Insights from a Multicenter Study on Adult H3 K27M-Mutated Glioma: Surgical Resection's Limited Influence on Overall Survival, ATRX as Molecular Prognosticator.

BACKGROUND: H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 WHO classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults. METHODS: We included molecularly confirmed H3 K27M-mutated glioma cases in patients >18 years diagnosed between 2016 and 2022. Clinical, radiological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Among 70 patients with a mean age of 36.1 years, the median overall survival (OS) was 13.6 + 14 months. Gross-total resection was achieved in 14.3% of patients, whereas 30% had a subtotal resection and 54.3% a biopsy.Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location in the mesencephalon/metencephalon showed a significantly longer OS (8.7 vs. 25.0 months, p=0.007). Preoperative Karnofsky Performance Score (KPS) < 80 showed a reduced OS (4.2 vs. 18 months, p=0.02). Furthermore, ATRX loss, found in 25.7%, was independently associated with an increased OS (31 vs. 8.3 months, p=0.0029). Notably, patients undergoing resection showed no survival benefit over biopsy (12 vs. 11 months, p=0.4006). CONCLUSION: The present study describes surgical features of H3 K27M-mutated glioma in adulthood in a large multicentric study. Our data reveal that ATRX status, location and KPS significantly impact OS in H3 K27M-mutated glioma. Importantly, our dataset indicates that resection does not offer a survival advantage over biopsy.

Technical report: surgical preparation of human brain tissue for clinical and basic research.

BACKGROUND: The study of the distinct structure and function of the human central nervous system, both in healthy and diseased states, is becoming increasingly significant in the field of neuroscience. Typically, cortical and subcortical tissue is discarded during surgeries for tumors and epilepsy. Yet, there is a strong encouragement to utilize this tissue for clinical and basic research in humans. Here, we describe the technical aspects of the microdissection and immediate handling of viable human cortical access tissue for basic and clinical research, highlighting the measures needed to be taken in the operating room to ensure standardized procedures and optimal experimental results. METHODS: In multiple rounds of experiments (n = 36), we developed and refined surgical principles for the removal of cortical access tissue. The specimens were immediately immersed in cold carbogenated N-methyl-D-glucamine-based artificial cerebrospinal fluid for electrophysiology and electron microscopy experiments or specialized hibernation medium for organotypic slice cultures. RESULTS: The surgical principles of brain tissue microdissection were (1) rapid preparation (<1 min), (2) maintenance of the cortical axis, (3) minimization of mechanical trauma to sample, (4) use of pointed scalpel blade, (5) avoidance of cauterization and blunt preparation, (6) constant irrigation, and (7) retrieval of the sample without the use of forceps or suction. After a single round of introduction to these principles, multiple surgeons adopted the technique for samples with a minimal dimension of 5 mm spanning all cortical layers and subcortical white matter. Small samples (5-7 mm) were ideal for acute slice preparation and electrophysiology. No adverse events from sample resection were observed. CONCLUSION: The microdissection technique of human cortical access tissue is safe and easily adoptable into the routine of neurosurgical procedures. The standardized and reliable surgical extraction of human brain tissue lays the foundation for human-to-human translational research on human brain tissue.

Piezosurgery for safe and efficient petrous bone cutting in cerebellopontine angle and petroclival meningioma surgery.

Intradural petrous bone drilling has become a widespread practice, providing extended exposure in the removal of cerebellopontine angle (CPA) or petroclival tumors. Adjacent neurovascular structures are at risk, however, when drilling is performed in this deep and narrow area. Hence, this study evaluates the use of Piezosurgery (PS) as a non-rotating tool for selective bone cutting in CPA surgery. A Piezosurgery® device was used in 36 patients who underwent microsurgery for extra-axial CPA or petroclival tumors in our Neurosurgical Department between 2013 and 2019. The clinical and radiological data were retrospectively analyzed. The use of PS was evaluated with respect to the intraoperative applicability and limitations as well as efficacy and safety of the procedure. Piezosurgical petrous bone cutting was successfully performed in the removal of meningiomas or extra-axial metastases arising from the dura of the petroclival region (21 patients) or petrous bone (15 patients). PS proved to be very helpful in the deep and narrow CPA region, considerably reducing the surgeon's distress toward bone removal in close proximity to cranial nerves and vessels in comparison to common rotating drills. The use of PS was safe without injuries to neurovascular structures. Gross total resection was achieved in 67% of petroclival and 100% of petrous bone tumors. Piezosurgery proved to be an effective and safe method for selective petrous bone cutting in CPA surgery avoiding rotating power and associated risks. This technique can particularly be recommended for bone cutting in close vicinity to critical neurovascular structures.

[Epilepsy-associated tumors of the central nervous system: Epilepsy surgery and oncological aspects]. / Epilepsieassoziierte Tumoren des Zentralnervensystems : Epilepsiechirurgische und onkologische Aspekte.

