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BRAINLIFE NEWSLETTER
Volume 4, Number 44 - 25 October 2005

Volume 4
Archive
1: Cancer Res. 2005 Oct 15;65(20):9398-405.
 
Tissue inhibitor of metalloproteinase-3 expression from an oncolytic adenovirus inhibits matrix metalloproteinase activity in vivo without affecting antitumor efficacy in malignant glioma.

Lamfers ML, Gianni D, Tung CH, Idema S, Schagen FH, Carette JE, Quax PH, Van Beusechem VW, Vandertop WP, Dirven CM, Chiocca EA, Gerritsen WR.

Department of Neurosurgery, Division of Gene Therapy, VU University Medical Center, Amsterdam, The Netherlands. M.Lamfers@vumc.nl

Oncolytic adenoviruses exhibiting tumor-selective replication are promising anticancer agents. Insertion and expression of a transgene encoding tissue inhibitor of metalloproteinase-3 (TIMP-3), which has been reported to inhibit angiogenesis and tumor cell infiltration and induce apoptosis, may improve the antitumor activity of these agents. To assess the effects of TIMP-3 gene transfer to glioma cells, a replication-defective adenovirus encoding TIMP-3 (Ad.TIMP-3) was employed. Ad.TIMP-3 infection of a panel of glioma cell cultures decreased the proliferative capacity of these cells and induced morphologic changes characteristic for apoptosis. Next, a conditionally replicating adenovirus encoding TIMP-3 was constructed by inserting the TIMP-3 expression cassette into the E3 region of the adenoviral backbone containing a 24-bp deletion in E1A. This novel oncolytic adenovirus, AdDelta24TIMP-3, showed enhanced oncolytic activity on a panel of primary cell cultures and two glioma cell lines compared with the control oncolytic virus AdDelta24Luc. In vivo inhibition of matrix metalloproteinase (MMP) activity by AdDelta24TIMP-3 was shown in s.c. glioma xenografts. The functional activity of TIMP-3 was imaged noninvasively using a near-IR fluorescent MMP-2-activated probe. Tumoral MMP-2 activity was significantly reduced by 58% in the AdDelta24TIMP-3-treated tumors 24 hours after infection. A study into the therapeutic effects of combined oncolytic and antiproteolytic therapy was done in both a s.c. and an intracranial model for malignant glioma. Treatment of s.c. (U-87MG) or intracranial (U-87deltaEGFR) tumors with AdDelta24TIMP-3 and AdDelta24Luc both significantly inhibited tumor growth and prolonged survival compared with PBS-treated controls. However, expression of TIMP-3 in the context of AdDelta24 did not significantly affect the antitumor efficacy of this oncolytic agent.

PMID: 16230403 [PubMed - in process]
 
2: Cancer Res. 2005 Oct 15;65(20):9338-46.
 
Low-density lipoprotein receptor-related protein contributes to the antiangiogenic activity of thrombospondin-2 in a murine glioma model.

Fears CY, Grammer JR, Stewart JE Jr, Annis DS, Mosher DF, Bornstein P, Gladson CL.

Departments of Pathology and Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.

Host antiangiogenesis factors defend against tumor growth. The matricellular protein, thrombospondin-2 (TSP-2), has been shown to act as an antiangiogenesis factor in a carcinogen-induced model of skin cancer. Here, using an in vivo malignant glioma model in which the characteristics of the tumors formed after intracerebral implantation of GL261 mouse glioma cells are assessed, we found that tumor growth and microvessel density were significantly enhanced in tumors propagated in TSP-2(-/-) mice. Mechanistically, matrix metalloproteinase (MMP)-2 has been associated with neoangiogenesis and it has been proposed that the levels of available MMP-2 may be down-regulated by formation of a complex with TSP-2 that is internalized by low-density lipoprotein receptor-related protein 1 (LRP1). We found elevated expression of MMP-2 and MMP-9 in tumors propagated in TSP-2(-/-) mice, with a preferential localization in the microvasculature. In wild-type mice, MMP-2 was coexpressed with TSP-2 in the tumor microvasculature. In vitro, addition of recombinant (rec) TSP-2 to mouse brain microvessel endothelial cells reduced MMP-2 levels and invasion through mechanisms that could be inhibited by a competitive inhibitor of ligand binding to LRP1 or by siLRP1. Thus, the antiangiogenic activity of TSP-2 is capable of inhibiting the growth of gliomas in part by reducing the levels of MMP-2 in the tumor microvasculature. This mechanism is mediated by LRP1.

PMID: 16230396 [PubMed - in process]
 
3: Childs Nerv Syst. 2005 Nov;21(11):1000-3. Epub 2005 Jan 27.
 
Gliomatosis cerebri in children Case report and clinical considerations.

Caroli E, Orlando ER, Ferrante L.

Department of Neurological Sciences, Neurosurgery, Policlinico S. Andrea, University of Rome La Sapienza, Rome, Italy.

OBJECTIVE: Gliomatosis cerebri (GC) is an uncommon entity characterised by the diffuse overgrowth of large parts of the brain by glial cells. Reports in the literature often refer to adult patients, its occurrence in children being even more rare. CASE REPORT: We report the case of an 8-year-old boy with GC and discuss the problem of intra vitam diagnosis. CONCLUSIONS: Diagnosis of GC is very difficult; thus, cases diagnosed during life are rare.

PMID: 16240166 [PubMed - in process]
 
4: Int J Radiat Oncol Biol Phys. 2005 Oct 11; [Epub ahead of print]
 
Perfusion and diffusion mri of glioblastoma progression in a four-year prospective temozolomide clinical trial.

Leimgruber A, Ostermann S, Yeon EJ, Buff E, Maeder PP, Stupp R, Meuli RA.

Department of Radiology, Lausanne State and University Hospital, Lausanne, Switzerland.

PURPOSE: This study was performed to determine the impact of perfusion and diffusion magnetic resonance imaging (MRI) sequences on patients during treatment of newly diagnosed glioblastoma. Special emphasis has been given to these imaging technologies as tools to potentially anticipate disease progression, as progression-free survival is frequently used as a surrogate endpoint. METHODS AND MATERIALS: Forty-one patients from a phase II temolozomide clinical trial were included. During follow-up, images were integrated 21 to 28 days after radiochemotherapy and every 2 months thereafter. Assessment of scans included measurement of size of lesion on T1 contrast-enhanced, T2, diffusion, and perfusion images, as well as mass effect. Classical criteria on tumor size variation and clinical parameters were used to set disease progression date. RESULTS: A total of 311 MRI examinations were reviewed. At disease progression (32 patients), a multivariate Cox regression determined 2 significant survival parameters: T1 largest diameter (p < 0.02) and T2 size variation (p < 0.05), whereas perfusion and diffusion were not significant. CONCLUSION: Perfusion and diffusion techniques cannot be used to anticipate tumor progression. Decision making at disease progression is critical, and classical T1 and T2 imaging remain the gold standard. Specifically, a T1 contrast enhancement over 3 cm in largest diameter together with an increased T2 hypersignal is a marker of inferior prognosis.

PMID: 16226399 [PubMed - as supplied by publisher]
 
5: J Clin Oncol. 2005 Oct 20;23(30):7621-7631.
 
Multiagent Chemotherapy and Deferred Radiotherapy in Infants With Malignant Brain Tumors: A Report From the Children's Cancer Group.

Geyer JR, Sposto R, Jennings M, Boyett JM, Axtell RA, Breiger D, Broxson E, Donahue B, Finlay JL, Goldwein JW, Heier LA, Johnson D, Mazewski C, Miller DC, Packer R, Puccetti D, Radcliffe J, Tao ML, Shiminski-Maher T.

