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BRAINLIFE NEWSLETTER
Volume 4, Number 21 - 10 May 2005	Volume 4 Archive

1: Arch Pathol Lab Med. 2004 Nov;128(11):1303-4.

 
Secondary leptomeningeal sarcomatosis.

Grier DD, Yachnis AT.

Department of Pathology, Immunology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610-0275, USA. grierdd@pathology.ufl.edu

Publication Types:

• Case Reports

PMID: 15504072 [PubMed - indexed for MEDLINE] 
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2: Arch Pathol Lab Med. 2004 Nov;128(11):1289-93.

 
Epithelioid hemangioendothelioma of the suprasellar area: a case report and review of the literature.

Baehring JM, Dickey PS, Bannykh SI.

Department of Neurology, Yale University School of Medicine, New Haven, Conn 06510, USA.

Intra-axial involvement of the brain by an epithelioid hemangioendothelioma is rare, and biological properties of the tumor are uncertain. Most of the primary brain manifestations are confined to the cerebral hemispheres. We report magnetic resonance imaging and microscopic findings of a case of suprasellar involvement by an epithelioid hemangioendothelioma. The tumor was treated with a subtotal resection only, and no progression of the disease was noted during a 6-month follow-up. Review of the literature suggested that most epithelioid hemangioendotheliomas in the brain are unifocal tumors with a rather favorable clinical outcome.

Publication Types:

• Case Reports
• Review
• Review of Reported Cases

PMID: 15504067 [PubMed - indexed for MEDLINE]
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3: Cancer. 2005 Apr 1;103(7):1457-67.

 
International Classification of Childhood Cancer, third edition.

Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch P.

International Agency for Research on Cancer, Lyon, France. steliarova@iarc.fr

BACKGROUND: The third edition of the International Classification of Diseases for Oncology (ICD-O-3), which was published in 2000, introduced major changes in coding and classification of neoplasms, notably for leukemias and lymphomas, which are important groups of cancer types that occur in childhood. This necessitated a third revision of the 1996 International Classification of Childhood Cancer (ICCC-3). METHODS: The tumor categories for the ICCC-3 were designed to respect several principles: agreement with current international standards, integration of the entities defined by newly developed diagnostic techniques, continuity with previous childhood classifications, and exhaustiveness. RESULTS: The ICCC-3 classifies tumors coded according to the ICD-O-3 into 12 main groups, which are split further into 47 subgroups. These 2 levels of the ICCC-3 allow standardized comparisons of the broad categories of childhood neoplasms in continuity with the previous classifications. The 16 most heterogeneous subgroups are broken down further into 2-11 divisions to allow study of important entities or homogeneous collections of tumors characterized at the cytogenetic or molecular level. Some divisions may be combined across the higher-level categories, such as the B-cell neoplasms within leukemias and lymphomas. CONCLUSIONS: The ICCC-3 respects currently existing international standards and was designed for use in international, population-based, epidemiological studies and cancer registries. The use of an international classification system is especially important in the field of pediatric oncology, in which the low frequency of cases requires rigorous procedures to ensure data comparability. Copyright 2005 American Cancer Society.

PMID: 15712273 [PubMed - indexed for MEDLINE]
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4: Cancer Res. 2005 May 1;65(9):3928-36.

 
Tumor necrosis factor reduces brain tumor growth by enhancing macrophage recruitment and microcyst formation.

Villeneuve J, Tremblay P, Vallieres L.

Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, Quebec City, Quebec, Canada. Luc.Vallieres@crchul.ulaval.ca

Recent findings implicate macrophages and some of their secreted products, especially tumor necrosis factor (TNF), as tumor promoters. Inhibitors of these inflammatory components are currently regarded as potential therapeutic tools to block tumor progression. Here, we show that infiltrating macrophages represented a significant population of nonneoplastic cells within malignant gliomas, in which they were the exclusive producers of TNF. Contrary to the reported pro-oncogenic effects of TNF in other types of solid tumors, glioma-bearing mice deficient in TNF developed larger tumors and had reduced survival compared with their wild-type controls. Histologic examinations revealed that glioma volume was negatively correlated with the number of macrophages and small cavities called microcysts. Overall, our results support the concept that macrophages alter brain tumor development through a TNF-dependent process that culminates in the formation of microcysts. This raises the question of whether anti-inflammatory drugs, such as those commonly administrated to patients with brain cancer, could interfere with antitumor mechanisms.

PMID: 15867393 [PubMed - in process]
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5: Cancer Res. 2005 May 1;65(9):3617-23.

 
Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8.

Hong C, Maunakea A, Jun P, Bollen AW, Hodgson JG, Goldenberg DD, Weiss WA, Costello JF.

Department of Neurological Surgery, Brain Tumor Research Center, University of California-San Francisco, San Francisco, California 94143-0875, USA.

