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OBJECTIVE: 30-day readmissions are a significant burden on the healthcare system. Postoperative transitional care protocols (TCPs) for safe and efficient discharge planning are being more widely adopted to reduce readmission rates. Currently, little evidence exists to justify the utility of TCPs for improving patient outcomes in elective neurosurgery. The objective of this systematic review was to determine the extent to which TCPs reduce adverse outcomes in patients undergoing elective neurosurgical procedures. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted after PROSPERO registration. Pubmed, Embase, and Cochrane review databases were searched through February 1, 2024. Keywords included: "transitional care AND neurosurgery", "Discharge planning AND neurosurgery". Articles were included if they assessed postoperative TCPs in an adult population undergoing elective neurosurgeries. Exclusion criteria were pediatric patients, implementation of Enhanced Recovery After Surgery (ERAS) protocols, or non-elective neurosurgical procedures. The primary outcome was readmission rates after implementation of TCPs. RESULTS: 16 articles were included in this review. 2 articles found that patients treated with TCPs had significantly higher chances of home discharge. 7 articles found a significant association between implementation of TCP and reduced length of stay and intensive care unit stay. 3 articles reported an increase in patient satisfaction after implementation of TCPs. 3 found that TCP led to a significant decrease in readmissions. After meta-analysis, TCPs were associated with significantly decreased readmission rates (OR: 0.68, p < 0.0001), length of stay (mean difference: -0.57, p < 0.00001), and emergency department visits (OR: 0.33, p < 0.0001). CONCLUSIONS: This systematic review and meta-analysis found that an overwhelming majority of the available literature supports the effectiveness of discharge planning on at least one measure of patient outcomes. However, the extent to which each facet of the TCP affects outcomes in elective neurosurgery remains unclear. Future efforts should be made to compare the effectiveness of different TCPs.
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Procedimientos Quirúrgicos Electivos , Procedimientos Neuroquirúrgicos , Cuidado de Transición , Humanos , Procedimientos Neuroquirúrgicos/métodos , Readmisión del Paciente/estadística & datos numéricos , Alta del Paciente , Resultado del Tratamiento , Tiempo de InternaciónRESUMEN
PURPOSE: There is a growing body of literature documenting glioma heterogeneity in terms of radiographic, histologic, molecular, and genetic characteristics. Incomplete spatial specification of intraoperative tumor samples may contribute to variability in the results of pathological and biological investigations. We have developed a system, termed geo-tagging, for routine intraoperative linkage of each tumor sample to its location via neuronavigation. METHODS: This is a single-institution, IRB approved, prospective database of undergoing clinically indicated surgery. We evaluated relevant factors affecting data collection by this registry, including tumor and surgical factors (e.g. tumor volume, location, grade and surgeon). RESULTS: Over a 2-year period, 487 patients underwent craniotomy for an intra-axial tumor. Of those, 214 underwent surgery for a newly diagnosed or recurrent glioma. There was significant variation in the average number of samples collected per registered case, with a range of samples from 2.53 to 4.75 per tumor type. Histology and grade impacted on sampling with a range of 2.0 samples per tumor in Grade four, IDH-WT gliomas to 4.5 samples in grade four, IDH-mutant gliomas. The range of cases with sampling per surgeon was 6 to 99 with a mean of 47.6 cases and there was a statistically significant differences between surgeons. Tumor grade did not have a statistically significant impact on number of samples per case. No significant correlation was found between the number of samples collected and enhancing tumor volume, EOR, or volume of tumor resected. CONCLUSION: We are using the results of this analysis to develop a prospective sample collection protocol.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirugía , Recurrencia Local de Neoplasia , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/cirugía , Imagen por Resonancia Magnética/métodos , Sistema de RegistrosRESUMEN
PURPOSE: Diffuse midline gliomas are rare midline CNS malignancies that primarily affect children but can also affect adults. While radiation is standard treatment, prognosis remains fatal. Furthermore, due to its sensitive anatomic location, many physicians have been reluctant to perform biopsies without potential for improved prognosis. However, recent advancements in molecular-targeted therapeutics have encouraged greater tissue sampling. While the literature reflects this progress, the landscape of how clinicians actually manage these patients remains unclear. Our goal was to assess the attitudes of current practicing neurosurgical oncologists towards management of adult diffuse midline gliomas, reasons behind their practices, and factors that might influence these practices. METHODS: We created and distributed a survey with 16 multiple choice and open-ended questions to members of the Tumor Section of the Congress of Neurological Surgeons. RESULTS: A total of 81 physicians responded to the survey. Although time since training and volume of glioma patients did not significantly affect the decision to consider clinical trials or to offer biopsy, those that operated on fewer gliomas (< 25/year) were more likely to cite surgical morbidity as the primary reason not to biopsy these midline locations. Further, surgeons with access to more advanced molecular testing were significantly more likely to consider clinical trial eligibility when offering biopsies. CONCLUSION: Factors that affect the management of diffuse midline gliomas and the role of biopsy are relatively uniform across the field, however, there were a few notable differences that reflect the changes within the neuro-oncology field in response to clinical trials.
