OBJECTIVE: Learning surgical skills is an essential part of neurosurgical training. Ideally, these skills are acquired to a sufficient extent in an ex vivo setting. The authors previously described an in vitro brain tumor model, consisting of a cadaveric animal brain injected with fluorescent agar-agar, for acquiring a wide range of basic neuro-oncological skills. This model focused on haptic skills such as safe tissue ablation technique and the training of fluorescence-based resection. As important didactical technologies such as mixed reality and 3D printing become more readily available, the authors developed a readily available training model that integrates the haptic aspects into a mixed reality setup. METHODS: The anatomical structures of a brain tumor patient were segmented from medical imaging data to create a digital twin of the case. Bony structures were 3D printed and combined with the in vitro brain tumor model. The segmented structures were visualized in mixed reality headsets, and the congruence of the printed and the virtual objects allowed them to be spatially superimposed. In this way, users of the system were able to train on the entire treatment process from surgery planning to instrument preparation and execution of the surgery. RESULTS: Mixed reality visualization in the joint model facilitated model (patient) positioning as well as craniotomy and the extent of resection planning respecting case-dependent specifications. The advanced physical model allowed brain tumor surgery training including skin incision; craniotomy; dural opening; fluorescence-guided tumor resection; and dura, bone, and skin closure. CONCLUSIONS: Combining mixed reality visualization with the corresponding 3D printed physical hands-on model allowed advanced training of sequential brain tumor resection skills. Three-dimensional printing technology facilitates the production of a precise, reproducible, and worldwide accessible brain tumor surgery model. The described model for brain tumor resection advanced regarding important aspects of skills training for neurosurgical residents (e.g., locating the lesion, head position planning, skull trepanation, dura opening, tissue ablation techniques, fluorescence-guided resection, and closure). Mixed reality enriches the model with important structures that are difficult to model (e.g., vessels and fiber tracts) and advanced interaction concepts (e.g., craniotomy simulations). Finally, this concept demonstrates a bridging technology toward intraoperative application of mixed reality.

Stummer et al. established fluorescence-guided surgery (FGS) for glioblastoma (GBM) using 5-aminolevulinic acid (5-ALA). Its metabolite, protoporphyrin IX (PPIX), is also a photosensitizer and can be used for photodynamic therapy (PDT) using a laser beam of 635 nm. The porphyrin derivate verteporfin (VP) was discovered to have properties to penetrate the brain, pharmacologically target glioma cells, and is approved for PDT of choroidal neovascularization in wet age-related macular degeneration at 689 nm. To elucidate whether GBM cell lines are susceptible to PDT with second-generation photosensitizer VP. Human glioma cell lines LN229, HSR-GBM1, and a low-passage patient-derived GBM cell line P1 were treated with variable concentrations of VP for 24 h, followed by PDT at 689 nm using a diode laser light. Cell viability was measured using the MTT assay and VP uptake was measured using a desktop cytometer. Significantly higher cell death following PDT with VP compared to VP treatment alone or no treatment was detected in all cell models (LN229, HSR-GBM1, P1). Flowcytometric measurements revealed a concentration-dependent cellular uptake of VP after 24 h incubation up to 99% at 10 µM (HSR-GBM1). This study demonstrates that PDT with VP causes cell death in GBM cells at marginal concentrations. Additionally, red spectrum fluorescence was detected at therapeutic concentrations in all cell lines, validating the cellular uptake of VP in GBM cells. VP, therefore, is not only a potential drug for targeting GBM pharmacologically but can be used as an optical imaging dye in surgery and photosensitizer to make GBM susceptible to PDT.

Until recently, a prerequisite for fluorescence-guided surgery (FGS) was the use of a specialized microscope. With the availability of a system that combines surgical loupes with an FGS-enabled headlamp, the standard approach to FGS of gliomas is challenged. We therefore investigated the potential change in practice of FGS for gliomas, if the surgeon had the choice between both systems. Patients with a lesion indicating FGS were included. Surgery was performed by 3 specialized neurooncological neurosurgeons, who were provided with a headlamp-loupe system (HLLS) (5-aminolevulinic acid headlamp and surgeon-adapted loupes, 3.5X, customized fitted). We recorded surgeons' choice between HLLS and microscope and semi-quantified the statements. Additionally, in one case, specificity and sensitivity of various protoporphyrin IX (PpIX) fluorescence (PpIX-f) were histopathologically evaluated. We report 206 procedures in 198 patients. Surgeons opted in 194 (94%) of the cases for HLLS and did not switch from HLLS to microscope in any case. Three biopsies taken from areas with negative, faint, and highly positive PpIX-f, as revealed by the HLLS but not by the microscope, corresponded to normal brain tissue (negative PpIX-f), infiltration zone (faint PpIX-f), and highly cellular tumor tissue with microvascular proliferation (strong PpIX-f). Our center changed the practice of FGS by switching from microscopes to loupes. The reported experience might have an important impact on the general use and availability of FGS, as the HLLS and the in-house preparation of 5-aminolevulinic acid come at a fraction of the costs of the commonly practiced approach.

