Category: Oncology

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Infundibulo-tuberal or not strictly intraventricular craniopharyngioma: evidence for a major topographical category

Acta Neurochir (2011) 153:2403–2426. DOI 10.1007/s00701-011-1149-4

This study investigates retrospectively the clinical, neuroradiological, pathological and surgical evidence verifying the infundibulo-tuberal topography for craniopharyngiomas (CPs). Infundibulo-tuberal CPs represent a surgical challenge due to their close anatomical relationships with the hypothalamus. An accurate definition of this topographical category is essential in order to prevent any undue injury to vital diencephalic centres.

Methods A systematic review of all scientific reports involving pathological, neuroradiological or surgical descriptions of either well-described individual cases or large series of CPs published in official journals and text books from 1892 to 2011 was carried out. A total of 1,232 documents providing pathological, surgical and/or neuroradiological evidence for the infundibulo-tuberal or hypothalamic location of CPs were finally analysed in this study.

Findings For a total of 3,571 CPs included in 67 pathological, surgical or neuroradiological series, 1,494 CPs (42%) were classified as infundibulo-tuberal lesions. This topography was proved in the autopsy of 122 nonoperated cases. The crucial morphological finding characterizing the tubero-infundibular topography was the replacement of the third ventricle floor by a lesion with a predominant intraventricular growth. This type of CP usually presents a circumferential band of tight adherence to the third ventricle floor remnants, formed by a functionless layer of rective gliosis of a variable thickness. After complete surgical removal of an infundibulo-tuberal CP, a wide defect or breach at the floor of the third ventricle is regularly observed both in the surgical field and on postoperative magnetic resonance imaging studies.

Conclusions Infundibulo-tuberal CPs represent a major topographical category of lesions with a primary subpial development at the floor of the third ventricle. These lesions expand within the hypothalamus itself and subsequently occupy the third ventricle; consequently, they can be classified as not strictly intraventricular CPs. A tight attachment to the hypothalamus and remnants of the third ventricle floor is the pathological landmark of infundibulotuberal CPs.

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

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

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

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

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

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

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

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Diffusion tensor imaging–based fiber tracking for prediction of the position of the facial nerve in relation to large vestibular schwannomas

J Neurosurg 115:1087–1093, 2011. DOI: 10.3171/2011.7.JNS11495

The reliable preoperative visualization of facial nerve location in relation to vestibular schwannoma (VS) would allow surgeons to plan tumor removal accordingly and may increase the safety of surgery. In this prospective study, the authors attempted to validate the reliability of facial nerve diffusion tensor (DT) imaging–based fiber tracking in a series of patients with large VSs. Furthermore, the authors evaluated the potential of this visualization technique to predict the morphological shape of the facial nerve (tumor compression–related flattening of the nerve).

Methods. Diffusion tensor imaging and anatomical images (constructive interference in steady state) were acquired in a series of 22 consecutive patients with large VSs and postprocessed with navigational software to obtain facial nerve fiber tracking. The location of the cerebellopontine angle (CPA) part of the nerve in relation to the tumor was recorded during surgery by the surgeon, who was blinded to the results of the fiber tracking. A correlative analysis was performed of the imaging-based location of the nerve compared with its in situ position in relation to the VS.

Results. Fibers corresponding to the anatomical location and course of the facial nerve from the brainstem to the internal auditory meatus were identified with the DT imaging–based fiber tracking technique in all 22 cases. The location of the CPA segment of the facial nerve in relation to the VS determined during surgery corresponded to the location of the fibers, predicted by the DT imaging–based fiber tracking, in 20 (90.9%) of the 22 patients. No DT imaging–based fiber tracking correlates were found with the 2 morphological types of the nerve (compact or flat).

Conclusions. The current study of patients with large VSs has shown that the position of the facial nerve in relation to the tumor can be predicted reliably (in 91%) using DT imaging–based fiber tracking. These are preliminary results that need further verification in a larger series.

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Primary Vertebral Tumors: A Review of Epidemiologic, Histological, and Imaging Findings, Part I: Benign Tumors

Neurosurgery 69:1171–1180, 2011 DOI: 10.1227/NEU.0b013e31822b8107

Primary vertebral tumors, although less common than metastases to the spine, make up a heterogeneous group of neoplasms that can pose diagnostic and treatment challenges. They affect both the adult and the pediatric population and may be benign, locally aggressive, or malignant.

