Tag: Glioma

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Intraoperative Contrast-Enhanced Ultrasound for Brain Tumor Surgery

INTRAOPERATIVE CEUS FOR BRAIN SURGERY

Neurosurgery 74:542–552, 2014 

Contrast-enhanced ultrasound (CEUS) is a dynamic and continuous modality that offers a real-time, direct view of vascularization patterns and tissue resistance for many organs. Thanks to newer ultrasound contrast agents, CEUS has become a wellestablished, live-imaging technique in many contexts, but it has never been used extensively for brain imaging. The use of intraoperative CEUS (iCEUS) imaging in neurosurgery is limited.

OBJECTIVE: To provide the first dynamic and continuous iCEUS evaluation of a variety of brain lesions.

METHODS: We evaluated 71 patients undergoing iCEUS imaging in an off-label setting while being operated on for different brain lesions; iCEUS imaging was obtained before resecting each lesion, after intravenous injection of ultrasound contrast agent. A semiquantitative, offline interobserver analysis was performed to visualize each brain lesion and to characterize its perfusion features, correlated with histopathology.

RESULTS: In all cases, the brain lesion was visualized intraoperatively with iCEUS. The afferent and efferent blood vessels were identified, allowing evaluation of the time and features of the arterial and venous phases and facilitating the surgical strategy. iCEUS also proved to be useful in highlighting the lesion compared with standard B-mode imaging and showing its perfusion patterns. No adverse effects were observed.

CONCLUSION: Our study is the first large-scale implementation of iCEUS in neurosurgery as a dynamic and continuous real-time imaging tool for brain surgery and provides the first iCEUS characterization of different brain neoplasms. The ability of CEUS to highlight and characterize brain tumor will possibly provide the neurosurgeon with important information anytime during a surgical procedure.

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Near-infrared imaging of brain tumors using the Tumor Paint BLZ-100 to achieve near-complete resection of brain tumors

Near-infrared imaging of brain tumors using the Tumor Paint BLZ-100 to achieve near-complete resection of brain tumors

Neurosurg Focus 36 (2):E1, 2014

The intraoperative clear delineation between brain tumor and normal tissue in real time is required to ensure near-complete resection without damaging the nearby eloquent brain. Tumor Paint BLZ-100, a tumor ligand chlorotoxin (CTX) conjugated to indocyanine green (ICG), has shown potential to be a targeted contrast agent. There are many infrared imaging systems in use, but they are not optimized to the low concentration and amount of ICG. The authors present a novel proof-of-concept near-infrared (NIR) imaging system using a standard charge-coupled device (CCD) camera for visualizing low levels of ICG attached to the tumors. This system is small, inexpensive, and sensitive. The imaging system uses a narrow-band laser at 785 nm and a notch filter in front of the sensor at the band. The camera is a 2-CCD camera, which uses identical CCDs for both visible and NIR light.

Methods. The NIR system is tested with serial dilution of BLZ-100 from 1 μM to 50 pM in 5% Intralipid solution while the excitation energy is varied from 5 to 40 mW/cm2. The analog gain of the CCD was changed from 0, 6, and 12 dB to determine the signal-to-noise ratio. In addition to the Intralipid solution, BLZ-100 was injected 48 hours before euthanizing the mice that were implanted with the human glioma cell line. The brain was removed and imaged using the NIR imaging system.

Results. The authors’ results show that the NIR imaging system using a standard CCD is able to visualize the ICG down to 50 nM of concentration with a high signal-to-noise ratio. The preliminary experiment on human glioma implanted in mouse brains demonstrated that BLZ-100 has a high affinity for glioma compared with normal brain tissue. Additionally, the results show that NIR excitation is able to penetrate deeply and has a potential to visualize metastatic lesions that are separate from the main tumor.

Conclusions. The authors have seen that BLZ-100 has a very high affinity toward human gliomas. They also describe a small, cost-effective, and sensitive NIR system for visualizing brain tumors tagged using BLZ-100. The authors hope that the use of BLZ-100 along with NIR imaging will be useful to delineate the brain tumors in real time and assist surgeons in near-complete tumor removal to increase survival and reduce neurological deficits.

