Surgical treatment of meningiomas improves neurocognitive functioning and quality of life - a prospective single-center study.

BACKGROUND AND PURPOSE: Early diagnosis and the refinement of treatment of patients with intracranial meningiomas have brought quality of life (QoL) and neurocognitive functioning as outcome measures into focus. The aim of this study is a comprehensive assessment of neurocognitive function, quality of life and the presence of depression in meningioma patients before and after surgery. METHODS: Patients with MRI diagnosis of intracranial meningioma and indication for surgery were prospectively included. A clinical neuropsychologist performed neurocognitive assessments within 3 months before and 12 months after surgery. The test battery included investigation of selective and divided attention, verbal and figural memory, executive functioning, and word fluency. Self-report questionnaires to assess depressive symptoms, QoL, and disease coping were administered. Raw values and t-values were compared pre-and postoperatively. Outcome was stratified by tumor- and peritumoral brain edema (PTBE) volumes, postoperative resolution of PTBE and WHO grade. The study included 18 predominantly female patients (83%) with a median age of 59 years and mostly CNS WHO grade 1 meningiomas (83%). RESULTS: There was a significant postoperative improvement in the ability to selectively react under stress, in working memory and improved delayed reproduction of verbal and visual memory content. QoL improved regarding a reduction in physical problems, an improvement in energy, and social functioning. There was a trend towards worse preoperative scores in all tests, and greater postoperative improvement in patients with PTBE. Tumor volume had no effect on the measured outcome. The patients did not suffer from depressive symptoms before the surgery but improved postoperatively and most patients had an active, problem-oriented coping strategy. CONCLUSION: Resection of intracranial meningiomas leads to an improvement in multiple neurocognitive domains and QoL. There is a trend towards poorer preoperative neurocognitive functioning and greater postoperative improvement in patients with PTBE. Depression appears to play a minor role in the context of neurocognitive functioning and disease coping.

Frailty indices predict mortality, complications and functional improvements in supratentorial meningioma patients over 80 years of age.

PURPOSE: To assess whether the Modified 5 (mFI-5) and 11 (mFI-11) Factor Frailty Indices associate with postoperative mortality, complications, and functional benefit in supratentorial meningioma patients aged over 80 years. METHODS: Baseline characteristics were collected from eight centers. Based on the patients' preoperative status and comorbidities, frailty was assessed by the mFI-5 and mFI-11. The collected scores were categorized as "robust (mFI=0)", "pre-frail (mFI=1)", "frail (mFI=2)", and "significantly frail (mFI≥3)". Outcome was assessed by the Karnofsky Performance Scale (KPS); functional benefit was defined as improved KPS score. Additionally, we evaluated the patients' functional independence (KPS≥70) after surgery. RESULTS: The study population consisted of 262 patients (median age 83 years) with a median preoperative KPS of 70 (range 20 to 100). The 90-day and 1-year mortality were 9.0% and 13.2%; we recorded surgery-associated complications in 111 (42.4%) patients. At last follow-up within the postoperative first year, 101 (38.5%) patients showed an improved KPS, and 183 (69.8%) either gained or maintained functional independence. "Severely frail" patients were at an increased risk of death at 90 days (OR 16.3 (CI95% 1.7-158.7)) and one year (OR 11.7 (CI95% 1.9-71.7)); nine (42.9%) of severely frail patients died within the first year after surgery. The "severely frail" cohort had increased odds of suffering from surgery-associated complications (OR 3.9 (CI 95%) 1.3-11.3)), but also had a high chance for postoperative functional improvements by KPS≥20 (OR 6.6 (CI95% 1.2-36.2)). CONCLUSION: The mFI-5 and mFI-11 associate with postoperative mortality, complications, and functional benefit. Even though "severely frail" patients had the highest risk morbidity and mortality, they had the highest chance for functional improvement.

Glioblastoma in the real-world setting: patterns of care and outcome in the Austrian population.

