Sarcopenia is associated with chemoradiotherapy discontinuation and reduced progression-free survival in glioblastoma patients.

PURPOSE: Sarcopenia may complicate treatment in cancer patients. Herein, we assessed whether sarcopenia measurements derived from radiation planning computed tomography (CT) were associated with complications and tumor progression during radiochemotherapy for glioblastoma. METHODS: Consecutive patients undergoing radiotherapy planning for glioblastoma between 2010 and 2021 were analyzed. Retrocervical muscle cross-sectional area (CSA) was measured via threshold-based semi-automated radiation planning CT analysis. Patients in the lowest sex-specific quartile of muscle measurements were defined as sarcopenic. We abstracted treatment characteristics and tumor progression from the medical records and performed uni- and multivariable time-to-event analyses. RESULTS: We included 363 patients in our cohort (41.6% female, median age 63 years, median time to progression 7.7 months). Sarcopenic patients were less likely to receive chemotherapy (p < 0.001) and more likely to be treated with hypofractionated radiotherapy (p = 0.005). Despite abbreviated treatment, they more often discontinued radiotherapy (p = 0.023) and were more frequently prescribed corticosteroids (p = 0.014). After treatment, they were more often transferred to inpatient palliative care treatment (p = 0.035). Finally, progression-free survival was substantially shorter in sarcopenic patients in univariable (median 5.1 vs. 8.4 months, p < 0.001) and multivariable modeling (hazard ratio 0.61 [confidence interval 0.46-0.81], p = 0.001). CONCLUSION: Sarcopenia is a strong risk factor for treatment discontinuation and reduced progression-free survival in glioblastoma patients. We propose that sarcopenic patients should receive intensified supportive care during radiotherapy and during follow-up as well as expedited access to palliative care.

Maximal cardiopulmonary exercise testing in glioblastoma patients undergoing chemotherapy: assessment of feasibility, safety, and physical fitness status.

PURPOSE: Maximal cardiopulmonary exercise testing (max. CPET) provides the most accurate measurement of cardiorespiratory fitness. However, glioblastoma (GBM) patients often undergo less intensive tests, e.g., 6-min walk test or self-rating scales. This study aims to demonstrate feasibility and safety of max. CPET in GBM patients, concurrently evaluating their physical fitness status. METHODS: Newly diagnosed GBM patients undergoing adjuvant chemotherapy were offered participation in an exercise program. At baseline, max. CPET assessed cardiorespiratory fitness including peak oxygen consumption (VO2peak), peak workload, and physical work capacity (PWC) at 75% of age-adjusted maximal heart rate (HR). Criteria for peak workload were predefined based on threshold values in HR, respiratory quotient, respiratory equivalent, lactate, and rate of perceived effort. Data were compared to normative values. Adverse events were categorized according to standardized international criteria. Further, self-reported exercise data pre- and post-diagnosis were gathered. RESULTS: All 36 patients (median-aged 60; 21 men) met the predefined criteria for peak workload. Mean absolute VO2peak was 1750 ± 529 ml/min, peak workload averaged 130 ± 43 W, and mean PWC was 0.99 ± 0.38 W/kg BW, all clinically meaningful lower than age- and sex-predicted normative values (87%, 79%, 90%, resp.). Only once (3%) a minor, transient side effect occurred (post-test dizziness, no intervention needed). Self-reported exercise decreased from 15.8 MET-h/week pre-diagnosis to 7.2 MET-h/week post-diagnosis. CONCLUSION: Max. CPET in this well-defined population proved feasible and safe. GBM patients exhibit reduced cardiorespiratory fitness, indicating the need for tailored exercise to enhance health and quality of life. CPET could be essential in establishing precise exercise guidelines.

The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Beyond fluorescence-guided resection: 5-ALA-based glioblastoma therapies.

Glioblastoma is the most common primary malignant brain tumor. Despite advances in multimodal concepts over the last decades, prognosis remains poor. Treatment of patients with glioblastoma remains a considerable challenge due to the infiltrative nature of the tumor, rapid growth rates, and tumor heterogeneity. Standard therapy consists of maximally safe microsurgical resection followed by adjuvant radio- and chemotherapy with temozolomide. In recent years, local therapies have been extensively investigated in experimental as well as translational levels. External stimuli-responsive therapies such as Photodynamic Therapy (PDT), Sonodynamic Therapy (SDT) and Radiodynamic Therapy (RDT) can induce cell death mechanisms via generation of reactive oxygen species (ROS) after administration of five-aminolevulinic acid (5-ALA), which induces the formation of sensitizing porphyrins within tumor tissue. Preliminary data from clinical trials are available. The aim of this review is to summarize the status of such therapeutic approaches as an adjunct to current standard therapy in glioblastoma.

