Explore the vast range of titles available.

Glioblastoma (GB) is one of the most aggressive brain tumors, characterized by high infiltrative capacity that enables tumor cells to invade healthy brain tissue and evade complete surgical resection. This invasiveness contributes to resistance against conventional therapies and a high recurrence rate. Strategies capable of eliminating residual tumor cells are urgently needed. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA), an FDA- and EMA-approved compound, induces selective accumulation of the photosensitizer protoporphyrin IX (PpIX) in metabolically active tumor cells, enabling targeted cytotoxicity through light activation. A major limitation to its clinical application is the unclear variation in the cytotoxic effect of PDT according to individual tumoral differences. In this study, we propose and validate an in vivo model of patient-derived GB initiating cells (GICs) and brain organoids to test the effects of PDT. First, patient-derived GICs were molecularly characterized by flow cytometry and copy number variation profiling using OncoScan CNV Assays, then co-cultured with human brain organoids to generate a hybrid model recapitulating key aspects of the tumor microenvironment. 5-ALA photodynamic therapy (PDT) efficacy was assessed in vitro by GFP-based viability measurements, LDH release assays, and TUNEL staining. Then, a murine model was generated to study PDT in vivo, based on a heterotopic (renal subcapsular engraftment) xenograft of the GICs-human brain organoid co-culture. PDT was tested in the model; in each subject, one kidney tumoral engraftment was treated and the contralateral served as a control. Immunofluorescence analysis was used to study the cell composition of the brain organoid-tumoral engraftment after PDT, and the effects on non-GIC cells. The antitumoral effect was determined by the degree of cell death analysis with the TUNEL technique. The GICs-brain organoid co-culture resulted in tumoral growth and infiltration both in vitro and in vivo. The pattern of growth and infiltration varied according to the tumoral genetic profile. 5-ALA PDT resulted in a reduction in the number of GICs and an increase in apoptotic cells in all four lines tested in vitro. A correlation was found between the induced phototoxicity in vivo with the molecular typification of GICs cell lines in vitro. There were no changes in the number or distribution of neuronal cells after the application of PDT, while a reduction in active astrocytes was observed. 5-ALA PDT could be effective in eradicating GICs with a heterogeneous molecular profile. The hybrid human-murine model presented here could be useful in investigating adjuvant therapies in GB, under the concept of personalized medicine.

Background and objectiveSurgical approaches to the petrous apex region are extremely challenging; while subtemporal approaches and variations represent the milestone of the surgical modules to reach such deep anatomical target, in a constant effort to develop minimally invasive neurosurgical routes, the endoscopic endonasal approach (EEA) has been tested to get a viable corridor to the petroclival junction. Lately, another ventral endoscopic minimally invasive route, i.e., the superior eyelid endoscopic transorbital approach, has been proposed to access the most lateral aspect of the skull base, including the petrous apex region. Our anatomic study aims to compare and combine such two endoscopic minimally invasive pathways to get full access to the petrous apex. Three-dimensional reconstructions and quantitative and morphometric data have been provided.Material and methodsFive human cadaveric heads (10 sides) were dissected. The lab rehearsals were run as follows: (i) preliminary pre-operative CT scans of each specimen, (ii) pre-dissection planning of the petrous apex removal and its quantification, (iii) petrous apex removal via endoscopic endonasal route, (iv) post-operative CT scans, (v) petrous apex removal via endoscopic transorbital route, and (v) final post-operative CT scan with quantitative analysis. Neuronavigation was used to guide all dissections.ResultsThe two endoscopic minimally invasive pathways allowed a different visualization and perspective of the petrous apex, and its surrounding neurovascular structures. After both corridors were completed, a communication between the surgical pathways was highlighted, in a so-called connection area, surrounded by the following important neurovascular structures: anteriorly, the internal carotid artery and the Gasserian ganglion; laterally, the internal acoustic canal; superiorly, the abducens nerve, the trigeminal root, and the tentorium cerebelli; inferomedially, the remaining clivus and the inferior petrosal sinus; and posteriorly, the exposed area of the brainstem. Used in a combined fashion, such multiportal approach provided a total of 97% of petrous apex removal. In particular, the transorbital route achieved a mean of 48.3% removal in the most superolateral portion of the petrous apex, whereas the endonasal approach provided a mean of 48.7% bone removal in the most inferomedial part. The difference between the two approaches was found to be not statistically significant (p = 0.67).ConclusionThe multiportal combined endoscopic endonasal and transorbital approach to the petrous apex provides an overall bone removal volume of 97% off the petrous apex. In this paper, we highlighted that it was possible to uncover a common path between these two surgical pathways (endonasal and transorbital) in a so-called connection area. Potential indications of this multiportal approach may be lesions placed in or invading the petrous apex and petroclival regions that can be inadequately reached via transcranial paths or via an endonasal endoscopic route alone.

