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We describe a case of a young patient with a recurrent pleomorphic xanthoastrocytoma (PXA) showing unusual cell-in-cell (CiC) phenomena. We observed mostly viable but also necrotic neutrophils engulfed within tumor cells. The recurrent tumor was immunopositive for BRAFV600E mutant protein and showed CDKN2 homozygous deletions typical of PXA. Both genetic alterations were also reported in the original primary tumor. Unlike the original tumor that was GFAP and Olig-2 immunopositive, the recurrent neoplasm was largely negative for GFAP and Olig-2 suggesting dedifferentiation. The large malignant cells that contained the neutrophils were negative for histiocytic and lymphohematopoietic markers. Whereas CDKN2 homozygous deletion is common in PXA, its presence is rare in histiocytic neoplasms. Both reactive astrocytes and glial neoplasms very rarely may engulf neutrophils in a process resembling emperipolesis or cellular cannibalism. Future work may clarify which type of CiC pathway is involved.
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BACKGROUND AND OBJECTIVE: Nonfunctional pituitary neuroendocrine tumors (PitNETs) exhibit wide variability in growth pattern based on subtype. Silent corticotroph adenomas (SCAs) demonstrate aggressive growth compared to other nonfunctional adenomas (NFPAs), especially into the cavernous sinus. In this study, we sought to characterize other growth patterns of SCAs in comparison to NFPAs. METHODS: We performed a retrospective analysis of all patients with nonfunctional PitNETs treated with surgical resection via endoscopic endonasal approach (EEA) at a single institution from August 1, 2018, to May 11, 2024. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) were reviewed to determine extension into the suprasellar space, sphenoid sinus, cavernous sinus, and clivus. RESULTS: Ninety-one patients were included, including 20 SCAs and 71 NFPAs. SCAs demonstrated significantly greater rates of growth into the sphenoid sinus (55.0% vs. 23.94%, p=0.013), clivus (65.0% vs. 16.9%, p<0.0001), and cavernous sinus (defined as Knosp grade 3 or 4; 55.0% vs. 23.35%, p=0.016). Other NFPAs were more likely to grow into the suprasellar space (92.96% vs. 75.0%, p=0.038). Tumor volume was similar between groups (11.93 cm3 vs. 9.06 cm3, p=0.2). CONCLUSIONS: Silent corticotroph PitNETs demonstrate predilection for invasion of bony structures, with higher rates of growing through the sellar floor into the sphenoid sinus, growing posteroinferiorly into the clivus, and laterally into the cavernous sinuses. Other nonfunctional PitNETs tended to follow the path of least resistance, growing superiorly into the suprasellar space. These differences in growth patterns may account for some of the clinical challenges of treating silent corticotroph PitNETs.
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BACKGROUND: Postoperative cerebrospinal fluid (CSF) leak remains a concerning complication of the endoscopic endonasal approach (EEA) for skull base pathology. Signs and symptoms suggesting CSF leak often trigger additional workup during the postoperative course. We systematically evaluate associations between subjectively reported clinical signs/symptoms noted during the immediate postoperative period and incidence of postoperative CSF leaks. METHODS: Retrospective chart review was conducted at a tertiary academic medical centre including 137 consecutive patients with intraoperative CSF leak during EEA with primary repair between July 2018 and August 2022. Postoperative CSF leak associations with clinical signs and symptoms were evaluated using positive (PPV) and negative predictive values (NPV), sensitivity, specificity and odds ratio (OR) via univariate logistic regression. RESULTS: Seventy-nine patients (57.7%) had high-flow leaks repaired and 5 (3.6%) developed CSF leaks postoperatively. Of reported symptoms, rhinorrhea was most common (n = 52, 38.0%; PPV [95% CI] = 7.6% [4.8%, 11.9%]), followed by severe headache (n = 47, 34.3%; 6.3% [3.1%, 12.5%]), dizziness (n = 43, 31.4%; 2.3% [0.4%, 12.1%]), salty or metallic taste (n = 20, 14.6%; 9.9% [3.3%, 25.8%]), and throat drainage (n = 10, 7.3%; 9.9% [1.7%, 41.4%]). Nausea or vomiting constituted the most reported sign concerning for CSF leak (n = 73, 53.3%; PPV [95% CI] = 4.1% [2.0%, 8.1%]). On univariate regression, no sign or symptom, including rhinorrhea (OR [95% CI] = 7.00 [0.76-64.44]), throat drainage (3.42 [0.35-33.86]), salty/metallic taste (4.22 [0.66-27.04]), severe headache (3.00 [0.48-18.62]), dizziness (0.54 [0.06-4.94]), fever (3.16 [0.50-19.99]), and nausea/vomiting (1.33 [0.22-8.21]), associated with postoperative CSF leak. CONCLUSIONS: A range of subjectively reported symptoms and signs failed to predict postoperative CSF leak. Further investigation is warranted to inform appropriate attention and response.
