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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.
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.
Posterior fossa tumor surgery is challenging due to the proximity and exposure of cerebellar structures. A favorable operative approach is unknown. Following lesions to the dentato–rubro–olivary-pathway, a neurodegenerative disease called hypertrophic olivary degeneration (HOD) can occur. This study for the first time demonstrates that paravermal trans-cerebellar approaches are associated with a significantly higher likelihood of HOD on MRI when compared to other approaches. This finding can well be attributed to dentate nucleus (DN) injury. Furthermore, cerebellar mutism syndrome (CMS) was discussed in the literature to be correlated with HOD due to a functional overlap of pathways involved. We found no such correlation in this study, but HOD was shown to be a reliable indicator for surgical disruption of efferent cerebellar pathways involving the DN. Henceforth, neurosurgeons should consider more midline or lateral approaches in posterior fossa surgery to spare the DN whenever feasible, and focus on cerebellar functional anatomy in their preoperative planning.
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%; p = 0.0015). In transfused patients, postoperative complications as well as hospital LOS was significantly higher (p < 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 (p = 0.0247), tumor size (p = 0.0006), surgical time (p = 0.0018) and intraoperative blood loss (p < 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.
Meningioma surgery in patients ≥70 years of age: clinical outcome and validation of the SKALE score
(2021)
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 (p < 0.0001). Pulmonary complications including pneumonia (10% vs. 3.2%; p = 0.0202) and pulmonary embolism (12.7% vs. 6%; p = 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%; p = 0.0033), six-month (7% vs. 0.3%; p = 0.0006) and one-year mortality (8.5% vs. 0.3%; p < 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%; p = 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.
To clip or coil has been matter of debates for several years and is the domain of interdisciplinary decision making. However, the microsurgical outcome has still been elusive concerning wide neck aneurysms (WNA). A retrospective single center study was performed with all patients with ruptured WNA (rWNA) and unruptured WNA (uWNA) admitted to author´s institute between 2007–2017. Microsurgical outcome was evaluated according to Raymond-Roy occlusion grade and follow-up angiography was performed to analyze the stability of neck/aneurysm remnants and retreatment poverty. Of 805 aneurysms, 139 were rWNA (17.3%) and 148 uWNA (18.4%). Complete occlusion was achieved in 102 of 139 rWNA (73.4%) and 112 of 148 uWNA (75.6%). Neck remnants were observed in 36 patients with rWNA (25.9%) and 30 patients with uWNA (20.3%), 1 (0.7%) and 6 (4.1%) patients had aneurysmal remnant, respectively. Overall complication rate was 11.5%. At follow-up (939/1504 months), all remnants were stable except for one, which was further conservatively treated with marginal retreatment rate under 1%. Even the risk of de-novo aneurysm was higher than the risk for remnant growth (2.6% vs 0% in rWNA; 8.7% vs 5.3% in uWNA) without significant difference. Microsurgical clipping is effective for complete occlusion of r/uWNA with low complication. Furthermore, the risk of remnant growth is marginal even lower than the risk of de-novo rate low retreatment rate.
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.