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: 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.

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 Recently, robotic arms have been incorporated into the implantation of electrodes for deep brain stimulation (DBS).This study aimed to determine the accuracy of brain electrode placement, initial clinical efficacy, and safety profile of the robotic arm Neuromate (Renishaw) compared to a stereotactic frame in movement disorders. Methods This study involved two retrospective cohorts: one cohort was operated on using a stereotactic frame and the other with a robotic arm. This study was conducted at Barcelona Hospital Clinic. Results Seventy-seven patients were included, of whom 30 underwent surgery using the robot and 47 using a stereotactic frame. The postoperative improvement percentage of the Unified Parkinson’s Disease Rating Scale at 3 months was similar in both groups (robot: 71.4 ± 18 vs. frame: 72.6% ± 17, P = 0.82). There were no significant differences in the perioperative complications (robot: 4% vs. frame: 4.3%, P = 0.93) or in the adverse reactions related to brain stimulation and medical treatment (robot: 18% vs. frame: 25%, P = 0.53). There was a slight improvement in the anatomical-radiological accuracy of brain electrode implantation assisted by the robotic arm, measured using radial error (robot: 1.01 ± 0.5 mm vs. frame: 1.32 ± 0.6 mm, P = 0.03). Conclusions Both systems (robotic and stereotactic frame) exhibited similar initial clinical efficacies and safety profiles. The use of the robotic arm Neuromate slightly improved the anatomical-radiological accuracy in the placement of DBS electrodes for movement disorders compared with the stereotactic frame.

to study the anatomical feasibility of laser fiber insertion for interstitial thermal therapy via transorbital approach to the temporo-mesial structures (amygdala-hippocampus-parahippocampus complex). Anatomical dissections were performed bilaterally on two human cadaveric heads via a transorbital approach, in which screws and laser fibers were used for magnetic resonance imaging-guided laser interstitial thermal therapy (MRIgLITT) assisted by neuronavigation. In addition, eight transorbital trajectories were simulated using the transorbital entry points obtained from a cadaveric radiological study of four patients previously operated on for mesial temporal lobe epilepsy. Successful placement of all four laser fibers was achieved in the anatomical specimens according to the predetermined plan, with an average vector error of 1.3 ± 0.2 mm, ensuring complete coverage of the amygdala-hippocampus-parahippocampus complex. Furthermore, simulations of patient trajectories confirmed safe vascular pathways. An optimal transorbital entry point was identified in the inferolateral quadrant of the orbit, specifically on the lateral wall above the greater wing of the sphenoid. However, the small size of the laser fiber-anchoring screw currently limits its clinical application. This technique may serve as a potential alternative to occipital access in laser surgery for epilepsy, in very specific situations. The placement of a transorbital laser fiber for MRIgLITT targeting the temporomesial structures in epilepsy is anatomically feasible; however, the small size of the anchoring screw presently precludes its clinical use. •Laser surgery is an effective, minimally invasive treatment for epilepsy.•The occipital approach is the standard for laser surgery in temporal lobe epilepsy.•The transorbital approach is anatomically feasible for laser epilepsy surgery.•Hardware modifications are needed to optimize this approach.•Clinical studies are required to validate our anatomical findings.

Purpose Oligodendroglioma is an adult-type diffuse glioma defined by 1p/19q codeletion and IDH1/2 mutation. Treatment includes surgery followed by observation alone in select low-grade tumors, or combination radiation and chemotherapy with procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ). While prospective studies investigating treatments for molecularly defined oligodendrogliomas are ongoing, this retrospective study analyzes the relationship between adjuvant regimens and progression-free survival (PFS). Methods Adults with IDH-mutant, 1p/19q codeleted oligodendroglioma (WHO grade 2 or 3) who underwent surgery between 2005 and 2021 were identified. Clinical data, disease characteristics, treatment, and outcomes were collected. Results A total of 207 patients with grade 2 and 70 with grade 3 oligodendrogliomas were identified. Median (IQR) follow-up was 57 (87) months. Patients with grade 3 tumors who received adjuvant radiation and PCV had longer median PFS (> 110 months) than patients who received radiation and TMZ (52 months, p  = 0.008) or no adjuvant chemoradiation (83 months, p  = 0.03), which was not seen in grade 2 tumors ( p  = 0.8). In multivariate analysis, patients who received PCV chemotherapy (Relative Risk [95% CI] = 0.24[0.05—1.08] and radiotherapy (0.46[0.21—1.02]) trended towards longer PFS, independently of grade. Conclusion Adjuvant radiation and PCV are associated with improved PFS over radiation with TMZ in patients with grade 3 molecularly defined oligodendrogliomas, and all-grade patients treated with PCV trended towards decreased risk of recurrence and progression. These results highlight the importance of ongoing clinical trials investigating these treatments.