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Actitud del Personal de Salud , Neoplasias Encefálicas/psicología , Glioma/psicología , Neurocirujanos/psicología , Procedimientos Neuroquirúrgicos/psicología , Técnicas Estereotáxicas/psicología , Adulto , Biopsia , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Glioma/patología , Glioma/cirugía , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Gangliogliomas are well-differentiated, slow-growing glioneuronal neoplasms frequently reported to harbor upregulating alterations in the mitogen-activated protein kinase pathway, particularly serine-threonine protein kinase B-RAF alterations. Fusions involving neurotrophin tyrosine receptor kinase (NTRK) genes have rarely been reported in ganglioglioma. Similarly, echinoderm microtubule-associated protein-like (EML) 4 gene fusion has been described in lung cancer, but none has been reported in ganglioglioma. OBSERVATIONS: This report discusses the care of a 72-year-old man presenting with medication-refractory, left-sided focal seizures who was found to have a nongadolinium-enhancing, T2-hyperintense, right frontoparietal lesion. The patient received resection, and histological analysis found a World Health Organization grade I ganglioglioma, with genetic analysis demonstrating an EML4-NTRK3 gene fusion protein. LESSONS: To our knowledge, this is the first report of an NTRK3 fusion, EML4-NTRK3, in an adult ganglioglioma, which is otherwise mostly associated with BRAF alterations and activation of the mitogen-activated protein kinase signaling pathway. Further studies are needed to elucidate the function of the resultant fusion protein and determine whether it may serve as a future therapeutic target.
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Spontaneous spinal subdural hematomas (SSH) are rare occurrences that can occur most commonly secondary to vascular malformations or coagulopathies. Only a small fraction of spontaneous SSHs are caused by acquired coagulation disorders such as leukemia, hemophilia, and thrombocytopenia. This case report describes a patient with a history of Guillain-Barré syndrome (GBS), hemophilia A, and mantle cell lymphoma, on zanubrutinib therapy, a Bruton tyrosine kinase inhibitor associated with a risk of spontaneous hemorrhage. This patient developed a spontaneous spinal subdural hematoma, most likely due to the zanubrutinib therapy and exacerbated due to hemophilia. Treatment was delayed due to the patient's history of GBS that confounded the clinical diagnosis. This case is the first report of a spontaneous SSH in a patient on zanubrutinib, highlighting the need for a high index of suspicion for CNS hemorrhage in patients on Bruton's tyrosine kinase (BTK) inhibitor therapy.
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Meningiomas are the most common intracranial primary tumor in adults. Surgery is the predominant therapeutic modality for symptomatic meningiomas. Although the majority of meningiomas are benign, there exists a subset of meningiomas that are clinically aggressive. Recent advances in genetics and epigenetics have uncovered molecular alterations that drive tumor meningioma biology with prognostic and therapeutic implications. In this review, we will discuss the advances on molecular determinants of therapeutic response in meningiomas to date and discuss findings of targeted therapies in meningiomas.
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BACKGROUND AND IMPORTANCE: Partially thrombosed basilar aneurysms have a high morbidity from the rupture risk and mass effect prompting early treatment. Depending on the size and location, they pose a surgical challenge often requiring multiple endovascular treatment modalities. Here we present a partially thrombosed mid-basilar aneurysm successfully coil embolized with direct vertebral artery access and discuss the technical limitations of direct V1 access. CLINICAL PRESENTATION: A 70-yr-old woman presented with acute onset headache, nausea, and vomiting. A computed tomography (CT) head demonstrated a hyperdense prepontine mass which was further characterized as a partially thrombosed basilar aneurysm on CT angiography. After multiple failed attempts to access the vertebral artery via femoral and radial access the patient was taken to the operating room (OR) for surgical exposure of the right V1 segment and direct cannulation of the vertebral artery. The aneurysm was successfully coiled and the vertebral artery closed primarily. The patient was discharged home without any neurological deficits. CONCLUSION: Partially thrombosed mid-basilar aneurysms are difficult to treat both surgically and endovascularly. We present a case where endovascular access to the aneurysm was very challenging requiring direct exposure and cannulation of the V1 segment to successfully embolize with coils and discuss the technical limitations of this approach.
