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Daily bibliographic and video review of the Neurosurgery Department. La Fe University Hospital. Valencia, Spain

Quantification of Glioma Removal by Intraoperative High-Field Magnetic Resonance Imaging: An Update

Neurosurgery 69:852–863, 2011 DOI: 10.1227/NEU.0b013e318225ea6b

The beneficial role of the extent of resection (EOR) in glioma surgery in correlation to increased survival remains controversial. However, common literature favors maximum EOR with preservation of neurological function, which is shown to be associated with a significantly improved outcome.

OBJECTIVE: In order to obtain a maximum EOR, it was examined whether high-field intraoperative magnetic resonance imaging (iMRI) combined with multimodal navigation contributes to a significantly improved EOR in glioma surgery.

METHODS: Two hundred ninety-three glioma patients underwent craniotomy and tumor resection with the aid of intraoperative 1.5 T MRI and integrated multimodal navigation. In cases of remnant tumor, an update of navigation was performed with intraoperative images. Tumor volume was quantified pre- and intraoperatively by segmentation of T2 abnormality in low-grade and contrast enhancement in high-grade gliomas.

RESULTS: In 25.9% of all cases examined, additional tumor mass was removed as a result of iMRI. This led to complete tumor resection in 20 cases, increasing the rate of grosstotal removal from 31.7% to 38.6%. In 56 patients, additional but incomplete resection was performed because of the close location to eloquent brain areas. Volumetric analysis showed a significantly (P , .01) reduced mean percentage of tumor volume following additional further resection after iMRI from 33.5% 6 25.1% to 14.7% 6 23.3% (World Health Organization [WHO] grade I, 32.8% 6 21.9% to 6.1% 6 18.8%; WHO grade II, 24.4% 6 25.1% to 10.8% 6 11.0%; WHO grade III, 35.1% 6 27.3% to 24.8% 6 26.3%; WHO grade IV, 34.2% 6 23.7% to 1.2% 6 16.2%).

CONCLUSION: MRI in conjunction with multimodal navigation and an intraoperative updating procedure enlarges tumor-volume reduction in glioma surgery significantly without higher postoperative morbidity.

Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas

J Neurosurg 115:740–748, 2011. DOI: 10.3171/2011.6.JNS11252

Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5- ALA)–induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection.

Methods. Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence.

Results. Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses.

Conclusions. Intraoperative confocal microscopy can visualize cellular 5-ALA–induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors’ institution.

Occipital WHO grade II gliomas: oncological, surgical and functional considerations

Acta Neurochir (2011) 153:1907–1917. DOI 10.1007/s00701-011-1125-z

Diffuse WHO grade II glioma (GIIG) involving the occipital lobe is a rare entity. Its surgical resection remains controversial as it implies inducing a permanent visual deficit. For the first time to our knowledge, we report a consecutive surgical series of patients who underwent an occipital lobectomy for an LGG invading visual structures.

Method Six right-handed patients harboring a GIIG revealed by seizures (normal examination except a quadrantanopsia in one case) and located within the occipital lobe (4 left and 2 right tumors) were submitted to surgery. Before making this decision, the benefit-to-risk ratio of the resection was extensively discussed with the patient and his/her family, especially concerning the price to pay to remove the tumor, that is, to voluntarily generate a permanent hemianopsia. All the procedures were performed under awake condition using intraoperative electrostimulation, in order to pursue the resection until sensory-motor and/or language structures were encountered.

Findings An extensive occipital lobectomy was achieved in the six patients, with identification and preservation of sensory-motor pathways in the two cases with a right tumor and detection of language pathways in the four cases with a left tumor. The mean extent of resection was 93% (range: 91–100%). All patients experienced an expected postoperative deficit of the visual field (homonymous hemianopsia). Nonetheless, the six patients resumed a normal social and professional life (KPS at 90 in the 6 cases) with a mean follow-up of 58 months (range: 3–147 months)—with adjuvant treatment in three cases (in addition to a reoperation in two of them).

Conclusions Our findings suggest that, despite a definitive hemianopsia, an extensive surgical resection can be considered in the rare cases of occipital GIIG involving the primary visual structures, with patients able to maintain a normal life—except regarding the medico-legal problem of driving.

