Category: Oncology

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Preoperative Functional Mapping for Rolandic Brain Tumor Surgery: Comparison of Navigated Transcranial Magnetic Stimulation to Direct Cortical Stimulation

Neurosurgery 69:581–589, 2011 DOI: 10.1227/NEU.0b013e3182181b89

Transcranial magnetic stimulation (TMS) is the only noninvasive method for presurgical stimulation mapping of cortical function. Recent technical advancements have significantly increased the focality and usability of the method.

OBJECTIVE: To compare the accuracy of a 3-dimensional magnetic resonance imaging– navigated TMS system (nTMS) with the gold standard of direct cortical stimulation (DCS).

METHODS: The primary motor areas of 20 patients with rolandic tumors were mapped preoperatively with nTMS at 110% of the individual resting motor threshold. Intraoperative DCS was available from 17 patients. The stimulus locations eliciting the largest electromyographic response in the target muscles (‘‘hotspots’’) were determined for both methods.

RESULTS: The nTMS and DCS hotspots were located on the same gyrus in all cases. The mean 6 SEM distance between the nTMS and DCS hotspots was 7.83 6 1.18 mm for the abductor pollicis brevis (APB) muscle (n = 15) and 7.07 6 0.88 mm for the tibialis anterior muscle (n = 8). When a low number of DCS stimulations was performed, the distance between the nTMS and DCS hotspots increased substantially (r = 20.86 for APB). After the exclusion of the cases with , 15 DCS APB responses, the mean 6 SEM distance between the hotspots was only 4.70 6 1.09 mm for APB (n = 8).

CONCLUSION: Peritumoral mapping of the motor cortex by nTMS agreed well with the gold standard of DCS. Thus, nTMS is a reliable tool for preoperative mapping of motor function.

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Convexity meningiomas: study of recurrence factors with special emphasis on the cleavage plane in a series of 100 consecutive patients

J Neurosurg 115:491–498, 2011. DOI: 10.3171/2011.4.JNS101922

Convexity meningiomas are expected to have a low recurrence rate given their classically “easy resectability.” Nonetheless, recurrence can occur. Factors playing a role in their recurrence are analyzed here, including the extent of resection and tumor histological type, among others, with a special emphasis on the cleavage plane.

Methods. The authors reviewed 100 cases of convexity meningiomas surgically treated between 1987 and 2001 with a median follow-up of 86 months (range 2–16 years). Preoperative and postoperative functional status, Simpson resection grade, histological type, and intraoperative surgical plane with pial vessel invasion were studied and cor- related with the recurrence rate.

Results. The average tumor size was 3.6 ± 0.4 cm. The pre- and postoperative Karnofsky Performance Scale scores were 92.6 ± 4.6 and 97.9 ± 2.2, respectively. Ninety-five lesions were benign (WHO Grade I) and 5 were atypical (WHO Grade II). Ninety-one and 9 tumors were subjected to Simpson Grade 1 and 3 resections (three Grade 3a and six Grade 3b), respectively. Surgical deaths did not occur. After a mean follow-up of 7.2 years, 4 meningiomas recurred; 2 (2.2%) after Simpson Grade 1 resections and 2 after Simpson Grade 3 (3a and 3b) resections (22.2%; p = 0.0034). When just the subgroup of Simpson Grade 1/WHO Grade I was studied, the recurrence rate decreased to 1.2% (1 of 86 cases). The recurrence of WHO Grade I tumors was higher in the subpial group than in the extrapial group (p = 0.025). No difference in recurrence according to the cleavage plane was seen in the WHO Grade II sub- group (p = 0.361). As for the subpial group, no difference in recurrence was noted between the WHO Grade I and II subgroups (p = 0.608). Importantly, however, the extrapial subgroup of WHO Grade II lesions had a higher recurrence rate compared with its counterpart in the WHO Grade I subgroup (p = 0.005).

Conclusions. Pial and vascular invasion affect the recurrence rate in convexity meningioma surgery. The recurrence rate of WHO Grade I tumors was higher among those with a subpial plane of dissection than among those with an extrapial one. Histological type did not determine the degree of pial invasion in WHO Grade I and II lesions.