PURPOSE: We present results of a retrospective population-based investigation of patterns of care and outcome of glioblastoma patients in Austria. PATIENTS AND METHODS: In this nation-wide cooperative project, all Austrian glioblastoma patients newly diagnosed between 2014 and 2018 and registered in the ABTR-SANOnet database were included. Histological typing used criteria of the WHO classification of CNS tumors, 4th edition 2016. Patterns of care were assessed, and all patients were followed until the end of 2019. RESULTS: 1,420 adult glioblastoma cases were identified. 813 (57.3%) patients were male and 607 (42.7%) female. Median age at diagnosis was 64 years (range: 18-88). Median overall survival (OS) was 11.6 months in the total cohort and 10.9 months in patients with proven IDH-wildtype. Median OS in the patient group ≤ 65 years receiving postoperative standard of care therapy was 16.1 months. In the patient group > 65 years with postoperative therapy, median OS was 11.2 months. Follow-up ≥ 5 years identified 13/264 (4.9%) long-term survivors. Brain tumor surgery frequently was assisted by 5-aminolevulinic acid (5-ALA) fluorescence (up to 55%). Postoperative treatment was initiated around one month after surgery (median: 31 days) following standardized protocols in 1,041/1,420 (73.3%) cases. In 830 patients (58.5%), concomitant radiochemotherapy was started according to the established standard of care. Treatment in case of progressive disease was considerably variable. 170/1,420 patients (12.0%) underwent a second surgical procedure, 467 (33.0%) received systemic treatment after progression, and 173 (12.2%) were re-irradiated. CONCLUSION: Our data illustrate and confirm nation-wide translation of effective standard of care to Austrian glioblastoma patients in the recent past. In the case of progressive disease, highly variable therapeutic approaches were used, most frequently accompanied by anti-angiogenic therapy. Long-term survival was observed in a minor proportion of mostly younger patients who typically had gross total tumor resection, a favorable postoperative ECOG score, and standard of care therapy.

Wound healing after intracutaneous vs. staple-assisted skin closure in lumbar, non-instrumented spine surgery: a multicenter prospective randomized trial.

PURPOSE: Superficial surgical site infection (SSSI) is a prominent problem in spine surgery. Intracutaneous sutures and staple-assisted closure are two widely used surgical techniques for skin closure. Yet, their comparative impact on wound healing and infection rates is underexplored. Our goal was to address this gap and compare wound healing between these two techniques. METHODS: This study was a multicenter international prospective randomized trial. Patient data were prospectively collected at three large academic centers, patients who underwent non-instrumented lumbar primary spine surgery were included. Patients were intraoperatively randomized to either intracutaneous suture or staple-assisted closure cohorts. The primary endpoint was SSSI within 30 days after surgery according to the wound infection Centers for Disease Control and Prevention (CDC) classification system. RESULTS: Of 207 patients, 110 were randomized to intracutaneous sutures and 97 to staple-assisted closure. Both groups were homogenous with respect to epidemiological as well as surgical parameters. Two patients (one of each group) suffered from an A1 wound infection at the 30-day follow up. Median skin closure time was faster in the staple-assisted closure group (198 s vs. 13 s, p < 0,001). CONCLUSION: This study showed an overall low superficial surgical site infection rate in both patient cohorts in primary non instrumented spine surgery.

Burr-hole drainage with or without irrigation for chronic subdural haematoma (FINISH): a Finnish, nationwide, parallel-group, multicentre, randomised, controlled, non-inferiority trial.