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Aneurisma Intracraneal , Trombosis , Angiografía , Femenino , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/terapia , Tomografía Computarizada por Rayos X , Arteria Vertebral/diagnóstico por imagen , Arteria Vertebral/cirugíaRESUMEN
We present the case of a 48-yr-old female who presented with persistent thigh pain and was found to have a heterogeneous mass caudal to the conus most consistent with a myxopapillary ependymoma. We performed L2-3 laminectomies for tumor resection. For this procedure, we used intraoperative ultrasound as well as neuromonitoring. This video illustrates the gross pathology of a myxopapillary ependymoma, effective circumferential blunt and sharp dissection of the cauda equina from the tumor, and identification, preparation, and sectioning of the filum terminale. This case also underlines the challenges of removing a large myxopapillary ependymoma when motor nerve rootlets are encapsulated in the tumor. In this case, we were obligated to enter the tumor capsule ventrally in order to dissect away cauda equina nerves passing through the tumor. The patient consented to be part of our research study.
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Cauda Equina/cirugía , Ependimoma/cirugía , Monitorización Neurofisiológica Intraoperatoria/métodos , Laminectomía/métodos , Neoplasias del Sistema Nervioso Periférico/cirugía , Cauda Equina/diagnóstico por imagen , Ependimoma/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Neoplasias del Sistema Nervioso Periférico/diagnóstico por imagen , Ultrasonografía Doppler/métodosRESUMEN
Immunotherapy is a promising new therapeutic field that has demonstrated significant benefits in many solid-tumor malignancies, such as metastatic melanoma and non-small cell lung cancer. However, only a subset of these patients responds to treatment. Glioblastoma (GBM) is the most common malignant primary brain tumor with a poor prognosis of 14.6 months and few treatment advancements over the last 10 years. There are many clinical trials testing immune therapies in GBM, but patient responses in these studies have been highly variable and a definitive benefit has yet to be identified. Biomarkers are used to quantify normal physiology and physiological response to therapies. When extensively characterized and vigorously validated, they have the potential to delineate responders from non-responders for patients treated with immunotherapy in malignancies outside of the central nervous system (CNS) as well as GBM. Due to the challenges of current modalities of radiographic diagnosis and disease monitoring, identification of new predictive and prognostic biomarkers to gauge response to immune therapy for patients with GBM will be critical in the precise treatment of this highly heterogenous disease. This review will explore the current and future strategies for the identification of potential biomarkers in the field of immunotherapy for GBM, as well as highlight major challenges of adapting immune therapy for CNS malignancies.
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Biomarcadores/metabolismo , Neoplasias Encefálicas/inmunología , Glioblastoma/inmunología , Inmunoterapia/métodos , Neoplasias Encefálicas/patología , Glioblastoma/patología , HumanosRESUMEN
Preclinical models that reliably recapitulate the immunosuppressive properties of human gliomas are essential to assess immune-based therapies. GL261 murine glioma cells are widely used as a syngeneic animal model of glioma, however, it has become common practice to transfect these cells with luciferase for fluorescent tumor tracking. The aim of this study was to compare the survival of mice injected with fluorescent or non-fluorescent GL261 cells and characterize the differences in their tumor microenvironment. Mice were intracranially implanted with GL261, GL261 Red-FLuc or GL261-Luc2 cells at varying doses. Cytokine profiles were evaluated by proteome microarray and Kaplan-Meier survival analysis was used to determine survival differences. Median survival for mice implanted with 5 × 104 GL261 cells was 18 to 21 days. The GL261 Red-FLuc implanted mice cells did not reach median survival at any tumor dose. Mice injected with 3 × 105 GL261-Luc2 cells reached median survival at 23 days. However, median survival was significantly prolonged to 37 days in mice implanted with 5 × 104 GL261-Luc2 cells. Additionally, proteomic analyses revealed significantly elevated inflammatory cytokines in the supernatants of the GL261 Red-FLuc cells and GL261-Luc2 cells. Our data suggest that GL261 Red-FLuc and GL261-Luc2 murine models elicit an anti-tumor immune response by increasing pro-inflammatory modulators.
