Publications by authors named "Peter Baumgarten"

53 Publications

Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated.

J Clin Oncol 2021 Dec 7;39(34):3839-3852. Epub 2021 Oct 7.

Department of Neurosurgery, NYU Langone Hospital, New York, NY.

Purpose: Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression for individual patients is of pivotal importance. However, only biomarkers for highly aggressive tumors are established ( and ), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma.

Methods: DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases.

Results: Both CNV- and methylation family-based subgrouping independently resulted in increased prediction accuracy of risk of recurrence compared with the WHO classification (c-indexes WHO 2016, CNV, and methylation family 0.699, 0.706, and 0.721, respectively). Merging all risk stratification approaches into an integrated molecular-morphologic score resulted in further substantial increase in accuracy (c-index 0.744). This integrated score consistently provided superior accuracy in all three cohorts, significantly outperforming WHO grading (c-index difference = .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34 [1.28-8.72] retrospective and prospective validation cohorts, respectively).

Conclusion: Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction.
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http://dx.doi.org/10.1200/JCO.21.00784DOI Listing
December 2021

Incidence, risk factors and clinical course of pyogenic spondylodiscitis patients with pulmonary embolism.

Eur J Trauma Emerg Surg 2021 Sep 2. Epub 2021 Sep 2.

Department of Neurosurgery, University Hospital, Goethe University, Schleusenweg 2-16, 60598, Frankfurt, Germany.

Purpose: In patients with pyogenic spondylodiscitis, surgery is considered the treatment of choice to conduct proper debridement, stabilise the spine and avoid extended bed rest, which in turn is a risk factor for complications such as deep vein thrombosis and pulmonary embolism.

Methods: We conducted a retrospective clinical study with analysis of a group of 99 patients who had undergone treatment for pyogenic discitis at our institution between June 2012 and August 2017. Included parameters were age, sex, disease pattern, the presence of deep vein thrombosis, resuscitation, in-hospital mortality, present anticoagulation, preexisting comorbidities, tobacco abuse, body mass index, microbiological germ detection and laboratory results.

Results: Among the analysed cohort, 12% of the treated patients for pyogenic spondylodiscitis suffered from a radiologically confirmed pulmonary embolism. Coronary heart disease (p < 0.01), female sex (p < 0.01), anticoagulation at admission (p < 0.01) and non-O blood type (p < 0.001) were associated with development of pulmonary embolism. Pulmonary embolism was significantly associated with resuscitation (p < 0.005) and deep vein thrombosis (p < 0.001). Neurosurgery was not associated with increased risk for pulmonary embolism compared to conservative-treated patients (p > 0.05).

Conclusion: Surgery for pyogenic spondylodiscitis was not associated with an elevated risk of pulmonary embolism in our analysis. However, we describe several risk factors for pulmonary embolism in this vulnerable cohort. Prospective studies are necessary to improve prevention and postoperative management in patients with pyogenic spondylodiscitis.
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http://dx.doi.org/10.1007/s00068-021-01776-zDOI Listing
September 2021

Two-step staged resection of giant olfactory groove meningiomas.

Acta Neurochir (Wien) 2021 12 10;163(12):3425-3431. Epub 2021 Aug 10.

Department of Neurosurgery, Goethe - University, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany.

Background: The surgical treatment of giant olfactory groove meningiomas (OGMs) with marked perilesional brain oedema is still a surgical challenge. After tumour resection, increase of brain oedema may occur causing dramatic neurological deterioration and even death of the patient. The objective of this paper is to describe surgical features of a two-step staged resection of these tumours performed to counter increase of postoperative brain oedema.

Methods: This two-step staged resection procedure was carried out in a consecutive series of 19 patients harbouring giant OGMs. As first step, a bifrontal craniectomy was performed followed by a right-sided interhemispherical approach. About 80% of the tumour mass was resected leaving behind a shell-shaped tumour remnant. In the second step, carried out after the patients' recovery from the first surgery and decline of oedema, the remaining part of the tumour was removed completely followed by duro- and cranioplasty.

Results: Ten patients recovered quickly from first surgery and the second operation was performed after a mean of 12.4 days. In eight patients, the second operation was carried out later between day 25 and 68 due to surgery-related complications, development of a trigeminal zoster, or to a persisting frontal brain oedema. Mean follow-up was 49.3 months and all but one patient had a good outcome regardless of surgery-related complications.

Conclusions: Our results suggest that a two-step staged resection of giant OGMs minimizes the increase of postoperative brain oedema as far as possible and translates into lower morbidity and mortality.
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http://dx.doi.org/10.1007/s00701-021-04910-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599346PMC
December 2021

Clinical Outcome and Risk Factors of Red Blood Cell Transfusion in Patients Undergoing Elective Primary Meningioma Resection.

Cancers (Basel) 2021 Jul 18;13(14). Epub 2021 Jul 18.

Department of Neurosurgery, University Hospital, Goethe University Frankfurt, 60528 Frankfurt am Main, Germany.

Transfusion of red blood cells (RBC) in patients undergoing major elective cranial surgery is associated with increased morbidity, mortality and prolonged hospital length of stay (LOS). This retrospective single center study aims to identify the clinical outcome of RBC transfusions on skull base and non-skull base meningioma patients including the identification of risk factors for RBC transfusion. Between October 2009 and October 2016, 423 patients underwent primary meningioma resection. Of these, 68 (16.1%) received RBC transfusion and 355 (83.9%) did not receive RBC units. Preoperative anaemia rate was significantly higher in transfused patients (17.7%) compared to patients without RBC transfusion (6.2%; = 0.0015). In transfused patients, postoperative complications as well as hospital LOS was significantly higher ( < 0.0001) compared to non-transfused patients. After multivariate analyses, risk factors for RBC transfusion were preoperative American Society of Anaesthesiologists (ASA) physical status score ( = 0.0247), tumor size ( = 0.0006), surgical time ( = 0.0018) and intraoperative blood loss ( < 0.0001). Kaplan-Meier curves revealed significant influence on overall survival by preoperative anaemia, RBC transfusion, smoking, cardiovascular disease, preoperative KPS ≤ 60% and age (elderly ≥ 75 years). We concluded that blood loss due to large tumors or localization near large vessels are the main triggers for RBC transfusion in meningioma patients paired with a potential preselection that masks the effect of preoperative anaemia in multivariate analysis. Further studies evaluating the impact of preoperative anaemia management for reduction of RBC transfusion are needed to improve the clinical outcome of meningioma patients.
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http://dx.doi.org/10.3390/cancers13143601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307823PMC
July 2021

The impact of timing of intravenous iron supplementation on preoperative haemoglobin in patients scheduled for major surgery.