Chordomas of the skull base and cervical spine: clinical outcomes associated with a multimodal surgical resection combined with proton-beam radiation in 40 patients

Neurosurg Rev DOI 10.1007/s10143-011-0334-5

Previous studies of chordoma have focused on either surgery, radiotherapy, or particular tumor locations. This paper reviewed the outcomes of surgery and proton radiotherapy with various tumor locations.

Between 2001 and 2008, 40 patients with chordomas of the skull base and cervical spine had surgery at our hospital. Most patients received proton therapy. Their clinical course was reviewed. Age, sex, tumor location, timing of surgery, extent of resection, and chondroid appearance were evaluated in regard to the progression-free survival (PFS) and overall survival (OS). The primary surgery (PS) group was analyzed independently. The extensive resection rate was 42.5%. Permanent neurological morbidity was seen in 3.8%. Radiotherapy was performed in 75% and the mean dose was 68.9 cobalt gray equivalents. The median followup was 56.5 months. The 5-year PFS and OS rates were 70% and 83.4%, respectively. Metastasis was seen in 12.5%. The tumor location at the cranio-cervical junction (CCJ) was associated with a lower PFS (P=0.007). In the PS group, a younger age and the CCJ location were related to a lower PFS (P=0.008 and P<0.001, respectively). The CCJ location was also related to a lower OS (P=0.043) and it was more common in young patients (P=0.002). Among the survivors, the median of the last Karnofsky Performance Scale score was 80 with 25.7% of patients experiencing an increase and 11.4% experiencing a decrease.

Multimodal surgery and proton therapy thus improved the chordoma treatment. The CCJ location and a younger age are risks for disease progression.

Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma

Neuro-Oncology DOI:10.1093/neuonc/nor169

Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma.

The objective of this pilot study was to identify differentially expressed microRNAs in CSF samples from patients with glioma as potential novel glioma biomarkers.

With use of a candidate approach of miRNA quantification by reverse-transcriptase polymerase chain reaction (qRT-PCR), miRNAs with significant levels in CSF samples from patients with gliomas were identified. MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases. Receiver- operating characteristic analysis of miR-15b level revealed an area under the curve of 0.96 in discriminating patients with glioma from patients without glioma. Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma.

In conclusion, the results of this pilot study demonstrate that miR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR. Accordingly, miRNAs in the CSF have the potential to serve as novel biomarkers for the detection of gliomas.

Surgical Management of Craniopharyngiomas in Children: Meta-analysis and Comparison of Transcranial and Transsphenoidal Approaches

Neurosurgery 69:630–643, 2011 DOI: 10.1227/NEU.0b013e31821a872d

Controversy persists regarding the optimal treatment of pediatric craniopharyngiomas.

OBJECTIVE: We performed a meta-analysis of reported series of transcranial (TC) and transsphenoidal (TS) surgery for pediatric craniopharyngiomas to determine whether comparisons between the outcomes in TS and TC approaches are valid.

METHODS: Online databases were searched for English-language articles reporting quantifiable outcome data published between 1990 and 2010 pertaining to the surgical treatment of pediatric craniopharyngiomas. Forty-eight studies describing 2955 patients having TC surgery and 13 studies describing 373 patients having TS surgery met inclusion criteria.

RESULTS: Before surgery, patients who had TC surgery had less visual loss, more frequent hydrocephalus and increased intracranial pressure, larger tumors, and more suprasellar disease. After surgery, patients in the TC group had lower rates of gross total resection (GTR), more frequent recurrence after GTR, higher neurological morbidity, more frequent diabetes insipidus, less improvement, and greater deterioration in vision. There was no difference in operative mortality, obesity/hyperphagia, or overall survival percentages.

CONCLUSION: Directly comparing outcomes after TC and TS surgery for pediatric craniopharyngiomas does not appear to be valid. Baseline differences in patients who underwent each approach create selection bias that may explain the improved rates of disease control and lower morbidity of TS resection. Although TS approaches are becoming increasingly used for smaller tumors and those primarily intrasellar, tumors more amenable to TC surgery include large tumors with significant lateral extension, those that engulf vascular structures, and those with significant peripheral calcification.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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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