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Surgical strategy in grade II astrocytoma

Surgical strategy in grade II astrocytoma

Acta Neurochir (2013) 155:2227–2235

We recently demonstrated a survival benefit of early resection in unselected diffuse low-grade gliomas (LGG). However, heterogeneity within the LGG entity warrants investigation in a homogenous subgroup. Astrocytoma represents the largest subgroup of LGG, and is characterized by diffuse growth and inferior prognosis. We aimed to study the effects of early resection compared to biopsy and watchful waiting in this subgroup.

Methods Patient data was retrospectively reviewed in two neurosurgical departments with regional referral practice. In one hospital, initial diagnostic biopsies and watchful waiting was favored, while early resections guided with three-dimensional (3D) ultrasound were advocated in the other hospital. This created a natural experiment with patient management heavy influenced by residential address. In the hospitals’ histopathology databases, all adult patients diagnosed with supratentorial LGG from 1998 through 2009 were screened (n =169) and underwent blinded histopathological review. Histopathological review concluded with 117 patients with grade II astrocytomas that were included in the present study. The primary end-point was overall survival assessed by a regional comparison.

Results Early resections were performed in 51 (82 %) versus 12 (22 %) patients in the respective hospitals (p <0.001). The two patient populations were otherwise similar. Median survival was 9.7 years (95 % CI 7.5–11.9) if treated in the hospital favoring early resections compared to 5.6 years (95 % CI 3.5– 7.6) if treated at the hospital favoring biopsy and watchful waiting (p =0.047). No difference in surgical-related neurological morbidity was seen (p =0.843).

Conclusions Early 3D ultrasound guided resections improve survival, apparently without increasedmorbidity, compared to biopsy and watchful waiting in patients with diffuse World Health Organization (WHO) grade II astrocytomas.

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Glioma Spheroids Obtained via Ultrasonic Aspiration Are Viable and Express Stem Cell Markers

Glioma, Immunohistochemistry, Organotypic, Spheroids, Tumor-initiating cells, Ultrasonic aspiration

Neurosurgery 73:868–886, 2013

Ultrasonic aspirators allow safe, rapid, and accurate removal of brain tumors. However, the tissue fragments removed are used surprisingly little in research.

OBJECTIVE: To investigate whether such tissue fragments could be cultured as organotypic multicellular spheroids because access to biopsy tissue is often limited.

METHODS: Tissue fragments obtained by ultrasonic aspiration from 10 glioblastomas and tumor biopsy tissue from 7 of these tumors were cultured in serum-containing and serum-free medium. On culturing, the fragments formed spheroids, which were prepared for histology. Two glioblastoma cell lines from ultrasonic fragments and biopsy tissue were established as well.

RESULTS: Hematoxylin and eosin staining showed viable glioma spheroids obtained from both ultrasonic and biopsy tissue in both types of medium. Endothelial growth factor receptor and PTEN/chromosome 10 status was found to be preserved in most spheroids (7-8 of 10 tumors), together with the level of glial fibrillary acidic protein, von Willebrand factor, and Ki-67. The levels of stem cell markers CD133, Bmi-1, nestin, and Sox2 also were preserved. The ultrasonic spheroids had higher levels of glial fibrillary acidic protein and von Willebrand factor and lower levels of Bmi-1, nestin, Sox2, and Olig2 compared with conventional biopsy spheroids. For both types of spheroids, the stem cell medium seemed to favor expression of stem cell markers. The established cell lines were capable of both spheroid formation at clonal density and tumor formation in vivo.

CONCLUSION: Viable organotypic and proliferating spheroids were easily obtained from ultrasonic tissue fragments. The preservation of markers and the establishment of cell lines with tumor-initiating cell properties suggest ultrasonic spheroids as a new tissue resource for glioma research.

