Extent of resection in patients with glioblastoma: Limiting factors, Perception of resectability, and effect on survival
Departments of Neurosurgery and. Journal of Neurosurgery
(Impact Factor: 3.74).
09/2012; 117(5). DOI: 10.3171/2012.8.JNS12234
The extent of resection (EOR) is a known prognostic factor in patients with glioblastoma. However, gross-total resection (GTR) is not always achieved. Understanding the factors that prevent GTR is helpful in surgical planning and when counseling patients. The goal of this study was to identify demographic, tumor-related, and technical factors that influence EOR and to define the relationship between the surgeon's impression of EOR and radiographically determined EOR.
The authors performed a retrospective review of the electronic medical records to identify all patients who underwent craniotomy for glioblastoma resection between 2006 and 2009 and who had both preoperative and postoperative MRI studies. Forty-six patients were identified and were included in the study. Image analysis software (FIJI) was used to perform volumetric analysis of tumor size and EOR based on preoperative and postoperative MRI. Using multivariate analysis, the authors assessed factors associated with EOR and residual tumor volume. Perception of resectability was described using bivariate statistics, and survival was described using the log-rank test and Kaplan-Meier curves.
The EOR was less for tumors in eloquent areas (p = 0.014) and those touching ventricles (p = 0.031). Left parietal tumors had significantly greater residual volume (p = 0.042). The average EOR was 91.0% in this series. There was MRI-demonstrable residual tumor in 69.6% of cases (16 of 23) in which GTR was perceived by the surgeon. Expert reviewers agreed that GTR could be safely achieved in 37.0% of patients (17 of 46) in this series. Among patients with safely resectable tumors, radiographically complete resection was achieved in 23.5% of patients (4 of 17). An EOR greater than 90% was associated with a significantly greater 1-year survival (76.5%) than an EOR less than 90% (p = 0.005).
The authors' findings confirm that tumor location affects EOR and suggest that EOR may also be influenced by the surgeon's ability to judge the presence of residual tumor during surgery. The surgeon's ability to judge completeness of resection during surgery is commonly inaccurate. The authors' study confirms the impact of EOR on 1-year survival.
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ABSTRACT: Forty patients with previously untreated intracranial glial neoplasms underwent stereotaxic serial biopsies assisted by computerized tomography (CT) and magnetic resonance imaging (MRI). Tumor volumes defined by computer reconstruction of contrast enhancement and low-attenuation boundaries on CT and T1 and T2 prolongation on MRI revealed that tumor volumes defined by T2-weighted MRI scans were larger than those defined by low-attenuation or contrast enhancement on CT scans. Histological analysis of 195 biopsy specimens obtained from various locations within the volumes defined by CT and MRI revealed that: contrast enhancement most often corresponded to tumor tissue without intervening parenchyma; hypodensity corresponded to parenchyma infiltrated by isolated tumor cells or in some instances to tumor tissue in low-grade gliomas or to simple edema; and isolated tumor cell infiltration extended at least as far as T2 prolongation on magnetic resonance images. This information may be useful in planning surgical procedures and radiation therapy in patients with intracranial glial neoplasms.
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In glioma surgery, the extent of resection (EOR) is one important predictor of progression-free survival. In 2006, fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) was shown to improve the EOR in malignant gliomas. However, the use of 5-ALA is complex and causes certain side effects. Sodium fluorescein (FL) is a fluorescent dye that is used for angiography in ophthalmic surgery. FL accumulates in areas of the disturbed blood-brain barrier and can be visualized under a 560-nm wavelength fluorescent light source (YELLOW 560 nm, Carl Zeiss Meditec, Oberkochen, Germany). Here, we present the first experiences with low-dose FL and YELLOW 560 nm in 35 patients with malignant brain tumors.
Patients and method:
A total of 200 mg of FL (3-4 mg/kg bodyweight) was administered in 35 patients during craniotomy as an off-label use between May and August 2012. We retrospectively analyzed the histology, pre-treatment, clinical parameters pre- and postoperatively and occurrence of any adverse effects. The feasibility and efficacy ('helpful,' 'not helpful') of FL under YELLOW 560 nm (demarcation of the tumor margin) was assessed by the responsible neurosurgeon (n = 5) for each surgical procedure.
Twenty-six patients had gliomas (1 WHO grade I, 3 WHO grade II, 5 WHO grade III, 17 WHO grade IV), 5 patients had cerebral metastases, 2 had non-malignant astrogliosis and 2 had post-radiation necrosis. The fluorescence signal was detected in all patients immediately after the FL administration. FL application was classified as 'helpful' in 28 patients, implying improved visualization of the tumor margins. The intensity of the fluorescence signal seemed to be correlated to the histology and was strongly dependent on the pre-treatment status. We did not record any allergic reactions or any other adverse effects.
The use of FL for the resection of brain tumors is safe and feasible. Presumably, the visualization of the tumor margin depends on the histopathology and on the pre-treatment status. A randomized evaluation of FL under the YELLOW 560 nm filter is planned to prospectively analyze the extent of resection in patients with malignant brain tumors.
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Arteriovenous shunting visualized by angiography is one of the major features of glioblastomas, and the visualization is dependent on the presence of extensive shunting. Extensive arteriovenous shunting is associated with the risk of poorly controlled intraoperative bleeding. When a tumor with extensive arteriovenous shunting is located in close proximity to the eloquent regions of the brain, a meticulous surgical procedure is necessary. In the present study, the site-oriented visualization of angiographical arteriovenous shunting was evaluated from the perspective of surgical treatment, with a particular focus on the perisylvian region that is in close proximity to motor and language regions (dominant hemisphere), as well as large arteries and veins.
Twenty-six consecutive patients underwent a resection of glioblastoma between February 2007 and September 2012. All patients were presurgically examined using digital subtraction angiography. The patients were subdivided into the following two groups based on the location of the tumor: 1) perisylvian glioblastoma (18 patients) and 2) non-perisylvian glioblastoma (eight patients). Angiography to detect the arteriovenous shunting was performed. In addition, the number of intratumoral vessels, tumor proliferative activity (MIB-1 labeling index), and volume of intraoperative bleeding were evaluated and compared between the two groups.
Angiographical arteriovenous shunting was definitively visualized in 13 of 18 (72 %) perisylvian glioblastomas, in contrast to only one of eight (13 %) non-perisylvian glioblastomas (p = 0.007). There were no significant differences between the two groups with respect to the number of intratumoral vessels, MIB-1 labeling index, and volume of intraoperative bleeding. However, massive intraoperative bleeding of > 2,000 mL occurred in one perisylvian glioblastoma patient.
Glioblastomas in the perisylvian region tend to be associated with extensive arteriovenous shunting that can be definitively visualized by performing an angiography. Because arteriovenous shunting carries the risk of intraoperative bleeding, perisylvian glioblastomas-particularly in the dominant hemisphere-should be resected with a meticulous surgical procedure and strategy.
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