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Supraorbital keyhole approach for removal of midline anterior cranial fossa meningiomas

Neurosurg Rev. DOI 10.1007/s10143-011-0340-7

The paper describes a retrospective study of a consecutive series of 20 midline anterior cranial fossa meningiomas (five of the olfactory groove, 14 of the tuberculum sellae, and one clinoidal), which were operated on via a supraorbital keyhole approach between 2002 and 2008.

The series includes three males and 17 females (mean age 57 years, mean size of the tumors 3.5×3 cm, and mean follow-up 48 months). Gross total excision was achieved in 18 cases and subtotal resection in two. Out of 14 patients with visual deficits, nine patients improved, one remained stable, and three deteriorated. Two patients presented a recurrence 3 years after surgery. One peri-operative death was recorded.

The subgroup of patients with tuberculum sellae meningiomas was analyzed in details. A meta-analysis of the major series of such meningiomas in the last 20 years has been performed in order to compare results of different surgical techniques. With regard to primary outcomes of these tumors, gross total removal, restoration of visual function, morbidity, mortality, and recurrence rates, the supraorbital approach, for selected cases, seems to offer valuable results, comparable with those reported in conventional and endoscopic approaches and with very low surgical aggressiveness. However, statistical data available from the literature, particularly on visual function, are still too limited to draw definitive conclusions.

The best surgical option for the individual patient cannot yet be standardized and should be chosen on the basis of tumor anatomy, pre-operative clinical symptoms, and surgeon’s experience.

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Neurocytomas: Long-term experience of a single institution

Neuro-Oncology 13(9):943–949, 2011. doi:10.1093/neuonc/nor074

There is a lack of studies reporting on outcomes of control and treatment toxicities for neurocytomas.

A 25-year retrospective review of a tertiary center’s experience with neurocytomas was completed to report on these outcomes. All cerebral neurocytoma cases (19 patients; median age, 31 years; range, 18–62 years; 18 intraventricular and 1 extraventricular) treated between 1984 and 2009 were analyzed, including central pathology and radiology reviews.

Median follow-up was 104.5 months (range, 0.75–261.7 months). Primary treatment was surgery alone (n = 18 patients), followed by surgery and adjuvant radiotherapy (n = 1). The crude local control rate after surgery was 68% for all cases (cerebral neurocytomas) and 74% for central neurocytomas. Salvage therapies included further surgery (n = 4), radiation (n = 3), and chemotherapy (n = 1). Ten-year Kaplan-Meier overall and relapse-free survival rates were 82% and 62% and 81% and 57%, respectively, for all cases and for central neurocytomas only. The median overall survival and relapse-free survival were 104.5 and 79.3 months, respectively, for all cases and for central neurocytomas. Ten patients had grade 3/4 toxicity, and 1 patient had a grade 5 perioperative hemorrhage that resulted in death 23 days after surgery. Late grade 3/4 toxicities occurred in 9 patients. Three patients had permanent grade 2 motor or cognitive deficits.

We provide the first report outlining toxicities and survival outcomes in a series of 19 patients. Our experience suggests that initial surgery provides durable local control rates in two-thirds of patients, with low risk for significant permanent deficits. Salvage therapy with surgery and/or radiation provides durable local control in tumors that recur after surgery.

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Motor-evoked potentials (MEP) during brainstem surgery to preserve corticospinal function

Acta Neurochir (2011) 153:1753–1759. DOI 10.1007/s00701-011-1065-7

Brainstem surgery bears a risk of damage to the corticospinal tract (CST). Motor-evoked potentials (MEPs) are used intraoperatively to monitor CST function in order to detect CST damage at a reversible stage and thus impede permanent neurological deficits. While the method of MEP is generally accepted, warning criteria in the context of brainstem surgery still have to be agreed on.

Method We analyzed 104 consecutive patients who underwent microsurgical resection of lesions affecting the brainstem. Motor grade was documented prior to surgery, early postoperatively and at discharge. A baseline MEP stimulation intensity threshold was defined and intraoperative testing aimed to keep MEP response amplitude constant. MEPs were considered deteriorated and the surgical team was notified whenever the threshold was elevated by ≥20 mA or MEP response fell under 50%.