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Tolerance of awake surgery for glioma: a prospective European Low Grade Glioma Network multicenter study

awake surgery for glioma

Acta Neurochir (2013) 155:1301–1308

Gross total removal of glioma is limited by proximity to eloquent brain. Awake surgery allows for intraoperative monitoring to safely identify eloquent regions. However, data on adverse psychological effects induced in these patients is limited.

Objective This study explored patients’ perception of awake surgery for glioma, with special focus on intraoperative pain and anxiety.

Methods This study was conducted at five neurosurgical centers within the European Low Grade Glioma Network. Patients underwent awake surgery for glioma according to the protocol of the individual center. Pain and discomfort were measured during the awake phase. Postoperatively, patients answered a questionnaire on aspects of their operation.

Results One hundred five patients were enrolled. Pain levels on a 10-cm visual analogue scale were 1.3 cm at the beginning, 1.9 cm the middle, and 2.1 cm at the end of awake phase. Levels of anxiety were 2.2 cm, 2.5 cm and 2.6 cm, respectively. Women and patients younger than 60 years exhibited highest mean anxiety levels. The patient questionnaire revealed that the majority of patients feel comfortable with the procedure. Discomfort resulted from head fixation or positioning on the operating table.

Conclusions We demonstrate that awake surgery is well tolerated, as neither intraoperative nor postoperative assessment revealed major disadvantages. Concerning practical lessons learned from this study, we emphasize the importance of minimizing pain and preparing patients thoroughly to reduce anxiety and maximize cooperation. Awake surgery is an excellent treatment modality for brain tumors with very positive perception by patients. Keywords

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Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas

GIIG

J Neurosurg 118:1157–1168, 2013

The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed.

Methods. Cases of GIIGs treated before December 2007 were extracted from a multicenter database retrospectively collected since January 1985 and prospectively collected since 1996. Inclusion criteria were a patient age ≥ 18 years at diagnosis, histological diagnosis of WHO GIIG, and MRI evaluation of tumor volume at diagnosis and after initial surgery. One thousand ninety-seven lesions were included in the analysis. The mean follow-up was 7.4 years since radiological diagnosis. Factors significant in a univariate analysis (with a p value ≤ 0.1) were included in the multivariate Cox proportional hazard regression model analysis.

Results. At the time of radiological diagnosis, independent spontaneous factors of a poor prognosis were an age ≥ 55 years, an impaired functional status, a tumor location in a nonfrontal area, and, most of all, a larger tumor size. When the study starting point was set at the time of first treatment, independent favorable prognostic factors were limited to a smaller tumor size, an epileptic symptomatology, and a greater extent of resection.

Conclusions. This large series with its volumetric assessment refines the prognostic value of previously stressed clinical and radiological parameters and highlights the importance of tumor size and location. The results support additional arguments in favor of the predominant role of resection, in accordance with recently reported experiences.

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Prognostic factors of Grade II gliomas

neuronBig

J Neurosurg 118:1157–1168, 2013

The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed.

Methods. Cases of GIIGs treated before December 2007 were extracted from a multicenter database retrospectively collected since January 1985 and prospectively collected since 1996. Inclusion criteria were a patient age ≥ 18 years at diagnosis, histological diagnosis of WHO GIIG, and MRI evaluation of tumor volume at diagnosis and after initial surgery. One thousand ninety-seven lesions were included in the analysis. The mean follow-up was 7.4 years since radiological diagnosis. Factors significant in a univariate analysis (with a p value ≤ 0.1) were included in the multivariate Cox proportional hazard regression model analysis.

Results. At the time of radiological diagnosis, independent spontaneous factors of a poor prognosis were an age ≥ 55 years, an impaired functional status, a tumor location in a nonfrontal area, and, most of all, a larger tumor size. When the study starting point was set at the time of first treatment, independent favorable prognostic factors were limited to a smaller tumor size, an epileptic symptomatology, and a greater extent of resection.

