Glioblastoma multiforme, the deadliest primary brain tumor, is characterized by an excessive and aberrant neovascularization. The initial expectations raised by anti-angiogenic drugs were soon tempered due to their limited efficacy in improving the overall survival. Intrinsic resistance and escape mechanisms against anti-VEGF therapies evidenced that tumor angiogenesis is an intricate multifaceted phenomenon and that vessels not only support the tumor but exert indispensable interactions for resistance and spreading. This holistic review covers the essentials of the vascular microenvironment of glioblastoma, including the perivascular niche components, the vascular generation patterns and the implicated signaling pathways, the endothelial–tumor interrelation, and the interconnection between vessel aberrancies and immune disarrangement. The revised concepts provide novel insights into the preclinical models and the potential explanations for the failure of conventional anti-angiogenic therapies, leading to an era of new and combined anti-angiogenic-based approaches.

Background: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)-mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. Methods: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. Results: 5-ALA (50 and 100 µg/mL) was applied, and the release of protoporphyrin IX (PpIX) fluorescence measures demonstrated that the emission of PpIX increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. Conclusions: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies.

Objective: Intraoperative imaging is a chief asset in neurosurgical oncology, it improves the extent of resection and postoperative outcomes. Imaging devices have evolved considerably, in particular ultrasound (iUS) and magnetic resonance (iMR). Although iUS is regarded as a more economically convenient and yet effective asset, no formal comparison between the efficiency of iUS and iMR in neurosurgical oncology has been performed.Methods: A cost-effectiveness analysis comparing two single-center prospectively collected surgical cohorts, classified according to the intraoperative imaging used. iMR (2013-2016) and iUS (2021-2022) groups comprised low- and high-grade gliomas, with a maximal safe resection intention. Units of health gain were gross total resection and equal or increased Karnofsky performance status. Surgical and health costs were considered for analysis. The incremental cost-effectiveness ratio (ICER) was calculated for the two intervention alternatives. The cost-utility graphic and the evolution of surgical duration with the gained experience were also analyzed.Results: 50 patients followed an iMR-assisted operation, while 17 underwent an iUS-guided surgery. Gross total resection was achieved in 70% with iMR and in 60% with iUS. Median postoperative Karnofsky was similar in both group (KPS 90). Health costs were € 3,220 higher with iMR, and so were surgical-related costs (€ 1,976 higher). The ICER was € 322 per complete resection obtained with iMR, and € 644 per KPS gained or maintained with iMR. When only surgical-related costs were analyzed, ICER was € 198 per complete resection with iMR and € 395 per KPS gained or maintained.Conclusion: This is an unprecedented but preliminary cost-effectiveness analysis of the two most common intraoperative imaging devices in neurosurgical oncology. iMR, although being costlier and time-consuming, seems cost-effective in terms of complete resection rates and postoperative performance status. However, the differences between both techniques are small. Possibly, iMR and iUS are complementary aids during the resection: iUS real-time images assist while advancing towards the tumor limits, informing about the distance to relevant landmarks and correcting neuronavigation inaccuracy due to brain shift. Yet, at the end of resection, it is the iMR that reliably corroborates whether residual tumor remains.

Postoperative deserved outcomes in acromegalic patients are to normalize serum insulin-like growth factor (IGF-1), reduce the tumoral mass effect, improve systemic comorbidities, and reverse metabolic alterations. Pituitary neuroendocrine tumors (PitNET) are characterized to present a heterogeneous behavior, and growth hormone (GH)-secreting PitNET is not an exception. Promptly determining which patients are affected by more aggressive tumors is essential to guide the optimal postoperative decision-making process [prognostic-based approach]. From 2006 to 2019, 394 patients affected by PitNET were intervened via endoscopic endonasal transsphenoidal approach by the same senior surgeon. A total of 44 patients that met the criteria to be diagnosed as acromegalic and were followed up at least for 24 months (median of 66 months (26–156) were included in the present study. Multiple predictive variables [age, gender, preoperative GH and IGF-1 levels, maximal tumor diameter, Hardy’s and Knosp’s grade, MRI. T2-weighted tumor intensity, cytokeratin expression pattern, and clinicopathological classification] were evaluated through uni- and multivariate statistical analysis. Sparse probability of long-term remission was related to younger age, higher preoperative GH and- or IGF-1, group 2b of the clinicopathological classification, and sparsely granulated cytokeratin expression pattern. Augmented recurrence risk was related to elevated preoperative GH levels, tumor MRI T2-weighted hyperintensity, and sparsely granulated cytokeratin expression pattern. Finally, elevated risk for reintervention was related to group 2b of the clinicopathological classification, Knosp’s grade IV, and tumor MRI T2-weighted hyperintensity. In this study, the authors determined younger age, higher preoperative GH and- or IGF-1 levels, group 2b of the clinicopathological classification, Knosp’s grade IV, MRI T2-weighted tumor hyperintensity and sparsely granulated cytokeratin expression pattern are related to worse postoperative outcomes in long-term follow-up patients affected with GH-secreting PitNET.

Background: Subarachnoid hemorrhage (SAH) entails high morbidity and mortality rates. Convolutional neural networks (CNN) are capable of generating highly accurate predictions from imaging data. Our objective was to predict mortality in SAH patients by processing initial CT scans using a CNN-based algorithm. Methods: We conducted a retrospective multicentric study of a consecutive cohort of patients with SAH. Demographic, clinical and radiological variables were analyzed. Preprocessed baseline CT scan images were used as the input for training using the AUCMEDI framework. Our model’s architecture leveraged a DenseNet121 structure, employing transfer learning principles. The output variable was mortality in the first three months. Results: Images from 219 patients were processed; 175 for training and validation and 44 for the model’s evaluation. Of the patients, 52% (115/219) were female and the median age was 58 (SD = 13.06) years. In total, 18.5% (39/219) had idiopathic SAH. The mortality rate was 28.5% (63/219). The model showed good accuracy at predicting mortality in SAH patients when exclusively using the images of the initial CT scan (accuracy = 74%, F1 = 75% and AUC = 82%). Conclusion: Modern image processing techniques based on AI and CNN make it possible to predict mortality in SAH patients with high accuracy using CT scan images as the only input. These models might be optimized by including more data and patients, resulting in better training, development and performance on tasks that are beyond the skills of conventional clinical knowledge.

Background: Traditionally, functional neurosurgery relied in stereotactic atlases and intraoperative micro-registration in awake patients for electrode placement in Parkinson’s disease. Cumulative experience on target description, refinement of MRI, and advances in intraoperative imaging has enabled accurate preoperative planning and its implementation with the patient under general anaesthesia. Methods: Stepwise description, emphasising preoperative planning, and intraoperative imaging verification, for transition to asleep-DBS surgery. Conclusion: Direct targeting relies on MRI anatomic landmarks and accounts for interpersonal variability. Indeed, the asleep procedure precludes patient distress. A particular complication to avoid is pneumocephalus; it can lead to brain-shift and potential deviation of electrode trajectory.