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Purpose: Preclinical data indicate anti-invasive activity of APG101, a CD95 ligand (CD95L)–binding fusion protein, in glioblastoma.Experimental Design: Patients (N = 91) with glioblastoma at first or second progression were randomized 1:2 between second radiotherapy (rRT; 36 Gy; five times 2 Gy per week) or rRT+APG101 (400 mg weekly i.v.). Patient characteristics [N = 84 (26 patients rRT, 58 patients rRT+APG101)] were balanced.Results: Progression-free survival at 6 months (PFS-6) rates were 3.8% [95% confidence interval (CI), 0.1–19.6] for rRT and 20.7% (95% CI, 11.2–33.4) for rRT+APG101 (P = 0.048). Median PFS was 2.5 (95% CI, 2.3–3.8) months and 4.5 (95% CI, 3.7–5.4) months with a hazard ratio (HR) of 0.49 (95% CI, 0.27–0.88; P = 0.0162) adjusted for tumor size. Cox regression analysis adjusted for tumor size revealed a HR of 0.60 (95% CI, 0.36–1.01; P = 0.0559) for rRT+APG101 for death of any cause. Lower methylation levels at CpG2 in the CD95L promoter in the tumor conferred a stronger risk reduction (HR, 0.19; 95% CI, 0.06–0.58) for treatment with APG101, suggesting a potential biomarker.Conclusions: CD95 pathway inhibition in combination with rRT is an innovative concept with clinical efficacy. It warrants further clinical development. CD95L promoter methylation in the tumor may be developed as a biomarker. Clin Cancer Res; 20(24); 6304–13. ©2014 AACR.

Acknowledgement. List of investigators and other study stuff at the individual sites.

CONSORT Statement

Suppl Figures S1-S4. S1: Genomic Localization of the CpG2 in the CD95 L promoter. S2: Survival probability according to CpG2 methylation status. S3: Survival probability according to CD95L expression as detected by IHC. S4 a and b: Cox regression data for CpG1 and 2 in the CD95L promoter.

Background Little is known about delivery of neurosurgical care, complication rate and outcome of patients with high-grade glioma (HGG) during the coronavirus disease 2019 (Covid-19) pandemic. Methods This observational, retrospective cohort study analyzed routine administrative data of all patients admitted for neurosurgical treatment of an HGG within the Helios Hospital network in Germany. Data of the Covid-19 pandemic (March 1, 2020—May 31, 2022) were compared to the pre-pandemic period (January 1, 2016—February 29, 2020). Frequency of treatment and outcome (in-hospital mortality, length of hospital stay [LOHS], time in intensive care unit [TICU] and ventilation outside the operating room [OR]) were separately analyzed for patients with microsurgical resection (MR) or stereotactic biopsy (STBx). Results A total of 1763 patients underwent MR of an HGG (648 patients during the Covid-19 pandemic; 1115 patients in the pre-pandemic period). 513 patients underwent STBx (182 [pandemic]; 331 patients [pre-pandemic]). No significant differences were found for treatment frequency (MR: 2.95 patients/week [Covid-19 pandemic] vs. 3.04 patients/week [pre-pandemic], IRR 0.98, 95% CI: 0.89–1.07; STBx (1.82 [Covid-19 pandemic] vs. 1.86 [pre-pandemic], IRR 0.96, 95% CI: 0.80–1.16, P > .05). Rates of in-hospital mortality, infection, postoperative hemorrhage, cerebral ischemia and ventilation outside the OR were similar in both periods. Overall LOHS was significantly shorter for patients with MR and STBx during the Covid-19 pandemic. Conclusions The Covid-19 pandemic did not affect the frequency of neurosurgical treatment of patients with an HGG based on data of a large nationwide hospital network in Germany. LOHS was significantly shorter but quality of neurosurgical care and outcome was not altered during the Covid-19 pandemic.

Ronald Seidel,1 Marc Tietke,2 Oliver Heese,3 Uwe Walter4 1Asklepios Medical Center, Department of Anesthesiology and Intensive Care, Schwedt, Germany; 2Helios Medical Center, Department of Neuroradiology, Schwerin, Germany; 3Helios Medical Center, Department of Neurosurgery, Schwerin, Germany; 4University Medical Center Rostock, Department of Neurology, Rostock, GermanyCorrespondence: Ronald SeidelAsklepios Medical Center, Department of Anesthesiology and Intensive Care, Am Klinikum 1, Schwedt, 16303, GermanyTel +49 3332 534521Email ronald-seidel@t-online.deAbstract: Thoracic epidural analgesia (TEA) is a standard procedure in multimodal analgesia applied in major thoracic and abdominal surgeries. Two cases are presented with serious complications related to TEA. In both cases, earlier reaction of the treating physicians to patient-reported sensory symptoms could have prevented the complicated course. The first case was a 73-year-old patient with bronchial carcinoma who underwent right lower lobe resection. In this case, dabigatran 150 mg/d (indication: permanent atrial fibrillation) had been discontinued 72 hours before surgery, and enoxaparin 80 mg (every 12 hours) had been started 11 hours after surgery. An epidural hematoma developed postoperatively. Magnetic resonance imaging (MRI) was performed only after paraplegia had developed the next day. Unfortunately, delayed hematoma evacuation could not prevent persistent paraplegia in this case, which was complicated by hospital-acquired pneumonia with sepsis and acute renal failure. The second case was a 39-year-old patient with ulcerative colitis and an initially undetected malposition of the epidural catheter. Immediately after test bolus injection, the patient reported paresthesia and overall discomfort, which however could not be safely attributed to either the test dose or the already started general anesthesia. The patient could only be extubated after stopping the epidural infusion. Accidental re-start of epidural infusion led to coma, conjugate eye deviation, and respiratory arrest, necessitating re-intubation. Computed tomography (CT) ruled out intracerebral pathology and showed a catheter position centrally in the spinal canal. Fortunately, no neurological deficits were detected after catheter removal.Keywords: epidural analgesia, dabigatran, paraplegia, perioperative complications

Background The full impact of the COVID-19 pandemic on surgical spine care is difficult to assess due to a lack in nationwide evidence from more recent phases of the pandemic. We aimed to describe changes in in-hospital processes associated with spinal fusion procedures in the treatment of spinal infections (SI) during different phases of the pandemic. Methods In this retrospective observational study, we examined the in-hospital prevalence and outcomes of spinal fusion procedures for SI (along with patient characteristics, rates of transfer to intensive care units, and mortality rates) during the first four waves of the pandemic compared with the corresponding prepandemic periods in 2019. We used administrative data from a nationwide network of 76 hospitals managing 7% of all in-hospital cases in Germany. Results We observed no significant change in the prevalence of SI fusion procedures during the pandemic, neither in total numbers (349 vs. 373) nor for each wave separately. On a patient level, we found no differences in age, sex, and the prevalence of paresis, and no relevant differences in associated comorbidities. The rate of mechanical ventilation did not change during any of the examined pandemic waves: it ranged between 9.5 and 18.6% during the pandemic and 3.1 and 16.0% during the corresponding prepandemic control periods. The rate of transfer to intensive care changed only during wave 4 (from 70.4 to 54.8%; p = 0.046) but not in any other pandemic phases. We observed no changes in in-hospital mortality rates (range: 2.9–9.7% vs. 6.2–11.3%) or in duration of hospital stay (range: 26.2–30.8 days vs. 20.8–29.2 days). Conclusions The main finding of our study is that within this nationwide network of spine care centers in Germany, the delivery of surgical treatment of SI by means of spinal fusion procedures was maintained throughout the first four waves of the pandemic. Furthermore, there were no relevant changes in patient demographics, in-hospital processes, and mortality rates.

