Awake Craniotomy for Tumor Resection: Further Optimizing Therapy of Brain Tumors.

In recent years more and more data have emerged linking the most radical resection to prolonged survival in patients harboring brain tumors. Since total tumor resection could increase postoperative morbidity, many methods have been suggested to reduce the risk of postoperative neurological deficits: awake craniotomy with the possibility of continuous patient-surgeon communication is one of the possibilities of finding out how radical a tumor resection can possibly be without causing permanent harm to the patient.In 1994 we started to perform awake craniotomy for glioma resection. In 2005 the use of intraoperative high-field magnetic resonance imaging (MRI) was included in the standard tumor therapy protocol. Here we review our experience in performing awake surgery for gliomas, gained in 219 patients.Patient selection by the operating surgeon and a neuropsychologist is of primary importance: the patient should feel as if they are part of the surgical team fighting against the tumor. The patient will undergo extensive neuropsychological testing, functional MRI, and fiber tractography in order to define the relationship between the tumor and the functionally relevant brain areas. Attention needs to be given at which particular time during surgery the intraoperative MRI is performed. Results from part of our series (without and with ioMRI scan) are presented.

Low-grade Glioma Surgery in Intraoperative Magnetic Resonance Imaging: Results of a Multicenter Retrospective Assessment of the German Study Group for Intraoperative Magnetic Resonance Imaging.

BACKGROUND: The ideal treatment strategy for low-grade gliomas (LGGs) is a controversial topic. Additionally, only smaller single-center series dealing with the concept of intraoperative magnetic resonance imaging (iMRI) have been published. OBJECTIVE: To investigate determinants for patient outcome and progression-free-survival (PFS) after iMRI-guided surgery for LGGs in a multicenter retrospective study initiated by the German Study Group for Intraoperative Magnetic Resonance Imaging. METHODS: A retrospective consecutive assessment of patients treated for LGGs (World Health Organization grade II) with iMRI-guided resection at 6 neurosurgical centers was performed. Eloquent location, extent of resection, first-line adjuvant treatment, neurophysiological monitoring, awake brain surgery, intraoperative ultrasound, and field-strength of iMRI were analyzed, as well as progression-free survival (PFS), new permanent neurological deficits, and complications. Multivariate binary logistic and Cox regression models were calculated to evaluate determinants of PFS, gross total resection (GTR), and adjuvant treatment. RESULTS: A total of 288 patients met the inclusion criteria. On multivariate analysis, GTR significantly increased PFS (hazard ratio, 0.44; P < .01), whereas "failed" GTR did not differ significantly from intended subtotal-resection. Combined radiochemotherapy as adjuvant therapy was a negative prognostic factor (hazard ratio: 2.84, P < .01). Field strength of iMRI was not associated with PFS. In the binary logistic regression model, use of high-field iMRI (odds ratio: 0.51, P < .01) was positively and eloquent location (odds ratio: 1.99, P < .01) was negatively associated with GTR. GTR was not associated with increased rates of new permanent neurological deficits. CONCLUSION: GTR was an independent positive prognostic factor for PFS in LGG surgery. Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors. Use of high-field iMRI was significantly associated with GTR. However, the field strength of iMRI did not affect PFS. ABBREVIATIONS: EoR, extent of resectionFLAIR, fluid-attenuated inversion recoveryGTR, gross total resectionIDH1, isocitrate dehydrogenase 1iMRI, intraoperative magnetic resonance imagingLGG, low-grade gliomaMGMT, methylguanine-deoxyribonucleic acid methyltransferasenPND, new permanent neurological deficitOS, overall survivalPFS, progression-free survivalSTR, subtotal resectionWHO, World Health Organization.

Neuroendoscopy and high-field intraoperative MRI: first experience.