Children's Hospital and Regional Medical Center, Department of Pediatric Hematology-Oncology, 4800 Sand Point Way NE, MS: CH-29, Seattle, WA 98105; e-mail: russ.geyer@seattlechildrens.org.

PURPOSE To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis. PATIENTS AND METHODS Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed. Results Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% +/- 3%, and the survival rate was 43% +/- 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% +/- 5%, 17% +/- 6%, and 32% +/- 6%, and 14% +/- 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy. CONCLUSION Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.

PMID: 16234523 [PubMed - as supplied by publisher]
 
6: J Neurooncol. 2005 Sep 16; [Epub ahead of print]
 
Dendritic Cells Pulsed with Total Tumor RNA for Activation NK-like T Cells Against Glioblastoma Multiforme.

Vichchatorn P, Wongkajornsilp A, Petvises S, Tangpradabkul S, Pakakasama S, Hongeng S.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.

Dendritic cells (DCs) are potent antigen presenting cells and play critical role in T cell-mediated immunity. DCs have been shown to induce strong anti-tumor responses both in vitro and in vivo. Their efficacies in tumor therapy are being investigated in clinical trials. Previous evidence has shown that these DCs enhance the cytotoxicity of NK cells. We generated NK-like T cells (CD3(+)CD56(+)), a novel type of effector cells differentiated from normal lymphocyte, which is now being used for adoptive immunotherapy in clinical trials. This study aimed to elucidate the effects of NK-like T cells after co-culturing with DCs against tumor cells. The result revealed that tumor-derived RNA-pulsed DCs can enhance the immune responses of NK-like T cells against glioblastoma multiforme cell line but these effector cells did not appear to have the cytotoxic effect against normal cells (human umbilical vein endothelial cells (HUVEC) and fibroblasts) in vitro. This study may be beneficial for the development of new immunologic effector cells for using in adoptive immunotherapy for glioblastoma multiforme in the future.

PMID: 16234988 [PubMed - as supplied by publisher]
 
7: J Neurooncol. 2005 Sep 16; [Epub ahead of print]
 
Role of MIB1 in predicting survival in patients with glioblastomas.

Moskowitz SI, Jin T, Prayson RA.

Department of Neurosurgery, The Cleveland Clinic Foundation, Cleveland, OH, USA.

BACKGROUND: Histologic immunomarkers of cell cycle proteins have been utilized for prognosis in high-grade astrocytic tumors. One such marker, MIB1, an antibody immunoreactive throughout the cell cycle, is predictive of more aggressive disease and poorer prognosis in astrocytomas. An independent role of MIB1 analysis for survival prediction and clinical management within histologic grades has not been clearly proven. METHODS: This study retrospectively evaluated MIB1 reactivity in tissue samples from 116 patients with glioblastomas on initial medical presentation. Clinical variables considered included gender, age, Karnofsky Performance Scores (KPS), extent of surgical resection, adjuvant radiation and survival. RESULTS: Univariate and multivariate analyses were used to correlate these variables with MIB1 staining. MIB1 staining does not predict overall survival or response to adjuvant therapy as an independent risk factor. CONCLUSION: MIB1 labeling does not predict patient survival as an independent variable and does not predict response to additional therapies. Patient survival with glioblastoma was predicted by KPS, age, extent of resection and use of adjuvant radiotherapy.

PMID: 16234986 [PubMed - as supplied by publisher]
 
8: J Neurooncol. 2005 Sep 16; [Epub ahead of print]
 
Discoidin Domain Receptor-1a (DDR1a) Promotes Glioma Cell Invasion and Adhesion in Association with Matrix Metalloproteinase-2.

Ram R, Lorente G, Nikolich K, Urfer R, Foehr E, Nagavarapu U.

AGY Therapeutics, Inc., 270 East Grand Avenue, 94080, South San Francisco, CA, USA, efoehr@agyinc.com.

Invasion of glioma cells involves the attachment of invading tumor cells to extracellular matrix(ECM), disruption of ECM components, and subsequent cell penetrationinto adjacent brain structures. Discoidin domain receptor 1 (DDR1) tyrosine kinases constitute a novel family of receptors characterized by a unique structure in the ectodomain (discoidin-I domain). These cell surface receptors bind to several collagens and facilitate cell adhesion. Little is known about DDR1 expression and function in glioblastoma multiforme. In this study we demonstrate that DDR1 is overexpressed in glioma tissues using cDNA arrays, immunohistochemistry and Western blot analysis. Functional comparison of two splice variants of DDR1 (DDR1a and DDR1b) reveal novel differences in cell based glioma models. Overexpression of either DDR1a or DDR1b caused increased cell attachment. However, glioma cells overexpressing DDR1a display enhanced invasion and migration. We also detect increased levels of matrix metalloproteinase-2 in DDR1a overexpressing cells as measured by zymography. Inhibition of MMP activity using MMP inhibitor suppressed DDR1a stimulated cell-invasion. Similarly, an antibody against DDR1 reduced DDR1a mediated invasion as well as the enhanced adhesion of DDR1a and DDR1b overexpressing cells. These results suggest that DDR1a plays a critical role in inducing tumor cell adhesion and invasion, and this invasive phenotype is caused by activation of matrix metalloproteinase-2.

PMID: 16234985 [PubMed - as supplied by publisher]
9: J Neurooncol. 2005 Aug;74(1):71-6.
 
Magnetic resonance imaging and biological markers in pituitary adenomas with invasion of the cavernous sinus space.

Pan LX, Chen ZP, Liu YS, Zhao JH.

Department of Neurosurgery, Cancer Center, Sun Yat-Sen University, 651, Dongfeng Road East, 510060, Guangzhou, Guangdong, China.

The preoperative diagnosis of cavernous sinus invasion remains difficult and controversial, and there are currently no reliable histological or molecular markers that predict pituitary tumour behaviour and response to treatment. We evaluated 45 patients with pituitary adenoma. The results have shown that the sensitivity of MRI for indicating cavernous sinus invasion in this prospective study was 60%, specificity 85%, positive predictive value 83.33%, negative predictive value 62.96%. Forty-five specimens of pituitary adenomas were analyzed for expression of F8, VEGF, Ki-67, c-myc, bcl-2, nm23 and MMP-9 immunoreactivity using immunoperoxidase staining. MVD was assessed using F8-related antigen. The results have shown that MVD of invasive pituitary adenomas was significantly higher than that of noninvasive (P < 0.001). There was an association between the invasion of pituitary adenomas and Ki-67 LI (P = 0.039) or the expression of VEGF (P < 0.001) and MMP-9 (P < 0.001). But c-myc LI and bcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 vs. P = 0.201). On the other hand, there is an inverse relationship between nm23 expression and tumor invasion (P < 0.001). In conclusion, parasellar extension of pituitary adenomas through the medial wall of the cavernous sinus diagnosed at surgery, can be determined by radiology with sensitive gadolinium-enhanced MRI. Although our study has shown that MVD and the expression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas, they are lack of specificity. These markers can only provide some useful informations on the therapeutic strategy of pituitary adenomas.

PMID: 16078111 [PubMed - indexed for MEDLINE]
 
10: J Neurooncol. 2005 Aug;74(1):65-9.
 
Cerebellopontine angle paraganglioma - report of a case and review of literature.

Deb P, Sharma MC, Gaikwad S, Gupta A, Mehta VS, Sarkar C.

Department of Pathology, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, 110029, New Delhi, India.

Majority of the cerebellopontine angle (CPA) tumors are acoustic neuromas, while bulk of the non-acoustic tumors are formed by meningiomas and epidermoid cysts. Primary paraganglioma is a rare tumor in this location, with only two such cases having been reported in the literature, till date. Recently, a case has been described wherein a paraganglioma was apparently arising as a primary lesion in the cerebellar hemisphere. We report another case of an intracranial paraganglioma of the CPA in a 40-year-old female, which did not have any vascular attachment but had focal cerebellar extension.