BACKGROUND: Chronic subdural haematoma is a common surgically treated intracranial emergency. Burr-hole drainage surgery, to evacuate chronic subdural haematoma, involves three elements: creation of a burr hole for access, irrigation of the subdural space, and insertion of a subdural drain. Although the subdural drain has been established as beneficial, the therapeutic effect of subdural irrigation has not been addressed. METHODS: The FINISH trial was an investigator-initiated, pragmatic, multicentre, nationwide, randomised, controlled, parallel-group, non-inferiority trial in five neurosurgical units in Finland that enrolled adults aged 18 years or older with a chronic subdural haematoma requiring burr-hole drainage. Patients were randomly assigned (1:1) by computer-generated block randomisation with block sizes of four, six, or eight, stratified by site, to burr-hole drainage either with or without subdural irrigation. All patients and staff were masked to treatment assignment apart from the neurosurgeon and operating room staff. A burr hole was drilled at the site of maximum haematoma thickness in both groups, and the subdural space was either irrigated or not irrigated before inserting a subdural drain, which remained in place for 48 h. Reoperations, functional outcome, mortality, and adverse events were recorded for 6 months after surgery. The primary outcome was the reoperation rate within 6 months. The non-inferiority margin was set at 7·5%. Key secondary outcomes that were also required to conclude non-inferiority were the proportion of participants with unfavourable functional outcomes (ie, modified Rankin Scale score of 4-6, where 0 indicates no symptoms and 6 indicates death) and mortality rate at 6 months. The primary and key secondary analyses were done in both the intention-to-treat and per-protocol populations. The trial was registered with ClinicalTrials.gov (NCT04203550) and is completed. FINDINGS: From Jan 1, 2020, to Aug 17, 2022, we assessed 1644 patients for eligibility and 589 (36%) patients were randomly assigned to a treatment group and treated (294 assigned to drainage with irrigation and 295 assigned to drainage without irrigation; 165 [28%] women and 424 [72%] men). The 6-month follow-up period extended until Feb 14, 2023. In the intention-to-treat analysis, 54 (18·3%) of 295 participants required reoperation in the group assigned to receive no irrigation versus 37 (12·6%) of 294 in the group assigned to receive irrigation (difference of 6·0 percentage points, 95% CI 0·2-11·7; p=0·30; adjusted for study site). There were no significant between-group differences in the proportion of people with modified Rankin Scale score of 4-6 (37 [13·1%] of 283 in the no-irrigation group vs 36 [12·6%] of 285 in the irrigation group; p=0·89) or mortality rate (18 [6·1%] of 295 in the no-irrigation group vs 21 [7·1%] of 294 in the irrigation group; p=0·58). The findings of the primary intention-to-treat analysis were not materially altered in the per-protocol analysis. There were no significant between-group differences in the number of adverse events, and the most frequent severe adverse events were systemic infections (26 [8·8%] of 295 participants who did not receive irrigation vs 22 [7·5%] of 294 participants who received irrigation), intracranial haemorrhage (13 [4·4%] vs seven [2·4%]), and epileptic seizures (five [1·7%] vs nine [3·1%]). INTERPRETATION: We could not conclude non-inferiority of burr-hole drainage without irrigation. The reoperation rate was 6·0 percentage points higher after burr-hole drainage without subdural irrigation than with subdural irrigation. Considering that there were no differences in functional outcome or mortality between the groups, the trial favours the use of subdural irrigation. FUNDING: State Fund for University Level Health Research (Helsinki University Hospital), Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, and Svenska Kulturfonden.

Pituitary Apoplexy in Macroadenoma After Minor Surgery: An Unusual Case and Literature Review.

Pituitary apoplexy is a rare and severe complication of pituitary adenoma that may present with new-onset headache, ocular palsy, visual disturbances, life-threatening electrolyte imbalance, and endocrinological disturbances due to pituitary hemorrhage and/or infarction. We report the case of a 58-year-old previously healthy patient who developed isolated mild oculomotor nerve palsy of the left eye following osteosynthesis of a traumatic right distal radius fracture. Initial cerebral magnetic resonance imaging showed a pituitary macroadenoma without characteristic signs of pituitary infarction or hemorrhage. The patient presented to the neurology department on the fifth postoperative day with malaise and fatigue due to pituitary insufficiency, deteriorated rapidly and required intensive care monitoring. Clinical stabilization was achieved through the administration of hydrocortisone, and transsphenoidal resection of the pituitary lesion was performed on the 10th day after acute symptom onset. Histological examination revealed a necrotic pituitary adenoma. Pituitary apoplexy may occur after minor surgery in patients with pituitary adenoma. Clinicians should pay particular attention to laboratory signs of pituitary insufficiency in new-onset oculomotor nerve palsy associated with sellar lesions, as cerebral imaging may miss pituitary apoplexy and therefore delay diagnosis and treatment. In our case, delayed decompressive transsphenoidal resection resulted in the normalization of the oculomotor nerve palsy while the pituitary insufficiency persisted. The potential impact of an earlier surgical intervention on the outcome of pituitary function remains uncertain.

