Category: Oncology

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Treatment decision making based on the published natural history and growth rate of small meningiomas

J Neurosurg 113:1036–1042, 2010, DOI: 10.3171/2010.3.JNS091966

Definitive data allowing clinicians to predict which meningioma patients will fail to respond to conservative management are lacking. To address this need, the authors systematically reviewed the published literature regarding the natural history of small, untreated meningiomas.

Methods. The authors performed a systematic review of the existing literature on untreated meningiomas that were followed with serial MR imaging. They summarize the published linear rates of tumor growth, and the risk factors for development of new or worsened symptoms during follow-up by using a stratified chi-square test.

Results. The search methods identified 22 published studies reporting on 675 patients with untreated meningiomas followed by serial MR imaging. Linear growth rates varied significantly: no growth was the most common rate, although reports of more aggressive tumors noted growth rates of up to a 93% linear increase in size per year. The authors found that few patients with initial tumor diameters < 2 cm went on to develop new or worsened symptoms over a median follow-up period of 4.6 years. Patients with initial tumor diameters of 2–2.5 cm demonstrated a marked difference in the rate of symptom progression if their tumors grew > 10% per year, compared with those tumors growing ≤ 10% per year (42% vs 0%; p < 0.001, chi-square test). Patients with tumors between > 2.5 and 3 cm in initial size went on to develop new or worsened symptoms 17% of the time.

Conclusions. This systematic review of the literature regarding the clinical behavior of untreated meningiomas suggests that most meningiomas ≤ 2.5 cm in diameter do not proceed to cause symptoms in the approximately 5-year period following their discovery. Those that do cause symptoms can usually be predicted with close radiographic follow-up. Based on these findings, the authors suggest the importance of observation in the early course of treatment for small asymptomatic meningiomas, especially those with an initial diameter < 2 cm.

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Trigeminal schwannomas: experience with 57 cases and a review of the literature

Neurosurg Rev. DOI 10.1007/s10143-010-0289-y

Trigeminal schwannoma is a mostly benign tumor that can be cured by complete resection. Over the last few decades, several pioneers have developed surgical approaches enabling the total removal of such tumors.

We analyzed 57 patients who underwent radical surgery, including 45 patients who underwent skull base surgery as their initial treatment, for removal of trigeminal schwannomas. Here, we report the surgical management of these cases. Since 1990, all such patients have been treated using three main types of middle fossa skull base approaches, which minimize the exposure of the brain: the anterior transpetrosal approach, subtemporal interdural approach (Dolenc), or a combination of these approaches.

Before 1990, total tumor removal was achieved in only three of eight patients (38%). After 1990, the tumors were totally removed in 43 patients (90%) and were nearly completely removed in an additional three patients (6%). Among the patients who underwent skull base surgery as their initial treatment, a complete resection was achieved in 93% (42/45 patients) of the cases. However, total surgical removal after surgery and Gamma knife surgery was very difficult because of dense adhesions to the brain stem and cranial nerves. No surgery-related mortalities occurred in this series, and the individual KPS scores were more than 90% among the patients who underwent skull base surgery. No recurrences requiring additional surgery have occurred after an average follow-up period of 4.9 years.

Most of the trigeminal schwannomas could be removed totally and safely during a single operation after the introduction of skull base surgery. Therefore, radiosurgery should not be applied as the treatment of first choice for younger patients. A correct anatomical knowledge is critical for minimizing brain exposure and avoiding surgical complications.

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Clival chordomas: clinical management, results, and complications in 71 patients

J Neurosurg 113:1059–1071, 2010. DOI: 10.3171/2009.9.JNS08596

Chordomas are rare malignant neoplasms arising predominantly at the sacrum and skull base. They are uniformly lethal unless treated with aggressive resection and proton beam irradiation. The authors present results of the surgical management of a large number of patients with clivus chordomas. Factors that influence the surgeon’s ability to achieve radical tumor resection are also evaluated.

Methods. Between 1991 and 2005, 71 patients with clivus chordomas underwent surgery. The average followup was 66 months (median 60 months, range 3–189 months). Sixty-five patients had complete records that were analyzed in the present report. Thirty-five percent of them had undergone surgery before being treated by the authors. They were evaluated with MR imaging and CT scanning and underwent surgery utilizing a variety of skull base techniques aimed at achieving radical excision. Many also underwent postoperative radiation, usually in the form of proton beam therapy. The patients were followed up with serial imaging at regular intervals as well as with neurological evaluation.