An understanding of typical imaging findings will aid in accurate diagnosis and help neurosurgeons appreciate anatomic subtleties that may increase their effective resection. An understanding of the histological similarities and differences between these tumors is imperative for all members of the clinical team caring for these patients. In this first review of 2 parts, we discuss the epidemiological, histological, and imaging features of the most common benign primary vertebral tumors— aneurysmal bone cyst, chondroma and enchondroma, hemangioma, osteoid osteoma, and osteoblastoma—and lesions related to eosinophilic granuloma and fibrous dysplasia.

In addition, we discuss the basic management paradigms for each of these diagnoses. In combination with part II of the review, which focuses on locally aggressive and malignant tumors, this article provides a comprehensive review of primary vertebral tumors

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Microsurgical Management of Hypoglossal Schwannomas Over 3 Decades: A Modified Grading Scale to Guide Surgical Approach

Neurosurgery 69[ONS Suppl 2]:ons121–ons140, 2011. DOI: 10.1227/NEU.0b013e31822a547b

Schwannomas originating from the hypoglossal nerve are extremely rare. Microsurgical resection with the goal for cure has traditionally been associated with a high risk of postoperative deficits.

OBJECTIVE: To summarize our clinical experience using tailored cranial base approaches for these formidable lesions.

METHODS: The clinical records of 13 patients were retrospectively reviewed. In addition, all reported patients in the literature were reviewed. The extreme lateral infrajugular transcondylar-transtubercular exposure approach was used in all of our patients. Based on our experience and literature analysis, we propose the following modified grading scale to facilitate surgical planning: type A, intradural tumors; type B, dumbbell-shaped tumors; type C, extracranial tumors; and type D, peripheral tumors.

RESULTS: All 13 patients underwent total, near-total, or subtotal tumor resection. Eight patients were men, 5 were women (mean age, 41.7 years). Sural nerve graft reconstruction for the hypoglossal nerve was performed in 4 patients. Three of the 4 patients in whom nerve reconstruction was performed regained satisfactory movement of their tongue. In the review of the literature, the mean patient age was 45.8 years. Patients presented with tongue atrophy (91.6%), headache (60.9%), and dysphagia (31.8%). The tumors were categorized as type A in 31.7% of these patients, type B in 38.6%, type C in 6.2%, and type D in 23.4%.

CONCLUSION: The extreme lateral infrajugular transcondylar-transtubercular exposure approach, which is a modification of the extreme lateral suboccipital approach, provides sufficient exposure for most intracranial dumbbell-shaped hypoglossal schwannomas. Hypoglossal nerve reconstruction using a sural nerve graft improves tongue atrophy and movement for patients with resected nerves.

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Multisession Radiosurgery for Optic Nerve Sheath Meningiomas

Neurosurgery 69:1116–1123, 2011 DOI: 10.1227/NEU.0b013e31822932fe
Traditional treatment options for optic nerve sheath meningiomas (ONSMs) include observation, surgery, and radiotherapy, but to date none of these has become the clear treatment of choice.
OBJECTIVE: To evaluate the effectiveness and safety of multisession radiosurgery for ONSMs.
METHODS: From May 2004 to June 2008, 21 patients with ONSMs were treated by radiosurgery using the frameless CyberKnife system. Patient age ranged from 36 to 73 years (mean, 54 years). All patients were treated using multisession radiosurgery, with 5 fractions of 5 Gy each to a total dose of 25 Gy prescribed to the 75% to 85% isodose line. Patients were evaluated for tumor growth control and visual function.
RESULTS: The median pretreatment tumor volume was 2.8 mL (range, 0.3-23 mL). The mean follow-up was 30 months (range, 11-68 months). All patients tolerated treatment well, with only 1 patient in whom a mild optic neuropathy developed (which remitted after systemic steroid therapy). No other acute or late radiation-induced toxicities were observed. No patients showed ONSM progression on follow-up magnetic resonance imaging. Two patients (10%) had a partial response. No patients had worsening of visual function; visual function was stable in 65% and improved in 35% of patients.
CONCLUSION: Multisession radiosurgery for ONSMs was found to be safe and effective. The preliminary results from this study, in terms of growth control, visual function improvement, and toxicity, are quite promising. Further investigations are warranted.

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The molecular biology and novel treatments of vestibular schwannomas

J Neurosurg 115:906–914, 2011. DOI: 10.3171/2011.6.JNS11131

Vestibular schwannomas are histopathologically benign tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product merlin.