Blood Transfus 2021 May 26. Epub 2021 May 26.

Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, Germany.

Background: Anaemia is frequent and an independent risk factor for morbidity and mortality in patients undergoing surgery. Iron deficiency (ID) is the main cause for anaemia and can be corrected by intravenous (IV) iron. The aim of this study was to investigate the timing of preoperative IV iron supplementation on preoperative haemoglobin (Hb) level.

Materials And Methods: Surgical patients were screened for the presence of anaemia and ID from November 2015 to January 2020. In case of ID or iron deficiency anaemia (IDA), patients received IV iron supplementation. The timing of IV iron supplementation on preoperative Hb level was analysed by days and time frames clustered by 5 days before surgery.

Results: In total, 404 patients with IV iron supplementation were analysed. In all patients, IV iron was administered with a median (interquartile range [IQR]) of 3.0 (1.0; 9.0) days before surgery. Preoperative Hb level increased steadily starting from 6 days (0.13 [±1.2] g/dL) until 16 days before surgery (1.75 [±1.1] g/dL). Group comparison revealed a median preoperative Hb change of -0.2 (-0.5; 0.2) g/dL for days 1-5, 0.2 (0.0; 0.7) g/dL for days 6-10, 0.7 (0.2; 1.1) g/dL for days 11-15, 0.7 (0.2; 1.8) g/dL for days 16-20, 0.9 (0.3; 1.7) g/dL for days 21-25, 1.5 (0.4; 2.6) g/dL for days 26-30, and 0.6 (0.0; 1.7) g/dL for >31 days. Three patients received multiple administrations of IV iron which resulted in an increase in Hb of >4 g/dL.

Discussion: Supplementation of IV iron to increase Hb concentration preoperatively may be most effective if administered at least ten days before surgery.
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http://dx.doi.org/10.2450/2021.0058-21DOI Listing
May 2021

Meningioma Surgery in Patients ≥70 Years of Age: Clinical Outcome and Validation of the SKALE Score.

J Clin Med 2021 Apr 22;10(9). Epub 2021 Apr 22.

Department of Neurosurgery, University Hospital Frankfurt, Goethe University, 60528 Frankfurt, Germany.

Along with increasing average life expectancy, the number of elderly meningioma patients has grown proportionally. Our aim was to evaluate whether these specific patients benefit from surgery and to investigate a previously published score for decision-making in meningioma patients (SKALE). Of 421 patients who underwent primary intracranial meningioma resection between 2009 and 2015, 71 patients were ≥70 years of age. We compared clinical data including World Health Organization (WHO) grade, MIB-1 proliferation index, Karnofsky Performance Status Scale (KPS), progression free survival (PFS) and mortality rate between elderly and all other meningioma patients. Preoperative SKALE scores (Sex, KPS, ASA score, location and edema) were determined for elderly patients. SKALE ≥8 was set for dichotomization to determine any association with outcome parameters. In 71 elderly patients (male/female 37/34) all data were available. Postoperative KPS was significantly lower in elderly patients ( < 0.0001). Pulmonary complications including pneumonia (10% vs. 3.2%; = 0.0202) and pulmonary embolism (12.7% vs. 6%; = 0.0209) occurred more frequently in our elderly cohort. Analyses of the Kaplan Meier curves revealed differences in three-month (5.6% vs. 0.3%; = 0.0033), six-month (7% vs. 0.3%; = 0.0006) and one-year mortality (8.5% vs. 0.3%; < 0.0001) for elderly patients. Statistical analysis showed significant survival benefit in terms of one-year mortality for elderly patients with SKALE scores ≥8 (5.1 vs. 25%; = 0.0479). According to our data, elderly meningioma patients face higher postoperative morbidity and mortality than younger patients. However, resection is reasonable for selected patients, particularly when reaching a SKALE score ≥ 8.
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http://dx.doi.org/10.3390/jcm10091820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122404PMC
April 2021

Direct oral anticoagulants vs. low-molecular-weight heparin for pulmonary embolism in patients with glioblastoma.

Neurosurg Rev 2021 Apr 26. Epub 2021 Apr 26.

Department of Neurosurgery, University Hospital, Goethe University, Schleusenweg 2-16, 60598, Frankfurt, Germany.

Glioblastoma (GBM) is a cancer type with high thrombogenic potential and GBM patients are therefore at a particularly high risk for thrombotic events. To date, only limited data on anticoagulation management after pulmonary embolism (PE) in GBM is available and the sporadic use of DOACs remains off-label. A retrospective cohort analysis of patients with GBM and postoperative, thoracic CT scan confirmed PE was performed. Clinical course, follow-up at 6 and 12 months and the overall survival (OS) were evaluated using medical charts and neuroradiological data. Out of 584 GBM patients, 8% suffered from postoperative PE. Out of these, 30% received direct oral anticoagulants (DOACs) and 70% low-molecular-weight heparin (LMWH) for therapeutic anticoagulation. There was no significant difference in major intracranial hemorrhage (ICH), re-thrombosis, or re-embolism between the two cohorts. Although statistically non-significant, a tendency to reduced mRS at 6 and 12 months was observed in the LMWH cohort. Furthermore, patients receiving DOACs had a statistical benefit in OS. In our analysis, DOACs showed a satisfactory safety profile in terms of major ICH, re-thrombosis, and re-embolism compared to LMWH in GBM patients with postoperative PE. Prospective, randomized trials are urgent to evaluate DOACs for therapeutic anticoagulation in GBM patients with PE.
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http://dx.doi.org/10.1007/s10143-021-01539-9DOI Listing
April 2021

DCE-MRI in Glioma, Infiltration Zone and Healthy Brain to Assess Angiogenesis: A Biopsy Study.

