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Relative cerebral blood volume maps corrected for
contrast agent extravasation significantly correlate with glioma tumor
grade, whereas uncorrected maps do not.
Boxerman
JL, Schmainda
KM, Weisskoff
RM.
Department of Radiology, Rhode Island Hospital and Brown University Medical
School, Providence, RI.
BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) estimates for
high-grade gliomas computed with dynamic susceptibility contrast MR imaging
are artificially lowered by contrast extravasation through a disrupted
blood-brain barrier. We hypothesized that rCBV corrected for agent leakage
would correlate significantly with histopathologic tumor grade, whereas
uncorrected rCBV would not. METHODS: We performed dynamic T2*-weighted
perfusion MR imaging on 43 patients with a cerebral glioma after prebolus
gadolinium diethylene triamine penta-acetic acid administration to diminish
competing extravasation-induced T1 effects. The rCBV was computed from
non-necrotic enhancing tumor regions by integrating the relaxivity-time
data, with and without contrast extravasation correction by using a linear
fitting algorithm, and was normalized to contralateral brain. We determined
the statistical correlation between corrected and uncorrected normalized
rCBV and histopathologic tumor grade with the Spearman rank correlation
test. RESULTS: Eleven, 9, and 23 patients had WHO grades II, III, and IV
glioma, respectively. Mean uncorrected normalized rCBVs were 1.53, 2.51, and
2.14 (grade II, III, and IV). Corrected normalized rCBVs were 1.52, 2.84,
and 3.96. Mean absolute discrepancies between uncorrected and corrected
rCBVs were 2% (0%-15%), 16% (0%-106%), and 74% (0%-411%). The correlation
between corrected rCBV and tumor grade was significant (0.60; P < .0001),
whereas it was not for uncorrected rCBV (0.15; P = .35). CONCLUSION: For
gliomas, rCBV estimation that correlates significantly with WHO tumor grade
necessitates contrast extravasation correction. Without correction,
artificially lowered rCBV may be construed erroneously to reflect lower
tumor grade.
PMID: 16611779 [PubMed - in process]
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Do cerebral blood volume and contrast transfer
coefficient predict prognosis in human glioma?
Mills
SJ, Patankar
TA, Haroon
HA, Baleriaux
D, Swindell
R, Jackson
A.
Department of Imaging Science and Biomedical Engineering, Christie Hospital
NHS Trust, Manchester, United Kingdom.
INTRODUCTION: Noninvasive measurements of cerebral blood volume (CBV) and
contrast transfer coefficient (K(trans)) have potential benefits in the
diagnosis and therapeutic management of adult glioma. This study examines
the relationship between CBV, K(trans), and overall survival. METHODS AND
MATERIALS: Twenty-seven adult patients with glioma underwent T1-weighted
dynamic contrast-enhanced MR imaging, and parametric maps of CBV and K(trans)
were calculated. The relationship of histologic grade, CBV, K(trans), age,
sex, surgical resection, and use of adjuvant therapy to survival were
analyzed by using the logrank method and Cox regression analysis. The
Kaplan-Meier method for displaying survival curves was used. The
relationship of factors such as comorbidity, elevated intracranial pressure,
size of nonenhancing tumor, and peritumoral edema were not considered.
RESULTS: Both CBV (P < .01) and K(trans) (P < .01) show a significant
relationship to histologic grade. CBV (P = .004), K(trans) (P = .008), and
histologic grade (P < .001) all demonstrate a significant association
with patient survival when analyzed individually. Cox regression analysis
identified only histologic grade (P < .01) and K(trans) (P < .05) as
independent significant prognostic indicators. Examination of survival data
from high-grade (III and IV) tumors demonstrated a linear relationship
between K(trans) and patient survival (P < .01). CONCLUSION: This study
suggests a direct relationship between K(trans) and length of survival in
high-grade gliomas, which could be of clinical importance. CBV relates
directly to histologic grade but provides no independent prognostic
information over and above that provided by grade. Further large prospective
studies should be planned to test whether this observation holds true.
PMID: 16611778 [PubMed - in process]>>>
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Remote cerebellar hemorrhage.
Amini
A, Osborn
AG, McCall
TD, Couldwell
WT.
Department of Neurological Surgery, University of Utah Health Sciences
Center, Salt Lake City, Utah 84132, USA.
Remote cerebellar hemorrhage (RCH) is a rare but benign, self-limited
complication of supratentorial craniotomies that, to the best of our
knowledge, has not been described in the imaging literature. RCH can be an
unexpected finding on routine postoperative imaging studies and should not
be mistaken for more ominous causes of bleeding such as coagulopathy,
hemorrhagic infarction, or cortical vein occlusion. Cerebellar hemorrhage in
the typical setting can be identified as RCH and does not require more
extensive or invasive evaluation.