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Pérdida de Líquido Cefalorraquídeo , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/diagnóstico , Estudios Retrospectivos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Valor Predictivo de las Pruebas , Rinorrea de Líquido Cefalorraquídeo/cirugía , Rinorrea de Líquido Cefalorraquídeo/etiología , Rinorrea de Líquido Cefalorraquídeo/diagnóstico , EndoscopíaRESUMEN
OBJECTIVES: Periodic imaging follow-up for patients with unruptured intracranial aneurysms (UIA) is crucial, as studies indicate higher rupture risk with aneurysm growth. However, few studies address patient adherence to follow-up recommendations. This study aims to identify compliance rates and factors influencing follow-up adherence. METHODS: Patients with a UIA were identified from our institution's database from 2011-2021. Follow-up imaging (CT/MR Angiogram) was advised at specific intervals. Patients were categorized into compliant and non-compliant groups based on first-year compliance. Factors contributing to compliance were assessed through multivariate logistic regression. Phone interviews were conducted with non-compliant patients to understand reasons for non-adherence. RESULTS: Among 923 UIA diagnosed patients, 337 were randomly selected for analysis. The median follow-up period was 1.4 years, with a 42% first-year compliance rate. The mean aneurysm size was 3.3 mm. Five patients had a rupture during follow-up, of which 4 died. Compared with patients consulting specialists at the initial diagnosis, those seen by non-specialists exhibited lower compliance (OR 0.25, p < 0.001). Loss to follow-up was greatest during transition from emergency service to specialist appointments. Patients who spoke languages other than English exhibited poorer compliance than those speaking English (OR 0.20, p = 0.01). CONCLUSIONS: Significant amounts of UIA patients at low rupture risk were lost to follow-up before seeing UIA specialists. Main non-compliance factors include inadequate comprehension of follow-up instructions, poor care transfer from non-specialists to specialist, and insurance barriers.
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Aneurisma Roto , Bases de Datos Factuales , Aneurisma Intracraneal , Cooperación del Paciente , Humanos , Aneurisma Intracraneal/terapia , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Factores de Riesgo , Factores de Tiempo , Aneurisma Roto/terapia , Aneurisma Roto/diagnóstico por imagen , Estudios Retrospectivos , Angiografía por Tomografía Computarizada , Angiografía por Resonancia Magnética , Adulto , Perdida de Seguimiento , Valor Predictivo de las Pruebas , Conocimientos, Actitudes y Práctica en Salud , Angiografía CerebralRESUMEN
Objective: Currently, diagnosis of cerebrospinal fluid (CSF) rhinorrhea relies on a multimodal approach, increasing costs and ultimately delaying diagnosis. In the United States and internationally, the crux of such a diagnosis relies on confirmation testing (via biomarkers) and localization (e.g., imaging). Biomarker testing may require analysis at an outside facility, resulting in delays diagnosis and treatment. In addition, specialized imaging may be nonspecific and often requires an active leak for diagnosis. There remains a clear need for innovative new technology. Methods: A comprehensive review was conducted on both foundational and innovative scholarly articles regarding current and emerging diagnosis modalities for CSF. Results: Current modalities in CSF rhinorrhea diagnosis and localization include laboratory tests (namely, B2T immunofixation), imaging (CT and/or MRI) with or without intrathecal administration, and surgical exploration. Each of these modalities carry flaws, risks, and benefits, ultimately contributing to delays in diagnosis and morbidity. Promising emerging technologies include lateral flow immunoassays (LFI) and biologically functionalized field-effect transistors (BioFET). Nevertheless, these carry some drawbacks of their own, and require further validation. Conclusion: CSF rhinorrhea remains a challenging diagnosis, requiring a multimodal approach to differentiate from nonpathologic causes of rhinorrhea. Current methods in diagnosis are imperfect, as the ideal test would be a readily accessible, inexpensive, rapid, highly accurate point-of-care test without the need for excess fluid or specialized processing. Critical work is being done to develop promising, new, improved tests, though a clear successor has not yet emerged. Level of Evidence: N/A.