Tumors arise in part from the deleterious effects of genetic and epigenetic mechanisms on gene expression. In several mouse models of human tumors, the tumorigenic phenotype is reversible, suggesting that epigenetic mechanisms also contribute significantly to tumorigenesis in mice. It is not known whether these are the same epigenetic mechanisms in human and mouse tumors or whether they affect homologous genes. Using an integrated approach for genome-wide methylation and copy number analyses, we identified SLC5A8 on chromosome 12q23.1 that was affected frequently by aberrant methylation in human astrocytomas and oligodendrogliomas. SLC5A8 encodes a sodium monocarboxylate cotransporter that was highly expressed in normal brain but was significant down-regulated in primary gliomas. Bisulfite sequencing analysis showed that the CpG island was unmethylated in normal brain but frequently localized methylated in brain tumors, consistent with the tumor-specific loss of gene expression. In glioma cell lines, SLC5A8 expression was also suppressed but could be reactivated with a methylation inhibitor. Expression of exogenous SLC5A8 in LN229 and LN443 glioma cells inhibited colony formation, suggesting that it may function as a growth suppressor in normal brain cells. Remarkably, 9 of 10 murine oligodendroglial tumors (from p53+/- or ink4a/arf+/- animals transgenic for S100beta-v-erbB) showed a similar tumor-specific down-regulation of mSLC5A8, the highly conserved mouse homologue. Taken together, these data suggest that SLC5A8 functions as a growth suppressor gene in vitro and that it is silenced frequently by epigenetic mechanisms in primary gliomas. The shared epigenetic inactivation of mSLC5A8 in mouse gliomas indicates an additional degree of commonality in the origin and/or pathway to tumorigenesis between primary human tumors and these mouse models of gliomas.

PMID: 15867356 [PubMed - in process]
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6: Cancer Res. 2005 May 1;65(9):3562-7.

 
Inactivation of the invasion inhibitory gene IIp45 by alternative splicing in gliomas.

Song SW, Fuller GN, Zheng H, Zhang W.

Department of Pathology and Brain Tumor Center, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

The invasion inhibitory protein 45 (IIp45) we recently identified was underexpressed in glioblastoma multiforme, the most malignant form of glioma. The IIp45 gene is located at chromosome 1p36 where frequent deletions have been reported in various types of tumors, including gliomas, raising the possibility that IIp45 may be a classic tumor suppressor gene that can be inactivated by frequent point mutations. To test this hypothesis, we sequenced the IIp45 gene in 59 diffuse glioma samples of different grades and histologic subtypes and identified a possible point mutation or a rare polymorphism in only one sample (1.7%), suggesting that IIp45 is not a classic tumor suppressor gene such as p53. Instead, reverse transcription-PCR and subsequent sequencing results revealed a tumor-specific IIp45 spliced isoform (IIp45S) in 20 of 59 (34%) gliomas examined, particularly in glioblastoma multiformes, including native tissue samples (15 of 25; 60%) and cell lines (5 of 5; 100%). The alternative splicing event is independent of 1p36 deletion, which is not common in glioblastoma multiforme. The IIp45S transcript was not detected in any of 18 normal organs, including fetal and adult brain. We determined that the IIp45S isoform results from exclusion of IIp45 exon 7 and encodes a variant protein that carries a COOH terminus different from that of IIp45 due to a frame-shift mutation. IIp45S protein was undetectable in glioma tissues, although IIp45S mRNA was prevalent. We found that IIp45S, once translated, is rapidly degraded by an ubiquitin-proteasome mechanism. Thus, the IIp45 gene is inactivated by a tumor-specific alternative splicing that generates an aberrant and unstable IIp45 isoform in infiltrative gliomas.

PMID: 15867349 [PubMed - in process]
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7: Clin Cancer Res. 2005 May 1;11(9):3475-84.

 
The Antitumor Effects of Angelica sinensis on Malignant Brain Tumors In vitro and In vivo.

Tsai NM, Lin SZ, Lee CC, Chen SP, Su HC, Chang WL, Harn HJ.

Authors' Affiliations: Institute of Medical Sciences, Buddhist Tzu Chi University.

