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BRAINLIFE NEWSLETTER
Volume 4, Number 37 - 10 September 2005

Volume 4
Archive
1: Acta Cytol. 2005 Jul-Aug;49(4):464-5.

Rhabdoid meningioma diagnosed by imprint cytology.

Batoroev YK, Nguyen GK.

Publication Types:
  • Letter

PMID: 16124182 [PubMed - in process]
 
2: Acta Cytol. 2005 Jul-Aug;49(4):431-4.

Intraventricular squamous papillary craniopharyngioma: report of a case with intraoperative imprint cytology.

Madhavan M, P JG, Abdullah Jafri J, Idris Z.

Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. madhavan@kb.usm.my

BACKGROUND: Squamous papillary craniopharyngioma is a distinct entity, and its cytologic features may be misleading. Because of the rarity of this tumor, this case is being reported with a note on the cytologic features. CASE: A 56-year-old Malay man who had 1-month history of generalized lethargy was admitted for altered sensorium. On examination, he was found to have neck stiffness, bilateral papilledema and generalized atrophy of muscles, with reduced power in all limbs. Magnetic resonance imaging of the brain showed a solid mass in the third ventricle causing obstructive hydrocephalus. Intraoperative cytology of the mass diagnosed intraventricular meningioma. However, the final histopathologic examination revealed squamous papillary craniopharyngioma. CONCLUSION: Craniopharyngioma, squamous papillary type, is a rare entity and usually occurs in adults as an intraventricular solid tumor. Awareness of this entity will aid in arriving at the correct cytologic diagnosis.

PMID: 16124175 [PubMed - in process]
 
3: Ann Neurol. 2005 Sep;58(3):483-7.
 
Two types of chromosome 1p losses with opposite significance in gliomas.

Idbaih A, Marie Y, Pierron G, Brennetot C, Hoang-Xuan K, Kujas M, Mokhtari K, Sanson M, Lejeune J, Aurias A, Delattre O, Delattre JY.

Unite Institut National de la Sante et de la Recherche Medicale (INSERM) U509, Laboratoire Pathologie Moleculaire des Cancers, Institut Curie, Paris, France.

Deletion of the short arm of chromosome 1 (1p) is considered a favorable prognostic factor in glial tumors. High-density array-comparative genomic hybridization analysis of 108 gliomas shows two distinct types of 1p deletions. Complete hemizygous losses of 1p, which are tightly associated with 19q loss and oligodendroglial phenotype, and partial 1p deletions mainly observed in astrocytic tumors and not associated with 19q loss. Whereas the first type predicts longer overall and progression-free survival (p < 0.0001), the second type has a pejorative prognostic value. Complete 1p-arm evaluation therefore is required to appreciate the real clinical significance of 1p loss in gliomas. Ann Neurol 2005;58:483-487.

PMID: 16130103 [PubMed - in process]
 
4: Cancer. 2005 Aug 29; [Epub ahead of print]
 
Marital status, treatment, and survival in patients with glioblastoma multiforme.

Chang SM, Barker FG 2nd.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.

BACKGROUND: Social factors influence cancer treatment choices, potentially affecting patient survival. In the current study, the authors studied the interrelations between marital status, treatment received, and survival in patients with glioblastoma multiforme (GM), using population-based data. METHODS: The data source was the Surveillance, Epidemiology, and End Results (SEER) Public Use Database, 1988-2001, 2004 release, all registries. Multivariate logistic, ordinal, and Cox regression analyses adjusted for demographic and clinical variables were used. RESULTS: Of 10,987 patients with GM, 67% were married, 31% were unmarried, and 2% were of unknown marital status. Tumors were slightly larger at the time of diagnosis in unmarried patients (49% of unmarried patients had tumors larger than 45 mm vs. 45% of married patients; P = 0.004, multivariate analysis). Unmarried patients were less likely to undergo surgical resection (vs. biopsy; 75% of unmarried patients vs. 78% of married patients) and were less likely to receive postoperative radiation therapy (RT) (70% of unmarried patients vs. 79% of married patients). On multivariate analysis, the odds ratio (OR) for resection (vs. biopsy) in unmarried patients was 0.88 (95% confidence interval [95% CI], 0.79-0.98; P = 0.02), and the OR for RT in unmarried patients was 0.69 (95% CI, 0.62-0.77; P < 0.001). Unmarried patients more often refused both surgical resection and RT. Unmarried patients who underwent surgical resection and RT were found to have a shorter survival than similarly treated married patients (hazard ratio for unmarried patients, 1.10; P = 0.003). CONCLUSIONS: Unmarried patients with GM presented with larger tumors, were less likely to undergo both surgical resection and postoperative RT, and had a shorter survival after diagnosis when compared with married patients, even after adjustment for treatment and other prognostic factors. Cancer 2005. (c) 2005 American Cancer Society.

PMID: 16130137 [PubMed - as supplied by publisher]
 
5: Childs Nerv Syst. 2005 Aug;21(8-9):778-84. Epub 2005 Jun 14.
 
Craniopharyngioma in children: Marseille experience.

Lena G, Paredes AP, Scavarda D, Giusiano B.

Department of Pediatric Neurosurgery, Hopital des Enfants La Timone, 264, Rue Saint Pierre, 13385, Marseille, Cedex 05, France, gabriel.lena@ap-hm.fr.