Publication Types:
PMID: 16078110 [PubMed - indexed for MEDLINE]
 
11: J Neurooncol. 2005 Aug;74(1):59-63.
 
Gliosarcomas: analysis of 11 cases do two subtypes exist?

Salvati M, Caroli E, Raco A, Giangaspero F, Delfini R, Ferrante L.

Department of Neurological Sciences - Neurosurgery, INM Neuromed IRCCS, Pozzilli (Is), Italy.

There are conflicting reports regarding gliosarcomas. The goal of this study is to examine clinical, radiological, surgical and therapeutic aspects of 11 patients with gliosarcoma. Between 1993 and 2001, 11 patients with cerebral gliosarcoma were treated at our Institute. Ten patients underwent surgery and one patient had stereotactic biopsy. Four patients received whole brain radiotherapy with (60)Co, five underwent radiotherapy with LINAC extended 2 cm beyond the edema margins. One patient refused any additional treatment after surgery and one patient was not treated postoperatively for poor clinical conditions (KPS 40). Chemotherapy (temozolomide) was administered to four patients. Four patients had a prevalence of sarcomatous component that corresponded to surgical and radiological aspects similar to meningioma while six patients showed a prevalence of gliomatous component and radiological and surgical aspects similar to those of glioblastomas. Surgical resection was total in six and subtotal in four patients. Patients with prevalent sarcomatous component showed median survival time more prolonged than patients with prevalent gliomatous component (71 +/- 6 weeks vs. 63 +/- 6; P=0.0417). Moreover, the survival rate differed in relation to the therapy: patients treated with multimodality therapy (surgery, radiotherapy and chemotherapy) had a longer survival time than patients treated in single or bimodality. Despite prognosis of gliosarcomas remains poor, a multidisciplinary approach (surgery, radiotherapy and chemotherapy) seems to be associated with slight more prolonged survival times.

PMID: 16078109 [PubMed - indexed for MEDLINE]
 
12: J Neurooncol. 2005 Aug;74(1):53-7.
 
Osseous metastasis of pineoblastoma: a case report and review of the literature.

Constantine C, Miller DC, Gardner S, Balmaceda C, Finlay J.

Department of Pediatrics, New York University of School of Medicine, New York, USA.

PURPOSE: To review the literature on the occurrence of osseous metastases in recurrent pineoblastoma, and to report upon the feasibility and efficacy of treatment using intensive conventional chemotherapy to achieve a remission, followed by consolidation with marrow ablative chemotherapy and autologous hemopoietic stem cell rescue. PATIENT AND METHODS: An adult with isolated extraneural, osseous and bone marrow metastases from a pineoblastoma, received conventional cyclical chemotherapy, followed by consolidation with marrow ablative chemotherapy (thiotepa, carboplatin and temozolomide) and autologous hemopoietic stem cell rescue. RESULTS: A complete radiographic and histopathologic response was achieved after almost one year of conventional chemotherapy that was tolerated without significant sequelae. Following successful harvesting of peripheral blood stem cells, the patient underwent myeloablative chemotherapy with autologous stem cell rescue, without difficulty in hemopoietic reconstitution and without serious or permanent side effects. CONCLUSIONS: Osseous metastases from pineoblastoma are an extremely rare occurrence. We conclude that conventional chemotherapy can achieve a complete response, and subsequent consolidation with marrow ablative chemotherapy and autologous hemopoietic stem cell rescue is feasible and well tolerated.

Publication Types:
PMID: 16078108 [PubMed - indexed for MEDLINE]
 
13: J Neurooncol. 2005 Aug;74(1):47-52.
 
Primary neurocytoma of the spinal cord: a case report and review of literature.

Sharma S, Sarkar C, Gaikwad S, Suri A, Sharma MC.

Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India. .

Most central neurocytomas (CN) and spinal neurocytomas (SN) have a bland well-differentiated histologic picture and uneventful clinical course. However, rare examples showing histologic atypia, recurrence and even CSF dissemination have been reported. Herein we report a case of recurrent spinal neurocytoma in a 24-year-old male who presented with a 2-month history of weakness and numbness of the left upper and lower limbs, and was previously operated at the same site 10 months ago. MRI revealed a contrast enhancing intramedullary mass involving C5-T1 region. Radiologic and operative impression at both surgeries was that of a glioma, possibly anaplastic. Histologic and immunohistochemical features in both resections were those of an atypical neurocytoma. The tumor showed rare mitoses, focal mild vascular proliferation in both specimens, and necrosis in the initial specimen. MIB1 labeling indices were 9 and 10%, respectively. Based on the analysis of this case and limited data from the literature, it is hypothesized that SN shows a histopathologic picture, immunoprofile and biologic behavior very similar to CN. However, the presence of histologic atypia and increased MIB1 index in SN appear to more closely correlate with tumor recurrence and a worse overall outcome, in part due to their location in the critical region of cervical spinal cord. Therefore, we hypothesize that SN with atypia requires a close clinical follow up. As in CN, radiation therapy is perhaps best reserved for atypical, progressive and recurrent SN.

Publication Types:
PMID: 16078107 [PubMed - indexed for MEDLINE]
14: J Neurooncol. 2005 Aug;74(1):1-8.
 
Immunohistochemical study of central neurocytoma, subependymoma, and subependymal giant cell astrocytoma.

You H, Kim YI, Im SY, Suh-Kim H, Paek SH, Park SH, Kim DG, Jung HW.

Neuro-Oncology Clinic, Center for Specific Organ Center, National Cancer, Seoul, Korea.

For investigation of histogenesis of central neurocytomas (CNs), subependymoma (SEs), subependymal giant cell astrocytomas (SEGAs), we studied expression of various neuronal and glial biomarkers by immunohistochemical (IHC) study and reverse transcriptase-polymerase chain reaction (RT-PCR). The materials for IHC were paraffin section of seven CNs, three SEs, and eight SEGAs and those for RT-PCR were frozen tissues of seven CNs, three SEs, and five SEGAs. Control group was five ependymomas (EPs) and four pilocytic astrocytomas (PAs). The neuronal biomarkers included nestin, chromogranin A (chrA), synaptophysin (SNP), neuronal cell adhesion molecule (NCAM), neuron specific enolase (NSE), neuronal nuclear antigen (NeuN), neurofilament (NF) and the glial marker was GFAP. CNs expressed all neuronal markers except NF (0%), SNP (100%), NCAM (100%), NSE (100%), NeuN (100%), nestin (29%) and chrA (43%), but GFAP expression was found only in one case (14%). SEGA coexpressed several neuronal markers and a glial marker; NeuN (100%), NSE (88%), NCAM (63%), nestin (100%), SNP (weakly and focally, 100%), and GFAP (100%), however, other neuronal markers including chrA, SNP and NF were all negative. SE expressed nonspecific neuronal markers (NCAM (100%) and NSE (100%)) which showed weak intensity and a GFAP (100%), but not nestin. Among control cases of EPs and PAs, no one case expressed neuronal markers except nonspecific neuronal marker of NCAM, but robustly expressed GFAP. RT-PCR product of nestin was expressed in 29% of CNs (2/7cases), 60% of SEGAs (3/5 cases), 100% of SEs (3/3 cases), 80% of EPs (4/5 cases), and 25% of PAs (1/4 cases). Conclusively, coexpression of neuronal and glial markers and expression of nestin in CNs, SEGAs and SEs suggested the origin of these tumor cells might be the stem cells being able to differentiate into both neuronal and glial phenotypes. But CNs might be originated from rather neuronally committed stem cells and SEs from rather glially committed stem cells.

PMID: 16078101 [PubMed - indexed for MEDLINE]
 
15: J Neurosurg. 2005 Sep;103(3):559-63.