Findings On the first postoperative day, 18 patients experienced new paresis that resolved by discharge in 11. MEPs deteriorated in 39 patients, and 16 of these showed new postoperative paresis, indicating a 41% risk of new paresis. In the remaining 2/18 patients, intraoperative MEPs were stable, although new paresis appeared postoperatively. In one of these patients, intraoperative hemorrhage caused postoperative swelling, and the new motor deficit persisted until discharge. Of all 104 patients, 7 deteriorated in motor grade at discharge, 92 remained unchanged, and 5 patients have improved.

Conclusions Adjustment of surgical strategy contributed to good motor outcome in 33/39 patients. MEP monitoring may help significantly to prevent motor deficits during demanding neurosurgical procedures on the brainstem.

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Molecular imaging of gliomas with PET: Opportunities and limitations

Neuro-Oncology 13(8):806–819, 2011. doi:10.1093/neuonc/nor054

Neuroimaging enables the noninvasive evaluation of glioma and is considered to be one of the key factors for individualized therapy and patient management, since accurate diagnosis and demarcation of viable tumor tissue is required for treatment planning as well as assessment of treatment response. Conventional imaging techniques like MRI and CT reveal morphological information but are of limited value for the assessment of more specific and reproducible information about biology and activity of the tumor. Molecular imaging with PET is increasingly implemented in neuro-oncology, since it provides additional metabolic information of the tumor, both for patient management as well as for evaluation of newly developed therapeutics.Different molecular processes have been proposed to be useful, like glucose consumption, expression of amino acid transporters, proliferation rate, membrane biosynthesis, and hypoxia. Thus, PET might help neuro-oncologists gain further insights into tumor biology by “true molecular imaging” as well as understand treatment-related phenomena. This review describes the method of PET acquisition as well as the tracers used to image biological processes in gliomas. Furthermore, it considers the clinical impact of PET on the use of currently available radiotracers, which were shown to be potentially valuable for discrimination between neoplastic and nonneoplastic tissue, as well as on tumor grading, determinination of treatment response, and providing an outlook toward further developments.

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Awake surgery for WHO Grade II gliomas within “noneloquent” areas in the left dominant hemisphere: toward a “supratotal” resection

J Neurosurg 115:232–239, 2011. DOI: 10.3171/2011.3.JNS101333

It has been demonstrated that an extensive resection (total or subtotal) may significantly increase the overall survival in patients with WHO Grade II gliomas (low-grade gliomas [LGGs]). Yet, recent data have shown that conventional MR imaging underestimates the spatial extent of LGG, since tumor cells were found up to 20 mm around MR imaging abnormalities. Thus, it was hypothesized that an extended resection with a margin beyond MR imaging–defined abnormalities—a “supratotal” resection—might improve the outcome of LGG. However, because of the frequent location of LGG within “eloquent” brain areas, it is often difficult to achieve such a supratotal resection. This could nevertheless be possible when LGGs involve “noneloquent” areas, even in the left dominant hemisphere.

The authors report on their use of awake electrical mapping to tailor the resection according to functional boundaries, that is, to pursue the resection beyond MR imaging–defined abnormalities, until corticosubcortical eloquent structures are encountered. Their aim was to apply this reliable surgical technique to LGGs located not within eloquent areas but distant from eloquent areas, to take a margin around the LGG visible on MR imaging while preserving brain function.

Methods. Fifteen right-handed patients with a total of 17 tumors underwent resection of WHO Grade II gliomas involving nonfunctional areas within the left dominant hemisphere. In all patients, seizures were the initial manifestation of the tumors. Awake surgery with intraoperative electrostimulation was performed in all cases. The resection was continued until the surgeon reached cortical and subcortical areas crucial for brain function, especially language, as defined by the intrasurgical electrical mapping. The extent of resection was evaluated on postoperative FLAIRweighted MR images.

