Volume 5
Archive

1: AJNR Am J Neuroradiol. 2006 May;27(5):1098-100.

 
Intrasphenoidal rathke cleft cyst.

Megdiche-Bazarbacha H, Ben Hammouda K, Aicha AB, Sebai R, Belghith L, Khaldi M, Touibi S.

Neuroradiology Service, National Neurology Institute, Tunis, Tunisia.

Symptomatic Rathke cleft cysts (RCC) are reported in the sellar and suprasellar regions, but no case of sphenoidal RCC has been reported. We report a case of sphenoidal RCC in a 41-year-old man. The lesion was revealed by headaches and diplopia. Symptoms disappeared transiently after a spontaneous rhinorrhea but relapsed 4 months later. MR imaging showed a cystic sphenoidal lesion, isointense on T1-weighted images (WI) with peripheral gadolinium enhancement and hyperintense on T2 WI. The patient underwent surgery through a transrhinoseptal approach. The wall of the sphenoid sinus was paper-thin. The cyst contained a motor-oil-like fluid and communicated widely with the nasal fossa. Its wall was partially extracted. Symptoms and signs ceased after surgery. MR imaging performed 1 year later showed the disappearance of the sphenoidal cyst. Embryological origin of RCCs is discussed. The hypothesis of a continuum between the different epithelial cystic lesions of the sellar and parasellar region is discussed. Imaging has an important impact on the diagnosis; nevertheless, the specific characterization remains difficult.

Publication Types:

• Case Reports

PMID: 16687551 [PubMed - indexed for MEDLINE]

 

2: AJNR Am J Neuroradiol. 2006 May;27(5):962-71.

 
Primary intracranial atypical teratoid/rhabdoid tumors of infancy and childhood: MRI features and patient outcomes.

Meyers SP, Khademian ZP, Biegel JA, Chuang SH, Korones DN, Zimmerman RA.

Departments of Radiology, University of Rochester School of Medicine, Strong Memorial Hospital, Rochester, NY 14642, USA.

BACKGROUND AND PURPOSE: Primary atypical teratoid/rhabdoid tumors (AT/RTs) are rare malignant intracranial neoplasms, usually occurring in young children. The objectives of this study were to characterize the MR imaging features and locations of primary intracranial AT/RTs, to determine the frequency of disseminated disease in the central nervous system (CNS) at diagnosis and postoperatively, and to assess patient outcomes. METHODS: The preoperative cranial MR images of 13 patients with AT/RTs were retrospectively reviewed for evaluation of lesion location, size, MR signal intensity and enhancement characteristics, and the presence of disseminated intracranial tumor. Postoperative MR images of the head and spine for 17 patients were reviewed for the presence of locally recurrent or residual tumor and disseminated neoplasm. Imaging data were correlated with patient outcomes. RESULTS: Patients ranged in age from 4 months to 15 years (median age, 2.9 years). Primary AT/RTs were intra-axial in 94% of patients. The single primary extra-axial lesion was located in the cerebellopontine angle cistern. AT/RTs were infratentorial in 47%, supratentorial in 41%, and both infra- and supratentorial in 12%. A germ-line mutation of the hSNF5/INI1 tumor-suppressor gene was responsible for the simultaneous occurrence of an intracranial AT/RT and a malignant renal rhabdoid tumor in a 4-month-old patient. Mean tumor sizes were 3.6 x 3.8 x 3.9 cm. On short TR images, AT/RTs typically had heterogeneous intermediate signal intensity, as well as zones of low (54%), high (8%), or both low and high (31%) signal intensity from cystic and/or necrotic regions, hemorrhage, or both, respectively. On long TR/long TE images, solid portions of AT/RTs typically had heterogeneous intermediate-to-slightly-high signal intensity with additional zones of high (54%) or both high and low signal intensity (38%), secondary to cystic and/or necrotic regions, edema, prior hemorrhage, and/or calcifications. AT/RT had isointense and/or slightly hyperintense signal intensity relative to gray matter on fluid-attenuated inversion-recovery (FLAIR) and long TR/long TE images, and showed restricted diffusion. All except 1 AT/RT showed contrast enhancement. The fraction of tumor volume showing enhancement was greater than two thirds in 58%, between one third and two thirds in 33%, and less than one third in 9%. Disseminated tumor in the leptomeninges was seen with MR imaging in 24% of patients at diagnosis/initial staging and occurred in another 35% from 4 months to 2.8 years (mean, 1.1 years) after surgery and earlier imaging examinations with negative findings. The overall 1-year and 5-year survival probabilities were 71% and 28%, respectively. Patients with MR imaging evidence of disseminated leptomeningeal tumor had a median survival rate of 16 months compared with 149 months for those without disseminated tumor (P < .004, logrank test). CONCLUSION: AT/RTs are typically intra-axial lesions, which can be infra- and/or supratentorial. The unenhanced and enhanced MR imaging features of AT/RT are often variable secondary to cystic/necrotic changes, hemorrhage, and/or calcifications. Poor prognosis is associated with MR imaging evidence of disseminated leptomeningeal tumor.

PMID: 16687525 [PubMed - indexed for MEDLINE]

 

3: Acta Cytol. 2006 Sep-Oct;50(5):542-4.

Cytologic diagnosis of a metastatic oligodendroglioma in a pleural effusion. A case report.

Lee CC, Jiang JS, Chen ET, Yokoo H, Pan YH, Tsai MD.

Department of Pathology and Laboratory Medicine, Chest Medicine, Orthopedics and Neurosurgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.

BACKGROUND: Extraneural metastasis of oligodendroglioma is extremely rare and is diagnosed primarily by biopsy or autopsy and very occasionally by fine needle cytologic examination. We report a case of metastatic oligodendroglioma diagnosed by cytologic examination of a pleural effusion. Such a diagnosis has not been reported before. CASE: A 64-year-old woman developed anemia and bilateral pleural effusion 7 years after an operation for an oligodendroglioma over the left frontal lobe. Cytologic examination of the pleural effusion showed aggregates of atypical polygonal cells containing round, hyperchromatic nuclei and scanty, granular cytoplasm in Liu's and Papanicolaou stain and cell blocks. Immunohistochemical staining of the tumor cells revealed a positive reaction for antibodies to glial fibrillary acidic protein, S-100 and Olig2. Pleural biopsy confirmed the cytologic diagnosis of pleural effusion. A pathologic fracture of the right humeral and femoral bones was noted 1 month later, and the specimen also showed infiltrating oligodendroglioma cells in bone tissue. CONCLUSION: To the best of our knowledge, this is the first metastatic oligodendroglioma diagnosed by pleural cytology. Fine needle cytology can provide a reliable and rapid way to detect an extracranial metastatic oligodendroglioma in different organs.

Publication Types:

• Case Reports

PMID: 17017442 [PubMed - indexed for MEDLINE]

 

4: Cancer Res. 2006 Nov 1;66(21):10247-52.

 
Neurospheres Enriched in Cancer Stem-Like Cells Are Highly Effective in Eliciting a Dendritic Cell-Mediated Immune Response against Malignant Gliomas.

Pellegatta S, Poliani PL, Corno D, Menghi F, Ghielmetti F, Suarez-Merino B, Caldera V, Nava S, Ravanini M, Facchetti F, Bruzzone MG, Finocchiaro G.

Units of Experimental Neuro-Oncology, Neuroradiology, and Neuromuscular Diseases and Neuroimmunology, Fondazione IRCCS Istituto Neurologico Besta, Milan, Italy.