Publication Types:
PMID: 16484416 [PubMed - indexed for MEDLINE]
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Optic nerve hyperintensity on T2-weighted images among
patients with pituitary macroadenoma: correlation with visual impairment.
Tokumaru
AM, Sakata
I, Terada
H, Kosuda
S, Nawashiro
H, Yoshii
M.
Department of Radiology, Tokyo Metropolitan Geriatric Hospital, Tokyo,
Japan.
PURPOSE: Visual acuity (VA) disturbance other than field defect is important
in evaluating patients with pituitary macroadenoma. The purpose of this
study was to evaluate MR imaging appearances of optic nerves in patients
with pituitary macroadenoma and to ascertain whether visual impairment was
correlated with abnormality in optic nerve signal intensity. PATIENTS AND
METHODS: Twenty-seven patients with pituitary macroadenoma were examined.
Optic nerves were evaluated on T2-weighted images and correlations of signal
intensity abnormality with VA disturbance, visual field disturbance, degree
of optic chiasm compression, pathologic findings of surgical specimen, and
disease duration were statistically analyzed. Correlations between recovery
of VA after treatment and the above-mentioned factors were also determined.
RESULTS: Coronal T2-weighted images demonstrated unilateral optic nerve
hyperintensity lesions in 9 patients. Bilateral signal intensity abnormality
of the optic nerve was seen in 5 patients. Signal intensity abnormality of
the optic nerve was seen at the site of compression and in the ventral side
of the tumor. These patients did not demonstrate signal intensity
abnormality posterior to the tumor. Presence of such signal intensity
abnormalities was correlated with the degree of optic chiasmal compression
and with VA disturbance. Recovery of VA after treatment was correlated with
disease duration. CONCLUSION: Hyperintensity of the optic nerves ventral to
the pituitary macroadenoma was associated with VA impairment. Recovery of VA
after treatment was correlated with disease duration. MR imaging of the
optic nerves can provide valuable information for management of pituitary
macroadenoma.
PMID: 16484385 [PubMed - indexed for MEDLINE]
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Cytologic diagnosis of meningioma metastatic to the
pleural cavity.
Maly
B, Maly
A, Doviner
V, Reinhartz
T, Sherman
Y.
Publication Types:
PMID: 16610700 [PubMed - in process]
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Malignant disseminated chordoid meningioma in a
12-year-old child: a role for early cranial and spinal radiation treatment
after subtotal resection.
Mullassery
D, O'brien
DF, Williams
D, Crooks
D, Mallucci
C, Pizer
B, Thorp
N, McDowell
H.
Department of Neurosurgery, Neuropathology and Neuro-oncology, Royal
Liverpool Children's Hospital NHS Trust, Alder Hey and the Walton Centre for
Neurology and Neurosurgery NHS Trust, Liverpool, UK.
CASE REPORT: We present a case of a chordoid meningioma, a tumour sub-type
which comprises less than 0.5% of all meningiomas. The patient, a
12-year-old Somalian girl with a history of having had a craniotomy for a
brain tumour in her native country 11 months previously, presented with
seizures. Imaging revealed an isolated left frontal tumour, which at the
time was felt to be a residual mass. She underwent a macroscopically
complete resection of this tumour. Histology revealed it to be a grade 2
chordoid meningioma. Recurrence with additional local meningeal lesions was
detected on follow-up magnetic resonance imaging (MRI) at 2 months post
surgery. These were resected and she was treated with adjuvant cranial
radiation treatment that resulted in non-progression of the cranial tumour
on imaging 6 and 12 months post surgery. However, at 12 months post initial
presentation, she re-presented with disseminated spinal disease refractory
to salvage radiation treatment and succumbed to her illness. OUTCOME: This
is the first reported case of cranial radiation treatment being used to
treat sub-totally resected recurrent chordoid meningioma. Whilst
intra-cranial control of the tumour was achieved with this management, it
did not prevent spinal progression. The authors advise a high-surveillance
management strategy when treating these lesions and to employ cranial and
spinal radiation treatment at the first sign of disease progression.
PMID: 16607533 [PubMed - as supplied by publisher]
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Use of an Orthotopic Xenograft Model for Assessing the
Effect of Epidermal Growth Factor Receptor Amplification on Glioblastoma
Radiation Response.
Sarkaria
JN, Carlson
BL, Schroeder
MA, Grogan
P, Brown
PD, Giannini
C, Ballman
KV, Kitange
GJ, Guha
A, Pandita
A, James
CD.
