression.
Topics: Apoptosis Regulatory Proteins; Basic Helix-Loop-Helix Transcription Factors; Brain Neoplasms; Cell Hypoxia; Cell Line, Tumor; Gene Knockdown Techniques; Gene Silencing; Glioblastoma; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Repressor Proteins; Ubiquitin-Protein Ligases
PubMed: 26742768
DOI: 10.1007/s00441-015-2340-3 -
Journal of Neurosurgery. Pediatrics Apr 2016Acute hemorrhagic presentation in pilocytic astrocytomas (PAs) has become increasingly recognized. This type of presentation poses a clinically emergent situation in...
Acute hemorrhagic presentation in pilocytic astrocytomas (PAs) has become increasingly recognized. This type of presentation poses a clinically emergent situation in those hemorrhages arising in PAs of the cerebellum, the most frequent site, because of the limited capacity of the posterior fossa to compensate for mass effect, predisposing to rapid neurological deterioration. As examples, we describe two cases of fatal hemorrhagic cerebellar PAs: one of a child with a slowly growing stereotypical WHO Grade I PA with a 1-year period of symptomatology that preceded a rapid clinical deterioration, and another of an asymptomatic child having a PA variant, presenting with progressive obtundation following a presumed Valsalva event. These two scenarios parallel previous reports in the literature of either a setting of progressive expression of cerebellar dysfunction and transient episodes of raised intracranial pressure (ICP), or abrupt onset of features of increased ICP in a previously well child. The literature is further reviewed for a current understanding of the factors that predispose, initiate and propagate bleeding, with specific reference to the role of vascular endothelial growth factor and other angiogenic agents in the genesis and stability of the vasculature in PAs. In this context, we propose that obliterative vascular mural hyalinization with associated altered flow dynamics and microaneurysm formation was the pathogenesis of the hemorrhage in our first case. In the second case, large tumor size, increased growth rate, looseness of the background myxoid matrix, and thinness of the tumor blood vessels with calcospherite deposition predisposed to vascular leakage and bleeding concurrent with sudden increases in intravascular hydrostatic pressure. In that cerebellar PAs are common, this report underscores the importance of considering in the differential diagnosis the possibility of a spontaneous hemorrhage in a posterior fossa PA in a child presenting with a sudden neurological ictus and raised ICP.
Topics: Astrocytoma; Cerebellar Neoplasms; Child; Child, Preschool; Fatal Outcome; Female; Humans; Intracranial Hemorrhages; Male
PubMed: 26684764
DOI: 10.3171/2015.10.PEDS1580 -
Journal of Visualized Experiments : JoVE Nov 2015Brain tumors are a major cause of cancer-related morbidity and mortality. Developing new therapeutics for these cancers is difficult, as many of these tumors are not...
Brain tumors are a major cause of cancer-related morbidity and mortality. Developing new therapeutics for these cancers is difficult, as many of these tumors are not easily grown in standard culture conditions. Neurosphere cultures under serum-free conditions and orthotopic xenografts have expanded the range of tumors that can be maintained. However, many types of brain tumors remain difficult to propagate or study. This is particularly true for pediatric brain tumors such as pilocytic astrocytomas and medulloblastomas. This protocol describes a system that allows primary human brain tumors to be grown in culture. This quantitative assay can be used to investigate the effect of microenvironment on tumor growth, and to test new drug therapies. This protocol describes a system where fluorescently labeled brain tumor cells are grown on an organotypic brain slice from a juvenile mouse. The response of tumor cells to drug treatments can be studied in this assay, by analyzing changes in the number of cells on the slice over time. In addition, this system can address the nature of the microenvironment that normally fosters growth of brain tumors. This brain tumor organotypic slice co-culture assay provides a propitious system for testing new drugs on human tumor cells within a brain microenvironment.
Topics: Animals; Astrocytoma; Brain Neoplasms; Coculture Techniques; Fluorescent Dyes; Mice; Microscopy, Fluorescence; Microspheres; Organ Culture Techniques; Tumor Microenvironment
PubMed: 26575352
DOI: 10.3791/53304 -
Journal of Clinical Neuroscience :... Mar 2016Optic nerve gliomas (ONG) are rare and seldom encountered in clinical practice. The pilocytic (astrocytoma) variant of ONG almost always presents during the first two...
Optic nerve gliomas (ONG) are rare and seldom encountered in clinical practice. The pilocytic (astrocytoma) variant of ONG almost always presents during the first two decades of life. In this report, the authors discuss an unusual presentation of pilocytic astrocytoma of the juvenile type in an elderly Indian male. With this unusual presentation, ONG affecting the visual pathway should be considered as a possible differential of visual diminution in the elderly population.
Topics: Aged; Astrocytoma; Humans; Male; Optic Nerve Glioma; Vision Disorders
PubMed: 26549677
DOI: 10.1016/j.jocn.2015.05.060 -
Indian Journal of Pediatrics Jul 2016
Topics: Astrocytoma; Brain Neoplasms; Hallucinations; Humans; Magnetic Resonance Imaging
PubMed: 26548431
DOI: 10.1007/s12098-015-1935-8 -
Journal of Pediatric Hematology/oncology Aug 2015Juvenile pilocytic astrocytoma, the most common pediatric central nervous system (CNS) neoplasm, characteristically displays an indolent growth pattern and rarely...
Juvenile pilocytic astrocytoma, the most common pediatric central nervous system (CNS) neoplasm, characteristically displays an indolent growth pattern and rarely demonstrates metastatic dissemination. Reports of infections mimicking CNS metastatic disease are also rare and can impact treatment. We report the youngest known case of a child with a CNS Nocardia farcinica infection who had a known cerebellar pilocytic astrocytoma, review other infections that may masquerade as CNS neoplasms, and discuss N. farcinica CNS infections.
Topics: Astrocytoma; Brain Neoplasms; Cerebellar Neoplasms; Child, Preschool; Diagnosis, Differential; Humans; Male; Meningeal Neoplasms; Meningitis; Nocardia; Nocardia Infections; Prognosis
PubMed: 26181420
DOI: 10.1097/MPH.0000000000000360 -
Pediatric Neurology Sep 2015
Topics: Astrocytoma; Brain; Brain Neoplasms; Cerebellar Diseases; Child, Preschool; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Male; Mutism
PubMed: 26145481
DOI: 10.1016/j.pediatrneurol.2015.06.001