Cancer stem-like cells (CSC) could be a novel target for cancer therapy, including dendritic cell (DC) immunotherapy. To address this, we developed experiments aimed at DC targeting of neurospheres (NS) from GL261 glioma cells because neurospheres can be enriched in CSC. We obtained murine neurospheres by growing GL261 cells in epidermal growth factor/basic fibroblast growth factor without serum. GL261-NS recapitulated important features of glioblastoma CSC and expressed higher levels of radial glia stem cell markers than GL261 cells growing under standard conditions (GL261 adherent cells, GL261-AC), as assessed by DNA microarray and real-time PCR. GL261-NS brain gliomas were highly infiltrating and more rapidly lethal than GL261-AC, as evidenced by survival analysis (P < 0.0001), magnetic resonance imaging and histology. DC from the bone marrow of syngeneic mice were then used for immunotherapy of GL261-NS and GL261-AC tumors. Strikingly, DC loaded with GL261-NS (DC-NS) cured 80% and 60% of GL261-AC and GL261-NS tumors, respectively (P < 0.0001), whereas DC-AC cured only 50% of GL261-AC tumors (P = 0.0022) and none of the GL261-NS tumors. GL261-NS expressed higher levels of MHC and costimulatory molecules (CD80 and CD86) than GL261-AC; the JAM assay indicated that DC-NS splenocytes had higher lytic activity than DC-AC splenocytes on both GL261-NS and GL261-AC, and immunohistochemistry showed that DC-NS vaccination was associated with robust tumor infiltration by CD8+ and CD4+ T lymphocytes. These findings suggest that DC targeting of CSC provides a higher level of protection against GL261 gliomas, a finding with potential implications for the design of clinical trials based on DC vaccination. (Cancer Res 2006; 66(21): 10247-52).

PMID: 17079441 [PubMed - in process]

 

5: Childs Nerv Syst. 2006 Oct 28; [Epub ahead of print]

 
Spinal intramedullary metastasis of medulloblastoma at initial diagnosis.

Inoue T, Kumabe T, Takahashi T, Nakajima T, Watanabe M, Tominaga T.

Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan, kuma@nsg.med.tohoku.ac.jp.

CASE REPORT: Spinal magnetic resonance imaging of a 4-year-old boy with medulloblastoma at the initial presentation showed intramedullary lesion without enhancement effect and slight cord swelling from C-5 to T-1. After complete response to the initial therapy, this lesion recurred and slowly expanded. Cervical (11)C-methionine-positron emission tomography could establish the diagnosis of intramedullary metastasis. CONCLUSION: Spinal intramedullary metastasis of medulloblastoma at initial diagnosis is extremely rare, but must be considered.

PMID: 17072662 [PubMed - as supplied by publisher]

 

6: Int J Cancer. 2006 Oct 30; [Epub ahead of print]

 
Intracranial therapy of glioblastoma with the fusion protein DTAT in immunodeficient mice.

Rustamzadeh E, Hall WA, Todhunter DA, Vallera VD, Low WC, Liu H, Panoskaltsis-Mortari A, Vallera DA.

Department of Neurosurgery, University of Minnesota Cancer Center, Minneapolis, MN.

A gene splicing technique was used to create a hybrid fusion protein DTAT encoding the 390 amino acid portion of diphtheria toxin (DT(390)), a linker, and the downstream 135-amino terminal fragment portion of human urokinase plasminogen activator. DTAT was assembled to target human glioblastoma cell lines in a murine intracranial model. Previously published in vitro studies demonstrated that DTAT was highly selective and toxic to human glioblastoma cell lines in a flank tumor model. The purpose of this study was to determine the toxicity, specificity and possible therapeutic efficacy of DTAT in an intracranial model. Convection enhanced delivery of DTAT resulted in about a 16-fold increase in maximum tolerated dose. Intracranial administration of DTAT on an every-other-day basis in nude mice with established U87 MG brain tumors resulted in significant reductions in tumor volume and significantly prolonged survival (p < 0.0001). Magnetic resonance imaging proved to be a powerful tool in mice and rats for demonstrating tumor growth in a xenograft intracranial model, assessing the efficacy of DTAT in tumor volume reduction and detecting DTAT-associated intracranial toxicity and vascular damage. These results suggest that the DTAT recombinant fusion protein is highly effective in an intracranial model and DTAT might be an effective treatment for glioblastoma. (c) 2006 Wiley-Liss, Inc.

PMID: 17075792 [PubMed - as supplied by publisher]

 

7: Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4 Suppl):S82-6.

 
Comparative dosimetric study of three-dimensional conformal, dynamic conformal arc, and intensity-modulated radiotherapy for brain tumor treatment using Novalis system.

Ding M, Newman F, Kavanagh BD, Stuhr K, Johnson TK, Gaspar LE.

Department of Radiation Oncology, University of Colorado Health Science Center, Aurora, CO.

Purpose: To investigate the dosimetric differences among three-dimensional conformal radiotherapy (3D-CRT), dynamic conformal arc therapy (DCAT), and intensity-modulated radiotherapy (IMRT) for brain tumor treatment. Methods and Materials: Fifteen patients treated with Novalis were selected. We performed 3D-CRT, DCAT, and IMRT plans for all patients. The margin for the planning target volume (PTV) was 1 mm, and the specific prescription dose was 90% for all plans. The target coverage at the prescription dose, conformity index (CI), and heterogeneity index were analyzed for all plans. Results: For small tumors (PTV </=2 cm(3)), the three dosimetric parameters had approximate values for both 3D-CRT and DCAT plans. The CI for the IMRT plans was high. For medium tumors (PTV >2 to </=100 cm(3)), the three plans were competitive with each other. The IMRT plans had a greater CI, better target coverage at the prescription dose, and a better heterogeneity index. For large tumors (PTV >100 cm(3)), the IMRT plan had good target coverage at the prescription dose and heterogeneity index and approximate CI values as those in the 3D-CRT and DCAT plans. Conclusion: The results of our study have shown that DCAT is suitable for most cases in the treatment of brain tumors. For a small target, 3D-CRT is useful, and IMRT is not recommended. For larger tumors, IMRT is superior to 3D-CRT and very competitive in sparing critical structures, especially for big tumors.

PMID: 17070414 [PubMed - in process]

 

8: Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4 Suppl):S7-S13.

 
Stereotactic radiotherapy of meningiomas compressing optical pathways.

Hamm KD, Henzel M, Gross MW, Surber G, Kleinert G, Engenhart-Cabillic R.

Department for Stereotactic Neurosurgery and Radiosurgery, HELIOS Klinikum Erfurt, Erfurt, Germany.