Merlin acts as a tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to vestibular schwannoma development.

Recently, there have been major advances in our knowledge of the molecular biology of vestibular schwannomas as well as the development of novel therapies for its treatment.

In this article the authors comprehensively review the recent advances in the molecular biology and characterization of vestibular schwannomas as well as the development of modern treatments for vestibular schwannoma. For instance, merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently, merlin was also shown to interact in the nucleus with E3 ubiquitin ligase CRL4DCAF1.

A greater understanding of the molecular mechanisms behind vestibular schwannoma tumorigenesis has begun to yield novel therapies. Some authors have shown that Avastin induces regression of progressive schwannomas by over 40% and improves hearing. An inhibitor of VEGF synthesis, PTC299, is currently in Phase II trials as a potential agent to treat vestibular schwannoma.

Furthermore, in vitro studies have shown that trastuzumab (an ERBB2 inhibitor) reduces vestibular schwannoma cell proliferation.

With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing tumor burden, tumor volume, hearing loss, and cranial nerve deficits seen in vestibular schwannomas.

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F-18 FDG PET-CT for predicting survival in patients with recurrent glioma: a prospective study

Neuroradiology (2011) 53:1017–1024. DOI 10.1007/s00234-011-0898-3

Recurrent gliomas are usually histologically high grade; either due to recurrence of a de novo high-grade primary or anaplastic transformation in case of low-grade tumors. Survival in these patients is variable. The objective of the present study is to evaluate the role of FDG PET-CT for predicting survival in a large group of patients with suspected recurrent glioma.

Methods A total of 81 previously treated histopathologically proven glioma patients; with clinical and conventional imaging findings suspicious of recurrence were included in this study. All patients underwent FDG PET-CT study. Based on tumor to white matter (T/W) and tumor to grey matter (T/G) ratios, all lesions were scored on PET-CT (PET scores 0, 1 and 2). Patients were followed up clinically and by repeated imaging. Data was censored, if the patient died of disease or at the end of the study. Survival analysis was done for each variable employing univariate analysis followed by multivariate analysis, using variables found significant on univariate analysis.

Results PET score was found to be the most significant predictor of survival in univariate and multivariate analysis (p 0.003). Patients having PET score 2 had poorer survival compared to both PET score 0 (p 0.001) and PET score 1 (p 0.004). Other covariates found to have significant correlation with survival were primary treatment modality and clinical symptoms at the time of recurrence.

Conclusion FDG uptake on PET-CT is a strong predictor of survival in patients with suspected recurrent glioma.

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Management of large vestibular schwannoma. Part II. Primary Gamma Knife surgery: radiological and clinical aspects

J Neurosurg 115:885–893, 2011.DOI: 10.3171/2011.6.JNS101963

In large vestibular schwannomas (VSs), microsurgery is the main treatment option. A wait-and-scan policy or radiosurgery are generally not recommended given concerns of further lesion growth or increased mass effect due to transient swelling. Note, however, that some patients do not present with symptomatic mass effect or may still have serviceable hearing. Moreover, others may be old, suffer from severe comorbidity, or refuse any surgery. In this study the authors report the results in patients with large, growing VSs primarily treated with Gamma Knife surgery (GKS), with special attention to volumetric growth, control rate, and symptoms.

Methods. The authors retrospectively analyzed 33 consecutive patients who underwent GKS for large, growing VSs, which were defined as > 6 cm3 and at least indenting the brainstem. Patients with neurofibromatosis Type 2 were excluded from analysis, as were patients who had undergone previous treatment. Volume measurements were performed on contrast-enhanced T1-weighted MR images at the time of GKS and during follow-up. Medical charts were analyzed for clinical symptoms.

Results. Radiological growth control was achieved in 88% of cases, clinical control (that is, no need for further treatment) in 79% of cases. The median follow-up was 30 months, and the mean VS volume was 8.8 cm3 (range 6.1–17.7 cm3). No major complications occurred, although ventriculoperitoneal shunts were placed in 2 patients. The preservation of serviceable hearing and facial and trigeminal nerve function was achieved in 58%, 91%, and 86% of patients, respectively, with any facial and trigeminal neuropathy being transient. In 92% of the patients presenting with trigeminal hypesthesia before GKS, the condition resolved during follow-up. No patient- or VS-related feature was correlated with growth.