Conclusions. This large series with its volumetric assessment refines the prognostic value of previously stressed clinical and radiological parameters and highlights the importance of tumor size and location. The results support additional arguments in favor of the predominant role of resection, in accordance with recently reported experiences.

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Discriminating radiation necrosis from tumor progression in gliomas: a systematic review what is the best imaging modality?

Radiation necrosis

J Neurooncol (2013) 112:141–152

Differentiating post radiation necrosis from progression of glioma and pseudoprogression poses a diagnostic conundrum for many clinicians. As radiation therapy and temozolomide chemotherapy have become the mainstay of treatment for higher-grade gliomas, radiation necrosis and post treatment changes such as pseudoprogression have become a more relevant clinical problem for neurosurgeons and neurooncologists. Due to their radiological similarity to tumor progression, accurate recognition of these findings remains paramount given their vastly different treatment regimens and prognoses. However, no consensus has been reached on the optimal technique to discriminate between these two lesions.

In order to clarify the types of imaging modalities for recurrent enhancing lesions, we conducted a systematic review of case reports, case series, and prospective studies to increase our current understanding of the imaging options for these common lesions and their efficacy. In particular, we were interested in distinguishing radiation necrosis from true tumor progression. A PubMed search was performed to include all relevant studies where the imaging was used to differentiate between radiation necrosis and recurrent gliomas with post-radiation enhancing lesions.

After screening for certain parameters in our study, seventeen articles with 435 patients were included in our analysis including 10 retrospective and 7 prospective studies. The average time from the end of radiation therapy to the onset of a recurrent enhancing lesion was 13.2 months. The most sensitive and specific imaging modality was SPECT with a sensitivity of 87.6 % and specificity of 97.8 %.

Based on our review, we conclude that certain imaging modalities may be preferred over other less sensitive/specific techniques. Overall, tests such as SPECT may be preferable in differentiating TP (tumor progression) from RN (radiation necrosis) due to its high specificity, while nonspecific imaging such as conventional MRI is not ideal.

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Use of diffusion tensor imaging in glioma resection

DTI.glioma

Neurosurg Focus 34 (4):E1, 2013 

Diffusion tensor imaging (DTI) is increasingly used in the resection of both high- and low-grade gliomas. Whereas conventional MRI techniques provide only anatomical information, DTI offers data on CNS connectivity by enabling visualization of important white matter tracts in the brain

Importantly, DTI allows neurosurgeons to better guide their surgical approach and resection. Here, the authors review basic scientific principles of DTI, include a primer on the technology and image acquisition, and outline the modality’s evolution as a frequently used tool for glioma resection.

Current literature supporting its use is summarized, highlighting important clinical studies on the application of DTI in preoperative planning for glioma resection, preoperative diagnosis, and postoperative outcomes.

The authors conclude with a review of future directions for this technology.

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Potential of MR spectroscopy for assessment of glioma grading

Glioma grading by MR spectroscopy

Clinical Neurology and Neurosurgery 115 (2013) 146– 153

Magnetic resonance spectroscopy (MRS) is an imaging diagnostic method based that allows non-invasive measurement of metabolites in tissues. There are a number of metabolites that can be identified by standard brain proton MRS but only a few of them has a clinical significance in diagnosis of gliomas including N-acetylaspartate, choline, creatine, myo-inositol, lactate, and lipids.

Methods: In this review, we describe potential of MRS for grading of gliomas.

Results: Low-grade gliomas are generally characterized by a relatively high concentration of Nacetylaspartate, low level of choline and absence of lactate and lipids. The increase in creatine concentration indicates low-grade gliomas with earlier progression and malignant transformation. Progression in grade of a glioma is reflected in the progressive decrease in the N-acetylaspartate and myo-inositol levels on the one hand and elevation in choline level up to grade III on the other. Malignant transformation of the glial tumors is also accompanied by the presence of lactate and lipids in MR spectra of grade III but mainly grade IV gliomas. It follows that MRS is a helpful method for detection of glioma regions with aggressive growth or upgrading due to favorable correlation of the choline and N-acetylaspartate levels with histopathological proliferation index Ki-67. Thus, magnetic resonance spectroscopy is also a suitable method for the targeting of brain biopsies.