Purpose: Microsurgical resection is usually the treatment of choice for meningiomas, especially for those that compress the optical pathways. However, in many cases of skull-base meningiomas a high risk of neurological deficits and recurrences exist in cases where the complete tumor removal was not possible. In such cases, (fractionated) stereotactic radiotherapy (SRT) can offer an alternative treatment option. We evaluated the local control rate, symptomatology, and toxicity. Patients and Methods: Between 1997 and 2003, 183 patients with skull-base meningiomas were treated with SRT, among them were 65 patients with meningiomas that compressed optical pathways (64 benign, 1 atypical). Of these 65 cases, 20 were treated with SRT only, 27 were subtotally resected before SRT, and 18 underwent multiple tumor resections before SRT. We investigated the results until 2005, with a median follow-up of 45 months (range, 22-83 months). The tumor volume (TV = gross tumor volume) ranged from 0.61 to 90.20 cc (mean, 18.9 cc). Because of the risk of new visual disturbances, the dose per fraction was either 2 or 1.8 Gy for all patients, to a total dose of 50 to 60 Gy. Results: The overall survival and the progression-free survival rates for 5 years were assessed to 100% in this patient group. To date, no progression for these meningiomas have been observed. Quantitatively, tumor shrinkage of more than 20%, or more than 2 mm in diameter, was proved in 35 of the 65 cases after SRT. In 29 of the 65 patients, at least 1 of the symptoms improved. On application of the Common Toxicity Criteria (CTC), acute toxicity (Grade 3) was seen in 1 case (worsening of conjunctivitis). Another 2 patients developed late toxicity by LENT-SOMA score, 1 x Grade 1 and 1 x Grade 3 (field of vision loss). Conclusion: As a low-risk and effective treatment option for tumor control, SRT with 1.8 to 2.0 Gy per fraction can also be recommended in case of meningiomas that compress optical pathways. An interdisciplinary decision is very important for each patient.

PMID: 17070411 [PubMed - in process]

 

9: Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4 Suppl):S3-6.

 
Stereotactic fractionated radiotherapy for the treatment of benign meningiomas.

Candish C, McKenzie M, Clark BG, Ma R, Lee R, Vollans E, Robar J, Gete E, Martin M.

Department of Radiation Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.

Purpose: To assess the use of stereotactic fractionated radiotherapy (SRT) for the treatment of meningiomas. Methods and Materials: Between April 1999 and October 2004, 38 patients underwent SRT. Of 34 patients (36 tumors) assessed, the median age was 53 years. The indication was primary treatment in 26 cases (no histology) and postoperative in 10 cases. The most common sites were cavernous sinus (17), optic nerve (6), and cerebellopontine angle (5). The median gross target volume and planning target volume were 8.9 cm(3) and 18.9 cm(3), respectively. Stereotactic treatment was delivered with 6-MV photons with static conformal fields (custom-made blocks, 9 patients, and micromultileaf collimator, 25 patients). Median number of fields was six. The median dose prescribed was 50 Gy (range, 45-50.4 Gy) in 28 fractions. The median homogeneity and conformality indices were 1.1 and 1.79, respectively. Results: Treatment was well tolerated. Median follow-up was 26 months with 100% progression-free survival. One patient developed an area of possible radionecrosis related to previous radiotherapy, and 2 men developed mild hypogonadism necessitating testosterone replacement. The vision of 5 of 6 patients with optic pathway meningiomas improved or remained static. Conclusions: Stereotactic fractionated radiotherapy for the treatment of meningiomas is practical, and with early follow-up, seems to be effective.

PMID: 17070403 [PubMed - in process]

 

10: Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4 Suppl):S26-32.

 
Hypofractionated stereotactic radiotherapy combined with topotecan in recurrent malignant glioma.

Wurm RE, Kuczer DA, Schlenger L, Matnjani G, Scheffler D, Cosgrove VP, Ahlswede J, Woiciechowsky C, Budach V.

Department of Radiation Oncology, Campus Charite Mitte, Berlin, Germany.

Purpose: To assess hypofractionated stereotactic radiotherapy (H-SRT) with concurrent topotecan in patients with recurrent malignant glioma. Methods and Materials: Between February 1998 and December 2001, 25 patients with recurrent malignant glioma were treated in a phase I-II study (8 females and 17 males; median age, 45 years; range, 11-66 years; median Karnofsky performance status, 80%, range, 50-100%; median Mini Mental Standard Examination score, 25 points; range, 10-30 points). Of the 25 patients, 20% had World Health Organization Grade III and 80% World Health Organization Grade IV glioma. All patients had been treated previously by external beam radiotherapy with 54.4 Gy in 34 fractions twice daily, at least 6 h apart, within 3.5 weeks or 60 Gy in 30 fractions within 6 weeks. In addition, 84% had already received at least one chemotherapy regimen for recurrence. The median H-SRT dose at the 80% isodose was 25 Gy, and the maximal dose was 30 Gy delivered in five to six fractions on consecutive days. Topotecan (1.1 mg/m(2)/d) was given as a continuous i.v. infusion during H-SRT. Depending on the toxicity and compliance, patients received an additional 48 topotecan courses. Results: For all patients, the actuarial median progression-free survival was 10.5 months (range, 1.4-47.8 months), the median functional survival was 12.6 months (range, 1.6-49.5 months), and the median overall survival was 14.5 months (range, 3-56.4 months). Twelve percent of patients developed presumed adverse radiation effects (Radiation Therapy Oncology Group Grade 2). According to the Common Toxicity Criteria, version 2.0, no topotecan-related Grade 4 toxicity was noted. Grade 3 neutropenia was documented after 14 and Grade 3 thrombopenia after 12 courses. Conclusion: H-SRT with topotecan is feasible and well-tolerated in patients with recurrent high-grade glioma and results in similar survival compared with other repeat treatment modalities.

PMID: 17070402 [PubMed - in process]

 

11: Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4 Suppl):S20-5.

 
Stereotactic radiosurgery as therapy for melanoma, renal carcinoma, and sarcoma brain metastases: Impact of added surgical resection and whole-brain radiotherapy.

Rao G, Klimo P Jr, Thompson CJ, Samlowski W, Wang M, Watson G, Shrieve D, Jensen RL.

Department of Neurosurgery, University of Utah, Salt Lake City, Utah, UT.

Purpose: Brain metastases of melanoma, renal carcinoma, and sarcoma have traditionally responded poorly to conventional treatments, including surgery and whole-brain radiotherapy (WBRT). Several studies have suggested a beneficial effect of stereotactic radiosurgery (SRS). We evaluated our institutional experience with systematic SRS in patients harboring these "radioresistant" metastases. Methods and Materials: A total of 68 patients with brain metastases from melanoma, renal carcinoma, and sarcoma underwent SRS with or without WBRT or surgical resection. All patients had Karnofsky performance scores >70, and SRS was performed before the initiation of systemic therapy. The survival time was calculated from the diagnosis of brain metastases using the Kaplan-Meier product-limit method. Statistical significance was calculated using the log-rank test. Factors influencing survival, including surgical resection, WBRT, gender, number of SRS sessions, and histologic type, were evaluated retrospectively using Cox univariate models. Results: The overall median survival was 427 days (14.2 months), which appears superior to the results obtained with conventional WBRT. The addition of neither surgery nor WBRT to SRS provided a statistically significant increase in survival. Conclusion: Our results suggest that patients undergoing SRS for up to five cerebral metastases from "radioresistant" tumors (melanoma, renal cell carcinoma, and sarcoma) have survival rates comparable to those in other series of more selected patients. The addition of surgical resection or WBRT did not result in improved survival in our series.

PMID: 17070401 [PubMed - in process]

 

12: Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4 Suppl):S14-9.

 
Neuropsychological status in children and young adults with benign and low-grade brain tumors treated prospectively with focal stereotactic conformal radiotherapy.

Jalali R, Goswami S, Sarin R, More N, Siddha M, Kamble R.

Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India.