Results. Radical tumor resection was achieved in 58% of the group. The overall 5-year survival rate was 75%. Radical resection had a positive impact on survival. The ability to achieve radical resection was dependent on the preoperative tumor volume and the number of anatomical areas involved by the tumor. Cranial nerve impairment and CSF leakage were the most frequent postoperative complications.

Conclusions. Radical excision is the ideal surgical goal in the treatment of clival chordomas and can be achieved with reasonable risks. Several different surgical approaches may be necessary to accomplish this.

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Surgical management of giant pediatric craniopharyngiomas

J Neurosurg Pediatrics 6:000–000, 2010.DOI: 10.3171/2010.8.PEDS09385

Prior work by the authors’ group and reports of other authors suggest worse functional outcomes and decreased survival in children with larger craniopharyngiomas. The purpose of this study was to assess the oncological, endocrinological, and functional outcomes in children who underwent radical resection of giant craniopharyngiomas (defined as 5 cm or greater in largest diameter).

Methods. Between 1986 and 2006, 26 children under the age of 18 (14 boys, 12 girls; mean age 10.5 years) underwent radical resection of giant craniopharyngiomas performed by the senior author. Data were retrospectively collected to assess the outcome of surgical treatment.

Results. Twenty (77%) of 26 patients underwent gross-total resection (GTR) confirmed by intraoperative inspection and postoperative imaging. All primary tumors (17 of 17) and 3 (33%) of 9 recurrent tumors were treated with GTR. There was no operative mortality, and 18 of 26 patients (69%) were alive at a mean follow-up of 8.9 years (median 9.3 years). Disease control was achieved in 21 (84%) of the 25 patients followed up for more than 6 months and was more successful in patients who underwent GTR (95%) than in those who underwent STR (50%, p = 0.03). New-onset diabetes insipidus (DI) occurred in 63.2% of patients (73% of patients had DI postoperatively). New or worsened deficits in visual acuity and visual fields occurred in 16% and 28%, respectively, of the 25 patients for whom postoperative visual data were available. Five patients (19%) experienced significant, permanent neurological deficits, and 5 (19%) had mild to moderate deficits. New or worsened hypothalamic disturbance occurred in 35% and 22% of patients, respectively, but obesity developed in only 15%.

Conclusions. In this retrospective series, radical resection of giant craniopharyngiomas in children was found to lead to excellent rates of disease control with acceptable or good functional outcomes but slightly higher rates of neurological complications compared with rates in patients with smaller tumors. Radical resection is less successful in recurrent tumors that reach very large sizes, especially previously irradiated tumors, with resultant diminished survival.

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Trigeminal neurinomas with extracranial extension: analysis of 28 surgically treated cases

J Neurosurg 113:1079–1084, 2010.DOI: 10.3171/2009.10.JNS091149

The object of this paper was to review the authors’ experience with 28 cases of trigeminal neurinomas having an extracranial extension.

Methods. The authors analyzed 28 cases of trigeminal neurinoma in which there was an extracranial extension of the tumor. All patients were treated in their department between the years 1989 and 2009.

Results. There was tumor extension along the ophthalmic division of the nerve in 4 cases, along the maxillary division in 5, and along the mandibular division in 13. In 6 tumors there was diffuse extracranial extension and the exact extracranial division of nerve involvement could not be ascertained. In 10 cases, the tumor had a multicompartmental location—in the posterior fossa, the middle fossa, and the extracranial compartment. Tingling paraesthesiae, numbness, and diffuse pain in the distribution of the trigeminal nerve were common symptoms and were present in 90% of patients. The extracranial component had a well-defined perineural/meningeal membrane cover that was continuous with the middle fossa dura mater and isolated the tumor tissue from the adjoining critical structures. In 7 out of 10 cases, even the posterior fossa component of the tumor was entirely “interdural” (within the confines of the dura). The maximum dimension of the tumor was > 4 cm in 22 cases. A limited “transcranial” approach with (12 cases) or without (16 cases) zygomatic osteotomy was found suitable for resection of these tumors. In 4 cases a lateral orbitotomy was performed. Total tumor resection was performed in 20 cases and partial resection in 8. The duration of follow-up ranged from 6 months to 19 years. Two patients required additional surgery for symptomatic recurrence.

Conclusions. Extracranial extensions of trigeminal neurinomas have a well-defined meningeal covering. In most cases resection was performed via a minimally invasive cranial avenue (a “reverse skull base approach”). Radical resection was associated with an excellent long-term outcome.

