Abstract Modern glioma surgery has evolved from the principle belief that safe, maximal tumor resection improves symptom management, quality of life, progression-free survival (PFS), and overall ...survival (OS) in both low- and high-grade glioma (LGG and HGG, respectively). However, in the absence of level I data, the overwhelming support for this idea is derived largely from retrospective series. As a result, the influence of increasing extent of resection (EOR) and reducing tumor burden on the efficacy of postoperative chemotherapy and radiotherapy, and ultimately survival, remains inadequately defined. This is particularly true as gliomas represent a widely heterogeneous group of tumors with varying behaviors and prognoses rooted in their complex molecular profile. The neurosurgical community has put forth a large effort to define the clinical benefits of maximizing tumor resection, with particular attention paid to the ever-evolving understanding of glioma molecular heterogeneity. Important new technologies have been developed concurrently to mitigate neurological risks related to the pursuit of maximizing EOR. These advances reflect the modern goal of glioma surgery to find the optimal balance between tumor removal and neurologic compromise. We review the current literature supporting safe, maximal resection for gliomas.
Drug delivery in diffuse intrinsic pontine glioma is significantly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), when combined with the administration of microbubbles can ...effectively open the BBB permitting the entry of drugs across the cerebrovasculature into the brainstem. Given that the utility of FUS in brainstem malignancies remains unknown, the purpose of our study was to determine the safety and feasibility of this technique in a murine pontine glioma model. A syngeneic orthotopic model was developed by stereotactic injection of PDGF-B
PTEN
p53
murine glioma cells into the pons of B6 mice. A single-element, spherical-segment 1.5 MHz ultrasound transducer driven by a function generator through a power amplifier was used with concurrent intravenous microbubble injection for tumor sonication. Mice were randomly assigned to control, FUS and double-FUS groups. Pulse and respiratory rates were continuously monitored during treatment. BBB opening was confirmed with gadolinium-enhanced MRI and Evans blue. Kondziela inverted screen testing and sequential weight lifting measured motor function before and after sonication. A subset of animals were treated with etoposide following ultrasound. Mice were either sacrificed for tissue analysis or serially monitored for survival with daily weights. FUS successfully caused BBB opening while preserving normal cardiorespiratory and motor function. Furthermore, the degree of intra-tumoral hemorrhage and inflammation on H&E in control and treated mice was similar. There was also no difference in weight loss and survival between the groups (p > 0.05). Lastly, FUS increased intra-tumoral etoposide concentration by more than fivefold. FUS is a safe and feasible technique for repeated BBB opening and etoposide delivery in a preclinical pontine glioma model.
Abstract Intradural spinal metastases significantly impair neurological function and quality of life, necessitating multimodal, palliative management to preserve mobility and alleviate pain. The ...effectiveness of systemic chemotherapy and radiotherapy is limited due to the blood-spinal cord barrier and the tumours’ radioresistance, respectively. This highlights the urgency for alternative treatments given the rapid neurological decline. Surgical intervention becomes crucial, focusing on maximum tumour debulking to enhance disease control, restore ambulation, and palliate symptoms without compromising neurological function. Achieving this involves meticulous preoperative planning and aggressive intraoperative neuromonitoring. Combining surgery with adjuvant therapies may improve local control and potentially delay recurrence. This case-based review emphasizes the surgical considerations and outcomes in two cases of intradural spinal metastases, underscoring the value of surgery in multimodal therapy.
Malignant Glioma Wang, Linda M; Englander, Zachary K; Miller, Michael L ...
