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1.
Acta Neurochir (Wien) ; 166(1): 230, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789840

RESUMEN

BACKGROUND: Superior Semicircular Canal Dehiscence (SSCD) is a dehiscence of the otic capsule which normally lies over the superior semicircular canal. This database constitutes the largest series of SSCD patients to date. OBJECTIVE: To determine what preoperative factors, if any, contribute to postoperative outcomes and evaluate symptom resolution in a large SSCD patient cohort. METHODS: A single-institution, retrospective chart review collected patient demographics, intraoperative findings, and pre-and postoperative symptoms. Fisher's exact t-test was performed for unpaired categorical variables, with a significance level of p < 0.05. RESULTS: 350 SSCD repairs were performed. The median age was 52 years (range: 17-86 years, ± 6.4 years), and the median follow-up duration was 4.6 months (range: 0.03-59.5 months, ± 6.8 months). Preoperative hearing loss was significantly associated with female sex (p = 0.0028). The most reported preoperative symptoms were tinnitus (77.4%), dizziness (74.0%), autophony (66.3%), amplification (63.7%), and disequilibrium (62.6%). Between patients who received unilateral versus bilateral SSCD repair, the greatest postoperative symptomatic resolution was seen in autophony (74.9%, p < 0.001), amplification (77.3%, p = 0.00027), hyperacusis (77.4%, p = 0.023), hearing (62.9%, p = 0.0063), and dizziness (54.6%, p < 0.001) for patients with unilateral SSCD repair. CONCLUSION: Surgical repair via the middle cranial fossa approach can significantly resolve auditory, vestibular, and neurological symptoms of patients with SSCD. Although this is one of the largest single-institution SSCD studies to date, future multi-institutional, prospective studies would be beneficial to validate these results.


Asunto(s)
Dehiscencia del Canal Semicircular , Humanos , Persona de Mediana Edad , Femenino , Masculino , Adulto , Anciano , Anciano de 80 o más Años , Adolescente , Adulto Joven , Estudios Retrospectivos , Dehiscencia del Canal Semicircular/cirugía , Resultado del Tratamiento , Canales Semicirculares/cirugía , Complicaciones Posoperatorias/etiología , Acúfeno/etiología , Acúfeno/cirugía
2.
Int J Mol Sci ; 25(11)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38892305

RESUMEN

Glioblastoma is a highly aggressive neoplasm and the most common primary malignant brain tumor. Endothelial tissue plays a critical role in glioblastoma growth and progression, facilitating angiogenesis, cellular communication, and tumorigenesis. In this review, we present an up-to-date and comprehensive summary of the role of endothelial cells in glioblastomas, along with an overview of recent developments in glioblastoma therapies and tumor endothelial marker identification.


Asunto(s)
Neoplasias Encefálicas , Células Endoteliales , Glioblastoma , Neovascularización Patológica , Glioblastoma/patología , Glioblastoma/metabolismo , Glioblastoma/terapia , Humanos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo , Animales , Biomarcadores de Tumor/metabolismo
3.
J Neurooncol ; 161(3): 583-591, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36786952

RESUMEN

OBJECTIVE: Surgical recovery of meningiomas relies on a variety of factors, including tumor volume, vascularity, embolization status, and blood loss during excision. Although hypervascular meningiomas can potentially be amendable to embolization, methods for determining optimal vascularity for this procedure are currently lacking. Our group previously established the meningioma vascularity index (MVI) as a marker of tumor vascularity. In this study, we aim to build on our previous work and further examine the relationship between MVI and intraoperative estimated blood loss (EBL). METHODS: A retrospective data extraction was conducted between August 2010 and October 2019 from patients undergoing craniotomy for meningioma. Of the 85 intracranial meningiomas included, 39 were embolized. Demographic data, extent of resection, embolization status, and EBL were among the extracted variables. Flow void volumes were measured on T2-weighted MRI images using a segmentation software with a voxel-based segmentation method. RESULTS: MVI was a predictor of EBL within the entire cohort, when controlling for tumor volume (R2 adjusted = 0.26; P = 0.027). A high MVI (> 2.01 cm3) was associated with higher likelihood of receiving subtotal resection (STR) (OR 4.07, 95% CI 1.17-14.15; P = 0.035). Although the mean MVI and tumor volume were higher in the embolized cohort (P = 0.009 and P = 0.005), there were no significant differences in EBL, or blood transfusion rates regardless of embolization status. CONCLUSIONS: MVI may be used as a non-invasive radiological marker to gauge meningioma vascularity, predict EBL, and guide the decision-making process when it comes to embolization and surgical planning.