Decompression is one of the most common interventions in spinal surgery. Obesity has become an increasing issue in surgical patients. Therefore, the aim of this study was to analyze the clinical outcome following lumbar microsurgical decompression in correlation with the patient’s body mass index (BMI). A toal of 744 patients with spinal claudication that were seen at two specialized spine centers were included in this study. All patients underwent a bilateral microsurgical decompression in over-the-top technique. Patients were allocated in 4 groups based in their BMI category: 18.5–24.9 (n = 204), 25.0–29.9 (n = 318), 30.0–34.9 (n = 164) and ≥ 35 (n = 58). Clinical outcome data were recorded at baseline as well as 3, 12 and 24 months thereafter within a prospective study framework. The minimum follow-up was 12 months. For statistical analysis, data were adjusted for age, length of surgery and ASA and were analyzed by generalized linear gamma-based models. Postoperative changes in all outcome parameters were clearly dependent on BMI. Patients with higher BMI were characterized by inferior baseline values for VAS Back (p

Objective To validate with a prospective study a decision-supporting coding system for the surgical approach for multilevel degenerative cervical myelopathy. Methods Ten cases were presented on an internet platform, including clinical and imaging data. A single-approach (G1), a choice between 2 (G2), or 3 approaches (G3) were options. Senior and junior spine surgeons analyzed 7 parameters: location and extension of the compression of the spinal cord, C-spine alignment and instability, general morbidity and bone diseases, and K-line and multilevel corpectomy. For each parameter, an anterior, posterior, or combined approach was suggested. The most frequent letter or the last letter (if C) of the resulting 7-letter code (7LC) suggested the surgical approach. Each surgeon performed 2 reads per case within 8 weeks. Results G1: Interrater reliability between junior surgeons improved from the first read (κ = 0.40) to the second (κ = 0.76, p < 0.001) but did not change between senior surgeons (κ = 0.85). The intrarater reliability was similar for junior (κ = 0.78) and senior (κ = 0.71) surgeons. G2: Junior/senior surgeons agreed completely (58%/62%), partially (24%/23%), or did not agree (18%/15%) with the 7LC choice. G3: junior/senior surgeons agreed completely (50%/50%) or partially (50%/50%) with the 7LC choice. Conclusion The 7LC showed good overall reliability. Junior surgeons went through a learning curve and converged to senior surgeons in the second read. The 7LC helps less experienced surgeons to analyze, in a structured manner, the relevant clinical and imaging parameters influencing the choice of the surgical approach, rather than simply pointing out the only correct one.

Purpose As an essential part of the health care system, the requirements for specialist training are subject to a continuous process of change. The aim of the present study was to evaluate the current specialist training situation of all departments in a tertiary care hospital in Germany. Differences between assistant and chief physicians should be pointed out. Materials and methods The analysis of the current training situation was carried out on the basis of an individually created questionnaire. The questionnaire content included career goal and specialism. The characteristic values initial training (IT), training structure (TS) and training content were measured on a numeric scale from 1 to 5. In addition, an overall assessment of the trainers’ competences was performed. The questionnaire was sent to 208 assistant physicians (AP) and 34 chief physicians (CP). Results Totally 92 APs (44.2%) and 22 CPs (64.7%) participated. Senior physician was the most common career goal (34.1%), followed by the branch (28.6%). The importance of the topics initial training (IT) and training structure (TS) were evaluated as mean value: ITCP=1.5, ITAP=1.6; p=0.701 and TSCP=1.4, TSAP=1.5; p=0.669. The results concerning the implementation of the topics IT and TS in the daily routine show significant differences between APs and CPs (ITCP=2.0, ITAP=3.2; p=0.002; TSCP=1.9, TSAP=3.0; p Conclusion Our data underline the importance of specialist training subjects. These are partly perceived very differently by APs and CPs. Innovative concepts for the induction phase, well-structured training curricula, providing management skills, the overall use of skills labs and digital documentation might support the satisfaction and the outcome of specialist training. This could also improve quality in patient care.

Catheter-tip-associated granulomas (CTG) are a rare but serious complication of intrathecal analgesic delivery pumps (IADP), which interfere with pain modulation and can cause irreversible neurologic deficits. The treatment of symptomatic CTG generally involves surgical resection and catheter removal. We present a case of an unresectable CTG, which we managed using progressive lowering of the intrathecal morphine sulfate (ITMS) dosage as well as spinal cord stimulation (SCS). A 55-year-old female with failed back surgery syndrome (FBSS) presented with new-onset left-sided lumbar radiculopathy after five years of moderately successful ITMS therapy. An MRI study suggested an unknown mass associated with the tip of the catheter. The tumor’s adherence to nerve roots of the conus terminalis prevented a complete resection and only allowed for a biopsy. After the SCS implantation, we progressively lowered the ITMS dose. In a follow-up consultation, the patient reported the regression of the radiculopathy as well as satisfactory pain levels without oral opiates. In this case of CTG, cessation of intrathecal morphine prevented the further growth of the granuloma. SCS effectively addressed both the chronic lumbar back pain as well as the new-onset radicular pain caused by the CTG.