Advances in experimental medicine and biology,
2023, Letnik:
1405
Journal Article
Recenzirano
This chapter provides a comprehensive overview of malignant gliomas, the most common primary brain tumor in adults. These tumors are varied in their cellular origin, genetic profile, and morphology ...under the microscope, but together they share some of the most dismal prognoses of all neoplasms in the body. Although there is currently no cure for malignant glioma, persistent efforts to improve outcomes in patients with these tumors have led to modest increases in survival, and researchers worldwide continue to strive toward a deeper understanding of the factors that influence glioma development and response to treatment. In addition to well-established epidemiology, clinical manifestations, and common histopathologic and radiologic features of malignant gliomas, this section considers recent advances in molecular biology that have led to a more nuanced understanding of the genetic changes that characterize the different types of malignant glioma, as well as their implications for treatment. Beyond the traditional classification of malignant gliomas based on histopathological features, this chapter incorporates the World Health Organization's 2016 criteria for the classification of brain tumors, with special focus on disease-defining genetic alterations and newly established subcategories of malignant glioma that were previously unidentifiable based on microscopic examination alone. Traditional therapeutic modalities that form the cornerstone of treatment for malignant glioma, such as aggressive surgical resection followed by adjuvant chemotherapy and radiation therapy, and the studies that support their efficacy are reviewed in detail. This provides a foundation for additional discussion of novel therapeutic methods such as immunotherapy and convection-enhanced delivery, as well as new techniques for enhancing extent of resection such as fluorescence-guided surgery.
Abstract
BACKGROUND
Accurate tissue sampling in nonenhancing (NE) gliomas is a unique surgical challenge due to their intratumoral histological heterogeneity and absence of contrast enhancement as a ...guide for intraoperative stereotactic guidance. Instead, T2/fluid-attenuated inversion-recovery (FLAIR) hyperintensity on MRI is commonly used as an imaging surrogate for pathological tissue, but sampling from this region can yield nondiagnostic or underdiagnostic brain tissue. Sodium fluorescein is an intraoperative fluorescent dye that has a high predictive value for tumor identification in areas of contrast enhancement and NE in glioblastomas. However, the underlying histopathological alterations in fluorescent regions of NE gliomas remain undefined.
OBJECTIVE
To evaluate whether fluorescein can identify diagnostic tissue and differentiate regions with higher malignant potential during surgery for NE gliomas, thus improving sampling accuracy.
METHODS
Thirteen patients who presented with NE, T2/FLAIR hyperintense lesions suspicious for glioma received fluorescein (10%, 3 mg/kg intravenously) during surgical resection.
RESULTS
Patchy fluorescence was identified within the T2/FLAIR hyperintense area in 10 of 13 (77%) patients. Samples taken from fluorescent regions were more likely to demonstrate diagnostic glioma tissue and cytologic atypia (P < .05). Fluorescein demonstrated a 95% positive predictive value for the presence of diagnostic tissue. Samples from areas of fluorescence also demonstrated greater total cell density and higher Ki-67 labeling than nonfluorescent biopsies (P < .05).
CONCLUSION
Fluorescence in NE gliomas is highly predictive of diagnostic tumor tissue and regions of higher cell density and proliferative activity.
Purpose To determine the effect that R132H mutation status of diffuse glioma has on extent of vascular dysregulation and extent of residual blood oxygen level-dependent (BOLD) abnormality after ...surgical resection. Materials and Methods This study was an institutional review board-approved retrospective analysis of an institutional database of patients, and informed consent was waived. From 2010 to 2017, 39 treatment-naïve patients with diffuse glioma underwent preoperative echo-planar imaging and BOLD functional magnetic resonance imaging. BOLD vascular dysregulation maps were made by identifying voxels with time series similar to tumor and dissimilar to healthy brain. The spatial overlap between tumor and vascular dysregulation was characterized by using the Dice coefficient, and areas of BOLD abnormality outside the tumor margins were quantified as BOLD-only fraction (BOF). Linear regression was used to assess effects of R132H status on the Dice coefficient, BOF, and residual BOLD abnormality after surgical resection. Results When compared with R132H wild-type (R132H-) gliomas, R132H-mutated (R132H+) gliomas showed greater spatial overlap between BOLD abnormality and tumor (mean Dice coefficient, 0.659 ± 0.02 standard error for R132H+ and 0.327 ± 0.04 for R132H-; P < .001), less BOLD abnormality beyond the tumor margin (mean BOF, 0.255 ± 0.03 for R132H+ and 0.728 ± 0.04 for R132H-; P < .001), and less postoperative BOLD abnormality (residual fraction, 0.046 ± 0.0047 for R132H+ and 0.397 ± 0.045 for R132H-; P < .001). Receiver operating characteristic curve analysis showed high sensitivity and specificity in the discrimination of R132H+ tumors from R132H- tumors with calculation of both Dice coefficient and BOF (area under the receiver operating characteristic curve, 0.967 and 0.977, respectively). Conclusion R132H mutation status is an important variable affecting the extent of tumor-associated vascular dysregulation and the residual vascular dysregulation after surgical resection.
