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2.
J Neurosurg Pediatr ; : 1-7, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502999

RESUMO

OBJECTIVE: Postoperative pain can limit the recovery of children undergoing craniotomy for tumor resection, and pain management is highly variable between institutions and practitioners. Nonsteroidal antiinflammatory drugs (NSAIDs) are effective in treating postoperative pain following craniotomy, but their use has been limited by concerns about postoperative hemorrhage. The risk of postoperative hemorrhage is not insignificant in patients undergoing craniotomy for tumor resection. No study has specifically addressed the safety of NSAIDs in the immediate postoperative setting following craniotomy for tumor resection in pediatric patients. METHODS: The authors performed a retrospective cohort study in patients younger than 18 years of age who underwent craniotomy for tumor resection at a single tertiary referral center between 2009 and 2019. The study outcomes were 1) postoperative hemorrhage requiring return to the operating room for decompression, evacuation, or CSF diversion for hemorrhage-associated hydrocephalus; and 2) more-than-minimal hemorrhage on routine postoperative imaging. Patients receiving any NSAID in the hospital formulary on the same day as surgery (postoperative day zero [POD0]) were designated as such. RESULTS: Two hundred seventy-six children underwent 308 craniotomies for tumor resection over the study period. One hundred fifty-four patients (50.0%) received at least one dose of an NSAID on POD0. Six patients (1.9%) required a return to the operating room for a hemorrhagic complication, including 3 who received an NSAID on POD0 (OR 1.00, 95% CI 0.20-5.03). Seventeen patients (6.3% of patients imaged) had more-than-minimal hemorrhage on routine postoperative imaging, 9 of whom received an NSAID on POD0 (OR 1.08, 95% CI 0.40-2.89). CONCLUSIONS: Use of NSAIDs on POD0 was not associated with either an increased risk of hemorrhage requiring a return to the operating room or asymptomatic hemorrhage on routine postoperative imaging. The overall incidence of clinically significant postoperative intracranial hemorrhage is low. These data support the use of NSAIDs as a safe measure for pain control in the postoperative setting for children undergoing craniotomy for tumor resection.

3.
Aging (Albany NY) ; 12(7): 5781-5791, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32235007

RESUMO

Hypoxia-inducible factors (HIFs) regulate oxygen sensing and expression of genes involved in angiogenesis and erythropoiesis. Polycythemia has been observed in patients with hepatocellular carcinoma (HCC), but the underlying molecular basis remains unknown. Liver tissues from 302 HCC patients, including 104 with polycythemia, were sequenced for HIF2A mutations. A germline HIF2A mutation was detected in one HCC patient with concurrent polycythemia. Three additional family members carried this mutation, but none exhibited polycythemia or were diagnosed with HCC. The gain-of-function mutation resulted in a HIF-2α protein that was transcribed normally but resistant to degradation. HIF-2α target genes EDN1, EPO, GNA14, and VEGF were significantly upregulated in the tumor bed but not in the surrounding liver tissue. Polycythemia resolved upon total resection of the tumor tissue. This newly described HIF2A mutation may promote HCC oncogenesis.

4.
World Neurosurg ; 133: e828-e834, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31622680

RESUMO

OBJECTIVE: It is generally accepted that larger saccular intracranial aneurysms are at greater risk to rupture. We investigated whether aneurysm location influences the effect of aneurysm size on the propensity of rupture. METHODS: We reviewed patient and aneurysm characteristics in a consecutive series of patients with unruptured and ruptured aneurysms presenting to our institution between 2006 and 2018. Differences between unruptured and ruptured aneurysms at different locations were subsequently investigated. RESULTS: A total of 766 aneurysms in 568 patients were included, with 355 and 411 unruptured and ruptured aneurysms, respectively. There were significant differences in the distribution of aneurysm location between unruptured and ruptured aneurysms (P < 0.001). The most common locations of unruptured aneurysms were the middle cerebral artery (MCA) (27.6%) and paraclinoid internal carotid artery (ICA) (25.4%), whereas the most common locations of ruptured aneurysms were the anterior communicating artery (ACOM) (34.8%) and posterior communicating artery (17.8%). Ruptured aneurysms were larger than unruptured aneurysms at all locations except at the ACOM, where there was no difference in size between unruptured and ruptured aneurysms (5.4 vs. 5.8 mm, respectively; P = 0.40). Ruptured ACOM aneurysms were also smaller than ruptured aneurysms of the paraclinoid ICA (5.8 vs. 10.3 mm; P < 0.001), MCA (5.8 vs. 8.0 mm; P = 0.021), and basilar apex (5.8 vs. 10.5 mm; P < 0.001), respectively. CONCLUSIONS: We observed no difference in size between unruptured and ruptured ACOM aneurysms, possibly suggesting a greater susceptibility for ACOM aneurysms to rupture at smaller sizes.