Background Antimicrobial stewardship (AMS) strategies worldwide focus on optimising the use of antibiotics. Selective susceptibility reporting is recommended as an effective AMS tool although there is a lack of representative studies investigating the impact of selective susceptibility reporting on antibiotic use. The aim of this study was to investigate the impact of selective susceptibility reporting of Staphylococcus aureus (S. aureus) on antibiotic consumption. Enhancing the use of narrow-spectrum beta-lactam antibiotics such as flucloxacillin/cefazolin/cefalexin is one of the main goals in optimising antibiotic therapy of S. aureus infections. Methods This interventional study with control group was conducted at a tertiary care hospital in Germany. During the one-year interventional period susceptibility reports for all methicillin-sensitive S. aureus (MSSA) were restricted to flucloxacillin/cefazolin/cefalexin, trimethoprim-sulfamethoxazole, clindamycin, gentamicin and rifampin/fosfomycin, instead of reporting all tested antibiotics. The impact of implementing selective reporting was analysed by monitoring total monthly antibiotic consumption in our hospital and in a reference hospital (recommended daily dose/100 occupied bed days: RDD/100 BD), as well as on an individual patient level by analysing days of therapy adjusted for bed days (DOT/ 100 BD) for patients with S. aureus bacteremia (SAB) and respectively skin and soft tissue infections (SSTI). Results MSSA-antibiograms were acquired for 2836 patients. The total use of narrow-spectrum beta-lactams more than doubled after implementing selective reporting (from 1.2 to 2.8 RDD/100 BD, P Conclusions As narrow-spectrum beta-lactams are not widely used for other infections, their increase in the overall consumption of the entire hospital was a strong indicator that selective reporting guided clinicians to an optimised antibiotic therapy of S. aureus infections. On a patient level, this assumption was verified by a significant improved treatment of S. aureus infections in the subgroups of SAB and SSTI. As useful AMS tool, we recommend implementing selective reporting rules into the national/international standards for susceptibility reporting.

Decompression is one of the most common interventions in spinal surgery. Obesity has become an increasing issue in surgical patients. Therefore, the aim of this study was to analyze the clinical outcome following lumbar microsurgical decompression in correlation with the patient's body mass index (BMI).A toal of 744 patients with spinal claudication that were seen at two specialized spine centers were included in this study. All patients underwent a bilateral microsurgical decompression in over-the-top technique. Patients were allocated in 4 groups based in their BMI category: 18.5-24.9 (n = 204), 25.0-29.9 (n = 318), 30.0-34.9 (n = 164) and ≥ 35 (n = 58). Clinical outcome data were recorded at baseline as well as 3, 12 and 24 months thereafter within a prospective study framework. The minimum follow-up was 12 months. For statistical analysis, data were adjusted for age, length of surgery and ASA and were analyzed by generalized linear gamma-based models.Postoperative changes in all outcome parameters were clearly dependent on BMI. Patients with higher BMI were characterized by inferior baseline values for VAS Back (p 0.05). Over the follow-up period, the groups with BMI 30-34.9 and BMI ≥ 35 benefitted significantly less from the surgery than the two slimmer groups (p 0.05).The data obtained from this large, homogenous cohort demonstrate that the quality of life improved substantially in all patients that were treated microsurgically for spinal stenosis. However, a BMI ≥ 30 may be considered as a negative predictor for a significantly inferior clinical outcome.

Background During the course of disease, most glioma patients learn that there is no cure for their tumor. It is therefore not uncommon for patients or caregivers to seek complementary and alternative medicine (CAM) treatments. Patterns of CAM use vary across the globe, but little is known about the type of, and motivation for, CAM use in most countries. Methods Here we conducted a cross-sectional survey of CAM use in patients harboring gliomas of World Health Organization (WHO) grades II to IV at 3 specialized neuro-oncology centers in Switzerland. Results Of 208 patients who returned the survey, approximately half reported having used or using CAM. CAM use was associated with younger age. Patients suffering from WHO grade II gliomas were less likely to indicate CAM use. The leading motivation for CAM use was to contribute actively to the treatment of the disease. CAM use was commonly not counseled or supervised by a health care professional. Cost and issues of reimbursement were not an important factor in the decision against or for CAM use. Conclusions Physicians caring for glioma patients should be aware of and explore CAM use to better understand patients’ attitudes toward their disease, to provide counseling, and to identify potential interactions of CAM with standard treatments for gliomas.

SummaryObjective Selective amygdalohippocampectomy (sAHE) is a well-established treatment for temporal lobe epilepsy, commonly with favorable neuropsychological outcome. Yet, it is still unknown if subsequent resection of the anteromesial temporal lobe (AMTLR), when necessary, deteriorates neuropsychological performance in this selected group of patients. Thus, we evaluated the clinical and neuropsychological data of patients who, due to insufficient seizure control after sAHE, received a subsequent ipsilateral AMTLR and compared these findings with patients who did not receive a second resection (control group). Methods Patients’ characteristics and neuropsychological data were assessed and analyzed in the reoperated as well as in the control group at each step of treatment. Experienced neuropsychologists conducted the standardized examination focusing on verbal, figural and working memory, speech fluency and attention. Preoperative diagnostics included further continuous video-electroencephalography monitoring, high-resolution magnetic resonance imaging and functional transcranial Doppler sonography. Results Eighty patients having received sAHE in our center from 11/2007 to 02/2013 were included in this study. Seventeen of these patients underwent subsequent AMTLR. Thirteen of these were available for follow-up after the second surgery and twelve had a comprehensive neuropsychological testing at all three steps. Analyzing the neuropsychological data revealed no significant differences compared with controls. On the individual level, the data demonstrated that improvement in a subdomain was more frequent than decline, if the performance had already deteriorated after the first procedure. Seizure control improved significantly (p < 0.001) in all patients after subsequent AMTLR resulting in seven patients being seizure-free at follow-up. Significance Subsequent AMTLR following sAHE can be a safe procedure to improve seizure outcome in selected patients. In our series the risk for further neuropsychological deterioration after the second procedure was low. The neuropsychological performance after the sAHE can be a valuable criterion to advise patients who are eligible for a second surgery on their risk of further cognitive decline.

BACKGROUND: Patients suffering from brain tumors, as other cancer patients, may rely on additional support of complementary and alternative medicine (CAM) treatment during the course of disease. However, the assessment and documentation of CAM is not necessarily part of the clinical routine in oncological consultations. Moreover, CAM comprises different agents and treatments that may vary depending on the country the patient lives. Overall, there is a lack of information on type and motivation for CAM use in glioma patients in Switzerland. MATERIAL AND METHODS: A multi-center cross-sectional survey analysis of CAM use in glioma patients was conducted in 3 specialized Neuro-Oncology Centers in Switzerland from 2012–2015. On the occasion of a regular consultation, a questionnaire including multiple choice questions as well as open response questions was provided to patients suffering from a glioma WHO II-IV. RESULTS: Overall, 208 patients completed the survey. Approximately half of the patients (n=101 patients, 49 %) reported the use of CAM during the course of the disease. Patients reported the wish to contribute actively to the cancer treatment as the most important motivation for CAM use. CAM user were most likely younger patients, usually using CAM without medical supervision and without necessarily being reimbursed by the insurance company. CAM use was distributed amongst WHO grades and both genders. CONCLUSIONS: In this multi-center survey analysis conducted in Switzerland, almost half of the glioma patients reported to have used CAM during the course of the disease. This demand should be addressed by the treating physicians. An accurate documentation and counseling could improve patient care, by avoiding potential interactions with the standard treatment and by incorporation of patients’ needs into therapy. Funded by the Swiss Brain Tumor Foundation