Asunto(s)
Embolización Terapéutica , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Pérdida de Sangre Quirúrgica , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Estudios Retrospectivos , Cuidados Preoperatorios
4.
J Neurooncol ; 163(2): 417-427, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37294422

RESUMEN

PURPOSE: There is limited knowledge about the associations between sodium and proton MRI measurements in brain tumors. The purpose of this study was to quantify intra- and intertumoral correlations between sodium, diffusion, and perfusion MRI in human gliomas. METHODS: Twenty glioma patients were prospectively studied on a 3T MRI system with multinuclear capabilities. Three mutually exclusive tumor volumes of interest (VOIs) were segmented: contrast-enhancing tumor (CET), T2/FLAIR hyperintense non-enhancing tumor (NET), and necrosis. Median and voxel-wise associations between apparent diffusion coefficient (ADC), normalized relative cerebral blood volume (nrCBV), and normalized sodium measurements were quantified for each VOI. RESULTS: Both relative sodium concentration and ADC were significantly higher in areas of necrosis compared to NET (P = 0.003 and P = 0.008, respectively) and CET (P = 0.02 and P = 0.02). Sodium concentration was higher in CET compared to NET (P = 0.04). Sodium and ADC were higher in treated compared to treatment-naïve gliomas within NET (P = 0.006 and P = 0.01, respectively), and ADC was elevated in CET (P = 0.03). Median ADC and sodium concentration were positively correlated across patients in NET (r = 0.77, P < 0.0001) and CET (r = 0.84, P < 0.0001), but not in areas of necrosis (r = 0.45, P = 0.12). Median nrCBV and sodium concentration were negatively correlated across patients in areas of NET (r=-0.63, P = 0.003). Similar associations were observed when examining voxel-wise correlations within VOIs. CONCLUSION: Sodium MRI is positively correlated with proton diffusion MRI measurements in gliomas, likely reflecting extracellular water. Unique areas of multinuclear MRI contrast may be useful in future studies to understand the chemistry of the tumor microenvironment.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Protones , Imagen por Resonancia Magnética , Glioma/diagnóstico por imagen , Glioma/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Imagen de Difusión por Resonancia Magnética , Perfusión , Necrosis , Microambiente Tumoral
5.
J Neurooncol ; 159(1): 81-94, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35704158

RESUMEN

PURPOSE: Gliomas are the most common primary tumors of the central nervous system and are categorized by the World Health Organization into either low-grade (grades 1 and 2) or high-grade (grades 3 and 4) gliomas. A subset of patients with glioma may experience no tumor-related symptoms and be incidentally diagnosed. These incidental low-grade gliomas (iLGG) maintain controversial treatment course despite scientific advancements. Here we highlight the recent advancements in classification, neuroimaging, and surgical management of these tumors. METHODS: A review of the literature was performed. The authors created five subtopics of focus: histological criteria, diagnostic imaging, surgical advancements, correlation of surgical resection and survival outcomes, and clinical implications. CONCLUSIONS: Alternating studies suggest that these tumors may experience higher mutational rates than their counterparts. Significant progress in management of gliomas, regardless of the grade, has been made through modern neurosurgical treatment modalities, diagnostic neuroimaging, and a better understanding of the genetic composition of these tumors. An optimal treatment approach for patients with newly diagnosed iLGG remains ill-defined despite multiple studies arguing in favor of safe maximal resection. Our review emphasizes the not so benign nature of incidental low grade glioma and further supports the need for future studies to evaluate survival outcomes following surgical resection.


