Single-center experience in resection of 120 cases of intradural spinal tumors.

BACKGROUND: Our study presents a single center experience in resection of intradural spinal tumors either with or without using intraoperative CT (iCT)-based registration and microscope-based augmented reality (AR). Microscope-based AR was recently described for improved orientation in the operative field in spine surgery, using superimposed images of segmented structures of interest in a two- (2D) or three-dimensional (3D) mode. MATERIALS AND METHODS: All patients who underwent surgery for resection of intradural spinal tumors at our department were retrospectively included in the study. Clinical outcomes in terms of postoperative neurological deficits and complications were evaluated, as well as neuroradiological outcomes for tumor remnants and recurrence. RESULTS: 112 patients (57 female, 55 male, median age 55.8 ± 17.8 years) who underwent 120 surgeries for resection of intradural spinal tumors with use of intraoperative neuromonitoring were included in the study, with median follow up of 39 ± 34.4 months. Nine patients died during the follow-up to reasons unrelated to surgery. Most common tumors were meningioma (n= 41), schwannoma (n= 37), myopapillary ependymomas (n= 12), ependymomas (n= 10), and others (20). Tumors were in thoracic spine (n= 46), lumbar spine (n= 39), cervical spine (n= 32), lumbosacral spine (n= 1), thoracic and lumbar spine (n= 1) and one tumor in cervical, thoracic, and lumbar spine. Four biopsies were performed, ten partial resections, 13 subtotal resections, and 93 gross total resections. Laminectomy was the common approach. In 79 cases, patients experienced neurological deficits prior to surgery, with ataxia and paraparesis as the most common ones. Following surgery, 67 cases were unchanged, in 49 improved and in 4 worsened. Operative time, extent of resection, clinical outcome and complication rate did not differ between the AR and non-AR group. However, use of AR improved orientation in the operative field by identification of important neurovascular structures. CONCLUSION: High rates of GTR with favorable neurological outcome in a vast majority of patients as well as low recurrence rate with comparable complication rates was noted in our single center experience. AR improved intraoperative orientation and increased surgeons comfort by enabling early identification of important anatomical structures , however clinical and radiological outcomes did not differ, when AR was not used.

Four-level ACDF surgical series 2000-2022: a systematic review of clinical and radiological outcomes and complications.

OBJECTIVE: The primary objective of this investigation is to systematically scrutinize extant surgical studies delineating Four-Level Anterior Cervical Discectomy and Fusion (4L ACDF), with a specific emphasis on elucidating reported surgical indications, clinical and radiological outcomes, fusion rates, lordosis correction, and the spectrum of complication rates. METHODS: The literature review was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, employing the MEDLINE (PubMed), Embase, and Scopus databases. This analysis encompasses studies implementing the 4L ACDF procedure, with detailed extraction of pertinent data pertaining to surgical methodologies, types of employed interbody cages, clinical and radiological endpoints, rates of fusion, and the incidence of complications. RESULTS: Among the 15 studies satisfying inclusion criteria, a marginal increment in the year 2022 (21.4%) was discerned, with a preponderance of study representation emanating from China (35.7%) and the United States (28.6%). 50% of the studies were single-surgeon studies. Concerning follow-up, studies exhibited variability, with 42.9% concentrating on periods of five years or less, and an equivalent proportion extending beyond this timeframe. Across the amalgamated cohort of 2457 patients, males constituted 51.6%, manifesting a mean age range of 52.2-61.3 years. Indications for surgery included radiculopathy (26.9%) and myelopathy (46.9%), with a predilection for involvement at C3-7 (24.9%). Meta-analysis yielded an overall complication rate of 16.258% (CI 95%: 14.823%-17.772%). Dysphagia (4.563%), haematoma (1.525%), hoarseness (0.205%), C5 palsy (0.176%) were the most prevalent complications of 4L ACDF. Fusion rates ranging from 41.3% to 94% were documented. CONCLUSION: The 4L ACDF is commonly performed to address mylopathy and radiculopathy. While the surgery carries a complication rate of around 16%, its effectiveness in achieving bone fusion can vary considerably.