Purpose: To present prospective neuropsychological data at baseline and follow-up in children and young adults with benign and low-grade gliomas treated with focal stereotactic conformal radiotherapy (SCRT). Methods and Materials: A total of 22 patients (age 4-25 years) with residual/progressive benign and low-grade brain tumors considered suitable for SCRT underwent detailed and in-depth neuropsychological and cognitive testing at baseline before SCRT. The test battery included measurement of age-adjusted intelligence quotients (IQs) and cognitive parameters of visual, spatial, visuomotor, and attention concentrations. Anxiety was measured using the State-Trait Anxiety Inventory for Children and Hamilton Anxiety Rating Scale for patients >16 years old. Patients were treated with high-precision conformal radiotherapy under stereotactic guidance to a dose of 54 Gy in 30 fractions. All neuropsychological assessments were repeated at 6 and 24 months after SCRT completion and compared with the baseline values. Results: The baseline mean full-scale IQ before starting RT for patients <16 years was 82 (range, 33-105). For those >16 years, the corresponding value was 72 (range, 64-129). Of 20 evaluable patients, 14 (70%) had less than average IQs at baseline, even before starting radiotherapy. The verbal IQ, performance IQ, and full-scale IQ, as well as other cognitive scores, did not change significantly at the 6- and 24-month follow-up assessments for all patients. The memory quotient in older children and young adults was maintained at 6 and 24 months after SCRT, with a mean value of 93 and 100, respectively, compared with a mean baseline value of 81 before RT. The mean anxiety score in children measured by the C1 and C2 components of the State-Trait Anxiety Inventory for Children (STAIC) was 48 and 40, respectively, which improved significantly to mean values of 30 and 26, respectively, at the 24-month follow-up assessment (p = 0.005). The mean depression score in patients >16 years old was 23 at baseline and had improved to 17 and 14 at the 6-month and 24-month follow-up assessments, respectively. Conclusion: Our data demonstrated neuropsychological impairment in a cohort of young patients with benign and low-grade tumors even before starting radiotherapy. SCRT, however, did not result in any additional worsening. These encouraging results need to be validated in a study with a larger number of patients and longer follow-up.

PMID: 17070399 [PubMed - in process]

 

13: J Clin Oncol. 2006 Oct 10;24(29):4754-7. Epub 2006 Sep 11.

 
Detection of subclinical systemic disease in primary CNS lymphoma by polymerase chain reaction of the rearranged immunoglobulin heavy-chain genes.

Jahnke K, Hummel M, Korfel A, Burmeister T, Kiewe P, Klasen HA, Muller HH, Stein H, Thiel E.

Department of Hematology, Charite-Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. kristoph.jahnke@charite.de

PURPOSE: To search for subclinical systemic disease in bone marrow and peripheral blood in patients with primary CNS lymphoma (PCNSL) to elucidate whether extracerebral relapse may represent a sequel of initial occult systemic disease rather than true extracerebral spread. PATIENTS AND METHODS: Bone marrow and peripheral-blood specimens of 24 PCNSL patients were examined using polymerase chain reaction (PCR) for analysis of clonally rearranged immunoglobulin heavy-chain (IgH) genes. RESULTS: Identical dominant PCR products were found in bone marrow aspirates, blood samples, and tumor biopsy specimens of two patients, indicating that the same tumor cell population is present in the CNS and in extracerebral sites. Follow-up IgH PCR performed in one of these patients in complete remission 24 months after diagnosis yielded a persistent monoclonal product in the blood. An oligoclonal IgH rearrangement pattern was found in the tumor specimen of two other patients, whereas bone marrow and blood samples demonstrated the same dominant PCR products. Follow-up PCR showed a persistent monoclonal amplificate in blood in one of these patients 27 months after diagnosis. CONCLUSION: It could be demonstrated for the first time that subclinical systemic disease can be present in PCNSL patients at initial diagnosis. Our findings may have an impact on the understanding of PCNSL pathogenesis and the extent of staging and treatment.

PMID: 16966685 [PubMed - indexed for MEDLINE]

 

14: J Clin Oncol. 2006 Oct 10;24(29):4746-53. Epub 2006 Sep 5.

 
Correlations between O6-methylguanine DNA methyltransferase promoter methylation status, 1p and 19q deletions, and response to temozolomide in anaplastic and recurrent oligodendroglioma: a prospective GICNO study.

Brandes AA, Tosoni A, Cavallo G, Reni M, Franceschi E, Bonaldi L, Bertorelle R, Gardiman M, Ghimenton C, Iuzzolino P, Pession A, Blatt V, Ermani M; GICNO.

Department of Medical Oncology, Bellaria Hospital, Via Altura 3, Bologna, Italy. aa.brandes@yahoo.it

PURPOSE: To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting. PATIENTS AND METHODS: From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction. RESULTS: The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09). CONCLUSION: TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.

Publication Types:

• Clinical Trial

PMID: 16954518 [PubMed - indexed for MEDLINE]

 

15: J Natl Cancer Inst. 2006 Nov 1;98(21):1546-57.

 
Effects of intravenously administered recombinant vesicular stomatitis virus (VSV(deltaM51)) on multifocal and invasive gliomas.

Lun X, Senger DL, Alain T, Oprea A, Parato K, Stojdl D, Lichty B, Power A, Johnston RN, Hamilton M, Parney I, Bell JC, Forsyth PA.

Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.

BACKGROUND: An ideal virus for the treatment of cancer should have effective delivery into multiple sites within the tumor, evade immune responses, produce rapid viral replication, spread within the tumor, and infect multiple tumors. Vesicular stomatitis virus (VSV) has been shown to be an effective oncolytic virus in a variety of tumor models, and mutations in the matrix (M) protein enhance VSV's effectiveness in animal models. METHODS: We evaluated the susceptibility of 14 glioma cell lines to infection and killing by mutant strain VSV(deltaM51), which contains a single-amino acid deletion in the M protein. We also examined the activity and safety of this strain against the U87 and U118 experimental models of human malignant glioma in nude mice and analyzed the distribution of the virus in the brains of U87 tumor-bearing mice using fluorescence labeling. Finally, we examined the effect of VSV(deltaM51) on 15 primary human gliomas cultured from surgical specimens. All statistical tests were two-sided. RESULTS: All 14 glioma cell lines were susceptible to VSV(deltaM51) infection and killing. Intratumoral administration of VSV(deltaM51) produced marked regression of malignant gliomas in nude mice. When administered systemically, live VSV(deltaM51) virus, as compared with dead virus, statistically significantly prolonged survival of mice with unilateral U87 tumors (median survival: 113 versus 46 days, P = .0001) and bilateral U87 tumors (median survival: 73 versus 46 days, P = .0025). VSV(deltaM51) infected multifocal gliomas, invasive glioma cells that migrated beyond the main glioma, and all 15 primary human gliomas. There was no evidence of toxicity. CONCLUSIONS: Systemically delivered VSV(deltaM51) was an effective and safe oncolytic agent against laboratory models of multifocal and invasive malignant gliomas, the most challenging clinical manifestations of this disease.

PMID: 17077357 [PubMed - in process]

 

16: J Neurol Neurosurg Psychiatry. 2006 Nov;77(11):1271-2.

 
Neurological picture. Production of oil in a brain abscess caused by Propionibacterium acnes.

Vajramani GV, Mandal N, Goyal KK, Sparrow OC.

Department of Neurosurgery, Wessex Neurological Centre, Southampton General Hospital, Southampton SO16 6YD, UK.

Publication Types:

• Case Reports

PMID: 17043293 [PubMed - indexed for MEDLINE]

 

17: J Neurooncol. 2006 Nov 3; [Epub ahead of print]

 
Toxicity and efficacy of protracted low dose temozolomide for the treatment of low grade gliomas.

