Glioma stem cells activate platelets by plasma-independent thrombin production to promote glioblastoma tumorigenesis.

Background: The interaction between platelets and cancer cells has been underexplored in solid tumor models that do not metastasize, for example, glioblastoma (GBM) where metastasis is rare. Histologically, it is known that glioma stem cells (GSCs) are found in perivascular and pseudsopalisading regions of GBM, which are also areas of platelet localization. High platelet counts have been associated with poor clinical outcomes in many cancers. While platelets are known to promote the progression of other tumors, mechanisms by which platelets influence GBM oncogenesis are unknown. Here, we aimed to understand how the bidirectional interaction between platelets and GSCs drives GBM oncogenesis. Methods: Male and female NSG mice were transplanted with GSC lines and treated with antiplatelet and anti-thrombin inhibitors. Immunofluorescence, qPCR, and Western blots were used to determine expression of coagulation mechanism in GBM tissue and subsequent GSC lines. Results: We show that GSCs activate platelets by endogenous production of all the factors of the intrinsic and extrinsic coagulation cascades in a plasma-independent manner. Therefore, GSCs produce thrombin resulting in platelet activation. We further demonstrate that the endogenous coagulation cascades of these cancer stem cells are tumorigenic: they activate platelets to promote stemness and proliferation in vitro and pharmacological inhibition delays tumor growth in vivo. Conclusions: Our findings uncover a specific preferential relationship between platelets and GSCs that drive GBM malignancies and identify a therapeutically targetable novel interaction.

En Plaque Meningiomas: A Narrative Review.

Background En plaque meningiomas are a rare subtype of meningiomas that are frequently encountered in the spheno-orbital region. Characterized by a hyperostotic and dural invasive architecture, these tumors present unique diagnostic and treatment considerations. Objective The authors conduct a narrative literature review of clinical reports of en plaque meningiomas to summarize the epidemiology, clinical presentation, diagnostic criteria, and treatment considerations in treating en plaque meningiomas. Additionally, the authors present a case from their own experience to illustrate its complexity and unique features. Methods A literature search was conducted using the MEDLINE database using the following terminology in various combinations: meningioma , meningeal neoplasms, en plaque , skull base , spheno-orbital, and sphenoid wing . Only literature published in English between 1938 and 2018 was reviewed. All case series were specifically reviewed for sufficient data on treatment outcomes, and all literature was analyzed for reports of misdiagnosed cases. Conclusion En plaque meningiomas may present with a variety of symptoms according to their location and degree of bone invasion, requiring a careful diagnostic and treatment approach. While early and aggressive surgical resection is generally accepted as the optimal goal of treatment, these lesions require an individualized approach, with further investigation needed regarding the role of new therapies.

Aneurysmal subarachnoid hemorrhage, a presentation of metastatic carcinoma: A case report and review of the literature.

BACKGROUND: Neoplastic cerebral aneurysms related to metastatic processes are exceptionally rare and carry a dismal prognosis. Only four previous reports exist of neoplastic aneurysms secondary to metastatic adenocarcinoma, all of which were found to be lung cancer in origin. We present the fifth reported metastatic adenocarcinomatous cerebral aneurysm, and the first case is secondary to a non-lung cancer primary. CASE DESCRIPTION: The patient presented with complaining of headache and was found to have a large right-sided intraparenchymal hemorrhage and smaller left-sided hemorrhage on head CT, and CTA revealed a vascular pouch in the region of the hemorrhage. The patient showed sudden neurologic decline, and repeat imaging revealed enlargement of the hematoma with significant brain compression. The patient underwent emergent angiography revealing a distal cortical middle cerebral artery aneurysm, suspicious for mycotic etiology, which was treated through microsurgical excision at the time of hematoma evacuation. The aneurysm specimen was sent for cultures and pathology, revealing the diagnosis of metastatic non-small-cell carcinoma. Further inpatient workup did not reveal the primary neoplastic source. CONCLUSION: Although diagnostic workup should search for more common pathologic mimics than metastatic neoplastic cerebral aneurysms, clinicians must be able to recognize and expeditiously treat this devastating lesion. Further investigation and analysis of treatment options are necessary to better understand this rare pathology and improve patient outcomes.