Asunto(s)
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Glioma/diagnóstico por imagen , Glioma/patología , Glioma/cirugía , Humanos , Procedimientos Neuroquirúrgicos/métodos , Resultado del Tratamiento
6.
J Neurooncol ; 160(3): 545-553, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36445608

RESUMEN

PURPOSE: Spheno-orbital meningiomas are rare tumors, accounting for up to 9% of all intracranial meningiomas. Patients commonly present with proptosis, and visual deficits. These slow growing tumors are hard to resect due to extension into several anatomical compartments, resulting in recurrence rates as high as 35-50%. Although open surgical approaches have been historically used for resection, a handful of endoscopic approaches have been reported in recent years. We aimed to review the literature and describe a case of spheno-orbital meningioma with severe vision loss which was resected with an endoscopic endonasal approach achieving complete resolution of visual symptoms. METHODS: A systematic review of literature was conducted in accordance with the PRISMA guidelines. PubMed, Cochrane, and Web of Science databases were queried for spheno-orbital meningiomas resected via an endoscopic endonasal approach. Furthermore, the presentation, surgical management, and post-operative outcomes of a 53-year-old female with a recurrent spheno-orbital meningioma are described. RESULTS: The search yielded 26 articles, of which 8 were included, yielding 19 cases. Average age at presentation was 60.5 years (range: 44-82), and 68.4% of patients were female. More than half of the cases achieved subtotal resection. Common complications associated with endoscopic endonasal surgery included CN V2 or CN V2/V3 hypoesthesia. Following surgical intervention, visual acuity and visual field remained stable or improved in the majority of the patients. CONCLUSION: Endoscopic approaches are slowly gaining momentum for treatment of spheno-orbital meningiomas. Further studies on the clinical benefits of this approach on patient outcomes and post-operative complications is warranted.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Neoplasias Orbitales , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Meningioma/complicaciones , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Hueso Esfenoides/cirugía , Hueso Esfenoides/patología , Neoplasias Orbitales/complicaciones , Neoplasias Orbitales/cirugía , Procedimientos Neuroquirúrgicos/métodos , Resultado del Tratamiento , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/patología , Neoplasias Meníngeas/complicaciones , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología , Estudios Retrospectivos
7.
Neurosurg Rev ; 45(2): 1041-1088, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34613526

RESUMEN

The history of academic research on ependymoma is expansive. This review summarizes its history with a bibliometric analysis of the 100 most cited articles on ependymoma. In March 2020, we queried the Web of Science database to identify the most cited articles on ependymoma using the terms "ependymoma" or "ependymal tumors," yielding 3145 publications. Results were arranged by the number of times each article was cited in descending order. The top 100 articles spanned across nearly a century; the oldest article was published in 1924, while the most recent was in 2017. These articles were published in 35 unique journals, including a mix of basic science and clinical journals. The three institutions with the most papers in the top 100 were St. Jude Children's Research Hospital (16%), the University of Texas MD Anderson Cancer Center (6%), and the German Cancer Research Center (5%). We analyzed the publications that may be considered the most influential in the understanding and treatment management of ependymoma. Studies focused on the molecular classification of ependymomas were well-represented among the most cited articles, reflecting the field's current area of focus and its future directions. Additionally, this article also offers a reference for further studies in the ependymoma field.


Asunto(s)
Bibliometría , Ependimoma , Niño , Bases de Datos Factuales , Ependimoma/genética , Humanos , Biología Molecular , Publicaciones
8.
Cell Tissue Res ; 386(1): 47-57, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34302219

RESUMEN

The present study reports the feasibility and successful production of rabbit cG-CAOMECS, designed to reconstruct corneal epithelium of patients with bilateral limbal stem cell deficiency. To produce a safe, chemically defined and FDA compliant cG-CAOMECS, oral mucosal epithelial cells were isolated from a biopsy of rabbit buccal tissue and seeded on a cGMP-certified cell culture surface coated with GMP-grade extracellular matrix. A newly designed clinical-grade medium (KaFa™ medium) was utilized to carry out cell expansion. Detachment and harvesting of the produced cell sheet was accomplished using collagenase treatment. Live cell imaging and morphological analysis techniques were used to examine cell growth. Cells attached onto the surface and self-assembled into colony-forming units (CFUs). Microscopic examination showed that CFUs formed during the first 5 days, and basal monolayer cell sheet formed in less than 10 days. Cells expanded to form a multilayered epithelial cell sheet that was harvested after 17-19 days in culture. Immunostaining and Western blot analyses showed that deltaNp63 was expressed in the basal cells and K3/K12 was expressed in the apical cells, indicating the presence of corneal epithelial-like cells in the produced cell sheet. Adhesion molecules, E-cadherin, beta-catenin, and Cnx43 were also expressed and exhibited the epithelial integrity of the cell sheet. The expression of integrin-beta1 and beta4 confirmed that the collagenase treatment used for detaching and harvesting the cell sheet did not have adverse effects. Our results showed that the utilization of clinical-grade and FDA-approved reagents successfully supported the production of cG-CAMECS.