OBJECTIVES: The management of craniopharyngioma in children represents a challenging problem. If radical excision is recommended by many authors as the initial treatment, in some cases, particularly in recurrent tumours, other methods (gamma knife surgery and intracystic bleomycin) can be very useful. Even if craniopharyngioma is a benign tumour, recurrences are frequent, and the aim of our study was to analyse our results, to try to determine some prognostic factors of recurrences and to discuss about a new strategy concerning the initial management of these tumours. METHODS: Forty-seven children with craniopharyngioma were treated in the Department of Pediatric Neurosurgery. All of the patients, but five children treated by intracystic bleomycin, underwent a surgical resection of the tumour as initial treatment with the goal of achieving gross total removal (GTR) of the tumour. Two children had radiotherapy and gamma knife treatment, respectively, following surgery for a tumoural residue. All the children had a magnetic resonance imaging (MRI) study 3 months after surgery to evaluate the results of the initial treatment. Using statistical analysis, some prognostic factors (age, sex, location, aspect, size of the tumour and result of the first MRI) have been studied. RESULTS: Forty-two children were operated on, but one died in the immediate postoperative period from a major stroke due to carotid spasm. GTR, defined as the absence of residue on the first MRI control, was achieved in 27 children (65.8%), but 7 patients (25.9%) presented recurrence. Subtotal removal (STR) was obtained in 14 children (34.2%), but 9 patients (64.3%) developed a recurrence defined as the growth of the residual tumour with or without clinical symptoms. Five children having a small- or moderate-size cystic craniopharyngioma were treated using one-stage (three cases) or two-stage (two cases) intracystic bleomycin and any presented recurrence. All the prognostic factors studied, except one (presence of a residue on the first MRI control), do not have a statistical significance. CONCLUSION: Craniopharyngioma in children remains a formidable tumour, and regardless of whatever progress made in their management, the incidence of recurrences is still elevated and severe sequelae can be observed. There are no prognostic factors among those studied concerning the recurrences of these tumours except the quality of the exeresis confirmed by the first postoperative MRI.

PMID: 16133277 [PubMed - in process]
 
6: Childs Nerv Syst. 2005 Aug;21(8-9):719-24. Epub 2005 Jun 14.
 
Use of interferon alpha in intratumoral chemotherapy for cystic craniopharyngioma.

Cavalheiro S, Dastoli PA, Silva NS, Toledo S, Lederman H, da Silva MC.

Department of Neurology and Neurosurgery, Pediatric Oncology Institute, Federal University of Sao Paulo-Escola Paulista de Medicina, Rua Botucatu 591/42, 4023-061, Sao Paulo, Brazil, iscava@uol.com.br.

OBJECTIVES: This study analyzed the intratumoral activity of interferon alpha (IFN-alpha) in the treatment of cystic craniopharyngiomas. PATIENTS AND METHODS: From January 2000 to January 2004, nine patients presenting with cystic craniopharyngiomas were treated with intratumoral injection of IFN-alpha at the Pediatric Oncology Institute of the Federal University of Sao Paulo-Escola Paulista de Medicina. Age ranged from 1 year and 10 months to 18 years (mean 10 years). All intratumoral catheters were inserted by a subfrontal approach. Doses varied from 36 to 108 MU. RESULTS: There was complete disappearance of the lesion in seven cases. In two cases, partial reduction of tumor size was observed at follow-up. Follow-up varied from 1 year to 3 years and 6 months (mean 1 year 8 months). CONCLUSIONS: IFN-alpha proved to be an effective drug in the control of cystic craniopharyngiomas. Additional studies should be carried out to determine the optimal dose of IFN-alpha in the treatment of cystic craniopharyngioma. In addition, other drugs possessing high efficacy and low neurotoxicity should be analyzed.

PMID: 16133276 [PubMed - in process]
 
7: Childs Nerv Syst. 2005 Aug;21(8-9):679-90. Epub 2005 Jun 14.
 
Radical resection of craniopharyngioma.

Zuccaro G.

Department of Neurosurgery, Hospital Nacional de Pediatria Juan P. Garrahan, Buenos Aires, Argentina.

INTRODUCTION: The best management of craniopharyngioma in children remains a controversial topic among neurosurgeons. The two treatments for craniopharyngioma most commonly discussed in the literature are primary total resection and limited resection followed by radiotherapy. Without ignoring the challenging behavior of these tumors, we strongly believe that the first approach in a child with a craniopharyngioma is to attempt total removal. Trying to remove a craniopharyngioma that has been treated previously with other methods is, in our experience, much more dangerous because of adherences of the tumor to vascular and neural structures. MATERIAL AND METHODS: Between 1988 and 2004, we operated on 153 patients with craniapharyngioma (40% female and 60% male), whose ages at the time of surgery ranged from 15 days to 21 years (mean 10.5 years). Eighty-seven percent of the patients were found to have some visual disturbance and 42% endocrinological alterations. Fifty-four percent of the patients presented hydrocephalus, but only 18% had shunting. Gross total removal was attempted in all patients. Among the 153 patients, the tumor was prechiasmatic in 35 and retrochiasmatic in 112; in ten, these were considered giant forms, and eight had a posterior fossa extension. We performed 84 single and 69 combined approaches. RESULTS: We achieved total removal in 69% of our patients. None of our patients regarded as having undergone total tumor resection disclosed recurrence after a follow-up of 1-16 years. Radiation therapy was administered in children with subtotal removal. All children underwent total removal, but only 62% of those who underwent subtotal removal had good outcomes. After surgery, endocrinological status worsened in almost all patients, but visual status improved markedly. CONCLUSIONS: The treatment of choice in craniopharyngioma in childhood is total resection in order to avoid radiation therapy and recurrence. When total resection is not possible, subtotal resection plus radiation therapy is the alternative.

PMID: 16133275 [PubMed - in process]
 
8: Childs Nerv Syst. 2005 Aug 16; [Epub ahead of print]
 
Giant cell glioblastoma multiforme: report of a case with prolonged survival and transformation to gliosarcoma.

Deb P, Sharma MC, Chander B, Mahapatra AK, Sarkar C.

Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India, drchitrasarkar@yahoo.com.

INTRODUCTION: Giant cell glioblastomas (GCGs) and gliosarcomas are rare histological variants of glioblastoma multiforme (GBMs). The mean age of occurrence in GCG is 42 years, but occasional cases have been documented in children under 10 years of age. Clinically, they are associated with a better prognosis than conventional GBMs, with few reports documenting prolonged survival up to 17 years after diagnosis. In contrast, gliosarcomas have age distribution and survival characteristics similar to conventional GBMs. They either arise de novo (primary) or secondary to irradiation to GBM. CASE REPORT: We report a rare case of childhood GCG in an 8-year-old boy surviving for more than 10 years since initial diagnosis. He has had two recurrences at the ages of 16 and 17 years, respectively, with histopathology at second recurrence showing evidence of gliosarcoma. DISCUSSION: No such case of gliosarcoma following treatment for GCG has been reported in the literature. Hence, the origin of the gliosarcoma whether radiation induced or only a phenotypic change in the GBM remains conjectural.