Cryopreserved bone flaps from decompressive craniectomies: a microbiological analysis.

PURPOSE: Surgical site infection (SSI) is a serious complication after cranioplasty. Due to the relatively frequent occurrence of post-cranioplasty SSI, the utility of autologous bone flap swab cultures surrounding cryopreservation as a reliable predictor has been the subject of an ongoing debate. This bicentric study aims to contribute to this topic by conducting an in-depth analysis of bone flaps obtained via decompressive craniectomies. This study had three major aims: assessments of 1) bacterial contamination of bone flaps after decompressive craniotomy, 2) impact of cryoconservation on contamination rates and 3) potential effectiveness of anti-infective treatment to reduce the germ load prior to cranioplasty. METHODS: Cryopreserved bone flaps from two centers were used. Microbiological cultivations of swabs prior to and after cryopreservation were taken and assessed for aerobic and anaerobic growth over a 14-day incubation period. Additionally, in a subset of bone flaps, swab testing was repeated after thorough rinsing with an anti-infectant (octenidine-phenoxyethanol) followed by saline. RESULTS: All 63 bone flaps (patients median age at surgery: 59 years) were obtained via decompressive craniectomies. Swabs done prior to cryopreservation revealed a 54% infection rate with Propionibacterium acnes being the most common microorganism in 65% of those cases. After thorough disinfection of the preserved bone flaps, all but one case showed no bacterial growth in swab testing. Furthermore, no relevant risk factors for bacterial contamination could be identified. CONCLUSION: This retrospective study showed the common presence of bacterial growth in cryopreserved bone flaps before and after freezing. Rinsing with octenidine-phenoxyethanol and saline effectively prevented bacterial growth in a notable percentage of cases, suggesting a potential strategy to reduce contamination. However, persistent bacterial growth in some cases underscores the need for further research to optimize antiseptic measures during autologous cranioplasty.

Surgical Outcome of Patients With Supratentorial Meningiomas Aged 80 Years or Older-Retrospective International Multicenter Study.

BACKGROUND AND OBJECTIVES: Demographic changes will lead to an increase in old patients, a population with significant risk of postoperative morbidity and mortality, requiring neurosurgery for meningiomas. This multicenter study aims to report neurofunctional status after resection of patients with supratentorial meningioma aged 80 years or older, to identify factors associated with outcome, and to validate a previously proposed decision support tool. METHODS: Neurofunctional status was assessed by the Karnofsky Performance Scale (KPS). Patients were categorized in poor (KPS ≤40), intermediate (KPS 50-70), and good (KPS ≥80) preoperative subgroups. Volumetric analyses of tumor and peritumoral brain edema (PTBE) were performed; volumes were scored as small (<10 cm 3 ), medium (10-50 cm 3 ), and large (>50 cm 3 ). RESULTS: The study population consisted of 262 patients, and the median age at surgery was 83.0 years. The median preoperative KPS was 70; 117 (44.7%) patients were allotted to the good, 113 (43.1%) to the intermediate, and 32 (12.2%) to the poor subgroup. The median tumor and PTBE volumes were 30.2 cm 3 and 27.3 cm 3 ; large PTBE volume correlated with poor preoperative KPS status ( P = .008). The 90-day and 1-year mortality rates were 9.0% and 13.2%, respectively. Within the first postoperative year, 101 (38.5%) patients improved, 87 (33.2%) were unchanged, and 74 (28.2%) were functionally worse (including deaths). Each year increase of age associated with 44% (23%-70%) increased risk of 90-day and 1-year mortality. In total, 111 (42.4%) patients suffered from surgery-associated complications. Maximum tumor diameter ≥5 cm (odds ratio 1.87 [1.12-3.13]) and large tumor volume (odds ratio 2.35 [1.01-5.50]) associated with increased risk of complications. Among patients with poor preoperative status and large PTBE, most (58.3%) benefited from surgery. CONCLUSION: Patients with poor preoperative neurofunctional status and large PTBE most often showed postoperative improvements. The decision support tool may be of help in identifying cases that most likely benefit from surgery.