Laser interstitial thermotherapy (LITT) for the treatment of tumors of the brain and spine: a brief review.

INTRODUCTION: Laser Interstitial Thermotherapy (LITT; also known as Stereotactic Laser Ablation or SLA), is a minimally invasive treatment modality that has recently gained prominence in the treatment of malignant primary and metastatic brain tumors and radiation necrosis and studies for treatment of spinal metastasis has recently been reported. METHODS: Here we provide a brief literature review of the various contemporary uses for LITT and their reported outcomes. RESULTS: Historically, the primary indication for LITT has been for the treatment of recurrent glioblastoma (GBM). However, indications have continued to expand and now include gliomas of different grades, brain metastasis (BM), radiation necrosis (RN), other types of brain tumors as well as spine metastasis. LITT is emerging as a safe, reliable, minimally invasive clinical approach, particularly for deep seated, focal malignant brain tumors and radiation necrosis. The role of LITT for treatment of other types of tumors of the brain and for spine tumors appears to be evolving at a small number of centers. While the technology appears to be safe and increasingly utilized, there have been few prospective clinical trials and most published studies combine different pathologies in the same report. CONCLUSION: Well-designed prospective trials will be required to firmly establish the role of LITT in the treatment of lesions of the brain and spine.

A Liquid Biopsy to Assess Brain Tumor Recurrence: Presence of Circulating Mo-MDSC and CD14+ VNN2+ Myeloid Cells as Biomarkers That Distinguish Brain Metastasis From Radiation Necrosis Following Stereotactic Radiosurgery.

BACKGROUND: Brain metastases (BM) are the most common type of brain tumor malignancy in the US. They are also the most common indication for stereotactic radiosurgery (SRS). However, the incidence of both local recurrence and radiation necrosis (RN) is increasing as treatments improve. MRI imagery often fails to differentiate BM from RN; thus, patients must often undergo surgical biopsy or resection to obtain a definitive diagnosis. OBJECTIVE: To hypothesize that a marker of immunosuppression might serve as a surrogate marker to differentiate patients with active vs inactive cancer-including RN. METHODS: We thus purified and quantified Monocytic Myeloid-Derived Suppressor Cells (Mo-MDSC) by flow cytometry in patients proven by biopsy to represent BM or RN. RESULTS: We report the utility of the previously reported HLA-Dr-Vnn2 Index or DVI to discriminate recurrent BM from RN using peripheral blood. The presence of CD14+ HLA-DRneg/low Mo-MDSC is significantly increased in the peripheral blood of patients with brain metastasis recurrence compared to RN (Average 61.5% vs 7%, n = 10 and n = 12, respectively, P < .0001). In contrast, expression of VNN2 on circulating CD14+ monocytes is decreased in BM patients compared to patients with RN (5.5% vs 26.5%, n = 10 and n = 12, respectively, P = .0008). In patients with biopsy confirmed recurrence of brain metastasis, the average DVI was 11.65, whereas the average DVI for RN patients was consistently <1 (Avg. of 0.17). CONCLUSION: These results suggest that DVI could be a useful diagnostic tool to differentiate recurrent BM from RN using a minimally invasive blood sample.

Comparative epidemiology of gliosarcoma and glioblastoma and the impact of Race on overall survival: A systematic literature review.