PMID: 16133270 [PubMed - as supplied by publisher]
 
9: Clin Cancer Res. 2005 Jun 1;11(11):3987-4002.
 
Boron neutron capture therapy of cancer: current status and future prospects.

Barth RF, Coderre JA, Vicente MG, Blue TE.

Department of Pathology, The Ohio State University, Columbus, Ohio 43210, USA. barth.1@osu.edu

BACKGROUND: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas and either cutaneous primaries or cerebral metastases of melanoma, most recently, head and neck and liver cancer. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the United States, Japan, several European countries, and Argentina. Accelerators also can be used to produce epithermal neutrons and these are being developed in several countries, but none are currently being used for BNCT. BORON DELIVERY AGENTS: Two boron drugs have been used clinically, sodium borocaptate (Na(2)B(12)H(11)SH) and a dihydroxyboryl derivative of phenylalanine called boronophenylalanine. The major challenge in the development of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations ( approximately 20 microg/g tumor) sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal tissue toxicity. Over the past 20 years, other classes of boron-containing compounds have been designed and synthesized that include boron-containing amino acids, biochemical precursors of nucleic acids, DNA-binding molecules, and porphyrin derivatives. High molecular weight delivery agents include monoclonal antibodies and their fragments, which can recognize a tumor-associated epitope, such as epidermal growth factor, and liposomes. However, it is unlikely that any single agent will target all or even most of the tumor cells, and most likely, combinations of agents will be required and their delivery will have to be optimized. CLINICAL TRIALS: Current or recently completed clinical trials have been carried out in Japan, Europe, and the United States. The vast majority of patients have had high-grade gliomas. Treatment has consisted first of "debulking" surgery to remove as much of the tumor as possible, followed by BNCT at varying times after surgery. Sodium borocaptate and boronophenylalanine administered i.v. have been used as the boron delivery agents. The best survival data from these studies are at least comparable with those obtained by current standard therapy for glioblastoma multiforme, and the safety of the procedure has been established. CONCLUSIONS: Critical issues that must be addressed include the need for more selective and effective boron delivery agents, the development of methods to provide semiquantitative estimates of tumor boron content before treatment, improvements in clinical implementation of BNCT, and a need for randomized clinical trials with an unequivocal demonstration of therapeutic efficacy. If these issues are adequately addressed, then BNCT could move forward as a treatment modality.

Publication Types:
  • Review

PMID: 15930333 [PubMed - indexed for MEDLINE]
 
10: Clin Cancer Res. 2005 Apr 15;11(8):3032-7.
 
Gefitinib as a first-line therapy of advanced or metastatic adenocarcinoma of the lung in never-smokers.

Lee DH, Han JY, Lee HG, Lee JJ, Lee EK, Kim HY, Kim HK, Hong EK, Lee JS.

Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea.

PURPOSE: A subset of patients with adenocarcinoma of the lung who had never smoked cigarettes showed excellent tumor responses to gefitinib therapy. To evaluate the efficacy of gefitinib as a first-line therapy in this subgroup of patients, we conducted a phase II study. EXPERIMENTAL DESIGN: Eligible patients had no smoking history, stage IIIB or IV adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ functions. Treatment consisted of daily oral administration ofF 250 mg gefitinib for 28 days until disease progression. Responses were assessed after every two cycles of therapy. RESULTS: Of 37 patients enrolled, 36 were assessed for response. Twenty-five patients (69%) had partial response, 4 (11%) had stable disease, and 7 (19%) had progressive disease. Of 10 patients with evaluable brain metastases, 7 had objective responses in both intracranial and extracranial lesions, 1 had stable disease in the brain and dramatic response in the extracranial lesions, and 2 had progressive disease in both sites. After a median follow-up of 48 weeks (range, 4-70 weeks), 26 patients had disease progression, with median progression-free survival of 33 weeks, and 9 patients died, all due to disease progression. The median survival time has not been reached yet but the estimated 1-year survival rate was 73%. Common toxicities were skin rash and mild diarrhea but there was no significant hematologic toxicity. CONCLUSIONS: Gefitinib showed very dramatic antitumor activity, even in the brain, with unprecedented survival outcome in never-smoker adenocarcinoma patients. These data support the use of gefitinib as a first-line therapy in this particular subgroup.

Publication Types:
  • Clinical Trial
  • Clinical Trial, Phase II

PMID: 15837758 [PubMed - indexed for MEDLINE]
 
11: Clin Cancer Res. 2005 Apr 15;11(8):2907-18.
 
Array comparative genomic hybridization identifies genetic subgroups in grade 4 human astrocytoma.

Misra A, Pellarin M, Nigro J, Smirnov I, Moore D, Lamborn KR, Pinkel D, Albertson DG, Feuerstein BG.

Brain Tumor Research Center, Department of Neurosurgery, University of California San Francisco, San Francisco, California, USA. amisra@cc.ucsf.edu

Alterations of DNA copy number are believed to be important indicators of tumor progression in human astrocytoma. We used an array of bacterial artificial chromosomes to map relative DNA copy number in 50 primary glioblastoma multiforme tumors at approximately 1.4-Mb resolution. We identified 33 candidate sites for amplification and homozygous deletion in these tumors. We identified three major genetic subgroups within these glioblastoma multiforme tumors: tumors with chromosome 7 gain and chromosome 10 loss, tumors with only chromosome 10 loss in the absence of chromosome 7 gain, and tumors without copy number change in chromosomes 7 or 10. The significance of these genetic groups to therapeutics needs further study.

PMID: 15837741 [PubMed - indexed for MEDLINE]
 
12: J Clin Oncol. 2005 Sep 1;23(25):6207-19.
 
Current management of brain metastases, with a focus on systemic options.

Langer CJ, Mehta MP.