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Utility of diffusion tensor-imaged (DTI) motor fiber tracking for the resection of intracranial tumors near the corticospinal tract

Acta Neurochir. DOI 10.1007/s00701-010-0817-0

Treatment of intracranial tumors near the corticospinal tract remains a surgical challenge. Several technical tools to map and monitor the motor tract have been implemented. The present study aimed to assess the utility of diffusion tensor imaging (DTI) fiber tracking in the surgical treatment of motor eloquent tumors at our institution.

Methods Patients operated for intracranial tumors close to the motor tract with the use of intraoperative image guidance including DTI fiber tracking of the corticospinal tract and intraoperative motor evoked potential (MEP) monitoring were analyzed. The intraoperative utility of fiber tracking data was analyzed. Furthermore, preoperative MRI scans with and without motor fiber tracking were reevaluated post hoc for tumor relation to the motor tract, estimated resectability, and best approach. Thereby, the utility of fiber tracking in surgical planning was assessed.

Results Nineteen patients were analyzed. The estimation of tumor localization in relation to the motor tract and of resectability was not influenced by fiber tracking in any of the cases. Only in one single case did evaluating surgeons change their surgical approach after the addition of the fiber tracking data. In all cases, fiber tracking included in image guidance did not change the intraoperative strategy, while MEP monitoring did.

Conclusions DTI fiber tracking did not influence the surgical planning or the intraoperative course. However, it is still used at our institution due to its ease in acquisition and its potential impact in a larger series. Furthermore, more experience with this technique is required to lead to a technical improvement.

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Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival

J Neurooncol. DOI 10.1007/s11060-010-0429-9

According to recent developments the best treatment options for glioblastoma (GBM) consist in maximum safe resection and additional adjuvant treatment with radiotherapy (RT) and alkylating chemotherapy (CHX).

These options have been evaluated for populations with a median age of approximately 58 years. We therefore addressed the issue of whether elderly patients ([65years) could also benefit from cytoreductive surgery (CS) and adjuvant treatment using alkylating chemotherapy.

Onehundred and three patients suffering from newly diagnosed, primary supratentorial glioblastoma multiforme[65 years (median 70.8 years) were identified in our single-center glioma database (2002–2007) and retrospectively divided into group A (n = 31) treated with surgery alone (biopsy, BY, n = 21, CS n = 10), group B (n = 37) surgery plus radiation (BY n = 18, CS n = 19), and group C (n = 35) surgery, RT and CHX (BY n = 4, CS n = 31). Progression- free survival (PFS) and overall survival (OAS) were determined in each group and correlated to age, Karnofsky performance score (KPS), and extent of resection (biopsy (BY), partial (PR), and complete resection (CR)). Progression was defined according the Macdonald criteria. For all patients PFS and OAS were 3.2 months and 5.1 months (m) respectively. PFS and OAS for groups A/B/C were 1.8/ 3.2/6.4 m (P = 0.000) and 2.2/4.4/15.0 m (P = 0.000), respectively. Median age for groups A/B/C was 74.4/70.6/ 68.5 years and median KPS was 60/70/80. Age (\75, C75) was inversely correlated with OAS (5.8/2.5 m, P = 0.01). KPS (\70, C70) was correlated with OAS 2.4/6.5 m (P = 0.000). Extent of resection (BY, PR, or CR) correlated with PFS (2.1/3.4/6.4 m, P = 0,000) and OS (2.2/7.0/ 13.9 m, P = 0,000), respectively.

Our study shows that elderly GBM patients can benefit from maximum treatment procedures with cytoreductive microsurgery, radiation therapy, and chemotherapy. Treatment options are obviously affected by KPS and age. The most impressive outcome predictor in this population was the extent of microsurgical resection for patients treated with adjuvant radiotherapy and chemotherapy. To conclude, elderly GBM patients should not be per se excluded from intensive treatment procedures.

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Brain surface motion imaging to predict adhesions between meningiomas and the brain surface

Neuroradiology (2010) 52:1003–1010. DOI 10.1007/s00234-010-0671-z

“Brain surface motion imaging” (BSMI) is the subtraction of pulse-gated, 3D, heavily T2-weighted image of two different phases of cerebrospinal fluid (CSF) pulsation, which enables the assessment of the dynamics of brain surface pulsatile motion. The purpose of this study was to evaluate the feasibility of this imaging method for providing presurgical information about adhesions between meningiomas and the brain surface.