Assuntos
Aneurisma Roto/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Adulto , Idoso , Angiografia Cerebral , Artérias Cerebrais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Neurooncol Pract ; 6(3): 163-178, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31386032

RESUMO

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare CNS cancer that typically occurs in children younger than 3 years of age. Histologically, AT/RTs are embryonal tumors that contain a rhabdoid component as well as areas with primitive neuroectodermal, mesenchymal, and epithelial features. Compared to other CNS tumors of childhood, AT/RTs are characterized by their rapid growth, short symptomatic prodrome, and large size upon presentation, often leading to brain compression and intracranial hypertension requiring urgent intervention. For decades, the mainstay of care has been a combination of maximal safe surgical resection followed by adjuvant chemotherapy and radiotherapy. Despite advances in each of these modalities, the relative paucity of data on these tumors, their inherently aggressive course, and a lack of molecular data have limited advances in treatment over the past 3 decades. Recent large-scale, multicenter interdisciplinary studies, however, have significantly advanced our understanding of the molecular pathogenesis of these tumors. Multiple clinical trials testing molecularly targeted therapies are underway, offering hope for patients with AT/RT and their families.

6.
J Neurosurg ; : 1-9, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174190

RESUMO

OBJECTIVE: Although ventricular shunting is an effective therapy for idiopathic normal pressure hydrocephalus (iNPH), the effect of shunt valve type on the incidence of revision surgery is not well defined. To address this issue, shunt revision rates between patients with iNPH receiving a fixed-setting valve (FSV) versus a programmable valve (PV) were compared. METHODS: Patients with iNPH treated with ventricular shunting between 2001 and 2017 were included for analysis. The incidence of shunt revision was noted and risk factors for revision were identified using a Cox proportional hazards model. Costs associated with admission for ventricular shunt procedures were obtained from the Vizient national database. RESULTS: There were 348 patients included for analysis, with 98 patients (28.1%) receiving a PV. Shunt revision occurred in 73 patients (21.0%), with 12 patients (3.4%) undergoing multiple revisions. Overall revision rates were lower in patients receiving a PV (13.3% vs 24.0%; p = 0.027), as was the incidence of multiple revisions (0.0% vs 4.8%; p = 0.023). Patients with initial placement of an FSV were also more likely to undergo valve exchange during follow-up (12.4% vs 2.0%; p = 0.003). Patients with a PV were less likely to undergo revision due to persistent symptoms without obstruction (2.0% vs 8.8%; p = 0.031) and distal obstruction (1.0% vs 6.8%; p = 0.030). In a multivariate Cox proportional hazards model, initial placement of a PV was associated with reduced risk of revision due to persistent symptoms without obstruction (OR 0.27, 95% CI 0.04-0.93; p = 0.036). PVs were associated with more frequent shunt series (1.3 vs 0.6; p < 0.001) and head CT scans (3.6 vs 2.7; p = 0.038) during follow-up. There was no significant difference in mean total costs between patients receiving an FSV and a PV ($24,282.50 vs $24,396.90; p = 0.937). CONCLUSIONS: The authors' results suggest that PVs lead to reduced rates of shunt revision in patients with iNPH, and decreased risk of revision due to persistent symptoms of iNPH, thereby justifying the higher upfront cost of PVs despite similar overall treatment costs between these devices.