PURPOSE: In this study, we have examined the antitumor effects of chloroform extract of Angelica sinensis (AS-C), a traditional Chinese medicine, on glioblastoma multiforme (GBM) brain tumors in vitro and in vivo.EXPERIMENTAL DESIGN: In vitro, GBM cells were treated with AS-C, and the cell proliferation, changes in distributions of cell cycle, and apoptosis were determined. In vivo, human DBTRG-05MG and rat RG2 GBM tumor cells were injected s.c. or i.c. and were treated with AS-C. Effects on tumor growth were determined by tumor volume, magnetic resonance imaging, survival, and histology analysis.RESULTS: The AS-C displays potency in suppressing growth of malignant brain tumor cells without cytotoxicity to fibroblasts. Growth suppression of malignant brain tumor cells by AS-C results from cell cycle arrest and apoptosis. AS-C can up-regulate expression of cdk inhibitors, including p21, to decrease phosphorylation of Rb proteins resulting in cell arrest at the G(0)-G(1) phase for DBTRG-05MG and RG2 cells. The apoptosis-associated proteins are dramatically increased and activated in DBTRG-05MG cells and RG2 cells by AS-C but RG2 cells without p53 protein expression. In vitro results showed AS-C triggered both p53-dependent and p53-independent pathways for apoptosis. In in vivo studies, AS-C not only can suppress growths of malignant brain tumors of rat and human origin but also shrink the volumes of in situ GBM, significantly prolonging survivals.CONCLUSIONS: The in vitro and in vivo anticancer effects of AS-C indicate that it has sufficient potential to warrant further investigation and development as a new anti-brain tumor agent.

PMID: 15867250 [PubMed - in process]
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8: Clin Cancer Res. 2005 May 1;11(9):3326-34.

 
YKL-40 Expression is Associated with Poorer Response to Radiation and Shorter Overall Survival in Glioblastoma.

Pelloski CE, Mahajan A, Maor M, Chang EL, Woo S, Gilbert M, Colman H, Yang H, Ledoux A, Blair H, Passe S, Jenkins RB, Aldape KD.

Authors' Affiliations: Departments of Radiation Oncology, Neuro-Oncology, and Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, and Department of Pathology and Laboratory Medicine, Mayo Clinic and Foundation, Rochester, Minnesota.

PURPOSE: YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function is unknown. Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here we test these findings in a larger series of patients with glioblastoma, and in particular, determine if tumor YKL-40 expression is associated with radiation response.EXPERIMENTAL DESIGN: Patients (n = 147) with subtotal resections were studied for imaging-assessed changes in tumor size in serial studies following radiation therapy. An additional set (n = 140) of glioblastoma patients who underwent a gross-total resection was tested to validate the survival association and extend them to patients with minimal residual disease.RESULTS: In the subtotal resection group, higher YKL-40 expression was significantly associated with poorer radiation response, shorter time to progression and shorter overall survival. The association of higher YKL-40 expression with poorer survival was validated in the gross-total resection group. In multivariate analysis with both groups combined (n = 287), YKL-40 was an independent predictor of survival after adjusting for patient age, performance status, and extent of resection. YKL-40 expression was also compared with genetically defined subsets of glioblastoma by assessing epidermal growth factor receptor amplification and loss at chromosome 10q, two of the common recurring aberrations in these tumors, using fluorescent in situ hybridization. YKL-40 was significantly associated with 10q loss.CONCLUSIONS: The findings implicate YKL-40 as an important marker of therapeutic response and genetic subtype in glioblastomas and suggest that it may play an oncogenic role in these tumors.

PMID: 15867231 [PubMed - in process]
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9: Clin Cancer Res. 2004 Nov 1;10(21):7109-11.

Comment on:

• Clin Cancer Res. 2004 Nov 1;10(21):7182-91.

 
Imaging molecular signatures in oligodendroglioma.

Cairncross JG.

Department of Clinical Neurosciences, University of Calgary and Tom Baker Cancer Centre, Calgary, Alberta, Canada. jgcairnx@ucalgary.ca

Publication Types:

• Comment

PMID: 15534080 [PubMed - indexed for MEDLINE]

Clin Cancer Res. 2004 Nov 1;10(21):7182-91.

Correlation of molecular genetics with molecular and morphological imaging in gliomas with an oligodendroglial component.

Walker C, du Plessis DG, Fildes D, Haylock B, Husband D, Jenkinson MD, Joyce KA, Broome J, Kopitski K, Prosser J, Smith T, Vinjamuri S, Warnke PC.

JK Douglas Laboratories and Clatterbridge Centre for Oncology, Clatterbridge Hospital, Bebington, Wirral, United Kingdom. carol.walker@ccrt.nhs.uk