The prognosis for glioma remains dismal, and little is known about the final disease phase. To obtain information about this period, we surveyed caregivers of patients who were registered in the German Glioma Network and who died from the disease.A questionnaire with 15 items, focusing on medical, logistic, and mental health support and symptom control during the final 4 weeks, was sent to caregivers. For some of the questions, a scale from 1 (inadequate) to 10 (excellent) was used.Of 1655 questionnaires, 605 were returned (36.6%) and evaluated. We found that 67.9% of the patients were taken care of at home for the last 4 weeks; 47.7% died at home, 22.6% died in hospitals, and 19.3% died in hospice facilities. Medical support was provided by general practitioners in 72.3% of cases, by physicians affiliated with a nursing home or hospice in 29.9%, and by general oncologists in 17%. Specialized neuro-oncologists were involved in 6%. The caregivers ranked the medical support with a mean of 7.2 (using a 10-point scale), nursing service with 8.1, and mental health support with 5.5. In 22.9% of cases, no support for the caregivers themselves was offered by medical institutions.Although these data reflect the caregivers' subjective views, they are useful in understanding and improving current patterns of care. While patients and their caregivers are supported mainly by neuro-oncologists for most of the disease phase, the end-of-life phase is managed predominantly by general practitioners and specialists in palliative care. Close cooperation between these specialties is necessary to meet the specific needs of glioma patients.

Objective Shunt obstructions may partly be caused by brain debris, which intrude into the ventricular catheter during ventricle puncture. Avoiding contact between the catheter and brain tissue, by using a peel-away sheath, should reduce the number of shunt failures caused by obstruction. To test this hypothesis, we conducted a randomized, prospective multicenter study. Methods 201 patients from 6 different neurosurgical centers in Germany receiving a ventriculo-peritoneal shunt were included in this study. Of these, 177 patients completed a 1-year follow-up period. Surgery was randomized in a 1 to 1 fashion, such that out of 177 procedures, 91 were performed using a peel-away sheath and 86 were performed without. The rate of surgical re-interventions and shunt obstructions within a 12-month period was recorded. Results Within 1 year post-surgery, 17 shunt obstructions (9.6%) leading to shunt revisions were recorded. However, no difference was found between surgeries performed using a peel-away sheath (9.9%) or not (9.3%). The overall shunt infection rate was 2.8% and the shunt revision rate for overdrainage was 3.9%. Conclusions The theoretical advantages attributed to the use of a peel-away sheath to introduce a ventricular catheter could not be confirmed in this randomized study, suggesting that the proposed role of brain debris in shunt obstructions may be overestimated.

Different compositions of the extra cellular matrix with changing concentrations of more or less hydrophilic components like proteins may have a major influence on the diffusion phenomena found in gliomas. 24 patients (14 male / 10 female) with histologically confirmed non necrotic glioma underwent preoperative MRI, including magnetisation transfer (MTR), triple echo T2 weighted (T2W) and diffusion weighted (DWI) sequences. Apparent diffusion coefficient (ADC), quantitative T2 and MTR maps were calculated and regions of interest (ROIs) were placed in the tumour centre (TU) and in the contralateral hemisphere (NWM). Informed consent was obtained. The study was approved by the local ethic comity. Mean values evaluated in the NWM / TU were (± standard deviation); ADC: 0.78 (±0.08) × 10-3 mm2/s / 1.32 (±0.27) × 10-3 mm2/s, T2: 101.66 (±12.00) ms / 252.11 (±104.53) ms, MTR: 0.52 (±0.01) / 0.40 (±0.04). The mean value of each parameter correlated highly significant with the others (p

T2' values reflect the presence of deoxyhaemoglobin related to high local oxygen extraction. We assessed the feasibility of T2' imaging to display regions with high metabolic activity in brain gliomas.MRI was performed in 25 patients (12 female; median age 46 years; range 2-69) with brain gliomas with additional T2 and T2* sequences. T2' maps were derived from T2 and T2*. Dynamic susceptibility weighted contrast (DSC) perfusion was performed in 12/25 patients. Images were visually assessed by two readers and five ROIs were evaluated for each patient. Pearson correlation, Mann-Whitney and Kruskal-Wallis tests were applied for statistical analysis.Three patients were not further evaluated because of artefacts. Mean values of high-grade (III-IV) gliomas showed significantly lower T2' values than low-grade (II) gliomas (p0.001). An inverse relationship was observed between rCBV and sqr (T2') (r = -0.463, p0.001). No correlation was observed between T2' and rCBV for grade II tumours (r = 0.038; p = 0.875).High-grade tumours revealed lower T2' values, presumably because of higher oxygen consumption in proliferating tissue. Our results indicate that T2' imaging can be used as an alternative to DSC perfusion in the detection of subtle deviations in tumour metabolism.

The median survival of glioblastoma patients is approximately 12 months. However, 3-5% of the patients survives for more than 3 years and are referred to as long-term survivors. The clinical and molecular factors that contribute to long-term survival are still unknown. To identify specific parameters that might be associated with this phenomenon, we performed a detailed clinical and molecular analysis of 55 primary glioblastoma long-term survivors recruited at the six clinical centres of the German Glioma Network and one associated centre. An evaluation form was developed and used to document demographic, clinical and treatment-associated parameters. In addition, environmental risk factors, associated diseases and occupational risks were assessed. These patients were characterized by young age at diagnosis and a good initial Karnofsky performance score (KPS). None of the evaluated socioeconomic, environmental and occupational factors were associated with long-term survival. Molecular analyses revealed MGMT hypermethylation in 28 of 36 tumours (74%) investigated. TP53 mutations were found in 9 of 31 tumours (29%) and EGFR amplification in 10 of 38 tumours (26%). Only 2 of 32 tumours (6%) carried combined 1p and 19q deletions. Comparison of these data with results from an independent series of 141 consecutive unselected glioblastoma patients registered in the German Glioma Network revealed significantly more frequent MGMT hypermethylation in the long-term survivor group. Taken together, our findings underline the association of glioblastoma long-term survival with prognostically favourable clinical factors, in particular young age and good initial performance score, as well as MGMT promoter hypermethylation.