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Neoplasias Encefálicas/metabolismo , Citocinas/metabolismo , Glioma/metabolismo , Luciferasas/inmunología , Regulación hacia Arriba , Animales , Línea Celular Tumoral , Supervivencia Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Estimación de Kaplan-Meier , Luciferasas/genética , Ratones , Trasplante de Neoplasias , Proteómica/métodos , Microambiente TumoralRESUMEN
BACKGROUND: Checkpoint inhibition has demonstrated clinical efficacy in a variety of solid tumors. Reports of programmed death ligand 1 (PD-L1) expression in glioblastoma are highly variable (ranging from 6% to 88%) and its role as a prognostic marker has yielded conflicting results. OBJECTIVE: To validate the prevalence and prognostic role of PD-L1 expression in a large cohort of diffuse gliomas according to the 2016 revised WHO classification. METHODS: Using tissue microarrays, we compared 5 PD-L1 monoclonal antibodies (n = 56) and validated expression (n = 183) using quantitative immunohistochemistry (IHC) and RNA in situ hybridization (RISH). Expression data from The Cancer Genome Atlas (TCGA) and published studies were compared with clinical outcome. Multiplexed immunophenotyping was used to identify PD-L1+ cell populations in post-treatment glioblastoma. RESULTS: Using a 5% cut-off, PD-L1 expression was significantly associated with a poor prognosis in both histologically defined (n = 125, log-rank P < .001) and recurrent isocitrate dehydrogenase (IDH)-wildtype glioblastoma (n = 60, log-rank P = .015). PD-L1 remained a significant negative prognosticator in Cox regression analysis (hazard ratio: 1.96, P = .021). Analysis of TCGA data confirmed decreased overall survival in recurrent non-glioma CpG island methylator phenotype (G-CIMP) glioblastoma (n = 12, log-rank P = .023), but not in glioblastoma as a group (n = 444, log-rank P = .135). PD-L1 RISH showed a significant correlation with IHC (P < .0001). PD-L1 was observed in the proliferating perivascular stem cell and immune niche of post-treatment glioblastoma. CONCLUSION: A 5% PD-L1 expression cut-off identified a subset of glioblastoma that is associated with a worse clinical outcome. This association remained significant within the newly defined IDH-wildtype classification. These findings could have implications for patient stratification in future clinical trials of PD-1/PD-L1 blockade.
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Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/patología , Glioblastoma/patología , Adolescente , Adulto , Antígeno B7-H1/análisis , Neoplasias Encefálicas/genética , Niño , Preescolar , Estudios de Cohortes , Femenino , Glioblastoma/genética , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Glioblastoma is the most common primary malignancy of the brain, with a dismal prognosis. Immunomodulation via checkpoint inhibition has provided encouraging results in non-CNS malignancies, but prediction of responders has proven to be challenging in glioblastoma patients. OBJECTIVE: To determine the proportion of patients who have a measurable increase of interferon gamma levels in brain tumor tissue after their first dose of nivolumab, and to evaluate the safety of using brain tumor microdialysis to monitor for immune response while evaluating the safety of the combination of anti-programmed death 1 (PD-1) and anti-lymphocyte activation gene 3 (LAG-3) checkpoint inhibition. METHODS: The study design is a single-center, nonrandomized phase 1 clinical trial. Up to 15 adult patients with recurrent glioblastoma will be enrolled with the goal of 10 patients completing the trial over an anticipated 18 mo. Patients will undergo biopsy; placement of microdialysis catheters and lumbar drains; treatment with anti-PD-1 checkpoint inhibition; comprehensive immune biomarker collection; tumor resection; and then treatment with anti-PD-1 and anti-LAG-3 checkpoint inhibition until progression. EXPECTED OUTCOMES: We expect interferon gamma levels to increase in the brain as measured via microdialysis in treated patients. Based on published reports, microdialysis in this patient population is expected to be safe, and anti-LAG-3 and anti-PD-1 combined will likely have a similar side effect profile to other checkpoint inhibitor combinations. DISCUSSION: The failure of recent trials of immune therapies in glioblastoma underscores the need to appropriately measure response in the treated tissue. This trial may provide insight on indicators of which patients will respond to immune therapy.