PURPOSE: Since the recognition that oligodendrogliomas may be chemosensitive, their diagnosis and clinical management has become highly controversial. Histopathology diagnosis remains challenging and new tools such as molecular genetics or molecular imaging require evaluation. EXPERIMENTAL DESIGN: In a single-center, population-based prospective study, allelic imbalance in chromosomes 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 has been investigated in 19 oligodendroglioma WHO grade 2 (OII), 20 oligoastrocytoma WHO grade 2 (OAII), 8 oligodendroglioma WHO grade 3 (OIII), and 12 oligoastrocytoma WHO grade 3 (OAIII), and compared with pretherapy histopathology, computed tomography and/or magnetic resonance (CT and/or MR), [fluorine-18]fluoro-2-deoxyglucose (18F-FDG), and thallium-201 single-photon emission computed tomography (201Tl SPECT). RESULTS: In 50 cases, 18F-FDG uptake correlated with 201Tl uptake; however, 8 cases had increased 201Tl uptake but were hypometabolic for 18F-FDG, and 1 case was hypermetabolic with normal 201Tl uptake. Sixteen cases enhanced on CT/MR but failed to show 201Tl uptake; and 2 low-grade non-enhancing oligodendrogliomas had increased 201Tl uptake. Increased metabolism was more likely in high-grade cases, with 201Tl uptake more strongly correlated with grade than was 18F-FDG uptake. Tumors with 1p/19q loss were more likely to show increased 201Tl uptake and, to a lesser degree, increased 18F-FDG uptake than those without these losses. Elevated metabolism in 28% of low-grade tumors was significantly more common in tumors with 1p/19q loss, and increased uptake of both 18F-FDG and 201Tl in low-grade cases was found only in those with 1p/19q loss. CONCLUSIONS: In this study, dissociation of uptake of contrast agents and radiotracers suggests independent deregulation of the blood-brain barrier breakdown and metabolism during disease progression of oligodendroglial neoplasms, and the association of elevated metabolism with 1p/19q loss, particularly in low-grade tumors, may have implications for clinical management.

PMID: 15534091 [PubMed - indexed for MEDLINE]
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10: J Neurosurg. 2005 Apr;102(4):738-44.

Malignant glioma-induced neuronal cell death in an organotypic glioma invasion model. Technical note.

Eyupoglu IY, Hahnen E, Heckel A, Siebzehnrubl FA, Buslei R, Fahlbusch R, Blumcke I.

Department of Neurosurgery, University of Erlangen-Nuremberg Department of Neuropathology, University of Erlangen-Nuremberg, Erlangen, Germany. eyupoglu@gmx.net

Rapid growth and diffuse brain infiltration are hallmarks of malignant gliomas. The underlying molecular pathomechanisms of these tumors, however, remain to be determined. The authors present a novel glioma invasion model that allows researchers to monitor consecutively tumor cell proliferation and migration in an organotypic brain environment. Enhanced green fluorescent protein-labeled F98 rat glioma cells were implanted into slice cultures obtained from a rat hippocampus, and tumor growth was microscopically documented up to 20 days in vitro. Invasion along radially oriented migratory streams could be observed 5 days after implantation of rat F98, human U87MG, and mouse GL261 glioma cells, whereas human Be(2)c neuroblastoma cells and mouse HT22 hippocampal neurons failed to invade the brain parenchyma. Following implantation of F98 glioma cells into the entorhinal cortex, cell death was observed within the infiltrated brain parenchyma as well as in the neuroanatomically connected dentate gyrus. Application of the N-methyl-D-aspartate receptor antagonist MK801 to the culture medium significantly reduced neuronal degeneration in the dentate gyrus, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist GYKI 52466 inhibited peritumoral cytotoxicity. This new model allows researchers to address in a systematic manner the molecular pathways of brain invasion as well as specific tumor-host interactions such as necrosis.

PMID: 15871520 [PubMed - in process]
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11: J Neurosurg. 2005 Apr;102(4):733-7.

Intraventricular chordoid meningioma presenting with Castleman disease due to overproduction of interleukin-6. Case report.

Arima T, Natsume A, Hatano H, Nakahara N, Fujita M, Ishii D, Wakabayashi T, Doyu M, Nagasaka T, Yoshida J.

Department of Neurosurgery, Division of Pathology, Clinical Laboratory, Center for Genetic and Regenerative Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

A rare case of chordoid meningioma in the lateral ventricle observed in an adult is reported. The first clinical manifestation of the disease was a prolonged fever of unknown origin. Abnormalities in the patient's blood chemistry, principally polyclonal hypergammaglobulinemia (immunoglobulin [Ig]G, IgA, and markedly IgE) and an elevated serum level of C-reactive protein, were associated with the disease. The tumor was histologically confirmed to be a chordoid meningioma, and its surgical removal resulted in complete resolution of the patient's symptoms. By combining reverse transcription-polymerase chain reaction and immunohistochemical analysis, it may be shown that cytokine production, including that of interleukin (IL)-6, IL-1beta, and vascular endothelial growth factor, plays a role in the pathogenesis of chordoid meningioma associated with Castleman syndrome.

PMID: 15871519 [PubMed - in process]
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12: J Neurosurg. 2005 Apr;102(4):706-14.

Combined cimetidine and temozolomide, compared with temozolomide alone: significant increases in survival in nude mice bearing U373 human glioblastoma multiforme orthotopic xenografts.

Lefranc F, James S, Camby I, Gaussin JF, Darro F, Brotchi J, Gabius J, Kiss R.

Department of Neurosurgery, Erasmus University Hospital, Belgium.