To prospectively evaluate whether diffusion-tensor magnetic resonance (MR) imaging depicts differences in World Health Organization (WHO) grade II and III glial brain tumors on the basis of tumor architecture and peritumoral tract invasion.The study protocol was approved by the local ethics committee, and written informed consent was obtained. Diffusion-tensor MR imaging was performed in 23 patients (15 men, eight women; mean age, 47 years) with histologically confirmed brain gliomas. Eleven of the 23 tumors were low-grade gliomas (WHO grade II) and 12 were anaplastic gliomas (WHO grade III). Regions of interest were placed in the tumor center, tumor border, normal-appearing white matter (NAWM) adjacent to the tumor, and NAWM of the contralateral hemisphere. fractional anisotropy (FA) ratios were calculated for regions of interest in relation to the NAWM of the contralateral hemisphere. Pairwise comparisons were performed by using the Mann-Whitney U test.Median FA ratios for grade II versus grade III gliomas were 0.406 versus 0.405, respectively, for tumor center, 0.733 versus 0.449, respectively, for tumor border, and 0.962 versus 0.943, respectively, for NAWM adjacent to the tumor. Differences in FA ratio between low-grade and high-grade tumors were significant in the tumor border only (P = .01). Differences in FA ratio were not significant between low-grade and high-grade gliomas in the tumor center or in the NAWM adjacent to the tumor.The periphery of low-grade gliomas contains a considerable amount of preserved fiber tracts. In high-grade gliomas, however, most of these tracts are disarranged. Low FA ratios in the tumor center are consistent with a high degree of disorganization of myelinated fiber tracts in the center of both low-grade and high-grade gliomas.

Early postoperative dysphagia after anterior cervical surgery is a well-known phenomenon with so far unknown etiology. We hypothesised that direct pressure induced by the medial retractor blade on pharynx/esophagus mucosal wall leads to local ischemia. Subsequently postoperative hyperemia and swelling of the pharynx/esophagus may result in swallowing disturbance. To prove the hypothesis local blood flow inside the pharynx/esophagus wall during anterior cervical surgery was measured using a laser Doppler (LD) perfusion monitor unit. Fifteen patients underwent standard anterior cervical discectomy and fusion (ACDF). The LD probe was placed underneath the medial retractor blade in order to gain information at the maximum point of pressure applied onto the pharynx/esophagus wall. Local perfusion was measured prior to retractor opening (5 min), during spreading of the retractor and after its closure (5 min). Perfusion was measured semiquantitatively in perfusion units (PU). Local perfusion ranged from 30 to 210 PU (mean 107) prior to retractor opening, from 7 to 60 PU (mean 30) with open retractor and from 15 to 280 PU (mean 117) after retractor closure. In all 15 patients the open retractor led to hypoperfusion ranging from 21 to 93% compared to the baseline level. In seven patients a reactive hyperemia at the end of the procedure was detected (32-89% compared to baseline level). In four patients after hypoperfusion during spreading of the retractor the baseline levels were reached again and in four patients perfusion remained diminished even after retractor closure. To best of our knowledge, this is the first report on intraoperative measurement of local perfusion of the pharynx/esophagus wall during anterior cervical surgery. Diminished local perfusion was observed in all patients during spreading of the retractor and post-procedure hyperemia was recorded in 46% of the patients. The local ischemia of the pharynx/esophagus wall may be a crucial step in the development of postoperative dysphagia.

Purpose: Preclinical data indicate anti-invasive activity of APG101, a CD95 ligand (CD95L)–binding fusion protein, in glioblastoma. Experimental Design: Patients (N = 91) with glioblastoma at first or second progression were randomized 1:2 between second radiotherapy (rRT; 36 Gy; five times 2 Gy per week) or rRT+APG101 (400 mg weekly i.v.). Patient characteristics [N = 84 (26 patients rRT, 58 patients rRT+APG101)] were balanced. Results: Progression-free survival at 6 months (PFS-6) rates were 3.8% [95% confidence interval (CI), 0.1–19.6] for rRT and 20.7% (95% CI, 11.2–33.4) for rRT+APG101 (P = 0.048). Median PFS was 2.5 (95% CI, 2.3–3.8) months and 4.5 (95% CI, 3.7–5.4) months with a hazard ratio (HR) of 0.49 (95% CI, 0.27–0.88; P = 0.0162) adjusted for tumor size. Cox regression analysis adjusted for tumor size revealed a HR of 0.60 (95% CI, 0.36–1.01; P = 0.0559) for rRT+APG101 for death of any cause. Lower methylation levels at CpG2 in the CD95L promoter in the tumor conferred a stronger risk reduction (HR, 0.19; 95% CI, 0.06–0.58) for treatment with APG101, suggesting a potential biomarker. Conclusions: CD95 pathway inhibition in combination with rRT is an innovative concept with clinical efficacy. It warrants further clinical development. CD95L promoter methylation in the tumor may be developed as a biomarker. Clin Cancer Res; 20(24); 6304–13. ©2014 AACR.

Purpose A randomised, open label phase III trial was conducted to evaluate efficacy of nimotuzumab, a monoclonal antibody against epidermal growth factor receptor (EGF-R) added to standard therapy for newly diagnosed glioblastoma. Patients and methods 149 glioblastoma patients stratified as with or without residual tumour were randomly assigned to receive either intravenous nimotuzumab 400 mg weekly added to standard radiochemotherapy followed by 400 mg biweekly after twelve weeks or standard radiochemotherapy. Progression status after 52 weeks (12moPFS) and progression-free survival (PFS) based on Macdonald criteria were co-primary and overall survival (OS), toxicity and quality of life secondary end-points. Results 142 patients were evaluated for efficacy (per protocol cohort). 12moPFS was 25.6% in the experimental arm and 20.3% in the control group. In residual tumour patients (n = 81) median PFS was 5.6 versus 4.0 months, (hazard ratio (HR), 0.87; 95% confidence interval (CI), 0.55–1.37), for patients without residual tumour (n = 61) it was 10.6 versus 9.9 months, (HR, 1.01; 95% CI, 0.57–1.77). Median OS in patients with residual tumour was 19.5 versus 16.7 months, (HR, 0.90; 95% CI, 0.52–1.57; P = 0.7061), for patients without 23.3 versus 21.0 months (HR, 0.77; 95% CI, 0.41–1.44; P = 0.4068). A small cohort of MGMT non-methylated patients with residual tumour showed PFS of 6.2 versus 4.0 months (HR, 0.77; 95% CI, 0.35–1.67; P = 0.4997) and OS of 19.0 versus 13.8 months (HR, 0.66; 95% CI, 0.27–1.64; P = 0.3648). EGF-R amplification did not correlate with clinical efficacy of nimotuzumab. Nimotuzumab was well tolerated. Conclusion This study, albeit negative, contains hypothesis generating signals supporting evaluation of correlative, efficacy-predicting tumour parameters for nimotuzumab in the treatment of glioblastoma.

