Expertise in surgical neuro-oncology. Results of a survey by the EANS neuro-oncology section.

Introduction: Technical advances and the increasing role of interdisciplinary decision-making may warrant formal definitions of expertise in surgical neuro-oncology. Research question: The EANS Neuro-oncology Section felt that a survey detailing the European neurosurgical perspective on the concept of expertise in surgical neuro-oncology might be helpful. Material and methods: The EANS Neuro-oncology Section panel developed an online survey asking questions regarding criteria for expertise in neuro-oncological surgery and sent it to all individual EANS members. Results: Our questionnaire was completed by 251 respondents (consultants: 80.1%) from 42 countries. 67.7% would accept a lifetime caseload of >200 cases and 86.7% an annual caseload of >50 as evidence of neuro-oncological surgical expertise. A majority felt that surgeons who do not treat children (56.2%), do not have experience with spinal fusion (78.1%) or peripheral nerve tumors (71.7%) may still be considered experts. Majorities believed that expertise requires the use of skull-base approaches (85.8%), intraoperative monitoring (83.4%), awake craniotomies (77.3%), and neuro-endoscopy (75.5%) as well as continuing education of at least 1/year (100.0%), a research background (80.0%) and teaching activities (78.7%), and formal interdisciplinary collaborations (e.g., tumor board: 93.0%). Academic vs. non-academic affiliation, career position, years of neurosurgical experience, country of practice, and primary clinical interest had a minor influence on the respondents' opinions. Discussion and conclusion: Opinions among neurosurgeons regarding the characteristics and features of expertise in neuro-oncology vary surprisingly little. Large majorities favoring certain thresholds and qualitative criteria suggest a consensus definition might be possible.

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.

Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

How I do it-optimizing radiofrequency ablation in spinal metastases using iCT and navigation.

BACKGROUND: Exact positioning of the radiofrequency ablation (RFA) probe for tumor treatment under fluoroscopic guidance can be difficult because of potentially small inaccessible lesions and the radiation dose to the medical staff in RFA. In addition, vertebroplasty (VP) can be significantly high. METHOD: Description and workflow of RFA in spinal metastasis using iCT (intraoperative computed tomography) and 3D-navigation-based probe placement followed by VP. CONCLUSION: RFA and VP can be successfully combined with iCT-based navigation, which leads to a reduction of radiation to the staff and optimal probe positioning due to 3D navigation.

Preoperative prediction of language function by diffusion tensor imaging.

For surgery of eloquent tumors in language areas, the accepted gold standard is functional mapping through direct cortical stimulation (DCS) in awake patients. Ever since, neuroscientists are searching for reliable noninvasive detection of function in the human brain, with variable success. The potential of diffusion tensor imaging (DTI) in combination with computational cortical parcellation to predict functional areas in language eloquent tumors has not been assessed so far. We present a proof-of-concept report involving awake surgery for a temporodorsal tumor. Postoperatively, the imaging was extensively studied and a predictive value of multimodal MR imaging for the possible extent of resection was analyzed. After resection using DCS, the extent of resection and functional outcome were correlated with the processed imaging. Preoperative imaging of our patient was taken to compute the lesion volume as a seed for tractography (DTI) and combined with a tractography of the entire hemisphere. For better spatial resolution, an elastic image fusion was performed to correct the distortion of DTI data. After subtotal resection and imaging analysis, the status of the superior part of the lesion could be identified and predicted as functional cortex. There was a strong correlation between the tumor remnant during surgery and the imaging parameters of DTI connectivity of the eloquent tissue. A combination of complex DTI processing may be able to predict function in a patient suffering eloquent brain tumors and thus allow estimation of extent of resection.

Serious tumor seeding after brainstem biopsy and its treatment-a case report and review of the literature.

