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1.
N Am Spine Soc J ; 17: 100292, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38193109

RESUMO

Background: Anterior cervical discectomy and fusion (ACDF) interbody implants are shaped anatomically, with a convex superior aspect, or lordotically, with an angle and flat surfaces. However, the effect of implant shape on cervical sagittal balance (CSB) is not well described. Methods: Of the 192 cases reviewed from 2018 to 2019, 118 were included with matching pre- and postoperative imaging. Cases were categorized by interbody implant type (anatomic or lordotic) and number of levels fused (1-level, 2-level, etc.). SurgiMap was used to measure cervical lordosis (CL), C2-C7 sagittal vertical axis (cSVA), T1 slope (T1S), and T1S minus CL (T1S-CL) on pre- and postoperative imaging. Pre- and postoperative parameters were compared within and between each cohort. Change in CL (ΔCL), cSVA (ΔcSVA), and T1S-CL (ΔT1S-CL) were calculated as the difference between pre- and postoperative values and were compared accordingly (1) anatomic versus lordotic and (2) 1-level versus 2-level versus 3-level fusion. Results: Thirty-nine (33.1%), 57 (48.3%), and 22 (18.6%) cases comprised the anatomic, lordotic, and mixed (anatomic and lordotic) groups, respectively. ACDFs improved CL and T1S-CL by 5.71° (p<.001) and 3.32° (p<.01), respectively. CL was improved in the lordotic (5.27°; p<.01) and anatomic (4.57°; p<.01) groups, while only the lordotic group demonstrated improvement in T1S-CL (3.4°; p=.02). There were no differences in ΔCL (p=.70), ΔcSVA (p=.89), or ΔT1S-CL (p=.1) between the groups. Two- and 3-level fusions improved CL by 7.48° (p<.01) and 9.62° (p<.01), and T1S-CL by 4.43° (p<.01) and 5.96° (p<.01), respectively. Conclusions: Overall, ACDFs significantly improved CL and T1S-CL however, there were no differences in CSB correction between the anatomic and lordotic groups. Two- and 3-level fusions more effectively improved CL (vs. single-level) and T1S-CL (vs. 3-level). These results suggest that implants should continue to be personalized to the patient's anatomy, however, future research is needed to validate these findings and incorporate the effects of preoperative deformities.

2.
Medicine (Baltimore) ; 102(47): e36142, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38013300

RESUMO

The anterior lumbar interbody fusion (ALIF) procedure involves several surgical specialties, including general, vascular, and spinal surgery due to its unique approach and anatomy involved. It also carries its own set of complications that differentiate it from posterior lumbar fusion surgeries. The demonstrated benefits of treatment guidelines, such as Enhanced Recovery after Surgery in other surgical procedures, and the lack of current recommendations regarding the anterior approach, underscores the need to develop protocols that specifically address the complexities of ALIF. We aimed to create an evidence-based protocol for pre-, intra-, and postoperative care of ALIF patients and implementation strategies for our health system. A 12-member multidisciplinary workgroup convened to develop an evidence-based treatment protocol for ALIF using a Delphi consensus methodology and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for rating the quality of evidence and strength of protocol recommendations. The quality of evidence, strength of the recommendation and specific implementation strategies for Methodist Health System for each recommendation were described. The literature search resulted in 295 articles that were included in the development of protocol recommendations. No disagreements remained once the authors reviewed the final GRADE assessment of the quality of evidence and strength of the recommendations. Ultimately, there were 39 protocol recommendations, with 16 appropriate preoperative protocol recommendations (out of 17 proposed), 9 appropriate intraoperative recommendations, and 14 appropriate postoperative recommendations. This novel set of evidence-based recommendations is designed to optimize the patient's ALIF experience from the preoperative to the postoperative period.