7.
Neurology ; 92(20): e2385-e2394, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-30996058

RESUMO

OBJECTIVE: To define the in-hospital course, complications, short- and long-term functional outcomes of patients with angiographically negative subarachnoid hemorrhage (anSAH), particularly those with aneurysmal-pattern anSAH (aanSAH). METHODS: Retrospective cohort study of patients with aneurysmal subarachnoid hemorrhage (aSAH), aanSAH, and perimesencephalic-pattern anSAH (panSAH) treated at a single tertiary referral center between January 2006 and April 2018. Ninety-nine patients with anSAH (33 aanSAH and 66 panSAH) and 464 patients with aSAH were included in this study. Outcomes included symptomatic hydrocephalus requiring CSF drainage, need for ventriculoperitoneal shunt, radiographic vasospasm, delayed cerebral ischemia (DCI), radiographic infarction, disability level within 1 year of ictus, and at last clinical follow-up as defined by the modified Rankin Scale. RESULTS: Patients with aanSAH and panSAH had similar rates of DCI and radiologic infarction, and patients with aanSAH had significantly lower rates compared to aSAH (p ≤ 0.018). Patients with aanSAH were more likely than those with panSAH to require temporary CSF diversion and ventriculoperitoneal shunt (p ≤ 0.03), with similar rates to those seen in aSAH. Only one patient with anSAH died in the hospital. Compared to those with aSAH, patients with aanSAH were significantly less likely to have a poor functional outcome within 1 year of ictus (odds ratio 0.26, 95% confidence interval 0.090-0.75) and at last follow-up (hazard ratio 0.30, 95% confidence interval 0.19-0.49, p = 0.002). CONCLUSIONS: DCI is very uncommon in anSAH, but patients with aanSAH have a similar need for short- and long-term CSF diversion to patients with aSAH. Nevertheless, patients with aanSAH have significantly better short- and long-term outcomes.


Assuntos
Isquemia Encefálica/fisiopatologia , Hidrocefalia/fisiopatologia , Hemorragia Subaracnóidea/fisiopatologia , Vasoespasmo Intracraniano/fisiopatologia , Adulto , Idoso , Aneurisma Roto , Angiografia Digital , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/etiologia , Infarto Encefálico/fisiopatologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Angiografia Cerebral , Estudos de Coortes , Drenagem , Feminino , Humanos , Hidrocefalia/etiologia , Hidrocefalia/terapia , Aneurisma Intracraniano , Masculino , Pessoa de Meia-Idade , Prognóstico , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/etiologia , Derivação Ventriculoperitoneal
8.
Res Sports Med ; 26(sup1): 57-70, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30431361

RESUMO

Motocross is a competitive outdoor extreme sport in which motorcyclists race across vast courses of jumps, berms and long straightaways of unpredictable terrain. While the sport has gained notoriety in adult popular culture through contests like the X Games, motocross is also increasingly popular among youth in the Unites States and beyond. In the setting of contemporary discussions on traumatic brain injury, this poses an obvious challenge to those advising children and parents on the risks of motocross to the developing brain and spine. The available literature demonstrates that even when practiced with appropriate protective equipment, motocross poses an increased risk for acquiring major trauma to the brain, spine and limbs for which the long-term consequences have been poorly studied. Riders and parents should be counseled about the risks of these injuries prior to participation and in accordance with state laws. Furthermore, formal return-to-play guidelines following concussions should be developed.


Assuntos
Traumatismos em Atletas/epidemiologia , Motocicletas , Adolescente , Criança , Humanos , Fatores de Risco
9.
Oncotarget ; 8(34): 56110-56125, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28915577

RESUMO

Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi. Through an in-vitro and in-vivo approach utilizing cell lines for hepatocellular carcinoma (HCC), osteosarcoma (OS), and glioblastoma (GBM), we demonstrate that SAHA potently inhibits HIF-a nuclear translocation via direct acetylation of its associated chaperone, heat shock protein 90 (Hsp90). In the presence of SAHA we found elevated levels of acetyl-Hsp90, decreased interaction between acetyl-Hsp90 and HIF-a, decreased nuclear/cytoplasmic HIF-α expression, absent HIF-α association with its nuclear karyopharyin Importin, and markedly decreased HIF-a transcriptional activity. These changes were associated with downregulation of downstream hypoxia molecules such as endothelin 1, erythropoietin, glucose transporter 1, and vascular endothelial growth factor. Findings were replicated in an in-vivo Hep3B HRE-Luc expressing xenograft, and were associated with significant decreases in xenograft tumor size. Altogether, this study highlights a novel mechanism of action of an important class of chemotherapeutic.