Summary Objective Epilepsy surgery is a standard treatment option for medically intractable temporal lobe epilepsy. Selective amygdalohippocampectomy (SAH) and anterior temporal lobectomy (ATL) are two of the standard surgical procedures in these cases. We conducted a retrospective analysis of patients treated with SAH via a modified transsylvian approach in our epilepsy center between 2008 and 2011, and we analyzed the impact of adjacent procedure-related infarctions on seizure outcome in these patients. Methods Infarctions were detected by magnetic resonance imaging (MRI) within the first week postoperatively and by a second MRI 9 months after surgical intervention. Neuropsychological testing was performed preoperatively. Evaluation of seizure outcome and postoperative neuropsychological testing were conducted approximately 1 year after epilepsy surgery. Correlative clinical data were analyzed by retrospective chart review. Results The postoperative MRI revealed temporal infarctions in 47.9% (n = 23/48) and frontal infarctions in 10.4% (n = 5/48) of the patients. These vascular events were asymptomatic in terms of focal neurologic deficits. Of the patients, 68.5% (n = 37/54) were free of disabling seizures (Engel class I) 1 year after the procedure. Patients with temporal infarctions were significantly more often free of disabling seizures (Engel class I, p = 0.046) than patients without temporal infarctions. Neuropsychological testing indicated a deterioration in verbal memory after SAH in patients with infarctions on the language-lateralized hemisphere compared to patients without infarction (p = 0.011). All other tested neuropsychological categories showed no significant differences between patients with or without infarctions. Significance Our results indicate a surprisingly high number of procedure-related temporal infarctions after transsylvian SAH. Hence, the volume of nonfunctional “eliminated” tissue is enlarged unintentionally, which is a possible explanation for better seizure outcome in these patients. This result supports the notion that ATL is the favorable procedure for temporal lobe epilepsy compared to SAH in the nondominant hemisphere, as neuropsychological deficits are rarely to be expected. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Supplemental education is desirable for neurosurgical training, and the use of human cadaver specimen and virtual reality models is routine. An in vivo porcine training model for cranial neurosurgery was introduced in 2005, and our recent experience with this unique model is outlined here. For the first time, porcine anatomy is illustrated with particular respect to neurosurgical procedures. The pros and cons of this model are described. The aim of the course was to set up a laboratory scenery imitating an almost realistic operating room in which anatomy of the brain and neurosurgical techniques in a mentored environment free from time constraints could be trained. Learning objectives of the course were to learn about the microsurgical techniques in cranial neurosurgery and the management of complications. Participants were asked to evaluate the quality and utility of the programme via standardized questionnaires by a grading scale from A (best) to E (worst). In total, 154 residents have been trained on the porcine model to date. None of the participants regarded his own residency programme as structured. The bleeding and complication management (97 %), the realistic laboratory set-up (89 %) and the working environment (94 %) were favoured by the vast majority of trainees and confirmed our previous findings. After finishing the course, the participants graded that their skills in bone drilling, dissecting the brain and preserving cerebral vessels under microscopic magnification had improved to level A and B. In vivo hands-on courses, fully equipped with microsurgical instruments, offer an outstanding training opportunity in which bleeding management on a pulsating, vital brain represents a unique training approach. Our results have shown that education programmes still lack practical training facilities in which in vivo models may act as a complementary approach in surgical training.

We report the isolation by RT-PCR of partial cDNAs encoding the human peroxisome proliferator-activated receptor (PPAR) isoforms PPARbeta and -gamma in human primary astrocytes (HPA) as well as in the human malignant astrocytoma cell line T98G. In contrast, we failed to detect PPARalpha mRNA in either of these two cell types. Because PPARbeta is ubiquitously expressed but has, as yet, no known function, we pursued our functional studies of these cells with regard to PPARgamma. To that end, we showed that PPARgamma protein is abundantly expressed in both cell types, having a molecular weight of approximately 50 kDa. Immunocytochemistry revealed a predominantly nuclear localization of this receptor. Moreover, incubation of the two cell types with 1-12 mcM 15-deoxy PGJ(2) or 1-12 mcM ciglitazone, both of which are agonists of PPARgamma, induced loss of cellular viability as assessed by the MTT assay after a 4 hr incubation. Reduced cellular viability as a consequence of exposure to PGJ(2) or ciglitazone resulted from induction of apoptosis, as assessed by DNA fragmentation and Hoechst staining, and involves activation of the CPP32 (caspase-3) protease. These data show that modulation of the process of apoptosis is one function of PPARgamma in cells derived from the human astrocytic lineage.

It has become well accepted that solid tumors must create a vascular system for nutrient delivery and waste removal in order to grow appreciably. This process, angiogenesis, is critical to the progression of gliomas, with vascular changes accompanying the advancement of these tumors. The cascade of events in this process of blood vessel formation involves a complex interplay between tumor cells, endothelial cells, and their surrounding basement membranes in which enzymatic degradation of surrounding ground substance and subsequent endothelial cell migration, proliferation, and tube formation occurs. It is likely that a host of growth factors is responsible for mediating these key events. To date, a role for Vascular Endothelial Growth Factor (VEGF) in glioma angiogenesis has been convincingly demonstrated. This review explores the contribution of other growth factors–-Fibroblast Growth Factors (FGFs), Platelet-Derived Growth Factor (PDGF), Epidermal Growth Factor (EGF), and Transforming Growth Factors (TGFs)–-to glioma angiogenesis. These growth factors may influence glioma angiogenesis by directly stimulating endothelial cell proliferation, by mediating the expression of key proteases on endothelial cells necessary for angiogenesis, or by regulating the expression of VEGF and of each other.

Ischemic strokes, intracranial hemorrhages (ICH) and deep venous thromboembolism (DVT) are clinically important events in patients with gliomas. In this multicentre, noninterventional observational study, current data pertaining to frequency, contributing factors and outcomes of vascular events during times of anti-angiogenic therapy with the antibody against vascular endothelial growth factor, bevacizumab (BEV) was collected from the German Glioma Network. Among 3,889 glioma patients, 70 ischemic strokes (1.8 %) and 123 ICH (3.2 %) were recorded. 143 DVT (5.0 %) were recorded in 2,855 patients. Rates of DVT and ICH, but not of ischemic strokes, increased with the World Health Organization (WHO) grade of glioma. In 81 BEV-treated patients, five ischemic strokes (6.2 %), one ICH (1.2 %) and six DVT (7.4 %) were documented. Compared to patients that were not treated with BEV, ischemic stroke rate was significantly higher during treatment with BEV (p

Introduction: Percutaneous needle trephination is a well known neurosurgical procedure. The aim of this study was to develop a new instrument, which allows a stable fixation of an 18-G spinal needle in order to improve handling and precision of percutaneous needle trephinations. Methods and Instrumentation: The needle stabilizer was designed in a T-shape fashion morphologically similar to a corkscrew. The length of the uncovered needle tip is adjustable for individual requirements. Results: Using the new needle stabilizing device a total number of 18 percutaneous needle trephinations were performed for the following indications: subdural hematoma [8], epidural hygroma [4], bifrontal air accumulation [3], superficial tumor cyst, superficial brain abscess [11. No complications have been observed. Discussion: Our experience using this device shows that the modified technique fulfils criteria for clinical acceptance such as simplicity, low risk, reliability and cost effectiveness.