Pouratian N, Gasco J, Sherman JH, Shaffrey ME, Schiff D.

Department of Neurological Surgery, University of Virginia, Box 800212, Charlottesville, VA, 22908-0212, USA, np5k@virginia.edu.

Protracted low dose temozolomide (75 mg/m(2)/day on days 1-21 of 28 days) offers potential advantages over standard temozolomide schedules (200 mg/m(2)/day on days 1-5 of 28 days) including greater cumulative drug exposure and depletion of O(6)-alkylguanine DNA alkyltransferase levels, theoretically overcoming intrinsic chemoresistance. We retrospectively review our experience in 25 patients with pathologically proven low grade gliomas (LGG) treated with protracted low dose temozolomide to primarily quantify its toxicity and secondarily to assess efficacy. None had previously received radiation. Tumor response was graded based on changes in tumor size, steroid requirements, and clinical exam. About 243 cycles of protracted low dose temozolomide were administered. Three patients (12%) were changed to standard temozolomide dosing due to side effects, including intractable nausea (n = 2) and multiple cytopenias (n = 1). The most frequent toxicities were fatigue (76%), lymphopenia (72% [48% high grade]), constipation (56%), and nausea (52%). High grade toxicities (other than lymphopenia) included secondary malignancy, pruritis, hyponatremia, neutropenia, leukopenia, and cognitive decline (n = 1 for each). Tumor response rate was 52% and and disease control rate was 84%. Six month PFS was 92% and 12 month PFS was 72%. Response rates and PFS were independent of pathological subtype, deletion status, and indication for chemotherapy. Protracted low dose temozolomide has a distinct spectrum of toxicities compared to standard dosing but is well tolerated in most patients and may provide improved response rates compared to standard dosing. The results of larger randomized trials are needed to assess its potential advantages over other management schemes.

PMID: 17082887 [PubMed - as supplied by publisher]

 

18: J Neurooncol. 2006 Nov 1; [Epub ahead of print]

 
Expression of MHC I and NK ligands on human CD133(+) glioma cells: possible targets of immunotherapy.

Wu A, Wiesner S, Xiao J, Ericson K, Chen W, Hall WA, Low WC, Ohlfest JR.

Department of Neurosurgery, University of Minnesota Medical School, 2001 6th St. SE, 3500B LRB/MTRF, Minneapolis, MN, 55455, USA.

Mounting evidence suggests that gliomas are comprised of differentiated tumor cells and brain tumor stem cells (BTSCs). BTSCs account for a fraction of total tumor cells, yet are apparently the sole cells capable of tumor initiation and tumor renewal. BTSCs have been identified as the CD133-positive fraction of human glioma, whereas their CD133-negative daughter cells have limited proliferative ability and are not tumorogenic. It is well established that the bulk tumor mass escapes immune surveillance by multiple mechanisms, yet little is known about the immunogenicity of the CD133-positive fraction of the tumor mass. We investigated the immunogenicity of CD133-positive cells in two human astrocytoma and two glioblastoma multiforme samples. Flow cytometry analyses revealed that the majority of CD133-positive cells do not express detectable MHC I or natural killer (NK) cell activating ligands, which may render them resistant to adaptive and innate immune surveillance. Incubating CD133-positive cells in interferon gamma (INF-gamma) significantly increased the percentage of CD133-positive cells that expressed MHC I and NK cell ligands. Furthermore, pretreatment of CD133-positive cells with INF-gamma rendered them sensitive to NK cell-mediated lysis in vitro. There were no consistent differences in immunogenicity between the CD133-positive and CD133-negative cells in these experiments. We conclude that CD133-posistive and CD133-negative glioma cells may be similarly resistant to immune surveillance, but that INF-gamma may partially restore their immunogenicity and potentiate their lysis by NK cells.

PMID: 17077937 [PubMed - as supplied by publisher]

 

19: J Neurooncol. 2006 Sep;79(2):153-7. Epub 2006 Jul 20.

 
Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial.

Taliansky-Aronov A, Bokstein F, Lavon I, Siegal T.

Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah Hebrew University Hospital, Ein-Kerem, Jerusalem, Israel.

PURPOSE: Chemotherapy with alkylating agents is of proven efficacy in recurrent anaplastic oligodendroglioma (AO) with reported response rates ranging between 50% and 70%. The response of newly diagnosed AO to initial treatment with temozolomide (TMZ) has not yet been reported. This study evaluated the response and time to tumor progression of newly diagnosed AO initially treated with TMZ. PATIENTS AND METHODS: Twenty patients with a median age of 47 (range: 26-65) received a median of 14 (range: 3-24) cycles of TMZ as their first modality of therapy following diagnosis of AO. Treatment was given every 28 days for 5 days at a starting dose of 200 mg/m2/d and was continued for 24 cycles unless toxicity or tumor progression required withdrawal of TMZ. MRI evaluations were repeated every 8 weeks and scales of Karnofsky performance status (KPS) and of neurological function were used to assess clinical response. RESULTS: Clinical improvement was observed in 60% of the patients with statistically significant gain measured by KPS and the neurologic function scales. The objective response rate was 75%, and median time to tumor progression was 24 months. Maximal objective response was reached within a median of 6 months (range: 3-12). Tumors with 1p loss had longer progression free survival compared to tumors without deletions (PFS at 24 months: 1p LOH = 100%, 1p intact = 20%; P = 0.057). TMZ was well tolerated with only two events of grade 3/4 hematological toxicity. CONCLUSIONS: Newly diagnosed AO demonstrates a high rate of response to initial therapy with TMZ, similar to the response reported for PCV combination therapy. Further studies are needed to determine the optimal duration of treatment and whether radiotherapy should immediately follow chemotherapy.

Publication Types:

• Clinical Trial

PMID: 16855865 [PubMed - indexed for MEDLINE]

 

20: J Neurooncol. 2006 Sep;79(2):171-9. Epub 2006 Jul 19.

 
Expression of survivin, platelet-derived growth factor A (PDGF-A) and PDGF receptor alpha in primary central nervous system lymphoma.

Karabatsou K, Pal P, Dodd S, Mat A, Haylock B, Aguirreburualde M, Moxam N, Pinson-Ellis W, Broome J, Rainov NG.

Department of Neurosurgery, The Walton Centre for Neurology and Neurosurgery NHS Trust, L9 7LJ, Liverpool, UK.

PURPOSE: Primary central nervous system lymphomas (PCNSL) are rare tumours occurring in the brain. Their biology and the factors predicting survival are not well known. This study investigated expression of the antiapoptotic protein survivin and platelet-derived growth factor A (PDGF-A) and receptor (PDGFRalpha) in PCNSL. EXPERIMENTAL DESIGN: A total of 44 patients with histologically confirmed PCNSL treated between 1992 and 2004 were included in this study, and tumour specimens were investigated immunohistochemically for expression of survivin, PDGF-A and PDGFRalpha. Protein expression and clinical variables were analyzed statistically. RESULTS: Of the 44 tumours 43(98%) were diffuse large B-cell non-Hodgkin's lymphomas (NHL) and one was a T-cell NHL. Around 37 (84%) of the examined PCNSL specimens showed expression of survivin, 16 (36%) of PDGF-A and 34 (77%) of PDGFRalpha. Tumours expressing surviving co-expressed PDGFRalpha frequently and PDGF-A occasionally. Expression of the above proteins was not predictive for survival in this patient group. Except for age and therapy, no other clinical variables correlated significantly with overall survival. CONCLUSIONS: PCNSL express survivin and PDGFRalpha in the majority of investigated cases. PDGF-A is expressed less frequently. Immunohistochemical detection of these proteins does not correlate with overall survival and cannot be used as a prognostic factor.