10.
World Neurosurg ; 103: 951.e13-951.e20, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28434965

RESUMO

BACKGROUND: Schwannomas arising from the cranial nerves controlling extraocular eye movements are very rare and usually present with some degree of diplopia. CASE PRESENTATION: We report a 50-year-old woman who presented with isolated left-sided trigeminal neuralgia of 6 months' duration. Imaging demonstrated a homogeneously enhancing mass in the left ambient cistern, and the patient was brought to the operating room for resection. A retrosigmoid approach was used, and the mass was directly visualized arising from the trochlear nerve and compressing the dorsal root entry zone of the trigeminal nerve. A gross total resection of the mass was achieved, and microvascular decompression of the trigeminal nerve was performed. The tumor was pathologically confirmed as a schwannoma. At 3-month follow-up, the patient's facial pain was resolved, and her extraocular eye movements were intact. CONCLUSIONS: A total of 32 pathology-confirmed cases of trochlear schwannoma have been previously reported in the English-language literature. Most of these tumors arose from the cisternal segment of the nerve, and most patients presented with frank trochlear nerve palsy on exam. We report the first case of trochlear schwannoma presenting with isolated trigeminal neuralgia.


Assuntos
Neoplasias dos Nervos Cranianos/complicações , Neurilemoma/complicações , Neuralgia do Trigêmeo/etiologia , Doenças do Nervo Troclear/complicações , Neoplasias dos Nervos Cranianos/diagnóstico por imagem , Neoplasias dos Nervos Cranianos/patologia , Neoplasias dos Nervos Cranianos/cirurgia , Feminino , Humanos , Imagem por Ressonância Magnética , Cirurgia de Descompressão Microvascular , Pessoa de Meia-Idade , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Neurilemoma/cirurgia , Procedimentos Neurocirúrgicos , Neuralgia do Trigêmeo/cirurgia , Doenças do Nervo Troclear/diagnóstico por imagem , Doenças do Nervo Troclear/patologia , Doenças do Nervo Troclear/cirurgia
11.
J Neurooncol ; 130(1): 111-122, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27568035

RESUMO

Transcription factors that induce epithelial-mesenchymal transition (EMT) promote invasion, chemoresistance and a stem-cell phenotype in epithelial tumors, but their roles in central nervous system tumors are not well-understood. We hypothesized these transcription factors have a functional impact in grades II-III gliomas. Using the National Cancer Institute (NCI) Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the Cancer Genome Atlas (TCGA) Lower-Grade Glioma (LGG) data, we determined the impact of EMT-promoting transcription factors (EMT-TFs) on overall survival in grades II-III gliomas, compared their expression across common genetic subtypes and subsequently validated these findings in a set of 31 tumors using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. Increased expression of the gene coding for the transcriptional repressor Zinc Finger E box-binding Homeobox 1 (ZEB1) was associated with a significant increase in overall survival (OS) on Kaplan-Meier analysis. Genetic subtype analysis revealed that ZEB1 expression was relatively increased in IDH1/2-mutant gliomas, and IDH1/2-mutant gliomas expressed significantly lower levels of many ZEB1 transcriptional targets. Similarly, IDH1/2-mutant tumors expressed significantly higher levels of targets of microRNA 200C (MIR200C), a key regulator of ZEB1. In a validation study, ZEB1 mRNA was significantly increased in IDH1-mutant grades II-III gliomas, and ZEB1 protein expression was more pronounced in these tumors. Our findings demonstrate a novel relationship between IDH1/2 mutations and expression of ZEB1 and its transcriptional targets. Therapy targeting ZEB1-associated pathways may represent a novel therapeutic avenue for this class of tumors.


Assuntos
Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Glioma/metabolismo , Isocitrato Desidrogenase/genética , Mutação/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Glioma/genética , Glioma/mortalidade , Humanos , Isocitrato Desidrogenase/metabolismo , Estimativa de Kaplan-Meier , Masculino , RNA Mensageiro/metabolismo , Estatística como Assunto
12.
J Neurosurg Spine ; 25(3): 383-93, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27058497