Clin Neuroradiol 2021 Apr 26. Epub 2021 Apr 26.

Department of Neuroradiology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Purpose: To explore the focal predictability of vascular growth factor expression and neovascularization using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioma.

Methods: 120 brain biopsies were taken in vital tumor, infiltration zone and normal brain tissue of 30 glioma patients: 17 IDH(isocitrate dehydrogenase)-wildtype glioblastoma (GBM), 1 IDH-wildtype astrocytoma °III (together prognostic group 1), 3 IDH-mutated GBM (group 2), 3 anaplastic astrocytomas IDH-mutated (group 3), 4 anaplastic oligodendrogliomas and 2 low-grade oligodendrogliomas (together prognostic group 4). A mixed linear model evaluated the predictabilities of microvessel density (MVD), vascular area ratio (VAR), mean vessel size (MVS), vascular endothelial growth factor and receptors (VEGF-A, VEGFR‑2) and vascular endothelial-protein tyrosine phosphatase (VE-PTP) expression from Tofts model kinetic and model-free curve parameters.

Results: All kinetic parameters were associated with VEGF‑A (all p < 0.001) expression. K, k and v were associated with VAR (p = 0.006, 0.004 and 0.01, respectively) and MVS (p = 0.0001, 0.02 and 0.003, respectively) but not MVD (p = 0.84, 0.74 and 0.73, respectively). Prognostic groups differed in K (p = 0.007) and v (p = 0.004) values measured in the infiltration zone. Despite significant differences of VAR, MVS, VEGF‑A, VEGFR‑2, and VE-PTP in vital tumor tissue and the infiltration zone (p = 0.0001 for all), there was no significant difference between kinetic parameters measured in these zones.

Conclusion: The DCE-MRI kinetic parameters show correlations with microvascular parameters in vital tissue and also reveal blood-brain barrier abnormalities in the infiltration zones adequate to differentiate glioma prognostic groups.
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http://dx.doi.org/10.1007/s00062-021-01015-3DOI Listing
April 2021

Proposed definition of competencies for surgical neuro-oncology training.

J Neurooncol 2021 May 21;153(1):121-131. Epub 2021 Apr 21.

Department of Neurosurgery, Justus-Liebig University Giessen, Giessen, Germany.

Objective: The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established.

Methods: We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology.

Result: In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families.

Conclusions And Relevance: The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.
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http://dx.doi.org/10.1007/s11060-021-03750-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131302PMC
May 2021

Association of Isocitrate Dehydrogenase (IDH) Status With Edema to Tumor Ratio and Its Correlation With Immune Infiltration in Glioblastoma.

Front Immunol 2021 25;12:627650. Epub 2021 Mar 25.

Department of Neurosurgery, Goethe University Hospital, Frankfurt, Germany.

Purpose: The extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival.

Methods: A volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the Brainlab® software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myelocytic (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records.

Results: The edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myelocytic tumor infiltration (p=0.78, p=0.74) between these groups.

Conclusion: In our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms.
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http://dx.doi.org/10.3389/fimmu.2021.627650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044904PMC
September 2021

TGF-β activates pericytes via induction of the epithelial-to-mesenchymal transition protein SLUG in glioblastoma.

Neuropathol Appl Neurobiol 2021 10 5;47(6):768-780. Epub 2021 May 5.

Laboratory of Molecular Neuro-Oncology, Department of Vascular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.

Aims: In primary central nervous system tumours, epithelial-to-mesenchymal transition (EMT) gene expression is associated with increased malignancy. However, it has also been shown that EMT factors in gliomas are almost exclusively expressed by glioma vessel-associated pericytes (GA-Peris). In this study, we aimed to identify the mechanism of EMT in GA-Peris and its impact on angiogenic processes.

Methods: In glioma patients, vascular density and the expression of the pericytic markers platelet derived growth factor receptor (PDGFR)-β and smooth muscle actin (αSMA) were examined in relation to the expression of the EMT transcription factor SLUG and were correlated with survival of patients with glioblastoma (GBM). Functional mechanisms of SLUG regulation and the effects on primary human brain vascular pericytes (HBVP) were studied in vitro by measuring proliferation, cell motility and growth characteristics.

Results: The number of PDGFR-β- and αSMA-positive pericytes did not change with increased malignancy nor showed an association with the survival of GBM patients. However, SLUG-expressing pericytes displayed considerable morphological changes in GBM-associated vessels, and TGF-β induced SLUG upregulation led to enhanced proliferation, motility and altered growth patterns in HBVP. Downregulation of SLUG or addition of a TGF-β antagonising antibody abolished these effects.

Conclusions: We provide evidence that in GA-Peris, elevated SLUG expression is mediated by TGF-β, a cytokine secreted by most glioma cells, indicating that the latter actively modulate neovascularisation not only by modulating endothelial cells, but also by influencing pericytes. This process might be responsible for the formation of an unstructured tumour vasculature as well as for the breakdown of the blood-brain barrier in GBM.
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http://dx.doi.org/10.1111/nan.12714DOI Listing
October 2021

Influence of VEGF-A, VEGFR-1-3, and neuropilin 1-2 on progression-free: and overall survival in WHO grade II and III meningioma patients.

J Mol Histol 2021 Apr 2;52(2):233-243. Epub 2021 Feb 2.