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KEY POINTS: Patients with giant adenomas are more likely to have tumor extension into the paranasal sinuses. Compared to macroadenomas, giant adenomas are not associated with worse preoperative SNOT-22 scores.
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Adenoma , Medición de Resultados Informados por el Paciente , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/diagnóstico , Adenoma/patología , Adenoma/cirugía , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Senos Paranasales/patología , Senos Paranasales/cirugíaRESUMEN
OBJECTIVE: Despite significant advances in understanding of skull base reconstruction principles, the role of tissue sealants in modifying postoperative cerebrospinal fluid (CSF) leak outcomes remains controversial. We evaluate postoperative CSF leak incidence associated with tissue sealant use in skull base defect repair during endoscopic skull base surgery (ESBS). DATA SOURCES: Web of Science, PubMed/MEDLINE, Scopus, and Cochrane Library. REVIEW METHODS: Systematic review and meta-analysis of risk differences (RD). A search strategy identified original studies reporting CSF leakage following ESBS with disaggregation by tissue sealant use and/or type. RESULTS: 27 non-randomized studies (n = 2,403) were included for qualitative and meta-analysis. Reconstruction with a tissue sealant did not significantly reduce postoperative CSF leak risk compared with reconstruction without sealant (RD[95% CI] = 0.02[-0.01, 0.05]). Sub-analyses of dural sealant (-0.02[-0.11, 0.07]) and fibrin glue (0.00[-0.07, 0.07]) compared with no sealant were similarly unremarkable. Postoperative CSF leakage was not significantly modulated in further sub-analyses of DuraSeal (0.02[-0.02, 0.05]), Adherus (-0.03[-0.08, 0.03]), or Bioglue (-0.06[-0.23, 0.12]) versus no dural sealant use, or Tisseel/Tissucol versus fibrin glue nonuse (0.00[-0.05, 0.05]). No significant association was seen comparing dural sealant use versus fibrin glue use on pairwise (0.01[-0.03, 0.05]) or network meta-analysis (-0.01[-0.05, 0.04]). Limitations in source literature prevented sub-analyses stratified by leak characteristics, defect size and location, and accompanying reconstruction materials. CONCLUSION: Tissue sealant use did not appear to impact postoperative CSF leak incidence when compared with nonuse. Higher quality studies are warranted to thoroughly elucidate the clinical value of adjunct sealant use in endoscopic skull base reconstruction. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:3425-3436, 2024.
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Pérdida de Líquido Cefalorraquídeo , Procedimientos de Cirugía Plástica , Complicaciones Posoperatorias , Base del Cráneo , Adhesivos Tisulares , Humanos , Base del Cráneo/cirugía , Adhesivos Tisulares/uso terapéutico , Pérdida de Líquido Cefalorraquídeo/prevención & control , Pérdida de Líquido Cefalorraquídeo/etiología , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Adhesivo de Tejido de Fibrina/uso terapéutico , Endoscopía/métodos , Resultado del TratamientoRESUMEN
INTRODUCTION: Despite centuries of joint investigation of philosophy and neurological interventions, a founding account for the philosophy of neurosurgery has yet to be rigorously constructed or defended. This paper reviews recent work on the philosophy of neurosurgery, spanning metaphysics, epistemology, and value theory, to establish a framework and clinical relevance for study in the philosophy of neurosurgery. METHODS: A systematic review of an online database was conducted using the broad search terms, "Philosophy AND (Neurosurgery OR Neurological Surgery)." Records were included if they demonstrated relevance to the philosophy of neurosurgery and analytical rigor, but were excluded if solely legal, clinical, or ethical principles were considered without substantive discussion of underlying ethical frameworks and philosophical principles. RESULTS: Of 8025 candidates from online and print records, 16 records (14 from online sources and 2 from an edited volume) met inclusion criteria for the systematic review. Three dealt with metaphysics, 3 dealt with epistemology, 4 dealt with value theory, 5 dealt with metaphysics/epistemology, and 1 dealt with value theory/metaphysics. Questions of free will, consciousness, personal identity, neurosurgical knowledge, ascription of other minds, deontology, and minimalism, among others, were considered. DISCUSSION: Based on identified studies, the philosophy of neurosurgery is defined as the discipline of rigorously and methodically addressing metaphysical, epistemological, and value-theoretic questions arising from physically intervening in the nervous system. We discuss future directions for questions within the philosophy of neurosurgery and consider their relevance for patient care and the practice of neurosurgery.
