Search Results (9)

Gliomas present a complex challenge in neuro-oncology, often accompanied by the debilitating complication of epilepsy. Understanding the biological interaction and common pathways between gliomagenesis and epileptogenesis is crucial for improving the current understanding of tumorigenesis and also for developing effective management strategies. Shared genetic and molecular mechanisms, such as IDH mutations and dysregulated glutamate signaling, contribute to both tumor progression and seizure development. Targeting these pathways, such as through direct inhibition of mutant IDH enzymes or modulation of glutamate receptors, holds promise for improving patient outcomes. Additionally, advancements in surgical techniques, like supratotal resection guided by connectomics, offer opportunities for maximally safe tumor resection and enhanced seizure control. Advanced imaging modalities further aid in identifying epileptogenic foci and tailoring treatment approaches based on the tumor’s metabolic characteristics. This review aims to explore the complex interplay between gliomagenesis, epileptogenesis, and neural circuit remodeling, offering insights into shared molecular pathways and innovative treatment strategies to improve outcomes for patients with gliomas and associated epilepsy. Full article

Low-grade gliomas (LGGs) are optimally treated with up-front maximal safe surgical resection, typically defined as maximizing the extent of tumor resection while minimizing neurologic risks of surgery. Supratotal resection of LGG may improve outcomes beyond gross total resection by removing tumor cells invading beyond the tumor border as defined on MRI. However, the evidence regarding supratotal resection of LGG, in terms of impact on clinical outcomes, such as overall survival and neurologic morbidities, remains unclear. Authors independently searched the PubMed, Medline, Ovid, CENTRAL (Cochrane Central Register of Controlled Trials), and Google Scholar databases for studies evaluating overall survival, time to progression, seizure outcomes, and postoperative neurologic and medical complications of supratotal resection/FLAIRectomy of WHO-defined LGGs. Papers in languages other than English, lacking full-text availability, evaluating supratotal resection of WHO-defined high-grade gliomas only, and nonhuman studies were excluded. After literature search, reference screening, and initial exclusions, 65 studies were screened for relevancy, of which 23 were evaluated via full-text review, and 10 were ultimately included in the final evidence review. Studies were evaluated for quality using the MINORS criteria. After data extraction, a total of 1301 LGG patients were included in the analysis, with 377 (29.0%) undergoing supratotal resection. The main measured outcomes were extent of resection, pre- and postoperative neurological deficits, seizure control, adjuvant treatment, neuropsychological outcomes, ability to return to work, progression-free survival, and overall survival. Overall, low- to moderate-quality evidence was supportive of aggressive, functional boundary-based resection of LGGs due to improvements in progression-free survival and seizure control. The published literature provides a moderate amount of low-quality evidence supporting supratotal surgical resection along functional boundaries for low-grade glioma. Among patients included in this analysis, the occurrence of postoperative neurological deficits was low, and nearly all patients recovered within 3 to 6 months after surgery. Notably, the surgical centers represented in this analysis have significant experience in glioma surgery in general, and supratotal resection specifically. In this setting, supratotal surgical resection along functional boundaries appears to be appropriate for both symptomatic and asymptomatic low-grade glioma patients. Larger clinical studies are needed to better define the role of supratotal resection in LGG. Full article

Background: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults; despite advances in the understanding of GBM pathogenesis, significant achievements in treating this disease are still lacking. The aim of this study was to evaluate the prognostic significance of the extent of surgical resection (EOR), beyond the neoplastic mass, on the overall survival (OS). Methods: A retrospective review of a single-institution glioblastoma patient database (January 2012–September 2021) was undertaken. The series is composed of 64 patients who underwent surgery at the University Department of Neurosurgery of Ancona; the series was divided into four groups based on the amount of tumor mass excision with the fluid-attenuated inversion recovery (FLAIR) abnormalities (SUPr-supratotal resection, GTR-gross total resection, STR-subtotal resection, BIOPSY). The hypothesis was that the maximal resection of FLAIR abnormalities may improve the overall survival compared to the resection of the visible T1 contrast-enhanced neoplastic area only. Results: In the univariate analysis, SUPr and GTR are correlated with the overall survival (p = 0.001); the percentage of total neoplastic removal threshold conditioning outcome was 90% (p = 0.027). These results were confirmed by the multivariate analysis. Conclusions: Maximal surgical resection, when feasible, involving areas of FLAIR abnormalities represents an advantageous approach for the OS in GBM patients. Full article