Asunto(s)
Células Epiteliales/metabolismo , Mucosa Bucal/metabolismo , Animales , Células Cultivadas , Células Epiteliales/citología , Humanos , Mucosa Bucal/citología , Conejos
9.
J Neurooncol ; 152(2): 205-216, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33635510

RESUMEN

INTRODUCTION: Meningiomas comprise 33% of all CNS tumors. The World Health Organization (WHO) describes meningiomas as benign (BM), atypical (AM), and malignant/anaplastic (MM). High-grade meningiomas such as AMs and MMs are more aggressive, recur more frequently, and portend a worse prognosis than BMs. Currently, the standard treatment for high-grade meningiomas, especially AMs, is ill-defined. In particular, the benefit to survival outcomes of adjuvant radiotherapy post-surgical resection remains unclear. In this study, we investigated the effect of adjuvant radiotherapy (ART) post-surgery on survival outcomes compared to surgery alone for high-grade meningiomas. METHODS: PRISMA guidelines were a foundation for our literature review. We screened the PubMed database for studies reporting overall survival (OS), progression free survival (PFS), and tumor recurrence for intracranial, primary AM and MMs treated with surgery+ART or surgery alone. Fixed and random effect models compared tumor control rate for AM aforementioned groups. RESULTS: Mean 5-year PFS was 76.9% for AM (surgery+ART) and 55.9% for AM (surgery alone) patients. Mean 5-year OS was 81.3% and 74% for AM (surgery+ART) and AM (surgery alone) groups, respectively. Overall, the mean 5-year PFS for aggregated high-grade meningiomas AM+MM (surgery+ART) was 67.6%. Fixed effect models revealed tumor control rate as 76% for AM (surgery+ART) and 69% for AM (surgery alone) groups. ART induced toxicity incidence ranged from 12.0% to 35.5% for AM and MM patients. CONCLUSIONS: Our analysis suggests that (surgery+ART) may increase PFS, OS, and tumor control rates in high-grade meningiomas. However, further studies involving surgery+ ART should be conducted to fully evaluate the ideal radiosurgical candidate, modality, and dosage.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Radioterapia Adyuvante/métodos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Humanos , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Meningioma/patología , Meningioma/cirugía
10.
Acta Neurochir (Wien) ; 163(7): 1921-1934, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33796887

RESUMEN

BACKGROUND: High-grade gliomas (HGG) comprise the most common primary adult brain cancers and universally recur. Combination of re-irradiation therapy (reRT) and bevacizumab (BVZ) therapy for recurrent HGG is common, but its reported efficacy is mixed. OBJECTIVE: To assess clinical outcomes after reRT ± BVZ in recurrent HGG patients receiving stereotactic radiosurgery (SRS), hypofractionated radiosurgery (HFSRT), or fully fractionated radiotherapy (FFRT). METHODS: We performed a systematic review of PubMed, Web of Science, Scopus, Embase, and Cochrane databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified studies reporting outcomes for patients with recurrent HGG treated via reRT ± BVZ. Cohorts were stratified by BVZ treatment status and re-irradiation modality (SRS, HFSRT, and FFRT). Outcome variables were overall survival (OS), progression-free survival (PFS), and radiation necrosis (RN). RESULTS: Data on 1399 patients was analyzed, with 954 patients receiving reRT alone and 445 patients receiving reRT + BVZ. All patients initially underwent standard-of-care therapy for their primary HGG. In a multivariate analysis that adjusted for median patient age, WHO grade, RT dosing, reRT fractionation regimen, time between primary and re-irradiation, and re-irradiation target volume, BVZ therapy was associated with significantly improved OS (2.51, 95% CI [0.11, 4.92] months, P = .041) but no significant improvement in PFS (1.40, 95% CI [- 0.36, 3.18] months, P = .099). Patients receiving BVZ also had significantly lower rates of RN (2.2% vs 6.5%, P < .001). CONCLUSIONS: Combination of reRT + BVZ may improve OS and reduce RN rates in recurrent HGG, but further controlled studies are needed to confirm these effects.


