Purpose: Glioblastoma (GBM) is the most common primary brain tumor. The identification of blood biomarkers reflecting the tumor status represents a major unmet need for optimal clinical management of patients with GBM. Their high number in body fluids, their stability, and the presence of many tumor-associated proteins and RNAs make extracellular vesicles potentially optimal biomarkers. Here, we investigated the potential role of plasma extracellular vesicles from patients with GBM for diagnosis and follow-up after treatment and as a prognostic tool. Experimental Design: Plasma from healthy controls (n = 33), patients with GBM (n = 43), and patients with different central nervous system malignancies (n = 25) were collected. Extracellular vesicles were isolated by ultracentrifugation and characterized in terms of morphology by transmission electron microscopy, concentration, and size by nanoparticle tracking analysis, and protein composition by mass spectrometry. An orthotopic mouse model of human GBM confirmed human plasma extracellular vesicle quantifications. Associations between plasma extracellular vesicle concentration and clinicopathologic features of patients with GBM were analyzed. All statistical tests were two-sided. Results: GBM releases heterogeneous extracellular vesicles detectable in plasma. Plasma extracellular vesicle concentration was higher in GBM compared with healthy controls (P < 0.001), brain metastases (P < 0.001), and extra-axial brain tumors (P < 0.001). After surgery, a significant drop in plasma extracellular vesicle concentration was measured (P < 0.001). Plasma extracellular vesicle concentration was also increased in GBM-bearing mice (P < 0.001). Proteomic profiling revealed a GBM-distinctive signature. Conclusions: Higher extracellular vesicle plasma levels may assist in GBM clinical diagnosis: their reduction after GBM resection, their rise at recurrence, and their protein cargo might provide indications about tumor, therapy response, and monitoring.
Background. Contrast enhanced ultrasound (CEUS) is a dynamic and continuous modality providing real-time view of vascularization and flow distribution patterns of different organs and tumors. Nevertheless its intraoperative use for brain tumors visualization has been performed few times, and a thorough characterization of cerebral glioma had never been performed before.Aim. To perform the first characterization of cerebral glioma using CEUS and to possibly achieve an intraoperative differentiation of different gliomas.Methods. We performed CEUS in an off-label setting in 69 patients undergoing surgery for cerebral glioma. An intraoperative qualitative analysis was performed comparing iCEUS with B-mode imaging. A postprocedural semiquantitative analysis was then performed for each case, according to EFSUMB criteria. Results were related to histopathology.Results. We observed different CE patterns: LGG show a mild, dotted CE with diffuse appearance and slower, delayed arterial and venous phase. HGG have a high CE with a more nodular, nonhomogeneous appearance and fast perfusion patterns.Conclusion. Our study characterizes for the first time human brain glioma with CEUS, providing further insight regarding these tumors’ biology. CEUS is a fast, safe, dynamic, real-time, and economic tool that might be helpful during surgery in differentiating malignant and benign gliomas and refining surgical strategy.
The main goal in meningioma surgery is to achieve complete tumor removal, when possible, while improving or preserving patient neurological functions. Intraoperative imaging guidance is one fundamental tool for such achievement. In this regard, intra-operative ultrasound (ioUS) is a reliable solution to obtain real-time information during surgery and it has been applied in many different aspect of neurosurgery. In the last years, different ioUS modalities have been described: B-mode, Fusion Imaging with pre-operative acquired MRI, Doppler, contrast enhanced ultrasound (CEUS), and elastosonography. In this paper, we present our US based multimodal approach in meningioma surgery. We describe all the most relevant ioUS modalities and their intraoperative application to obtain precise and specific information regarding the lesion for a tailored approach in meningioma surgery. For each modality, we perform a review of the literature accompanied by a pictorial essay based on our routinely use of ioUS for meningioma resection.
Post-craniotomy neurosurgical infections (PCNIs) significantly challenge daily neurosurgical practice, affecting patient outcomes and imposing economic burdens on healthcare systems. Despite advances in surgical techniques and infection control protocols, PCNIs still contribute to surgical-related morbidity and mortality. To address these unresolved questions through a comprehensive literature review. We conducted a detailed literature review using the keywords "Infection, Craniotomy, Neurosurgery," on PubMed, which yielded 2330 articles. Out of these, 171 were selected, based on relevance, and rigorously reviewed. The review aimed to answer thirteen major questions stemming from the management of PCNIs. PCNI incidences range from 0.7% to 8%, predominantly caused by gram-positive bacteria, especially Staphylococcus species. Significant risk factors identified include CSF leakage, emergency surgery, and certain tumour types, with infections typically manifesting post-discharge. Diagnostic approaches integrate clinical, radiological, and laboratory assessments, with advances in molecular diagnostics showing promising precision. While antibiotic prophylaxis remains effective, emerging resistance warrants cautious application. Surgical intervention is often indispensable for managing organ-space infections, with a trend towards bone flap preservation and one-step cranioplasty procedures in certain cases. The management of PCNIs remains a major challenge. There is a critical need for standardization of definitions and data reporting. Advancements in diagnostic and therapeutic strategies may bring future improvements in clinical outcomes, despite antibiotic resistance phenomena and the complexity of surgical decisions required. Ultimately, major engagement is aimed at refining and updating clinical protocols to improve and standardize the management of PCNIs.