Conclusions. Primary GKS for large VSs leads to acceptable radiological growth rates and clinical control rates, with the chance of hearing preservation. Although a higher incidence of clinical control failure and postradiosurgical morbidity is noted, as compared with that for smaller VSs, primary radiosurgery is suitable for a selected group of patients. The absence of symptomatology due to mass effect on the brainstem or cerebellum is essential, as are close clinical and radiological follow-ups, because there is little reserve for growth or swelling.

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Management of large vestibular schwannoma. Part I. Planned subtotal resection followed by Gamma Knife surgery: radiological and clinical aspects

J Neurosurg 115:875–884, 2011. DOI: 10.3171/2011.6.JNS101958

In large vestibular schwannoma (VS), microsurgery is the main treatment option, and complete resection is considered the primary goal. However, previous studies have documented suboptimal facial nerve outcomes in patients who undergo complete resection of large VSs. Subtotal resection is likely to reduce the risk of facial nerve injury but increases the risk of lesion regrowth. Gamma Knife surgery (GKS) can be performed to achieve long-term growth control of residual VS after incomplete resection. In this study the authors report on the results in patients treated using planned subtotal resection followed by GKS with special attention to volumetric growth, control rate, and symptoms.

Methods. Fifty consecutive patients who underwent the combined treatment strategy of subtotal microsurgical removal and GKS for large VSs between 2002 and 2009 were retrospectively analyzed. Patients with neurofibromatosis Type 2 were excluded. Patient charts were reviewed for clinical symptoms. Audiograms were evaluated to classify hearing pre- and postoperatively. Preoperative and follow-up contrast-enhanced T1-weighted MR images were analyzed using volume-measuring software.

Results. Surgery was performed via a translabyrinthine (25 patients) or retrosigmoid (25 patients) approach. The median follow-up was 33.8 months. Clinical control was achieved in 92% of the cases and radiological control in 90%. One year after radiosurgery, facial nerve function was good (House-Brackmann Grade I or II) in 94% of the patients. One of the two patients who underwent surgery to preserve hearing maintained serviceable hearing after resection followed by GKS.

Conclusions. Considering the good tumor growth control and facial nerve function preservation as well as the possibility of preserving serviceable hearing and the low number of complications, subtotal resection followed by GKS can be the treatment option of choice for large VSs.

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Endoscopic Endonasal Approach for Nonvestibular Schwannomas

Neurosurgery 69:1046–1057, 2011 DOI: 10.1227/NEU.0b013e3182287bb9

Nonvestibular schwannomas of the skull base often represent a challenge owing to their anatomic location. With improved techniques in endoscopic endonasal skull base surgery, resection of various ventral skull base tumors, including schwannomas, has become possible.

OBJECTIVE: To assess the outcomes of using endoscopic endonasal approach (EEA) for nonvestibular schwannomas of the skull base.

METHODS: Seventeen patients operated on for skull base schwannomas by EEA at the University of Pittsburgh Medical Center from 2003 to 2009 were reviewed.

RESULTS: Three patients underwent combined approaches with retromastoid craniectomy (n = 2) and orbitopterional craniotomy (n = 1). Three patients underwent multistage EEA. The rest received a single EEA operation. Data on degree of resection were found for 15 patients. Gross total resection (n = 9) and near-total (.90%) resection (n = 3) were achieved in 12 patients (80%). There were no tumor recurrences or postoperative cerebrospinal fluid leaks. In 3 of 7 patients with preoperative sensory deficits of trigeminal nerve distribution, there were partial improvements. Patients with preoperative reduced vision (n = 1) and cranial nerve VI or III palsies (n = 3) also showed improvement. Five patients had new postoperative trigeminal nerve deficits: 2 had sensory deficits only, 1 had motor deficit only, and 2 had both motor and sensory deficits. Three of these patients had partial improvement, but 3 developed corneal neurotrophic keratopathy.

CONCLUSION: An EEA provides adequate access for nonvestibular schwannomas invading the skull base, allowing a high degree of resection with a low rate of complications.

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Postoperative Infection May Influence Survival in Patients With Glioblastoma: Simply a Myth?

Neurosurgery 69:864–869, 2011 DOI: 10.1227/NEU.0b013e318222adfa

It is a prevalent myth that a postoperative infection may actually confer a survival advantage in patients with malignant glioma. This contention is based largely on anecdotal reports. Recently, a single-center study showed there was no survival advantage in those patients who had glioblastoma with postoperative infection.