Conceptual development of an intensive exercise program for glioma patients (ActiNO): summary of clinical experience.

PURPOSE: Exercise proved to reduce cancer-related symptoms and prolong survival in some cancer types. However, brain tumor patients are often advised against strenuous exercise. Here, we summarize our experience with a submaximal exercise program for glioma patients: ActiNO (Active in Neuro-Oncology). METHODS: Glioma patients were invited to participate in the program. Since 2011, a sports scientist individualized two one-hour sessions per week adapted to the patients' symptoms. One session consisted of bicycle ergometry (average workload: 75% of maximum heart rate), the other of whole-body resistance training. Both sessions were further complimented by coordinative elements. Cardiorespiratory fitness was assessed using the "Physical Work Capacity" procedure. Patients were followed up regularly to assess adherence to the program and disease activity. RESULTS: Until December 2019, 45 glioma patients, median-aged 49 years (IQR 42-59), were included in the analysis. Most patients suffered from glioblastoma (58%), followed by diffuse lower-grade astrocytoma (29%). In overall 1828 training sessions, two minor epileptic events occurred (1 speech arrest; 1 focal seizure). During fitness assessment, all patients achieved at least 75% of their age-adjusted maximum heart rate. Peak workload averaged 172 W (95% CI 156-187). Median survival of participating glioblastoma patients was 24.1 months (95% CI 8.6-39.5). CONCLUSION: This supervised training program with submaximal exertion was feasible and safe in glioma regardless of WHO grading. Based on these experiences, we initiated a prospective multicenter study to objectify improvements in physical performance and quality of life in patients with glioblastoma.

Molecular predictors for decitabine efficacy in meningiomas - a pilot study.

PURPOSE: Effective chemotherapeutical agents for the treatment of meningiomas are still lacking. Previous in-vitro analyses revealed efficacy of decitabine (DCT), a DNA methyltransferase (DNMT) inhibitor established in the treatment of leukemia, in a yet undefined subgroup of meningiomas. METHODS: Effects of DCT on proliferation and viability was analyzed in primary meningioma cells by immunofluorescence and MTT assays, and cases were classified as drug responders and non-responders. Molecular preconditions for efficacy were analyzed using immunofluorescence for Ki67, DNMT1, and five oncogenes (TRIM58, FAM84B, ELOVL2, MAL2, LMO3) previously found to be differentially methylated after DCT exposition, as well as by genome-wide DNA methylation analyses. RESULTS: Efficacy of DCT (10µM) was found in eight (62%) of 13 meningioma cell lines 48 h after drug exposition (p < .05). DCT significantly reduced DNMT1 expression in all but two cell lines, and median ΔDNMT1 reduction 48 h after drug exposition was lower in DCT-resistant (-11.1%) than in DCT-sensitive (-50.5%, p = .030) cells. Rates of cell lines responsive to DCT exposition distinctly decreased to 25% after 72 h. No significant correlation of the patients´ age, sex, histological subtype, location of the paternal tumor, expression of Ki67, DNMT1 or the analyzed oncogenes with treatment response was found (p > .05, each). DCT efficacy was further independent of the methylation class and global DNA methylation of the paternal tumor. CONCLUSION: Early effects of DCT in meningiomas are strongly related with DNMT1 expression, while clinical, histological, and molecular predictors for efficacy are sparse. Kinetics of drug efficacy might indicate necessity of repeated exposition and encourage further analyses.

Undetected pseudoprogressions in the CeTeG/NOA-09 trial: hints from postprogression survival and MRI analyses.