RESUMO

OBJECTIVE Paraplegia and paraparesis following aortic aneurysm repair occur at a substantially high rate and are often catastrophic to patients, their families, and the overall health care system. Spinal cord injury (SCI) following open thoracoabdominal aortic aneurysm (TAAA) repair is reported to be as high as 20% in historical controls. The goal of this study was to determine the impact of CSF drainage (CSFD) on SCI following TAAA repair. METHODS In August 2015 a systematic literature search was performed using clinicaltrials.gov , the Cochrane Library, PubMed/MEDLINE, and Scopus that identified 3478 articles. Of these articles, 10 met inclusion criteria. Random and fixed-effect meta-analyses were performed using both pooled and subset analyses based on study type. RESULTS The meta-analysis demonstrated that CSFD decreased SCI by nearly half (relative risk 0.42, 95% confidence interval 0.25-0.70; p = 0.0009) in the pooled analysis. This effect remained in the subgroup analysis of early SCI but did not remain significant in late SCI. CONCLUSIONS This meta-analysis showed that CSFD could be an effective strategy in preventing SCI following aortic aneurysm repair. Care should be taken to prevent complications related to overdrainage. No firm conclusions can be drawn about the newer endovascular procedures at the current time.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Drenagem/instrumentação , Drenagem/métodos , Traumatismos da Medula Espinal/prevenção & controle , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Torácica/complicações , Líquido Cefalorraquidiano , Drenagem/efeitos adversos , Humanos , Traumatismos da Medula Espinal/etiologia
13.
Oncotarget ; 7(12): 15200-14, 2016 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-26934654

RESUMO

Metabolomics has shown significant potential in identifying small molecules specific to tumor phenotypes. In this study we analyzed resected tissue metabolites using capillary electrophoresis-mass spectrometry and found that tissue hypotaurine levels strongly and positively correlated with glioma grade. In vitro studies were conducted to show that hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2. This leads to the activation of hypoxia signaling as well as to the enhancement of glioma cell proliferation and invasion. In contrast, taurine, the oxidation metabolite of hypotaurine, decreased intracellular hypotaurine and resulted in glioma cell growth arrest. Lastly, a glioblastoma xenograft mice model was supplemented with taurine feed and exhibited impaired tumor growth. Taken together, these findings suggest that hypotaurine is an aberrantly produced oncometabolite, mediating tumor molecular pathophysiology and progression. The hypotaurine metabolic pathway may provide a potentially new target for glioblastoma diagnosis and therapy.


Assuntos
Encéfalo/patologia , Glioma/patologia , Hipóxia/fisiopatologia , Metabolômica , Transdução de Sinais , Taurina/análogos & derivados , Animais , Apoptose , Encéfalo/metabolismo , Estudos de Casos e Controles , Ciclo Celular , Proliferação de Células , Seguimentos , Glioma/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fenótipo , Prognóstico , Taurina/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Case Rep Radiol ; 2016: 1762195, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28053799

RESUMO

Gliosarcoma is an uncommon variant of glioblastoma, which commonly demonstrates dural attachment. However, skull base invasion is rarely seen with this entity. Herein, we report a 44-year-old female patient diagnosed with primary intracranial gliosarcoma extensively invading the skull base and muscles of mastication. She presented to our institution with a three-month history of difficult right jaw opening and retro-orbital pressure and one week of severe right-sided postauricular headache. Head CT demonstrated a 6 cm mass with marked bony erosion. Brain MRI at a one-week interval more clearly characterized tumor extension through the right orbit and muscles of mastication, with overall growth to 7 cm and worsening midline shift. The patient underwent a right frontotemporal craniotomy for gross total resection. Pathology confirmed the diagnosis of gliosarcoma, IDH-wildtype (WHO grade IV). Her postoperative course was uneventful and she was discharged at preoperative neurologic baseline. To our knowledge, this is the third reported case of a primary intracranial gliosarcoma with direct invasion of skull base, brain parenchyma, and extracranial compartment. However, this is the first report case of primary GS invading the surrounding musculature and orbit. This case report highlights the rapid aggressiveness of gliosarcomas and further a prior undescribed radiographic and anatomic finding of skull base invasion with this entity.

15.
J Neurosurg Pediatr ; 17(1): 57-65, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26474099

RESUMO

OBJECT Malignant tumors of the brainstem, excluding classic diffuse intrinsic pontine gliomas (DIPGs), are a very rare, heterogeneous group of neoplasms that have been infrequently described in the literature. In this paper, the authors present their experiences with treating these unique cancers. METHODS A retrospective chart review was conducted to identify eligible cases over a 15-year period. All tumors involving the pons were, by consensus, felt not to be DIPGs based on their neuroimaging features. Demographic information, pathological specimens, neuroimaging characteristics, surgical and nonsurgical management plans, and survival data were gathered for analysis. RESULTS Between January 2000 and December 2014, 29 patients were identified. The mean age at diagnosis was 8.4 years (range 2 months to 25 years), and 17 (59%) patients were male. The most common presenting signs and symptoms were cranial neuropathies (n = 24; 83%), hemiparesis (n = 12; 41%), and ataxia or gait disturbance (n = 10; 34%). There were 18 glial and 11 embryonal tumors. Of the glial tumors, 5 were radiation-induced and 1 was a malignant transformation of a previously known low-grade tumor. Surgical intervention consisted of biopsy alone in 12 patients and some degree of resection in another 15 patients. Two tumors were diagnosed postmortem. The median overall survival for all patients was 196 days (range 15 to 3999 days). There are currently 5 (17%) patients who are still alive: 1 with an anaplastic astrocytoma and the remaining with embryonal tumors. CONCLUSIONS In general, malignant non-DIPG tumors of the brainstem carry a poor prognosis. However, maximal cytoreductive surgery may be an option for select patients with focal tumors. Long-term survival is possible in patients with nonmetastatic embryonal tumors after multimodal treatment, most importantly maximal resection.