Department of Neurosurgery, University Hospital Frankfurt, Goethe University, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany.

Higher grade meningiomas tend to recur. We aimed to evaluate protein levels of vascular endothelial growth factor (VEGF)-A with the VEGF-receptors 1-3 and the co-receptors Neuropilin (NRP)-1 and -2 in WHO grade II and III meningiomas to elucidate the rationale for targeted treatments. We investigated 232 specimens of 147 patients suffering from cranial meningioma, including recurrent tumors. Immunohistochemistry for VEGF-A, VEGFR-1-3, and NRP-1/-2 was performed on tissue micro arrays. We applied a semiquantitative score (staining intensity x frequency). VEGF-A, VEGFR-1-3, and NRP-1 were heterogeneously expressed. NRP-2 was mainly absent. We demonstrated a significant increase of VEGF-A levels on tumor cells in WHO grade III meningiomas (p = 0.0098). We found a positive correlation between expression levels of VEGF-A and VEGFR-1 on tumor cells and vessels (p < 0.0001). In addition, there was a positive correlation of VEGF-A and VEGFR-3 expression on tumor vessels (p = 0.0034). VEGFR-2 expression was positively associated with progression-free survival (p = 0.0340). VEGF-A on tumor cells was negatively correlated with overall survival (p = 0.0084). The VEGF-A-driven system of tumor angiogenesis might still present a suitable target for adjuvant therapy in malignant meningioma disease. However, its role in malignant tumor progression may not be as crucial as expected. The value of comprehensive testing of the ligand and all receptors prior to administration of anti-angiogenic therapy needs to be evaluated in clinical trials.
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http://dx.doi.org/10.1007/s10735-020-09940-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012320PMC
April 2021

Early and Late Postoperative Seizures in Meningioma Patients and Prediction by a Recent Scoring System.

Cancers (Basel) 2021 Jan 25;13(3). Epub 2021 Jan 25.

Department of Neurosurgery, University Hospital, Goethe University Frankfurt, 60528 Frankfurt am Main, Germany.

Seizures are among the most common symptoms of meningioma. This retrospective study sought to identify risk factors for early and late seizures in meningioma patients and to evaluate a modified STAMPE2 score. In 556 patients who underwent meningioma surgery, we correlated different risk factors with the occurrence of postoperative seizures. A modified STAMPE2 score was applied. Risk factors for preoperative seizures were edema ( = 0.039) and temporal location ( = 0.038). For postoperative seizures preoperative tumor size ( < 0.001), sensomotory deficit ( = 0.004) and sphenoid wing location ( = 0.032) were independent risk factors. In terms of postoperative status epilepticus; sphenoid wing location ( = 0.022), tumor volume ( = 0.045) and preoperative seizures ( < 0.001) were independent risk factors. Postoperative seizures lead to a KPS deterioration and thus an impaired quality of life ( < 0.001). Late seizures occurred in 43% of patients with postoperative seizures. The small sub-cohort of patients (2.7%) with a STAMPE2 score of more than six points had a significantly increased risk for seizures ( < 0.001, total risk 70%). We concluded that besides distinct risk factors, high scores of the modified STAMPE2 score could estimate the risk of postoperative seizures. However, it seems not transferable to our cohort.
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http://dx.doi.org/10.3390/cancers13030450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865990PMC
January 2021

A Paravermal Trans-Cerebellar Approach to the Posterior Fossa Tumor Causes Hypertrophic Olivary Degeneration by Dentate Nucleus Injury.

Cancers (Basel) 2021 Jan 12;13(2). Epub 2021 Jan 12.

Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, 60528 Frankfurt am Main, Germany.

In brain tumor surgery, injury to cerebellar connectivity pathways can induce a neurodegenerative disease called hypertrophic olivary degeneration (HOD), along with a disabling clinical syndrome. In children, cerebellar mutism syndrome (CMS) is another consequence of damage to cerebello-thalamo-cortical networks. The goal of this study was to compare paravermal trans-cerebellar to other more midline or lateral operative approaches in their risk of causing HOD on MR-imaging and CMS. We scanned our neurosurgical database for patients with surgical removal of pilocytic astrocytoma, ependymoma and medulloblastoma in the posterior fossa. Fifty patients with a mean age of 22.7 (±16.9) years were identified and analyzed. HOD occurred in = 10/50 (20%) patients within four months (median), always associated with contralateral dentate nucleus (DN)-lesions ( < 0.001). Patients with paravermal trans-cerebellar approach significantly more often developed HOD (7/11; 63.6%) when compared to other approaches (3/39; 7.7%; < 0.001). Injury to the DN occurred more frequently after a paravermal approach (8/11 vs. 13/39 patients; < 0.05). CMS was described for = 12/50 patients (24%). Data indicated no correlation of radiological HOD and CMS development. A paravermal trans-cerebellar approach more likely causes HOD due to DN-injury when compared to more midline or lateral approaches. HOD is a radiological indicator for surgical disruption of cerebellar pathways involving the DN. Neurosurgeons should consider trajectories and approaches in the planning of posterior fossa surgery that spare the DN, whenever feasible.
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http://dx.doi.org/10.3390/cancers13020258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826586PMC
January 2021

Direct oral anticoagulants for therapeutic anticoagulation in postoperative pulmonary embolism after meningioma resection.

J Clin Neurosci 2020 Nov 16;81:265-269. Epub 2020 Oct 16.

Department of Neurosurgery, University Medicine of Rostock, Rostock, Germany.

Background: Acute postoperative pulmonary embolism (PE) is a dreaded complication with severe mortality rates. Brain tumor patients are at the highest risk for postoperative PE. The juxtaposition of low-molecular-weight heparin (LMWH), vitamin K antagonists (VKA) and direct oral anticoagulation (DOAC) in the treatment of postoperative PE in meningioma patients is largely unexplored.