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Neurocirugia , Humanos , Conocimiento , Metafisica , Filosofía MédicaRESUMEN
Introduction Meningiomas-the most common extra-axial tumors-are benign, slow-growing dural-based lesions that can involve multiple cranial fossae and can progress insidiously for years until coming to clinical attention secondary to compression of adjacent neurovascular structures. For complex, multicompartmental lesions, multistaged surgeries have been increasingly shown to enhance maximal safe resection while minimizing adverse sequela. Here, we systematically review the extant literature to highlight the merits of staged resection. Methods PubMed, Scopus, and Web of Science databases were queried to identify articles reporting resections of intracranial meningiomas using a multistaged approach, and articles were screened for possible inclusion in a systematic process performed by two authors. Results Of 118 identified studies, 36 describing 169 patients (mean age 42.6 ± 21.3 years) met inclusion/exclusion criteria. Petroclival lesions comprised 57% of cases, with the most common indications for a multistaged approach being large size, close approximation of critical neurovascular structures, minimization of brain retraction, identification and ligation of deep vessels feeding the tumor, and resection of residual tumor found on postoperative imaging. Most second-stage surgeries occurred within 3 months of the index surgery. Few complications were reported and multistaged resections appeared to be well tolerated overall. Conclusions Current literature suggests multistaged approaches for meningioma resection are well-tolerated. However, there is insufficient comparative evidence to draw definitive conclusions about its advantages over an unstaged approach. There are similarly insufficient data to generate an evidence-based decision-making framework for when a staged approach should be employed. This highlights the need for collaborative efforts among skull base surgeons to establish an evidentiary to support the use of staged approaches and to outline those indications that merit such an approach.
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KEY POINTS: Nasal packing type was not associated with postoperative cerebrospinal fluid leaks Nondissolvable packing conferred an increased risk for postoperative sinonasal infections Nasal packing type did not influence short- and long-term quality-of-life scores.
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Procedimientos de Cirugía Plástica , Humanos , Pérdida de Líquido Cefalorraquídeo/cirugía , Estudios Retrospectivos , Base del Cráneo/cirugía , Endoscopía/efectos adversos , Complicaciones Posoperatorias/etiología , Calidad de VidaRESUMEN
BACKGROUND: Craniopharyngiomas are uncommon benign sellar and parasellar tumors with high overall survival (OS) and recurrence rates. Treatment is often surgical but may include adjuvant therapies. The impact of adjuvant therapy and surgical approach have been evaluated, however, facility volume and type have not. The purpose of this study is to analyze the influence of facility volume and type on treatment modalities, extent of surgery and survival of craniopharyngioma. METHODS: The 2004-2016 National Cancer Database (NCDB) was queried for patients diagnosed with craniopharyngioma. Facilities were classified by type (academic vs. non-academic) and low-volume center (LVC) (Treating < 8 patients over the timeline) versus high-volume center (HVC), (Treating ≥ 8 patients over the timeline). Differences in treatment course, outcomes, and OS by facility type were assessed. RESULTS: 3730 patients (51.3% female) with mean age 41.2 ± 22.0 were included with a 5-year estimated OS of 94.8% (94.0-95.5%). 2564 (68.7%) patients were treated at HVC, of which 2142 (83.5%) were treated at academic facilities. Patients treated at HVC's were more likely to undergo both surgery and radiation. Surgical approach at HVC was more likely to be endoscopic. Patients treated at HVC demonstrated significantly higher 5-year OS compared to patients treated at LVC (96% [95% CI 95.6-97.1% versus 91.2% [95% CI 89-92.7%] with lower risk of mortality (Hazard ratio [95% CI] = 0.69 [0.56-0.84]). CONCLUSION: Treatment of craniopharyngioma at HVC compared to LVC is associated with improved OS, lower 30- and 90-day postoperative mortality risk, and more common use of both radiotherapy and endoscopic surgical approach.