Results. Despite transient neurological worsening in 60% of cases, all patients recovered and returned to a normal life. Seizure control was obtained in all patients with a decrease of antiepileptic drug therapy. Postoperative MR imaging showed that total resection was achieved in all 17 tumors and supratotal resection in 15. The average volume of the postoperative cavity (36.8 cm3) was significantly larger than the mean preoperative tumor volume (26.6 cm3) (p = 0.009). Neuropathological examination confirmed the diagnosis of WHO Grade II glioma in all cases. The mean duration of postoperative follow-up was 35.7 months (range 6–135 months). Only 4 of 15 patients experienced recurrence (without anaplastic transformation); the average time to recurrence in these cases was 38 months; radiotherapy was performed 6 years after the relapse in 1 case; no other patients received any adjuvant treatment. This series was compared with a control group of 29 patients who had “only” complete resection: anaplastic transformation was observed in 7 cases in the control group but not in any case in the series of patients who underwent supracomplete resection (p = 0.037). Furthermore, adjuvant treatment was administered in 10 patients in the control group compared with 1 patient who underwent supracomplete resection (p = 0.043).

Conclusions. These findings support the usefulness of awake surgery with intraoperative functional (language) mapping with the attempt to perform supratotal resection of LGGs involving noneloquent areas in the left hemisphere. Indeed, the extent of resection was significantly increased in all cases but 2, with no additional permanent deficit and with control of seizures in all patients. The goal of supracomplete resection is currently to delay the anaplastic transformation, even if it does not (yet) enable a cure.

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Delta-aminolevulinic acid–induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy

Neuro-Oncology 13(8):846–856, 2011. doi:10.1093/neuonc/nor086

Extent of resection is a major goal and prognostic factor in the treatment of gliomas. In this study we evaluate whether quantitative ex vivo tissue measurements of d-aminolevulinic acid–induced protoporphyrin IX (PpIX) identify regions of increasing malignancy in low- and high-grade gliomas beyond the capabilities of current fluorescence imaging in patients undergoing fluorescence-guided resection (FGR).

Surgical specimens were collected from 133 biopsies in 23 patients and processed for ex vivo neuropathological analysis: PpIX fluorimetry to measure PpIX concentrations (CPpIX) and Ki-67 immunohistochemistry to assess tissue proliferation. Samples displaying visible levels of fluorescence showed significantly higher levels of CPpIX and tissue proliferation. CPpIX was strongly correlated with histopathological score (nonparametric) and tissue proliferation (parametric), such that increasing levels of CPpIX were identified with regions of increasing malignancy. Furthermore, a large percentage of tumor-positive biopsy sites (∼40%) that were not visibly fluorescent under the operating microscope had levels of CPpIX greater than 0.1 mg/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging.

Although PpIX fluorescence is recognized as a visual biomarker for neurosurgical resection guidance, these data show that it is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas. This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery.

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Lateral supracerebellar transtentorial approach for petroclival meningiomas: operative technique and outcome

J Neurosurg 115:49–54, 2011. DOI: 10.3171/2011.2.JNS101759

The retrosigmoid intradural suprameatal approach with the patient in a semisitting position is an effective alternative to transpetrosal approaches for the treatment of petroclival meningiomas. The authors have made a simple modification to the retrosigmoid intradural suprameatal approach by using the lateral oblique position and preferentially dividing the tentorium with limited drilling of the suprameatal bone, which is termed the “lateral su- pracerebellar transtentorial approach.”

Methods. Twenty-six patients with petroclival meningiomas surgically treated via the lateral supracerebellar transtentorial approach were analyzed. All tumors had most of their bulk in the posterior fossa with some degree of extension into the middle fossa and/or Meckel cave. The patient is placed in the lateral oblique position, and a standard retrosigmoid craniotomy is performed. The tentorium medial to the trigeminal nerve is incised toward the free edge, which improves exposure to the petroclival region without extensive resection of the suprameatal petrous bone.

Results. Gross-total resection was achieved in 11 patients (42%). Ten patients (38%) underwent subtotal resection, and 5 patients (19%) underwent partial resection. There was no incidence of operative death, and the postoperative permanent morbidity rate was 15%. All patients except one did well postoperatively and were independent at the time of their last follow-up examinations.