Division of Thoracic Oncology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA. CJ_Langer@fccc.edu

Brain metastases are an important sequelae of many types of cancer, most commonly lung cancer. Current treatment options include whole-brain radiation therapy (WBRT), surgical resection, stereotactic radiosurgery, and chemotherapy. Corticosteroids and antiepileptic medications are commonly used for palliation of mass effect and seizures, respectively. The overall median survival is only 4 months after WBRT. Combined-modality strategies of WBRT with either chemotherapy or novel anticancer agents are under clinical investigation. Promising results have been obtained with several experimental agents and confirmatory phase III trials are underway. Although improvement in overall survival has not been seen universally, reduction in death due to progression of brain metastases and prolongation of the time to neurologic and neurocognitive progression have been reported in selected series. On the basis of these findings, it might be possible to identify new agents that may enhance the efficacy of WBRT.

PMID: 16135488 [PubMed - in process]
 
13: J Neurooncol. 2005 Jul 30; [Epub ahead of print]
 
Hypoxia Inducible Factor 1-alpha Regulates of Platelet Derived Growth Factor-B in Human Glioblastoma Cells.

Yoshida D, Kim K, Noha M, Teramoto A.

Department of Neurosurgery, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan, dyoshida@nms.ac.jp.

Hypoxia inducible factors (HIF) are transcription factors regulating expression of several genes related to oxygen homeostasis in response to hypoxic stress. Although HIF1-alpha and platelet derived growth factor-B (PDGF-B) are expressed in glioma tissue and closely related to tumor angiogenesis mediating vascular endothelial growth factor (VEGF) activity, their direct relationship has not yet been clarified. The aim of this study is to investigate whether HIF1-alpha regulates PDGF-B expression. The human glioblastoma cell lines, U87MG, U251MG, and A172, were exposed to 1-21% oxygen for 24 h. PDGF-B mRNA expression were quantitatively analyzed by real time RT-PCR, their intracellular protein levels were determined by computerized image analysis supported by flow cytometry to detect intracellular PDGF-B, and the concentration of secreted PDGF-B protein was assayed by ELIA. We also assayed following transfection of the cells with short interference RNA (siRNA) targeting HIF1-alpha mRNA. Relative PDGF-B mRNA and secretion of PDGF-B protein were significantly elevated at 1% oxygen. Following transfection of HIF1-alpha siRNA at 1% oxygen, PDGF-B expression was significantly suppressed at mRNA level. Our findings indicated that HIF1-alpha up-regulated expression of PDGF-B in human glioblastoma cells and showed the feasibility of siRNA technology in glioblastoma cell lines.

PMID: 16136272 [PubMed - as supplied by publisher]
 
14: J Neurooncol. 2005 Aug 25;:1-8 [Epub ahead of print]
 
Expression of syndecans, a heparan sulfate proteoglycan, in malignant gliomas: participation of nuclear factor-kappaB in upregulation of syndecan-1 expression.

Watanabe A, Mabuchi T, Satoh E, Furuya K, Zhang L, Maeda S, Naganuma H.

Department of Neurosurgery, University of Yamanashi, Faculty of Medicine, 409 3898, Nakakoma-gun, Yamanashi, Japan.

Invasion of tumor cells into the surrounding normal brain tissues is a prominent feature of malignant gliomas. Malignant glioma cells secrete thrombospondin-1 which participates in the motility of glioma cells and binds cell surface heparan sulfate proteoglycan. To clarify the invasion mechanism of tumor cells, expression of the syndecans (syndecan-1, -2, -3, and -4), a major cell surface heparan sulfate proteoglycan family, was analyzed in malignant gliomas. Involvement of nuclear factor-kappaB (NF-kappaB) on syndecan-1 expression was also investigated. Using reverse transcription-PCR, the authors analyzed the expression of syndecan-1, -2, -3, and -4 in 10 malignant glioma cell lines, 2 glioblastoma specimens, and 2 normal brain specimens. All malignant glioma cell lines and glioblastoma specimens expressed all types of syndecan mRNA, except in one glioma cell line that lacked syndecan-3 expression. On the other hand, normal brain specimens expressed syndecan-2, -3, and -4 mRNA, but did not syndecan-1 mRNA. Syndecan-1 protein was localized in the cell surface of all malignant glioma cell lines by flow cytometry. Various levels of active nuclear factor-kappa B (NF-kappaB) was detected in all malignant glioma cell lines using immunoblotting. The expression of active NF-kappaB and syndecan-1 increased in U251 glioma cells after tumor necrosis factor-alpha or interleukin-1beta treatment, which can activate NF-kappaB. The amplification of active NF-kappaB and syndecan-1 by tumor necrosis factor-alpha or interleukin-1beta was suppressed by an inhibitor of NF-kappaB activation (emodin). Emodin also downregulated the expression of syndecan-1 mRNA in U251 cells. These results indicate that malignant glioma cells express all types of syndecans and suggest that NF-kappaB participates in the upregulation of the syndecan-1 expression at the transcriptional level, and increased expression of syndecan-1 could associate with extracellular matrices including thrombospondin-1.

PMID: 16132527 [PubMed - as supplied by publisher]
 
15: J Neurooncol. 2005 Aug 11; [Epub ahead of print]
 
Giant Nondural-Based Cauda Equina Meningioma with Multiple Cysts.

Hwang SL, Liu CS, Su YF, Shen WJ, Chuo CY, Liu GC, Howng SL, Lee KS.

Division of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

A very rare case of a giant nondural-based cauda equina meningioma with multiple cysts was presented. Spinal meningioma most commonly occurs in the thoracic or cervical region and typically adheres to the dura. Only six cases of nondural-based meningioma have been reported in English literature. All occurred in the cauda equina region. These patients were predominantly female and younger than those with typical intraspinal meningioma. A 46-year-old woman had a 4-year history of lower back pain and right leg pain. Progressive weakness of both lower extremities occurred. Magnetic resonance imaging revealed a giant cauda equina tumor with multiple cysts from T(12) to L(4.) Following laminectomies from T(11) to L(5) and intradural exposure, the tumor was found to be draped loosely by the roots of the cauda equina and attached to a root without any firm connection with dura mater. Complete removal of the tumor was achieved after microdissection of arachnoid and sacrifice of an involved rootlet of the cauda equina. The appearance of tumor was that of a typical neurilemmoma. However, histological and immunohistochemical analyses were consistent with meningioma. Nondural-based intraspinal meningiomas are very rare, particularly a giant tumor with multiple cysts as our presenting case. All of the cases previously reported, including our case, have been located in the cauda equina region. Most of the patients were female and were young, suggesting that the nondural-based cauda equina meningiomas are age- and sex-related. An accurate preoperative and operative diagnosis are difficult. Care must be taken in the management of cauda equina tumors resembling neurilemmoma which may in fact represent meningioma, particularly in the younger female.