Methods Eighteen cases with surgically resected meningioma in whom BSMI was presurgically obtained were studied. BSMI consisted of two sets of pulse-gated, 3D, heavily T2-weighted, fast spin echo scans. Images of the systolic phase and the diastolic phase were obtained, and subtraction was performed with 3D motion correction. We analyzed the presence of band-like texture surrounding the tumor and judged the degree of motion discrepancy as “total,” “partial,” or “none.” The correlation between BSMI and surgical findings was evaluated. For cases with partial adhesions, agreements in the locations of the adhesions were also evaluated.

Results On presurgical BSMI, no motion discrepancy was seen in eight cases, partial in six cases, and total in four cases. These presurgical predictions about adhesions and surgical findings agreed in 13 cases (72.2%). The locations of adhesions agreed in five of six cases with partial adhesions.

Conclusion In the current study, BSMI could predict brain and meningioma adhesions correctly in 72.2% of cases, and adhesion location could also be predicted. This imaging method appears to provide presurgical information about brain/meningioma adhesions.

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Intraoperative 5-aminolevulinic-acid-induced fluorescence in meningiomas

Acta Neurochir (2010) 152:1711–1719. DOI 10.1007/s00701-010-0708-4

5-aminolevulinic acid (5-ALA) has gained importance as an intraoperative photodynamic diagnostic agent for the extirpation of malignant gliomas. The application of this technique for resection of meningiomas has barely been explored. The aim of this study was to evaluate the utility of 5-ALA-induced fluorescence as a visual tool in meningioma resection and its correlation with histological findings.

Methods A total of 33 consecutive patients undergoing resection of intracranial meningiomas from December 2007 to August 2009 were included in this study. After confirmation of normal liver function, 5-ALA was administered orally (20 mg/kg) within 3–5 h prior to skin incision. All cases were operated on using standard microsurgical and neuronavigation-guided techniques. Intraoperative 440 nm fluorescence was applied periodically during and at the end of resection in order to detect tumor-infiltrated sites. The fluorescence of the tumor was evaluated intraoperatively by the surgeon and confirmed by subsequent video analysis.

Results A total of 32 (97%) patients presented with benign meningiomas (WHO I–II). In 1 (3%) patient, histological anaplastic signs (WHO III) could be demonstrated. 5-ALAinduced fluorescence of the tumor was confirmed in a total of 31 (94%) patients. The fluorescence did not correlate with the histological findings (n=30 WHO I–II, n=1 WHO grade III) or with preoperative brain edema and administration of steroids. A total resection could be postoperatively demonstrated in 25 (76%) patients. No adverse effects attributable to 5-ALA occurred.

Conclusions 5-ALA-induced fluorescence is a useful and promising intraoperative tool for the visualization of meningioma tissue. The novel findings demonstrated in this study in terms of high fluorescence and poor correlation with histological findings highlight the usefulness of this technique as a routine visual tool to achieve optimal resection of meningiomas.

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First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience

Neurosurg Rev (2010) 33:441–449. DOI 10.1007/s10143-010-0280-7

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity.

We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m2/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59±10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity.

Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments.

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Postauricular, transpetrous, presigmoid approach for extensive skull base tumors in the petroclival region: the successes and the travails

Acta Neurochir (2010) 152:1633–1645.DOI 10.1007/s00701-010-0701-y

Postauricular, transpetrous, presigmoid approach combines a supra/infratentorial exposure with partial petrosectomy to access third to the twelfth cranial nerves and extraaxial lesions situated anterolateral to brainstem. It provides a shorter working distance to large petrosal, petroclival, cerebellopontine, and cerebellomedullary cisternal lesions and their extensions to the subtemporal–infratemporal areas. This study reviews the surgical technique, corridors of extension, and complications encountered utilizing this approach for excising extensive lesions in these locations.

Methods The lesions (n=14) included petroclival meningiomas [(n=5), including three recurrent lesions], dumbbell lower cranial nerve schwannomas (n=2), giant acoustic schwannomas (n=2), recurrent giant trigeminal nerve schwannoma (n=1), glomus jugulare (n=3), and recurrent petrous aneurysmal bone cyst (n=1). The approach was combined with a retrosigmoid suboccipital craniectomy (n=3), with an infratemporal approach (n=2), and with an extreme lateral transcondylar approach and a translabyrinthine approach in one patient each, respectively. External auditory canal was not ligated in nine patients, superior petrosal sinus and tentorial division was performed in all patients, and sigmoid sinus–internal jugular vein was excised in three patients (with a glomus jugulare (n=1) and petroclival meningioma (n=2), respectively). Repair was performed with fat–fascia, pedicled pericranium, and temporalis muscle. Lumbar drain was placed for three to five postoperative days.