Conclusions. The lateral supracerebellar transtentorial approach provides the simplest and safest access to the petroclival region. It offers an advantageous approach to petroclival meningiomas exclusively located in the posterior fossa with minimal extension into the Meckel cave and middle fossa.

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Use of Movable High-Field-Strength Intraoperative Magnetic Resonance Imaging With Awake Craniotomies for Resection of Gliomas: Preliminary Experience

Neurosurgery 69:194–206, 2011 DOI: 10.1227/NEU.0b013e31821d0e4c

Awake craniotomy with electrocortical mapping and intraoperative magnetic resonance imaging (iMRI) are established techniques for maximizing tumor resection and preserving function, but there has been little experience combining these methodologies.

OBJECTIVE: To report our experience of combining awake craniotomy and iMRI with a 1.5-T movable iMRI for resection of gliomas in close proximity to eloquent cortex.

METHODS: Twelve patients (9 male and 3 female patients; age, 32-60 years; mean, 41 years) undergoing awake craniotomy and iMRI for glioma resections were identified from a prospective database. Assessments were made of how these 2 modalities were integrated and what impact this strategy had on safety, surgical decision making, workflow, operative time, extent of tumor resection, and outcome.

RESULTS: Twelve craniotomies were safely performed in an operating room equipped with a movable 1.5-T iMRI. The extent of resection was limited because of proximity to eloquent areas in 5 cases: language areas in 3 patients and motor areas in 2 patients. Additional tumor was identified and resected after iMRI in 6 patients. Average operating room time was 7.9 hours (range, 5.9-9.7 hours). Compared with preoperative neurological function, immediate postoperative function was stable/improved in 7 and worse in 5; after 30 days, it was stable/improved in 11 and worse in 1.

CONCLUSION: Awake craniotomy and iMRI with a movable high-field-strength device can be performed safely to maximize resection of tumors near eloquent language areas.

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Application of intraoperative indocyanine green videoangiography to brain tumor surgery

Acta Neurochir (2011) 153:1487–1495. DOI 10.1007/s00701-011-1046-x

Videoangiography using indocyanine green (ICG) has been used in the ophthalmologic field for a long time. It was introduced to the neurosurgical field several years ago but has been limited to vascular surgeries. We applied ICG videoangiography to brain tumor surgery and evaluated the usefulness.

Methods Twenty-three patients with a brain tumor who underwent microsurgical resection were analyzed. The pathological diagnosis was meningioma in 15 patients, metastasis in three, glioma in three, and hemangioblastoma in two. A microscope with a special filter and infrared excitation light to illuminate the operating field was used in this study. The intravascular fluorescence was imaged with a video camera attached to the microscope. ICG was injected intravenously with the dose of 5–25 mg, and overall, ICG was injected intraoperatively 32 times.

Results ICG videoangiography allowed for an excellent evaluation of blood flow in the tumoral and peri-tumoral vessels both before and after the resection in all cases.

Conclusions ICG videoangiography is a useful method for monitoring blood flow in the exposed vessels during microsurgery for a brain tumor. This noninvasive method is simple, safe, cost-effective, and easily repeatable. Before resection, it provides information on the tumoral and peritumoral circulation including sequential visualization of vessels or direction of the blood flow. After resection, it checks the patency of the peri-tumoral vessels and is especially useful for the vein. This ICG videoangiography can be an alternative tool to intraoperative angiography or Doppler ultrasonography in selective cases.

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Neuropathological and Neuroradiological Spectrum of Pediatric Malignant Gliomas: Correlation With Outcome

Neurosurgery 69:215–224, 2011 DOI: 10.1227/NEU.0b013e3182134340

The diagnostic accuracy and reproducibility for glioma histological diagnosis are suboptimal.

OBJECTIVE: To characterize radiological and histological features in pediatric malignant gliomas and to determine whether they had an impact on survival.