PURPOSE: In the randomized CeTeG/NOA-09 trial, lomustine/temozolomide (CCNU/TMZ) was superior to TMZ therapy regarding overall survival (OS) in MGMT promotor-methylated glioblastoma. Progression-free survival (PFS) and pseudoprogression rates (about 10%) were similar in both arms. Further evaluating this discrepancy, we analyzed patterns of postprogression survival (PPS) and MRI features at first progression according to modified RANO criteria (mRANO). METHODS: We classified the patients of the CeTeG/NOA-09 trial according to long vs. short PPS employing a cut-off of 18 months and compared baseline characteristics and survival times. In patients with available MRIs and confirmed progression, the increase in T1-enhancing, FLAIR hyperintense lesion volume and the change in ADC mean value of contrast-enhancing tumor upon progression were determined. RESULTS: Patients with long PPS in the CCNU/TMZ arm had a particularly short PFS (5.6 months). PFS in this subgroup was shorter than in the long PPS subgroup of the TMZ arm (11.1 months, p = 0.01). At mRANO-defined progression, patients of the CCNU/TMZ long PPS subgroup had a significantly higher increase of mean ADC values (p = 0.015) and a tendency to a stronger volumetric increase in T1-enhancement (p = 0.22) as compared to long PPS patients of the TMZ arm. CONCLUSION: The combination of survival and MRI analyses identified a subgroup of CCNU/TMZ-treated patients with features that sets them apart from other patients in the trial: short first PFS despite long PPS and significant increase in mean ADC values upon mRANO-defined progression. The observed pattern is compatible with the features commonly observed in pseudoprogression suggesting mRANO-undetected pseudoprogressions in the CCNU/TMZ arm of CeTeG/NOA-09.

Vascular anomalies in patients with growth hormone-secreting pituitary adenomas: illustrative case report and systematic review of the literature.

PURPOSE: Endonasal resection is the first-line treatment for patients harboring growth hormone (GH)-secreting pituitary adenomas. The complexity of the parasellar neurovascular structures makes pre-operative diagnostic imaging essential to understanding the anatomy of this region. We aimed to describe vascular anomalies in acromegalic patients and emphasize their relevance for surgery and preoperative planning. METHODS: A systematic review following the PRISMA statement was performed in July 2021. RESULTS: Thirty-three studies were evaluated. Elevated GH and insulin-like growth factor-1 (IGF-1) levels are linked to the occurrence of cardiovascular risk factors. This is attributed to endothelial dysfunction, mainly caused by changes in flow-mediated dilatation (FMD), which is probably the main cause of vascular anomalies in acromegaly. The occurrence of protrusions of the internal carotid artery (ICA) (35-53%), a narrow intercarotid distance, and an asymmetrical course was described. In 13-18% of acromegalic patients, the presence of an intracerebral aneurysm could be reported (incidence in the general population:0.8-1.3%). The selected studies were however performed with a small patient sample (range:1-257). We present a case report of a 57y/o male patient with anomalies of the ICA ("kissing carotid arteries") harboring a GH-secreting adenoma, which was resected via an endoscopic endonasal approach. CONCLUSIONS: There is an association between acromegaly and endothelial dysfunction, which increases cardiovascular risk factors and vascular anomalies. Preoperative vascular imaging, e.g., CT angiography, should be implemented as a standard to identify patients at risk and estimate surgical morbidity. However, no evidence-based recommendations exist so far, so future studies are necessary.

Prognosis and histology of sporadic synchronous and metachronous meningiomas and comparative analyses with singular lesions.

Synchronous or metachronous growth of multiple tumors (≥ 2) is found in up to 20% of meningioma patients. However, biological as well as histological features and prognosis are largely unexplored. Clinical and histological characteristics were retrospectively investigated in 95 patients harboring 226 multiple meningiomas (MMs) and compared with 135 cases of singular meningiomas (SM) using uni- and multivariate analyses. In MM, tumors occurred synchronously and metachronously in 62% and 38%, respectively. WHO grade was intra-individually constant in all but two MMs, and histological subtype varied in 13% of grade 1 tumors. MM occurred more commonly in convexity/parasagittal locations, while SM were more frequent at the skull base (p < .001). In univariate analyses, gross total resection (p = .014) and high-grade histology in MM were associated with a prolonged time to progression (p < .001). Most clinical characteristics and rates of high-grade histology were similar in both groups (p ≥ .05, each). Multivariate analyses showed synchronous/metachronous meningioma growth (HR 4.50, 95% CI 2.26-8.96; p < .001) as an independent predictor for progression. Compared to SM, risk of progression was similar in cases with two (HR 1.56, 95% CI .76-3.19; p = .224), but exponentially raised in patients with 3-4 (HR 3.25, 1.22-1.62; p = .018) and ≥ 5 tumors (HR 13.80, 4.06-46.96; p < .001). Clinical and histological characteristics and risk factors for progression do not relevantly differ between SM and MM. Although largely constant, histology and WHO grade occasionally intra-individually vary in MM. A distinctly higher risk of disease progression in MM as compared to SM might reflect different underlying molecular alterations.