Spinal intradural clear cell meningioma following resection of a suprasellar clear cell meningioma. Case report and recommendations for management.

Dhall SS, Tumialan LM, Brat DJ, Barrow DL.

Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, USA.

The authors report on 32-year-old woman with a history of a previously resected suprasellar clear cell meningioma (CCM), who returned to their institution after 3 years suffering from progressively worsening leg and back pain associated with leg weakness and bowel and bladder dysfunction. A magnetic resonance image of the thoracic and lumbar spine demonstrated a homogeneously enhancing intradural mass that filled and expanded the thecal sac. The patient underwent multiple-level laminectomies for resection of the lesion. Results of pathological studies confirmed distant recurrence of a CCM. Since its initial recognition as a rare but aggressive histological variant of meningothelial tumors, the body of literature on CCMs has grown to include more than 40 cases. Nevertheless, the natural history of this neoplastic entity remains ill defined, as are the recommendations for management. Of particular concern is the treatment of patients who have undergone subtotal resection or present with recurrence. To the authors' knowledge, the present case represents the sixth distant recurrence of CCM reported in the literature. The radiographic and histological studies are reviewed along with the current literature on this subtype of meningioma. Recommendations for surveillance and treatment are made.

PMID: 16235691 [PubMed - in process]
 
16: J Neurosurg. 2005 Sep;103(3):555-8.

Pyrogenic cytokine interleukin-6 expression by a chordoid meningioma in an adult with a systemic inflammatory syndrome. Case report and review of the literature.

Denaro L, Di Rocco F, Gessi M, Lauriola L, Lauretti L, Pallini R, Fernandez E, Maira G.

Department of Neurosurgery, Catholic University School of Medicine, Rome, Italy.

Chordoid meningioma is a rare meningothelial tumor characterized by chordoma-like histological features with lymphoplasmacellular infiltration. This tumor is often seen in children, but not in adults, with a systemic inflammatory syndrome (iron-resistant microcytic anemia and/or dysgammaglobulinemia) and very rarely with a persistent moderate hyperthermia. In the present report the authors describe a temporal chordoid meningioma in a 30-year-old woman who presented with fever, headache, and a serological inflammatory syndrome. The clinical symptomatology, chiefly the fever, disappeared immediately after removal of the tumor. To the authors' knowledge, only one similar patient with such clinical presentation and response to surgery has been mentioned in the literature. Interestingly, at immunohistochemical examination, the neoplasm showed focal positivity for the pyrogenic cytokine interleukin-6. The capacity of the tumor to produce this pyrogenic cytokine could explain both the patient's clinical presentation and her response to the surgical management.

PMID: 16235690 [PubMed - in process]
 
17: J Neurosurg. 2005 Sep;103(3):526-37.

The role of contortrostatin, a snake venom disintegrin, in the inhibition of tumor progression and prolongation of survival in a rodent glioma model.

Pyrko P, Wang W, Markland FS, Swenson SD, Schmitmeier S, Schonthal AH, Chen TC.

Department of Neurosurgery, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA.

OBJECT: Malignant gliomas are not curable because of diffuse brain invasion. The tumor cells invade the surrounding brain tissue without a clear tumor-brain demarcation line, making complete resection impossible. Therapy aimed at inhibition of invasion is crucial not only for prevention of tumor spread, but also for selectively blocking migrating cells that may be more resistant to chemotherapy and radiation. Recently, investigations have shown that the snake venom disintegrin contortrostatin specifically binds to certain integrins on the surface of glioma cells and thereby inhibits their interaction with the extracellular matrix (ECM), resulting in a blockage of cell motility and invasiveness. To translate these in vitro findings into clinical settings, the authors examined the effect of contortrostatin on glioma progression in a rodent model. METHODS: Athymic mice were intracranially or subcutaneously injected with U87 glioma cells, and the effect of intratumorally administered contortrostatin on tumor progression and animal survival was then studied. In addition, the authors evaluated the pharmacological safety of contortrostatin use in the brains of tumor-free animals. CONCLUSIONS: The results demonstrate that contortrostatin is able to inhibit tumor growth and angiogenesis and to prolong survival in a rodent glioma model. Moreover, contortrostatin appears to be well tolerated by the animal and lacks obvious neurotoxic side effects. Thus, contortrostatin may have potential as a novel therapeutic agent for the treatment of malignant gliomas.

PMID: 16235686 [PubMed - in process]
 
18: J Neurosurg. 2005 Sep;103(3):508-17.

Ubiquitous expression of cyclooxygenase-2 in meningiomas and decrease in cell growth following in vitro treatment with the inhibitor celecoxib: potential therapeutic application.

Ragel BT, Jensen RL, Gillespie DL, Prescott SM, Couldwell WT.

Department of Neurosurgery, University of Utah; and Huntsman Cancer Institute, Salt Lake City, Utah 84132, USA.

OBJECT: Meningiomas are the second most common symptomatic primary central nervous system tumor in adults. Findings of epidemiological studies link meningiomas with a history of head trauma, indicating a causal relationship between the inflammatory response and meningioma tumorigenesis. Cyclooxygenase-2 (COX-2), an inducible inflammatory enzyme, converts arachidonic acid to prostaglandins, which have angiogenic, cell-proliferative, and antiapoptotic effects. The authors investigated COX-2 expression in meningiomas and the effects of celecoxib, a COX-2 inhibitor, on meningioma cell growth in vitro. METHODS: Four meningioma surgical specimens were immunohistochemically stained and graded (0 to 4) for COX-2. In addition, a Western blot analysis was performed to detect the presence of COX-2. Human meningioma cells grown in cell culture were treated with vehicle or celecoxib (0.25-1 mM). An immunohistochemical analysis of COX-2, a methylthiotetrazole cell proliferation assay, a TUNEL apoptosis assay, and a Western blot analysis for the proapoptotic protein BAX were performed in vitro. One hundred eleven (87%) of 128 benign meningiomas and six (86%) of seven atypical meningiomas displayed a high COX-2 immunoreactivity (Grade 4 staining). In the Western blot analysis all four surgical specimens (100%) stained positive for a 70-kD band consistent with COX-2. Celecoxib inhibited cell growth in a dose-dependent fashion and induced apoptosis by Day 2, with no change noted in the expression of the BAX protein. CONCLUSIONS: The COX-2 enzyme is universally expressed in meningiomas. Celecoxib inhibits meningioma growth in vitro in a dose-dependent fashion, with evidence of apoptosis. Inhibitors of COX-2 may have a role in the treatment of recurrent meningiomas.

PMID: 16235684 [PubMed - in process]
 
19: J Neurosurg. 2005 Sep;103(3):498-507.

Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma.

Nariai T, Tanaka Y, Wakimoto H, Aoyagi M, Tamaki M, Ishiwata K, Senda M, Ishii K, Hirakawa K, Ohno K.

Department of Neurosurgery, Tokyo Medical and Dental University, Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. nariai.nsrg@tmd.ac.jp

OBJECT: The authors retrospectively analyzed the data obtained in patients who had undergone L-[methyl-11C] methionine (MET)-positron emission tomography (PET) studies to clarify the relationship between MET uptake and tumor biological features and to discuss the clinical usefulness of MET-PET studies. METHODS: One hundred ninety-four patients with cerebral glioma or suspected glioma underwent PET scanning 20 minutes after injection of MET, whose uptake into the tumor was expressed as a ratio to contralateral healthy brain tissue (T/N ratio). Analyses were performed to determine how MET uptake correlated with tumor pathological features and prognosis. The T/N ratios before and after various treatments were also examined. There were significant differences in the T/N ratio among the nonneoplastic lesions, low-grade gliomas, and malignant gliomas. Furthermore, there were significant correlations between patient survival and pretreatment T/N ratios. Among patients with malignant gliomas, a significant difference in survival was observed between cases with and without postoperative tumor remnant based on elevated MET uptake. The MET uptake was heterogeneous even among the homogeneous tumor areas demonstrated on MR imaging. Malignant pathological features were detected in the areas with the highest MET uptake. The effectiveness of radiotherapy or chemotherapy was expressed as a significantly decreased T/N ratio in some of the tumor types. CONCLUSIONS: The ability of MET-PET to reflect the biological nature of gliomas makes it an excellent method for monitoring active tumor tissue, and treatments based on its findings should provide a powerful clinical protocol in the course of glioma therapy.