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Neoplasias Encefálicas , Citocinas , Glioblastoma , Microdiálisis , Monitorización Inmunológica , Adulto , Química Encefálica , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Citocinas/análisis , Citocinas/aislamiento & purificación , Glioblastoma/inmunología , Glioblastoma/metabolismo , Glioblastoma/terapia , Humanos , Interferón gamma/análisis , Interferón gamma/aislamiento & purificación , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/terapiaRESUMEN
Meningiomas are the most common adult primary tumor of the central nervous system, but there are no known effective medical therapies for recurrent meningioma, particularly for World Health Organization grade II and III tumors. Meningiomas arise from the meninges, located outside the blood-brain barrier, and therefore may be directly targeted by antibody-mediated immunotherapy. We found that programmed cell death ligand 1 (PD-L1) was highly expressed in multiple human malignant meningioma cell lines and patient tumor samples. PD-L1 was targeted with the anti-PD-L1 antibody avelumab and directed natural killer cells to mediate antibody-dependent cellular cytotoxicity (ADCC) of PD-L1-expressing meningioma tumors both in vitro and in vivo. ADCC of meningioma cells was significantly increased in target cells that upregulated PD-L1 expression and, conversely, abrogated in tumor cells that were depleted of PD-L1. Additionally, the high-affinity natural killer cell line, haNK, outperformed healthy donor NK cells in meningioma ADCC. Together, these data support a clinical trial designed to target PD-L1 with avelumab and haNK cells, potentially offering a novel immunotherapeutic approach for patients with malignant meningioma.
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Anticuerpos Monoclonales Humanizados/farmacología , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Inmunoterapia/métodos , Células Asesinas Naturales/trasplante , Neoplasias Meníngeas/terapia , Meningioma/terapia , Animales , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Línea Celular Tumoral , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Neoplasias Meníngeas/inmunología , Meningioma/inmunología , Ratones , Resultado del Tratamiento , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Glioblastoma is in need of innovative treatment approaches. Immune therapy for cancer refers to the use of the body's immune system to target malignant cells in the body. Such immune therapeutics have recently been very successful in treating a diverse group of cancerous lesions. As a result, many new immune therapies have gained Food and Drug Administration approval for the treatment of cancer, and there has been an explosion in the study of immune therapeutics for cancer treatment over the past few years. However, the immune suppression of glioblastoma and the unique immune microenvironment of the brain make immune therapeutics more challenging to apply to the brain than to other systemic cancers. Here, we discuss the existing barriers to successful immune therapy for glioblastoma and the ongoing development of immune therapeutics. We will discuss the discovery and classification of immune suppressive factors in the glioblastoma microenvironment; the development of vaccine-based therapies; the use of convection-enhanced delivery to introduce tumoricidal viruses into the tumor microenvironment, leading to secondary immune responses; the emerging use of adoptive cell therapy in the treatment of glioblastoma; and future frontiers, such as the use of cerebral microdialysis for immune monitoring and the use of sequencing to develop patient-specific therapeutics. Armed with a better understanding of the challenges inherent in immune therapy for glioblastoma, we may soon see more successes in immune-based clinical trials for this deadly disease.
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Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/uso terapéutico , Humanos , Lenalidomida/uso terapéutico , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Talidomida/uso terapéutico , Resultado del Tratamiento , Reino UnidoRESUMEN
In human gliomas, the RTK/RAS/PI(3)K signaling pathway is nearly always altered. We present a model of experimental gliomagenesis that elucidates the contributions of genes involved in this pathway (PDGF-B ligand, HRAS-G12V, and AKT). We also examine the effect on gliomagenesis by the potential modifier gene, IDH1-R132H. Injections of lentiviral-encoded oncogenes induce de novo gliomas of varying penetrance, tumor progression, and histological grade depending on the specific oncogenes used. Our model mimics hallmark histological structures of high-grade glioma, such as pseudopalisades, glomeruloid microvascular proliferation, and diffuse tumor invasion. We use our model of gliomagenesis to test the efficacy of an experimental brain tumor gene therapy. Our model allowed us to test the contributions of oncogenes in the RTK/RAS/PI(3)K pathway, and their potential modification by over-expression of mutated IDH1, in glioma development and progression in rats. Our model constitutes a clinically relevant system to study gliomagenesis, the effects of modifier genes, and the efficacy of experimental therapeutics.