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Craneofaringioma , Neoplasias Hipofisarias , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Masculino , Craneofaringioma/cirugía , Modelos de Riesgos Proporcionales , Terapia Combinada , Bases de Datos Factuales , Neoplasias Hipofisarias/cirugía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
KEY POINTS: In a single-center cohort of pituitary adenoma patients, non-White race independently predicted larger tumor size at initial presentation. Uninsured patients suffered a significantly higher rate of pituitary apoplexy at initial presentation. Geographically distant care appeared to present a greater barrier for non-White and Hispanic patients relative to their White and non-Hispanic counterparts.
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Adenoma , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/cirugía , Adenoma/cirugía , Nariz/patología , Estudios RetrospectivosRESUMEN
Objectives Skull base chordomas are locally aggressive malignant tumors derived from the notochord remnant. There are limited large-scale studies examining the role and extent of surgery and radiation therapy. Design Analysis of the National Cancer Database (NCDB) was performed to evaluate the survival outcomes of various treatments, and to assess for predictors of overall survival (OS). Participants This is a retrospective, population-based cohort study of patients diagnosed with a clival/skull base chordoma between 2004 and 2015 in the NCDB. Main Outcome Measures The primary outcome was overall survival (OS). Results In all, 468 cases were identified. Forty-nine percent of patients received surgery and 20.7% had positive margins. Mean age at diagnosis was 48.4 years in the surgical cohort, and 55% were males. Of the surgical cohort, 33.8% had negative margins, 20.7% had positive margins, and 45.5% had unknown margin status. Age ≥ 65 (hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 1.63-5.76; p < 0.001), diagnosis between 2010 and 2015 (HR: 0.49; 95% CI: 0.26-0.90; p = 0.022), tumor size >5 cm (HR: 2.29; 95% CI: 1.26-4.15; p = 0.007), and government insurance (HR: 2.28; 95% CI: 1.24-4.2; p = 0.008) were independent predictors of OS. When comparing surgery with or without adjuvant radiation, no survival differences were found, regardless of margin status ( p = 0.66). Conclusion Surgery remains the mainstay of therapy. Advanced age (>65 years), large tumor size, and government insurance were predictors of worse OS. Whereas negative margins and the use of adjuvant radiation did not appear to impact OS, these may very well reduce local recurrences. A multidisciplinary approach is critical in achieving optimal outcomes in this challenging disease.
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BACKGROUND: Craniopharyngiomas account for 1.2% to 4.6% of all intracranial tumors. Although age at presentation is distributed bimodally, with a pediatric peak occurring between 5 and 15 years and an adult peak between 50 and 70 years, presentation, treatment, and outcome differences between these two craniopharyngioma populations have not been thoroughly characterized. OBJECTIVE: To compare treatments and outcomes between adult and pediatric craniopharyngiomas. METHODS: This is a systematic review and meta-analysis. Web of Science, MEDLINE, and Scopus databases were searched for primary studies reporting postoperative complications, functional outcomes, recurrence, and overall survival in patients with craniopharyngioma undergoing surgery. RESULTS: The search yielded 1,202 unique articles, of which 106 (n=4,202 patients) met criteria for qualitative synthesis and 23 (n=735 patients) met criteria for meta-analysis. Compared with adult, pediatric craniopharyngiomas were less likely to present with visual defects (odds ratio [OR] 0.54, 95% CI 0.36-0.80) or cognitive impairment (OR 0.29, 95% CI 0.12-0.71) and more likely with headaches (OR 2.08, 95% CI 1.16-3.73). Children presented with significantly larger tumors compared with adults (standardized mean difference 0.68, 95% CI 0.38-0.97). Comparing functional outcomes, pediatric patients sustained higher rates of permanent diabetes insipidus (OR 1.70, 95% CI 1.13-2.56), obesity (OR 3.15, 95% CI 1.19-8.31), and cranial nerve and/or neurological defects (OR 4.87, 95% CI 1.78-13.31) than adults. No significant differences were found in rates of postoperative cerebrospinal fluid leak, overall or progression-free survival, or recurrence. CONCLUSION: Adult and pediatric craniopharyngiomas seem to have fundamental differences in clinical presentation and functional outcomes. These patients frequently require multimodality treatment and are best managed with a multidisciplinary team and an individualized approach.