PMID: 16235683 [PubMed - in process]
 
20: J Neurosurg. 2005 Sep;103(3):491-7.

Sphenoorbital meningiomas: surgical limitations and lessons learned in their long-term management.

Shrivastava RK, Sen C, Costantino PD, Della Rocca R.

Department of Neurosurgery, The Center for Cranial Base Surgery, St. Luke's-Roosevelt Medical Center, New York, New York 10019, USA.

OBJECT: Sphenoorbital meningiomas (SOMs) are complex tumors involving the sphenoid wing, orbit, and cavernous sinus, which makes their complete resection difficult or impossible. Sphenoidal hyperostosis that results in incomplete resection makes these tumors prone to high rates of recurrence with postoperative morbidity resulting in a nonfunctional globe. High-dose radiation therapy has often been described as the only treatment capable of achieving tumor control, although often at the expense of the patient's progressive visual deterioration. METHODS: This series consisted of 25 patients who were retrospectively analyzed over a 12-year period. Visual function was evaluated pre- and postoperatively in all patients. A standardized surgical approach to a frontotemporal craniotomy and orbitozygomatic osteotomy with intra- and extradural drilling of the optic canal and all the hyperostotic bone was performed. Orbital and cranial reconstruction was performed in all patients. The follow-up period was 6 months to 12 years (average 5 years). The patients presented with the classic triad of SOM: proptosis (86%), visual impairment (78%), and ocular paresis (20%). A gross-total resection was achieved in 70% of patients with surgery limited by the superior orbital fissure and the cavernous sinus. Proptosis improved in 96% of patients with 87% improvement in visual function. Ocular paresis improved in 68%, although 20% of patients experienced a temporary ocular paresis postoperatively. There were no perioperative deaths or morbidity related to the surgical approach or reconstruction. Ninety-five percent of patients reported an improved functional orbit. There was tumor recurrence in 8% of patients; in one case recurrence was delayed for longer than 11 years. CONCLUSIONS: Sphenoorbital meningiomas are a distinct category of tumors complicated by potentially extensive hyperostosis of the skull base. Successful resection requires extensive intra- and extradural surgery, necessitating drilling of the optic canal and an orbital osteotomy within anatomical limitations. The bone resection requires reconstruction with autograft, allografts, or alloplast for improved orbital function. All aspects of the clinical triad improved. A radical resection can be achieved with low morbidity, providing a significantly improved clinical outcome in the long-term period.

PMID: 16235682 [PubMed - in process]
 
21: J Neurosurg. 2005 Sep;103(3):473-84.

Spontaneous intracranial meningioma bleeding: clinicopathological features and outcome.

Bosnjak R, Derham C, Popovic M, Ravnik J.

Department of Neurosurgery, University Hospital Center, and Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. roman.bosnjak@mf.uni-lj.si

OBJECT: The aim of this study was to determine the clinicopathological features of patients with intracranial bleeding from unsuspected meningioma and to relate these data to surgery-related outcome. METHODS: The authors report on two cases in which hemorrhage of an unsuspected meningioma occurred in the tentorial ridge and in the falx, and they discuss the details of 143 cases described in the literature. A bleeding propensity index of the meningioma, related to the patient's age, sex, and the lesion's intracranial location and histological type was computed as a ratio between the frequencies of bleeding meningioma and all meningiomas. This was tested by independent samples t-test for proportions. A chi-square test was used to determine the correlations between several variables: location and type of bleeding; survival and type of bleeding; and consciousness and survival. Increased bleeding tendency was found to be associated with two age groups (< 30 years and > 70 years), convexity and intraventricular locations, and fibrous meningiomas. The overall mortality rate documented in cases of bleeding meningiomas was 21.1% (13.9% in the computerized tomography [CT] scanning era), and that in surgically treated cases was 9.5% (7.5% in the CT scanning era). The overall major morbidity rate was 36% (33.8% in the CT scanning era). Overall 96.2% of conscious patients survived after their meningiomas spontaneously hemorrhaged. In patients who were unconscious before surgery, overall mortality rate was 74.1%, and that in surgically treated cases was 46.2%. CONCLUSIONS: The mortality rate in preoperatively conscious patients (those in whom acute deterioration and irreversible brain damage were prevented by early diagnosis and definitive surgery) was similar (< 3% in the CT scanning era) to that documented in cases in which meningiomas did not bleed. In contrast, the associated morbidity rates were much higher. One-stage total removal of the hemorrhagic meningioma and hematoma is the treatment of choice in such patients.

PMID: 16235680 [PubMed - in process]
 
22: J Neurosurg. 2005 Sep;103(3):428-38.

Serial diffusion-weighted magnetic resonance imaging in cases of glioma: distinguishing tumor recurrence from postresection injury.

Smith JS, Cha S, Mayo MC, McDermott MW, Parsa AT, Chang SM, Dillon WP, Berger MS.

Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco School of Medicine, San Francisco, California 94143-0112, USA. jsmith1@itsa.ucsf.edu

OBJECT: Diffusion-weighted magnetic resonance (MR) imaging is an invaluable tool in the diagnosis of acute stroke and other types of brain injury. Abnormalities in and around the resection cavity on diffusion-weighted imaging have been observed following surgery for infiltrating glioma. The purpose of this study was to investigate prospectively the incidence, time course, and ultimate outcome of these abnormalities. METHODS: Forty-four consecutive patients with newly diagnosed gliomas were prospectively observed using serial MR imaging including diffusion-weighted sequences. Clinical and surgical data were also collected. Immediately postoperatively neuroimaging identified 28 patients (64%) in whom areas of reduced diffusion appeared in or around the resection cavity (mean volume 8.2 +/- 1.5 cm3). Complete resolution of this reduced diffusion was demonstrated within 90 days in 24 patients (86%). On subsequent neuroimages these areas demonstrated Gd enhancement as early as postoperative Day 15 and as late as Day 198 and ultimately took on the appearance of encephalomalacia in 26 (93%) of 28 cases. Postoperative reduced diffusion was not predicted by the clinical or surgical parameters that were assessed. No clinical deficits were attributable to the reduced diffusion. CONCLUSIONS: An abnormality related to diffusion-weighted sequences on postoperative MR imaging can occur after resection of newly diagnosed gliomas. In this study the abnormality typically resolved and was replaced by contrast enhancement on follow-up imaging, ultimately demonstrating encephalomalacia on long-term follow up. Findings on neuroimaging during the period of enhancement could be confused with recurrent tumor and interpreted as early treatment failure. Based on the findings of this study the authors strongly suggest that the inclusion of diffusion-weighted sequences in postoperative MR imaging is essential, as is MR imaging immediately before radiation therapy to monitor disease progression. A new enhancement observed after glioma surgery should be interpreted in the context of the diffusion-weighted image obtained immediately postoperatively.

PMID: 16235673 [PubMed - in process]
 
23: J Neurosurg. 2005 Sep;103(3):414-23.

Imaging of somatotopic representation of sensory cortex with intrinsic optical signals as guides for brain tumor surgery.

Nariai T, Sato K, Hirakawa K, Ohta Y, Tanaka Y, Ishiwata K, Ishii K, Kamino K, Ohno K.