Confounders of intraoperative frozen section pathology during glioma surgery.

Although frozen section pathology (FSP) is commonly performed during surgery for glioma-suspicious lesions, confounders of accuracy are largely unknown. FSP and final diagnosis were compared in 398 surgeries for glioma-suspicious lesions. Diagnostic accuracy, risk factors for diagnostic shift from neoplastic to non-neoplastic tissue and vice versa according to the final diagnosis, and the impact on intraoperative and postoperative decision-making were analyzed. Diagnostic shift occurred in 70 cases (18%), and sensitivity, specificity, and the positive (PPV) and negative (NPV) predictive value of FSP were 82.5%, 77.8%, 99.4%, and 9.3%, respectively. No correlations between shift and patients' age and sex, sample fluorescence or volume, tumor location, correct information on the pathology form, final high- or low-grade histology, or molecular alterations were found (p > .05, each). Shift was more common after irradiation (25% vs 15%; p = .025) or chemotherapy (26% vs 15%; p = .022) than in treatment naïve cases and correlated with the type of surgery (p = .002). FSP altered intraoperative decision-making in 25 cases (6%). Postoperative shift led to repeated surgery in 12 patients (3%). In 45 cases, in which FSP and final diagnosis based on the same tissue, shift occurred in only 5 patients (11%), and sensitivity, specificity, PPV, and NPV for FSP were 77.4%, 78.6%, 88.9%, and 61.1%, respectively. No correlations between diagnostic shift and any of the analyzed variables were found (p > .05, each). Although accuracy of FSP during glioma surgery is sufficient, moderate NPV should be considered during intraoperative decision-making. While confounders are sparse, accuracy might be increased by repeated sampling. Diagnostic shift rarely alters postoperative treatment strategy.

Iatrogenic lumbosacral infiltration with petroleum (hydrodesulfurized heavy) with secondary intrathecal distribution-a case report.

Petroleum is commonly used as a solvent, and primary intrathecal administration or secondary diffusion and subsequent clinical management has not been reported. We report the case of a male patient with intrathecal petroleum diffusion following accidental lumbar infiltration. After the onset of secondary myeloencephalopathy with coma and tetraparesis, continuous cranio-lumbar irrigation using an external ventricular and a lumbar drain was established. Cranial imaging revealed distinct supra- and infratentorial alterations. The patient improved slowly and was referred to rehabilitation. Intrathecal petroleum leads to myeloencephalopathy and continuous cranio-lumbar irrigation might be a safe treatment option.

Mixed Reality as a Teaching Tool for Medical Students in Neurosurgery.

Background and Objectives: Simulation-based learning within neurosurgery provides valuable and realistic educational experiences in a safe environment, enhancing the current teaching model. Mixed reality (MR) simulation can deliver a highly immersive experience through head-mounted displays and has become one of the most promising teaching tools in medical education. We aimed to identify whether an MR neurosurgical simulation module within the setting of an undergraduate neurosurgical hands-on course could improve the satisfaction of medical students. Materials and Methods: The quasi-experimental study with 223 medical students [120 in the conventional group (CG) and 103 in the MR-group (MRG)] was conducted at the University Hospital Münster, Münster, Germany. An MR simulation module was presented to the intervention group during an undergraduate neurosurgical hands-on course. Images of a skull fracture were reconstructed into 3D formats compatible with the MR-Viewer (Brainlab, Munich, Germany). Participants could interact virtually with the model and plan a surgical strategy using Magic Leap goggles. The experience was assessed by rating the course on a visual analog scale ranging from 1 (very poor) to 100 (very good) and an additional Likert-scale questionnaire. Results: The satisfaction score for CG and MRG were 89.3 ± 13.3 and 94.2 ± 7.5, respectively. The Wilcoxon rank-sum test showed that MR users (Mdn = 97.0, IQR = 4, n = 103) were significantly more satisfied than CG users (Mdn = 93.0, IQR = 10, n = 120; ln(W) = 8.99, p < 0.001) with moderate effect size (r^biserial = 0.30, CI95 [0.15, 0.43]), thus indicating that the utilization of MR-simulation is associated with greater satisfaction. Conclusions: This study reports a positive response from medical students towards MR as an educational tool. Feedback from the medical students encourages the adoption of disruptive technologies into medical school curricula.