Results Total excision was performed in nine patients. Small tumor remnants were left attached to the brainstem (n=3, petroclival meningioma), carotid canal and cavernous sinus (n=1, glomus jugulare), and sigmoid sinus–jugular bulb (n=1, recurrent trigeminal schwannoma). A two-staged procedure was performed in three patients. Two patients with recurrent giant petroclival meningiomas died: one with lower cranial nerve paresis due to aspiration pneumonitis and the other with cerebrospinal fluid otorrhoea and secondary meningitis.

Conclusions The approach facilitates direct tumor decompression and its retraction away from the brainstem without initially encountering the intracisternal cranial nerves and neuraxis. It provides multiple corridors for excising extensive posterior fossa tumors. Preoperative assessment of sigmoid sinus dominance, jugular bulb height, labyrinth, vein of Labbe, and space available through Trautman’s triangle considerably helps in complication avoidance.

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Prognostic factors for long-term outcome of patients with surgical resection of skull base chordomas—106 cases review in one institution

Neurosurg Rev (2010) 33:451–456. DOI 10.1007/s10143-010-0273-6

Skull base chordoma are still challenging. Between May 1993 and June 2005, 106 consecutive patients with skull base chordoma underwent surgical removal at Skull Base Division of Neurosurgery, Beijing Tiantan Hospital, China. Retrospective analysis included medical charts and images.

The age of the patients ranged from 7 to 65 years old, with an average age of 35.6 years. Sixty patients were male; the other 46 were female (1.3:1). Follow up data were available in 79 cases ranging from 10 to 158 months (average 63.9 months) after operation.

The prognostic factors for recurrence and survival were analyzed with Kaplan‐Meier, Cox regression and t‐test. Overall, 1, 3, 5 and 10 years survival rates were 87.2%, 79.4%, 67.6% and 59.5% respectively. One, 3, 5 and 10 year recurrent rates were 19.1%, 34.7%, 52.9% and 88.3%, respectively.

The long term outcome of the skull base chordomas is poor. The previous radiotherapy or surgery, dedifferentiated pathology, and less tumor resection are risk factors for longterm survival and recurrence (p<0.05). Although there is no statistic significant role of tumor adherent to vital structure for outcome (p=0.051), it can not exclude its importance for favorable outcome.

Gender, age, tumor size and staging are not independent risk factors for outcome. Surgical technique leading to radical tumor resection with less morbidity is advocatory and beneficial for patients with skull base chordoma with long term outcome, if the tumor could be exposed and resected completely, the recurrence rate was very low for most benign chordomas.

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Perioperative and Long-term Outcomes From the Management of Parasagittal Meningiomas Invading the Superior Sagittal Sinus

Neurosurgery 67:885–893, 2010 DOI: 10.1227/NEU.0b013e3181ef2a18

Parasagittal meningiomas invading the superior sagittal sinus (SSS) pose formidable obstacles to surgical management. Invasion is often considered a contraindication to surgery because of associated morbidity, such as cerebral venous thrombosis.

OBJECTIVE: We report our most recent experience with the resection of parasagittal meningiomas invading the SSS.

METHODS: Between 1992 and 2004, 110 patients with parasagittal meningiomas underwent surgery at the Johns Hopkins Medical Institutions. Clinical charts, radiological studies, pathological features, and operative notes were retrospectively analyzed; only those patients with minimum 24 months follow-up (n = 61) were further studied.

RESULTS: Tumor distribution by location along the SSS was: 21% anterior, 62% middle, and 17% posterior. All patients were managed with initial surgical resection with radiosurgery for residual/recurrent disease if indicated (19.6%). Pathological examination revealed 80% grade I meningiomas, 13% grade II meningiomas, and 7% grade III meningiomas. Simpson grade I/II resection was achieved in 81% of patients. Major complications included venous thrombosis/infarction (7%), intraoperative air embolism (1.5%), and death (1.5%); long-term outcomes assessed included recurrence (11%) and improvement in Karnofsky Performance Score (85%).