METHODS: We retrospectively reviewed a series of 96 pediatric malignant gliomas. All histological samples were blindly and independently reviewed and classified according to World Health Organization 2007 and Sainte-Anne classifications. Radiological features were reviewed independently. Statistical analyses were performed to investigate the relationship between clinical, radiological, and histological features and survival.

RESULTS: Cohort median age was 7.8 years; median follow-up was 4.8 years. Tumors involved cerebral hemispheres or basal ganglia in 82% of cases and brainstem in the remaining 18%. After histopathological review, low-grade gliomas and nonglial tumors were excluded (n = 27). The World Health Organization classification was not able to demonstrate differences between groups and patients survival. The Sainte-Anne classification identified a 3-year survival rate difference between the histological subgroups (oligodendroglioma A, oligodendroglioma B, malignant glioneuronal tumors, and glioblastomas; P = .02). The malignant glioneuronal tumor was the only glioma subtype with specific radiological features. Tumor location was significantly associated with 3-year survival rate (P = .005). Meningeal attachment was the only radiological criteria associated with longer survival (P = .02).

CONCLUSION: The Sainte-Anne classification was better able to distinguish pediatric malignant gliomas in terms of survival compared with the World Health Organization classification. In this series, neither of these 2 histological classifications provided a prognostic stratification of the patients.

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Endonasal endoscopic resection of esthesioneuroblastoma: the Johns Hopkins Hospital experience and review of the literature

Neurosurg Rev. DOI 10.1007/s10143-011-0329-2

Esthesioneuroblastoma is an uncommon malignant tumor originating in the upper nasal cavity. The surgical treatment for this tumor has traditionally been via an open craniofacial resection. Over the past decade, there has been tremendous development in endoscopic techniques.

In this report, we performed a retrospective analysis of patients with esthesioneuroblastomas treated with a purely endonasal endoscopic approach and resection at the Johns Hopkins Hospital between January 2005 and April 2010.

A total of eight patients with esthesioneuroblastoma, five men and three women, were identified. Six patients were treated for primary disease, and two were treated for tumor recurrence. The modified Kadish staging was A in one patient (12.5%), B in two patients (25%), C in four patients (50%), and D in one patient (12.5%). All patients had a complete resection with negative intraoperative margins. One patient had intraoperative hypertension; there were no perioperative complications. With a mean follow-up of over 27 months, all patients are without evidence of disease. In addition, we reviewed the literature and identified several overlapping case series of patients with esthesioneuroblastoma treated via a purely endoscopic technique.

Our series adds to the growing experience of expanded endonasal endoscopic surgery in the treatment of skull base tumors including esthesioneuroblastoma. Longer follow-up on a larger number of patients is required to further demonstrate the utility of endoscopic approaches in the management of this malignancy.

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An extent of resection threshold for newly diagnosed glioblastomas

J Neurosurg 115:3–8, 2011. DOI: 10.3171/2011.2.JNS10998

The value of extent of resection (EOR) in improving survival in patients with glioblastoma multiforme (GBM) remains controversial. Specifically, it is unclear what proportion of contrast-enhancing tumor must be resected for a survival advantage and how much survival improves beyond this threshold. The authors attempt to define these values for the patient with newly diagnosed GBM in the modern neurosurgical era.

Methods. The authors identified 500 consecutive newly diagnosed patients with supratentorial GBM treated at the University of California, San Francisco between 1997 and 2009. Clinical, radiographic, and outcome parameters were measured for each case, including MR imaging–based volumetric tumor analysis.

Results. The patients had a median age of 60 years and presented with a median Karnofsky Performance Scale (KPS) score of 80. The mean clinical follow-up period was 15.3 months, and no patient was unaccounted for. All patients underwent resection followed by chemotherapy and radiation therapy. The median postoperative tumor volume was 2.3 cm3, equating to a 96% EOR. The median overall survival was 12.2 months. Using Cox proportional hazards analysis, age, KPS score, and EOR were predictive of survival (p < 0.0001). A significant survival advantage was seen with as little as 78% EOR, and stepwise improvement in survival was evident even in the 95%–100% EOR range. A recursive partitioning analysis validated these findings and provided additional risk stratification parameters related to age, EOR, and tumor burden.