OBJECTIVE: Gliosarcoma (GSM) is a rare subtype of glioblastoma (GBM) that accounts for approximately four percent of high-grade gliomas. There is scarce epidemiological data on patients with GSM as a distinct subgroup of GBM. METHODS: A systematic literature review was performed of peer-reviewed databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the impact of race and ethnicity on survival in patients with GSM compared to patients with GBM. RESULTS: Following initial abstract screening, a total of 138 articles pertaining to GSM and 275 pertaining to GBM met criteria for full-text review, with 5 and 27 articles included in the final analysis for GSM and GBM, respectively. The majority of patients in both cohorts were non-Hispanic Whites, representing 85.6 % of total GSM patients and 87.7 % of GBM patients analyzed. Two GSM studies stratified survival by race, with one reporting the longest median survival for the Hispanic population of 10.6 months and the shortest median survival for the Asian population of 9 months. Among the GBM studies analyzed, the majority of studies reported shorter survival and higher risk of mortality among White Non-Hispanics compared to non-White patients; and of the 15 studies which reported data for the Asian population, 12 studies reported this race category to have the longest survival compared to all other races studied. Younger age, female sex, MGMT promoter methylation status, and adjuvant chemoradiation therapy were associated with improved survival in both GSM and GBM cohorts, although these were not further stratified by race. CONCLUSION: GSM portends a similarly poor prognosis to other GBM subtypes; however, few studies exist which have examined factors associated with differences in survival between these histologic variants. This review of the literature suggests there is a possible association between race and survival for patients with GBM, however data supporting this conclusion for patients with GSM is lacking. These findings suggest that GSM is a distinct disease from other GBM subtypes, with epidemiologic differences that should be further explored.

Outcomes and Clinical Characteristics of Intracranial Hemorrhage in Patients with Hematologic Malignancies: A Systematic Literature Review.

BACKGROUND: Many clinical and demographic factors can influence survival of patients with hematologic malignancies who have intracranial hemorrhages (ICHs). Understanding the influence of these factors on patient survival can guide treatment decisions and may inform prognostic discussions. We conducted a systematic literature review to determine survival of patients with intracranial hemorrhages and concomitant hematologic malignancy. METHODS: A systematic literature review was conducted and followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. PubMed/MEDLINE, Web of Science, Ovid, SCOPUS, and Embase databases were queried with the following terms: ("intracranial hemorrhages" OR "brain hemorrhage" OR "cerebral hemorrhage" OR "subdural hematoma" OR "epidural hematoma" OR "intraparenchymal hemorrhage") AND ("Hematologic Neoplasms" OR "Myeloproliferative Disorders" OR "Myelofibrosis" OR "Essential thrombocythemia" OR "Leukemia"). Abstracts and articles were screened according to inclusion and exclusion criteria that were determined a priori. RESULTS: Literature review yielded 975 abstracts from which a total of 68 full-text articles were reviewed. Twelve articles capturing 634 unique patients were included in the final qualitative analysis. Median overall survival for all patients ranged from 20 days to 1.5 months while median overall survival for the subset of patients having ICH within 10 days of diagnosis of hematologic malignancy was 5 days. Intraparenchymal hemorrhages, multiple foci of hemorrhage, transfusion-resistant low platelet counts, leukocytosis, low Glasgow Coma Scale scores at presentation, and ICH early in treatment course were associated with worse outcomes. CONCLUSIONS: Survival for patients with hematologic malignancies and concomitant ICHs remains poor. Early detection, recognition of poor prognostic factors, and correction of hematologic abnormalities essential to prevention and treatment of ICHs in this patient population.

Association of Race with Survival in Intracranial World Health Organization Grade II and III Meningioma in the United States: Systematic Literature Review.

BACKGROUND: Recent literature has shown significant differences in meningioma incidence among different races, but minimal conclusive data exist on the role of race and ethnicity in overall survival for patients with high-grade intracranial meningioma. We conducted a systematic review to investigate the impact of race and ethnicity on survival in patients with high-grade intracranial meningioma. METHODS: A systematic literature review was conducted for studies using Ovid, PubMed, Cochrane, Embase, and Scopus databases. Databases were queried for the following: Meningioma AND [Ethnic OR Demography, OR African American OR Arab OR Hispanic OR Asian, OR White OR race OR racial] AND [survival OR survival analysis OR survival rate OR treatment outcome OR Survivor OR Outcome]. RESULTS: A literature search yielded a total of 412 abstracts, which were screened according to criteria that were determined a priori, and a total of 129 full-text articles were reviewed. Four articles were included in the final analysis, reporting on a total of 13,424 patients. Three studies saw an overall survival benefit in White non-Hispanics compared with Black non-Hispanics, and 1 reported a survival benefit in White non-Hispanics and Black non-Hispanics among patients who received gross total resection. One study additionally reported an increased likelihood of White patients receiving gross total resection when compared with non-White patients. CONCLUSIONS: The limited data available suggest that White patients have improved measures of survival compared with nonw-White patients, for reasons that are likely complex and multifactorial. Further studies are needed to explore these survival differences seen.