Cauda equina, conus medullaris and syndromes mimicking sciatic pain: WFNS spine committee recommendations.

Introduction: Cauda equina syndrome (CES), conus medullaris syndrome (CMS), and sciatica-like syndromes or "sciatica mimics" (SM) may present as diagnostic and/or therapeutic dilemmas for the practicing spine surgeon. There is considerable controversy regarding the appropriate definition and diagnosis of these entities, as well as indications for and timing of surgery. Our goal is to formulate the most current, evidence-based recommendations for the definition, diagnosis, and management of CES, CMS, and SM syndromes. Methods: We performed a systematic literature search in PubMed from 2012 to 2022 using the keywords "cauda equina syndrome", "conus medullaris syndrome", "sciatica", and "sciatica mimics". Standardized screening criteria yielded a total of 43 manuscripts, whose data was summarized and presented at two international consensus meetings of the World Federation of Neurosurgical Societies (WFNS) Spine Committee. Utilizing the Delphi method, we generated seven final consensus statements. Results and conclusion: s: We provide standardized definitions of cauda equina, cauda equina syndrome, conus medullaris, and conus medullaris syndrome. We advocate for the use of the Lavy et al classification system to categorize different types of CES, and recommend urgent MRI in all patients with suspected CES (CESS), considering the low sensitivity of clinical examination in excluding CES. Surgical decompression for CES and CMS is recommended within 48 h, preferably within less than 24 h. There is no data regarding the role of steroids in acute CES or CMS. The treating physician should be cognizant of a variety of other pathologies that may mimic sciatica, including piriformis syndrome, and how to manage these.

Lumbar disc herniation: Epidemiology, clinical and radiologic diagnosis WFNS spine committee recommendations.

Objective: To formulate the most current, evidence-based recommendations regarding the epidemiology, clinical diagnosis, and radiographic diagnosis of lumbar herniated disk (LDH). Methods: A systematic literature search in PubMed, MEDLINE, and CENTRAL was performed from 2012 to 2022 using the search terms "herniated lumbar disc", "epidemiology", "prevention" "clinical diagnosis", and "radiological diagnosis". Screening criteria resulted in 17, 16, and 90 studies respectively that were analyzed regarding epidemiology, clinical diagnosis, and radiographic diagnosis of LDH. Using the Delphi method and two rounds of voting at two separate international meetings, ten members of the WFNS (World Federation of Neurosurgical Societies) Spine Committee generated eleven final consensus statements. Results: The lifetime risk for symptomatic LDH is 1-3%; of these, 60-90% resolve spontaneously. Risk factors for LDH include genetic and environmental factors, strenuous activity, and smoking. LDH is more common in males and in 30-50 year olds. A set of clinical tests, including manual muscle testing, sensory testing, Lasegue sign, and crossed Lasegue sign are recommended to diagnose LDH. Magnetic resonance imaging (MRI) is the gold standard for confirming suspected LDH. Conclusions: These eleven final consensus statements provide current, evidence-based guidelines on the epidemiology, clinical diagnosis, and radiographic diagnosis of LDH for practicing spine surgeons worldwide.

Augmented Reality Integration in Skull Base Neurosurgery: A Systematic Review.

Background and Objectives: To investigate the role of augmented reality (AR) in skull base (SB) neurosurgery. Materials and Methods: Utilizing PRISMA methodology, PubMed and Scopus databases were explored to extract data related to AR integration in SB surgery. Results: The majority of 19 included studies (42.1%) were conducted in the United States, with a focus on the last five years (77.8%). Categorization included phantom skull models (31.2%, n = 6), human cadavers (15.8%, n = 3), or human patients (52.6%, n = 10). Microscopic surgery was the predominant modality in 10 studies (52.6%). Of the 19 studies, surgical modality was specified in 18, with microscopic surgery being predominant (52.6%). Most studies used only CT as the data source (n = 9; 47.4%), and optical tracking was the prevalent tracking modality (n = 9; 47.3%). The Target Registration Error (TRE) spanned from 0.55 to 10.62 mm. Conclusion: Despite variations in Target Registration Error (TRE) values, the studies highlighted successful outcomes and minimal complications. Challenges, such as device practicality and data security, were acknowledged, but the application of low-cost AR devices suggests broader feasibility.

CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review.

This scoping review examines the use of CRISPR/Cas9 gene editing in glioblastoma (GBM), a predominant and aggressive brain tumor. Categorizing gene targets into distinct groups, this review explores their roles in cell cycle regulation, microenvironmental dynamics, interphase processes, and therapy resistance reduction. The complexity of CRISPR-Cas9 applications in GBM research is highlighted, providing unique insights into apoptosis, cell proliferation, and immune responses within the tumor microenvironment. The studies challenge conventional perspectives on specific genes, emphasizing the potential therapeutic implications of manipulating key molecular players in cell cycle dynamics. Exploring CRISPR/Cas9 gene therapy in GBMs yields significant insights into the regulation of cellular processes, spanning cell interphase, renewal, and migration. Researchers, by precisely targeting specific genes, uncover the molecular orchestration governing cell proliferation, growth, and differentiation during critical phases of the cell cycle. The findings underscore the potential of CRISPR/Cas9 technology in unraveling the complex dynamics of the GBM microenvironment, offering promising avenues for targeted therapies to curb GBM growth. This review also outlines studies addressing therapy resistance in GBM, employing CRISPR/Cas9 to target genes associated with chemotherapy resistance, showcasing its transformative potential in effective GBM treatments.

The New Era of Spinal Surgery: Exploring the Use of Exoscopes as a Viable Alternative to Operative Microscopes-A Systematic Review and Meta-Analysis.

BACKGROUND: The growing interest in exoscopic (EX) technology has prompted a comprehensive evaluation of its clinical, functional, and financial outcomes in neurosurgery. This systematic review and meta-analysis aimed to explore the utilization of EX in spine surgery and assess their safety, efficacy, and impact on surgical outcomes. METHODS: A thorough literature review was conducted using PubMed, Scopus, and Embase databases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study focused on articles concerning the application of EXs in spinal surgical procedures. The inclusion criteria encompassed various study designs presenting clinical data and intraoperative experiences related to EX utilization in spine surgery. RESULTS: The meta-analysis included studies examining various aspects of EX utilization, such as intraoperative complications, video/image quality, surgical field visualization, ease of manipulation, ergonomic characteristics, educational utility, surgical duration, and team involvement. Findings indicated that EXs offered superior video quality and favorable ergonomic features. Comparable outcomes were observed in surgical duration, intraoperative blood loss, time to discharge, and postoperative pain levels between EX and conventional microscope approaches. CONCLUSIONS: This study provides valuable insights into the utilization of EXs in spine surgery, demonstrating their potential advantages and comparable outcomes with conventional microscopes.

Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings.

This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, with a male-to-female ratio of 1.59/1), were analyzed. In laboratory studies, 52.52% primarily used human glioblastoma cell cultures (HCC), and 43.17% employed animal samples (mainly mice). Clinical participants ranged from 18 to 100 years, with 60.2% using combined therapies and 39.8% monotherapies. Mechanistic categories included Protein Kinase Phosphorylation (41.6%), Cell Cycle-Related Mechanisms (18.1%), Microenvironmental Targets (19.9%), Immunological Targets (4.2%), and Other Mechanisms (16.3%). Key molecular targets included Epidermal Growth Factor Receptor (EGFR) (10.8%), Mammalian Target of Rapamycin (mTOR) (7.2%), Vascular Endothelial Growth Factor (VEGF) (6.6%), and Mitogen-Activated Protein Kinase (MEK) (5.4%). This review provides a comprehensive assessment of molecular therapies for GBM, highlighting their varied efficacy in clinical and laboratory settings, ultimately impacting overall and progression-free survival in GBM management.

Breaking Barriers in Cranioplasty: 3D Printing in Low and Middle-Income Settings-Insights from Zenica, Bosnia and Herzegovina.