OBJECT: Malignant gliomas consist of both heterogeneous proliferating and migrating cell subpopulations, with migrating glioma cells exhibiting less sensitivity to antiproliferative or proapoptotic drugs than proliferative cells. Therefore, the authors combined cimetidine, an antiinflammatory agent already proven to act against migrating epithelial cancer cells, with temozolomide to determine whether the combination induces antitumor activities in experimental orthotopic human gliomas compared with the effects of temozolomide alone. METHODS: Cimetidine added to temozolomide compared with temozolomide alone induced survival benefits in nude mice with U373 human glioblastoma multiforme (GBM) cells orthotopically xenografted in the brain. Computer-assisted phase-contrast microscopy analyses of 9L rat and U373 human GBM cells showed that cimetidine significantly decreased the migration levels of these tumor cells in vitro at concentrations at which tumor growth levels were not modified (as revealed on monotetrazolium colorimetric assay). Computer-assisted microscope analyses of neoglycoconjugate-based glycohistochemical staining profiles of 9L gliosarcomas grown in vivo revealed that cimetidine significantly decreased expression levels of endogenous receptors for fucose and, to a lesser extent, for N-acetyl-lactosamine moieties. Endogenous receptors of this specificity are known to play important roles in adhesion and migration processes of brain tumor cells. CONCLUSIONS: Cimetidine, acting as an antiadhesive and therefore an antimigratory agent for glioma cells, could be added in complement to the cytotoxic temozolomide compound to combat both migrating and proliferating cells in GBM.

PMID: 15871514 [PubMed - in process]
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13: J Neurosurg. 2005 Apr;102(4):699-705.

Functional and phenotypic differences between glioblastoma multiforme-derived and normal human brain endothelial cells.

Charalambous C, Hofman FM, Chen TC.

Department of Molecular Microbiology, University of Southern California Keck School of Medicine, Los Angeles, California, USA.

OBJECT: Glioblastomas multiforme (GBMs) are hypervascular tumors characterized by endothelial cell (EC) proliferation. There is increasing evidence that ECs that infiltrate systemic tumors are different from normal blood vessel cells; whether this difference is seen in the central nervous system between GBM and normal brain tissue is not known. The goal of this investigation was to characterize and compare the functional and phenotypic properties of GBM-associated ECs and normal brain ECs. METHODS: Human ECs were isolated from fresh tissue specimens, purified using flow cytometry, and characterized by immunostaining. Proliferation was measured by determining bromodeoxyuridine incorporation and Ki-67 staining, and by performing the monotetrazolium assay. The migration rate of the cells was determined using the modified Boyden chamber technique. Apoptosis was evaluated by performing the TUNEL assay, cell death enzyme-linked immunosorbent assay (ELISA), and annexin V staining. Growth factor production was analyzed using the ELISA technique. The brain tumor ECs differed from normal brain ECs morphologically and by their expression and distribution of specific markers (that is, vascular endothelial cadherin [VE-cadherin] and CD31). Functional differences between the two cell populations were also evident. The brain tumor ECs proliferated more slowly and underwent less apoptosis than normal brain ECs; however, the tumor ECs migrated faster than the normal ECs. The normal ECs were sensitive to growth factors such as vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1), whereas the tumor ECs were not. In addition, the brain tumor ECs constitutively produced higher levels of ET-1 and VEGF, compared with the normal ECs. CONCLUSIONS: The data demonstrated that ECs derived from normal brain and from GBMs have significant phenotypic and functional distinctions. Further characterization of brain tumor ECs is essential for efficient antiangiogenic treatment of gliomas.

PMID: 15871513 [PubMed - in process]
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14: J Neurosurg. 2005 Apr;102(4):650-7.

Long-term neurological, visual, and endocrine outcomes following transnasal resection of craniopharyngioma.

Chakrabarti I, Amar AP, Couldwell W, Weiss MH.

Department of Neurological Surgery, University of Southern California, Los Angeles, California 90032, USA. Ichakrab@usc.edu