PMID: 16132526 [PubMed - as supplied by publisher]
 
16: J Neurooncol. 2005 Jul 30; [Epub ahead of print]
 
CXCL12 Expression is Predictive of a Shorter Time to Tumor Progression in Low-Grade Glioma: A Single-Institution Study in 50 Patients.

Salmaggi A, Gelati M, Pollo B, Marras C, Silvani A, Balestrini MR, Eoli M, Fariselli L, Broggi G, Boiardi A.

Andrea Salmaggi MD, Istituto Nazionale Neurologico , Via Celoria 11, 20133 , C.Besta, Milano, Italy, salmaggi@istituto-besta.it.

The clinical course of 50 patients with low-grade glioma (31 male, 19 female) undergoing surgery at a single Institution from 1992 to 1996 was analyzed in relationship with known prognostic factors as far as time to tumor progression (TTP) and survival time (ST) are concerned. Moreover, microvessel density (MVD) and expression of the angiogenesis-related chemokine CXCL12 were investigated in surgical specimens. Age at diagnosis ranged from 1 to 68 years (median 30). Histology revealed 11 fibrillary, 6 protoplasmatic, 5 gemistocytic astrocytoma, 18 oligoastrocytoma and 10 oligodendroglioma. Mean follow-up was 86 months. Four patients were lost to follow-up. Of the remaining 46, twenty-four have shown disease progression and 14 have died. Median overall survival was not achieved; an estimated 75% percentage of survivors was found at 78 months. Complete gross tumor removal was associated to a longer TTP (P=0.04 logrank). Of the investigated immunohistochemical parameters, while MVD was not predictive of subsequent TTP, expression of CXCL12 was associated with a significantly shorter TTP (P=0.01 logrank): this predictive value remained significant (P=0.02) at multivariate analysis. The data suggest the possible prognostic value for CXCL-12 (an angiogenesis- and tumor-growth-related chemokine) on TTP in low-grade gliomas.

PMID: 16132525 [PubMed - as supplied by publisher]
 
17: J Neurooncol. 2005 Jul 29; [Epub ahead of print]
 
Intracavitary Chemotherapy (paclitaxel/Carboplatin Liquid Crystalline Cubic Phases) for Recurrent Glioblastoma - Clinical Observations.

Eckardstein KL, Reszka R, Kiwit JC.

Department of Neurosurgery, Klinikum Buch, HELIOS Klinikum Berlin, Hobrechtsfelder Chaussee 96, 13125, Berlin, Germany, keckardstein@berlin.helios-kliniken.de.

Human malignant brain tumors have a poor prognosis in spite of surgery and radiation therapy. Cubic phases consist of curved biocontinuous lipid bilayers, separating two congruent networks of water channels. Used as a host for cytotoxic drugs, the gel-like matrix can easily be applied to the walls of a surgical resection cavity. For human glioblastoma recurrences, the feasibility, safety, and short-term effects of a surgical intracavitary application of paclitaxel and carboplatin encapsulated by liquid crystalline cubic phases are examined in a pilot study. A total of 12 patients with a recurrence of a glioblastoma multiforme underwent re-resection and received an intracavitary application of paclitaxel and carboplatin cubic phases in different dosages. Six of the patients received more than 15 mg paclitaxel and suffered from moderate to severe brain edema, while the remaining patients received only a total of 15 mg paclitaxel. In the latter group, brain edema was markedly reduced and dealt medically. Intracavitary chemotherapy in recurrent glioblastoma using cubic phases is feasible and safe, yet the clinical benefit remains to be examined in a clinical phase II study.

PMID: 16132524 [PubMed - as supplied by publisher]
 
18: J Neurooncol. 2005 Jul 30; [Epub ahead of print]
 
Gliomatosis cerebri and pituitary adenoma: case report and literature review.

Mangiola A, Bonis PD, Guerriero M, Pompucci A, Anile C.

Institute of Neurosurgery, Catholic University School of Medicine, Roma, Italy, amangiola@rm.unicatt.it.

The diagnosis of Gliomatosis cerebri (GC) is known to be difficult and is still a matter of debate. We describe an in vivo case of GC associated with a pituitary tumor. A 47-year-old woman presented with short-term memory loss. A MRI revealed the presence of a pituitary enhancing tumor and a diffuse lesion involving the brain. A left pterional craniotomy with partial temporal lobectomy and removal of the pituitary lesion were performed in order to obtain diagnosis. The histological analyses showed a pituitary non-functioning tumor and a GC consisting of neoplastic oligodendrocytes and astrocytes. Both lesions showed nuclear immunoreactivity for progesterone receptors (PGr) and estrogen receptors (EGr). This result could suggest there is a common receptor substrate in these tumors. In this case hormones could constitute a common step in tumorigenesis of both lesions.

PMID: 16132522 [PubMed - as supplied by publisher]
 
19: J Neurooncol. 2005 Aug 1; [Epub ahead of print]
 
An in vitro study on the suppressive effect of glioma cell growth induced by plasmid-based small interference RNA (siRNA) targeting human epidermal growth factor receptor.

Kang CS, Pu PY, Li YH, Zhang ZY, Qiu MZ, Huang Q, Wang GX.

Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, 300052, Tianjin, P.R. China, pupeiyu33@hotmail.com.