Asunto(s)
Neoplasias Encefálicas , Glioma , Adulto , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Femenino , Glioma/tratamiento farmacológico , Glioma/radioterapia , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Radiocirugia
11.
J Neurooncol ; 148(1): 1-7, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32383063

RESUMEN

PURPOSE: Glioblastoma prognosis remains grim despite maximal, multimodal management. Recent literature has demonstrated an increase in research devoted to experimental treatments, particularly those relying on the foundations of active immunotherapy with promising results. We hypothesize that the utilization of bioengineered recombinant vault nanoparticles coupled with glioma-associated antigens, such as the NY-ESO-1 peptide, may be capable of stimulating native dendritic cell (DC) maturation and inducing an anti-tumor response. METHODS: Immature DCs were cultured from the bone marrow of 4-6-week-old C57BL/6 mice. The three treatment groups consisted of: (1) DC and media, (2) DC with mCherry vault, and (3) DC with NYESO and vault. DC maturity was assessed via flow cytometric evaluation of CD11c, CD86, and MHC-II. Increase in CD86 Median Fluorescence Intensity (MFI) was analyzed in the CD11c+CD86+MHC-II+ population to determine the extent of maturation RESULTS: Our findings suggest that CP-MVP-NY-ESO-1-INT recombinant vault nanoparticles are efficiently bioengineered with exceptional integrity, are quickly internalized by immature DCs for antigen processing, and result in DC maturation. CONCLUSION: This study reports our preliminary results, which demonstrate the feasibility and progress regarding our immunotherapeutic technique utilizing NY-ESO-1 packaged vault nanoparticles to prime DCs for subsequent anti-cancer therapies.


Asunto(s)
Antígenos de Neoplasias/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Células Dendríticas/inmunología , Glioma/inmunología , Glioma/terapia , Nanopartículas/administración & dosificación , Animales , Anticuerpos , Bioingeniería , Sistemas de Liberación de Medicamentos/métodos , Ratones Endogámicos C57BL , Proteínas Recombinantes/administración & dosificación
12.
J Neurooncol ; 147(1): 15-24, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31981014

RESUMEN

PURPOSE: Although intracranial meningiomas are the most common primary brain tumor in adults, treatment options are few and have traditionally been limited to surgical resection and radiotherapy. Additional targeted therapies and biomarkers are needed, especially as complete surgical resection is frequently not feasible in many patients. METHODS: Non-pathologic brain tissue from 3 patients undergoing routine autopsies and tumor specimens from 16 patients requiring surgical resection for meningioma were collected. EMP2 protein expression was evaluated by immunohistochemistry and western blot analysis. EMP2 mRNA expression was also investigated using surgical specimens and validated by analysis of several independent NCBI GEO databases. RESULTS: EMP2 mRNA expression levels were found to be higher in meningioma relative to non-pathologic meninges (P = 0.0013) and brain (P = 0.0011). Concordantly, strong EMP2 protein expression was demonstrated in 100% of meningioma specimens from all 16 patients, with no observable protein expression in normal brain tissue samples from 3 subjects (P < 0.001). EMP2 expression was confirmed by western blot analysis in five samples, with EMP2 protein intensity positively correlating with histologic staining score (R2 = 0.780; P = 0.047). No association was found between EMP2 mRNA or protein levels and WHO grade or markers of proliferation. However, EMP2 expression was positively associated with an angiomatous pattern on histologic evaluation (P = 0.0597), VEGF-A mRNA expression (P < 0.001), and clinical markers of tumor vascularity such as operative blood loss (P = 0.037). CONCLUSIONS: EMP2 is not found in normal brain tissue, yet has shown consistently high mRNA and protein expression in meningiomas, and may serve as a useful molecular marker for these tumors.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Glicoproteínas de Membrana/metabolismo , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patología , Meningioma/metabolismo , Meningioma/patología , Neovascularización Patológica/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Masculino , Glicoproteínas de Membrana/genética , Neoplasias Meníngeas/complicaciones , Neoplasias Meníngeas/genética , Meningioma/complicaciones , Meningioma/genética , Persona de Mediana Edad , Neovascularización Patológica/complicaciones , Neovascularización Patológica/genética , ARN Mensajero/metabolismo
13.
J Neurooncol ; 147(3): 599-605, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32274629