Assuntos
Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia , Região Lombossacral/cirurgia , Procedimentos Neurocirúrgicos , Resultado do Tratamento , Literatura de Revisão como Assunto
3.
Cureus ; 12(8): e10005, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32983702

RESUMO

Introduction Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread throughout the world with a large medical and economic impact. On March 12, 2020, the World Health Organization (WHO) classified SARS-CoV-2 as a pandemic. As a result of this worldwide public health crisis, politicians, elected officials, and healthcare professionals emergently began trialing hydroxychloroquine (HCQ) in efforts to treat and prevent the transmission of the virus. This meta-analysis was performed to assess the effects of HCQ on patients with COVID-19. Methods  This meta-analysis adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMA) guidelines. Selected articles published between December 2019 and July 2020 were found utilizing the following search engines: PubMed, Google Scholar, Cochrane Library, DisasterLit, Clinicaltrials.gov, Medrxiv, and Embase. Two independent physician reviewers screened eligible articles that met the inclusion and exclusion criteria of the analysis. The outcome measures analyzed were mortality rate, rate of disease progression/improvement, rate of disease severity, and adverse effects of treatment. Six out of 14 studies that met the study's eligibility criteria were selected and further analyzed, with a total of 381 participants (n= 381). Conclusion From the studies analyzed, it was found that groups treated with HCQ had an overall mortality rate that was 2.5 times greater than that of the control group. HCQ treated patients had higher rates of adverse clinical outcomes and side effects compared with the control populations. Lastly, there was a 1.2 times higher rate of improvement in the group of HCQ treated patients with mild to moderate symptoms as compared to the control group.

4.
Cureus ; 12(12): e12322, 2020 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-33520520

RESUMO

Candida (C.) auris is an opportunistic ascomycetous budding yeast that has been emerging as an invasive, multidrug-resistant pathogen over the past 11 years since its discovery. Candida auris infection has raised considerable attention in public health organizations due to its rising number of cases, virulence, and unique resistance to commonly used mycofungal therapy. This case follows a 64-year-old male with multiple comorbidities from the nursing home presenting with polybacterial sepsis along with a urinary tract infection growing Candida auris. Along with treatment for sepsis, the patient was placed on the Centers for Disease Control and Prevention's (CDC's) recommended regimen of micafungin to eradicate C. auris infection and isolation precautions. Cases should be approached carefully and reported to public agencies such as the CDC and state health department.

5.
J Neurooncol ; 120(2): 353-60, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25106865

RESUMO

Choroid plexus carcinoma (CPCs) is a rare, malignant, primary brain tumor with a poor prognosis. Currently, there is no consensus on the use of adjuvant therapy, and few large-scale studies focus exclusively on the pediatric population. We performed a comprehensive systematic review of pediatric CPCs to determine the effects of various adjuvant therapy modalities on overall survival (OS). A literature search was performed to identify studies reporting children with CPC who underwent surgical resection. Only patients who had clearly received adjuvant therapy, or were described as not selected for adjuvant therapy were analyzed in our comparison groups. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine the effects of different types of adjuvant therapies on OS. A total of 135 children (age ≤ 18 years) with CPC who had known adjuvant therapy status and OS were identified from 53 articles. Kaplan-Meier analysis showed that while adjuvant therapy overall improved OS (p = 0.001), different modes of adjuvant therapies had varying effects on OS (p = 0.034). Specifically, combined chemo-radiotherapy as well as chemotherapy alone improved OS (p = 0.001), but radiation did not (p = 0.129). Multivariate Cox proportional hazard model adjusting for confounding factors showed that combined therapy was associated with better OS compared to chemotherapy alone (HR: 0.291, p = 0.027). Both chemotherapy alone and combined chemo-radiation improved OS independent of age, gender, tumor location and extent of resection, while radiation alone did not.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/mortalidade , Carcinoma/mortalidade , Quimiorradioterapia Adjuvante/mortalidade , Neoplasias do Plexo Corióideo/mortalidade , Adolescente , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Carcinoma/patologia , Carcinoma/terapia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Neoplasias do Plexo Corióideo/patologia , Neoplasias do Plexo Corióideo/terapia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
6.
J Clin Neurosci ; 21(12): 2096-101, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25037313