Objectives: To study the inhibitory effects of plasmid-based siRNA targeting human epidermal growth factor receptor (EGFR) on tumor proliferation and invasion of TJ905 glioblastoma cells.Methods: Two siRNA expression constructs targeting human EGFR extracellular domain (516-536) and catalytic domain (2400-2420) were transfected into TJ905 cell as mediated by Lipofectamine. Immunofluorescence assay and Western blotting were used to detect EGFR expression. Cell cycle was analyzed by flow cytometry, cell proliferative activity was measured by MTT assay. The expression and enzymatic activity of MMP9 were measured by Western blotting and gelatin zymography. Cell invasive capability was evaluated by Transwell method. Results: The expression of EGFR was knocked-down by 90% and 92%, respectively in siRNA constructs transfected groups as indicated by immunofluorescence assay and Western blotting. The flow cytometric analysis showed that the S phase fraction (SPF) was lowered in both siRNAs transfected cells than that in parental cells and the cells transfected with empty vector. Compared to parental cells and the cells transfected with empty vector, the survival rates of glioma cells transfected with the siRNAs dramatically dropped down from the first day after implantation (P<0.05) as indicated by MTT assay. Meanwhile, the expression and enzymatic activity of MMP9 decreased significantly in siRNAs transfected in TJ905 cells, and cell invasive potential was also greatly inhibited in the Transwell study.Conclusion: The siRNA expression constructs targeting EGFR could specifically suppress EGFR expression, inhibit cell growth, induce cell cycle arrest and suppress invasion. The plasmid-based siRNA targeting human EGFR approach should be a new strategy for gene therapy of malignant gliomas.

PMID: 16132520 [PubMed - as supplied by publisher]
 
20: J Neurooncol. 2005 Jul 29; [Epub ahead of print]
 
The Boron-neutron Capture Agent beta-D: -5-o-carboranyl-2'-deoxyuridine Accumulates Preferentially in Dividing Brain Tumor Cells.

Moore C, Hernandez-Santiago BI, Hurwitz SJ, Tan C, Wang C, Schinazi RF.

Department of Nuclear Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

Boron-neutron capture therapy (BNCT) is based on the preferential targeting of tumor cells with (10)B and subsequent irradiation with epithermal neutrons to produce a highly localized field of lethal alpha particles, while sparing neighboring non-targeted cells. BNCT treatment of 9L brain tumors in a rat model using beta-D: -5-o-carboranyl-2'-deoxyuridine (d-CDU) resulted in greater efficacy than predicted based on the assumption of a uniform tumor distribution of (10)B. Thus, the geometric heterogeneity of dividing cells in brain tumors warranted studies on the cell cycle dependency of D: -CDU accumulation, metabolism and entrapment in a relevant brain tumor cell system. U-271 human glioma cells were synchronized in G(1) or S-phases of the cell cycle. The cellular accumulation and phosphorylation of D: -CDU was measured in the G(1) and S-phase cells using high-performance liquid chromatography (HPLC). Cells synchronized in the S-phase accumulated significantly higher amounts of D: -CDU and produced larger amounts of negatively charged D: -CDU monophosphate (D: -CDU-MP) and nido-CDU metabolites than resting cells. Since brain tumors contain a larger proportion of cycling cells than neighboring tissue, these results support the hypothesis that in addition to breakdown of the blood-brain-barrier (BBB) in tumors, the preferential phosphorylation of D: -CDU in cycling cells may further enrich the distribution of (10)B in dividing cells. Therefore, dosimetry calculations that include the spatial distribution of cycling cells may be warranted for D: -CDU.

PMID: 16132519 [PubMed - as supplied by publisher]
 
21: J Neurooncol. 2005 Jun 22; [Epub ahead of print]
 
Pediatric Adrenal Cortical Carcinoma: Brain Metastases and Relationship to NF-1, Case Reports and Review of the Literature.

Wagner AS, Fleitz JM, Kleinschmidt-Demasters BK.

Department of Pathology, University of Colorado Health Sciences Center, B-216, Denver, Colorado, 80262, U.S.A.

Adrenal cortical carcinoma (ACC) is a rare childhood neoplasm that seldom manifests brain metastases; hence few papers in the literature focus on neurological manifestations associated with ACC. Although ACC is known to be a signature tumor type in several inherited cancer predisposition syndromes, particularly Li Fraumeni, ACC has not been previously associated with neurofibromatosis, type 1 (NF-1), an inherited disorder with frequent CNS lesions that might prompt concern for metastatic disease by neuroimaging studies. We present two pediatric patients with ACC and unusual CNS findings. The first child developed metastasis to the brain 4 years after resection of his adrenal primary and 2 and 1 years, respectively, after metastases to the liver and lungs. Soon after our experience with this patient, a girl with known NF-1 presented with virilization; adrenalectomy disclosed an ACC and systemic metastases were found within months. Disseminated disease prompted concern that her complex intracranial lesions identified by neuroimaging studies might represent brain metastases, but this proved to be NF1-related hamartomatous lesions. We review the literature on ACCs in pediatric patients regarding brain metastases and previous associations with NF-1.

PMID: 16132517 [PubMed - as supplied by publisher]
 
22: J Neurooncol. 2005 Jul 30; [Epub ahead of print]
 
Breast Adenocarcinoma Metastatic to Epidural Cervical Spine Meningioma: Case Report and Review of the Literature.

Aghi M, Kiehl TR, Brisman JL.

Department of Neurosurgery, Massachusetts General Hospital, White Building, Room 502, 55 Fruit Street, 02114, Boston, MA, USA, maghi@partners.org.

While several cases of cancer metastatic to cranial meningiomas have been reported, metastasis to spinal meningioma has been reported only once, and a mechanism for such metastases has not been investigated. We report a case of breast carcinoma metastatic to an epidural cervical meningioma, summarize the literature on metastases to central nervous system meningiomas, and suggest a possible mechanism. Our patient, a 55-year-old woman, presented with difficulty walking, back pain, and quadriparesis. Magnetic resonance imaging revealed an enhancing C3-4 epidural lesion and an L4 compression fracture. Because of concern that the fracture and epidural lesion might represent metastases, we performed a metastatic work-up, which revealed a right breast mass. The patient underwent C3-C4 laminectomies and an epidural lesion was encountered. Intraoperative frozen section revealed mixed meningioma and breast adenocarcinoma. A gross total resection was achieved and the patient subsequently received spinal irradiation and hormonal therapy. Whereas a literature review revealed numerous reports of metastases to cranial meningiomas, this represents only the second reported case of such pathology in the spine. Mechanisms of this unusual process likely include meningiomas' vascularity, meningiomas' slow growth providing nutrient availability, and perhaps, as suggested by our analysis, E-cadherin expression by both meningiomas and breast cancer. Metastasis to meningioma must be considered in an epidural spinal lesion in all patients with a known malignancy, with surgical aggressiveness tailored to the intraoperative pathologic diagnosis.