PMID: 16850112 [PubMed - indexed for MEDLINE]

 

21: J Neurooncol. 2006 Sep;79(2):151-2. Epub 2006 Jul 19.

 
Images in neuro-oncology: anaplastic pleomorphic xanthoastrocytoma.

Baehring JM, Vives KP, Bannykh S.

Department of Neurosurgery,Yale University School of Medicine, New Haven, CT, USA, joachim.baehring@yale.edu

Publication Types:

• Case Reports

PMID: 16850109 [PubMed - indexed for MEDLINE]

 

22: J Neurooncol. 2006 Sep;79(2):159-68.

 
Proposal of a scoring scale as a survival predictor in intracranial oligodendrogliomas.

Hamlat A, Saikali S, Chaperon J, Carsin-Nicol B, Calve ML, Lesimple T, Ben-hassel M, Guegan Y.

Department of Neurosurgery, CHU Pontchaillou, Rennes, France. hamlat.abd@wanadoo.fr

INTRODUCTION: Histological, clinical and radiological features, and molecular genetic analysis are among the factors that have been considered in defining the prognosis of oligodendrogliomas (OD), but they have yielded conflicting results. The purpose of this study was to test out a scoring scale based on clinical, radiological, pathological and molecular features. MATERIAL AND METHOD: To identify factors with prognostic significance, we analyzed 87 treated patients with a histological diagnosis of OD. Of the parameters analyzed, age, onset, clinical status, radiological enhancement, histological necrosis, mitosis and chromosomal anomalies emerged as significant prognosis factors using univariate analysis. Multivariate analysis revealed age and chromosomal anomalies as independent factors of survival. RESULTS: The factors with a significant prognostic value were combined to determine which grouping factors best predict outcome. The proposed score is a pure number resulting from a combination of: 2 major factors: age and chromosomal anomalies (scored 3-0); 5 minor factors: onset, clinical examination, necrosis, mitoses (scored 1-0), and radiological enhancement (scored 2-0). According to our scale, 10 survival curves were produced for overall survival. Recursive partitioning of patients with the nearest score and outcome produced four groups with a significant difference in survival (p=10(-5)). The power of both the scale and the partitioned groups for predicting outcome was more accurate than the WHO and St Anne grading systems, and the molecular sub-classification. CONCLUSIONS: Our scale is a plausible way of classifying patients harboring intracranial OD according to expected survival.

Publication Types:

• Evaluation Studies

PMID: 16821091 [PubMed - indexed for MEDLINE]

 

23: J Neurooncol. 2006 Sep;79(2):169-70. Epub 2006 Jul 5.

 
Large cystic cavernous angioma of the cerebellum mimicking pilocytic astrocytoma.

Lim SC, Hong R, Kim YS, Jang SJ.

Department of Pathology, Chosun University College of Medicine, Gwangju, Korea. sclim@chosun.ac.kr

OBJECTIVE AND IMPORTANCE: Cavernous angiomas are relatively rare vascular malformations. They are generally located supratentorially with a rare incidence in the cerebellum. Cavernous angiomas, accompanied by a large cyst, are very rare. We present a case of a cavernous angioma with the unusual MRI findings of a large cyst and a small mural nodule. CLINICAL PRESENTATION: The patient was a 48-year-old man who complained of a history of dizziness for several weeks. The neurologic examination in the neurosurgery clinic was without deficit. INTERVENTION: The cyst measured 4.7x4.0 cm and contained serous fluid with a nodular mass in the lower part of the cyst. The cystic wall and the solid mural nodule were completely removed through a midline suboccipital approach. Postoperatively, the patient remained neurologically intact. CONCLUSION: When a large cystic lesion is present in the cerebellum, preoperative radiological and intraoperative findings led to misdiagnosis. Therefore, a rare cystic angioma must be considered in the differential diagnosis of infratentorial cystic masses.

Publication Types:

• Case Reports

PMID: 16821089 [PubMed - indexed for MEDLINE]

 

24: J Neurooncol. 2006 Sep;79(2):187-90. Epub 2006 Apr 28.

 
Extraneural metastasis in intracranial tumors in children: the experience of a single center.

Varan A, Sari N, Akalan N, Soylemezoglu F, Akyuz C, Kutluk T, Buyukpamukcu M.

Department of Pediatric Oncology, Hacettepe University Institute of Oncology, Ankara, Turkey. hupog@tr.net

Our aim is to evaluate the clinical features and outcomes of children with primary central nervous system (CNS) tumors who develop extraneural metastasis (ENM).We retrospectively evaluated children diagnosed with primary CNS tumors treated at our institution between 1972 and 2004. Of 1,011 patients these tumors, 10 (0.98%) developed ENM. The histopathologic diagnosis was medulloblastoma in six patients, germ cell tumors in two patients, and ependymoma and atypical teratoid rhabdoid tumor (ATRT) in one patient each. In six patients, the primary tumor was located in the posterior fossa; it had a supratentorial location in the patient with ATRT, was located in the sellar and suprasellar region in the two patients with germ cell tumors, and was found in the distal spinal cord in the patient with an ependymoma. In two patients ENM was detected at the time of diagnosis. In other patients ENM developed between 9 and 25 months after diagnosis. Metastatic sites included bone, bone marrow, lung, cervical lymph nodes, liver, and paranasal sinuses. Of the 10 patients who developed ENM, 8 died of their disease 0.27-16.2 months (median, 2.60 months) after it was detected. One patient with dysgerminoma is alive, without disease, 117.80 months after diagnosis of the ENM. One patient with germ cell tumor is alive with disease 11.3 months after diagnosis of the ENM.Systemic metastasis to other extraneural sites is extremely rare in children with intracranial tumors. In our series the rate of ENM is 0.98%. The liver and lung are the most common site for metastasis, followed by the bone and bone marrow. The outcome is poor in patients with CNS tumors with ENM.

PMID: 16645723 [PubMed - indexed for MEDLINE]

 

25: J Neurooncol. 2006 Sep;79(2):197-201. Epub 2006 Apr 6.

 
Disseminated pilocytic astrocytoma involving brain stem and diencephalon: a history of atypical eating disorder and diagnostic delay.

Distelmaier F, Janssen G, Mayatepek E, Schaper J, Gobel U, Rosenbaum T.

Department of General Pediatrics, Heinrich-Heine-University, Dusseldorf, Germany.

The association of weight loss and pediatric brain tumors that affect the diencephalon or brain stem with weight loss is a recognized, but not fully understood phenomenon. Tumors located in the hypothalamic region may induce the diencephalic syndrome (DS), which is characterized by profound emaciation with almost complete loss of subcutaneous fatty tissue. Tumors that compress or infiltrate the brain stem rarely cause both psychological disturbance and emaciation. The clinical presentation may be different, depending on the location of the lesion and age of the patient.In this report we present an unusual case of severe emaciation in a 4(9)/(12)-year-old girl with a juvenile pilocytic astrocytoma of the hypothalamic region and brain stem with neuroaxis dissemination. This case illustrates the importance of considering intracranial mass-lesions in the differential diagnosis of weight loss, psychological disturbance and atypical eating disorder. We discuss the importance of tumor multifocality and the role of patient age in the clinical presentation with reference to the literature.