Background and Objectives: Cranial defects pose significant challenges in low and middle-income countries (LIMCs), necessitating innovative and cost-effective craniofacial reconstruction strategies. The purpose of this study was to present the Bosnia and Herzegovina model, showcasing the potential of a multidisciplinary team and 3D-based technologies, particularly PMMA implants, to address cranial defects in a resource-limited setting. Materials and Methods: An observational, non-experimental prospective investigation involved three cases of cranioplasty at the Department of Neurosurgery, Cantonal Hospital Zenica, Bosnia and Herzegovina, between 2019 and 2023. The technical process included 3D imaging and modeling with MIMICS software (version 10.01), 3D printing of the prototype, mold construction and intraoperative modification for precise implant fitting. Results: The Bosnia and Herzegovina model demonstrated successful outcomes in cranioplasty, with PMMA implants proving cost-effective and efficient in addressing cranial defects. Intraoperative modification contributed to reduced costs and potential complications, while the multidisciplinary approach and 3D-based technologies facilitated accurate reconstruction. Conclusions: The Bosnia and Herzegovina model showcases a cost-effective and efficient approach for craniofacial reconstruction in LIMICs. Collaborative efforts, 3D-based technologies, and PMMA implants contribute to successful outcomes. Further research is needed to validate sustained benefits and enhance craniofacial reconstruction strategies in resource-constrained settings.

Accessible Spinal Surgery: Transformation Through the Implementation of Exoscopes As Substitutes for Conventional Microsurgery in Low- and Middle-Income Settings.

Advancements in neurosurgical visualization have been made possible by the introduction of the operating microscope (OM) and the emergence of exoscopic technology (EX). Both OMs and EXs provide enhanced magnification and illumination, but they come with their own set of advantages and disadvantages. OMs provide high-quality magnification and illumination and have been used successfully in a variety of surgical procedures. They can be customized to fit the specific needs of the surgeon and are a well-established technology. However, they can be bulky, expensive, and cause discomfort during extended procedures. EXs provide high-definition magnification and illumination, improved depth perception and ergonomics, and can be cost-effective. They can be customized to fit the specific needs of the surgeon and can be made using locally available materials, reducing the need for expensive imports. However, they may require adjustment and have a learning curve for surgeons who are used to operating with OMs. Additionally, they may have limited availability in some healthcare settings. The choice between OMs and EXs will depend on the specific needs of the surgeon and the healthcare setting. The integration of 3D EX systems has revolutionized neurosurgery, offering improved depth perception and ergonomics. EX's cost-effectiveness addresses accessibility concerns, making it an attractive alternative, particularly for low and middle-income healthcare settings. The exoscope seems to be a safe alternative compared to an operative microscope for the most common brain and spinal procedures. The exoscope may help expand access to neurosurgical care and training worldwide. In conclusion, both technologies have their own set of advantages and disadvantages, and the choice between them will depend on the specific needs of the surgeon and the healthcare setting.

Adult Chiari Malformation Type I: Surgical Anatomy, Microsurgical Technique, and Patient Outcomes.

In this study, the authors summarize the current knowledge on epidemiology, demographics, risk factors, and prognostic factors that influence outcomes in patients with adult Chiari malformation type I (CM-I) who underwent posterior fossa decompression surgery with duraplasty. Furthermore, they describe the contribution of their research group to the field of adult CM-I treatment, including association of increased body mass index with severity of CM-I and syringomyelia, relevant surgical anatomy, and surgical technique of 270° microsurgical decompression of foramen magnum. The authors also report on common complications in the literature and describe techniques for prevention of complications.

Spontaneous Bleeding in Vestibular Schwannoma in Patients on Oral Anticoagulant Therapy: Report of Two Cases and Review of Literature.

