34 research outputs found
Atypical Teratoid/Rhabdoid Tumors in Adults: A Case Report and Treatment-Focused Review
Atypical teratoid/rhabdoid tumor is predominantly a childhood tumor and has only been rarely reported in adults; therefore, treatment regimens are often extrapolated from the pediatric experience. Typically, children are treated with craniospinal radiation therapy which is often followed by systemic chemotherapy. Employing pediatric regimens to treat this tumor in adult patients poses a particular risk for myelosuppression, as the prescribed doses in pediatric protocols exceed those tolerated by adults, and conventional craniospinal radiation can be associated with prolonged myelotoxicity and a depletion of the bone marrow reserve in vertebrae of adults. Here we present a case of a woman with a pineal region atypical teratoid/rhabdoid tumor, an unusual adult cancer presenting in an atypical location. This is followed by a review of the disease in adult patients with an emphasis on treatment and suggestions to minimize myelotoxicity
yuDetecting the percent of peripheral blood mononuclear cells displaying p-STAT-3 in malignant glioma patients
<p>Abstract</p> <p>Background</p> <p>The signal transducer and activator of transcription 3 (STAT-3) is frequently overexpressed in cancer cells, propagates tumorigenesis, and is a key regulator of immune suppression in cancer patients. The presence of phosphorylated STAT-3 (p-STAT-3) in the tumor can induce p-STAT-3 in tumor-associated immune cells that can return to the circulatory system. We hypothesized that the number of peripheral blood mononuclear cells (PBMCs) displaying p-STAT-3 would be increased in glioma patients, which would correlate with the extent of tumor-expressed p-STAT-3, and that higher p-STAT-3 levels in peripheral blood would correlate with a higher fraction of immune-suppressive regulatory T cells (Tregs).</p> <p>Methods</p> <p>We measured the percentage of PBMCs displaying p-STAT-3 in 19 healthy donors and 45 patients with primary brain tumors. The level of p-STAT-3 in tumor tissue was determined by immunohistochemistry. The degree of immune suppression was determined based on the fraction of Tregs in the CD4 compartment.</p> <p>Results</p> <p>Healthy donors had 4.8 ± 3.6% of PBMCs that expressed p-STAT-3, while the mean proportion of PBMCs displaying p-STAT-3 in patients with GBM was 11.8 ± 13.5% (<it>P </it>= 0.03). We did not observe a correlation by Spearman correlation between the degree of p-STAT-3 levels in the tumor and the percent of PBMCs displaying p-STAT-3. Furthermore, the percent of PBMCs displaying p-STAT-3 in glioma patients was not directly correlated with the fraction of Tregs in the CD4 compartment.</p> <p>Conclusion</p> <p>We conclude that the percent of PBMCs displaying p-STAT-3 may be increased in malignant glioma patients.</p
Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target.
A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and the molecular heterogeneity of immune infiltrates in gliomas. Here, we report an integrated analysis of 201,986 human glioma, immune, and other stromal cells at the single cell level. In doing so, we discover extensive spatial and molecular heterogeneity in immune infiltrates. We identify molecular signatures for nine distinct myeloid cell subtypes, of which five are independent prognostic indicators of glioma patient survival. Furthermore, we identify S100A4 as a regulator of immune suppressive T and myeloid cells in GBM and demonstrate that deleting S100a4 in non-cancer cells is sufficient to reprogram the immune landscape and significantly improve survival. This study provides insights into spatial, molecular, and functional heterogeneity of glioma and glioma-associated immune cells and demonstrates the utility of this dataset for discovering therapeutic targets for this poorly immunogenic cancer
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Intraoperative magnetic resonance imaging-guided tractography with integrated monopolar subcortical functional mapping for resection of brain tumors. Clinical article
The object of this study was to describe the utility and safety of using a single probe for combined intraoperative navigation and subcortical mapping in an intraoperative MR (iMR) imaging environment during brain tumor resection.
The authors retrospectively reviewed those patients who underwent resection in the iMR imaging environment, as well as functional electrophysiological monitoring with continuous motor evoked potential (MEP) and direct subcortical mapping combined with diffusion tensor imaging tractography. RESULTS As a navigational tool the monopolar probe used was safe and accurate. Positive subcortical fiber MEPs were obtained in 10 (83%) of the 12 cases. In 10 patients in whom subcortical MEPs were recorded, the mean stimulus intensity was 10.4 ± 5.2 mA and the mean distance from the probe tip to the corticospinal tract (CST) was 7.4 ± 4.5 mm. There was a trend toward worsening neurological deficits if the distance to the CST was short, and a small minimum stimulation threshold was recorded indicating close proximity of the CST to the resection margins. Gross-total resection (95%-100% tumor removal) was achieved in 11 cases (92%), whereas 1 patient (8%) had at least a 90% tumor resection. At the end of 3 months, 2 patients (17%) had persistent neurological deficits.