Patients/methods: This is a single center observational analysis of meningioma patients who underwent neurosurgical resection with a thoracic CT scan confirmation of postoperative PE. The treatment modality, clinical course and outcome were investigated.

Results: Of 538 meningioma patients operated, 30 (6%) developed acute postoperative PE. After diagnosis, these patients received different long-term anticoagulation regimes. No significant difference in postoperative hemorrhage (p < 0.56), re-operation rate (p < 0.70) or Karnofsky performance scale (KPS) at 3 (p < 0.34) and 12 months (p = 1) were identified, when compared according to the different anticoagulation regimes.

Conclusion: DOACs were not associated with elevated risk for hemorrhage, recurrent thrombosis or poor outcome when compared with traditional anticoagulation regimes. Prospective randomized trials are necessary to verify the non-inferiority of DOACs for long-term anticoagulation in postoperative pulmonary embolism after meningioma resection.
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http://dx.doi.org/10.1016/j.jocn.2020.09.059DOI Listing
November 2020

Linking epigenetic signature and metabolic phenotype in IDH mutant and IDH wildtype diffuse glioma.

Neuropathol Appl Neurobiol 2021 04 7;47(3):379-393. Epub 2020 Nov 7.

Neurological Institute (Edinger Institute), University Hospital, Goethe University Frankfurt am Main, Frankfurt, Germany.

Aims: Changes in metabolism are known to contribute to tumour phenotypes. If and how metabolic alterations in brain tumours contribute to patient outcome is still poorly understood. Epigenetics impact metabolism and mitochondrial function. The aim of this study is a characterisation of metabolic features in molecular subgroups of isocitrate dehydrogenase mutant (IDHmut) and isocitrate dehydrogenase wildtype (IDHwt) gliomas.

Methods: We employed DNA methylation pattern analyses with a special focus on metabolic genes, large-scale metabolism panel immunohistochemistry (IHC), qPCR-based determination of mitochondrial DNA copy number and immune cell content using IHC and deconvolution of DNA methylation data. We analysed molecularly characterised gliomas (n = 57) for in depth DNA methylation, a cohort of primary and recurrent gliomas (n = 22) for mitochondrial copy number and validated these results in a large glioma cohort (n = 293). Finally, we investigated the potential of metabolic markers in Bevacizumab (Bev)-treated gliomas (n = 29).

Results: DNA methylation patterns of metabolic genes successfully distinguished the molecular subtypes of IDHmut and IDHwt gliomas. Promoter methylation of lactate dehydrogenase A negatively correlated with protein expression and was associated with IDHmut gliomas. Mitochondrial DNA copy number was increased in IDHmut tumours and did not change in recurrent tumours. Hierarchical clustering based on metabolism panel IHC revealed distinct subclasses of IDHmut and IDHwt gliomas with an impact on patient outcome. Further quantification of these markers allowed for the prediction of survival under anti-angiogenic therapy.

Conclusion: A mitochondrial signature was associated with increased survival in all analyses, which could indicate tumour subgroups with specific metabolic vulnerabilities.
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http://dx.doi.org/10.1111/nan.12669DOI Listing
April 2021

Cholinergic innervation and ganglion cell distribution in Hirschsprung's disease.

BMC Pediatr 2020 08 24;20(1):399. Epub 2020 Aug 24.

Institute of Neurology (Edinger Institute), Goethe University, Frankfurt, Germany.

Background: The diagnostic gold standard of Hirschsprung's disease (HD) is based on the histopathological assessment of colorectal biopsies. Although data on cholinergic innervation and ganglion cell (GC) distribution exist, only few studies have examined these two key features together. We assessed the pattern of cholinergic innervation and the amount of GCs in colorectal specimens of 14 HD patients.

Methods: We established a semi-quantitative score for cholinergic innervation using acetylcholinesterase (AChE) enzyme histochemistry and quantitatively analyzed the number of GCs via NADH tetrazolium reductase (NADH) enzyme histochemistry. We examined both the entire length of the resected specimens as well as defined areas of the transition zone of both pathological and healthy appearing segment.

Results: High AChE score values were associated with absence of GCs, and AChE scores were inversely correlated with the number of GCs. Nevertheless, we observed several cases in which one of the two features revealed a normal distribution pattern, whereas the other still displayed pathological features.

Conclusions: Our data support the need for transmural colon biopsies, to enable the best evaluation of both cholinergic innervation and GCs for a reliable assessment of HD.
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http://dx.doi.org/10.1186/s12887-020-02299-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445925PMC
August 2020

Delayed Occurrence of Hypertrophic Olivary Degeneration after Therapy of Posterior Fossa Tumors: A Single Institution Retrospective Analysis.

J Clin Med 2019 Dec 16;8(12). Epub 2019 Dec 16.

Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe-University, 60528 Frankfurt am Main, Germany.

(1) Background: A lesion within the dentato-rubro-olivary pathway (DROP) in the posterior fossa can cause secondary neurodegeneration of the inferior olivary nucleus: so-called hypertrophic olivary degeneration (HOD). The clinical syndrome of HOD occurs slowly over months and may be overlooked in progressive neuro-oncological diseases. Posterior fossa tumors are often located near these strategic structures. The goal of this study was to analyze the systematics of HOD occurrence in neuro-oncological patients. (2) Methods: The neuroradiological database of the university healthcare center was scanned for HOD-related terms from 2010 to 2019. After excluding patients with other causes of HOD, 12 datasets from neuro-oncological patients were analyzed under predetermined criteria. (3) Results: Patients received multimodal tumor treatments including neurosurgery, radiotherapy, and chemotherapy. HOD occurred both unilaterally (left = 4; right = 5) and bilaterally ( = 3). Though the mass effect of posterior fossa tumors had already affected strategic structures of the DROP, none of the patients showed signs of HOD on MRI until therapeutic measures including neurosurgery affecting the DROP were applied. HOD was visible on MRI within a median of 6 months after the neurosurgical intervention. In 67%, the presumed underlying surgical lesion in the DROP lay in the contralateral dentate nucleus. (4) Conclusion: In a selected cohort of neuro-oncological patients, therapeutic lesions within the DROP were associated with HOD occurrence.
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http://dx.doi.org/10.3390/jcm8122222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947510PMC
December 2019

DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management.