RESUMO

Intracranial ependymomas are rare tumors in adults. Thus, factors affecting prognosis are poorly understood. We performed a study to investigate whether tumor location is an important prognostic factor in adults who undergo surgery for intracranial ependymomas. PubMed was searched to identify studies that reported clinical outcomes in adult patients with intracranial ependymoma. Data were extracted for patient and tumor characteristics, extent of resection, progression-free survival (PFS), and overall survival (OS). Tumors were categorized as supratentorial or infratentorial and extraventricular or intraventricular. Presenting clinical features and tumor characteristics were tabulated. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine PFS and OS by tumor location. Extent of resection was also analyzed by tumor location. A total of 183 patients were included in the meta-analysis. Patients presented at a mean of 8.2months with a myriad of clinical features. The mean tumor size was 3.38 cm, and 19.3% of tumors were cystic. Supratentorial tumors were most commonly located in the frontal and parietal lobes, and infratentorial tumors in the fourth ventricle. Supratentorial tumors demonstrated significantly poorer PFS (p<0.001) and OS (p=0.003) than infratentorial tumors, despite a higher rate of gross total resection (GTR) for the supratentorial tumors (72.6% versus 42.1%). Extraventricular ependymomas displayed significantly poorer PFS than intraventricular ependymomas (p=0.009). In summary, supratentorial ependymomas have significantly poorer PFS and OS than their infratentorial counterparts, despite being more conducive to GTR, suggesting increased clinical aggressiveness. Extraventricular location is also associated with significantly poorer PFS than intraventricular location.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Ependimoma/fisiopatologia , Ependimoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Intervalo Livre de Doença , Ependimoma/patologia , Feminino , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Supratentoriais/cirurgia , Adulto Jovem
7.
J Neurosurg Pediatr ; 13(4): 393-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24506340

RESUMO

OBJECT: Ependymomas are a common type of CNS tumor in children, although only 13% originate from the spinal cord. Aside from location and extent of resection, the factors that affect outcome are not well understood. METHODS: The authors performed a search of an institutional neuropathology database to identify all patients with spinal cord ependymomas treated over the past 20 years. Data on patient age, sex, clinical presentation, symptom duration, tumor location, extent of resection, use of radiation therapy, surgical complications, presence of tumor recurrence, duration of follow-up, and residual symptoms were collected. Pediatric patients were defined as those 21 years of age or younger at diagnosis. The extent of resection was defined by the findings of the postoperative MR images. RESULTS: A total of 24 pediatric patients with spinal cord ependymomas were identified with the following pathological subtypes: 14 classic (Grade II), 8 myxopapillary (Grade I), and 2 anaplastic (Grade III) ependymomas. Both anaplastic ependymomas originated in the intracranial compartment and spread to the spinal cord at recurrence. The mean follow-up duration for patients with classic and myxopapillary ependymomas was 63 and 45 months, respectively. Seven patients with classic ependymomas underwent gross-total resection (GTR), while 4 received subtotal resection (STR), 2 received STR as well as radiation therapy, and 1 received radiation therapy alone. All but 1 patient with myxopapillary ependymomas underwent GTR. Three recurrences were identified in the Grade II group at 45, 48, and 228 months. A single recurrence was identified in the Grade I group at 71 months. The mean progression-free survival (PFS) was 58 months in the Grade II group and 45 months in the Grade I group. CONCLUSIONS: Extent of resection is an important prognostic factor in all pediatric spinal cord ependymomas, particularly Grade II ependymomas. These data suggest that achieving GTR is more difficult in the upper spinal cord, making tumor location another important factor. Although classified as Grade I lesions, myxopapillary ependymomas had similar outcomes when compared with classic (Grade II) ependymomas, particularly with respect to PFS. Long-term complications or new neurological deficits were rare. Among patients with long-term follow-up, those who underwent GTR had a recurrence rate of 20% compared with 40% among those with STR or biopsy only, suggesting that extent of resection is perhaps a more important prognostic factor than histological grade in predicting PFS, which has been suggested by other data in the literature. Given the relative paucity of these lesions, collaborative multiinstitutional studies are needed, and such efforts should also focus on molecular and genetic analysis to refine the current classification system.


Assuntos
Ependimoma/diagnóstico , Ependimoma/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/cirurgia , Adolescente , Criança , Intervalo Livre de Doença , Ependimoma/patologia , Ependimoma/radioterapia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Gradação de Tumores , Recidiva Local de Neoplasia/radioterapia , Procedimentos Neurocirúrgicos , Estudos Retrospectivos , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/radioterapia , Resultado do Tratamento , Adulto Jovem
8.
Neurosurg Rev ; 37(2): 179-92; discussion 192, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24068529