Purpose: Complete resection (CR) of contrast-enhancing (CE) and non-contrast-enhancing (nCE) tumour compartments is a key prognostic factor in diffuse gliomas. However, despite an intraoperative impression of CR, early postoperative MRI may reveal residual tumour. This study evaluated outcomes of patients undergoing early second-look surgery for unplanned residual tumour volume. Methods: Patients undergoing surgery for diffuse gliomas between 2013 and 2023 were screened for surgical re-intervention within six weeks after initial resection. Patients undergoing early second-look surgery due to unplanned residual tumour on postoperative MRI were included. Volumetric MRI analyses, RANO resection classification, functional neurological outcomes, perioperative complications, and survival were assessed. Results: Among 1.558 glioma patients (CNS WHO grade 2–4), 447 underwent multiple surgeries, of whom 46 received second-look surgery for residual tumour. Resection status shifted from 80.4% submaximal after first surgery to supramaximal or maximal resection in 86.96% after second-look surgery. Residual tumour volumes were significantly reduced for both T1-CE and T2-nCE components ( p < .001). Functional and neurological status remained stable (KPS and NIHSS, p > .5). In newly diagnosed glioblastoma patients ( n = 28), RANO class 1 after second-look surgery was associated with longer overall survival compared to RANO 2B (13.8 vs. 8.0 months; p = .043). The 2- and 3-year OS rates were 33.34% and 16.67% in RANO class 1, while no patients in RANO class 2B survived beyond 2 years. Conclusion: Early second-look surgery for unplanned residual tumour enables a high rate of (supra-)maximal resections without compromising functional outcomes and may improve survival in selected patients.

Introduction: Significant studies have substantiated the evidence for complete resection of intrinsic brain tumours in recent years. However, achieving this through a single surgery is not always possible due to tumour localisation in eloquent areas. Therefore, the present analysis aimed to evaluate surgical outcomes in a cohort of patients undergoing planned two-stage glioma surgery. Methods: Patients who underwent surgery for diffusely infiltrating brain tumours between 2013 and 2023 at the Department of Neurosurgery at Düsseldorf University Hospital were screened for undergoing two-stage surgery, defined by a priori-considered surgical re-intervention up to 6 weeks after the initial surgery. Results: Of 1558 patients with glioma, 447 underwent multiple surgeries, of whom 36 underwent planned two-stage surgery during the course of their disease. Two-stage surgery was performed mostly as glioma surgery at first diagnosis (75%). The mean time between the first and second surgery was 11.67 days (±7.59). Two-stage surgery was performed due to various reasons, mostly in localisations that required multifocal approaches (47.2%), due to non-compliance during initial awake surgery (30.6%), or cases with primary debulking for subsequent awake-surgery approaches (22.2%). Tumours were mainly located in the left hemisphere (50%) (right hemisphere 25%, or bilateral 25%) and motor- or speech-eloquent in 61.11%. Tumours were 72.2% IDH-wildtype. An intended complete resection result was achieved in 58.88% after the second surgery, changing from 93.94% submaximal resection to 58.88% supramaximal and maximal resection after the second surgery. Second surgery significantly reduced residual tumour volume of both T1-CE (Wilcoxon signed-rank test, Z = −4.62, p < 0.001) and T2-nCE (Z = −4.62, p < 0.001). In contrast, functional (KPS: Z = −0.93, p = 0.350) and neurological status (NIHSS: Z = −0.89, p = 0.372) did not significantly change. Perioperative complications of the second surgery occurred in nine (25%) cases, requiring surgical intervention under general anaesthesia or ICU treatment (Clavien–Dindo grade IIIb/IV) in six (16.67%) cases. Conclusion: Planned two-stage surgery was mostly performed as a surgical strategy in eloquent locations to achieve supramaximal or maximal resection. A two-staged surgery significantly extended resection results without neurological and functional deterioration. Despite relevant complication rates, primary debulking followed by staged resection as well as two-staged multifocal approaches may yield a favourable risk–benefit profile.