Objective: Supratotal resection (SupTR) of glioblastoma allows for a superior long-term disease control and increases overall survival. On the other hand, aggressive conventional approaches, including gross total resections (GTR), are limited by the impairment risk of adjacent eloquent areas, which may cause severe postoperative functional morbidity. This study aimed to analyze institutional cases with respect to the potential survival benefits of additional resection, including lobectomy, as a paradigm for SupTR in patients of glioblastoma. Methods: Between 2014 and 2018, 15 patients with glioblastoma underwent SupTR (GTR and additional lobectomy) at the authors’ institution. The postoperative Karnofsky performance score (KPS), progression-free survival (PFS), and overall survival (OS) were analyzed for the patients. Results: Patients with SupTR showed significantly prolonged PFS and OS. The median PFS and OS values for the entire study group were 33.5 months (95% confidence intervals (CI): 18.5–57.3 months) and 49.1 months (95% CI: 24.7–86.6 months), respectively. Multivariate analysis revealed that the O6-DNA-methylguanine methyltransferase (MGMT) promoter methylation status was the only predictor for both superior PFS (p = 0.03, OR 5.7, 95% CI 1.0–49.8) and OS (p = 0.04, OR 6.5, 95% CI 1.1–40.2). There was no significant difference between the pre- and postoperative KPS scores. Conclusions: Our results suggest that SupTR with lobectomy allows for a superior PFS and OS without negatively affecting patient performance. However, due to the small number of patients, further studies that include more patients are needed. Full article

Diffuse low-grade gliomas (DLGGs) are heterogeneous and poorly circumscribed neoplasms with isolated tumor cells that extend beyond the margins of the lesion depicted on MRI. Efforts to demarcate the glioma core from the surrounding healthy brain led us to define an intermediate region, the so-called peritumoral zone (PTZ). Although most studies about PTZ have been conducted on high-grade gliomas, the purpose here is to review the cellular, metabolic, and radiological characteristics of PTZ in the specific context of DLGG. A better delineation of PTZ, in which glioma cells and neural tissue strongly interact, may open new therapeutic avenues to optimize both functional and oncological results. First, a connectome-based “supratotal” surgical resection (i.e., with the removal of PTZ in addition to the tumor core) resulted in prolonged survival by limiting the risk of malignant transformation, while improving the quality of life, thanks to a better control of seizures. Second, the timing and order of (neo)adjuvant medical treatments can be modulated according to the pattern of peritumoral infiltration. Third, the development of new drugs specifically targeting the PTZ could be considered from an oncological (such as immunotherapy) and epileptological perspective. Further multimodal investigations of PTZ are needed to maximize long-term outcomes in DLGG patients. Full article

Background: Although awake resection using intraoperative cortico-subcortical functional brain mapping is the benchmark technique for diffuse gliomas within eloquent brain areas, it is still rarely proposed for IDH-wildtype glioblastomas. We have assessed the feasibility, safety, and efficacy of awake resection for IDH-wildtype glioblastomas. Methods: Observational single-institution cohort (2012–2018) of 453 adult patients harboring supratentorial IDH-wildtype glioblastomas who benefited from awake resection, from asleep resection, or from a biopsy. Case matching (1:1) criteria between the awake group and asleep group: gender, age, RTOG-RPA class, tumor side, location and volume and neurosurgeon experience. Results: In patients in the awake resection subgroup (n = 42), supratotal resections were more frequent (21.4% vs. 3.1%, p < 0.0001) while partial resections were less frequent (21.4% vs. 40.1%, p < 0.0001) compared to the asleep (n = 222) resection subgroup. In multivariable analyses, postoperative standard radiochemistry (aHR = 0.04, p < 0.0001), supratotal resection (aHR = 0.27, p = 0.0021), total resection (aHR = 0.43, p < 0.0001), KPS score > 70 (HR = 0.66, p = 0.0013), MGMT promoter methylation (HR = 0.55, p = 0.0031), and awake surgery (HR = 0.54, p = 0.0156) were independent predictors of overall survival. After case matching, a longer overall survival was found for awake resection (HR = 0.47, p = 0.0103). Conclusions: Awake resection is safe, allows larger resections than asleep surgery, and positively impacts overall survival of IDH-wildtype glioblastoma in selected adult patients. Full article