RESUMO

Choroid plexus carcinoma (CPC) is a World Health Organization (WHO) grade III brain tumor with a poor prognosis that occurs mainly in children. Gross total resection of CPC is highly recommended and is associated with improved overall survival, although it is often associated with increased morbidity. The use of adjuvant therapies has yet to be standardized, although evidence suggests that for patients with incompletely resected CPCs, a combination of chemotherapy and radiation therapy may be beneficial. The use of radiation therapy for younger children (<3 years old) with CPC, however, is not recommended, due to the potential negative neurological sequelae associated with radiation to the developing brain. Given that the majority of CPC patients are young children, questions regarding optimal radiation dose, chemotherapy agents, and how to combine these two adjuvant treatment modalities to achieve the best outcomes remain unanswered. In this paper we summarize the current management of CPC in the literature. Further studies are needed to standardize the treatment paradigm for this malignant brain tumor.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Carcinoma/patologia , Carcinoma/terapia , Neoplasias do Plexo Corióideo/patologia , Neoplasias do Plexo Corióideo/terapia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Carcinoma/diagnóstico , Carcinoma/epidemiologia , Neoplasias do Plexo Corióideo/diagnóstico , Neoplasias do Plexo Corióideo/epidemiologia , Terapia Combinada/métodos , Humanos , Resultado do Tratamento
9.
Oncol Rev ; 8(1): 242, 2014 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-25992231

RESUMO

G-protein coupled receptors (GPCRs) are among the most diverse and ubiquitous proteins in all of biology. The epidermal growth factor-seven span transmembrane (EGF-TM7) subfamily of adhesion GPCRs is a small subset whose members are mainly expressed on the surface of leukocytes. The EGF domains on the N-terminus add significant size to these receptors and they are considered to be among the largest members of the TM7 family. Although not all of their ligands or downstream targets have been identified, there is evidence implicating the EGF-TM7 family diverse processes such as cell adhesion, migration, inflammation, and autoimmune disease. Recent studies have identified expression of EGF-TM7 family members on human neoplasms including those of the thyroid, stomach, colon, and brain. Their presence on these tissues is not surprising given the ubiquity of GPCRs, but because their functional significance and pathways are not completely understood, they are of tremendous clinical and scientific interest. Current evidence suggests that expression of certain EGF-TM7 receptors is correlated with tumor grade, confers a more invasive phenotype, and increases the likelihood of metastatic disease. In this review, we will discuss the structure, function, and regulation of these receptors. We also describe the expression of these receptors in human cancers and explore their potential mechanistic significance.

10.
J Neurooncol ; 116(1): 179-85, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24166581

RESUMO

Choroid plexus carcinoma (CPC) is a rare, malignant, primary brain tumor with a poor prognosis. While previous reports have shown benefits of aggressive surgery, very few large-scale studies have focused exclusively on the pediatric population, for whom the risks of aggressive surgery must be weighed carefully against the benefits. We performed a comprehensive systematic review of pediatric CPCs to test the effects of gross total resection (GTR) on overall survival (OS) and progression-free survival (PFS). A Pubmed search was performed to identify children with CPC who underwent surgical resection. Only disaggregated clinical cases in which extent of resection was confirmed by CT or MRI were included for analysis. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine the effects of extent of resection on OS and PFS. Disaggregated clinical data from a total of 102 pediatric CPC patients (age ≤18 years) with known extent of resection and overall survival were analyzed. GTR was significantly associated with better OS by Kaplan-Meier analysis (logrank p < 0.001). Multivariate Cox regression analysis adjusting for age, gender, tumor location (supratentorial vs. infratentorial), and type of adjuvant therapy (chemotherapy, radiation, and combined therapy), showed that GTR independently increased OS (p = 0.006). While GTR also improved PFS on Kaplan-Meier analysis (p = 0.027), the effect did not meet our criteria for significance in our multivariate Cox model (p = 0.120). GTR improved OS of pediatric CPC and is recommended if it can be safely performed.


Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Carcinoma/mortalidade , Carcinoma/cirurgia , Neoplasias do Plexo Corióideo/mortalidade , Neoplasias do Plexo Corióideo/cirurgia , Procedimentos Neurocirúrgicos/métodos , Criança , Pré-Escolar , Feminino , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Modelos de Riscos Proporcionais , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Int J Oncol ; 43(5): 1343-50, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23969601

RESUMO

G-protein coupled receptors (GPCRs) represent the most diverse and biologically ubiquitous protein receptors. The epidermal growth factor seven-span transmembrane (EGF-TM7) family consists of adhesion GPCRs with a diverse functional repertoire. CD97 is the most broadly expressed member with roles in cell adhesion, migration and regulation of intercellular junctions. CD97 is also expressed in a variety of human malignancies including those of the thyroid, stomach, colon and brain. CD97 confers an invasive phenotype and has been shown to correlate with tumor grade, lymph node invasion, metastatic spread and overall prognosis. More recently, CD97 was found to signal through Gα12/13, resulting in increased RHO-GTP levels. Proven roles in tumor invasion and signaling make CD97 an exciting novel therapeutic target. In this review, we will discuss the structure and function of this receptor, with a specific focus on its mechanistic significance in neoplastic diseases.