CONCLUSION: On the basis of our study, the incidence of postoperative venous sinus thrombosis is 7% in the setting of a recurrence rate of 11% with a mean follow-up of 41 months. In comparison with the published literature, the data corroborate the rationale for our treatment paradigm; lesions invading the sinus can initially be resected to the greatest extent possible without excessive manipulation of vascular structures, whereas residual/recurrent disease can be observed and managed with radiosurgery.

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Diffusion tensor imaging tractography in patients with intramedullary tumors: comparison with intraoperative findings and value for prediction of tumor resectability

J Neurosurg Spine 13:371–380, 2010. DOI: 10.3171/2010.3.SPINE09399

The aim of this retrospective study was to evaluate the predictive value of diffusion tensor (DT) imaging with respect to resectability of intramedullary spinal cord tumors and to determine the concordance of this method with intraoperative surgical findings.

Methods. Diffusion tensor imaging was performed in 14 patients with intramedullary lesions of the spinal cord at different levels using a 3-T magnet. Routine MR imaging scans were also obtained, including unenhanced and enhanced T1-weighted images and T2-weighted images. Patients were classified according to the fiber course with respect to the lesion and their lesions were rated as resectable or nonresectable. These results were compared with the surgical findings (existence vs absence of cleavage plane). The interrater reliability was calculated using the κ coefficient of Cohen.

Results. Of the 14 patients (7 male, 7 female; mean age 49.2 ± 15.5 years), 13 had tumors (8 ependymomas, 2 lymphomas, and 3 astrocytoma). One lesion was proven to be a multiple sclerosis plaque during further diagnostic workup. The lesions could be classified into 3 types according to the fiber course. In Type 1 (5 cases) fibers did not pass through the solid lesion. In Type 2 (3 cases) some fibers crossed the lesion, but most of the lesion volume did not contain fibers. In Type 3 (6 cases) the fibers were completely encased by tumor. Based on these results, 6 tumors were considered resectable, 7 were not. During surgery, 7 tumors showed a good cleavage plane, 6 did not. The interrater reliability (Cohen κ) was calculated as 0.83 (p < 0.003), which is considered to represent substantial agreement. The mean duration of follow-up was 12.0 ± 2.9. The median McCormick grade at the end of follow-up was II.

Conclusions. These preliminary data suggest that DT imaging in patients with spinal cord tumors is capable of predicting the resectability of the lesion. A further prospective study is needed to confirm these results and any effect on patient outcome.

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Image-guided frameless stereotactic biopsy without intraoperative neuropathological examination. Clinical article

Journal of Neurosurgery, August 2010 Volume 113, Number 2
DOI: 10.3171/2009.12.JNS09573
Stereotactic biopsy is a safe and effective technique for the diagnosis of brain tumors. The use of intraoperative neuropathological examination has been routinely advocated to increase diagnostic yield, but the procedure lengthens surgical time, may produce false-negative and -positive results, and current biopsy techniques have a very low nondiagnostic rate. Therefore, the authors questioned the need for intraoperative histological evaluation.
Methods
The authors prospectively studied all patients undergoing image-guided biopsy under the care of a single surgeon (P.L.G.) between July 2005 and October 2007. A Stryker neuronavigation system with a trajectory guide was used to plan a single trajectory, and, using a side-cutting biopsy cannula, multiple biopsy samples were taken from between 1 and 4 sites within the tumor. Tissue was inspected macroscopically by the surgeon and was only submitted for neuropathological assessment postoperatively.
Results
One hundred thirty-four biopsies were performed during the study. A positive diagnosis was established in 133 cases (99.3%). One biopsy was negative (0.7%) and postoperative imaging (performed because the tissue was macroscopically normal) demonstrated inaccurate targeting of the lesion. Significant complications were seen in 3 patients (2.2%) who all had preoperative WHO performance scores of III or IV. Two patients suffered delayed deterioration and died due to probable surgical complications—one with thalamic glioblastoma multiforme (GBM) and one with gliomatosis cerebri. One patient with GBM suffered an intracerebral hematoma that was managed conservatively. Postoperative seizures were seen in 4 patients (3%), and 2 patients (1.5%) experienced a transient neurological deficit. Histological diagnosis showed a GBM in 64 cases, Grade III glioma in 19, Grade I or II in 23, metastasis in 10, lymphoma in 13, and other disease in 4. There were 32 patients discharged to home on the same day as surgery. Compared with the authors’ previous retrospective audit into 127 biopsies, this technique showed improved diagnostic yield (99.3 vs 94.5%, p = 0.032) with fewer complications (2.2 vs 4.7% [not statistically significant]).
Conclusions
This technique of image-guided biopsy has high diagnostic yield with acceptably low morbidity and may be performed as a day case. Intraoperative neuropathological examination would not have increased the diagnostic yield further in this study, and its routine use may not be necessary. In the authors’ department £70,350 (UK)/$114,522 (US) would have been saved by not using intraoperative neuropathology in this series. Therefore, intraoperative neuropathology should no longer be routinely recommended.