Conclusions. For patients with newly diagnosed GBMs, aggressive EOR equates to improvement in overall survival, even at the highest levels of resection. Interestingly, subtotal resections as low as 78% also correspond to a survival benefit.

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Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker

J Neurosurg 115:11–17, 2011. DOI: 10.3171/2011.2.JNS101451

Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following d-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies.

Methods. The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo.

Results. A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon’s visual perception were classified correctly in an analysis of all tumors.

Conclusions. These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.

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Cytokine networks in glioma

Neurosurg Rev (2011) 34:253–264. DOI 10.1007/s10143-011-0320-y

Glioma is the most frequently occurring brain tumor, but the prognosis of patients with gliomas remains poor despite advances in surgery, radiotherapy, and chemotherapy. Therefore, great efforts have been made to develop improved therapeutic strategies.

Cytokines are a heterogeneous group of soluble small polypeptides or glycoproteins that exert pleiotropic and redundant effects that promote the growth, differentiation, and activation of normal cells. Cytokines have either pro- or anti-inflammatory activity and immunosuppressive activity, depending on the microenvironment surrounding the tumor. The microenvironment consists of heterogeneous tumor cells, immune cells, and extracellular matrix.

Modulation of the microenvironment by the tumor is essential for its growth and progress. Cytokine production acts as a means of communication in the tumor microenvironment.

In this article, we review the cross-talk between cytokines in the tumor microenvironment and the cytokine therapies that have been used till date for glioma treatment.

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Lateral Supraorbital Approach Applied to Anterior Clinoidal Meningiomas: Experience With 73 Consecutive Patients

Neurosurgery 68:1632–1647, 2011 DOI: 10.1227/NEU.0b013e318214a840

Anterior clinoidal meningiomas (ACMs) are a subgroup of meningiomas accounting for less than 10% of supratentorial meningiomas.

OBJECTIVE: To assess the reliability and safeness of the lateral supraorbital approach (LSO) to remove ACMs.

METHODS: Between September 1997 and October 2009, a total of 73 ACM patients were operated on at the Department of Neurosurgery, Helsinki University Central Hospital, by the senior author (J.H.). We retrospectively analyzed the clinical data, radiological findings, surgical treatment, histology, and outcome of patients, and discuss the operative technique.

RESULTS: Seventy-three patients were operated on by applying the LSO approach. Apparently complete removal was achieved in 57 patients (78%). Anterior clinoidectomy was performed in 21 cases. Preexisting visual deficit improved in 11 of 39 patients and worsened in 4; 3 had de novo visual deficit. At 3 months after discharge, 60 (82%) patients had a good recovery, 9 (12%) patients were moderately disabled, 1 presented with severe disability, and 3 (4%) patients died of surgery-related causes. Sixteen (22%) patients had residual tumors, 6 of which required reoperation. During the median followup of 36 months (range, 3-146), tumor recurred in 3 patients: 2 were followed-up and 1 was reoperated on.

CONCLUSION: ACMs can be removed via the LSO approach with relatively low morbidity and mortality. Anterior clinoidectomy is required only in selected cases, and we prefer the intradural approach during the LSO approach. High-power coagulation should be avoided in proximity of the optic nerve.

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Gamma Knife surgery for parasellar meningiomas: long-term results including complications, predictive factors, and progression-free survival

J Neurosurg 114:1571–1577, 2011. DOI: 10.3171/2011.1.JNS091939

Stereotactic radiosurgery serves as an important primary and adjuvant treatment option for patients with many types of intracranial meningiomas. This is particularly true for patients with parasellar meningiomas. In this study, the authors evaluated the outcomes of Gamma Knife surgery (GKS) used to treat parasellar meningiomas.

Methods. The study is a retrospective review of the outcomes in 138 patients with meningiomas treated at the University of Virginia from 1989 to 2006; all patients had a minimum follow-up of 24 months. There were 31 men and 107 women whose mean age was 54 years (range 19–85 years). Eighty-four patients had previously undergone resection. The mean pre-GKS tumor volume was 7.5 ml (range 0.2–54.8 ml). Clinical and radiographic evaluations were performed, and factors related to favorable outcomes in each case were assessed.

