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BACKGROUND: Despite the aggressiveness of multimodal treatment, glioblastoma (GBM) is still a challenge for neurosurgeons, neurooncologists, and radiotherapists. A surgical approach is still a cornerstone in GBM therapeutic management, as the extent of resection is strongly related both to overall survival and progression-free survival. From this perspective, the use of photodynamic molecules could represent an interesting tool to achieve maximal and safe resection. Being able to trace the lesion's edges, indeed, could allow to improve the extent of resection and to minimize residual tumor while sparing normal tissue. The use of 5-aminolevulinic acid (5-ALA) as a photodynamic tracer is well established due to its strict correlation both with cellularity and metabolic activity of the GBM cell clones. OBJECTIVE: Our study aims to define whether a different molecular asset of GBM (especially investigating IDH 1/2 mutation, proliferation index, and MGMT promoter methylation) results in different fluorescence expression, possibly because of differences in metabolic pathways due to different genotypes. METHODS: Patients undergoing surgery for GBM removal at our Institute (Dep. Of Neurosurgery, Ospedale Città della Salute e della Scienza, University of Turin, Italy) were retrospectively reviewed. Patients with histological diagnosis confirmation and to whom 5-ALA was given before surgery were included. The whole surgical procedure was recorded and then analyzed by three different people (a medical student, a resident, and a senior surgeon with an interest in neurooncology and experience in using 5-ALA) and a score was assigned to the different degrees of intraoperative fluorescence. The degree of fluorescence was then matched with the genotype. RESULTS: A trend of grade 2 fluorescence (i.e., "strong") was observed in the IDH 1/2 wild-type (WT) genotype, suggesting a more intense metabolic activity in this particular subgroup, while, no or weak fluorescence was observed more often in the IDH 1/2 mutated tumors, suggesting a lower metabolic activity. No relations were found between fluorescence grade and MGMT promoter methylation or, interestingly, cellularity. As a secondary analysis, more epileptogenicity of the IDH 1/2 mutated GBM was noticed, similarly to other recent literature. CONCLUSION: Our results do not support the use of 5-ALA as a diagnostic tool, or a way to substitute the molecular profiling, but confirm 5-ALA as a powerful metabolic tracer, able to easily detect the pathological cells, especially in the IDH WT genotype, and in this perspective, further studies will be necessary to better describe the metabolic activity of GBM cells.
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PURPOSE: Advances in intraoperative imaging and neuronavigation techniques have positively affected glioma surgery. The desire to reduce brain-shift-related problems while achieving the real-time identification of lesions and residual and anatomical relationships has strongly supported the introduction of intraoperative ultrasound (ioUS) in neuro-oncological surgery. This paper presents tips based on our experience with ioUS in neurosurgery. METHODS: We retrospectively analyzed 264 patients who underwent high-grade glioma (HGG) resection at the University of Turin and 60 patients who were treated at the University of Rome. RESULTS: The main issues are the correct choice of the probe and how to evaluate the anatomy to understand how the information from the three common US planes (axial, sagittal and coronal plane) can be used in each case. It is also important to correctly identify anatomical structures in ioUS imaging. In a normal brain, the sulci, sickle, tentorium, choroid plexus, ependyma and the walls of the vessels are all hyperechoic. In addition, some structures are hypoechoic with a homogeneous acoustic gradient: ventricles, cysts and everything that contains liquor. Tumors are usually hyperechoic in ioUS because of their higher cellularity. Conversely, acute edema that contains fluid is hypoechoic, while chronic edema is hyperechoic. CONCLUSIONS: IoUS is a real-time, accurate and inexpensive imaging method. The difficulties of interpretation can be overcome by experience in US imaging and a better understanding of the interaction between navigation and imaging fusion techniques. Training on a large number of cases is important for the correct assessment of ioUS information to obtain valuable, real-time information during HGG surgery.