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Functional Magnetic Resonance Imaging and Diffusion Tensor Tractography Incorporated Into an Intraoperative 3-Dimensional Ultrasound-Based Neuronavigation System: Impact on Therapeutic Strategies, Extent of Resection, and Clinical Outcome

Neurosurgery 67:251-264, 2010 DOI: 10.1227/01.NEU.0000371731.20246.AC

Functional neuronavigation with intraoperative 3-dimensional (3D) ultrasound may facilitate safer brain lesion resections than conventional neuronavigation.

OBJECTIVE: In this study, functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTT) were used to map eloquent areas. We assessed the use of fMRI and DTT for preoperative assessments and determined whether using these data together with 3D ultrasound during surgery enabled safer lesion resection.

METHODS:We reviewed 51 consecutive patients with intracranial lesions in whom fMRI with or without DTT was used to map eloquent areas. To assess a possible impact of fMRI/DTT, we reviewed and analyzed the quality of the fMRI/DTT data, any change in therapeutic strategies, lesion to eloquent area distance (LEAD), extent of resection, and clinical outcome.

RESULTS: As a result of the fMRI/DTT mapping, the therapeutic strategies were changed in 4 patients. The median tumor residue for glioma patients was 11% (n = 33) and 0% for nonglioma lesions (n = 12). For gliomas, there was a significant correlation between decreasing LEAD and increasing tumor residue. Of the glioma patients, 42% underwent gross total resection (≥ 95%) and 12% suffered neurological worsening after surgery as a result of complications. Of glioma patients with an LEAD of ≤ 5 mm, 24% underwent gross total resection and 10% experienced neurological deterioration.

CONCLUSION: This study demonstrates that preoperative fMRI and DTT had direct consequences for therapeutic strategies and indicates their impact on intraoperative strategies to spare eloquent cortex and tracts. Functional neuronavigation combined with intraoperative 3D ultrasound can, in most patients, enable resection of brain lesions with general anesthesia without jeopardizing neurological function.

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Trigonal and peritrigonal lesions of the lateral ventricle—surgical considerations and outcome analysis of 20 patients

Neurosurg Rev DOI 10.1007/s10143-010-0271-8

The aim of this study is to review the results and clinical outcome of patients with surgically treated lesions within the trigone of the lateral ventricle.

This is a retrospective case series of 20 (eight male, 12 female) patients with lesions of the trigone of the lateral ventricle operated between 1998 and 2008. All lesions were removed via the transcortical temporal and transcortical parietal route. Surgical complications and outcome were assessed using the modified Rankin Scale (mRS).

There were four children and 16 adults with a mean age of 42±22 years (min=1, max=74). Eight (40%) lesions grew within the trigone of the dominant hemisphere. In 17 cases, the lesion was purely intraventricular, and in three cases, a slight paraventricular extension was seen. The mean size was 4.5 cm of maximal diameter. Surgical removal was achieved via the transcortical parietal route in 13 cases (65%) and the transcortical temporal route in seven cases (35%). In all cases, complete resection was possible. According to the mRS, 13 patients improved, five remained the same, and two were lost to follow-up. One patient had an increased visual field deficit postoperatively and new hemiparesis and aphasia, but returned to the preoperative level within a few weeks. In one patient, an acute myocardial infarction occurred due to previous cardiac stent placement and instent stenosis.

Even large trigonal lesions can be resected with low morbidity using a transcortical approach depending on the peritrigonal extension of the tumor.

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First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience

Neurosurg Rev DOI 10.1007/s10143-010-0280-7

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m2/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59±10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments.