Attacks on humans by large predators are rare, especially in Northern Europe. In cases of involvement of the craniocervical compartment, most of the attacks are not survived. We report on a case where the patient survived a tiger attack despite severe head trauma and discuss the circumstances leading to the patient's survival and excellent outcome. The patient we report on is a 28-year-old tamer, who was attacked by three tigers during an evening show. A bite to the head resulted in multiple injuries including left-sided skull penetration wounds with dislocated fractures, dural perforations, and brain parenchyma lesions. The patient recovered without neurological deficits after initial ICU treatment. No infection occurred. In order to understand the mechanism of the tiger's bite to the patient's cranium, a simulation of the attack was performed using a human and a tiger skull put together at identical positions to the bite marks in a CT scan. It seems that during the bite, the animal was not able to clamp down on the patient's skull between its canine teeth and therefore reduced bite forces were applied. Survival of an attack by a large predator that targeted the cervical-cranial compartment with an excellent outcome is not described in the literature. We were surprised to find only minor lesions of the brain parenchyma despite the obvious penetration of the skull by the tiger's canines. This seems to be related to the specific dynamics of the cranial assault and the reduced forces applied to the patient's head demonstrated in a 3D bite simulation.

The overall survival of patients with BM-MM primarily depends on the number of metastases and pretreatment level of LDH. In the case of a single brain metastasis, stereotactic radiotherapy or neurosurgical metastasectomy is by far the most important factor for improving survival.

Objective: Despite novel multimodal therapeutic approaches, the vast majority of glial tumors are not curable. Patients may search for complementary therapies in order to contribute to the fight against their disease or to relieve symptoms induced by their brain tumor. The extent of the use of complementary or alternative therapies, the patients9 rationale behind it, and the cost of complementary therapy for gliomas are not known. We used a questionnaire and the database of the German Glioma Network to evaluate these questions. Methods: A total of 621 questionnaires were available for evaluation from patients with glial tumors of WHO grades II to grade IV. The patients were recruited from 6 neuro-oncologic centers in Germany. Complementary therapy was defined as methods or compounds not used in routine clinical practice and not scientifically evaluated. Results: Forty percent of the responding patients reported the use of complementary therapies. Significant differences between the group of complementary therapy users and nonusers were seen with respect to age (younger > older), gender (female > male), and education (high education level > low education level). The motivation for complementary therapy use was not driven by unsatisfactory clinical care by the neuro-oncologists, but by the wish to add something beneficial to the standard of care. Conclusions: In clinical practice, patients9 use of complementary therapies may be largely overseen and underestimated. The major motivation is not distrust in conventional therapies. Neuro-oncologists should be aware of this phenomenon and encourage an open but critical dialogue with their patients.

Carmustine (BCNU: N,N'-bis[2-chloroethyl]-N-nitrosourea) wafers are a local chemotherapeutic agent for the treatment of malignant glioma. They avoid the problems of high toxicity and short half-life associated with systemic delivery, and can bridge the traditional 'treatment gap' between surgery and subsequent conventional chemo- or radiotherapy. Clinical trials have demonstrated significant improvements in survival and quality of life for patients after complete tumour resection and BCNU wafer implantation. In practice, clinicians may use BCNU wafers in conjunction with other radio- and chemotherapies, in order to maximize the chance of a beneficial patient outcome. The purpose of these case reports is to exemplify how four experienced European clinicians employ BCNU wafers for the management of malignant glioma, and to illustrate how BCNU wafers can be effectively incorporated into treatment regimens. Four patients are described in whom BCNU wafers were implanted during the course of treatment for glioblastoma multiforme, the most severe and common type of malignant glioma. These include three patients with recurrent disease, and a single patient with a newly diagnosed tumour. All four patients received additional radio- and chemotherapy as appropriate. Treatment was well tolerated and patient survival from diagnosis ranged from 56 to 132 weeks. This compared favourably with the survival of approximately 58 weeks seen in the recent EORTC-NCIC clinical trial of combined radiotherapy with concomitant and adjuvant temozolomide. BCNU wafers are an effective means of increasing survival and quality of life in patients diagnosed with malignant glioma, and are a valuable addition to the overall multimodal treatment strategy for these tumours.

Purpose The prognostic value of genetic alterations characteristic of glioblastoma in patients treated according to present standards of care is unclear. Patients and Methods Three hundred one patients with glioblastoma were prospectively recruited between October 2004 and December 2006 at the clinical centers of the German Glioma Network. Two hundred fifty-eight patients had radiotherapy, 199 patients had temozolomide, 189 had both, and seven had another chemotherapy as the initial treatment. The tumors were investigated for TP53 mutation, p53 immunoreactivity, epidermal growth factor receptor, cyclin-dependent kinase CDK 4 or murine double minute 2 amplification, CDKN2A homozygous deletion, allelic losses on chromosome arms 1p, 9p, 10q, and 19q, O6-methylguanine methyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutations. Results Median progression-free (PFS) and overall survival (OS) were 6.8 and 12.5 months. Multivariate analysis revealed younger age, higher performance score, MGMT promoter methylation, and temozolomide radiochemotherapy as independent factors associated with longer OS. MGMT promoter methylation was associated with longer PFS (relative risk [RR], 0.5; 95% CI, 0.38 to 0.68; P < .001) and OS (RR, 0.39; 95% CI, 0.28 to 0.54; P < .001) in patients receiving temozolomide. IDH1 mutations were associated with prolonged PFS (RR, 0.42; 95% CI, 0.19 to 0.91; P = .028) and a trend for prolonged OS (RR, 0.43; 95% CI, 0.15 to 1.19; P = .10). No other molecular factor was associated with outcome. Conclusion Molecular changes associated with gliomagenesis do not predict response to therapy in glioblastoma patients managed according to current standards of care. MGMT promoter methylation and IDH1 mutational status allow for stratification into prognostically distinct subgroups.