Department of Neurosurgery and Physiology, Tokyo Medical and Dental University, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. nariai.nsrg@tmd.ac.jp

OBJECT: Intrinsic optical signals in response to somatosensory stimuli were intraoperatively recorded during brain tumor surgery. In the present study, the authors report on the use of this technique as an intraoperative guide for the safe resection of tumors adjacent to or within the sensorimotor cortex. METHODS: In 14 patients with tumors adjacent to or within the sensorimotor cortex, intrinsic optical signals in response to somatosensory stimuli were recorded by illuminating the brain surface with Xe white light and imaging the reflected light passing through a bandpass filter (605 nm). Results were compared with intraoperative recordings of sensory evoked potentials in all 14 patients and with noninvasive mapping modalities such as magnetoencephalography and positron emission tomography in selected patients. In all but two patients, the somatosensory optical signals were recorded on the primary sensory cortex. Optical signals elicited by stimulation of the first and fifth digits and the three branches of the trigeminal nerve were recorded at different locations on the sensory strip. This somatotopic information was useful in determining the resection border in patients with glioma located in the sensorimotor cortex. CONCLUSIONS: Optical imaging of intrinsic signals is a useful technique with superior spatial resolution for delineating the somatotopic representation of human primary sensory cortex. Furthermore, it can be used as an intraoperative monitoring tool to improve the safety and accuracy of resections of brain tumors adjacent to or within the sensorimotor cortex.

PMID: 16235671 [PubMed - in process]

24: J Neurosurg. 2005 Jan;102(1 Suppl):127-33.

Endoscopic fenestration and coagulation shrinkage of suprasellar arachnoid cysts. Technical note.

Sood S, Schuhmann MU, Cakan N, Ham SD.

Department of Pediatric Neurosurgery, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, Michigan 48201, USA. ssood@med.wayne.edu

The authors describe their experience with endoscopic fenestration of suprasellar cysts followed by shrinkage coagulation of the cysts to restore the anatomy in eight patients. Seven children ranging in age from 8 months to 4.5 years and one adult 24 years of age were treated. Four of the children presented with megacephaly and the other patients with malfunction of a shunt that had been placed previously for hydrocephalus. Endoscopic fenestration of the cyst dome was performed followed by shrinkage of the lesion by means of endoscopic coagulation. Follow-up studies included immediate and late postoperative magnetic resonance imaging, assessment of growth velocity and the body mass index (BMI), and an endocrine profile if indicated by a failure of growth or precocious puberty. Good intraoperative cyst shrinkage was achieved in all seven children. This was maintained on imaging studies at a mean follow-up period of 35 months. There was no significant procedure-associated morbidity. Hydrocephalus resolved in four patients who did not have a preexisting shunt. One of the four patients who had a shunt preoperatively became shunt free. The rest of the patients with preexisting shunts remained shunt dependent despite good resolution of the cyst. During a mean follow-up period of 52 months, the height, growth velocity, and BMI of each patient remained within two standard deviations of normal. In one patient there was a suspicion of precocious puberty, but the endocrine profile was normal; in another patient precocious puberty developed and required treatment. The presented technique is safe and prevents cyst recurrence and obstruction of the aqueduct by remnants of the cyst wall-the two main reasons for failure of a simple endoscopic fenestration.

Publication Types:
PMID: 16206748 [PubMed - indexed for MEDLINE]
 
25: J Neurosurg. 2005 Jan;102(1 Suppl):105-12.

Intracranial extracerebral glioneuronal heterotopia. Case report and review of the literature.

Oya S, Kawahara N, Aoki S, Hayashi N, Shibahara J, Izumi M, Kirino T.

Department of Neurosurgery, Faculty of Medicine, University of Tokyo, Japan.

The authors report a case of intracranial extracerebral glioneuronal heterotopia (IEGH) in an infant. Glioneuronal heterotopias are rare congenital disorders that arise in the head, face, spine, and thoracic cavity. They consist of nodular accumulations of neuronal and glial cells that have developed abnormally, ranging in size from small lesions to large masses. Among heterotopias, IEGHs are relatively rare. They cause various clinical symptoms, depending on their size and location. The neuroimaging studies, histological examinations, and intraoperative findings presented provide insight into the pathogenesis of this disorder. The findings support the separation and detachment theory, which proposes that IEGHs originate from a third telencephalon that erroneously forms between the 4th and 6th week of embryogenesis. More detailed case reports are necessary to understand fully the pathogenesis of IEGHs.

Publication Types:
PMID: 16206744 [PubMed - indexed for MEDLINE]
 
26: J Neurosurg. 2005 Jan;102(1 Suppl):101-4.

Radiation-induced spinal cord cavernous malformation. Case report.

Yoshino M, Morita A, Shibahara J, Kirino T.

Department of Neurosurgery, Faculty of Medicine, University of Tokyo, Japan.

The authors report a case of a 16-year-old girl who presented with progressive gait difficulty 8 years after undergoing spinal radiation therapy for spinal astrocytoma. Magnetic resonance imaging revealed intramedullary multicentric cavity formation in the T4-10 area. Extensive subtotal resection was performed and a pathological examination of the excised tissue demonstrated cavernous malformation with radiation-induced degeneration in the surrounding vessels. This is believed to be the third case of de novo formation of an intramedullary cavernous malformation following spinal radiation therapy.

Publication Types:
PMID: 16206743 [PubMed - indexed for MEDLINE]
 
27: J Neurosurg. 2005 Jan;102(1 Suppl):78-80.

Successful resection of a hypothalamic hamartoma and a Rathke cleft cyst. Case report.

Ng YT, Kerrigan JF, Prenger EC, White WL, Rekate HL.

Department of Pediatrics, Barrow Neurological Institute, St. Joseph's Hospital, Phoenix, Arizona 85013, USA. y2ng@chw.edu

The authors report the case of a 12-year-old girl with Pallister-Hall syndrome, long-standing refractory, symptomatic epilepsy, mental retardation, and panhypopituitarism in whom two rare, deep midline lesions were detected. She underwent successful transsphenoidal resection of the Rathke cleft cyst and transcallosal resection of the hypothalamic hamartoma within a 4-day period without complications. Neuropathological studies confirmed the neuroimaging diagnoses for the two lesions. The patient has been seizure free for 6 months postoperatively.

Publication Types:
PMID: 16206738 [PubMed - indexed for MEDLINE]
 
28: J Neurosurg. 2005 Jan;102(1 Suppl):65-71.

Spontaneous regression of a diffuse brainstem lesion in the neonate. Report of two cases and review of the literature.

Thompson WD Jr, Kosnik EJ.

Section of Pediatric Neurosurgery, Department of Surgery, Children's Hospital of Columbus, Ohio, USA. willarddthompson@earthlink.net

The authors present two cases of diffuse brainstem lesions that regressed without treatment. Two newborns presented with cranial nerve palsies and limb weakness at birth. Magnetic resonance (MR) images obtained in the 1st week of life revealed a large, expansive pontomedullary lesion in each patient. Findings of clinical and imaging examinations were highly consistent with the characteristics of diffuse brainstem glioma. After consultation with the parents of both infants, all parties agreed to forgo the treatment modalities available at the time. Neither patient underwent surgery, radiation treatment, or chemotherapy; both underwent routine neurological and MR imaging examinations. Within weeks the patient in Case 1 started to improve clinically and at 4 years of age has reached nearly all developmental milestones. Serial MR images demonstrated a steady decrease in the size of the lesion. The patient in Case 2 improved in a similar manner and is now 10 years old. The findings from these two cases should encourage families and clinicians to consider that a subcategory of diffuse lesions may exist, particularly in the neonatal period. It must be stressed, however, that nearly all patients with diffuse brainstem lesions experience a poor outcome, regardless of tumor grade or treatment. Brainstem gliomas, spontaneous regression of central nervous system tumors, and the differential diagnoses of brainstem lesions are discussed.