The monopolar probe can be safely implemented in an iMR imaging environment both for navigation and stimulation purposes during the resection of intrinsic brain tumors. In this study there was a trend toward worsening neurological deficits if the distance from the probe to the CST was short (< 5 mm) indicating close proximity of the resection cavity to the CST. This technology can be used in the iMR imaging environment as a surgical adjunct to minimize adverse neurological outcomes
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Simultaneous use of functional tractography, neuronavigation-integrated subcortical white matter stimulation and intraoperative magnetic resonance imaging in glioma surgery: technical note
The importance of preserving function during glioma surgery cannot be overemphasized. There are a number of techniques utilized including functional MRI, direct electrophysiological monitoring and functional neuronavigation to maximize and safely resect gliomas. The intraoperative MRI is an extremely valuable tool and adds to the neurosurgeon's armamentarium. Combining these technologies will enhance the safety and efficacy of glioma surgery. This is the first report in the literature where we successfully combine both functional neuronavigation and subcortical stimulation, using a single probe to safely resect a recurrent glioblastoma
Utilization of Intraoperative Motor Mapping in Glioma Surgery with High-Field Intraoperative Magnetic Resonance Imaging
Background/Aims: The main goal of glioma surgery is to maximize tumor resection while minimizing neurologic injury. The use of high-field intraoperative magnetic resonance imaging (iMRI) and intraoperative cortical mapping (IOM) together enable the surgeon to increase the extent of tumor resection (EOR) and preserve the neurological function. However, there is insufficient evidence to validate the use of IOM with high-field iMRI. Methods: To study the safety and utility of IOM in a high-field (1.5 T) iMRI suite, we retrospectively studied 38 patients with glioma who underwent surgery with IOM in the iMRI suite. Results: We were able to use IOM in the iMRI suite without any adverse side effects or difficulty. Median EOR was 97%. A new or worsening motor deficit occurred in 14 (37%) patients immediately after the surgery, with 3 (8%) patients exhibiting persistent deficit at 6 months. Conclusion: Our findings suggest that IOM can be successfully used in a high-field MRI environment and can help minimize postoperative motor deficit with a higher EOR. Copyright (C) 2010 S. Karger AG, Base
Intraoperative magnetic resonance imaging–guided tractography with integrated monopolar subcortical functional mapping for resection of brain tumors
The object of this study was to describe the utility and safety of using a single probe for combined intraoperative navigation and subcortical mapping in an intraoperative MR (iMR) imaging environment during brain tumor resection.
The authors retrospectively reviewed those patients who underwent resection in the iMR imaging environment, as well as functional electrophysiological monitoring with continuous motor evoked potential (MEP) and direct subcortical mapping combined with diffusion tensor imaging tractography. RESULTS As a navigational tool the monopolar probe used was safe and accurate. Positive subcortical fiber MEPs were obtained in 10 (83%) of the 12 cases. In 10 patients in whom subcortical MEPs were recorded, the mean stimulus intensity was 10.4 ± 5.2 mA and the mean distance from the probe tip to the corticospinal tract (CST) was 7.4 ± 4.5 mm. There was a trend toward worsening neurological deficits if the distance to the CST was short, and a small minimum stimulation threshold was recorded indicating close proximity of the CST to the resection margins. Gross-total resection (95%-100% tumor removal) was achieved in 11 cases (92%), whereas 1 patient (8%) had at least a 90% tumor resection. At the end of 3 months, 2 patients (17%) had persistent neurological deficits.
The monopolar probe can be safely implemented in an iMR imaging environment both for navigation and stimulation purposes during the resection of intrinsic brain tumors. In this study there was a trend toward worsening neurological deficits if the distance from the probe to the CST was short (< 5 mm) indicating close proximity of the resection cavity to the CST. This technology can be used in the iMR imaging environment as a surgical adjunct to minimize adverse neurological outcomes
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Impact of Multi-modality Monitoring Using Direct Electrical Stimulation to Determine Corticospinal Tract Shift and Integrity in Tumors using the Intraoperative MRI
Abstract
Introduction
Preserving the integrity of the corticospinal tract (CST) while maximizing the extent of tumor resection is one of the key principles of brain tumor surgery to prevent new neurologic deficits. Our goal was to determine the impact of the use of perioperative diffusion tensor imaging (DTI) fiber-tracking protocols for location of the CSTs, in conjunction with intraoperative direct electrical stimulation (DES) on patient neurologic outcomes. The role of combining DES and CST shift in intraoperative magnetic resonance imaging (iMRI) to enhance extent of resection (EOR) has not been studied previously.