OBJECTIVE: Anticoagulant therapy is a risk factor for repeated intratumoral hemorrhage and acute enlargement of a vestibular schwannoma (VS) with neurological deficits. Therefore, we describe two cases of patients on oral anticoagulant therapy with intratumoral hemorrhage in which anticoagulant therapy prior to surgical resection was discontinued. We also discuss other similar cases from the literature since this is a rare event. CASE REPORTS: We described the two cases of intratumoral hemorrhage in acoustic neurinoma and conducted a literature review of similar cases of patients with intratumoral hemorrhage in acoustic neurinoma who were also on oral anticoagulants. Both patients presented with CN-VII palsy prior to surgery; both also fully re-covered after surgery except for hearing loss on the tumor side. Our literature review found 50 cases of VS (reported as vestibular schwannomas in the literature) with intratumoral hemorrhage. From this total, 11 patients used oral anticoagulant therapy with reported poor outcomes and high mortality; 9 of these 11 cases were reported in the past 20 years. The incidence is expected to rise due to increased use of anticoagulant therapy due to onset of atrial fibrillation, atherosclerosis, and thromboembolism from longer human lifespan. CONCLUSION: Anticoagulant therapy represents a risk factor for intratumoral hemorrhage and acute enlargement of VS tumor mass with neurological deficits.

Augmented Reality to Compensate for Navigation Inaccuracies.

This study aims to report on the capability of microscope-based augmented reality (AR) to evaluate registration and navigation accuracy with extracranial and intracranial landmarks and to elaborate on its opportunities and obstacles in compensation for navigation inaccuracies. In a consecutive single surgeon series of 293 patients, automatic intraoperative computed tomography-based registration was performed delivering a high initial registration accuracy with a mean target registration error of 0.84 ± 0.36 mm. Navigation accuracy is evaluated by overlaying a maximum intensity projection or pre-segmented object outlines within the recent focal plane onto the in situ patient anatomy and compensated for by translational and/or rotational in-plane transformations. Using bony landmarks (85 cases), there was two cases where a mismatch was seen. Cortical vascular structures (242 cases) showed a mismatch in 43 cases and cortex representations (40 cases) revealed two inaccurate cases. In all cases, with detected misalignment, a successful spatial compensation was performed (mean correction: bone (6.27 ± 7.31 mm), vascular (3.00 ± 1.93 mm, 0.38° ± 1.06°), and cortex (5.31 ± 1.57 mm, 1.75° ± 2.47°)) increasing navigation accuracy. AR support allows for intermediate and straightforward monitoring of accuracy, enables compensation of spatial misalignments, and thereby provides additional safety by increasing overall accuracy.

Use of Neuronavigation and Augmented Reality in Transsphenoidal Pituitary Adenoma Surgery.

The aim of this study was to report on the clinical experience with microscope-based augmented reality (AR) in transsphenoidal surgery compared to the classical microscope-based approach. AR support was established using the head-up displays of the operating microscope, with navigation based on fiducial-/surface- or automatic intraoperative computed tomography (iCT)-based registration. In a consecutive single surgeon series of 165 transsphenoidal procedures, 81 patients underwent surgery without AR support and 84 patients underwent surgery with AR support. AR was integrated straightforwardly within the workflow. ICT-based registration increased AR accuracy significantly (target registration error, TRE, 0.76 ± 0.33 mm) compared to the landmark-based approach (TRE 1.85 ± 1.02 mm). The application of low-dose iCT protocols led to a significant reduction in applied effective dosage being comparable to a single chest radiograph. No major vascular or neurological complications occurred. No difference in surgical time was seen, time to set-up patient registration prolonged intraoperative preparation time on average by twelve minutes (32.33 ± 13.35 vs. 44.13 ± 13.67 min), but seems justifiable by the fact that AR greatly and reliably facilitated surgical orientation and increased surgeon comfort and patient safety, not only in patients who had previous transsphenoidal surgery but also in cases with anatomical variants. Automatic intraoperative imaging-based registration is recommended.

Dynamics in the Neurotrauma Catchment Area of a German University Hospital during the COVID-19 Pandemic.