PMID: 16132512 [PubMed - as supplied by publisher]
 
23: J Neurooncol. 2005 Jun 22; [Epub ahead of print]
 
Spinal Meningioma: Relationship Between Histological Subtypes and Surgical Outcome?

Schaller B.

Max-Planck-Institute for Neurological Research, Gleuelerstrasse, 50, D-50931, Cologne, Germany.

Intraspinal meningiomas are slow growing benign tumors that produce indolent neurological deficits, which are often reversible following operation. It is unclear, if there is a correlation between postoperative neurological restoration and histopathological parameters. The aim of the present work was to seek for existence of such parameters. Retrospectively, we reviewed the charts of 33 patients with spinal meningiomas who were operated on from January 1980 through December 1995. Histological classification was performed according to WHO criteria. Laminoplasty or hemilaminoplasty was performed in 29 patients (88%) and suboccipital craniotomy with cervical laminoplasty in 4 patients (12%). Mean age of the 30 women (91%) and the 3 men (9%) was 63 +/- 20 years (range 22-88). Spinal meningiomas were of high-cervical location in 9 (27%) and of low-cervico-thoracic location in 24 (73%) patients. Tumor position was laterally in 19 (58%), posteriorly in 8 (24%) and anteriorly in 6 (18%) patients. Histological classification was psammomatous in 22 (66%), fibroblastic in 7 (22%) and meningothelial in 4 (11%) patients. Following tumor resection, neurological deficits resolved in 26 of 33 patients (79%) and worsened in 7 of 33 patients (21%) all of the latter had meningiomas of the psammomatous type. Resection of psammomatous meningiomas of the spine is associated with a less favorable neurological outcome postoperatively than resection of spinal meningiomas of other pathological subtypes. Posterior or lateral tumor position in the spinal canal, location below C4, age less than 60 years, and duration of preoperative symptoms seem to be correlated with a good outcome.

PMID: 16132511 [PubMed - as supplied by publisher]
 
24: J Neurooncol. 2005 Jul 1; [Epub ahead of print]
 
ACNU-Cisplatin Continuous Infusion Chemotherapy as Salvage Therapy for Recurrent Glioblastomas: Phase II Study.

Gwak HS, Youn SM, Kwon AH, Lee SH, Kim JH, Rhee CH.

Department of Neurosurgery, Korea Institute of Radiological and Medical Science, Seoul, Korea, changhun@kcch.re.kr.

Purpose: To evaluate the activity and the toxicity of ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-cholroethyl)-3-nitrosourea hydrochloride) administered with cisplatin by intravenous infusion for 72 h in select patients with recurrent glioblastoma.Patients and methods: From April 1996 to 2002, 37 patients with histologically proven glioblastoma, who showed recurrence on image study after operation and radiation, met the eligibility criteria of our cohort. The mean time to recurrence was 9.7+/-7.0 (1-26 months). Treatment response was evaluated every 6 weeks using magnetic resonance imaging (MRI). Complete blood counts were collected every week to monitor and treat possible bone marrow suppression from the treatment. Survival rates were analyzed using the Kaplan-Meier and log rank test.Results: Post-chemotherapy MRI was available in 36 of 37 patients. Response to treatment was observed in 19 patients (53%) including two cases of complete remission. Six patients (17%) showed progression (PD) and 11 patients (31%) had stable disease (SD). Two or more cycles of chemotherapy was the only factor that predicted response to treatment. The overall median survival for all patients was 17.0+/-5.5 months. Age (<40 years) and time to recurrence (>/=1 year) were the clinical factors that predicted improved overall survival. Survival gain after chemotherapy was 9 months. Patients who responded and those with SD after treatment (11 months) had a longer median survival compared to PD (5 months) (P=0.01). Myelosuppression was severe (grade III/IV leukopenia in 15 patients (40%) and grade III/IV thrombocytopenia in 19 patients (52%)) but most recovered more than WHO grade II at the end of the chemotherapy cycles. There was only one fatality due to sepsis from pneumonia during the initial leukopenic state.Conclusion: ACNU and cisplatin chemotherapy can be an effective salvage therapy for recurrent glioblastoma patients. Myelosuppression from the chemotherapy regimen was the greatest side-effect but was manageable.

PMID: 16132508 [PubMed - as supplied by publisher]
 
25: J Neurooncol. 2005 Jul 23; [Epub ahead of print]
 
Brain metastasis of cardiac myxoma: case report and review of the literature.

Altundag MB, Ertas G, Ucer AR, Durmus S, Abanuz H, Calikoglu T, Ozbagi K, Demirkasimoglu A, Kaya B, Bakkal BH, Altundag K.

Department of Radiation Oncology, Ankara Oncology Hospital, Ankara, Turkey.

Cardiac myxoma is the most common benign heart tumor. Cardiac myxoma can be a sporadic lesion (93% of cases) and usually occurs in women over 30 years. Complete surgical removal of the myxoma and its cardiac attachment is usually curative. The frequency of recurrences in cardiac myxomas varies between 3% for sporadic cases and 22% for cases of Carney complex. Recurrence has been related to incomplete excision, multifocality, and embolism of tumor fragments. We report a case with multiple brain metastases presumably due to tumor embolization from previously operated cardiac myxoma.

PMID: 16132507 [PubMed - as supplied by publisher]
 
26: J Neurooncol. 2005 Jun 22; [Epub ahead of print]
 
Early Gross Recurrence of Atypical Meningioma.

Stark AM, Buhl R, Mehdorn HM.

Department of Nuerosurgery, University of Schleswig-Holstein Medical Center, Campus Kiel, Schittenhelmstrasse 10, D-24105, Kiel, Germany, starka@nch.uni-kiel.de.