Cerebrospinal Fluid Drainage During Endovascular Aortic Aneurysm Repair: A Systematic Review of the Literature and Treatment Recommendations.

INTRODUCTION: Spinal cord injury (SCI) is a known complication of aortic aneurysm repair. Previous reports indicate that cerebrospinal fluid drainage (CSFD) may reduce incidence of SCI during open aortic aneurysm repair but its utility in endovascular repair remains poorly understood. We performed a systematic review of the literature to examine the protocols and outcomes of CSFD in patients undergoing endovascular aortic aneurysm repair. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were utilized to conduct a systematic literature review. PubMed, Scopus, Ovid, Cochrane, and EMBASE were queried for articles published since 2016 using search terms "(cerebrospinal fluid diversion OR CSF diversion OR lumbar drain OR subarachnoid drain OR spinal) AND (aortic aneurysm AND thoracic AND endovascular OR TEVAR)." Ninety-two articles were identified and screened by 2 independent reviewers, and 23 studies met criteria for full-text review after initial screening. RESULTS: A total of 8 studies met full inclusion criteria for final analysis. Six studies reported incidence of SCI in patients with CSFD and 2 compared SCI incidence between patients with and without CSFD. Protocols for drainage most commonly included draining to a target pressure intra- and postoperatively, between 8 and 12 mm Hg. Incidence of SCI ranged from 0% to 17% in patients with CSFD, and from 0% to 50% in those without CSFD. Rates of CSFD-related complications ranged from <1% to 28%. CONCLUSION: There may be a protective benefit of CSFD in preventing SCI, but there remains significant variation in drain placement protocols. Significant potential bias exists in the reviewed data. Higher quality studies on the role of CSFD in endovascular aortic aneurysm repair are needed.

Bilateral vertebral artery transection following blunt trauma.

INTRODUCTION: Blunt vertebral artery injury (BVI) is a potentially catastrophic event associated with a variety of trauma mechanisms, particularly in the setting of cervical spine injury. Early detection and treatment of BVI and blunt carotid artery injury (BCI) - collectively termed blunt cerebrovascular injuries (BCVI) - is a known determinant of favorable outcomes, except in the case of complete transection injuries. The limited existing reports of these injuries demonstrate a 100% mortality rate regardless of the management approach taken, and further investigation is essential in better understanding the nature of the injury and improving patient outcomes. PRESENTATION OF CASE: A 55 year old previously healthy patient was brought to the Emergency Department following a motor vehicle collision. The patient was alert upon arrival to the ED and complained of neck pain. Initial assessment was significant for open fracture of the left upper extremity, swelling of the anterior neck, and no purposeful movements noted of the lower extremities. Shortly thereafter, the patient showed a sudden decline in mental status and became hemodynamically unstable. Focused Assessment with Sonography for Trauma was positive, and after remaining unstable despite resuscitation efforts, the patient was brought emergently to the operating room. DISCUSSION: Following exploratory laparotomy for bleeding control and washout of the open fracture, CT angiogram of the head and neck was obtained. This revealed significant C5-C6 dissociation as well as bilateral vertebral artery transection and large prevertebral hematoma. Prior to any further surgical intervention, the patient's neurologic function continued to decline, and brain CT demonstrated infarcts in the posterior cerebral artery distribution. Brain death was confirmed the next day, and all care was subsequently withdrawn. CONCLUSIONS: Analysis of outcomes in patients with BCVI suggests that BVI should be distinguished from the better-studied CVI. Each injury type has been found to possess its own distinct risk factors, likelihoods of progression, and surgical accessibility, all of which affect management. Data on complete vessel transections remains limited for all BCVIs, with no documented cases of bilateral BVI to date. Our case study supports the 100% mortality rate seen in previously reported BCVI transections. Furthermore, our findings suggest that BVI transections occur in patients with coexisting injuries, which challenges the ability to attribute a single neurologic outcome to any one injury.