RESUMEN

PURPOSE: Glioblastoma (GBM) is the most common and malignant primary adult brain tumor. Current care includes surgical resection, radiation, and chemotherapy. Recent clinical trials for GBM have demonstrated extended survival using interventions such as tumor vaccines or tumor-treating fields. However, prognosis generally remains poor, with expected survival of 20 months after randomization. Chemokine-based immunotherapy utilizing CCL21 locally recruits lymphocytes and dendritic cells to enhance host antitumor response. Here, we report a preliminary study utilizing CPZ-vault nanoparticles as a vehicle to package, protect, and steadily deliver therapy to optimize CCL21 therapy in a murine flank model of GBM. METHODS: GL261 cells were subcutaneously injected into the left flank of eight-week-old female C57BL/6 mice. Mice were treated with intratumoral injections of either: (1) CCL21-packaged vault nanoparticles (CPZ-CCL21), (2) free recombinant CCL21 chemokine empty vault nanoparticles, (3) empty vault nanoparticles, or 4) PBS. RESULTS: The results of this study showed that CCL21-packaged vault nanoparticle injections can decrease the tumor volume in vivo. Additionally, this study showed mice injected with CCL21-packaged vault nanoparticle had the smallest average tumor volume and remained the only treatment group with a negative percent change in tumor volume. CONCLUSIONS: This preliminary study establishes vault nanoparticles as a feasible vehicle to increase drug delivery and immune response in a flank murine model of GBM. Future animal studies involving an intracranial orthotopic tumor model are required to fully evaluate the potential for CCL21-packaged vault nanoparticles as a strategy to bypass the blood brain barrier, enhance intracranial immune activity, and improve intracranial tumor control and survival.


Asunto(s)
Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Quimiocina CCL21/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Glioblastoma/inmunología , Glioblastoma/patología , Inmunoterapia/métodos , Animales , Neoplasias Encefálicas/terapia , Línea Celular Tumoral , Quimiocina CCL21/inmunología , Femenino , Glioblastoma/terapia , Ratones Endogámicos C57BL , Nanopartículas
14.
J Neurooncol ; 145(2): 329-337, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31552587

RESUMEN

PURPOSE: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are noninvasive therapies for vestibular schwannomas providing excellent tumor control. However, delayed hearing loss after radiation therapy remains an issue. One potential target to for improving hearing rates is limiting radiation exposure to the cochlea. METHODS: We retrospectively reviewed 100 patients undergoing either SRS with 12 Gy (n = 43) or fSRT with 50 Gy over 28 fractions (n = 57) for vestibular schwannoma. Univariate and multivariate analysis were carried out to identify predictors of hearing loss as measured by the Gardner Robertson scale after radiation therapy. RESULTS: Deterioration of hearing occurred in 30% of patients with SRS and 26% with fSRT. The overall long term (> 2 year) progression rates were 20% for SRS and 16% for fSRT. Patients with a decrease in their Gardner Robertson hearing score and those that loss serviceable hearing had significantly higher average minimal doses to the cochlea in both SRS and fSRT cohorts. ROC analysis showed that a cut off of 5 Gy and 35 Gy, for SRS and fSRT respectively, predicted hearing loss with high sensitivity/specificity. CONCLUSION: Our data suggests the minimal dose of radiation that the cochlear volume is exposed to is a predictor of delayed hearing loss after either SRS or fSRT. A threshold of 5 Gy/35 Gy may lead to improved hearing preservation after radiotherapy. Further prospective multi center studies can further elucidate this mechanism.


