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Background: Glioblastoma resection guided by 5-aminolevulinic acid (5-ALA) fluorescence and intraoperative magnetic resonance imaging (iMRI) may improve surgical results and prolong survival., Objective: To evaluate 5-ALA fluorescence combined with subsequent low-field iMRI for resection control in glioblastoma surgery., Methods: Fourteen patients with suspected glioblastoma suitable for complete resection of contrast-enhancing portions were enrolled. The surgery was carried out using 5-ALA-induced fluorescence and frameless navigation. Areas suspicious for tumor underwent biopsy. After complete resection of fluorescent tissue, low-field iMRI was performed. Areas suspicious for tumor remnant underwent biopsy under navigation guidance and were resected. The histological analysis was blinded., Results: In 13 of 14 cases, the diagnosis was glioblastoma multiforme. One lymphoma and 1 case without fluorescence were excluded. In 11 of 12 operations, residual contrast enhancement on iMRI was found after complete resection of 5-ALA fluorescent tissue. In 1 case, the iMRI enhancement was in an eloquent area and did not undergo a biopsy. The 28 biopsies of areas suspicious for tumor on iMRI in the remaining 10 cases showed tumor in 39.3%, infiltration zone in 25%, reactive central nervous system tissue in 32.1%, and normal brain in 3.6%. Ninety-three fluorescent and 24 non-fluorescent tissue samples collected before iMRI contained tumor in 95.7% and 87.5%, respectively., Conclusion: 5-ALA fluorescence-guided resection may leave some glioblastoma tissue undetected. MRI might detect areas suspicious for tumor even after complete resection of all fluorescent tissue; however, due to the limited accuracy of iMRI in predicting tumor remnant (64.3%), resection of this tissue has to be considered with caution in eloquent regions.

Background: To determine predicting factors for repeated surgical drainage in patients with intracerebral brain abscesses., Methods: Patients operated between 01/2008 and 10/2013 with a single-burr-hole technique to drain an intracerebral brain abscess were included from our prospective database. Clinical and radiological characteristics were analyzed retrospectively and compared between patients requiring a single surgical abscess drainage (S group) vs. patients requiring multiple surgical abscess aspirations (M group)., Results: Thirty-five patients (mean age 42.6 years, 14 females) including 27 patients in the S group and 8 in the M group were included in this study. Age, gender, causing bacterial agent, surgical technique and abscess volume were comparable for both groups. Preoperative mean C-reactive protein (CRP) (13.9 mg/l vs. 56.1 mg/l, p=0.015) was significantly higher in the M group. Preoperative mean leukocyte count (12.3×10(9)/l vs. 8.9×10(9)/l, p=0.050) was borderline significantly higher in the M group. Although the origin in the overall population was cryptogenic in 43% of the cases, this was never the case in the patient population needing multiple surgeries., Discussion: Patients with multiple intracerebral brain abscess aspirations showed significantly higher preoperative CRP values than patients who needed surgery only once. Patients with high CRP values at admission and obvious origin of infection might need closer radiographic as well as clinical and laboratory exams after surgery to earlier select patients, which need repeated surgery., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Intraoperative Neurophysiological Mo-nitoring (IONM) identifies eloquent areas or nerves fibers during neurosurgical interventions and monitors their function. For several interventions IONM has become mandatory in neurosurgery. IONM increases patient safety during surgery as the risk of neurological deficits is reduced. Safer surgery reduces the time needed for the intervention and thereby reduces risk. IONM contributes to complete resection of tumors, which in turn prolongs patients' survival. Complicated surgical interventions associated with an elevated risk of neurological deficits have only become possible due to IONM. IONM comprises a variety of procedures that are selected for a particular intervention. With appropriate selection of the procedures IONM has been shown to improve neurological and functional outcome after neurosurgical interventions.

Object: The direct transnasal transsphenoidal approach to the sellar region has become a widely adopted surgical procedure among neurosurgeons and ear, nose, and throat specialists. Nasal complications and their incidence have been investigated, but a systematic testing of olfactory disturbance has not previously been performed. Considering that the sense of smell is deeply anchored and interwoven within the CNS, and that its impairment implies a considerable loss in quality of life, surgical practice should aim at its preservation., Methods: In this retrospective study, pre- and postoperative olfactory performance, nasal airway passage, septal perforation, and epistaxis were assessed in 96 patients who underwent direct transnasal transsphenoidal microsurgery at the authors' department between January 2007 and August 2009. Olfactory performance was assessed using the Sniffin' Sticks test and/or the Zürcher Geruchstest., Results: After surgery, 47 (49%) of 96 patients improved, 34 (35%) of 96 deteriorated, and 15 (16%) of 96 presented with unchanged olfactory performance. With respect to the underlying pathological entity, the authors noticed a remarkable difference between patients with acromegaly (23 cases) and all other patients (73 cases). Fifteen (65%) of 23 patients with acromegaly improved (others 44%), only 3 (13%) of 23 deteriorated (others 42%), and 5 (22%) of 23 remained unchanged (others 14%) in their ability to distinguish odors. This illustrates a significant shift toward improved postoperative olfactory performance (cross-tabulation, Fisher exact test; p = 0.028) in patients with acromegaly. In nasal breathing, 77 (80%) of 96 patients noticed no change, 11 (12%) of 96 improved, and 8 (8%) of 96 worsened postoperatively. Of the 11 patients with improved breathing, 6 (55%) had acromegaly. Improved nasal airway patency was more frequent in patients with acromegaly (cross-tabulation, Fisher exact test; p = 0.002)., Conclusions: The data provide the first significant evidence for improvement in olfactory performance in patients with acromegaly after transsphenoidal surgery (TSS) of growth hormone-producing adenomas. Furthermore, postoperative olfactory disturbance in patients treated with transnasal TSS is more frequent than previously reported. Nevertheless, recurrent transnasal TSS can be performed successfully, even multiple times, and does not involve a higher risk of nasal complications.