(1) Background: We investigated the role of [11C]-methionine PET in a cohort of newly diagnosed glioblastoma multiforme (GBM) patients to evaluate whether it could modify the extent of surgical resection and improve radiation therapy volume delineation. (2) Methods: Newly diagnosed GBM patients, ages 18–70, with a Karnofsky performance scale (KPS) ≥ 70 with available MRI and [11C]-methionine PET were included. Patients were treated with different amounts of surgical resection followed by radio-chemotherapy. The role of [11C]-methionine PET in surgical and RT planning was analyzed. A threshold of SUVmax was searched. (3) Results: From August 2013 to April 2016, 93 patients were treated and included in this analysis. Residual tumor volume was detected in 63 cases on MRI and in 78 on [11C]-methionine PET, including 15 receiving gross total resection. The location of uptake was mainly observed in FLAIR abnormalities. [11C]-methionine uptake changed RT volume in 11% of patients. The presence of [11C]-methionine uptake in patients receiving GTR proved to influence survival (p = 0.029). The threshold of the SUVmax conditioning outcome was five. (4) Conclusions: [11C]-methionine PET allowed to detect areas at higher risk of recurrence located in FLAIR abnormalities in patients affected by GBM. A challenging issue is represented by integrating morphological and functional imaging to better define the extent of surgical resection to perform. Full article

Cellular composition and molecular signatures of the glioma core compared with infiltrative margins are different, and it is well known that the tumor edge is enriched in microglia. In this review of the literature, we summarize the role of the peritumoral area in high-grade gliomas (HGGs) from surgical and biological points of view. There is evidence on the dual role of microglia in HGGs—a scavenger-tumoricidal role when microglia are activated in an M1 phenotype and a role favoring tumor growth and infiltration/migration when microglia are activated in an M2 phenotype. Microglia polarization is mediated by complex pathways involving cross-talk with glioma cells. In this scenario, extracellular vesicles and their miRNA cargo seem to play a central role. The switch to a specific phenotype correlates with prognosis and the pathological assessment of a specific microglial setting can predict a patient’s outcome. Some authors have designed an engineered microglial cell as a biologically active vehicle for the delivery of intraoperative near-infrared fluorescent dye with the aim of helping surgeons detect peritumoral infiltrated areas during resection. Furthermore, the pharmacological modulation of microglia-glioma cross-talk paves the way to more effective therapies. Full article

The primary treatment for malignant brain tumors is surgical resection. While gross total resection improves the prognosis, a supratotal resection may result in neurological deficits. On the other hand, accurate intraoperative identification of the tumor boundaries may be very difficult, resulting in subtotal resections. Histological examination of biopsies can be used repeatedly to help achieve gross total resection but this is not practically feasible due to the turn-around time of the tissue analysis. Therefore, intraoperative techniques to recognize tissue types are investigated to expedite the clinical workflow for tumor resection and improve outcome by aiding in the identification and removal of the malignant lesion. Hyperspectral imaging (HSI) is an optical imaging technique with the power of extracting additional information from the imaged tissue. Because HSI images cannot be visually assessed by human observers, we instead exploit artificial intelligence techniques and leverage a Convolutional Neural Network (CNN) to investigate the potential of HSI in twelve in vivo specimens. The proposed framework consists of a 3D–2D hybrid CNN-based approach to create a joint extraction of spectral and spatial information from hyperspectral images. A comparison study was conducted exploiting a 2D CNN, a 1D DNN and two conventional classification methods (SVM, and the SVM classifier combined with the 3D–2D hybrid CNN) to validate the proposed network. An overall accuracy of 80% was found when tumor, healthy tissue and blood vessels were classified, clearly outperforming the state-of-the-art approaches. These results can serve as a basis for brain tumor classification using HSI, and may open future avenues for image-guided neurosurgical applications. Full article