Methods
A total of 53 patients underwent resection of tumors adjacent to the motor gyrus and the underlying CST between June 5, 2009, and April 16, 2013. All cases were performed in the iMRI (BrainSuite 1.5 T). Preoperative DTI mapping and intraoperative cortical and subcortical DES including postoperative DTI mapping were performed in all patients. There were 32 men and 21 women with 40 high-grade gliomas (76%), 4 low-grade gliomas (8%), and 9 (17%) metastases. Thirty-four patients (64%) were newly diagnosed, and 19 (36%) had a previous resection. There were 31 (59%) right-sided and 22 (42%) left-sided tumors. Eighteen patients (34%) had a re-resection after the first intraoperative scan. Most patients had motor-only mapping, and one patient had both speech and motor mapping. Relative to the resection margin, the CST after the first iMRI was designated as having an outward shift (OS), inward shift (IS), or no shift (NS).
Results
A gross total resection (GTR) was achieved in 41 patients (77%), subtotal resection in 4 (7.5%), and a partial resection in 8 (15%). Eighteen patients had a re-resection, and the mean EOR increased from 84% to 95% (
p
= 0.002). Of the 18 patients, 7 had an IS, 8 an OS, and in 3 NS was noted. More patients in the OS group had a GTR compared with the IS or NS groups (
p
= 0.004). Patients were divided into four groups based on the proximity of the tumor to the CST as measured from the preoperative scan. Group 1 (32%) included patients whose tumors were 0 to 5 mm from the CST based on preoperative scans; group 2 (28%), 6 to 10 mm; group 3 (13%), 11 to 15 mm; and group 4 (26%), 16 to 20 mm, respectively. Patients in group 4 had fewer neurologic complications compared with other groups at 1 and 3 months postoperatively (
p
= 0.001 and
p
= 0.007, respectively) despite achieving a similar degree of resection (
p
= 0.61). Furthermore, the current of intraoperative DES was correlated to the distance of the tumor to the CST, and the regression equation showed a close linear relationship between the two parameters.
Conclusions
Combining information about intraoperative CST and DES in the iMRI can enhance resection in brain tumors (77% had a GTR). The relative relationship between the positions of the CST to the resection cavity can be a dynamic process that could further influence the surgeon's decision about the stimulation parameters and EOR. Also, the patients with an OS of the CST relative to the resection cavity had a GTR comparable with the other groups
Subcortical injury is an independent predictor of worsening neurological deficits following awake craniotomy procedures
Tailored craniotomies for awake procedures limit cortical exposure. Recently we demonstrated that the identification of eloquent areas increased the risk of postoperative deficits. However, it was not clear whether the observed neurological deficits were caused by proximity of functional cortex to the tumor [cortical injury] or subcortical injury.
We hypothesize that subcortical injury during tumor resection is an important predictor of postoperative neurological deficits compared to cortical injury.
A retrospective review of 214 patients undergoing awake craniotomy was carried out in whom preoperative functional magnetic resonance imaging (fMRI) and cortical mapping (CM) were performed. A radiologist blinded to the clinical data reviewed and graded the postoperative changes on diffusion-weighted MR-imaging (DWI).
Of the 40 cases who developed new intraoperative neurological deficit, 36 (90%) occurred during subcortical dissection, 3 (7.5%) during both subcortical and cortical dissection, and 1 (2.5%) during cortical dissection. Neurological dysfunction acquired during subcortical dissection was an independent predictor of postoperative deficits both in the immediate postoperative period (P < .001) and at the 3-month follow-up (P < .001). Significant DWI restriction in the subcortical white matter was predictive of neurological deficits both immediately and at 3 months, P = .011 and P < .001, respectively. New or worsening deficits were seen in 38% of patients; however, at 3 months 13% had a mild persistent neurological deficit.
Subcortical injury with significant DWI changes result in postoperative neurological decline despite our efforts to preserve cortical areas of function. This underscores the importance of preserving subcortical fiber tracts during awake craniotomy procedures