(1) Background: Neuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) represents a diagnostic and therapeutic challenge in neurosurgical practice, expanding the burden of care and exposing patients to additional risks related to further invasive procedures and treatment delays. In addition, atypical cases and overlapping features have not been entirely addressed by modern diagnostic research. The aim of this study was to validate a previously designed and internally validated ResNet101 deep learning model to differentiate glioblastomas, PCNSLs and BMs. (2) Methods: We enrolled 126 patients (glioblastoma: n = 64; PCNSL: n = 27; BM: n = 35) with preoperative T1Gd-MRI scans and histopathological confirmation. Each lesion was segmented, and all regions of interest were exported in a DICOM dataset. A pre-trained ResNet101 deep neural network model implemented in a previous work on 121 patients was externally validated on the current cohort to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans. (3) Results: The model achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.73; 95%CI: 0.62–0.85), glioblastomas (AUC: 0.78; 95%CI: 0.71–0.87) and moderate to low ability in differentiating BMs (AUC: 0.63; 95%CI: 0.52–0.76). The performance of expert neuro-radiologists on conventional plus advanced MR imaging, assessed by retrospectively reviewing the diagnostic reports of the selected cohort of patients, was found superior in accuracy for BMs (89.69%) and not inferior for PCNSL (82.90%) and glioblastomas (84.09%). (4) Conclusions: We investigated whether the previously published deep learning model was generalizable to an external population recruited at a different institution—this validation confirmed the consistency of the model and laid the groundwork for future clinical applications in brain tumour classification. This artificial intelligence-based model might represent a valuable educational resource and, if largely replicated on prospective data, help physicians differentiate glioblastomas, PCNSL and solitary BMs, especially in settings with limited resources.

Background: The exoscope is a high-definition telescope recently introduced in neurosurgery. In the past few years, several reports have described the advantages and disadvantages of such technology. No studies have compared results of surgery with standard microscope and exoscope in patients with glioblastoma multiforme (GBM). Methods: Our retrospective study encompassed 177 patients operated on for GBM (WHO 2021) between February 2017 and August 2022. A total of 144 patients were operated on with a microscope only and the others with a 3D4K exoscope only. All clinical and radiological data were collected. Progression-free survival (PFS) and overall survival (OS) have been estimated in the two groups and compared by the Cox model adjusting for potential confounders (e.g., sex, age, Karnofsky performance status, gross total resection, MGMT methylated promoter, and operator’s experience). Results: IDH was mutated in 9 (5.2%) patients and MGMT was methylated in 76 (44.4%). Overall, 122 patients received a gross total resection, 14 patients received a subtotal resection, and 41 patients received a partial resection. During follow-up, 139 (73.5%) patients experienced tumor recurrence and 18.7% of them received a second surgery. After truncation to 12 months, the median PFS for patients operated on with the microscope was 8.82 months, while for patients operated on with the exoscope it was >12 months. Instead, the OS was comparable in the two groups. The multivariable Cox model showed that the use of microscope compared to the exoscope was associated with lower progression-free survival (hazard ratio = 3.55, 95%CI = 1.66–7.56, p = 0.001). Conclusions: The exoscope has proven efficacy in terms of surgical resection, which was not different to that of the microscope. Furthermore, patients operated on with the exoscope had a longer PFS. A comparable OS was observed between microscope and exoscope, but further prospective studies with longer follow-up are needed.

The vacuolar proton-translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism underlying carcinogenesis is mainly based on anaerobic glycolytic reactions. Moreover, neoplastic cells use the V-ATPase to extrude chemotherapy drugs into the extra-cellular compartment as a drug resistance mechanism. In glioblastoma (GBM), the most malignant and incurable primary brain tumor, the expression of this pump is upregulated, making it a new possible therapeutic target. In this work, the bafilomycin A1-induced inhibition of V-ATPase in patient-derived glioma stem cell (GSC) lines was evaluated together with temozolomide, the first-line therapy against GBM. In contrast with previous published data, the proposed treatment did not overcome resistance to the standard therapy. In addition, our data showed that nanomolar dosages of bafilomycin A1 led to the blockage of the autophagy process and cellular necrosis, making the drug unusable in models which are more complex. Nevertheless, the increased expression of V-ATPase following bafilomycin A1 suggests a critical role of the proton pump in GBM stem components, encouraging the search for novel strategies to limit its activity in order to circumvent resistance to conventional therapy.