OBJECT: The authors report on a cohort of patients with craniopharyngioma treated principally through transnasal (TN) resection and followed up for a minimum of 5 years. More specifically, they evaluate the role of the TN approach in the management of craniopharyngioma. METHODS: Between 1984 and 1994, 68 patients underwent TN resection of craniopharyngiomas at the University of Southern California. The tumor was at least partially cystic in 88% of cases. Four tumors were purely intrasellar, 53 had intra- and suprasellar components, and 11 were exclusively suprasellar. During the same period, 18 patients underwent transcranial (TC) resection of purely suprasellar craniopharyngiomas. Long-term neurological, visual, and endocrine outcomes were reviewed for all patients. In 61 (90%) of 68 patients in the TN group, total resection was achieved, according to 3-month postoperative magnetic resonance images, although four patients suffered a recurrence. Three (43%) of the seven tumors that had been partially resected were enlarged on serial imaging. Fifty-four (87%) of 62 patients with preoperative visual loss experienced improvement in one or both eyes, but two patients (3%) with exclusively suprasellar tumors experienced postoperative visual worsening in one or both eyes. New instances of postoperative endocrinopathy (that is, not present preoperatively) occurred as follows: hypogonadism (eight of 22 cases), growth hormone (GH) deficiency (four of 18 cases), hypothyroidism (11 of 49 cases), hypocortisolemia (nine of 52 cases), and diabetes insipidus (DI; four of 61 cases). One case each of hypocortisolemia and hypothyroidism resolved after surgery. Hyperphagia occurred in 27 (40%) of 68 patients. One patient had short-term memory loss. Postoperative complications included one case of cerebrospinal fluid leak. Among the 18 patients in the TC group, 11 had complete resections. In one case (9%) the tumors recurred. Three (43%) of the seven subtotally resected tumors grew during the follow-up interval. Vision improved in 11 (61%) of 18 cases and worsened in three (17%) as a result of surgery. New instances of postoperative endocrinopathy occurred as follows: hypogonadism (one of six cases), GH deficiency (four of seven cases), hypothyroidism (11 of 14 cases), hypocortisolemia (eight of 15 cases), and DI (nine of 16 cases). No instance of preoperative endocrinopathy was corrected through TC surgery. Four patients (22%) exhibited short-term memory loss and 11 (61%) had hyperphagia after surgery. When compared with those in the TC group, patients in the TN group had shorter hospital stays. CONCLUSIONS: Use of the TN approach can render good outcomes in properly selected patients with craniopharyngioma, particularly when the tumor is cystic. Even in mostly suprasellar cases, an extended TN approach can afford complete resection. Note that endocrine function often worsens after surgery and that postoperative obesity can be a significant problem.

PMID: 15871507 [PubMed - in process]
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15: J Neurosurg. 2005 Apr;102(4):637-42.

Intraoperative auditory brainstem responses in patients with cerebellopontine angle meningiomas involving the inner auditory canal: analysis of the predictive value of the responses.

Nakamura M, Roser F, Dormiani M, Samii M, Matthies C.

Department of Neurosurgery, Nordstadt Hospital, Teaching Hospital of Hannover Medical School, Hannover, Germany. mnakamura@web.de

OBJECT: Meningiomas of the cerebellopontine angle (CPA) can either arise from or secondarily grow into the inner auditory canal (IAC). This location may have a great impact on hearing function following surgery to remove these lesions. The aim of this retrospective study was to investigate the reliability and predictive importance of auditory brainstem responses (ABRs) for the determination of postoperative auditory function in patients with CPA meningiomas in comparison with results obtained in patients who undergo surgery for vestibular schwannomas. METHODS: In a consecutive series of 1800 meningiomas surgically treated between 1978 and 2002, 421 lesions were located in the CPA. In 38 patients with CPA meningiomas involving the IAC, the findings of intraoperative ABR monitoring and the hearing status of each patient before and after surgery were retrospectively analyzed. On analysis, ABR monitoring demonstrated stable findings in 24 patients throughout tumor resection and fluctuating signals in 10 patients. Among the 24 patients with stable ABRs, postoperative hearing function improved in three patients, remained the same in 15, and worsened in six patients, including one patient who displayed postoperative deafness. There was even one patient recovering from preoperative deafness. Among the 10 patients with unstable ABRs, intermittent decreases in amplitude and deformations of variable duration in the ABR wave were noted. The risk of deafness was considerably higher in patients with prolonged phases of intermittent ABR deterioration. CONCLUSIONS: The presence and absence of ABRs during surgery for CPA meningiomas reliably predicted the presence and absence of postoperative auditory function. Intermittent deterioration of ABRs may result in postoperative deafness, depending on the duration of these events during surgery. Improvements in hearing are only seen when the ABRs are stable for amplitudes and latencies throughout surgery.

PMID: 15871505 [PubMed - in process]
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16: J Neurosurg. 2005 Apr;102(4):622-8.

Prognostic significance of intracranial dissemination of glioblastoma multiforme in adults.

Parsa AT, Wachhorst S, Lamborn KR, Prados MD, McDermott MW, Berger MS, Chang SM.

Department of Neurological Surgery, School of Medicine, University of California at San Francisco, California 94143, USA. parsaa@neurosurg.ucsf.edu