Network topology in brain tumor patients with and without structural epilepsy: a prospective MEG study.

Background: It was proposed that network topology is altered in brain tumor patients. However, there is no consensus on the pattern of these changes and evidence on potential drivers is lacking. Objectives: We aimed to characterize neurooncological patients' network topology by analyzing glial brain tumors (GBTs) and brain metastases (BMs) with respect to the presence of structural epilepsy. Methods: Network topology derived from resting state magnetoencephalography was compared between (1) patients and controls, (2) GBTs and BMs, and (3) patients with (PSEs) and without structural epilepsy (PNSEs). Eligible patients were investigated from February 2019 to March 2021. We calculated whole brain (WB) connectivity in six frequency bands, network topological parameters (node degree, average shortest path length, local clustering coefficient) and performed a stratification, where differences in power were identified. For data analysis, we used Fieldtrip, Brain Connectivity MATLAB toolboxes, and in-house built scripts. Results: We included 41 patients (21 men), with a mean age of 60.1 years (range 23-82), of those were: GBTs (n = 23), BMs (n = 14), and other histologies (n = 4). Statistical analysis revealed a significantly decreased WB node degree in patients versus controls in every frequency range at the corrected level (p1-30Hz = 0.002, pγ = 0.002, pß = 0.002, pα = 0.002, pθ = 0.024, and pδ = 0.002). At the descriptive level, we found a significant augmentation for WB local clustering coefficient (p1-30Hz = 0.031, pδ = 0.013) in patients compared to controls, which did not persist the false discovery rate correction. No differences regarding networks of GBTs compared to BMs were identified. However, we found a significant increase in WB local clustering coefficient (pθ = 0.048) and decrease in WB node degree (pα = 0.039) in PSEs versus PNSEs at the uncorrected level. Conclusion: Our data suggest that network topology is altered in brain tumor patients. Histology per se might not, however, tumor-related epilepsy seems to influence the brain's functional network. Longitudinal studies and analysis of possible confounders are required to substantiate these findings.

Extra- and Intracranial Diffuse Large B-Cell Lymphoma (DLBCL) Mimicking Meningioma: A Case Report and Literature Review.

Primary central nervous system lymphomas (PCNLSs) are malignant non-Hodgkin lymphomas solely affecting the central nervous system (CNS). Here, we present a rare case of extra- and intracranial manifestation without adjacent calvarial infiltration. We report a 67-year-old woman who presented with right leg paresis and hypoesthesia, facial hypoesthesia, focal epileptic seizures, and an indolent tumor on the left parietal scalp. MRI showed a left paramedian extra- and intracranial contrast-enhancing tumor with infiltration of the superior sagittal sinus, but without osseous infiltration on CT. The tumor was radiologically suspected to be a meningioma and resection was performed. Histological examination, however, revealed a diffuse large B-cell lymphoma (DLBCL). Thus, the patient received adjuvant treatment according to the MATRix protocol. We provide a detailed analysis of this rare case with a focus on preoperative radiological findings and differential diagnoses. To the best of our knowledge, this is one of only four published cases of DLBCL with extra- and intracranial manifestation without bone affection.

Dissecting the Methylomes of EGFR-Amplified Glioblastoma Reveals Altered DNA Replication and Packaging, and Chromatin and Gene Silencing Pathways.