Asunto(s)
Fraccionamiento de la Dosis de Radiación , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Neuroma Acústico/radioterapia , Radiocirugia/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cóclea/efectos de la radiación , Femenino , Pruebas Auditivas , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Adulto Joven
15.
Neurosurg Rev ; 42(1): 85-96, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28900754

RESUMEN

Neurofibromatosis type 2 (NF2) is a genetic neoplastic disorder that presents with hallmark bilateral vestibular schwannomas and multiple meningiomas. Though the current standard of care for meningiomas includes surgery, the multiplicity of meningiomas in NF2 patients renders complete resection of all developing lesions infeasible. Stereotactic radiosurgery (SRS) may be a viable non-invasive therapeutic alternative to surgery. We describe a particularly challenging case in a 39-year-old male with over 120 lesions who underwent more than 30 surgical procedures, and review the literature. We also searched three popular databases and compared outcomes of SRS versus surgery for the treatment of multiple meningiomas in patients with NF2. A total of 50 patients (27 radiosurgical and 23 surgical) were identified. For patients treated with SRS, local tumor control was achieved in 22 patients (81.5%) and distal control was achieved in 14 patients (51.8%). No malignant inductions were observed at an average follow-up duration of 90 months. Complications in the SRS-treated cohort were reported in 9 patients (33%). Eight patients (29.6%) died due to disease progression. Six patients experienced treatment failure and required further management. For NF2 patients treated with surgery, 11 patients (48%) showed tumor recurrence and 10 patients (43.5%) died due to neurological complications. SRS may be a safe and effective alternative for NF2-associated meningiomas. Further studies are required to identify the ideal radiosurgical candidate.


Asunto(s)
Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Neurofibromatosis 2/complicaciones , Radiocirugia , Adulto , Humanos , Masculino , Neoplasias Meníngeas/complicaciones , Meningioma/complicaciones , Insuficiencia del Tratamiento
16.
Acta Neurochir (Wien) ; 161(7): 1449-1456, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31129783

RESUMEN

BACKGROUND: Vestibular schwannomas (VSs) are benign neoplasms of the Schwann cells of cranial nerve VIII, and treatment of VS typically involves surgical resection. However, tumor recurrence may necessitate reintervention, and secondary treatment modalities include repeat surgical resection or adjuvant radiosurgery. The purpose of this study is to examine the scientific literature in order to determine whether surgical resection or radiosurgery for recurrent VS results in better tumor control, hearing preservation, and preservation of facial nerve function. METHODS: The PubMed, Scopus, Embase, Cochrane, and Web of Science databases were searched for studies reporting on patients undergoing either radiosurgery or repeat surgical resection after primary surgical resection for recurrent VS. Statistical analyses were performed on the compiled data, primarily outcome data involving tumor control, hearing preservation, and preservation of facial nerve function. RESULTS: We analyzed the data of 15 individual studies involving 359 total patients, and our results reveal that tumor control rates are comparable between adjuvant radiosurgery (91%, CI: 88-94%) and secondary resection (92%, CI 75-98%). However, adjuvant radiosurgery was shown to preserve good facial nerve function better (94%, CI 84-98%) compared to secondary surgical resection (56%, CI 41-69%). CONCLUSION: With comparable tumor control rates and better preservation of good facial nerve function, this study suggests that secondary radiosurgery for recurrent VS is associated with both optimal tumor control and preservation of good facial nerve function.


Asunto(s)
Nervio Facial/cirugía , Pérdida Auditiva/epidemiología , Neuroma Acústico/radioterapia , Complicaciones Posoperatorias/epidemiología , Radiocirugia/métodos , Humanos , Neuroma Acústico/cirugía , Radiocirugia/efectos adversos , Nervio Vestibulococlear/cirugía
18.
Neuropathology ; 2018 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-29781154

RESUMEN

Neuroglial ectopia is a rare entity of undetermined clinical significance. Here, we report a unique case of neuroglial ectopia of the vestibular nerve. A 27-year-old pharmacy student with a previous radiological diagnosis of vestibular schwannoma presented to our clinic for surgical evaluation. Magnetic resonance imaging (MRI) of the brain revealed a 17-mm T1 hypo- to isointense, T2 iso- to hyperintense, poorly enhancing left cerebellopontine angle mass extending into the left internal auditory canal compatible by imaging with a vestibular schwannoma. The lesion was resected under MRI guidance. The frozen specimen came back as a benign hypocellular lesion. Histological assessment revealed a peripheral nerve engulfed by glial fibrillary acidic protein-positive, S-100-negative cells, suggestive of neuroglial ectopia. There was no evidence of schwannoma. The main concerns were benign neoplasm with potential for progression or sampling artifact. The patient had an uncomplicated hospital course. This case report demonstrates an unusual case of neuroglial ectopia of the vestibular nerve. The differential diagnoses for a poorly enhancing cerebellopontine angle mass should include neuroglial ectopia.