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Craneofaringioma , Neoplasias Hipofisarias , Adolescente , Adulto , Niño , Preescolar , Humanos , Terapia Combinada , Craneofaringioma/cirugía , Diabetes Insípida/etiología , Procedimientos Neuroquirúrgicos/efectos adversos , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
OBJECTIVES: To characterize clinical factors associated with esthesioneuroblastoma treatment delays and determine the impact of these delays on overall survival. STUDY DESIGN: Retrospective database analysis. METHODS: The 2004-2016 National Cancer Database was queried for patients with esthesioneuroblastoma managed by primary surgery and adjuvant radiation. Durations of diagnosis-to-treatment initiation (DTI), diagnosis-to-treatment end (DTE), surgery-to-RT initiation (SRT), radiotherapy treatment (RTD), and total treatment package (TTP) were analyzed. The cohort was split into two groups for each delay interval using the median time as the threshold. RESULTS: A total of 814 patients (39.6% female, 88.5% white) with mean ± SD age of 52.6 ± 15.1 years who underwent both esthesioneuroblastoma surgery and adjuvant radiotherapy were queried. Median DTI, DTE, SRT, RTD, and TTP were 34, 140, 55, 45, and 101 days, respectively. A significant association was identified between increased regional radiation dose above 66 Gy and decreased DTI (OR = 0.54, 95% CI 0.35-0.83, p = 0.01) and increased RTD (OR = 3.94, 95% CI 2.36-6.58, p < 0.001) durations. Chemotherapy administration was linked with decreased SRT (OR = 0.64, 95% CI 0.47-0.89, p = 0.01) and TTP (OR = 0.59, 95% CI 0.43-0.82, p = 0.001) durations. Cox proportional-hazards analysis revealed that increased RTD was associated with decreased survival (HR = 1.80, 95% CI 1.26-2.57, p < 0.005), independent of age, sex, race, regional radiation dose, facility volume, facility type, insurance status, modified Kadish stage, chemotherapy status, Charlson-Deyo comorbidity index, and surgical margins. CONCLUSIONS: Delays during, and prolongation of radiotherapy for esthesioneuroblastoma appears to be associated with decreased survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:764-772, 2023.
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Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Masculino , Estudios Retrospectivos , Tiempo de Tratamiento , Neoplasias Nasales/cirugía , Cavidad Nasal/cirugía , Tasa de SupervivenciaAsunto(s)
Síndrome Metabólico , Neoplasias de la Base del Cráneo , Humanos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/cirugía , Obesidad/complicaciones , Factores de Riesgo , Procedimientos Neuroquirúrgicos/efectos adversos , Base del Cráneo/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Neoplasias de la Base del Cráneo/cirugíaRESUMEN
BACKGROUND: Vaccine immunotherapy may improve survival in Glioblastoma (GBM). A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing the Aivita GBM vaccine (AV-GBM-1), (2) Adverse Events (AE) associated with AV-GBM-1 administration, and (3) survival. METHODS: Fresh suspected glioblastoma tissue was collected during surgery, and patients with pathology-confirmed GBM enrolled before starting concurrent Radiation Therapy and Temozolomide (RT/TMZ) with Intent to Treat (ITT) after recovery from RT/TMZ. AV-GBM-1 was made by incubating autologous dendritic cells with a lysate of irradiated autologous Tumor-Initiating Cells (TICs). Eligible patients were adults (18 to 70 years old) with a Karnofsky Performance Score (KPS) of 70 or greater, a successful TIC culture, and sufficient monocytes collected. A cryopreserved AV-GBM-1 dose was thawed and admixed with 500 µg of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) before every subcutaneous (s.c.) administration. RESULTS: Success rates were 97% for both TIC production and monocyte collection. AV-GBM-1 was manufactured for 63/63 patients; 60 enrolled per ITT; 57 started AV-GBM-1. The most common AEs attributed to AV-GBM-1 were local injection site reactions (16%) and flu-like symptoms (10%). Treatment-emergent AEs included seizures (33%), headache (37%), and focal neurologic symptoms (28%). One patient discontinued AV-GBM-1 because of seizures. Median Progression-Free Survival (mPFS) and median Overall Survival (mOS) from ITT enrollment were 10.4 and 16.0 months, respectively. 2-year Overall Survival (OS) is 27%. CONCLUSIONS: AV-GBM-1 was reliably manufactured. Treatment was well-tolerated, but there were numerous treatment-emergent central nervous system AEs. mPFS was longer than historical benchmarks, though no mOS improvement was noted. TRIAL REGISTRATION: NCT, NCT03400917 , Registered 10 January 2018.