Study design Prospective study of 92 patients who underwent anterior cervical surgery. Intraoperative esophagus retraction and postoperative dysphagia were recorded and evaluated. Objective Early dysphagia after anterior cervical discectomy and fusion is an underestimated side effect. The aim of this study was to investigate whether postoperative swallowing disturbances correlate with the amount of intraoperative retraction of the pharynx/esophagus wall measured during the procedure. Summary of background data The anterior approach to the cervical spine is a routinely used and, in general, safe procedure. A recent prospective study focused on the underreported side effect of postoperative dysphagia, with an incidence of up to 50% at 1 month and 12.5% at 12 months. The etiology of postoperative dysphagia is not known in detail. Methods An online pressure transducer between the retractor and pharynx/esophagus recorded the epi-esophageal pressure in 92 patients. In 31 patients, a transducer was additionally inserted into the pharynx/esophagus in order to measure the endo-esophageal pressure. The patients rated swallowing difficulty during the first postoperative 5 days using a 10-point score. A control group of 32 lumbar surgery patients was also evaluated for swallowing disturbances. Results Mean epi-esophageal pressure after retractor opening was 76.3 mm Hg, and mean endo-esophageal pressure was 16.3 mm Hg. An adjustment to 75% and 76%, respectively, of the initial value occurred within the first hour. Of patients, 49.3% complained of swallowing disturbances. There was a significant prevalence of the female gender. No correlation between the amount of retraction and postoperative dysphagia was observed. Conclusions A correlation between intraoperative pharynx/esophagus retraction and postoperative swallowing disturbances could not be confirmed. The cause of the prevalence of the female gender is unknown. However, the absence of impaired deglutition in the control group suggests that a local phenomenon must be causative of swallowing disturbances following anterior cervical discectomy and fusion.

Various in vivo studies demonstrated a migration tendency of neural stem cells (NSCs) toward gliomas, making these cells a potential carrier for delivery of therapeutic genes to disseminated glioma cells. We analyzed which factors determine NSC migration and invasion in vitro. Conditioned media prepared from 10 different human glioma cell lines, as well as 13 different tumor-associated growth factors, were analyzed for their chemotactic effects on murine C17.2 NSCs. The growth factor receptor status was analyzed by reverse transcriptase–polymerase chain reaction. Invasion of NSCs into multicellular tumor spheroids generated from 10 glioma cell lines was quantified. NSCs displayed a heterogeneous migration pattern toward glioma spheroids as well as toward glioma-cell-conditioned medium. Chemotactic migration was stimulated up to fivefold by conditioned medium as compared to controls. In coculture assays, NSC invasion varied from single cell invasion into glioma spheroids to complete dissemination of NSCs into glioma spheroids of different cell lines. Among 13 different growth factors, scatter factor/hepatocyte growth factor (SF/HGF) was the most powerful chemoattractant for NSCs, inducing a 2.5-fold migration stimulation. An antibody against SF/HGF inhibited migratory stimulation induced by conditioned media. NSC migration can be stimulated by various growth factors, similar to glioma cell migration. The extent to which NSCs infiltrate three-dimensional glioma cell aggregates appears to depend on additional factors, which are likely to include cell-to-cell contacts and interaction with extracellular matrix proteins.

Background. Placement of ventricular catheters is a routine procedure in neurosurgery. Ventricle puncture is done using a flexible ventricular catheter stabilised by a solid steel mandrin in order to improve stability during brain penetration. A correct catheter placement is confirmed after removing the solid steel mandrin by observation of cerebrospinal fluid (CSF) flow out of the flexible catheter. Incorrect placement makes further punctures necessary. The newly developed device allows CSF flow observation during the puncture procedure and in addition precise intracranial pressure (ICP) measurement. Method. The developed mandrin is hollow with a blunt tip. On one side 4–5 small holes with a diameter of 0.8 mm are drilled corresponding exactly with the holes in the ventricular catheter, allowing CSF to pass into the hollow mandrin as soon as the ventricle is reached. By connecting a small translucent tube at the distal portion of the hollow mandrin ICP can be measured without loss of CSF. The system has been used in 15 patients with subarachnoid haemorrhage (SAH) or intraventricular haemeorrhage (IVH) and subsequent hydrocephalus. Findings. The new system improved the external ventricular drainage implantation procedure. In all 15 patients catheter placement was correct. ICP measurement was easy to perform immediately at ventricle puncture. In 4 patients at puncture no spontaneous CSF flow was observed, therefore by connecting a syringe and gentle aspiration of CSF correct placement was confirmed in this unexpected low pressure hydrocephalus. Otherwise by using the conventional technique further punctures would have been necessary. Conclusions. Advantages of the new technique are less puncture procedures with a lower risk of damage to neural structures and reduced risk of intracranial haemorrhages. Implantation of the ventricular catheter to far into the brain can be monitored and this complication can be overcome. Using the connected pressure monitoring tube an exact measurement of the opening intracranial pressure can be obtained performed without losing CSF.

Numerous growth factors have been implicated in glioma angiogenesis. This chapter focuses on the role of scatter factor/hepatocyte growth factor, fibroblast growth factor, platelet-derived growth factor and transforming growth factor beta. We review the expression pattern of these factors in gliomas, their functional contribution to tumor angiogenesis - also in relation to vascular endothelial growth factor, and the effects resulting from their inhibition or overexpression in gliomas in vivo.

Numerous growth factors have been implicated in glioma angiogenesis. This chapter focuses on the role of scatter factor/hepatocyte growth factor, fibroblast growth factor, platelet-derived growth factor and transforming growth factor P. We review the expression pattern of these factors in gliomas, their functional contribution to tumor angiogenesis — also in relation to vascular endothelial growth factor, and the effects resulting from their inhibition or overexpression in gliomas in vivo.

Human microvascular endothelial cells (ECs) are more difficult to isolate than macrovascular ECs. Pure cultures of human macrovascular ECs can be obtained easily from umbilical cord veins by incubation and subseqent flushing of the veins with enzymatic solutions (4). Cultures of human umbilical vein ECs (HUVECs) can be greatly expanded and usually retain markers of endothelial differentiation over more than ten passages until they eventually become senescent.

In order to avoid shunt occlusions through particles of brain parenchyma a new procedure was used. Conventionally during ventricle puncture brain tissue may intrude into perforating holes of the ventricular catheter and subsequently shunt dysfunction may occur. By using a peel-away sheath the ventricular catheter can be protected during puncture. The conventional technique (n=90) was compared with the peel-away sheath technique (n=20) in a retrospective analyses in regard to shunt revisions during a 1-year period. Shunt revision was done in 18% (16/90) within 1 year using the conventional technique, respectively, 5% (1/20) using the peel-away sheath technique. Although criteria for statistical significance were not reached these data are worth to be mentioned. A randomised prospective study is initiated and the key features are presented.

The major obstacles to successful eradication of central nervous system (CNS) tumors are, firstly, the extensive invasive and migratory capacity of malignant cells and, secondly, the devastating effects of injury to the brain due to tumor growth and unwanted side effects caused by conventional therapy.