Maximal resection has a pivotal role in the treatment of glioblastoma (GB), prolonging both progression free survival (PFS) and overall survival (OS). Only few studies analyze the delicate equilibrium between maximal resection, clinical outcome and prognosis. the aim of this work is to determine the impact of neurological impairment on PFS, OS and access to adjuvant therapies on patients with GB operated with perilesional resection technique. Material and Methods: this retrospective study encompassed patients operated for GB at Fondazione IRCCS San Gerardo dei Tintori Monza (IT), from 2015 to 2023. Histological diagnosis was performed according to the WHO 2021 classification. Patients were more than 18 years old, with pre- and postoperative MRI, who underwent surgery and adjuvant treatments at our Institution. A total of 209 patients fulfilled the criteria. Patients with improvement or complete regression of preoperative deficit had a higher rate of access to adjuvant therapies (p = 0.015). Patients with hemiparesis at discharge had the worst PFS (median 4.60 months) followed by patients with aphasia (6.60 months), and patients with normal neurological examination (9.67 months; p < 0.0001). The median OS was 17.93 months for patients with hemianopia, 6.40 for patients with hemiparesis and 15.7 months for those with aphasia (p < 0.0001). Hemianopia has no impact on the patient's prognosis, while hemiparesis and aphasia at discharge worsen both PFS and OS prolonging time-to-treatment. When resecting GB, it is mandatory to avoid major neurological deficits that concur which reduce OS and PFS.

The vacuolar proton translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism is mainly based on anaerobic glycolytic reactions. Moreover, the neoplastic cells use the V-ATPase to extrude chemotherapy drugs to the extra-cellular compartment, as a drug-resistance mechanism. In glioblastoma (GBM), the most malignant and incurable primary brain tumor, the expression of this pump is upregulated, making it a new possible therapeutic target. In this work, the bafilomycin A1 induced-inhibition of V-ATPase in patients-derived glioma stem cell (GSC) lines was evaluated together with temozolomide, the first-line line therapy against GBM. In contrast with previous published data, the proposed treatment did not overcome the resistance to the standard therapy. In addition, our data showed that nanomolar dosages of bafilomycin A1 lead to the blockage of the autophagy process and cellular necrosis, making the drug unusable in models that are more complex. Nevertheless, the increased expression of V-ATPase following bafilomycin A1 suggests a critical role of the proton pump in GBM stem component, encouraging the search for novel strategies to limit its activity in order to get around the resistance to the conventional therapy.

Glioblastoma (GB) is an uncurable tumor with poor prognosis despite resection plus adjuvant cares. When unresectable, even in case of a clear radiological imaging, guidelines require a formal histological diagnosis to confirm the diagnosis of GB. This study aims to assess the post-surgical complications and neuro-oncological outcomes of patients undergoing a confirmatory brain biopsy for diagnosing GB. We considered 125 adult patients who underwent stereotactic biopsy between January 2018 and December 2023 at the Neurosurgery Department of IRCCS San Gerardo dei Tintori. Among them, 74 patients with radiological diagnosis of GB underwent a purely confirmatory biopsy. The clinical history of each patient was evaluated from the onset of symptoms through subsequent neuro-oncological treatments. We evaluated the patients' clinical conditions at the time of biopsy and upon discharge, the radiological characteristics of the tumor, the histopathological diagnosis, biopsy-related complications, access to oncological treatments along with associated complications and neurological-functional outcomes. Unmethylated MGMT status, KPS≤70, tumor proximity to the internal capsule and absence of motor hemisyndrome at symptoms onset emerged as possible risk factors. Biopsied GB patients had an 11% complication rate and exhibited a dismal short-term prognosis, with a median survival of 4.7 months. Furthermore, about 40% of patients did not access subsequent treatment. Brain biopsy is still a minor procedure with not a negligible rate of complications. When performed as a purely confirmatory procedure, a great deal of patients does not access oncological treatments.