Neuro Oncol 2019 07;21(7):901-910

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Background: Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma.

Methods: DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts.

Results: The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03-0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8-7.2, P < 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22-0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3-11.1, P < 0.001) with clinical implications.

Conclusions: The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone.
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http://dx.doi.org/10.1093/neuonc/noz061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620635PMC
July 2019

Influence of pregnancy on glioma patients.

Acta Neurochir (Wien) 2019 03 29;161(3):535-543. Epub 2019 Jan 29.

Department of Neurosurgery, Goethe University Hospital, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany.

Background: Data about the influence of pregnancy on progression-free survival and overall survival of glioma patients are sparse and controversial. We aimed at providing further evidence on this relation.

Methods: The course of 18 glioma patients giving birth to 23 children after tumor surgery was reviewed and compared to the course of 18 nulliparous female patients matched for tumor diagnosis including molecular markers, extent of resection, and tumor location.

Results: Tumor pathology was astrocytoma, oligodendroglioma, and ependymoma in 9, 6, and 3 patients, respectively. Time interval between tumor resection and delivery was 5.3 ± 4.4 years. All newborns were healthy after uneventful deliveries. Tumor progression was diagnosed before pregnancy in 4 patients and during pregnancy in 1 patient, and 4 patients displayed progressive disease 31.0 ± 11 months after delivery. Three of these latter patients underwent second surgery, whereas resection of recurrent tumor had been performed in 2 women before pregnancy. Among nulliparous patients, 9 women suffered from tumor progression, resulting in re-operation in 7 patients and/or further adjuvant treatment in 6 cases. Progression-free survival did not differ between patients with and patients without children (p = 0.4). Moreover, in both groups, median overall survival was not reached after a mean follow-up period of 9.7 ± 5.7 years in glioma patients who gave birth to a child and 8.9 ± 4.2 years in nulliparous glioma patients.

Conclusion: Pregnancy does not seem to influence the clinical course of glioma patients. Likewise, glioma seems not to have an impact on delivered children's health.
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http://dx.doi.org/10.1007/s00701-019-03823-6DOI Listing
March 2019

Distribution and prognostic impact of microglia/macrophage subpopulations in gliomas.

Brain Pathol 2019 07 15;29(4):513-529. Epub 2019 Jan 15.

Edinger Institute, Institute of Neurology, Goethe University Frankfurt, Frankfurt am Main, Germany.

While the central nervous system is considered an immunoprivileged site and brain tumors display immunosuppressive features, both innate and adaptive immune responses affect glioblastoma (GBM) growth and treatment resistance. However, the impact of the major immune cell population in gliomas, represented by glioma-associated microglia/macrophages (GAMs), on patients' clinical course is still unclear. Thus, we aimed at assessing the immunohistochemical expression of selected microglia and macrophage markers in 344 gliomas (including gliomas from WHO grade I-IV). Furthermore, we analyzed a cohort of 241 IDH1R132H-non-mutant GBM patients for association of GAM subtypes and patient overall survival. Phenotypical properties of GAMs, isolated from high-grade astrocytomas by CD11b-based magnetic cell sorting, were analyzed by immunocytochemistry, mRNA microarray, qRT-PCR and bioinformatic analyses. A higher amount of CD68-, CD163- and CD206-positive GAMs in the vital tumor core was associated with beneficial patient survival. The mRNA expression profile of GAMs displayed an upregulation of factors that are considered as pro-inflammatory M1 (eg, CCL2, CCL3L3, CCL4, PTGS2) and anti-inflammatory M2 polarization markers (eg, MRC1, LGMN, CD163, IL10, MSR1), the latter rather being associated with phagocytic functions in the GBM microenvironment. In summary, we present evidence that human GBMs contain mixed M1/M2-like polarized GAMs and that the levels of different GAM subpopulations in the tumor core are positively associated with overall survival of patients with IDH1R132H-non-mutant GBMs.
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http://dx.doi.org/10.1111/bpa.12690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849857PMC
July 2019

Focused review on seizures caused by meningiomas.

Epilepsy Behav 2018 11 27;88:146-151. Epub 2018 Sep 27.

Department of Neurosurgery, University Hospital, Goethe University Frankfurt, Germany.

Background: Meningiomas belong to the most common intracranial neoplasms in adults. One of the most common symptoms patients with meningioma experience is seizures. However, it remains unclear whether prophylactic preoperative anticonvulsant treatment is worthwhile. Furthermore, it is not clear which patients are likely to experience seizures in the course of the disease. In recent years, many studies and meta-analyses addressed this question with particular contradictory results. Therefore, we aimed to identify the most important risk factors for seizures in patients with meningiomas.

Methods: For the search terms "meningioma and seizure", "meningioma and epilepsy", and "Simpson and seizure" Medline query identified 865 articles. After applying inclusion and exclusion criteria, 20 papers were chosen for further study. The papers were analyzed for all risk factors for pre- and postoperative risk factors for seizures.

Results: Preoperative seizures were mostly associated with extensive brain edema, localization, and bigger tumor size. Even though data were sometimes very contradictory, higher postoperative seizure rate in patients with meningioma was associated with distinct localizations, preoperative seizures, tumor size, brain edema, extent of resection, tumor recurrence, and new neurological deficits. There were no randomized trials showing a prophylactic effect of anticonvulsant drugs.