OBJECT: The clinical outcome and treatment of adult patients with disseminated intracranial glioblastoma multiforme (GBM) is unclear. The objective in the present study was to assess the prognostic significance of disseminated intracranial GBM in adults at presentation and at the time of tumor progression. METHODS: Clinical data from 1491 patients older than 17 years and harboring a GBM that had been diagnosed between 1988 and 1998 at the University of California at San Francisco neurooncology clinic were retrospectively reviewed. Dissemination of the GBM (126 patients) was determined based on Gd-enhanced magnetic resonance images. Classification of dissemination was as follows: Type I, single lesion with subependymal or subarachnoid spread; Type II, multifocal lesions without subependymal or subarachnoid spread; and Type III, multifocal lesions with subependymal or subarachnoid spread. Subgroups of patients were compared using Kaplan-Meier curves that depicted survival probability. The median postprogression survival (PPS), defined according to neuroimaging demonstrated dissemination, was 37 weeks for Type I (23 patients), 25 weeks for Type II (50 patients), and 10 weeks for Type III spread (19 patients). Patients with dissemination at first tumor progression (52 patients) overall had a shorter PPS than those in a control group with local progression, after adjusting for age, Kamofsky Performance Scale score, and time from tumor diagnosis to its progression (311 patients). When analyzed according to tumor dissemination type, PPS was significantly shorter in patients with Type II (33 patients, p < 0.01) and Type III spread (11 patients, p < 0.01) but not in those with Type I spread (eight patients, p = 0.18). CONCLUSIONS: Apparently, the presence of intracranial tumor dissemination on initial diagnosis does not in itself preclude aggressive treatment if a patient is otherwise well. A single focus of GBM that later demonstrates Type I dissemination on progression does not have a worse prognosis than a lesion that exhibits only local recurrence.

PMID: 15871503 [PubMed - in process]
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17: J Nucl Med. 2005 May;46(5):763-9.

 
Characterization of 68Ga-DOTA-D-Phe1-Tyr3-Octreotide Kinetics in Patients with Meningiomas.

Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S, Schuhmacher J, Strauss LG, Doll J, Macke HR, Eisenhut M, Debus J, Haberkorn U.

Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany.

Because biopsy has a high risk of hemorrhage and the findings of CT and MRI are often ambiguous, especially at the base of the skull, additional methods for the characterization of intracranial tumors are needed. Meningiomas show high expression of the somatostatin receptor subtype 2 and thus offer the possibility of receptor-targeted imaging. We used the somatostatin analog (68)Ga-DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) labeled with the positron emitter (68)Ga (half-life, 68 min), obtained from a (68)Ge/(68)Ga generator, for PET of these tumors. In contrast to (18)F-FDG, this ligand shows high meningioma-to-background ratios. The aim was to evaluate kinetic parameters in meningiomas before radiotherapy. METHODS: Dynamic PET scans (3-dimensional mode; 28 frames; ordered-subsets expectation maximization reconstruction) were acquired for 21 patients (mean age +/- SD, 51 +/- 13 y) before radiotherapy during the 60 min after intravenous injection of 156 +/- 29 MBq of (68)Ga-DOTA-TOC. We analyzed 28 meningiomas (median grade [I] according to the system of the World Health Organization) with volumes of at least 0.5 mL (mean volume, 13.1 mL) and nasal mucosa as reference tissue, showing a slight to moderate physiologic uptake. For evaluation of the (68)Ga-DOTA-TOC kinetics, the vascular fraction (vB) and the rate constants (k1, k2, k3, and k4 [1/min]) were computed using a 2-tissue-compartment model. Furthermore, receptor binding (RB) (k1 - k1 x k2) and the ratios k1/k2 and k3/k4 were calculated. RESULTS: Significant differences (P < 0.05; t test) between meningiomas and the reference tissue were found for the mean standardized uptake value (10.5 vs.1.3), vB (0.42 vs. 0.11), k2 (0.12 vs. 0.56), k3 (0.024 vs. 0.060), k4 (0.004 vs. 0.080), and RB (0.49 vs. 0.13). Although there was no significant difference for k1 (0.54 vs. 0.40), the ratios k1/k2 (4.50 vs. 0.71) and k3/k4 (6.00 vs. 0.75) were markedly greater in meningiomas than in reference tissue. CONCLUSION: The high uptake of (68)Ga-DOTA-TOC in meningiomas can be explained by the high values for vB and by the remarkably low values for k2 and k4, leading to significantly greater k1/k2 and k3/k4 ratios and RB in meningiomas than in reference tissue. Thus, pharmacokinetic modeling offers a more detailed analysis of biologic properties of meningiomas. In further studies, these data might serve as a basis for monitoring the somatostatin receptors of meningiomas after radiotherapy.

PMID: 15872348 [PubMed - in process]
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18: Pediatr Neurol. 2005 May 2; [Epub ahead of print]

 
Management of tectal glioma in childhood.

Stark AM, Fritsch MJ, Claviez A, Dorner L, Mehdorn HM.

Departments of Neurosurgery.