The efficacy of statin-treatment in aneurysmal subarachnoid hemorrhage (SAH) remains controversial. We aimed to investigate the effects of statin-treatment in non-aneurysmal (na)SAH in accordance with animal research data illustrating the pathophysiology of naSAH. We systematically searched PubMed using PRISMA-guidelines and selected experimental studies assessing the statin-effect on SAH. Detecting the accordance of the applied experimental models with the pathophysiology of naSAH, we analyzed our institutional database of naSAH patients between 1999 and 2018, regarding the effect of statin treatment in these patients and creating a translational concept. Patient characteristics such as statin-treatment (simvastatin 40 mg/d), the occurrence of cerebral vasospasm (CVS), delayed infarction (DI), delayed cerebral ischemia (DCI), and clinical outcome were recorded. In our systematic review of experimental studies, we found 13 studies among 18 titles using blood-injection-animal-models to assess the statin-effect in accordance with the pathophysiology of naSAH. All selected studies differ on study-setting concerning drug-administration, evaluation methods, and neurological tests. Patients from the Back to Bedside project, including 293 naSAH-patients and 51 patients with simvastatin-treatment, were recruited for this analysis. Patients under treatment were affected by a significantly lower risk of CVS (p < 0.01; OR 3.7), DI (p < 0.05; OR 2.6), and DCI (p < 0.05; OR 3). Furthermore, there was a significant association between simvastatin-treatment and favorable-outcome (p < 0.05; OR 3). However, dividing patients with statin-treatment in pre-SAH (n = 31) and post-SAH (n = 20) treatment groups, we only detected a tenuously significant higher chance for a favorable outcome (p < 0.05; OR 0.05) in the small group of 20 patients with statin post-SAH treatment. Using a multivariate-analysis, we detected female gender (55%; p < 0.001; OR 4.9), Hunt&Hess ≤III at admission (p < 0.002; OR 4), no anticoagulant-therapy (p < 0.0001; OR 0.16), and statin-treatment (p < 0.0001; OR 24.2) as the main factors improving the clinical outcome. In conclusion, we detected a significantly lower risk for CVS, DCI, and DI in naSAH patients under statin treatment. Additionally, a significant association between statin treatment and favorable outcome 6 months after naSAH onset could be confirmed. Nevertheless, unified animal experiments should be considered to create the basis for developing new therapeutic schemes.
Background: The incidence of pyogenic spinal infection has increased in recent years. In addition to treatment of the spinal infection, early diagnosis and therapy of coexisting infections, especially of secondary brain infection, are important. The aim of this study is to elucidate the added value of routine cerebral imaging in the management of these patients.
Methods: This was a retrospective single-center study. Cerebral imaging consisting of cerebral magnetic resonance imaging (cMRI) was performed to detect brain infection in patients with a primary pyogenic spinal infection. Results: We analyzed a cohort of 61 patients undergoing cerebral imaging after diagnosis of primary pyogenic spinal infection. The mean age in this cohort was 68.7 years and the gender distribution consisted of 44 males and 17 females. Spinal epidural abscess was proven in 32 (52.4%) patients. Overall positive blood culture was obtained in 29 (47.5%) patients, infective endocarditis was detected in 23 (37.7%) patients and septic condition at admission was present in 12 (19.7%) Patients. Coexisting brain infection was detected in 2 (3.3%) patients. Both patients revealed clinical signs of severe sepsis, reduced level of consciousness (GCS score 3), were intubated, and died due to multi-organ failure. Conclusions: Brain infection in patients with spinal infection is very rare. Of 61 patients with pyogenic spinal infection, two patients had signs of cerebral infection shown by imaging, both of whom were in a coma (GCS 3), and sepsis.
Purpose: Dexamethasone (Dex) is the most common corticosteroid to treat edema in glioblastoma (GBM) patients. Recent studies identified the addition of Dex to radiation therapy (RT) to be associated with poor survival. Independently, Tumor Treating Fields (TTFields) provides a novel anti-cancer modality for patients with primary and recurrent GBM. Whether Dex influences the efficacy of TTFields, however, remains elusive. Methods: Human GBM cell lines MZ54 and U251 were treated with RT or TTFields in combination with Dex and the effects on cell counts and cell death were determined via flow cytometry. We further performed a retrospective analysis of GBM patients with TTFields treatment +/- concomitant Dex and analysed its impact on progression-free (PFS) and overall survival (OS). Results: The addition of Dex significantly reduced the efficacy of RT in U251, but not in MZ54 cells. TTFields (200 kHz/250 kHz) induced massive cell death in both cell lines. Concomitant treatment of TTFields and Dex did not reduce the overall efficacy of TTFields. Further, in our retrospective clinical analysis, we found that the addition of Dex to TTFields therapy did not influence PFS nor OS. Conclusion: Our translational investigation indicates that the efficacy of TTFields therapy in patients with GBM and GBM cell lines is not affected by the addition of Dex.