Assuntos
Neoplasias do Tronco Encefálico , Glioma , Neoplasias Embrionárias de Células Germinativas , Adolescente , Adulto , Astrocitoma/mortalidade , Astrocitoma/patologia , Astrocitoma/terapia , Neoplasias do Tronco Encefálico/mortalidade , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Glioma/mortalidade , Glioma/patologia , Glioma/terapia , Humanos , Lactente , Masculino , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Estudos Retrospectivos , Adulto Jovem
16.
Clin Neuropathol ; 35(2): 78-83, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26709712

RESUMO

Although schwannoma and neurofibroma tumors are generally reported as distinct pathologic diagnoses, sporadic schwannoma/neurofibroma hybrid nerve sheath tumors have been reported in the general population with components of both entities. We report the clinicopathological features of these hybrid nerve sheath tumors in patients with neurofibromatosis type 2 (NF2). A retrospective review of nerve sheath tumor surgical specimens from patients with NF2 enrolled at the National Institutes of Health was performed. Those specimens reported to have schwannoma-like and neurofibromalike features were selected for further characterization by morphology, immunohistochemical panel (CD34, S100, neurofilament triplet protein (immunostain) (NFTP), epithelial membrane antigen (EMA)), and confirmation as hybrid tumors. Of 43 total NF2 patients undergoing resection of nerve sheath tumors, 11 specimens from 11 (26%) patients were found to be benign nerve sheath tumors exhibiting hybrid features of both neurofibroma and schwannoma. Immunohistochemical studies showed the schwannoma component to be S100+, CD 34- while the neurofibroma component was CD34+, variable S100+. Our experience emphasizes the importance of including this distinct tumor subtype, the schwannoma/neurofibroma hybrid tumor, in the differential diagnosis of nerve sheath tumors in NF2 patients and suggests that the relationship between neurofibroma and schwannoma tumors is closer than previously suspected..


Assuntos
Neurilemoma/patologia , Neurofibroma/patologia , Neurofibromatose 2/patologia , Adolescente , Biomarcadores Tumorais/análise , Criança , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Neurosurgery ; 77(3): 321-31; discussion 331, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26103441

RESUMO

BACKGROUND: Ventricular shunt placement for treating hydrocephalus is one of the most common neurosurgical procedures. The rate of shunt failure, however, has not appreciably changed with time. OBJECTIVE: To investigate whether intraoperative image guidance using ultrasound or stereotaxy contributes to accurate shunt catheter placement and survival. METHODS: We performed a systematic literature review using PubMed and MEDLINE databases for studies that use ultrasound and frameless stereotaxy for ventricular catheter placement for hydrocephalus. All articles assessed the accuracy of catheter tip placement and/or overall shunt survival, and the rate of accurate shunt catheter placement, the overall failure rate, and the average time to shunt failure were extracted for analysis. RESULTS: Although each modality (ultrasound/stereotaxy) did not increase catheter placement accuracy, a combined random-effects meta-analysis of 738 catheters (136 guided by ultrasound, 168 guided by frameless stereotaxy, and 434 freehand) demonstrated a weak benefit of image guidance (risk ratio: 1.19, 95% confidence interval: 1.02-1.39, P = .02), but this result was limited by considerable heterogeneity among studies (I² = 86%, P < .001 by Cochrane's Q test). A meta-analysis could not be performed for shunt survival due to heterogeneity in data reporting. CONCLUSION: Although image guidance offers a promising solution to lower the risk of inaccurate catheter placement, which could lead to lower premature failure of ventricular shunts, our review demonstrated that there is not yet a clear benefit of these technologies. Current literature is limited to case series and cohort studies, and significant between-study heterogeneity in methodology and reporting currently limits a higher order analysis.