Assuntos
Antígenos CD/metabolismo , Leucócitos/metabolismo , Neoplasias/metabolismo , Humanos , Neoplasias/patologia , Neoplasias/terapia , Receptores Acoplados a Proteínas G
12.
Neuro Oncol ; 15(11): 1518-31, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23887941

RESUMO

BACKGROUND: Mechanisms of glioma invasion remain to be fully elucidated. Glioma cells within glioblastoma multiforme (GBM) range from well-differentiated tumor cells to less-differentiated brain tumor-initiating cells (BTICs). The ß2-subunit of Na(+)/K(+)-ATPase, called the adhesion molecule on glia (AMOG), is highly expressed in normal glia but is thought to be universally downregulated in GBM. To test our hypothesis that expression of AMOG is heterogeneous in GBM and confers a less invasive phenotype, we compared it between BTICs and differentiated cells from patient-matched GBM and then tested GBM invasion in vitro after AMOG overexpression. METHODS: Immunohistochemistry, immunoblotting, and real-time PCR were used to characterize AMOG protein and mRNA expression in tumor samples, BTICs, and differentiated cells. Matrigel invasion assay, scratch assay, and direct cell counting were used for testing in vitro invasion, migration, and proliferation, respectively. RESULTS: While AMOG expression is heterogeneous in astrocytomas of grades II-IV, it is lost in most GBM. BTICs express higher levels of AMOG mRNA and protein compared with patient-matched differentiated tumor cells. Overexpression of AMOG decreased GBM cell and BTIC invasion without affecting migration or proliferation. Knockdown of AMOG expression in normal human astrocytes increased invasion. CONCLUSIONS: AMOG expression inhibits GBM invasion. Its downregulation increases invasion in glial cells and may also represent an important step in BTIC differentiation. These data provide compelling evidence implicating the role of AMOG in glioma invasion and provide impetus for further investigation.


Assuntos
Adenosina Trifosfatases/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proteínas de Transporte de Cátions/metabolismo , Moléculas de Adesão Celular Neuronais/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Neoplasias Encefálicas/mortalidade , Regulação para Baixo , Glioblastoma/mortalidade , Humanos , Invasividade Neoplásica , Taxa de Sobrevida , Células Tumorais Cultivadas
13.
J Clin Neurosci ; 20(10): 1390-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23768966

RESUMO

Although the World Health Organization (WHO) categorizes spinal ependymomas into three histological grades, difference in surgical outcomes between WHO grades I and II tumors are unclear. For these benign tumors, prognosis may be best determined by factors other than tumor grade alone, such as extent of resection. To analyze the effects of the extent of resection on different grades of spinal ependymomas, we performed a comprehensive literature review to identify adult spinal ependymoma patients who received surgical resection with a clearly identifiable WHO grade. A total of 175 patients were identified. While grade III tumors carried the worst prognosis as expected (p<0.001), grade I and II tumors did not differ significantly in outcomes following surgery. Overall, gross total resection (GTR, 68.7%, 114/166) provided significantly improved progression-free survival (PFS, p<0.001) and overall survival (OS, p=0.022) compared to the subtotal resection group. Surprisingly, the highest GTR rate was achieved for grade II tumors (78.8%, 78/99; p<0.001) followed by grade I (58.9%, 33/56) and grade III tumors (27.3%, 3/11). Interestingly, PFS was significantly improved by GTR for grade II tumors (p<0.001), but not for grade I (p=0.705). Similar trends, although not statistically significant, were found for OS. Our results show that while GTR provides the best overall outcomes, GTR is most effective for classic grade II ependymomas, but not for grade I ependymomas. Despite having a lower WHO grade, myxopapillary ependymomas have a lower GTR rate, and benefit less from GTR.