Glioblastoma IDH wildtype is the most frequent brain tumor in adults. It shows a highly malignant behavior and devastating outcomes. To date, there is still no targeted therapy available; thus, patients' median survival is limited to 12-15 months. Epithelial growth factor receptor (EGFR) is an interesting targetable candidate in advanced precision medicine for brain tumor patients. In this study, we performed integrated epigenome-wide DNA-methylation profiling of 866,895 methylation specific sites in 50 glioblastoma IDH wildtype samples, comparing EGFR amplified and non-amplified glioblastomas. We found 9849 significantly differentially methylated CpGs (DMCGs) with Δß ≥ 0.1 and p-value < 0.05 in EGFR amplified, compared to EGFR non-amplified glioblastomas. Of these DMCGs, 2380 were annotated with tiling (2090), promoter (117), gene (69) and CpG islands (104); 7460 are located at other loci. Interestingly, the list of differentially methylated genes allocated eleven functionally relevant RNAs: five miRNAs (miR1180, miR1255B1, miR126, miR128-2, miR3125), two long non-coding RNAs (LINC00474, LINC01091), and four antisense RNAs (EPN2-AS1, MNX1-AS2, NKX2-2-AS1, WWTR1-AS1). Gene ontology (GO) analysis showed enrichment of "DNA replication-dependent nucleosome assembly", "chromatin silencing at rDNA", "regulation of gene silencing by miRNA", "DNA packaging", "posttranscriptional gene silencing", "gene silencing by RNA", "negative regulation of gene expression, epigenetic", "regulation of gene silencing", "protein-DNA complex subunit organization", and "DNA replication-independent nucleosome organization" pathways being hypomethylated in EGFR amplified glioblastomas. In summary, dissecting the methylomes of EGFR amplified and non-amplified glioblastomas revealed altered DNA replication, DNA packaging, chromatin silencing and gene silencing pathways, opening potential novel targets for future precision medicine.

Coexistence of Two Distinct Tumor Types Within One Posterior Fossa Mass Lesion in an Adult Patient Verified by DNA-Methylation Analysis: A Case Report.

We report an 81-year-old patient who underwent microsurgical resection of a posterior fossa mass lesion. Intraoperative findings were suggestive of the presence of two distinctly different tumor types within the lesion, one of which was well-circumscribed and avascular, whereas the other one showed an adhesive growth pattern and extensive vascularisation. Histopathological analysis, including deoxyribonucleic acid (DNA)-methylation-based classification, substantiated the intraoperative impression and confirmed the presence of a subependymoma central nervous system (CNS) World Health Organization (WHO) grade 1 as well as the presence of a hemangioblastoma CNS WHO grade 1. To our knowledge, our patient represents only the second reported case of such a rare constellation. Even though DNA-methylation-based classification is not yet required for the classification of all CNS tumor types by the 2021 WHO classification of tumors of the CNS, it proved to be crucial to verify the final diagnosis in our patient. In the future, DNA-methylation analysis will most likely become an important asset in neuro-oncological diagnostics and further help to guide treatment strategies in complex or rare clinical cases.

Interstitial photodynamic therapy for newly diagnosed glioblastoma.

PURPOSE: Innovative, efficient treatments are desperately needed for people with glioblastoma (GBM). METHODS: Sixteen patients (median age 65.8 years) with newly diagnosed, small-sized, not safely resectable supratentorial GBM underwent interstitial photodynamic therapy (iPDT) as upfront eradicating local therapy followed by standard chemoradiation. 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX was used as the photosensitizer. The tumors were irradiated with light at 635 nm wavelength via stereotactically implanted cylindrical diffuser fibers. Outcome after iPDT was retrospectively compared with a positively-selected in-house patient cohort (n = 110) who underwent complete tumor resection followed by chemoradiation. RESULTS: Median progression-free survival (PFS) was 16.4 months, and median overall survival (OS) was 28.0 months. Seven patients (43.8%) experienced long-term PFS > 24 months. Median follow-up was 113.9 months for the survivors. Univariate regression revealed MGMT-promoter methylation but not age as a prognostic factor for both OS (p = 0.04 and p = 0.07) and PFS (p = 0.04 and p = 0.67). Permanent iPDT-associated morbidity was seen in one iPDT patient (6.3%). Patients treated with iPDT experienced superior PFS and OS compared to patients who underwent complete tumor removal (p < 0.01 and p = 0.01, respectively). The rate of long-term PFS was higher in iPDT-treated patients (43.8% vs. 8.9%, p < 0.01). CONCLUSION: iPDT is a feasible treatment concept and might be associated with long-term PFS in a subgroup of GBM patients, potentially via induction of so far unknown immunological tumor-controlling processes.

Robot-assisted versus navigated transpedicular spine fusion: A comparative study.