19.
Acta Neurochir (Wien) ; 160(6): 1219-1224, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29022108

RESUMEN

BACKGROUND: Superior semicircular canal dehiscence (SSCD) is a disorder of the skull base that is gaining increasing recognition among neurosurgeons. Traditionally, the middle cranial fossa (MCF) approach has been used for the surgical repair of SSCD. However, the transmastoid (TM) approach is an alternative strategy that has demonstrated promising results. METHODS: We performed independent searches of a popular database to identify studies that described outcomes following the surgical repair of SSCD through MCF and TM approaches. The primary outcome was symptom resolution. RESULTS: Our analysis included 24 studies that described 230 patients that underwent either an MCF (n = 148, 64%) approach or a TM (n = 82, 36%) approach for primary surgical repair of SSCD. A greater percentage of patients in the MCF group experienced resolution of auditory symptoms (72% vs 59%, p = 0.012), aural fullness (83% vs 55%, p = 0.049), hearing loss (57% vs 31%, p = 0.026), and disequilibrium (75% vs 44%, p = 0.001) when compared to the TM group. The MCF approach was also associated with higher odds of symptom resolution for auditory symptoms (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.14-2.82), aural fullness (OR 4.02, 95% CI 1.04-15.53), hearing loss (OR 2.91, 95% CI 1.14-7.42), and disequilibrium (OR 3.94, 95% CI 1.78-8.73). The mean follow-up was 9 months. CONCLUSIONS: The literature suggests that the MCF approach for the repair of SSCD is associated with greater symptom resolution when compared to the TM approach. This information could help facilitate patient discussions.


Asunto(s)
Fosa Craneal Media/cirugía , Pérdida Auditiva/epidemiología , Procedimientos Quirúrgicos Otológicos/métodos , Complicaciones Posoperatorias/epidemiología , Canales Semicirculares/cirugía , Pérdida Auditiva/etiología , Humanos , Procedimientos Quirúrgicos Otológicos/efectos adversos , Complicaciones Posoperatorias/etiología
20.
Cancer ; 123(12): 2274-2282, 2017 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-28178376

RESUMEN

BACKGROUND: Published guidelines regarding the optimal treatment strategies for brain metastases focus on patients with ≤3 lesions. As delivery techniques for stereotactic radiosurgery (SRS) improve, radiation oncologists are increasingly using it for patients with >3 metastases. In the current study, the authors sought to characterize practice patterns among practitioners to identify areas of controversy. METHODS: A survey of practicing radiation oncologists was distributed via e-mail. Responses were collected from April 1 to May 5, 2016. Survey data were analyzed. RESULTS: A total of 711 currently practicing radiation oncologists responded, for a response rate of 12.5%. Specialists in central nervous system tumors (CNS specialists) were more likely to treat higher numbers of patients with brain metastases with SRS. There was a significant difference in the optimal "cutoff number" used when deciding how many lesions to treat with SRS versus whole-brain radiotherapy. Cutoff numbers were significantly higher for high-volume CNS specialists (≥10 patients/month) than for either low-volume CNS specialists (5-9 patients/month) or high-volume, non-CNS specialists (8.1 vs 5.6 and 5.1, respectively; P<.001). A majority of respondents (56%) identified patients with 4 to 6 brain metastases as being the most challenging patients to treat. CONCLUSIONS: To the authors' knowledge, there appears to be no consensus regarding the optimal treatment strategy among patients with >3 brain metastases, and practice patterns are heterogeneous. Radiation oncologists, especially high-volume CNS specialists, are treating significantly more brain metastases with SRS than what currently is recommended by published consensus guidelines. Providers struggle with patients with a moderate intracranial disease burden. Further prospective studies are needed to support these practice patterns and guide decision making. Cancer 2017;123:2274-2282. © 2017 American Cancer Society.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Irradiación Craneana/tendencias , Pautas de la Práctica en Medicina/tendencias , Radiocirugia/tendencias , Neoplasias Encefálicas/secundario , Femenino , Humanos , Masculino , Metastasectomía , Guías de Práctica Clínica como Asunto , Oncólogos de Radiación , Encuestas y Cuestionarios
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