Assuntos
Ependimoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Medula Espinal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Bibliográficas/estatística & dados numéricos , Intervalo Livre de Doença , Ependimoma/mortalidade , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias da Medula Espinal/mortalidade , Índices de Gravidade do Trauma , Adulto Jovem
14.
J Clin Neurosci ; 20(10): 1333-41, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23768968

RESUMO

Tuberculosis is among the oldest and most devastating infectious diseases worldwide. Nearly one third of the world's population has active or latent disease, resulting in 1.5 million deaths annually. Central nervous system involvement, while rare, is the most severe form of tuberculosis. Manifestations include tuberculoma and tuberculous meningitis, with the majority of cases occurring in children and immunocompromised patients. Despite advancements in imaging and laboratory diagnostics, tuberculomas of the central nervous system remain a diagnostic challenge due to their insidious nature and nonspecific findings. On imaging studies tuberculous meningitis is characterized by diffuse basal enhancement, but tuberculomas may be indistinguishable from neoplasms. Early diagnosis is imperative, since clinical outcomes are largely dependent on timely treatment. Stereotactic biopsy with histopathological analysis can provide a definitive diagnosis, but is only recommended when non-invasive methods are inconclusive. Standard medical treatment includes rifampicin, isoniazid, pyrazinamide, and streptomycin or ethambutol. In cases of drug resistance, revision of the treatment regimen with second-line agents is recommended over the addition of a single drug to the first-line regimen. Advances in genomics have identified virulent strains of tuberculosis and are improving our understanding of host susceptibility. Neurosurgical referral is advised for patients with elevated intracranial pressure, seizures, or brain or spinal cord compression. This review synthesizes pertinent findings in the literature surrounding central nervous system tuberculoma in an effort to highlight recent advances in pathophysiology, diagnosis, and treatment.


Assuntos
Doenças do Sistema Nervoso Central , Tuberculoma , Doenças do Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Central/fisiopatologia , Doenças do Sistema Nervoso Central/terapia , Humanos , Tuberculoma/patologia , Tuberculoma/fisiopatologia , Tuberculoma/terapia
15.
PLoS One ; 8(4): e62765, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23658650

RESUMO

Mechanisms of invasion in glioblastoma (GBM) relate to differential expression of proteins conferring increased motility and penetration of the extracellular matrix. CD97 is a member of the epidermal growth factor seven-span transmembrane family of adhesion G-protein coupled receptors. These proteins facilitate mobility of leukocytes into tissue. In this study we show that CD97 is expressed in glioma, has functional effects on invasion, and is associated with poor overall survival. Glioma cell lines and low passage primary cultures were analyzed. Functional significance was assessed by transient knockdown using siRNA targeting CD97 or a non-target control sequence. Invasion was assessed 48 hours after siRNA-mediated knockdown using a Matrigel-coated invasion chamber. Migration was quantified using a scratch assay over 12 hours. Proliferation was measured 24 and 48 hours after confirmed protein knockdown. GBM cell lines and primary cultures were found to express CD97. Knockdown of CD97 decreased invasion and migration in GBM cell lines, with no difference in proliferation. Gene-expression based Kaplan-Meier analysis was performed using The Cancer Genome Atlas, demonstrating an inverse relationship between CD97 expression and survival. GBMs expressing high levels of CD97 were associated with decreased survival compared to those with low CD97 (p = 0.007). CD97 promotes invasion and migration in GBM, but has no effect on tumor proliferation. This phenotype may explain the discrepancy in survival between high and low CD97-expressing tumors. This data provides impetus for further studies to determine its viability as a therapeutic target in the treatment of GBM.


Assuntos
Antígenos CD/genética , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Antígenos CD/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Ensaios de Migração Celular , Movimento Celular , Proliferação de Células , Técnicas de Silenciamento de Genes , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Invasividade Neoplásica , Fenótipo , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores Acoplados a Proteínas G , Análise de Sobrevida
16.
Childs Nerv Syst ; 29(11): 2057-64, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23677177