Results. The mean follow-up duration was 84 months (median 75.5 months, range 24–216 months). In 118 patients (86%), the tumor volume was unchanged or had decreased at last follow-up. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 5 and 10 years to be 95.4% and 69%, respectively. Fourteen patients (10%) developed new cranial nerve palsies following GKS. Factors associated with tumor control included younger age, a higher isodose, and smaller tumor volume. A longer follow-up duration was associated with either a decrease or increase in tumor volume. Fourteen patients (10%) experienced new or worsening cranial nerve deficits after treatment. Factors associated with this occurrence were larger pretreatment tumor volume, lower peripheral radiation dose, lower maximum dose, tumor progression, and longer follow-up.

Conclusions. Gamma Knife surgery offers an acceptable rate of tumor control for parasellar meningiomas and accomplishes this with a low incidence of neurological deficits. Radiological control after radiosurgery is more likely in those patients with a smaller tumor volume and a higher prescription dose.

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Intraoperative Confocal Microscopy for Brain Tumors: A Feasibility Analysis in Humans

Neurosurgery 68[ONS Suppl 2]:ons282–ons290, 2011. DOI: 10.1227/NEU.0b013e318212464e

The ability to diagnose brain tumors intraoperatively and identify tumor margins during resection could maximize resection and minimize morbidity. Advances in optical imaging enabled production of a handheld intraoperative confocal microscope.

OBJECTIVE: To present a feasibility analysis of the intraoperative confocal microscope for brain tumor resection.

METHODS: Thirty-three patients with brain tumor treated at Barrow Neurological Institute were examined. All patients received an intravenous bolus of sodium fluorescein before confocal imaging with the Optiscan FIVE 1 system probe. Optical biopsies were obtained within each tumor and along the tumor-brain interfaces. Corresponding pathologic specimens were then excised and processed. These data was compared by a neuropathologist to identify the concordance for tumor histology, grade, and margins.

RESULTS: Thirty-one of 33 lesions were tumors (93.9%) and 2 cases were identified as radiation necrosis (6.1%). Of the former, 25 (80.6%) were intra-axial and 6 (19.4%) were extra-axial. Intra-axial tumors were most commonly gliomas and metastases, while all extra-axial tumors were meningiomas. Among high-grade gliomas, vascular neoproliferation, as well as tumor margins, were identifiable using confocal imaging. Meningothelial and fibrous meningiomas were distinct on confocal microcopy—the latter featured spindle-shaped cells distinguishable from adjacent parenchyma. Other tumor histologies correlated well with standard neuropathology tissue preparations.

CONCLUSION: Intraoperative confocal microscopy is a practicable technology for the resection of human brain tumors. Preliminary analysis demonstrates reliability for a variety of lesions in identifying tumor cells and the tumor-brain interface. Further refinement of this technology depends upon the approval of tumor-specific fluorescent contrast agents for human use.

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Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor

J Neurosurg 114:1410–1413, 2011. DOI: 10.3171/2010.11.JNS10250

The introduction of fluorescence-guided resection of primary malignant brain tumors was a milestone in neurosurgery. Deep-seated malignant brain tumors are often not approachable for microsurgical resection. For diagnosis and therapy, new strategies are recommended. The combination of endoscopy and 5-aminolevulinic acid–induced protoporphyrin IX (5-ALA-induced Pp IX) fluorescence–guided procedures supported by neuronavigation seems an interesting option. Here the authors report on a combined approach for 5-ALA fluorescence–guided biopsy in which they use an endoscopy system based on an Xe lamp (excitation approximately lambda = 407 nm; dichroic filter system lambda = 380–430 nm) to treat a malignant tumor of the thalamus and perform a ventriculostomy and septostomy. The excitation filter and emission filter are adapted to ensure that the remaining visible blue remission is sufficient to superimpose on or suppress the excited red fluorescence of the endogenous fluorochromes. The authors report that the lesion was easily detectable in the fluorescence mode and that biopsy led to histological diagnosis.

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