BACKGROUND: Among the tumors associated with chronic epilepsy, dysembryoplastic neuroepithelial tumor and ganglioglioma are the most common besides angiocentric glioma, pleomorphic xanthoastrocytoma and pilocytic astrocytoma. These tumors are usually considered as being benign. OBJECTIVE: To determine the best conservative and surgical treatment of tumors associated with epilepsy. MATERIAL AND METHODS: This article presents case reports of malignant transformation of a dysembryoplastic neuroepithelial tumor and of a tumor initially diagnosed as a ganglioglioma based on magnetic resonance imaging (MRI) criteria. Description of references in the literature on epilepsy surgery and the neuro-oncology of epilepsy-associated tumors. RESULTS: In the case of the initially histopathologically diagnosed dysembryoplastic neuroepithelial tumor, a malignant transformation occurred 5 years after incomplete resection. The differentiation from a glioblastoma was possible through the analysis of the methylation profile. In another case a tumor assumed to be a ganglioglioma showed an increase in size after 6 years. Initial histopathological results revealed a glioblastoma. The analysis of the methylation profile suggested the diagnosis of an anaplastic pleomorphic xanthoastrocytoma and as a differential diagnosis an anaplastic ganglioglioma. Tumor progress correlated with the worsening of seizures. CONCLUSION: Recent studies have shown that in the treatment of predominantly benign epilepsy-associated tumors neuro-oncological aspects should also be taken into account in addition to the epileptological considerations. In the case of malignant transformation epigenetic screening (methylation profiles) can help to classify the tumor entity more precisely.

Progression-free and overall survival in patients with recurrent Glioblastoma multiforme treated with last-line bevacizumab versus bevacizumab/lomustine.

Bevacizumab (BEV) is widely used for treatment of patients with recurrent glioblastoma multiforme (GBM). 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU, lomustine) monotherapy is an approved chemotherapeutical option for recurrent GBM. Recent evidence demonstrated a survival benefit of combined treatment with BEV and CCNU in patients with a first recurrence of GBM. We examined the outcome of recurrent GBM patients with BEV monotherapy versus BEV/CCNU therapy when used as last-line therapy. 35 patients with recurrent GBM treated between 2010 and 2014 were included in this retrospective study. Progression-free and overall survival was determined with reference to the beginning of BEV or BEV/CCNU therapy and initial diagnosis. 17 patients received BEV monotherapy, 18 patients received combined BEV and CCNU therapy. The impact of parameters such as IDH mutation, MGMT promoter methylation, tumor localization, histology and the number of surgeries were included in a multivariate ANOVA analysis. Furthermore, Karnofsky performance score (KPS), neurological function and toxicity were assessed. BEV/CCNU treatment led to an extension of PFS (6.11 months; 95% CL 3.41-12.98 months; log-rank p = 0.00241) and OS (6.59 months; 95% CL 5.51-16.3 months; log-rank p = 0.0238) of 2 months compared to BEV monotherapy. This survival advantage was independent of histology, IDH mutation status or the number of previous surgeries. Neurological function, KPS and toxicity were not significantly different between both treatment groups. Last-line therapy with BEV/CCNU results in a longer PFS and OS compared to BEV monotherapy and is well-tolerated. These findings confirm the role of these agents in the treatment of recurrent GBM and are in line with other studies.

Efficacy of a new video-based training model in spinal surgery.

BACKGROUND: An important part of neurosurgical training is the improvement of surgical skills. Acquiring microsurgical skills follows a learning curve, influenced by specific exercises, feedback, and training. Aim of training should be rapid learning success. The study shows the way in which video-based training can influence the learning curve. METHODS: Over a period of 18 months (2011-2012) 12 residents were evaluated in spinal surgery (12 cases per resident) by a skilled evaluator based on different criteria. The evaluation criteria (exposition of important anatomy, intraoperative bleeding, efficacy of using bipolar cauterization) were weighted and added to a single quality-score. The participating residents were divided into two groups. Only one group (n = 5) received video-based training. RESULTS: Residents showed an individually different but explicit increase in microsurgical skills. The quality-score during the first surgery compared with the end point of the study demonstrated a faster improvement of surgical skills in the group with video-based training than in the group without special training. Considering all residents together, the video-training group displayed a steeper gradient of microsurgical success. Comparison of the single resident's microsurgical skills showed individual disparities. Various biases that influence the learning success are under examination. CONCLUSION: Video-based training can improve microsurgical skills, leading to an improved learning curve. An earlier entry of the learning curve plateau in the video-training group promotes a higher acquisition of surgical skills. Because of the positive effect, we plan to apply the video-based training model to other neurosurgical subspecialties, especially neurovascular and skull base surgery.