RSNA, 2018 Online supplemental material is available for this article.
Subependymomas are infrequent, low-grade gliomas associated with the ventricular system and the spinal cord. Little is known about the origin and natural history of these slow-growing lesions.
We ...identified all patients with pathologically proven subependymomas presenting to our institution between 1998 and 2016. We retrospectively reviewed clinical, radiographic, histologic, and surgical outcomes data in all patients who underwent surgical resection. Immunohistochemical analyses for cell lineage markers were performed.
A total of 31 patients with pathologically proven subependymomas were identified. Of these, 7 asymptomatic lesions were discovered at autopsy and 24 symptomatic cases were treated surgically. There were 15 (48%) lateral ventricle tumors, 11 (35%) fourth ventricular tumors, and 5 (17%) spinal tumors. Symptomatic intracranial lesions most commonly presented with headaches and balance and gait abnormalities. Subependymomas had no distinguishing radiographic features that provided definitive preoperative diagnosis. At last follow-up, no patient treated surgically experienced recurrence. Immunohistochemical analyses demonstrated a diffusely GFAP-positive glial neoplasm with mixed populations of cells that were variably positive for Olig2, NHERF1, Sox2, and CD44. The Ki67 proliferation index was generally low (<1% in many of the tumors).
Subependymomas demonstrate mixed populations of cells expressing glial lineage markers as well as putative stem cell markers, suggesting these tumors may arise from multipotent glial progenitors that reside in the subventricular zone. Definitive diagnosis requires surgical sampling. Although the clinical course of subependymomas appears benign, the inability to radiographically diagnose these lesions, and the possibility of an alternative malignant lesion support a low threshold for early and safe maximal resection.
Abstract
INTRODUCTION
Mutation of the isocitrate dehydrogenase 1 (IDH1) gene is an important prognostic marker in diffuse gliomas. IDH1 wild-type tumors have worse clinical outcomes and more invasive ...imaging features than their IDH1 mutant counterparts. However, the degree of glioma infiltration outside radiologically-defined tumor borders has not been quantified. Blood oxygenation level dependent (BOLD) fMRI can detect glioma-induced disruption of normal vascular regulatory function that occurs beyond conventional tumor margins. The present study quantifies the spatial extent of vascular dysregulation associated with IDH1 mutation status in patients with treatment-naïve diffuse gliomas. We hypothesized that IDH1 wild-type gliomas will have larger areas of BOLD signal abnormality in the surrounding brain tissue and will ultimately demonstrate greater residual disease following surgical resection of the tumor.
METHODS
BOLD maps of vascular dysregulation were generated from preoperative fMRI scans of 34 treatment-naïve patients with WHO grades II-IV gliomas. IDH1 mutation status was determined by immunohistochemical staining for the mutant IDH1 R132H protein. We directly compared the spatial overlap of vascular dysregulation measured by BOLD fMRI and the radiologically-defined tumor using the Dice coefficient. We also performed a regression analysis to compare the relationship between percent of tumor resected and fraction of residual BOLD abnormality.
RESULTS
>The BOLD abnormality extended further beyond the tumor margins in IDH1 wild-type gliomas than in IDH1 mutants (P = 2 × 10−8). Furthermore, after controlling for patient age, histological subtype, WHO grade, and 1p/19q co-deletion status, IDH1 mutation status remained a significant predictor of the extent of vascular dysregulation beyond the tumor margins (P = 0.0001). Finally, surgical resection eliminated a smaller fraction of the BOLD abnormality in IDH1 wild-type tumors (P = 0.0016).
CONCLUSION
IDH1 mutation status is a critical variable affecting extent of infiltration and the volume of residual disease following surgical resection. BOLD fMRI may be clinically useful for guiding extent of resection in diffuse gliomas.
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