Conclusions: Gliomas of each grade have some specific MRS features that can be used for improvement of the diagnostic value of conventional magnetic resonance imaging in non-invasive assessment of glioma grade.

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Clinical Application of Motor Pathway Mapping Using Diffusion Tensor Imaging Tractography and Intraoperative Direct Subcortical Stimulation in Cerebral Glioma Surgery

Neurosurgery 71:1170–1184, 2012

Glioma surgery in eloquent areas remains a challenge because of the risk of postoperative motor deficits.

OBJECTIVE: To prospectively evaluate the efficiency of using a combination of diffusion tensor imaging (DTI) tractography functional neuronavigation and direct subcortical stimulation (DsCS) to yield a maximally safe resection of cerebral glioma in eloquent areas.

METHODS: A prospective cohort study was conducted in 58 subjects with an initial diagnosis of primary cerebral glioma within or adjacent to the pyramidal tract (PT). The white matter beneath the resection cavity was stimulated along the PT, which was visualized with DTI tractography. The intercept between the PT border and DsCS site was measured. The sensitivity and specificity of DTI tractography for PT mapping were evaluated. The efficiency of the combined use of both techniques on motor function preservation was assessed.

RESULTS: Postoperative analysis showed gross total resection in 40 patients (69.0%). Seventeen patients (29.3%) experienced postoperative worsening; 1-month motor deficit was observed in 6 subjects (10.3%). DsCS verified a high concordance rate with DTI tractography for PT mapping. The sensitivity and specificity of DTI were 92.6% and 93.2%, respectively. The intercepts between positive DsCS sites and imaged PTs were 2.0 to 14.7 mm (5.262.2 mm). The 6-month Karnofsky Performance Scale scores in 50 postoperative subjects were significantly increased compared with their preoperative scores.

CONCLUSION: DTI tractography is effective but not completely reliable in delineating the descending motor pathways. Integration of DTI and DsCS favors patient-specific surgery for cerebral glioma in eloquent areas.

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Cognitive functioning early after surgery of gliomas in eloquent areas

J Neurosurg 117:831–838, 2012

Patients with gliomas frequently have cognitive deficits, and surgery can exacerbate these deficits. Preoperative assessment is therefore crucial in patients undergoing surgery for glioma in eloquent areas, because the proximity of functional areas increases the risk of permanent postoperative cognitive disturbances. Although pre- and postoperative language and motor function in patients with glioma have been investigated frequently, data on good cognition studies are scarce. Most studies have focused on clinical neurological functioning or have only used brief neurological instruments. The authors investigated whether surgery for glioma in eloquent areas influences cognition early after surgery, by using an elaborate test protocol.

Methods. Twenty-eight patients with gliomas of the left hemisphere in language and nonlanguage areas were assessed before and 3 months after surgery with a comprehensive neuropsychological test protocol. The authors performed a correlation analysis between change in cognitive performance and tumor characteristics (that is, location, volume, pathological features, and histological grade) and between cognitive change and treatment-related factors (the extent of the resection and postoperative treatment with chemo- and radiotherapy).

Results. Both pre- and postoperatively, the mean performance of the patients was worse than the performance of the normal population in the language domain, the memory domain, and the executive functions (p < 0.05). Postoperatively, a decline was found in the language domain (t = 2.34, p = 0.027) and in the executive functions (t = 2.45, p = 0.022). However, cognitive change postsurgery was influenced by the location of the tumor; the decrease of cognitive score in the language domain was only observed in patients with tumors in or close to language areas (t = 2.33, p = 0.029). No effect on cognitive change was found for the other tumor characteristics and treatment-related factors.

Conclusions. This study underlines the importance of the use of a neuropsychological test protocol before and after surgery in patients with glioma, because several tasks in the domains of language, memory, and executive functions appeared to deteriorate after surgery. Tumor resection in language areas increases the risk of cognitive deficits in the language domain postoperatively.