Publication Types:
PMID: 16206736 [PubMed - indexed for MEDLINE]
 
29: J Neurosurg. 2005 Jan;102(1 Suppl):59-64.

The high incidence of tumor dissemination in myxopapillary ependymoma in pediatric patients. Report of five cases and review of the literature.

Fassett DR, Pingree J, Kestle JR.

Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah 84113, USA.

Myxopapillary ependymomas (MPEs) have historically been thought to be benign tumors occurring most frequently in adults. Only 8 to 20% of these tumors occur in the first two decades of life, making this tumor a rarity in pediatric neurosurgery. Five patients with intraspinal MPEs were treated by the authors between 1992 and 2003. Four (80%) of these five patients suffered from disseminated disease of the central nervous system (CNS) at the time of presentation; this incidence is much higher than that reported in the combined adult and pediatric literature. Combining five pediatric case series reported in the literature with the present series, the authors review a total of 26 cases of pediatric patients with intraspinal MPEs. In nine cases (35%) CNS metastases occurred. In those cases in which patients underwent screening for CNS tumor dissemination, however, the incidence of disseminated disease was 58% (seven of 12 patients). In pediatric patients MPEs may spread throughout the CNS via cerebrospinal fluid pathways; therefore, MR imaging of the entire CNS axis is recommended at both presentation and follow-up review to detect tumor dissemination.

Publication Types:
PMID: 16206735 [PubMed - indexed for MEDLINE]
 
30: J Neurosurg. 2005 Jan;102(1 Suppl):31-5.

Types, causes, and outcome of intracranial hemorrhage in children with cancer.

Kyrnetskiy EE, Kun LE, Boop FA, Sanford RA, Khan RB.

Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

OBJECT: The aim of this study was to investigate the cause and outcome of intracranial hemorrhage (ICH) in children with cancer. METHODS: The charts of 51 children who underwent treatment for both cancer and ICH between January 1985 and January 2003 were retrospectively reviewed. Assessment tools included the Karnofsky Performance Scale (KPS), Glasgow Coma Scale (GCS), and the Fisher exact and Student t-tests. Among the 51 cases, 30 involved brain tumors, 19 leukemia, and two lymphoma. The treatment group (Group 1) comprised 36 patients who suffered ICH during cancer treatment; the posttreatment group (Group 2) consisted of the 15 patients who suffered ICH after the completion of cancer treatment. The types of ICH included 22 cortical, four subcortical, 17 subdural, five brainstem, one subarachnoid, one epidural, and one ventricular. Thrombocytopenia was present in nine patients (25%) in Group 1. More patients in Group 2 (87%) than in Group 1 (44%) underwent cranial radiation treatment. Patients in Group 1 experienced a higher incidence of coagulopathy (37%) and ICH-related death (25%) than those in Group 2 (0 and 7%, respectively). Decrease in KPS and GCS scores of greater than 30 and greater than 3, respectively, at the time of ICH were indicators of increased mortality. Of the 17 children with subdural ICH, 13 suffered the hemorrhage following treatment for hydrocephalus and three patients suffered ICH associated with thrombocytopenia. In the 33 children alive at the 3-month follow-up examination after the ICH, no difference existed in the mean KPS scores pre- and post-ICH. CONCLUSIONS: Treatment for hydrocephalus, coagulopathy, thrombocytopenia, and hemorrhage into the tumor were the most probable causes of ICH among patients in Group 1. Radiation-induced vasculopathy was a possible cause of ICH in the patients in Group 2. Significant decline in the patient's neurological status at the time of ICH is a poor prognostic factor, but those patients who survive cancer and ICH are likely to regain neurological function.

PMID: 16206731 [PubMed - indexed for MEDLINE]
 
31: Neurosurgery. 2005 Oct;57(4):684-692.
 
Adjuvant gamma knife stereotactic radiosurgery at the time of tumor progression potentially improves survival for patients with glioblastoma multiforme.

Hsieh PC, Chandler JP, Bhangoo S, Panagiotopoulos K, Kalapurakal JA, Marymont MH, Cozzens JW, Levy RM, Salehi S.

Department of Neurological Surgery, Northwestern University McGaw Medical Center, Chicago, Illinois, USA. phsieh@md.northwestern.edu

OBJECTIVE: Gamma knife stereotactic radiosurgery (GK-SRS) is a safe and noninvasive treatment used as adjuvant therapy for patients with glioblastoma multiforme (GBM). Several studies have yielded conflicting results in the effectiveness of radiosurgery in GBM. This study is a retrospective review of our institutional experience with GK-SRS adjuvant therapy in the treatment of GBM. METHODS: From October 1998 to January 2003, 51 consecutive patients were treated with GK-SRS as an "upfront" adjuvant therapy after surgery or at the time of tumor progression at Northwestern Memorial Hospital. Survival analysis was performed using the Kaplan-Meier actuarial method. Univariate and multivariate analyses of patient characteristics and treatment variables were performed. RESULTS: Treatment with adjuvant GK-SRS yielded a median overall survival of 14.3 months for our cohort. Survival rate of the cohort was 68% at 12 months, 30% at 24 months, and 24% at 36 months. Karnofsky performance score greater than 90 and adjuvant chemotherapy were associated with increased survival on multivariate analysis. Adjuvant GK-SRS performed at tumor progression seems to increase median survival to 16.7 months compared with 10 months when performed after the time of initial tumor resection. Median survival rates by recursive partitioning analysis class breakdown in our cohort are greater than those predicted by other studies. CONCLUSION: GK-SRS is a relatively safe and noninvasive procedure that conferred an improvement in overall survival of GBM patients in our retrospective study. Particularly, GK-SRS may improve overall survival when performed at the time of tumor progression.

PMID: 16239880 [PubMed - as supplied by publisher]
 
32: Neurosurgery. 2005 Nov;57(5 Suppl):S66-77; discusssion S1-4.
 
Current treatment paradigms for the management of patients with brain metastases.

Ewend MG, Elbabaa S, Carey LA.

Division of Neurological Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7060, USA. ewend@med.unc.edu

Brain metastases continue to be a major and growing challenge in oncology, but recent advances in surgery, radiosurgery, and chemotherapy have broadened the number of treatment options. Current approaches to the management of brain metastases focus on individualizing patient care based on factors including the Karnofsky Performance Status, the tumor histology, the number of metastases, and the status of the systemic disease. A number of treatment approaches have been shown to be effective for brain metastases, including surgery; radiosurgery; whole-brain radiotherapy; and, more recently, chemotherapy. The use of adjuvant whole-brain radiotherapy with local therapies, such as surgery or radiosurgery, along with newer chemotherapy options, such as targeted biological agents, temozolomide, and implantable 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) Gliadel wafers, are at the forefront of recent advances in the treatment of patients with brain metastases that may provide longer survival and improved quality of life. Although there is no current standard treatment, some general guidelines are recommended for single metastases, oligometastases (two to three brain metastases), and multiple (four or more) brain metastases, and for new or recurrent disease. With advances in systemic therapy for cancer, the treatment of brain metastases is becoming an increasingly important determinant of the length of survival and quality of life for cancer patients.

PMID: 16237291 [PubMed - in process]
 
33: Neurosurgery. 2005 Nov;57(5 Suppl):S54-65; discusssion S1-4.
 
Chemotherapy in brain metastases.

Peereboom DM.