Objective: At the beginning of 2020, the COVID-19 pandemic enforced a rapid reallocation of healthcare resources. Our neurosurgical department is located in the German county of Marburg−Biedenkopf, about 80 km from the nearest major city. We were able to maintain our previously established open-door policy after the emergence of COVID-19. Here, we report on dynamics in the catchment area for neurotrauma patients at our department during the pandemic. Methods: 763 consecutive neurotrauma cases admitted to our department between 1 January 2018 and 31 December 2021 were analyzed retrospectively. Patients' age, gender, origin, diagnoses, and outcomes were recorded. The number of patients hospitalized with a COVID-19 infection in Germany (PHCG) were retrieved from the Robert Koch Institute (RKI). We defined calendar weeks with >1000 PHCG as high COVID-19 caseload weeks (HCLW). Chi-square and Fisher's exact served as statistical tests. Results: In 2020 and 2021, we observed a significantly increased number of neurotrauma patients who, with primary residence outside of our district, were admitted to our hospital compared to 2018 and 2019 (p < 0.001), while there were no significant differences in in-house mortality. During HCLW, a significantly increased number of neurotrauma patients with primary residence in the densely populated southwestern margin (SWM) of the contiguous part of our catchment area were referred to us compared to the time prior to the pandemic and between HCLW (p = 0.003). In neurotrauma patients admitted from the SWM during HCLW, there was no tendency towards higher in-house mortality. Conclusion: An open-door policy may moderate the risk of involuntarily triaging neurotrauma patients during a pandemic.

Microscope-Based Augmented Reality with Intraoperative Computed Tomography-Based Navigation for Resection of Skull Base Meningiomas in Consecutive Series of 39 Patients.

BACKGROUND: The aim of surgery for skull base meningiomas is maximal resection with minimal damage to the involved cranial nerves and cerebral vessels; thus, implementation of technologies for improved orientation in the surgical field, such as neuronavigation and augmented reality (AR), is of interest. METHODS: Included in the study were 39 consecutive patients (13 male, 26 female, mean age 64.08 ± 13.5 years) who underwent surgery for skull base meningiomas using microscope-based AR and automatic patient registration using intraoperative computed tomography (iCT). RESULTS: Most common were olfactory meningiomas (6), cavernous sinus (6) and clinoidal (6) meningiomas, meningiomas of the medial (5) and lateral (5) sphenoid wing and meningiomas of the sphenoidal plane (5), followed by suprasellar (4), falcine (1) and middle fossa (1) meningiomas. There were 26 patients (66.6%) who underwent gross total resection (GTR) of the meningioma. Automatic registration applying iCT resulted in high accuracy (target registration error, 0.82 ± 0.37 mm). The effective radiation dose of the registration iCT scans was 0.58 ± 1.05 mSv. AR facilitated orientation in the resection of skull base meningiomas with encasement of cerebral vessels and compression of the optic chiasm, as well as in reoperations, increasing surgeon comfort. No injuries to critical neurovascular structures occurred. Out of 35 patients who lived to follow-up, 33 could ambulate at their last presentation. CONCLUSION: A microscope-based AR facilitates surgical orientation for resection of skull base meningiomas. Registration accuracy is very high using automatic registration with intraoperative imaging.

Navigated Intraoperative 3D Ultrasound in Glioblastoma Surgery: Analysis of Imaging Features and Impact on Extent of Resection.

Background: Neuronavigation is routinely used in glioblastoma surgery, but its accuracy decreases during the operative procedure due to brain shift, which can be addressed utilizing intraoperative imaging. Intraoperative ultrasound (iUS) is widely available, offers excellent live imaging, and can be fully integrated into modern navigational systems. Here, we analyze the imaging features of navigated i3D US and its impact on the extent of resection (EOR) in glioblastoma surgery. Methods: Datasets of 31 glioblastoma resection procedures were evaluated. Patient registration was established using intraoperative computed tomography (iCT). Pre-operative MRI (pre-MRI) and pre-resectional ultrasound (pre-US) datasets were compared regarding segmented tumor volume, spatial overlap (Dice coefficient), the Euclidean distance of the geometric center of gravity (CoG), and the Hausdorff distance. Post-resectional ultrasound (post-US) and post-operative MRI (post-MRI) tumor volumes were analyzed and categorized into subtotal resection (STR) or gross total resection (GTR) cases. Results: The mean patient age was 59.3 ± 11.9 years. There was no significant difference in pre-resectional segmented tumor volumes (pre-MRI: 24.2 ± 22.3 cm3; pre-US: 24.0 ± 21.8 cm3). The Dice coefficient was 0.71 ± 0.21, the Euclidean distance of the CoG was 3.9 ± 3.0 mm, and the Hausdorff distance was 12.2 ± 6.9 mm. A total of 18 cases were categorized as GTR, 10 cases were concordantly classified as STR on MRI and ultrasound, and 3 cases had to be excluded from post-resectional analysis. In four cases, i3D US triggered further resection. Conclusion: Navigated i3D US is reliably adjunct in a multimodal navigational setup for glioblastoma resection. Tumor segmentations revealed similar results in i3D US and MRI, demonstrating the capability of i3D US to delineate tumor boundaries. Additionally, i3D US has a positive influence on the EOR, allows live imaging, and depicts brain shift.