BACKGROUND: To date, information about the use of intraoperative MRI (iMRI) in patients undergoing neuroendoscopic procedures is sparse. The benefit may be (re)definition of neuronavigation, confirmation of fenestrations and biopsies, detection of complications, and redefinition of anatomical changes during the operation. MATERIAL AND METHODS: Our setting consists of a fully integrated high-field 1.5-T MRI into the operating room. The operating room can be functionally divided into (1) the MRI scanner and (2) the operating table outside the 5 Gauss line where ferromagnetic surgical instruments can be used. We included a consecutive series of 11 adult patients who underwent 11 endoscopic operations in the iMRI setting between January 2007 and September 2011. RESULTS: The median age of patients was 54 years (range: 40-69 years). The male-to-female ratio was 4.5:1. Diagnoses leading to endoscopic treatment were aqueductal stenosis (n = 8; caused by tumors in three cases), pineal cyst (n = 1), tumor of the third ventricle (n = 1), and brain abscess with ventriculitis (n = 1). Endoscopic procedures were endoscopic third ventriculostomy with or without tumor biopsy (n = 5), aqueductoplasty (n = 4), tumor biopsy and septostomy (n = 1), and tumor resection (n = 1). All patients were scanned at least once, seven patients twice during surgery. The mean scan time per procedure was 19 minutes. The following sequences were regarded as most useful: T2 axial (placement of catheter, ruling out of complications), T2 sagittal (flow void signal), and true fast imaging (TRUFI) (fenestration defect). CONCLUSIONS: iMRI enables high-resolution imaging immediately after endoscopic operation. The combined use is technically feasible and of potential value in selected cases with complex hydrocephalus. In most of these cases, scanning can be limited to T2 axial, T2 sagittal, and TRUFI MR images.

High-field iMRI in glioblastoma surgery: improvement of resection radicality and survival for the patient?

Since the first patients underwent intracranial tumor removal with the radicality control of intraoperative MRI (ioMRI) in September 2005 in our department, the majority of operations performed in the ioMRI room have been indicated for high grade gliomas. In order to elucidate the role of ioMRI scanning in patients harboring high-grade gliomas (HGG) on their survival, one hundred ninety three patients with gliomas WHO grades III and IV were operated either in a standard microsurgical neuronavigated fashion or using additionally ioMRI and were included in a follow-up study. The series started with surgeries from September 2005 until October 2007. Patient attribution to the two groups was based on the logistical availability of the ioMRI on a scheduled surgery day, and on the assumed "difficulty" of the surgery based on the location of the glioma in or near to an eloquent area. Surgery was intended to be as radical as possible without reduction of quality of life. First surgery was performed in 103 patients (75 WHO IV and 28 WHO III) and will be the main topic of this paper. In 60 patients, ioMRI was used, while in 43 patients standard microsurgical neuronavigated resection techniques were applied. Patients were followed in regular intervals mostly until death. Statistical analysis showed a median survival time for patients in whom ioMRI had been used of 20, 37 months compared to 10, 3 months in the cohort who had undergone conventional microsurgical removal. Major influencing concomitants were WHO grades and age which were balanced in both groups.

Cholesterol modulates the membrane binding and intracellular distribution of annexin 6.

Annexins are Ca(2+)- and phospholipid-binding proteins that are widely expressed in mammalian tissues and that bind to different cellular membranes. In recent years its role in membrane traffic has emerged as one of its predominant functions, but the regulation of its intracellular distribution still remains unclear. We demonstrated that annexin 6 translocates to the late endocytic compartment in low density lipoprotein-loaded CHO cells. This prompted us to investigate whether cholesterol, one of the major constituents of low density lipoprotein, could influence the membrane binding affinity and intracellular distribution of annexin 6. Treatment of crude membranes or early and late endosomal fractions with digitonin, a cholesterol-sequestering agent, displayed a strong reduction in the binding affinity of a novel EDTA-resistant and cholesterol-sensitive pool of annexin 6 proteins. In addition, U18666A-induced accumulation of cholesterol in the late endosomal compartment resulted in a significant increase of annexin 6 in these vesicles in vivo. This translocation/recruitment correlates with an increased membrane binding affinity of GST-annexin 6 to late endosomes of U18666A-treated cells in vitro. In conclusion, the present study shows that changes in the intracellular distribution and concentration of cholesterol in different subcellular compartments participate in the reorganization of intracellular pools of Ca(2+)-dependent and -independent annexin 6.