Resection of Intramedullary Hemangioblastoma: Timing of Surgery and Its Impact on Neurological Outcome and Quality of Life.

Background and Objectives: Spinal intramedullary hemangioblastomas (SIMH) are benign vascular lesions that are pathological hallmarks of von Hippel-Lindau disease (vHL) and constitute the third most common intramedullary neoplasm in adults. So far, maximal and safe resection is the first choice of treatment. However, as SIMH show no malignant transformation, it remains unclear whether surgical resection is beneficial for all patients. Materials and Methods: We retrospectively analyzed the surgical outcomes of 27 patients who were treated between 2014 and 2022 at our neurosurgical department and investigated potential risk factors that influence the surgical outcome. Pre- and postoperative neurological status were classified according to the McCormick scale. Furthermore, surgical quality indicators, such as length of hospital stay (LOS; days), 90-day readmissions, nosocomial infections, and potential risk factors that might influence the surgical outcome, such as tumor size and surgical approach, have been analyzed. In addition to that, patients were asked to fill out the EQ-5D-3L questionnaire to assess their quality of life after surgery. Results: Surgery on SIMH patients that display no or minor neurological deficits (McCormick scale I or II) is associated with a favorable postoperative outcome and overall higher quality of life compared to those patients that already suffer from severe neurological deficits (McCormick scale III or IV). Conclusion: Early surgical intervention prior to the development of severe neurological deficits may offer a better neurological outcome and quality of life.

The use of radiosensitizing agents in the therapy of glioblastoma multiforme-a comprehensive review.

BACKGROUND: Glioblastoma is the most common malignant brain tumor in human adults. Despite several improvements in resective as well as adjuvant therapy over the last decades, its overall prognosis remains poor. As a means of improving patient outcome, the possibility of enhancing radiation response by using radiosensitizing agents has been tested in an array of studies. METHODS: A comprehensive review of clinical trials involving radiation therapy in combination with radiosensitizing agents on patients diagnosed with glioblastoma was performed in the National Center for Biotechnology Information's PubMed database. RESULTS: A total of 96 papers addressing this matter were published between 1976 and 2021, of which 63 matched the subject of this paper. All papers were reviewed, and their findings discussed in the context of their underlining mechanisms of radiosensitization. CONCLUSION: In the history of glioblastoma treatment, several approaches of optimizing radiation-effectiveness using radiosensitizers have been made. Even though several different strategies and agents have been explored, clear evidence of improved patient outcome is still missing. Tissue-selectiveness and penetration of the blood-brain barrier seem to be major roadblocks; nevertheless, modern strategies try to circumvent these obstacles, using novel sensitizers based on preclinical data or alternative ways of delivery.

The applicability of established clinical and histopathological risk factors for tumor recurrence during long-term postoperative care in meningioma patients.

Risk factors to predict late-onset tumor recurrence in meningioma patients are urgently needed to schedule control intervals during long-term follow-up. We therefore analyzed the value of established risk factors for postoperative meningioma recurrence for the prediction of long-term prognosis. Correlations of clinical and histopathological variables with tumor relapse after 3, 5, and 10 years following microsurgery were analyzed in uni- and multivariate analyses, and compared to findings in the entire cohort. In the entire cohort (N = 1218), skull base location (HR: 1.51, 95%CI 1.05-2.16; p = .026), Simpson ≥ IV resections (HR: 2.41, 95%CI 1.52-3.84; p < .001), high-grade histology (HR: 3.70, 95%CI 2.50-5.47; p < .001), and male gender (HR: 1.46, 95%CI 1.01-2.11; p = .042) were independent risk factors for recurrence. Skull base location (HR: 1.92, 95%CI 1.17-3.17; p = .010 and HR: 2.02, 95%CI 1.04-3.95; p = .038) and high-grade histology (HR: 1.87, 95%CI 1.04-3.38; p = .038 and HR: 2.29, 95%CI 1.07-4.01; p = .034) but not subtotal resection (HR: 1.53, 95%CI .68-3.45; p = .303 and HR: 1.75, 95%CI .52-5.96; p = .369) remained correlated with recurrence after a recurrence-free follow-up of ≥ 3 and ≥ 5 years, respectively. Postoperative tumor volume was related with recurrence in general (p < .001) but not beyond a follow-up of ≥ 3 years (p > .05). In 147 patients with a follow-up of ≥ 10 years, ten recurrences occurred and were not correlated with any of the analyzed variables. Skull base tumor location and high-grade histology but not the extent of resection should be considered when scheduling the long-term follow-up after meningioma surgery. Recurrences ≥ 10 years after surgery are rare, and predictors are lacking.