PMID: 16132505 [PubMed - as supplied by publisher]
 
27: J Neurooncol. 2005 Aug 1; [Epub ahead of print]
 
Temozolomide With or Without Radiotherapy in Melanoma With Unresectable Brain Metastases.

Hofmann M, Kiecker F, Wurm R, Schlenger L, Budach V, Sterry W, Trefzer U.

Department of Dermatology and Allergy, Charite-University Medicine Berlin, Schumannstrasse 20--21, 10117, Berlin, Germany, maja.hofmann@charite.de.

Brain metastases are a common complication in patients suffering from metastatic malignant melanoma. We analyzed efficacy and toxicity of the alkylating agent temozolomide with excellent CNS penetration and known activity in brain metastasis in 35 patients with unresectable melanoma brain metastases. Patients received 200 mg/m(2) temozolomide on days 1 to 5 every 28 days as first or second-line therapy. This therapy regimen was combined with radiotherapy of the brain metastases in 22/35 patients. Grade III and IV toxicity was observed in 8/35 patients (leukopenia, granulocytopenia, thrombocytopenia, anemia, nausea and obstipation). Complete remission was observed in 1/34, partial remission in 2/34 and stable disease in 9/34 patients. In 5/34 a mixed response was assessed, 17/34 had disease progression and in one patient tumor response was not evaluable. The median progression free time was 5 (0-8) months for all patients, the median survival time for all patients from start of therapy was 8 (0-28) months, 9 (2-28) months in patients with concurrent stereotactic radiotherapy and 7 (3-17) months in patients with concurrent whole brain radiotherapy. Our results demonstrate that temozolomide can be combined with radiotherapy for the treatment of brain metastases in malignant melanoma, and that this combination may prolong survival in this patient group.

PMID: 16132502 [PubMed - as supplied by publisher]
 
28: J Neurooncol. 2005 Jul 23; [Epub ahead of print]
 
Mediastinal Metastasis of Glioblastoma Multiforme Evolving from Anaplastic Astrocytoma.

Tuominen H, Lohi J, Maiche A, Tormanen J, Baumann P.

Department of Pathology, Oulu University Hospital, Oulu, P.O. Box 50, FI-90029, OYS, Finland, hannu.tuominen@ppshp.

PMID: 16132499 [PubMed - as supplied by publisher]
 
29: J Neurooncol. 2005 Jul 23; [Epub ahead of print]
 
Procarbazine, Lomustine, Vincristine Combination may be Effective in Adult Medulloblastoma Patients with Systemic Metastases.

Cakar M, Aksoy S, Kilickap S, Harputluoglu H, Erman M.

Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey.

PMID: 16132496 [PubMed - as supplied by publisher]
 
30: J Neurooncol. 2005 Jul 23; [Epub ahead of print]
 
Glioblastoma Multiforme in the Elderly: a Therapeutic Challenge.

Mangiola A, Maira G, De Bonis P, Porso M, Pettorini B, Sabatino G, Anile C.

Institute of Neurosurgery, Catholic University School of Medicine, Rome, Italy, debonisvox@interfree.it.

INTRODUCTION: Elderly patients with glioblastoma multiforme (GBM) are frequently excluded from cancer therapy trials, treated suboptimally or not treated at all. The average survival in elderly patients is 4-8 months. The goal of the present study was to evaluate the efficacy of different treatment options in terms of survival in an elderly population affected with GBM.MATERIALS AND METHODS: About 34 Patients with primary supratentorial GBM aged 65 or higher were included in this study. All patients underwent craniotomy and tumor mass resection. After surgery they received radiation therapy, chemotherapy and radioimmunotherapy in different combinations.RESULTS: Overall median survival was 10.5 months with one patient still alive at 35 months. Survival was longer for patients who underwent total resection instead of partial (13 months vs 4 months, P = 0.006). If total en-bloc resection was used a further survival advantage was obtained (16 months for en-bloc resection, 9 months for inside-out resection, P = 0.008). Where a second surgical intervention was performed median survival was 21 months (P = 0.05). Survival according to adjuvant therapy has been 21 months (radiotherapy, chemotherapy, radioimmunotheraphy), 18 months (radiotherapy, chemotherapy) and 7 months (radiotherapy) (P = 0.0001).CONCLUSIONS: We think that single prognostic factor such as age should be not a reason for undertreatment.

PMID: 16132492 [PubMed - as supplied by publisher]
 
31: Neuroradiology. 2005 Aug 20; [Epub ahead of print]
 
Proton MRS imaging in the follow-up of patients with suspected low-grade gliomas.

Reijneveld JC, van der Grond J, Ramos LM, Bromberg JE, Taphoorn MJ.

Department of Neurology, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.

We compared the value of changes in proton magnetic resonance spectroscopic imaging ((1)H-MRSI) with changes in clinical status and/or contrast-enhanced magnetic resonance imaging (MRI) in the monitoring of patients with suspected low-grade glioma (LGG). From June 1, 1999 till May 31, 2002, we included consecutive, neurologically intact adult patients suspected of having an LGG, demonstrating non-enhancing supratentorial lesions without edema or mass effect on MRI, and in whom all treatment (including a diagnostic biopsy) was deferred. Till January 1, 2003, patients were surveyed clinically and radiologically (contrast-enhanced MRI and (1)H-MRSI). Patients who showed progression on clinical examination and/or MRI were denoted as progressive disease. Other patients were denoted as stable disease. A decrease in NAA/CHO ratio of >/=20% compared to the baseline value was considered as indicative for progression on (1)H-MRSI. We included 14 patients with suspected LGG. Seven patients demonstrated progressive disease during the follow-up period, preceded or accompanied by concomitant (1)H-MRSI changes in five patients. Four of these five patients were operated on within the follow-up interval. The histological diagnosis demonstrated high-grade glioma in three and LGG in one patient. In the other two patients with progressive disease, no progression was found on (1)H-MRSI. The other seven patients demonstrated stable disease, but four of them showed progression on (1)H-MRSI. Our data do not show convincing evidence that (1)H-MRSI contributes to adequate monitoring and follow-up of patients with suspected LGG. Future research should preferably include pathological data at the time of (1)H-MRSI changes.

PMID: 16133483 [PubMed - as supplied by publisher]
 
 
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