Stereotactic brain biopsies for histopathological diagnosis are a common technique in case of intracranial lesions, particularly in those not amenable for resection. Tumor seeding alongside the surgical trajectory after fine-needle aspiration is a known problem in several visceral tumors. Whereas in these cases a complete resection of the biopsy trajectory may later be performed, this strategy is not feasible in stereotactic brain biopsy. We report a case of tumor seeding along the entire biopsy tract after stereotactic biopsy of a brainstem metastasis. A 68-year-old male patient with a concomitantly diagnosed kidney lesion presented with a singular lesion in the brainstem. After confirmation of metastasis by stereotactic biopsy, stereotactic radiosurgery (SRS) was applied. The primary tumor was treated by laparoscopic nephrectomy. Three months after SRS, the patient presented with a secondary clinical deterioration for only a few weeks. The MRI scan showed tumor seeding along the entire biopsy tract. Salvage treatment including hypofractionated stereotactical irradiation and seven cycles of bevacizumab was administered to obtain symptom control. Massive seeding of tumor after stereotactic biopsy accordingly rare, taking into account that stereotactic biopsy is a very common neurosurgical intervention. Nonetheless, we think that the potential risk has to be kept in mind, as it might be neglected.

Awake brain mapping of cortex and subcortical pathways in brain tumor surgery.

Awake surgery is not a new technique: this is a new philosophy. Indeed, in surgery for diffuse gliomas performed in awake patients, the goal is not anymore to remove a "tumor mass" according to oncological boundaries (which in essence do not exist in infiltrating neoplasms), but to resect a part of the brain invaded by a chronic tumoral disease, according to functional limits both at cortical and subcortical levels. Therefore, intraoperative electrical mapping is accepted as the gold standard in order to gain information about the functionality of the underlying tissue when performing neuro-oncological surgery. This review should give the reader an overview of principles and indications of mapping of eloquent cortex and subcortical pathways with practical considerations for cerebral tumors. In gliomas, awake mapping has been demonstrated as increasing the surgical indications in so-called "critical areas" with nonetheless a significant decrease of postoperative morbidity­while maximizing the extent of resection. Beyond clinical implications, awake surgery represents a unique opportunity to study neural networks underpinning sensorimotor, visuospatial, language, executive and even behavioral functions in humans. This led to propose new models of connectomics, breaking with the localizationist view of brain processing, and opening the window to the concept of neuroplasticity. In summary, awake mapping enables to make a link between surgical neurooncology and cognitive neurosciences, to improve both survival and quality of life of glioma patients.

Awake brain mapping of cortex and subcortical pathways in brain tumor surgery.

Awake surgery is not a new technique: this is a new philosophy. Indeed, in surgery for diffuse gliomas performed in awake patients, the goal is not anymore to remove a "tumor mass" according to oncological boundaries (which in essence do not exist in infiltrating neoplasms), but to resect a part of the brain invaded by a chronic tumoral disease, according to functional limits both at cortical and subcortical levels. Therefore, intraoperative electrical mapping is accepted as the gold standard in order to gain information about the functionality of the underlying tissue when performing neurooncological surgery. This review should give the reader an overview of principles and indications of mapping of eloquent cortex and subcortical pathways with practical considerations for cerebral tumors. In gliomas, awake mapping has been demonstrated as increasing the surgical indications in socalled "critical areas" with nonetheless a significant decrease of postoperative morbidity while maximizing the extent of resection. Beyond clinical implications, awake surgery represents a unique opportunity to study neural networks underpinning sensorimotor, visuospatial, language, executive and even behavioral functions in humans. This led to propose new models of connectomics, breaking with the localisationist view of brain processing, and opening the window to the concept of neuroplasticity. In summary, awake mapping enables to make a link between surgical neurooncology and cognitive neurosciences, to improve both survival and quality of life of glioma patients.

Prolonged administration of temozolomide in adult patients with anaplastic glioma.