Expression of decitabine-targeted oncogenes in meningiomas in vivo.

Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine (DCT, 5-aza-2'-deoxycytidine) to be effective in high-grade meningiomas and, moreover, to induce hypomethylation of distinct oncogenes only sparsely described in meningiomas in vivo yet.Expression of the corresponding onco- and tumor suppressor genes TRIM58, FAM84B, ELOVL2, MAL2, LMO3, and DIO3 were analyzed and scored by immunohistochemical staining and RT-PCR in samples of 111 meningioma patients. Correlations with clinical and histological variables and prognosis were analyzed in uni- and multivariate analyses.All analyzed oncogenes were highly expressed in meningiomas. Expression scores of TRIM58 tended to be higher in benign than in high-grade tumors 20 vs 16 (p = .002) and all 9 samples lacking TRIM58 expression displayed WHO grade II/III histology. In contrast, median expression scores for both FAM84B (6 vs 4, p ≤ .001) and ELOVL2 (9 vs 6, p < .001) were increased in high-grade as compared to benign meningiomas. DIO3 expression was distinctly higher in all analyzed samples as compared to the reference decitabine-resistant Ben-Men 1 cell line. Increased ELOVL2 expression (score ≥ 8) correlated with tumor relapse in both uni- (HR: 2.42, 95%CI 1.18-4.94; p = .015) and multivariate (HR: 2.09, 95%CI 1.01-4.44; p = .046) analyses.All oncogenes involved in DCT efficacy in vitro are also widely expressed in vivo, and expression is partially associated with histology and prognosis. These results strongly encourage further analyses of DCT efficiency in meningiomas in vitro and in situ.

Applicability of contemporary quality indicators in vestibular surgery-do they accurately measure tumor inherent postoperative complications of vestibular schwannomas?

BACKGROUND: Due to rising costs in health care delivery, reimbursement decisions have progressively been based on quality measures. Such quality indicators have been developed for neurosurgical procedures, collectively. We aimed to evaluate their applicability in patients that underwent surgery for vestibular schwannoma and to identify potential new disease-specific quality indicators. METHODS: One hundred and three patients operated due to vestibular schwannoma were subject to analysis. The primary outcomes of interest were 30-day and 90-day reoperation, readmission, mortality, nosocomial infection and surgical site infection (SSI) rates, postoperative cerebral spinal fluid (CSF) leak, facial, and hearing function. The secondary aim was the identification of prognostic factors for the mentioned primary outcomes. RESULTS: Thirty-day (90-days) outcomes in terms of reoperation were 10.7% (14.6%), readmission 9.7% (13.6%), mortality 1% (1%), nosocomial infection 5.8%, and SSI 1% (1%). A 30- versus 90-day outcome in terms of CSF leak were 6.8% vs. 10.7%, new facial nerve palsy 16.5% vs. 6.1%. Hearing impairment from serviceable to non-serviceable hearing was 6.8% at both 30- and 90-day outcome. The degree of tumor extension has a significant impact on reoperation (p < 0.001), infection (p = 0.015), postoperative hemorrhage (p < 0.001), and postoperative hearing loss (p = 0.026). CONCLUSIONS: Our data demonstrate the importance of entity-specific quality measurements being applied even after 30 days. We identified the occurrence of a CSF leak within 90 days postoperatively, new persistent facial nerve palsy still present 90 days postoperatively, and persisting postoperative hearing impairment to non-serviceable hearing as potential new quality measurement variables for patients undergoing surgery for vestibular schwannoma.