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Intermittent General Anesthesia With Controlled Ventilation for Asleep-Awake-Asleep Brain Surgery

Neurosurgery 71:764–772, 2012

Awake brain tumor surgery is a unique opportunity for mapping sensorimotor and cognitive functions, allowing the operator to optimize the resection while preserving the patient’s quality of life. During this type of procedure, active participation of the patient is necessary.

OBJECTIVE: To assess the efficacy and safety of a method of intermittent general anesthesia with controlled ventilation for performing invasive cerebral mapping. METHODS: We report our prospective and observational single-center study with an asleep-awake-asleep protocol. Aspects of feasibility, airway management, timing of each phase, and occurrence of adverse events were detailed.

RESULTS: During a 35-month period, 140 patients underwent resection of a glioma in an eloquent area. During the asleep phases, controlled ventilation with a laryngeal mask was always efficient. Orotracheal intubation was performed for some patients for the second asleep period. The patients remained fully awake for a mean time of 98 minutes. Postural discomfort was reported in 17.8% of cases. There was 1 case of aspiration of gastric contents with a favorable outcome and no mortality.

CONCLUSION: Intermittent general anesthesia with controlled ventilation for this type of neurosurgical procedure remains an anesthesiological challenge. However, the results of this study suggest that it may be feasible, reproducible, and relatively safe in the context of a standardized protocol involving members of both anesthesiology and surgery teams. Such a technique has a great potential to improve the surgical results, from both oncological and functional perspectives.

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High-Definition Fiber Tractography of the Human Brain: Neuroanatomical Validation and Neurosurgical Applications

Neurosurgery 71:430–453, 2012

High-definition fiber tracking (HDFT) is a novel combination of processing, reconstruction, and tractography methods that can track white matter fibers from cortex, through complex fiber crossings, to cortical and subcortical targets with subvoxel resolution.

OBJECTIVE: To perform neuroanatomical validation of HDFT and to investigate its neurosurgical applications.

METHODS: Six neurologically healthy adults and 36 patients with brain lesions were studied. Diffusion spectrum imaging data were reconstructed with a Generalized Q-Ball Imaging approach. Fiber dissection studies were performed in 20 human brains, and selected dissection results were compared with tractography.

RESULTS: HDFT provides accurate replication of known neuroanatomical features such as the gyral and sulcal folding patterns, the characteristic shape of the claustrum, the segmentation of the thalamic nuclei, the decussation of the superior cerebellar peduncle, the multiple fiber crossing at the centrum semiovale, the complex angulation of the optic radiations, the terminal arborization of the arcuate tract, and the cortical segmentation of the dorsal Broca area. From a clinical perspective, we show that HDFT provides accurate structural connectivity studies in patients with intracerebral lesions, allowing qualitative and quantitative white matter damage assessment, aiding in understanding lesional patterns of white matter structural injury, and facilitating innovative neurosurgical applications. High-grade gliomas produce significant disruption of fibers, and low-grade gliomas cause fiber displacement. Cavernomas cause both displacement and disruption of fibers.

CONCLUSION: Our HDFT approach provides an accurate reconstruction of white matter fiber tracts with unprecedented detail in both the normal and pathological human brain. Further studies to validate the clinical findings are needed.

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Cancer Immunoediting in Malignant Glioma

Neurosurgery 71:201–223, 2012

Significant work from many laboratories over the last decade in the study of cancer immunology has resulted in the development of the cancer immunoediting hypothesis. This contemporary framework of the naturally arising immune system–tumor interaction is thought to comprise 3 phases: elimination, wherein immunity subserves an extrinsic tumor suppressor function and destroys nascent tumor cells; equilibrium, wherein tumor cells are constrained in a period of latency under immune control; and escape, wherein tumor cells outpace immunity and progress clinically.