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Neoplasias Encefálicas , Glioblastoma , Vacunas , Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Adulto Joven , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Células Dendríticas , Glioblastoma/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Temozolomida , Resultado del Tratamiento , Vacunas/efectos adversosRESUMEN
We characterized the clinical and sociodemographic factors predictive of surgery refusal in pituitary adenoma (PA) patients. We queried the National Cancer Database (NCDB) to identify adult PA patients treated from 2004−2015 receiving or refusing surgery. Multivariate logistic regression and Cox proportional-hazards analysis identified clinical and/or sociodemographic factors predictive of surgery refusal or mortality, respectively. Of the 34,226 patients identified, 280 (0.8%) refused surgery. On multivariate logistic regression, age > 65 (OR: 2.64; p < 0.001), African American race (OR: 1.70; p < 0.001), Charlson-Deyo Comorbidity (C/D) Index > 2 (OR: 1.52; p = 0.047), and government insurance (OR: 2.03; p < 0.001) or being uninsured (OR: 2.16; p = 0.03) were all significantly associated with surgery refusal. On multivariate cox-proportional hazard analysis, age > 65 (HR: 2.66; p < 0.001), tumor size > 2 cm (HR: 1.30; p < 0.001), C/D index > 1 (HR: 1.53; p < 0.001), having government insurance (HR: 1.66; p < 0.001) or being uninsured (HR: 1.67; p < 0.001), and surgery refusal (HR: 2.28; p < 0.001) were all significant predictors of increased mortality. Macroadenoma patients receiving surgery had a significant increase in overall survival (OS) compared to those who refused surgery (p < 0.001). There are significant sociodemographic factors that influence surgery refusal in PA patients. An individualized approach is warranted that considers functional status, clinical presentations, and patient choice.
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BACKGROUND: Clinical and sociodemographic predictors of pituitary adenoma (PA) patients undergoing active surveillance (AS) versus definitive treatment (DT) are poorly understood. OBJECTIVE: This population-based analysis aims to identify clinical and sociodemographic predictors of undergoing AS versus DT. METHODS: The National Cancer Database (NCDB) was utilized to query PA patients diagnosed from 2010 to 2015 undergoing AS or DT. Independent-samples t-test and chi-squared test were used to compare differences in patient baseline characteristics and a stepwise binary logistic regression was performed to elucidate factors implicated in undergoing AS. RESULTS: The cohort consisted of 30,233 PA patients, with 5147 (17.0%) patients undergoing AS. On multivariable logistic regression, patients aged ≥ 65 years (OR=1.65; p < 0.001), African American race (OR=1.12; p = 0.035), having government insurance (OR=1.45; p < 0.001) or those uninsured (OR=1.58; p < 0.001) were significantly more likely to undergo AS compared to DT, while patients with larger tumors (OR=0.90; p < 0.001), receiving treatment at academic facilities (OR=0.75; p < 0.001), and living in West regions of the United States (OR=0.59; p < 0.001) were significantly less likely to undergo AS compared to DT. CONCLUSIONS: Significant sociodemographic disparities exist in patient selection for undergoing AS versus DT, which may modify patient clinical outcomes.