BACKGROUND: The aim of this study was to compare the intraoperative and postoperative outcomes between a robot-assisted versus a navigated transpedicular fusion technique. METHODS: This retrospective analysis included patients who underwent transpedicular posterior fusion of the spine due to trauma, pyogenic spondylodiscitis and osteoporosis. Surgery was done either with a robot-assisted or a percutaneous navigated transpedicular fusion technique. The outcome analysis included the duration of surgery, the radiation exposure, the postoperative screw position and complications. RESULTS: A total of 60 patients were operated and 491 screws were analysed. No statistical difference was seen in the applied cumulative effective radiation dose per patient. The radiological assessment revealed a more accurate screw placement with robot assistance. A learning curve could be observed in robot-assisted fusion. CONCLUSION: Robot-assisted and navigated transpedicular fusion techniques are both effective and safe. Robot-assisted transpedicular spine fusion goes along with higher placement accuracy but its implementation needs an adequate learning curve.

Surgeon experience in glioblastoma surgery of the elderly-a multicenter, retrospective cohort study.

PURPOSE: To assess the impact of individual surgeon experience on overall survival (OS), extent of resection (EOR) and surgery-related morbidity in elderly patients with glioblastoma (GBM), we performed a retrospective case-by-case analysis. METHODS: GBM patients aged ≥ 65 years who underwent tumor resection at two academic centers were analyzed. The experience of each neurosurgeon was quantified in three ways: (1) total number of previously performed glioma surgeries (lifetime experience); (2) number of surgeries performed in the previous five years (medium-term experience) and (3) in the last two years (short-term experience). Surgeon experience data was correlated with survival (OS) and surrogate parameters for surgical quality (EOR, morbidity). RESULTS: 198 GBM patients (median age 73.0 years, median preoperative KPS 80, IDH-wildtype status 96.5%) were included. Median OS was 10.0 months (95% CI 8.0-12.0); median EOR was 89.4%. Surgery-related morbidity affected 19.7% patients. No correlations of lifetime surgeon experience with OS (P = .693), EOR (P = .693), and surgery-related morbidity (P = .435) were identified. Adjuvant therapy was associated with improved OS (P < .001); patients with surgery-related morbidity were less likely to receive adjuvant treatment (P = .002). In multivariable testing, adjuvant therapy (P < .001; HR = 0.064, 95%CI 0.028-0.144) remained the only significant predictor for improved OS. CONCLUSION: Less experienced neurosurgeons achieve similar surgical results and outcome in elderly GBM patients within the setting of academic teaching hospitals. Adjuvant treatment and avoidance of surgery-related morbidity are crucial for generating a treatment benefit for this cohort.

The projected numbers of degenerative spine disease in Austria from 2017 to 2080: a perspective-based scenario analysis.

BACKGROUND: Spinal surgery has to address the challenge of a dramatic increase of the growing number of older persons. The purpose of the present study was to project the numbers of surgically treated degenerative spine disease (DSD) in Austria from 2017 until 2080 to provide potential future scenarios that the Austrian Health system might have to face. METHODS: Current numbers on demographic information from Austria as well as population projections for 2017-2080 were obtained from Statistics Austria (STAT). A lower/main/upper scenario reflecting low/main/high growth and ageing scenarios deducted from fertility, life expectancy and immigration calculations was used. Information on prevalence of surgically treated DSD was obtained from the Austrian Spine Register. RESULTS: The population in Austria (evaluated in 2017) was 8.78 millions and is estimated to evolve to 7.86/10.0/13.1 millions by 2080. The total number of surgically treated DSD recorded in the Spine Register was 9300 and was estimated to be 9300/11200/13700 in 2080. The number of subjects with surgically treated DSD were expected to increase in the age-strata (main scenario), 100% corresponds to the number in each age and gender stratum: 0-40 years by (male/female) 2%/2%, 40-50 years -7%/-7%, 50-59 years -11%/-9%, 60-69 years 21%/16%, 70-79 years 51%/31%, 80-89 years 211%/129% and 90+years 698%/411%. CONCLUSIONS: Total numbers of subjects with DSD in Austria will increase from 2017 to 2080. The increase will be substantial in those aged 80+ and those aged 90+. The assumptions of this analysis were taken conservatively. Hence, the future socio-economic burden to society might be greater as projected by the study.