In this review, we address in detail the relevance of the cancer immunoediting concept to neurosurgeons and neuro-oncologists treating and studying malignant glioma by exploring the de novo immune response to these tumors, how these tumors may persist in vivo, the mechanisms by which these cells may escape/attenuate immunity, and ultimately how this concept may influence our immunotherapeutic approaches.

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A review of the role of stem cells in the development and treatment of glioma

Acta Neurochir (2012) 154:951–969. DOI 10.1007/s00701-012-1338-9

The neurosurgical management of patients with intrinsic glial cancers is one of the most rapidly evolving areas of practice. This has been fuelled by advances in surgical technique not only in cytoreduction but also in drug delivery. Further innovation will depend on a deeper understanding of the biology of the disease and an appreciation of the limitations of current knowledge.

Here we review the controversial topic of cancer stem cells applied to glioma to provide neurosurgeons with a working overview. It is now recognised that the adult human brain contains regionally specified cell populations capable of self-renewal that may contribute to tumour growth and maintenance following accumulated mutational change. Tumour cells adapted to maintain growth demonstrate some stem-like characteristics and as such constitute a legitimate therapeutic target. Cellular reprogramming technologies raise the potential of developing stem cells as novel surgical tools to target disease and possibly ameliorate some of the consequences of treatment. Achieving these goals remains a significant challenge to neurosurgical oncologists, not least in challenging how we think about treating brain cancer.

This review will briefly examine our understanding of adult stem cells within the brain, the evidence that they contribute to the development of brain tumours as tumour-initiating cells, and the potential implications for therapy. It will also look at the role stem cells may play in the future management of glioma.

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Intraoperative Visualization of Fiber Tracking Based Reconstruction of Language Pathways in Glioma Surgery

Neurosurgery 70:911–920, 2012 DOI: 10.1227/NEU.0b013e318237a807 

For neuroepithelial tumors, the surgical goal is maximum resection with preservation of neurological function. This is contributed to by intraoperative magnetic resonance imaging (iMRI) combined with multimodal navigation.

OBJECTIVE: We evaluated the contribution of diffusion tensor imaging (DTI)-based fiber tracking of language pathways with 2 different algorithms (tensor deflection, connectivity analysis [CA]) integrated in the navigation on the surgical outcome.

METHODS: We evaluated 32 patients with neuroepithelial tumors who underwent surgery with DTI-based fiber tracking of language pathways integrated in neuronavigation. The tensor deflection algorithm was routinely used and its results intraoperatively displayed in all cases. The CA algorithm was furthermore evaluated in 23 cases. Volumetric assessment was performed in pre- and intraoperative MR images. To evaluate the benefit of fiber tractography, language deficits were evaluated pre- and postoperatively and compared with the volumetric analysis.

RESULTS: Final gross-total resection was performed in 40.6% of patients. Absolute tumor volume was reduced from 55.33 ± 63.77 cm3 to 20.61 ± 21.67 cm3 in first iMRI resection control, to finally 11.56 ± 21.92 cm3 (P < .01). Fiber tracking of the 2 algorithms showed a deviation of the displayed 3D objects by <5 mm. In long-term followup only 1 patient (3.1%) had a persistent language deficit.

CONCLUSION: Intraoperative visualization of language-related cortical areas and the connecting pathways with DTI-based fiber tracking can be successfully performed and integrated in the navigation system. In a setting of intraoperative high-field MRI this contributes to maximum tumor resection with low postoperative morbidity.

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Natural history and surgical management of incidentally discovered low-grade gliomas

J Neurosurg 116:365–372, 2012. DOI: 10.3171/2011.9.JNS111068

Low-grade gliomas (LGGs) are rarely diagnosed as an incidental, asymptomatic finding, and it is not known how the early surgical management of these tumors might affect outcome. The purpose of this study was to compare the outcomes of patients with incidental and symptomatic LGGs and determine any prognostic factors associated with those outcomes.