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Management of Anterolateral Foramen Magnum Meningiomas: Surgical Vs Conservative Decision Making

Neurosurgery 67[ONS Suppl 1]:ons00-ons00, 2010. DOI: 10.1227/01.NEU.0000382971.63877.DD

Anterolateral meningiomas of the foramen magnum (FMMs) represent a neurosurgical challenge because they grow in close contact with osteoarticular, nervous, and vascular structures that cannot be sacrificed or retracted. OBJECTIVE: To evaluate our strategy and results in 26 patients with FMMs and analyze factors affecting the decision-making process, resection, and outcome. METHODS: Among 26 consecutive symptomatic FMM (10 anterior, 16 lateral) patients (16 women, 10 men, ages 28-82 years), 4 older than 70 years of age were untreated. Twentytwo were operated on using a posterolateral approach, with the vertebral artery transposed in 19 and the occipital condyle drilled in 10. We analyzed the characteristics and outcome of untreated cases, the utility of THE occipital condyle drilled, the difficulties of microdissection, morbidity and total removal rates, the outcome of tumor residues, and the literature on radiosurgery. RESULTS: Three of 4 untreated patients remained clinically stable at 2 to 5 years. After systematic vertebral artery medial transposition and occipital condyle drilled in 6 cases, our technique evolved with experience in the next 16 (vertebral artery transposed in 13 of 16; occipital condyle drilled in 4 of 13) for dissecting anteriorly beyond midline (anterior FMMs). Retrocondylar access was sufficient for lateral FMMs. Tumors were totally removed in 16 of 22 (73%). One patient died, and 4 had permanent deficits. Follow-up of more than 5 years in 12 patients showed no C0-1 instability, and slight increase of tumor residue size 7 years after surgery. In the literature, 15 FMMs treated with radiosurgery are reported, 13 at diagnosis and 2 at recurrence, with short-term clinical and radiological safety and efficacy. CONCLUSION:We currently recommend (1) aiming for subtotal removal in difficult cases, (2) remaining conservative in asymptomatic or elderly patients with mild symptoms, and (3) considering radiosurgery at diagnosis for small (<30 mm) symptomatic FMMs or as an adjunct for evolving residues/recurrences in poor candidates for resection.

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Resection of malignant brain tumors in eloquent cortical areas: a new multimodal approach combining 5-aminolevulinic acid and intraoperative monitoring

J Neurosurg 113:352–357, 2010.DOI: 10.3171/2009.10.JNS09447

Object. Several studies have revealed that the gross-total resection (GTR) of malignant brain tumors has a significant influence on patient survival. Frequently, however, GTR cannot be achieved because the borders between healthy brain and diseased tissue are blurred in the infiltration zones of malignant brain tumors. Especially in eloquent cortical areas, resection is frequently stopped before total removal is achieved to avoid causing neurological deficits. Interestingly, 5-aminolevulinic acid (5-ALA) has been shown to help visualize tumor tissue intraoperatively and, thus, can significantly improve the possibility of achieving GTR of primary malignant brain tumors. The aim of this study was to go one step further and evaluate the utility and limitations of fluorescence-guided resections of primary malignant brain tumors in eloquent cortical areas in combination with intraoperative monitoring based on multimodal functional imaging data. Methods. Eighteen patients with primary malignant brain tumors in eloquent areas were included in this prospective study. Preoperative neuroradiological examinations included MR imaging with magnetization-prepared rapid gradient echo (MPRAGE), functional MR, and diffusion tensor imaging sequences to visualize functional areas and fiber tracts. Imaging data were analyzed offline, loaded into a neuronavigational system, and used intraoperatively during resections. All patients received 5-ALA 6 hours before surgery. Fluorescence-guided tumor resections were combined with intraoperative monitoring and cortical as well as subcortical stimulation to localize functional areas and fiber tracts during surgery. Results. Twenty-five procedures were performed in 18 consecutive patients. In 24% of all surgeries, resection was stopped because a functional area or cortical tract was identified in the resection area or because motor evoked potential amplitudes were reduced in an area where fluorescent tumor cells were still seen intraoperatively. Grosstotal resection could be achieved in 16 (64%) of the surgeries with preservation of all functional areas and fiber tracts. In 2 patients presurgical hemiparesis became accentuated postoperatively, and 1 of these patients also suffered from a new homonymous hemianopia following a second resection. Conclusions. The authors’ first results show that tumor resections with 5-ALA in combination with intraoperative cortical stimulation have the advantages of both methods and, thus, provide additional safety for the neurosurgeon during resections of primary malignant brain tumors in eloquent areas. Nonetheless, more cases and additional studies are necessary to further prove the advantages of this multimodal strategy.

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