OBJECTIVE: To examine the impact of postoperative infections on outcome in patients with glioblastoma treated at our center.

METHODS: This study included 197 patients with newly diagnosed primary glioblastoma treated from January 2001 to January 2008. Of the 197 patients, 10 (5.08%) had postoperative bacterial infection. The Kaplan-Meier method, log-rank test, and Breslow test were used in the univariate approach; Cox regression was used in the multivariable approach.

RESULTS: The median survival was 16 months (95% confidence interval [CI], 14-18 mo). The infection group had a significant advantage in the median survival: 30 months (95% CI, 21-39) vs 15 months (95% CI, 13-17) for patients without postoperative infection. This advantage was also confirmed by Cox regression; in fact, patients not developing a postoperative infection showed an adjusted hazard ratio for death of 2.3 (95% CI, 1-5.3).

CONCLUSION: The association between infection and prolonged survival is not definitive; we acknowledge the considerable difficulties in undertaking this type of study in a retrospective manner. Our results can instead stimulate further multicentric studies (to increase the number of patients) or experimental studies using genetically modified bacteria for treatment of glioblastoma.

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Cell Surface Receptors in Malignant Glioma

Neurosurgery 69:980–994, 2011 DOI: 10.1227/NEU.0b013e318220a672

Despite advances in surgery, radiation, and chemotherapy, malignant gliomas are still highly lethal tumors. Traditional treatments that rely on nonspecific, cytotoxic approaches have a marginal impact on patient survival.

However, recent advances in the molecular cancer biology underlying glioma pathogenesis have revealed that abnormalities in common cell surface receptors, including receptor tyrosine kinase and other cytokines, mediate the abnormal cellular signal pathways and aggressive biological behavior among the majority of these tumors.

Some cell surface receptors have been targeted by novel agents in preclinical and clinical development. Such cancer-specific targeted agents might offer the promise of improved cancer control without substantial toxicity.

Here, we review these common cell surface receptors with clinical significance for malignant glioma and discuss the molecular characteristics, pathological significance, and potential therapeutic application of these cell surface receptors.

We also summarize the clinical trials of drugs targeting these cell surface receptors in malignant glioma patients.

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Bilateral subfrontal approach for tuberculum sellae meningiomas in long-term postoperative visual outcome

J Neurosurg 115:802–810, 2011.DOI: 10.3171/2011.5.JNS101812

Various surgical approaches, such as uni- and bifrontal, frontolateral, and pterional approaches, havebeen advocated for tuberculum sellae meningiomas. The authors retrospectively reviewed the effectiveness of a bilateralsubfrontal approach for tuberculum sellae meningiomas with special attention to ophthalmological outcomesand complications.

Methods. Between 1993 and 2009, 34 patients underwent surgery for removal of tuberculum sellae meningiomasat Osaka City University. Tumor size ranged from 14 to 45 mm. Thirty-two of 34 patients presented with visualdisturbances before the surgery. The visual functions in all patients were assessed using a visual impairment score(VIS) before and after surgery. Postoperative visual examination was performed 2 weeks after surgery. Long-termfollow-up examinations were conducted 1 year after surgery.

Results. Radical resection (Simpson Grades I and II) was accomplished in 27 patients, and subtotal or partialresection (Simpson Grades III and IV) was achieved in 7. There was no deterioration in postoperative visual outcome.Twenty-nine (90.6%) of 32 patients showed improved VIS compared with preoperative VIS. The average VIS was38.1 preoperatively, 23.5 in the short-term postoperative period, and 21.8 in the long-term postoperative period. Inthe short-term postoperative period, the visual function in 6 patients normalized, and visual problems persisted in theremaining 26. Six (23%) of 26 patients showed further improvement in VIS during the long-term follow-up period,and no patient exhibited a worsened VIS during this time. One patient complained of hyposmia after surgery, butthere was no indication of related complications such as CSF leakage or frontal brain contusion.

Conclusions. The bilateral subfrontal approach was previously avoided because of the relatively high rate ofcomplications in earlier surgical series of tuberculum sellae meningiomas. However, after developments in microsurgicaltechniques in recent years, the bilateral subfrontal approach can now provide satisfactory visual outcomes withminimal postoperative complications. Careful preservation of the blood supply to optic apparatus and early unroofingof the optic canal using a bilateral subfrontal approach led to further improvement in long-term postoperative visual outcome.

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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.

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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.

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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.

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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.

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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.

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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.

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