Methods. All patients treated by the lead author for an LGG incidentally discovered between 1999 and 2010 were retrospectively reviewed. “Incidental” was defined as a finding on imaging that was obtained for a reason not attributable to the glioma, such as trauma or headache. Primary outcomes included overall survival, progression-free survival (PFS), and malignant PFS. Patients with incidental LGGs were compared with a previously reported cohort of patients with symptomatic gliomas.

Results. Thirty-five patients with incidental LGGs were identified. The most common reasons for head imaging were headache not associated with mass effect (31.4%) and trauma (20%). Patients with incidental lesions had significantly lower preoperative tumor volumes than those with symptomatic lesions (20.2 vs 53.9 cm3, p < 0.001), were less likely to have tumors in eloquent locations (14.3% vs 61.9%, p < 0.001), and had a higher prevalence of females (57.1% vs 36%, p = 0.02). In addition, patients with incidental lesions were also more likely to undergo gross-total resection (60% vs 31.5%, p = 0.001) and had improved overall survival on Kaplan-Meier analysis (p = 0.039, Mantel-Cox test). Progression and malignant progression rates did not differ between the 2 groups. Univariate analysis identified pre- and postoperative volumes as well as the use of motor or language mapping as significant prognostic factors for PFS.

Conclusions. In this retrospective cohort of surgically managed LGGs, incidentally discovered lesions were associated with improved patient survival as compared with symptomatic LGGs, with acceptable surgical risks.

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Accuracy of Diffusion Tensor Magnetic Resonance Imaging-Based Tractography for Surgery of Gliomas Near the Pyramidal Tract

Neurosurgery 70:283–294, 2012 DOI: 10.1227/NEU.0b013e31823020e6

Diffusion tensor (DT) imaging-based fiber tracking is a noninvasive magnetic resonance technique that can delineate the course of white matter fibers.

OBJECTIVE: To evaluate the accuracy and usefulness of this DT imaging-based fiber tracking for surgery in patients with gliomas near the pyramidal tract (PT).

METHODS: Subjects comprised 32 patients with gliomas near the PT. DT imagingbased fiber tracks of the PT were generated before and within 3 days after surgery in all patients. A tractography-integrated navigation system was used during the operation. Cortical and subcortical motor-evoked potentials (MEPs) were also monitored during resection to maximize the preservation of motor function. The threshold intensity for subcortical MEPs was examined by searching the stimulus points and changing the stimulus intensity. Minimum distance between the resection border and the illustrated PT was measured on postoperative tractography.

RESULTS: In all subjects, DT imaging-based tractography of the PT was successfully performed, preoperatively demonstrating the relationship between tumors and the PT. With the use of the tractography-integrated navigation system and intraoperative MEPs, motor function was preserved postoperatively in all patients. A significant correlation was seen between threshold intensity for subcortical MEPs and the distance between the resection border and PT on postoperative DT imaging.

CONCLUSION: DT imaging-based fiber tracking is a reliable and accurate method for mapping the course of subcortical PTs. Fiber tracking and intraoperative MEPs were useful for preserving motor function in patients with gliomas near the PT.

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Regression of Recurrent Malignant Gliomas With Convection-Enhanced Delivery of Topotecan

Neurosurgery 69:1272–1280, 2011 DOI: 10.1227/NEU.0b013e3182233e24

Convection-enhanced delivery of chemotherapeutics for the treatment of malignant glioma is a technique that delivers drugs directly into a tumor and the surrounding interstitium through continuous, low-grade positive-pressure infusion. This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs.

OBJECTIVE: To examine the safety profile of a conventional chemotherapeutic agent, topotecan, via convection-enhanced delivery in the treatment of recurrent malignant gliomas and secondarily to assess radiographic response and survival.

METHODS: We performed a prospective, dose-escalation phase Ib study of the topoisomerase- I inhibitor topotecan given by convection-enhanced delivery in patients with recurrent malignant gliomas.

RESULTS: Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated. A maximum tolerated dose was established for future phase II studies.

CONCLUSION: Topotecan by convection-enhanced delivery has significant antitumor activity at concentrations that are nontoxic to normal brain. The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials

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