Cleveland Clinic Brain Tumor Institute, Hematology/Medical Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, USA. peerebd@ccf.org

The use OF chemotherapy to treat patients with brain metastases has been viewed historically with skepticism. To date, a survival benefit has not been demonstrated with the use of systemic chemotherapy in patients with brain metastases. However, the introduction of novel agents and delivery techniques warrants a reexamination of the role of systemic chemotherapy in the management of brain metastases. Temozolomide has shown encouraging results in patients with nonsmall cell lung cancer, and implanted carmustine wafers have demonstrated excellent local tumor control rates. This review discusses clinical data from the past decade with emphasis on trial design, tumor histology, available agents, and multimodality strategies. In addition, delivery techniques that circumvent the blood-brain barrier are reviewed. Although chemotherapy is usually used as a salvage therapy, it may be considered for use in selected patients with newly diagnosed brain metastases. To better evaluate chemotherapy in brain metastases, future trials should evaluate novel agents in the preirradiation setting. Enhanced regional delivery methods warrant further investigation, and Phase III trials of current regimens stratified by histology and by prognostic factors will establish the role of specific chemotherapy regimens in the treatment of patients with brain metastases.

PMID: 16237290 [PubMed - in process]
 
34: Neurosurgery. 2005 Nov;57(5 Suppl):S33-44; discusssion S1-4.
 
Current strategies in whole-brain radiation therapy for brain metastases.

Mehta MP, Khuntia D.

University of Wisconsin Hospital, Madison, Wisconsin 53792, USA.

Whole-brain radiation therapy (WBRT) has been the primary treatment for patients with brain metastases for more than 50 years and provides effective palliative relief in most patients. Although advancements in radiotherapeutic technique continue to improve local and locoregional control, median survival for patients treated with WBRT monotherapy remains fixed at approximately 4 to 6 months. Key issues in the use of WBRT include optimizing its efficacy when it is used in conjunction with surgery, radiosurgery, radiosensitizers, and new chemotherapeutic agents. These multimodal approaches to brain metastases have resulted in significant increases in the median survival time in many patients. Radiosurgery is part of a continuing effort to improve the effects of radiation therapy, especially in brain metastases. The optimal combination of WBRT and radiosurgery remains to be elucidated, including appropriate timing or sequence and use in conjunction with other modalities. Newer radiosensitizing agents (e.g., efaproxiral [RSR-13] and motexafin gadolinium) have shown promise in the treatment of brain tumors, especially in specific patient subsets. Recently developed systemic chemotherapy agents, such as temozolomide, which crosses the blood-brain barrier, have a synergistic effect on brain metastases when used in conjunction with radiation. In addition, the use of interstitial chemotherapy agents provides highly focused local chemotherapy in the brain without increasing systemic toxicity; carmustine polymer wafer, in combination with WBRT, has shown promising results in treating brain metastases.

PMID: 16237287 [PubMed - in process]
 
35: Neurosurgery. 2005 Nov;57(5 Suppl):S24-32; discusssion S1-4.
 
Current treatment approaches to surgery for brain metastases.

Sills AK.

Department of Neurosurgery, University of Tennessee, Memphis, Tennessee 38163, USA. asills@semmes-murphey.com

The role for surgical treatment of brain metastases continues to evolve. Data have demonstrated survival and quality-of-life benefits for surgical treatment of appropriate lesions in selected patients. With improvements in surgical technique, along with therapeutic improvements in the management of systemic cancers, more patients are now eligible for surgical resection. Selection of patients for surgical treatment depends on performance status, size, location, and number of brain lesions, as well as the status of systemic disease. Although surgery has traditionally been performed for patients with a single brain metastasis, an increasing number of patients with multiple brain metastases may also be treated surgically. Surgical techniques, such as image guidance, intraoperative ultrasound, functional neuronavigation, cortical mapping, and awake craniotomies, have expanded the scope of lesions that can be removed safely to optimize outcomes. Seizures, peritumoral edema, and venous thromboembolic disease all contribute significantly to surgical morbidity and mortality and thus require aggressive treatment around the time of the surgical procedure to improve the quality of life and maximize survival time.

PMID: 16237284 [PubMed - in process]
 
36: Neurosurgery. 2005 Oct;57(4 Suppl):382-91; discussion 382-91.
 
Intraoperative optical spectroscopy identifies infiltrating glioma margins with high sensitivity.

Toms SA, Lin WC, Weil RJ, Johnson MD, Jansen ED, Mahadevan-Jansen A.

Brain Tumor Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. tomss@ccf.org

OBJECTIVE: Adult gliomas have indistinct borders. As the ratio of neoplastic cells to normal cells becomes lower, the ability to detect these cells diminishes. We describe a device designed to augment intraoperative identification of both solid tumor and infiltrating tumor margins. METHODS: A novel, intraoperative, optical spectroscopic tool, using both white light reflectance and 337-nm excitation fluorescence spectroscopy, is described. Discrimination algorithms have been developed to segregate neoplastic tissues from normal glial and neuronal elements. The spectroscopy device was used to measure 5 to 10 locations during glioma resection. Beneath the tool, a biopsy sample was obtained and the pathological results were reviewed in a blinded fashion. Samples were classified as solid tumor, infiltrating tumor, or normal gray or white matter. Comparisons were made between the optical spectra and the histopathological results of sampled areas in evaluating the sensitivity and specificity of the tool for tissue discrimination. RESULTS: Spectral data were obtained from 24 patients with glioma and from 11 patients with temporal lobe epilepsy. A sensitivity of 80% and a specificity of 89% in discriminating solid tumor from normal tissues were obtained. In addition, infiltrating tumor margins were distinguished from normal tissues with a sensitivity of 94% and a specificity of 93%. CONCLUSION: We have developed a handheld, optical spectroscopic device that may be used rapidly and in near real time with high sensitivity and reproducibility as an optical tissue discrimination tool in glioma surgery.

PMID: 16234690 [PubMed - in process]
 
37: Neurosurgery. 2005 Oct;57(4 Suppl):312-8; discussion 312-8.
 
Endoscopic surgery for intraventricular brain tumors in patients without hydrocephalus.

Souweidane MM.

Department of Neurological Surgery and Pediatrics, Weill Medical College of Cornell University, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. mmsouwei@med.cornell.edu

OBJECTIVE: Endoscopy usually is avoided in patients without hydrocephalus because of presumed difficulties with ventricular cannulation and intraventricular navigation. The feasibility of endoscopic tumor management in patients without hydrocephalus was assessed on the basis of achieving the surgical objective and assessing procedure-related morbidity. METHODS: Eighty patients who underwent endoscopic management for an intraventricular brain tumor were identified from a prospective database. Of these patients, 15 had an intraventricular tumor without concomitant hydrocephalus and underwent primary endoscopic surgery for biopsy or resection. The surgical technique, the success rate, and patient outcome were assessed and then compared with 65 hydrocephalic patients who underwent similar procedures. RESULTS: Tumors were located in the third ventricle in 11 patients and the lateral ventricle in 4 patients. The ventricular compartment was cannulated successfully and the intended goal was accomplished in all patients (100%); 12 had successful diagnostic sampling and 3 had complete colloid cyst resection. There were no operative complications related to the endoscopic procedure, and no patient required subsequent intervention for hydrocephalus. The results in this group of patients did not differ with the success and morbidity after endoscopic tumor surgery in patients with hydrocephalus. CONCLUSION: Endoscopic biopsy or resection of intraventricular brain tumors in patients without hydrocephalus is feasible. The described procedure uniformly satisfied the intended surgical goal. The absence of ventriculomegaly in patients with an intraventricular brain tumor should not serve as a contraindication to endoscopic tumor biopsy or resection.

PMID: 16234680 [PubMed - in process]
 
38: Neurosurgery. 2005 Oct;57(4 Suppl):268-80; discussion 268-80.
 
Olfactory groove meningiomas from neurosurgical and ear, nose, and throat perspectives: approaches, techniques, and outcomes.

Spektor S, Valarezo J, Fliss DM, Gil Z, Cohen J, Goldman J, Umansky F.

Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel. spektor@hadassah.org.il

OBJECTIVE: To