Andexanet-Alfa-Associated Heparin Resistance in the Context of Hemorrhagic Stroke.

BACKGROUND: With a growing number of patients on new oral anticoagulants, interest in reversal agents is rising. Andexanet alfa is used for reversal of factor Xa inhibitors in intracranial hemorrhage. METHODS: We provide a brief review on andexanet-alfa-associated heparin resistance and discuss potentially critical situations from different clinical perspectives. RESULTS: Case reports point out that andexanet alfa can cause unresponsiveness to heparin, leading to catastrophic events. As a result, regulatory bodies have issued warning notices to avoid heparinization parallel to the use of andexanet alfa. CONCLUSIONS: Although well known to hematologists, the phenomenon is underrecognized among stroke clinicians. However, patients with intracranial hemorrhage frequently undergo endovascular or surgical interventions that require periprocedural administration of heparin.

Minimally Invasive Facetectomy and Fusion for Resection of Extensive Dumbbell Tumors in the Lumbar Spine.

Background and Objectives: Resection of dumbbell tumors can be challenging, and facet joint sparing approaches carry the risk of incomplete resection. In contrast, additional facetectomy may allow better surgical exposure at the cost of spinal stability. The aim of this study is to compare facet-sparing and facetectomy approaches for the treatment of lumbar spine dumbbell tumors. Materials and Methods: In a cohort study setting, we analyzed Eden type 2 and 3 tumors operated in our department. Conventional facet-sparing microsurgical or facetectomy approaches with minimally invasive fusions were performed according to individual surgeons' preference. Primary outcomes were extent of resection and tumor progression over time. Secondary outcomes were perioperative adverse events. Results: Nineteen patients were included. Nine patients were operated on using a facet-sparing technique. Ten patients underwent facetectomy and fusion. While only one patient (11%) in the facet-sparing group experienced gross total resection (GTR), this was achieved for all patients in the facetectomy group (100%). The relative risk (RR) for incomplete resection in the facet-sparing cohort was 18.7 (95% CI 1.23-284.047; p = 0.035). In addition, time to progression was shorter in the facet-sparing cohort (p = 0.022) and all patients with a residual tumor underwent a second resection after a median follow-up time of 42 months (IQR 25-66). Conclusions: Minimally invasive resection of lumbar Eden type 2 and 3 dumbbell tumors including facetectomy in combination with instrumentation appears to be safe and superior to the facet-sparing approach in terms of local tumor control.

TERT promoter mutation and chromosome 6 loss define a high-risk subtype of ependymoma evolving from posterior fossa subependymoma.

Subependymomas are benign tumors characteristically encountered in the posterior fossa of adults that show distinct epigenetic profiles assigned to the molecular group "subependymoma, posterior fossa" (PFSE) of the recently established DNA methylation-based classification of central nervous system tumors. In contrast, most posterior fossa ependymomas exhibit a more aggressive biological behavior and are allocated to the molecular subgroups PFA or PFB. A subset of ependymomas shows epigenetic similarities with subependymomas, but the precise biology of these tumors and their potential relationships remain unknown. We therefore set out to characterize epigenetic traits, mutational profiles, and clinical outcomes of 50 posterior fossa ependymal tumors of the PFSE group. On histo-morphology, these tumors comprised 12 ependymomas, 14 subependymomas and 24 tumors with mixed ependymoma-subependymoma morphology. Mixed ependymoma-subependymoma tumors varied in their extent of ependymoma differentiation (2-95%) but consistently exhibited global epigenetic profiles of the PFSE group. Selective methylome analysis of microdissected tumor components revealed CpG signatures in mixed tumors that coalesce with their pure counterparts. Loss of chr6 (20/50 cases), as well as TERT mutations (21/50 cases), were frequent events enriched in tumors with pure ependymoma morphology (p < 0.001) and confined to areas with ependymoma differentiation in mixed tumors. Clinically, pure ependymoma phenotype, chr6 loss, and TERT mutations were associated with shorter progression-free survival (each p < 0.001). In conclusion, our results suggest that subependymomas may acquire genetic and epigenetic changes throughout tumor evolution giving rise to subclones with ependymoma morphology (resulting in mixed tumors) that eventually overpopulate the subependymoma component (pure PFSE ependymomas).