Publication Types:

• Case Reports

PMID: 16598421 [PubMed - indexed for MEDLINE]

 

26: J Neurooncol. 2006 Sep;79(2):203-9. Epub 2006 Apr 6.

 
Diffusion-weighted MR imaging abnormalities in pediatric patients with surgically-treated intracranial mass lesions.

Smith JS, Lin H, Mayo MC, Bannerjee A, Gupta N, Perry V, Cha S.

Department of Neurological Surgery, Brain Tumor Research Center, San Francisco school of medicine, University of California, San Francisco, CA 94143-0112, USA. jsmith1enator@gmail.com

INTRODUCTION: Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique that measures the degree of water diffusion in vivo. DWI abnormalities are frequently observed on immediate postoperative imaging following surgical resection of gliomas in adults. These abnormalities subsequently demonstrate contrast enhancement, which may be confused with lesion recurrence. The purpose of this study was to investigate the occurrence of these postoperative abnormalities in pediatric patients with intracranial mass lesions. METHODS: Thirty-three consecutive patients <or=18 years old with a newly diagnosed intracranial mass lesion underwent MRI, including DWI, before and immediately after surgical treatment. RESULTS: The median patient age was 9.9 years (range 0.2-18 years). Supratentorial and infratentorial lesions were identified in 22 and 11 patients, respectively. Infiltrative and noninfiltrative, as well as benign and malignant lesions, were included. Postoperative imaging demonstrated areas of reduced diffusion adjacent to the resection cavity in 20 (61%) cases. The median volume of these areas was 1.7 cm3 (range 0.3 cm3-12.0 cm3). Subsequent imaging studies in 9 of the 18 cases showed contrast enhancement in the area corresponding to the DWI abnormality. There were no clinical deficits attributable to any of the diffusion abnormalities. There was no association between the occurrence of these abnormalities and whether the lesion was infiltrative, non-infiltrative, benign, or malignant. CONCLUSIONS: DWI abnormality on immediate postoperative MRI is common following surgery for newly diagnosed intracranial mass lesions in pediatric patients. Focal contrast enhancement in the postoperative period may be confused with recurrence for some lesions. Our study suggests that immediate postoperative DWI is useful in interpreting new areas of focal contrast enhancement on subsequent imaging in children who have had surgery for brain tumors.

PMID: 16598419 [PubMed - indexed for MEDLINE]

 

27: J Neurooncol. 2006 Sep;79(2):143-50. Epub 2006 Apr 6.

 
Phosphorylation of cAMP response element binding protein (CREB) as a marker of hypoxia in pituitary adenoma.

Morimoto D, Yoshida D, Noha M, Suzuki M, Osamura RY, Teramoto A.

Department of Neurosurgery, Nippon Medical School, 113-8603, Tokyo, Japan. dai_sampo@yahoo.co.jp

Hypoxia appears to be causatively related to pituitary adenoma. Currently, no biomarkers are available for the postoperative assessment of hypoxia in patient samples. Since the cAMP response element binding protein (CREB) is phosphorylated under hypoxic conditions, we examined whether CREB phosphorylation levels may be exploited as a novel biomarker for hypoxia in pituitary adenoma tissues. HP-75 human pituitary adenoma cells were incubated in 21% or 1% oxygen (normoxia and hypoxia, respectively), and Western blotting was employed to compare the levels of CREB and phosphorylated CREB (p-CREB). Our results show that p-CREB levels are significantly elevated under 1% oxygen, whereas the total CREB concentration remains unchanged. We further tested whether this phosphorylation is applicable as a marker of hypoxia in pituitary adenoma tissues removed by transsphenoidal surgery from 45 patients (32 females and 13 males, 22-78 years old). Fluorescence double immunohistochemistry data revealed that p-CREB in adenoma tissues is significantly elevated, and displays a positive correlation with Knosp grading (Spearman rank correlation; P = 0.0483, r = 0.3412), but no significant association with tumor subtype (Kruskal-Wallis analysis, CREB, P = 0.1072; p-CREB, P = 0.1888; phosphorylation ratio, P = 0.4916). Our findings collectively suggest that CREB phosphorylation may be employed as an in situ marker for hypoxia. Moreover, hypoxia and/or phosphorylation of CREB are associated with the cell invasiveness of pituitary adenomas.

PMID: 16598418 [PubMed - indexed for MEDLINE]

 

28: J Neurooncol. 2006 Sep;79(2):211-6. Epub 2006 Mar 22.

 
Central neurocytomas with MIB-1 labeling index over 10% showing rapid tumor growth and dissemination.

Ogawa Y, Sugawara T, Seki H, Sakuma T.

Department of Neurosurgery, Iwate Prefectural Central Hospital, Morioka, Japan. yogawa@kohnan-sendai.or.jp

OBJECTIVE AND IMPORTANCE: Central neurocytoma is recognized as a indolent intraventricular tumor arising from the ependyma around the foramen of Monro and anterior part of the lateral ventricles, and well demarcated from the brain parenchyma. Surgical removal can be curative without postoperative therapy. However, malignant central neurocytoma refractory to even aggressive treatment is known. CLINICAL PRESENTATION: We report two cases of extraventricular central neurocytomas with significant vascular proliferation, mitoses, and MIB-1 labeling index of more than 10%. INTERVENTION: Subtotal removal for the one patient and open biopsy for other followed by radiotherapy with chemotherapy were performed. However, the disease progressed and dissemination occurred. Both patients subsequently died 23 and 18 month after the histological diagnosis was established. CONCLUSION: Extraventricular central neurocytoma may present with frequent vascular proliferation and high MIB-1 labeling index. Even if they lack malignant histological findings like frequent mitosis and/or necrosis, the prognosis for such patients is very poor.

Publication Types:

• Case Reports

PMID: 16552620 [PubMed - indexed for MEDLINE]

 

29: J Neurosurg. 2006 Oct;105(4):640-4.

Salvage of infected craniotomy bone flaps with the wash-in, wash-out indwelling antibiotic irrigation system. Technical note and case series of 12 patients.

Auguste KI, McDermott MW.

Department of Neurological Surgery, University of California, San Francisco School of Medicine, San Francisco, California 94143-0112, USA.

OBJECT: When complicated by infection, craniotomy bone flaps are commonly removed, discarded, and delayed cranioplasty is performed. This treatment paradigm is costly, carries the risks associated with additional surgery, and may cause cosmetic deformities. The authors present their experience with an indwelling antibiotic irrigation system used for the sterilization and salvage of infected bone flaps as an alternative to their removal and replacement. METHODS: The authors retrospectively reviewed the medical records for 12 patients with bone flap infections following craniotomy who received treatment with the wash-in, wash-out indwelling antibiotic irrigation system. Infected flaps were removed and scrubbed with povidone-iodine solution and soaked in 1.5% hydrogen peroxide while the wound was debrided. The bone flaps were returned to the skull and the irrigation system was installed. Antibiotic medication was infused through the system for a mean of 5 days. Intravenous antibiotic therapy was continued for 2 weeks and oral antibiotics for 3 months postoperatively. Wound checks were performed at clinic follow-up visits, and there was a mean follow-up period of 13 months. Eleven of the 12 patients who had undergone placement of the bone flap irrigation system experienced complete resolution of the infection. In five patients there was involvement of the nasal sinus cavities, and in four there was a history of radiation treatment. In the one patient whose infection recurred, there was both involvement of the nasal sinuses and a history of extensive radiation treatment. CONCLUSIONS: Infected bone flaps can be salvaged, thus avoiding the cost, risk, and possible disfigurement associated with flap removal and delayed cranioplasty. Although prior radiation treatment and involvement of the nasal sinuses may interfere with wound healing and clearance of the infection, these factors should not preclude the use of irrigation with antibiotic agents for bone flap salvage.