Methylome Profiling of PD-L1-Expressing Glioblastomas Shows Enrichment of Post-Transcriptional and RNA-Associated Gene Regulation.

Glioblastomas are the most frequent primary brain tumors in adults. They show highly malignant behavior and devastating outcomes. Since there are still no targeted therapies available, median survival remains in the range of 12 to 15 months for glioblastoma patients. Programmed Cell Death Ligand 1 (PD-L1) is a promising novel candidate in precision medicine. Here, we performed integrated epigenome-wide methylation profiling of 866,895 methylation-specific sites in 20 glioblastoma samples comparing PD-L1 high- (i.e., TPS (tumor proportion score) > 30%) and PD-L1 low-expressing glioblastomas (i.e., TPS < 10%). We found 12,597 significantly differentially methylated CpGs (DMCG) (Δß ≥ 0.1 and p-value < 0.05) in PD-L1 high- compared with PD-L1 low-expressing glioblastomas. These DMCGs were annotated to 2546 tiling regions, 139 promoters, 107 genes, and 107 CpG islands. PD-L1 high-expressing glioblastomas showed hypomethylation in 68% of all DMCGs. Interestingly, the list of the top 100 significantly differentially methylated genes showed the enrichment of regulatory RNAs with 19 DMCGs in miRNA, snoRNAs, lincRNAs, and asRNAs. Gene Ontology analysis showed the enrichment of post-transcriptional and RNA-associated pathways in the hypermethylated gene regions. In summary, dissecting the methylomes depending on PD-L1 status revealed significant alterations in RNA regulation and novel molecular targets in glioblastomas.

Meningeal Metastasis Causing Chronic Subdural Hematoma in a Cancer Patient with Bilateral Papilledema and Suspected Cerebral Venous Thrombosis: A Case Report.

Meningeal metastasis has been reported as a very rare cause of chronic subdural hematoma (CSH). Here, we report a female patient who had undergone initial burr hole drainage of a CSH at an outside hospital. Postoperatively, the patient additionally suffered from visual impairment due to bilateral papilledema and the patient was eventually transferred to our neurosurgical department for additional treatment. A craniotomy was performed and due to intraoperative suspicious findings, histopathologic samples were obtained that revealed a metastasis of thus far undiagnosed triple negative breast cancer. Furthermore, the patient was suspected to have a partial cerebral venous thrombosis (CVT). Our case report addresses this extremely rare clinical constellation. We provide a detailed overview on our patient's clinical and radiologic course, and discuss the potential association of CSH with meningeal metastasis and bilateral papilledema.

EGFR Amplification Is a Phenomenon of IDH Wildtype and TERT Mutated High-Grade Glioma: An Integrated Analysis Using Fluorescence In Situ Hybridization and DNA Methylome Profiling.

Gliomas are the most common intrinsic brain tumors in adults, and in accordance with their clinical behavior and patients' outcome, they are graded by the World Health Organization (WHO) classification of brain tumors. One very interesting candidate for targeted tumor therapy may be epidermal growth factor receptor (EGFR) amplification. Here, we performed an integrated comparative analysis of EGFR amplification in 34 glioma samples using standard fluorescence in situ hybridization (FISH) and Illumina EPIC Infinium Methylation Bead Chip and correlated results with molecular glioma hallmarks. We found that the EPIC analysis showed the same power of detecting EGFR amplification compared with FISH. EGFR amplification was detectable in high-grade gliomas (25%). Moreover, EGFR amplification was found to be present solely in IDH wildtype gliomas (26%) and TERT mutated gliomas (27%), occurring independently of MGMT promoter methylation status and being mutually exclusive with 1p/19q codeletion (LOH). In summary, EPIC Bead Chip analysis is a reliable tool for detecting EGFR amplification and is comparable with the standard method FISH. EGFR amplification is a phenomenon of IDH wildtype TERT mutated high-grade gliomas.