Conclusions: There are relevant risk factors for seizures in patients with meningioma. There is the need for a double blind randomized trial for the prophylactic use of antiepileptic drugs (AEDs).
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http://dx.doi.org/10.1016/j.yebeh.2018.09.002DOI Listing
November 2018

Pericytes/vessel-associated mural cells (VAMCs) are the major source of key epithelial-mesenchymal transition (EMT) factors SLUG and TWIST in human glioma.

Oncotarget 2018 May 8;9(35):24041-24053. Epub 2018 May 8.

Edinger Institute (Neurological Institute), Goethe University, Frankfurt, Germany.

Epithelial-to-mesenchymal transition (EMT) is supposed to be responsible for increased invasion and metastases in epithelial cancer cells. The activation of EMT genes has further been proposed to be important in the process of malignant transformation of primary CNS tumors. Since the cellular source and clinical impact of EMT factors in primary CNS tumors still remain unclear, we aimed at deciphering their distribution and clinico-pathological relevance in human gliomas. We investigated 350 glioma patients for the expression of the key EMT factors SLUG and TWIST by immunohistochemistry and immunofluorescence related to morpho-genetic alterations such as -amplification, (R132H) mutation and 1p/19q LOH. Furthermore, transcriptional cluster and survival analyses were performed. Our data illustrate that SLUG and TWIST are overexpressed in gliomas showing vascular proliferation such as pilocytic astrocytomas and glioblastomas. EMT factors are exclusively expressed by non-neoplastic pericytes/vessel-associated mural cells (VAMCs). They are not associated with patient survival but correlate with pericytic/VAMC genes in glioblastoma cluster analysis. In summary, the upregulation of EMT genes in pilocytic astrocytomas and glioblastomas reflects the level of activation of pericytes/VAMCs in newly formed blood vessels. Our results underscore that the negative prognostic potential of the EMT signature in the group of diffuse gliomas of WHO grade II-IV does most likely not derive from glioma cells but rather reflects the degree of proliferating mural cells thereby constituting a potential target for future alternative treatment approaches.
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http://dx.doi.org/10.18632/oncotarget.25275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963615PMC
May 2018

Pre- and early postoperative GFAP serum levels in glioma and brain metastases.

J Neurooncol 2018 Sep 24;139(3):541-546. Epub 2018 May 24.

Department of Neurosurgery, University Hospital, Goethe University Frankfurt, 60528, Frankfurt am Main, Germany.

Subject: To date there is no established tumor marker for the clinical follow-up of glioblastoma, WHO grade IV, (GBM) which constitutes the most frequent and malignant primary brain tumor. However, since there is promising data that the serum glial fibrillary acidic protein (sGFAP) may serve as a biomarker for glial brain tumors, this prospective study aimed at evaluating the diagnostic relevance of perioperative changes in sGFAP levels for the assessment of residual glial tumor tissue in patients undergoing surgery of intracerebral tumors.

Methods: Serum GFAP was measured using an electrochemiluminometric immunoassay (ElecsysR GFAP prototype test, Roche Diagnostics, Penzberg/Germany) in 32 prospectively recruited patients between September 2009 and August 2010. Twenty-five were diagnosed with glioma and seven with brain metastases (BM). We assessed sGFAP levels prior to and at different time points during the early postoperative phase until patient discharge.

Results: There were only significant differences in the pre-operative sGFAP levels of patients with gliomas compared to BM (0.18 vs. 0.08 µg/l; p = 0.0198, Welch's t-Test). Even though there was an increase of sGFAP after surgery, there were no significant differences between glioma and BM patients at any other time point. Peak sGFAP levels where reached on postoperative day 1 followed by a slight decrease, but not reaching pre-operative levels until postop day 7. There was no significant correlation between postoperative glioma tumor volume and sGFAP levels in univariate analyses.

Conclusion: According to our data sGFAP does not appear to be suitable to detect residual glioma tissue in the acute postoperative phase.
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http://dx.doi.org/10.1007/s11060-018-2898-1DOI Listing
September 2018

Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence.

Acta Neuropathol 2018 06 7;135(6):955-963. Epub 2018 Apr 7.

Department of Neuropathology, University Hospital Heidelberg, 69120, Heidelberg, Germany.

Epigenetic patterns on the level of DNA methylation have already been shown to separate clinically relevant subgroups of meningiomas. We here set out to identify potential prognostic implications of epigenetic modification on the level of histones with focus on H3K27 trimethylation (H3K27me3). H3K27me3 was assessed by immunohistochemistry on 232 meningiomas from 232 patients. In 194 cases, trimethylation was detected in tumor cells. In 25 cases, staining was limited to vessels while all tumor cells were negative. Finally, 13 cases yielded equivocal staining patterns. Reduced abundance of H3K27me3 in cases with staining limited to vessels was confirmed by mass spectrometry on a subset of cases. Lack of staining for H3K27me3 in all tumor cells was significantly associated with more rapid progression (p = 0.009). In line, H3K27me3-negative cases were associated with a DNA methylation pattern of the more aggressive types among the recently introduced DNA methylation groups. Also, NF2 and SUFU mutations were enriched among cases with complete lack of H3K27me3 staining in tumor cells (p < 0.0001 and p = 0.029, respectively). H3K27me3 staining pattern added significant prognostic insight into WHO grade II cases and in the compound subset of WHO grade I and II cases (p = 0.04 and p = 0.007, respectively). However, it did not further stratify within WHO grade III cases. Collectively, these data indicate that epigenetic modifications beyond DNA methylation are involved in the aggressiveness of meningioma. It also suggests that H3K27me3 immunohistochemistry might be a useful adjunct in meningioma diagnostics, particularly for cases with WHO grade II histology or at the borderline between WHO grade I and II.
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http://dx.doi.org/10.1007/s00401-018-1844-9DOI Listing
June 2018

Surgery for Glioblastoma in Light of Molecular Markers: Impact of Resection and MGMT Promoter Methylation in Newly Diagnosed IDH-1 Wild-Type Glioblastomas.

Neurosurgery 2019 01;84(1):190-197

Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.