Tectal glioma is a topographical diagnosis including tumors of different histology, mainly low-grade astrocytomas. Clinical symptoms are usually associated with increased intracranial pressure. This report discusses the management of this rare tumor in children. Clinical charts of 12 children with tectal glioma treated in our department between 1976 and 2001 were retrospectively reviewed. The mean age at the time of diagnosis was 6.75 years (range, 4 weeks to 16 years). The duration between first symptoms and the diagnosis of tectal glioma was in the range of 2 days to 9 years. Ten patients presented with symptoms associated with increased intracranial pressure, one patient presented with ataxia, and in one case tectal glioma was an incidental finding. First-line therapy was endoscopic third ventriculostomy in 5 cases (42%), ventriculoperitoneal shunting in 6 cases (50%), and combined partial tumor resection and shunting in one case. Histology was obtained in 5 cases (low-grade astrocytoma, n = 4; ependymoma, n = 1). All patients had good neurologic function at the end of follow-up. Tectal glioma represents a distinct subgroup of brainstem tumors associated with a good (or favorable) prognosis. Effective treatment for hydrocephalus is essential; the tumor should be monitored by regular clinical examination and magnetic resonance imaging. Biopsy is warranted in cases with tumor progression.

PMID: 15876519 [PubMed - as supplied by publisher]
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19: Brain. 2005 Apr;128(Pt 4):797-810. Epub 2005 Feb 10.

 
New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations.

Duffau H, Gatignol P, Mandonnet E, Peruzzi P, Tzourio-Mazoyer N, Capelle L.

Department of Neurosurgery, U 678, Hopital Salpetriere, 47-83 Bd de l'Hopital, 75651 Paris, Cedex 13, France. hugues.duffau@psl.ap-hop-paris.fr

Despite a better understanding of the organization of the cortical network underlying the semantic system, very few data are currently available regarding its anatomo-functional connectivity. Here, we report on a series of 17 patients operated on under local anaesthesia for a cerebral low-grade glioma located within the dominant hemisphere. Prior to and during resection, intraoperative electrical stimulation was used to map sensorimotor and language structures so that permanent neurological deficits could be avoided. In a number of cases, cortical and subcortical stimulation caused semantic paraphasias. Using postoperative MRI, we correlated these functional findings with the anatomical locations of the sites where semantic errors were elicited by stimulation, especially at the subcortical level, with the aim of studying the connectivity underlying the semantic system. In temporal gliomas, cortical sites involved in semantic processing were found around the posterior part of the superior temporal sulcus, with subcortical pathways reproducibly located under the depth of this sulcus. In insular gliomas, although stimulation elicited no semantic disturbances at the cortical level, such semantic paraphasias were generated at the level of the anterior floor of the external capsule. In frontal tumours, cortical regions implicated in semantics were detected in the lateral orbitofrontal region and dorsolateral prefrontal cortex, with subcortical fibres located under the inferior frontal sulcus. All these eloquent structures were systematically preserved, thereby avoiding permanent postoperative deficits. Our results provide arguments in favour of the existence of a main ventral subcortical pathway underlying the semantic system, within the dominant hemisphere, joining the two essential cortical epicentres of this network: the posterior and superior temporal areas, and the orbitofrontal and dorsolateral prefontal regions. Such a ventral stream might anatomically partly correspond to the inferior fronto-occipital fasciculus.

PMID: 15705610 [PubMed - indexed for MEDLINE]
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20: Cancer. 2005 Mar 15;103(6):1227-33.

 
Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance.

Claus EB, Horlacher A, Hsu L, Schwartz RB, Dello-Iacono D, Talos F, Jolesz FA, Black PM.

Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA. elizabeth.claus@yale.edu

BACKGROUND: No age-adjusted or histologic-adjusted assessments of the association between extent of resection and risk of either recurrence or death exist for neurosurgical patients who undergo resection of low-grade glioma using intraoperative magnetic resonance image (MRI) guidance. METHODS: The current data included 156 patients who underwent surgical resection of a unifocal, supratentorial, low-grade glioma in the MRI suite at Brigham and Women's Hospital between January 1, 1997, and January 31, 2003. Estimates of disease-free and overall survival probabilities were calculated using Kaplan-Meier methodology. The association between extent of resection and these probabilities was measured using a Cox proportional hazards model. Observed death rates were compared with the expected death rate using age-specific and histologic-specific survival rates obtained from the Surveillance, Epidemiology, and End Results Registry. RESULTS: Patients who underwent subtotal resection were at 1.4 times the risk of disease recurrence (95% confidence interval [95% CI], 0.7-3.1) and at 4.9 times the risk of death (95% CI, 0.61-40.0) relative to patients who underwent gross total resection. The 1-year, 2-year, and 5-year age-adjusted and histologic-adjusted death rates for patients who underwent surgical resection using intraoperative MRI guidance were 1.9% (95% CI, 0.3-4.2%), 3.6% (95% CI, 0.4-6.7%), and 17.6% (95% CI, 5.9-29.3%), respectively: significantly lower than the rates reported using national data bases. CONCLUSIONS: The data from the current study suggested a possible association between surgical resection and survival for neurosurgical patients who underwent surgery for low-grade glioma under intraoperative MRI guidance. Further study within the context of a large, prospective, population-based project will be needed to confirm these findings.

PMID: 15690327 [PubMed - indexed for MEDLINE]
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