Gliosarcoma is a variant of glioblastoma multiforme characterized by two components displaying gliomatous or sarcomatous differentiation. We investigated 38 gliosarcomas for aberrations of tumor-suppressor genes and proto-oncogenes that are commonly altered in glioblastomas. Amplification of CDK4, MDM2, EGFR, and PDGFRA were found in 11% (4/35), 8% (3/38), 8% (3/38), and 3% (1/35) of the tumors, respectively. Nine of 38 gliosarcomas (24%) carried TP53 mutations. PTEN mutations were identified in 45% (9/20) of the investigated tumors. Twenty gliosarcomas were analyzed by comparative genomic hybridization (CGH). Chromosomal imbalances commonly detected were gains on chromosomes 7 (15/20; 75%), X (4/20; 20%), 9q, and 20q (3/20, 15% each); and losses on chromosomes 10 and 9p (7/20, 35% each), and 13q (3/20, 15%). Five different high-level amplifications were mapped to 4q12-q21 (1 case), 6p21 (1 case), 7p12 (2 cases), proximal 12q (4 cases), and 14q32 (1 case) by CGH. Southern blot and/or differential PCR analyses identified amplification of PDGFRA (4q12), CCND3 (6p21), EGFR (7p12), CDK4 (12q14) and/or MDM2 (12q14.3-q15), and AKT1 (14q32.3) in the respective tumors. Separate analysis of the gliomatous and sarcomatous components of eight gliosarcomas by CGH after microdissection and universal DNA amplification revealed that both components shared 57% of the chromosomal imbalances detected. Taken together, our data indicate that the genomic changes in gliosarcomas closely resemble those found in glioblastomas. However, the number of chromosomes involved in imbalances in gliosarcomas was significantly lower than that in glioblastomas, indicating a higher genomic stability in gliosarcomas. In addition, we provide further support for the hypothesis that the gliomatous and sarcomatous components are derived from a single precursor cell clone, which progressed into subclones with distinct morphological features during tumor evolution. According to our data, gain/amplification of genes on proximal 12q may facilitate the development of a sarcomatous phenotype., (Copyright 2002 Wiley-Liss, Inc.)

We performed a genome wide screening for genomic alterations on a series of 19 sporadic primary central nervous system lymphomas (PCNSL) of the diffuse large B-cell type by comparative genomic hybridization (CGH). The tumors were additionally analyzed for amplification and rearrangement of the BCL2 gene at 18q21 as well as for mutation of the recently cloned BCL10 gene at 1p22. Eighteen tumors showed genomic imbalances on CGH analysis. On average, 2.1 losses and 4.7 gains were detected per tumor. The chromosome arm most frequently affected by losses of genomic material was 6q (47%) with a commonly deleted region mapping to 6q21-q22. The most frequent gains involved chromosome arms 12q (63%), 18q and 22q (37% each), as well as 1q, 9q, 11q, 12p, 16p and 17q (26% each). High-level amplifications were mapped to 9p23-p24 (1 tumor) and to 18q21-q23 (2 tumors). However, PCR-based analysis, Southern blot analysis and high-resolution matrix-CGH of the BCL2 gene revealed neither evidence for amplification nor for genetic rearrangement. Mutational analysis of BCL10 in 16 PCNSL identified four distinct sequence polymorphisms but no mutation. Taken together, our data do not support a role of BCL2 rearrangement/amplification and BCL10 mutation in PCNSL but indicate a number of novel chromosomal regions that likely carry yet unknown tumor suppressor genes or proto-oncogenes involved in the pathogenesis of these tumors.

Malignant gliomas frequently show genetic aberrations of genes coding for cell cycle regulatory proteins involved in the control of G1/S phase transition. These include mutation and/or deletion of the retinoblastoma (RB1) gene, homozygous deletion of the CDKN2A and CDKN2B genes, as well as amplification and overexpression of the CDK4 and CDK6 genes. The D-type cyclins (cyclin D1, D2, and D3) promote cell cycle progression from G1 to S phase by binding to and activating the cyclin dependent kinases Cdk4 and Cdk6. Here, we have investigated a series of 110 primary malignant gliomas and 8 glioma cell lines for amplification and expression of the D-type cyclin genes CCND1 (11q13), CCND2 (12p13), and CCND3 (6p21). We found the CCND1 gene amplified and overexpressed in one anaplastic astrocytoma of our tumor series. Two glioblastomas and one anaplastic astrocytoma showed CCND2 gene amplification, but lacked significant overexpression of CCND2 transcripts. Amplification and overexpression of the CCND3 gene was detected in the glioblastoma cell line CCF-STTG1, as well as in one primary glioblastoma and in the sarcomatous component of one gliosarcoma. Our data thus suggest that amplification and increased expression of CCND1 and CCND3 contribute to the loss of cell cycle control in a small fraction of human malignant gliomas.