RESUMO

PURPOSE: Prognostic factors affecting outcomes in pediatric spinal cord ependymomas are limited. We sought to investigate potential associations between extent of resection and histologic grade on progression-free survival (PFS) and overall survival (OS). METHODS: A comprehensive literature search was performed to identify pediatric patients who underwent surgical resection for spinal cord ependymomas. Only manuscripts with clearly defined age, tumor grade, extent of resection, and clinical follow-up were included. RESULTS: A total of 80 patients were identified with a histologic distribution as follows: 36 % myxopapillary (grade I), 54 % classical (grade II), and 10 % anaplastic (grade III). There was no association between tumor grade and PFS. The only factor associated with improved PFS was gross total resection (GTR), which remained significant in a multivariate model (hazard ratio (HR) = 0.248, p = 0.022). Moreover, older age (HR = 0.818, p = 0.026), GTR (HR = 0.042, p = 0.013), and anaplastic grade (HR = 19.847, p = 0.008) demonstrated a significant association with OS in a multivariate model. CONCLUSIONS: Among pediatric patients with spinal cord ependymomas, PFS did not differ across histologic grades but was prolonged among patients who underwent GTR. Age, extent of resection, and tumor grade were all significantly associated with survival.


Assuntos
Ependimoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Medula Espinal/cirurgia , Adolescente , Fatores Etários , Criança , Intervalo Livre de Doença , Ependimoma/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Recidiva Local de Neoplasia , Neoplasias da Medula Espinal/patologia , Resultado do Tratamento
17.
J Clin Neurosci ; 20(7): 1014-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23693024

RESUMO

Glioblastoma multiforme (GBM) is a grade IV malignant brain tumor with high mortality and has been well known to involve many molecular pathways, including G-protein coupled receptor (GPCR)-mediated signaling (such as epithelial growth factor receptor [EGFR] and platelet derived growth factor receptor [PDGFR]). G protein-coupled receptor kinases (GRK) directly regulate GPCR activity by phosphorylating activated agonist-bound receptors to desensitize signaling and internalize receptors through beta-arrestins. Recent studies in various cancers, including prostate and breast cancer, have highlighted the role of change in GRK expression to oncogenesis and tumor proliferation. In this study, we evaluated the expression of GRK5 in grade II to grade IV glioma specimens using immunohistochemistry and found that GRK5 expression levels are highly correlated with aggressiveness of glioma. We used culture conditions to selectively promote the growth of either glioblastoma cells with stem cell markers (GSC) or differentiated glioblastoma cells (DGC) from fresh GBM specimens. GSC are known to be highly invasive and mobile, and have the capacity to self-renew and are more resistant to chemotherapy and radiation compared to differentiated populations of GBM. We examined the expression of GRK5 in these two sets of culturing conditions for GBM cells and found that GRK5 expression is upregulated in GSC compared to differentiated GBM cells. To better understand the role of GRK5 in GBM-derived stem cells, we created stable GRK5 knockdown and evaluated the proliferation rate. Using an ATP chemiluminescence assay, we show, for the first time, that knocking down the expression of GRK5 decreased the proliferation rate of GSC in contrast to control.


Assuntos
Proliferação de Células , Quinase 5 de Receptor Acoplado a Proteína G/metabolismo , Glioblastoma/metabolismo , Células-Tronco Neoplásicas/enzimologia , Animais , Western Blotting , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Glioblastoma/patologia , Xenoenxertos , Humanos , Imuno-Histoquímica , Luminescência , Camundongos , Camundongos Nus , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Neurosurgery ; 73(2): 247-55; discussion 255, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23670032

RESUMO

BACKGROUND: Ependymomas constitute approximately 40% of primary intraspinal tumors. Current World Health Organization (WHO) grading may not correlate with observed progression-free survival (PFS). OBJECTIVE: This retrospective study of prospectively collected data examines whether PFS is influenced by the histological grade or by the extent of resection. It also analyzes the usage and effectiveness of postoperative adjuvant radiotherapy. METHODS: We reviewed 134 consecutive patients with ependymomas of all grades. Pathology slides were re-reviewed and the histological grades were confirmed by a single neuropathologist. Postoperative residual or recurrence was evaluated with follow-up magnetic resonance imaging. RESULTS: There were 85 male and 49 female patients, ranging from 10 to 79 (median 41) years of age. Thirty patients had WHO grade I tumors, 101 had grade II tumors, and 3 had grade III tumors. Kaplan-Meier analysis of PFS demonstrated a mean duration of 6 years for grade I, 14.9 years for grade II, and 3.7 years for grade III (P < .001). In grade II ependymomas, mean PFS was 11.2 years with subtotal resection and 17.8 years with gross total resection (P < .01). PFS of patients who underwent subtotal resection was not significantly changed by adjuvant radiotherapy (P < .36). CONCLUSION: Patients with grade II ependymoma have significantly longer PFS than patients with grade I ependymoma. The extent of resection did not affect PFS in grade I ependymoma but it did in grade II. Contrary to its higher grade, WHO grade II ependymoma carries a better prognosis than WHO grade I ependymoma.