Background: Previous studies addressing the influence of surgery on the outcome of patients with glioblastomas (GBM) have not addressed molecular markers. The value of surgery versus the tumor's major biological markers remains unclear.

Objective: We investigate the extent of resection as a prognosticator for patients with newly diagnosed primary GBM with the incorporation of molecular diagnostics as per the updated WHO 2016 diagnostic criteria for GBM.

Methods: Patients with newly diagnosed GBM who underwent resection were prospectively included within a database. We analyzed patients with newly diagnosed GBM and excluded patients who presented with IDH1 R132H mutations. Gross total resection (GTR) was defined as complete removal of enhancing disease.

Results: One hundred seventy-five patients were included within the analysis. One hundred four patients (59.4%) had GTR, 71 patients (40.6%) had subtotal or partial resection. Eighty patients (45.7%) displayed O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, 95 patients (54.3%) showed no MGMT promoter methylation. In Cox regression analysis, MGMT promoter methylation (hazard ratio [HR] 1.55; 95% confidence interval [CI], 1.01-2.19; P = .0133) and GTR (HR 1.48; 95% CI, 1.06-2.07; P = .0206) were significantly associated with favorable progression-free survival. MGMT promoter methylation (HR 2.13; 95% CI, 1.45-3.12; P = .0001) and GTR (HR 1.81; 95% CI, 1.24-2.63; P = .002) were associated with favorable overall survival (OS). Of other risk factors analyzed, age (>60 vs ≤ 60 yr) was significantly associated with progression-free survival (HR 1.60; 95% CI, 1.14-2.24; P = .006) and OS (HR 2.19; 95% CI, 1.51-3.19; P < .0001).

Conclusion: GTR and MGMT promoter methylation are independent prognosticators for improved overall and progression-free survival in a homogeneous cohort of newly diagnosed patients with IDH wild-type glioblastoma.
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http://dx.doi.org/10.1093/neuros/nyy049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500906PMC
January 2019

Motor Cortex Reorganization in Patients with Glioma Assessed by Repeated Navigated Transcranial Magnetic Stimulation-A Longitudinal Study.

World Neurosurg 2018 Apr 31;112:e442-e453. Epub 2018 Jan 31.

Department of Neurosurgery, Goethe University Hospital, Frankfurt, Germany; University Cancer Center Frankfurt (UCT), Goethe University Hospital, Frankfurt, Germany. Electronic address:

Objective: Evidence for cerebral reorganization after resection of low-grade glioma has mainly been obtained by serial intraoperative cerebral mapping. Noninvasively collected data on cortical plasticity in tumor patients over a surgery-free period are still scarce. The present study therefore aimed at evaluating motor cortex reorganization by navigated transcranial magnetic stimulation (nTMS) in patients after perirolandic glioma surgery.

Methods: nTMS was performed preoperatively and postoperatively in 20 patients, separated by 26.1 ± 24.8 months. Further nTMS mapping was conducted in 14 patients, resulting in a total follow-up period of 46.3 ± 25.4 months. Centers of gravity (CoGs) were calculated for every muscle representation area, and Euclidian distances between CoGs over time were defined. Results were compared with data from 12 healthy individuals, who underwent motor cortex mapping by nTMS in 2 sessions.

Results: Preoperatively and postoperatively pooled CoGs from the area of the dominant abductor pollicis brevis muscle and of the nondominant leg area differed significantly compared with healthy individuals (P < 0.05). Most remarkably, during the ensuing follow-up period, a reorganization of all representation areas was observed in 3 patients, and a significant shift of hand representation areas was identified in further 3 patients. Complete functional recovery of postoperative motor deficits was exclusively associated with cortical reorganization.

Conclusions: Despite the low potential of remodeling within the somatosensory region, long-term reorganization of cortical motor function can be observed. nTMS is best suited for a noninvasive evaluation of this reorganization.
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http://dx.doi.org/10.1016/j.wneu.2018.01.059DOI Listing
April 2018

"Two is not enough" - Impact of the number of tissue samples obtained from stereotactic brain biopsies in suspected glioblastoma.

J Clin Neurosci 2018 Jan 24;47:311-314. Epub 2017 Oct 24.

Department of Neurosurgery, Goethe University Frankfurt, Germany.

Objective: Stereotactic procedures are performed in many neurosurgical departments in order to obtain tumor tissue from brain lesions for histopathological evaluation. Biopsies can be performed frame-guided and frame less. Some departments use a biopsy needle (cylinder probe), others a forceps for repetitive smaller tissue samples. Although the applied techniques are somehow different, it is still unclear how many tissue samples have to be taken to establish reliably a final diagnosis based on histopathological and genetic examinations. Only precise histopathological diagnosis results in adequate therapy.

Methods: We included 43 consecutive patients who underwent stereotactic biopsy of a suspected glioblastoma between 02/2013 and 07/2015. All patients showed contrast enhancing tumors in the MRI. The patients underwent stereotactic biopsy with the Leksell frame attached to their head. All stereotactic procedures were performed in the presence of a neuropathologist. Target and Entry Points were calculated with BrainLab iplan software (BrainLab iplan 1.0, Munich, Germany). First the two samples 5mm before the Target (pre-target) and the "Targetpoint" itself were analyzed (group 1), then a histopathological evaluation of all samples was performed (group 2).

Results: Mean number of extracted samples was 14. Using classical hematoxylin-eosin stainings, in group 1 histopathological diagnosis was correct in only 30 cases accounting for 73%. Contrariwise a final diagnosis was made in 100% in group 2.

Conclusion: If only two tissue samples were evaluated in this group of patients with suspected glioblastoma, a correct diagnosis was possible in only 73% of the cases. We conclude that two samples are not enough to establish a final diagnosis even in a subgroup of suspected glioblastoma.
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http://dx.doi.org/10.1016/j.jocn.2017.09.032DOI Listing
January 2018
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