The Metalloprotease-Disintegrin ADAM8 Alters the Tumor Suppressor miR-181a-5p Expression Profile in Glioblastoma Thereby Contributing to Its Aggressiveness.

Glioblastoma (GBM) as the most common and aggressive brain tumor is characterized by genetic heterogeneity, invasiveness, radio-/chemoresistance, and occurrence of GBM stem-like cells. The metalloprotease-disintegrin ADAM8 is highly expressed in GBM tumor and immune cells and correlates with poor survival. In GBM, ADAM8 affects intracellular kinase signaling and increases expression levels of osteopontin/SPP1 and matrix metalloproteinase 9 (MMP9) by an unknown mechanism. Here we explored whether microRNA (miRNA) expression levels could be regulators of MMP9 expression in GBM cells expressing ADAM8. Initially, we identified several miRNAs as dysregulated in ADAM8-deficient U87 GBM cells. Among these, the tumor suppressor miR-181a-5p was significantly upregulated in ADAM8 knockout clones. By inhibiting kinase signaling, we found that ADAM8 downregulates expression of miR-181a-5p via activation of signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) signaling suggesting an ADAM8-dependent silencing of miR-181a-5p. In turn, mimic miR-181a-5p transfection caused decreased cell proliferation and lower MMP9 expression in GBM cells. Furthermore, miR-181a-5p was detected in GBM cell-derived extracellular vesicles (EVs) as well as patient serum-derived EVs. We identified miR-181a-5p downregulating MMP9 expression via targeting the MAPK pathway. Analysis of patient tissue samples (n=22) revealed that in GBM, miR-181a-5p is strongly downregulated compared to ADAM8 and MMP9 mRNA expression, even in localized tumor areas. Taken together, we provide evidence for a functional axis involving ADAM8/miR-181a-5p/MAPK/MMP9 in GBM tumor cells.

Radiogenomic Predictors of Recurrence in Glioblastoma-A Systematic Review.

Glioblastoma, as the most aggressive brain tumor, is associated with a poor prognosis and outcome. To optimize prognosis and clinical therapy decisions, there is an urgent need to stratify patients with increased risk for recurrent tumors and low therapeutic success to optimize individual treatment. Radiogenomics establishes a link between radiological and pathological information. This review provides a state-of-the-art picture illustrating the latest developments in the use of radiogenomic markers regarding prognosis and their potential for monitoring recurrence. Databases PubMed, Google Scholar, and Cochrane Library were searched. Inclusion criteria were defined as diagnosis of glioblastoma with histopathological and radiological follow-up. Out of 321 reviewed articles, 43 articles met these inclusion criteria. Included studies were analyzed for the frequency of radiological and molecular tumor markers whereby radiogenomic associations were analyzed. Six main associations were described: radiogenomic prognosis, MGMT status, IDH, EGFR status, molecular subgroups, and tumor location. Prospective studies analyzing prognostic features of glioblastoma together with radiological features are lacking. By reviewing the progress in the development of radiogenomic markers, we provide insights into the potential efficacy of such an approach for clinical routine use eventually enabling early identification of glioblastoma recurrence and therefore supporting a further personalized monitoring and treatment strategy.