Assuntos
Ependimoma/mortalidade , Ependimoma/patologia , Neoplasias da Medula Espinal/mortalidade , Neoplasias da Medula Espinal/patologia , Adolescente , Adulto , Idoso , Criança , Intervalo Livre de Doença , Ependimoma/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Procedimentos Neurocirúrgicos , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias da Medula Espinal/terapia , Resultado do Tratamento , Adulto Jovem
19.
J Clin Neurosci ; 20(6): 808-12, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23623658

RESUMO

Choroid plexus papillomas are rare neuroepithelial tumors found mainly in children. Although well studied in the pediatric population, there is a paucity of literature focusing specifically on adults. We sought to assess the relative advantage of gross total resection (GTR) and further characterize the natural history of this disease in adults. A comprehensive PubMed search was performed to identify adults who underwent surgical resection for choroid plexus papillomas with clearly reported age, tumor location, and extent of resection. Kaplan-Meier analysis was used to assess progression-free survival (PFS) and overall survival (OS). Multivariate analysis was performed using Cox proportional hazards models. A total of 193 patients were identified with a mean age of 39.9 ± 1.1 years. GTR was achieved in 72% of patients with subtotal resection (STR) in 28%. GTR was associated with a significant increase in both PFS (p = 0.015) and OS (p = 0.004) compared to STR. In a multivariate Cox proportional hazards model we found that only GTR was associated with recurrence (hazard ratio [HR] = 0.47, 95% confidence interval [CI] 0.25-0.90), while both age (HR = 1.03, 95% CI 1.00-1.05) and GTR (HR = 0.36, 95% CI 0.17-0.78) were associated with OS. Interestingly, our observed recurrence and death rates were higher than those in previously published studies. These findings demonstrate the benefit of GTR for the treatment of choroid plexus papillomas in adults. Our analysis suggests that these lesions are not as indolent as previously thought and while GTR is preferred, it is not always curative.


Assuntos
Procedimentos Neurocirúrgicos/métodos , Papiloma do Plexo Corióideo/cirurgia , Resultado do Tratamento , Adulto , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Papiloma do Plexo Corióideo/mortalidade , Papiloma do Plexo Corióideo/radioterapia , Modelos de Riscos Proporcionais , PubMed/estatística & dados numéricos , Radioterapia Adjuvante
20.
J Neurooncol ; 113(1): 117-25, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23468001

RESUMO

Choroid plexus papillomas (CPPs) are rare, indolent lesions that comprise less than 0.5 % of intracranial tumors. We sought to assess the long-term outcomes and associated surgical complications at our institution. A review of the University of California, San Francisco (UCSF) Brain Tumor Research Center (BTRC) database was performed to identify a cohort of patients treated for CPP from 1997 to 2011. Patients were grouped based on tumor location and extent of resection. Outcomes including progression-free survival and surgical complications were assessed. We identified 24 patients (16 female, 8 male) ranging in age from 6 months to 55 years (median 29 years) treated at our institution. Tumors were found in the following locations: 16 (67 %) fourth ventricle/cerebellopontine angle; 7 (29 %) lateral ventricle; 1 (4 %) third ventricle. Gross total resection (GTR) was achieved in 20 patients (83 %) with subtotal resection (STR) in 4 (17 %). Median follow-up time was 2.8 years with 3 recurrences identified at 1.6, 3.3, and 8.5 years. Extent of resection and tumor location were not associated with recurrence. There was one new permanent neurologic deficit detected after surgery. All patients were alive at most recent follow-up. Attempted gross total resection is the standard treatment for CPPs and generally associated with excellent outcomes. Since recurrences are rare, even among patients who undergo STR, radiation may be reserved for cases of tumor progression. This modern experience at a tertiary care center performed exclusively during the MRI-era demonstrates that CPPs can be safely removed with minimal morbidity and good tumor control.


Assuntos
Papiloma do Plexo Corióideo/cirurgia , Adolescente , Adulto , Criança , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Papiloma do Plexo Corióideo/mortalidade , Papiloma do Plexo Corióideo/patologia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Adulto Jovem
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