PMID: 17044572 [PubMed - indexed for MEDLINE]

 

30: J Neurosurg. 2006 Oct;105(4):627-30.

Commercial flight and patients with intracranial mass lesions: a caveat. Report of two cases.

Zrinzo LU, Crocker M, Zrinzo LV, Thomas DG, Watkins L.

Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London, United Kingdom.

The authors report two cases of neurological deterioration following long commercial flights. Both individuals harbored intracranial space-occupying lesions. The authors assert that preexisting reduced intracranial compliance diminishes an individual's reserve to accommodate the physiological changes resulting from a commercial flight. Airline passengers are exposed to a mild degree of hypercapnia as well as conditions that simulate those of high-altitude ascents. High-altitude cerebral edema following an ascent to great heights is one facet of acute mountain sickness and can be life threatening in conditions similar to those present on commercial flights. Comparable reports documenting neurological deterioration at high altitudes in patients with coexisting space-occupying lesions were also reviewed.

Publication Types:

• Case Reports

PMID: 17044569 [PubMed - indexed for MEDLINE]

 

31: J Neurosurg. 2006 Oct;105(4):621-6.

Long-term response of pituitary carcinoma to temozolomide. Report of two cases.

Fadul CE, Kominsky AL, Meyer LP, Kingman LS, Kinlaw WB, Rhodes CH, Eskey CJ, Simmons NE.

Department of Medicine, Section of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756-0001, USA. camilo.e.fadul@hitchcock.org

Pituitary carcinoma is a rare tumor characterized by poor responsiveness to therapy, leading to early death. Reported responses to standard chemotherapy have only been anecdotal, with no single agent or combination demonstrating consistent efficacy in the treatment of patients with this disease. The authors report rare examples of a persistent response to cytotoxic chemotherapy in two patients with pituitary carcinoma. One patient was a 38-year-old man with visual field loss caused by a luteinizing hormone-secreting pituitary carcinoma that had recurred despite multiple surgeries and radiation therapy. Intradural metastases to the spine that had failed to respond to radiation therapy were pathologically confirmed. The second patient was a 26-year-old man with hyperprolactinemia from a prolactin-secreting pituitary tumor. Spine magnetic resonance images obtained to search for causes of neck pain showed a vertebral tumor, which was later confirmed through pathological analysis to be a metastatic pituitary carcinoma. His disease progressed despite radiation therapy, high-dose bromocriptine, and chemotherapy. Both patients were treated monthly with temozolomide, which was administered orally on the first 5 days of a 28-day cycle. The patient in the first case underwent all 12 treatment cycles without serious side effects, and his visual field deficits improved. The patient in the second case had undergone only 10 cycles when the drug was stopped because of his severe fatigue. Nonetheless, his pain disappeared and his serum prolactin concentration decreased. Both patients continue to have partial responses and have been employed full-time for more than 1 year after discontinuing temozolomide therapy. These two examples demonstrate that temozolomide may be effective in treating pituitary carcinomas and thus should be considered in the treatment algorithm for these difficult cases.

Publication Types:

• Case Reports

PMID: 17044568 [PubMed - indexed for MEDLINE]

 

32: J Neurosurg. 2006 Oct;105(4):616-20.

Ependymoma of the pituitary fossa. Case report and review of the literature.

Mukhida K, Asa S, Gentili F, Shannon P.

Division of Neurosurgery, University of Toronto and Toronto Western Hospital, Toronto, Ontario, Canada. kmukhida@dal.ca

The authors describe a case of pituitary fossa ependymoma and discuss its immunohistochemical and ultrastructural characteristics. A 43-year-old man presented with decreased libido and panhypopituitarism. Magnetic resonance imaging demonstrated a well-demarcated enhancing lesion of the pituitary fossa that was completely resected via a transsphenoidal approach. Ependymomas rarely occur in the pituitary fossa, and have been reported in this location only three times in humans and once in a horse. This is the first study in which investigators examined the appearance of a pituitary ependymoma by using electron microscopy. Theories of the origin and treatment of these rare tumors are discussed as they relate to other articles on intracranial ependymomas.

Publication Types:

• Case Reports

PMID: 17044567 [PubMed - indexed for MEDLINE]

 

33: J Neurosurg. 2006 Oct;105(4):588-94.

Motor field sensitivity for preoperative localization of motor cortex.

Lin PT, Berger MS, Nagarajan SS.

Department of Neurology, Stanford Hospital and Clinics, Stanford, California, USA.

OBJECT: In this study the role of magnetic source imaging for preoperative motor mapping was evaluated by using a single-dipole localization method to analyze motor field data in 41 patients. METHODS: Data from affected and unaffected hemispheres were collected in patients performing voluntary finger flexion movements. Somatosensory evoked field (SSEF) data were also obtained using tactile stimulation. Dipole localization using motor field (MF) data was successful in only 49% of patients, whereas localization with movement-evoked field (MEF) data was successful in 66% of patients. When the spatial distribution of MF and MEF dipoles in relation to SSEF dipoles was analyzed, the motor dipoles were not spatially distinct from somatosensory dipoles. CONCLUSIONS: The findings in this study suggest that single-dipole localization for the analysis of motor data is not sufficiently sensitive and is nonspecific, and thus not clinically useful.

PMID: 17044563 [PubMed - indexed for MEDLINE]

 

34: J Neurosurg. 2006 Oct;105(4):576-80.

Microhemorrhage, a possible mechanism for cyst formation in vestibular schwannomas.

Park CK, Kim DC, Park SH, Kim JE, Paek SH, Kim DG, Jung HW.

Department of Neurosurgery, Seoul National University College of Medicine, Korea.

OBJECT: Cystic vestibular schwannoma (VS) is a unique subgroup of VSs characterized by unpredictable expansion of the cyst component. Little is known, however, about the mechanism of cyst formation. In this study the authors compared neuroimaging and histological characteristics of cystic with solid VS to determine the pathogenesis of the cystic subgroup. METHODS: Two cohorts, one comprising 10 patients with cystic VS and the other comprising 10 patients with solid VS, were studied. Surgery was chosen as the primary treatment in all patients, with no other modality applied. Preoperative magnetic resonance images and histological characteristics of the tumor in patients with cystic VSs were evaluated and compared with those in the group with solid VSs. Differences between the two groups were assessed using the chi-square test. Neuroimaging findings revealed that either fluid-fluid level or hemosiderin deposit was present in all cystic VSs. Histological evidence of microhemorrhage, such as hemosiderin-laden macrophages (p = 0.069), hemosiderin deposits (p = 0.019), thrombotic vessels (p = 0.008), and abnormal vessel proliferation (p = 0.006) were more prominent in cystic VSs compared with solid ones. There was no difference in Antoni type dominance and Ki-67 proliferative index between the two groups. CONCLUSIONS: Intratumoral microhemorrhage is a possible mechanism of pathogenesis in cystic VS.