PURPOSE: Prolonged administration of temozolomide is widely used in patients with glioblastoma; whereas the treatment of anaplastic glioma differs between neurooncological centres. The safety, feasibility and efficacy of prolonged temozolomide administration in patients with anaplastic gliomas was evaluated. PATIENTS AND METHODS: Forty-two patients with primary, recurrent or secondary anaplastic glioma were retrospectively analysed for the course of their disease. Treatment mostly consisted of surgery, followed by radiotherapy with concomitant and adjuvant temozolomide. In five patients with recurrence of primary anaplastic glioma, chemotherapy was initiated without previous surgery. Temozolomide was administered until evidence of tumour recurrence, appearance of serious side-effects or patients' wish to finish chemotherapy. RESULTS: The median overall survival (OS) was 39 months with a median cycle number of 7.5 (1-42). Treatment with temozolomide was stopped in 12 patients due to side-effects in general, whereas in only three patients (7.1%) treatment had to be discontinued due to haematological side-effects. There was no evidence of treatment related infections or grade IV toxicity. Extent of surgery had a significant influence on OS in anaplastic gliomas, the number of adjuvant temozolomide cycles showed a positive influence as well on time to progression (TTP) and OS. CONCLUSION: Prolonged administration of adjuvant temozolomide is safe and can be favorable for patients with anaplastic gliomas.

Effect of mouth opening on bypass function after combined revascularization for Moyamoya disease.

Moyamoya disease represents a rare steno-occlusive disease of the internal carotid artery (ICA) with a reactive and pathological basal network of collateral vessels. It may lead to ischemic stroke or intracerebral hemorrhage. Treatment options are either direct or indirect revascularization procedures or a combination thereof. Specialized centers report sufficient revascularization in most patients and low complication rates.Between 2005 and 2008, direct extra-intracranial bypass surgery in combination with encephalomyosynangiosis (EMS) was performed in 71 Moyamoya patients at the Mannheim University Medical Center.Following one case of reversible neurological deficits associated with mouth opening, we prospectively evaluated the effect of mouth opening on bypass function in this patient and four further consecutive patients by digital subtraction angiography.Three out of five patients showed alterations in bypass patency upon mouth opening. The obstruction was located at the junction of the bypass and the temporal muscle. Two temporary occlusions and one case of decreased flow were observed. One patient demonstrated reversible hemiparesis and aphasia.

Management of patients with low-grade gliomas - a survey among German neurosurgical departments.

BACKGROUND AND AIMS OF THE STUDY: The diagnosis and treatment of low-grade gliomas (LGG) are multimodal. Today, there is no defined standard in diagnosis and treatment. Controversies are, in general, about a "wait-and-see" strategy, diagnostic workup, surgical intervention, postoperative imaging, adjuvant treatment, and follow-up. The aim of this study is to gain an overview about management strategies of high-volume German neurosurgical departments treating these patients. MATERIAL AND METHODS: A questionnaire including diagnostic, preoperative, perioperative, and postoperative parameters and 5 cases with magnetic resonance imaging data with questions to various treatment options in these patients was sent to all 34 German neurosurgical departments at university hospitals. RESULTS: In total, 24 questionnaires were returned and analysed. Centres were divided into those who generally practice a "wait-and-see" strategy vs. those who do not or only in highly selected cases. Statistical analyses were performed with Fisher test and Chi (2)-test. Interestingly, 50% of all centres routinely follow a "wait-and-see" strategy. CONCLUSION: Although the management of patients with LGG is complex and a simple questionnaire will not be able to define a standard in diagnosis and treatment, this study offers an overview on strategies at high-volume academic centres dealing with these patients. There is consensus to resect superficially located lobar and circumscribed low-grade lesions. However, the differences between centres become apparent with increasing complexity of the lesions.

Response to temozolomide in supratentorial multifocal recurrence of malignant ependymoma.

Intracranial anaplastic ependymomas are a very rare entity within the group of adult CNS neoplasms. Thus, no standard adjuvant therapy after surgical resection has been defined so far. External radiotherapy is commonly administered, but the role of chemotherapy is still unclear in malignant ependymomas. The case of a 25-year-old female patient with multifocal recurrence of a supratentorial malignant ependymoma administered temozolomide as second-line therapy is reported. Currently, 5 months after initiation of temozolomide treatment, there is no evidence of radiographic progression. Temozolomide could constitute a promising approach to supratentorial recurrent and multifocal anaplastic ependymoma of adults.