Assuntos
Cateteres , Derivações do Líquido Cefalorraquidiano/métodos , Hidrocefalia/cirurgia , Imagens, Psicoterapia/métodos , Neuronavegação/métodos , Humanos , Procedimentos Neurocirúrgicos
19.
Oncotarget ; 6(14): 11882-93, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25957416

RESUMO

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), can attenuate tumor-associated edema and improve patient symptoms but based on magnetic resonance imaging, is associated with non-enhancing tumor progression and possibly gliosarcoma differentiation. To gain insight into these findings, we investigated the role of hypoxia and epithelial-mesenchymal transition (EMT)-associated proteins in GBM. Tumor markers of hypoxia and EMT were upregulated in bevacizumab-treated tumors from GBM patients compared to untreated counterparts. Exposure of glioma cells to 1% oxygen tension increased cell proliferation, expression of EMT-associated proteins and enhanced cell migration in vitro. These phenotypic changes were significantly attenuated by pharmacologic knockdown of hypoxia-inducible Factor 1α (HIF1α) or HIF2α, indicating that HIFs represent a therapeutic target for mesenchymal GBM cells. These findings provide insights into potential development of novel therapeutic targeting of angiogenesis-specific pathways in GBM.


Assuntos
Inibidores da Angiogênese/farmacologia , Bevacizumab/farmacologia , Neoplasias Encefálicas/patologia , Transformação Celular Neoplásica/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glioma/patologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/fisiologia , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Técnicas Analíticas Microfluídicas , Neovascularização Patológica/metabolismo , Fenótipo , RNA Interferente Pequeno , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
20.
J Neurosurg ; 121(2): 285-96, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24949675

RESUMO

OBJECT: Observational studies, such as cohort and case-control studies, are valuable instruments in evidence-based medicine. Case-control studies, in particular, are becoming increasingly popular in the neurosurgical literature due to their low cost and relative ease of execution; however, no one has yet systematically assessed these types of studies for quality in methodology and reporting. METHODS: The authors performed a literature search using PubMed/MEDLINE to identify all studies that explicitly identified themselves as "case-control" and were published in the JNS Publishing Group journals (Journal of Neurosurgery, Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery: Spine, and Neurosurgical Focus) or Neurosurgery. Each paper was evaluated for 22 descriptive variables and then categorized as having either met or missed the basic definition of a case-control study. All studies that evaluated risk factors for a well-defined outcome were considered true case-control studies. The authors sought to identify key features or phrases that were or were not predictive of a true case-control study. Those papers that satisfied the definition were further evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. RESULTS: The search detected 67 papers that met the inclusion criteria, of which 32 (48%) represented true case-control studies. The frequency of true case-control studies has not changed with time. Use of odds ratios (ORs) and logistic regression (LR) analysis were strong positive predictors of true case-control studies (for odds ratios, OR 15.33 and 95% CI 4.52-51.97; for logistic regression analysis, OR 8.77 and 95% CI 2.69-28.56). Conversely, negative predictors included focus on a procedure/intervention (OR 0.35, 95% CI 0.13-0.998) and use of the word "outcome" in the Results section (OR 0.23, 95% CI 0.082-0.65). After exclusion of nested case-control studies, the negative correlation between focus on a procedure/intervention and true case-control studies was strengthened (OR 0.053, 95% CI 0.0064-0.44). There was a trend toward a negative association between the use of survival analysis or Kaplan-Meier curves and true case-control studies (OR 0.13, 95% CI 0.015-1.12). True case-control studies were no more likely than their counterparts to use a potential study design "expert" (OR 1.50, 95% CI 0.57-3.95). The overall average STROBE score was 72% (range 50-86%). Examples of reporting deficiencies were reporting of bias (28%), missing data (55%), and funding (44%). CONCLUSIONS: The results of this analysis show that the majority of studies in the neurosurgical literature that identify themselves as "case-control" studies are, in fact, labeled incorrectly. Positive and negative predictors were identified. The authors provide several recommendations that may reverse the incorrect and inappropriate use of the term "case-control" and improve the quality of design and reporting of true case-control studies in neurosurgery.


Assuntos
Estudos de Casos e Controles , Neurocirurgia/tendências , Medicina Baseada em Evidências , Humanos , Editoração/tendências
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