Authors' Affiliations: Departments of Radiation Oncology, Laboratory
Medicine and Pathology, and Biostatistics, Mayo Clinic, Rochester, Minnesota
and the Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital
for Sick Children, University of Toronto, Toronto, Ontario, Canada.
PURPOSE: The influence of epidermal growth factor receptor (EGFR)
amplification on glioblastoma patient prognosis following definitive
radiotherapy has been extensively investigated in clinical studies, and yet
the relationship between EGFR status and radiation response remains unclear.
The intent of the current study was to address this relationship using
several EGFR-amplified glioblastoma xenografts in an orthotopic athymic
mouse model. EXPERIMENTAL DESIGN: We examined the effect of radiation on the
survival of nude mice with intracranial xenografts derived from 13 distinct
patient tumors, 7 of which have amplified EGFR. Mice with established
intracranial tumors were randomized to sham treatment or 12-Gy radiation in
six fractions delivered over 12 days. RESULTS: For six of the xenografts,
radiation of mice with intracranial tumor significantly extended survival,
and four of these xenografts had EGFR amplification. For seven other
xenografts, radiation treatment did not significantly extend survival, and
three of these, including GBM12, had EGFR amplification. Similar to EGFR,
the tumor genetic status of p53 or PTEN did not show preferential
association with radiation-sensitive or radiation-resistant xenografts
whereas hyperphosphorylation of Akt on Ser(473) was associated with
increased radioresistance. To specifically investigate whether inhibition of
EGFR kinase activity influences radiation response, we examined combined
radiation and EGFR inhibitor treatment in mice with intracranial GBM12. The
combination of oral erlotinib administered concurrently with radiation
resulted only in additive survival benefit relative to either agent alone.
CONCLUSIONS: Our results indicate that EGFR amplification, as a biomarker,
is not singularly predictive of glioblastoma response to radiation therapy,
nor does the inhibition of EGFR enhance the intrinsic radiation
responsiveness of glioblastoma tumors. However, efficacious EGFR inhibitor
and radiation monotherapy regimens can be used in combination to achieve
additive antitumor effect against a subset of glioblastoma.
PMID: 16609043 [PubMed - as supplied by publisher]>>>
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Glycoprotein nonmetastatic melanoma protein B, a
potential molecular therapeutic target in patients with glioblastoma
multiforme.
Kuan
CT, Wakiya
K, Dowell
JM, Herndon
JE 2nd, Reardon
DA, Graner
MW, Riggins
GJ, Wikstrand
CJ, Bigner
DD.
Authors' Affiliations: Preston Robert Tisch Brain Tumor Center at Duke,
Departments of Pathology and Biostatistics, Duke University Medical Center,
Durham, North Carolina and Department of Neurosurgery, Johns Hopkins
University, Baltimore, Maryland.
PURPOSE: More brain tumor markers are required for prognosis and targeted
therapy. We have identified and validated promising molecular therapeutic
glioblastoma multiforme (GBM) targets: human transmembrane glycoprotein
nonmetastatic melanoma protein B (GPNMB(wt)) and a splice variant form (GPNMB(sv),
a 12-amino-acid in-frame insertion in the extracellular domain).
EXPERIMENTAL DESIGN: We have done genetic and immunohistochemical evaluation
of human GBM to determine incidence, distribution, and pattern of
localization of GPNMB antigens in brain tumors as well as survival analyses.
RESULTS: Quantitative real-time PCR on 50 newly diagnosed GBM patient tumor
samples indicated that 35 of 50 GBMs (70%) were positive for GPNMB(wt+sv)
transcripts and 15 of 50 GBMs (30%) were positive for GPNMB(sv) transcripts.
Normal brain samples expressed little or no GPNMB mRNA. We have isolated and
characterized an anti-GPNMB polyclonal rabbit antiserum (2640) and two IgG2b
monoclonal antibodies (mAb; G11 and U2). The binding affinity constants of
the mAbs ranged from 0.27 x 10(8) to 9.6 x 10(8) M(-1) measured by surface
plasmon resonance with immobilized GPNMB, or 1.7 to 2.1 x 10(8) M(-1) by
Scatchard analyses with cell-expressed GPNMB. Immunohistochemical analysis
detected GPNMB in a membranous and cytoplasmic pattern in 52 of 79 GBMs
(66%), with focal perivascular reactivity in approximately 27%. Quantitative
flow cytometric analysis revealed GPNMB cell surface molecular density of
1.1 x 10(4) to 7.8 x 10(4) molecules per cell, levels sufficient for mAb
targeting. Increased GPNMB mRNA levels correlated with elevated GPNMB
protein expression in GBM biopsy samples. Univariate and multivariate
analyses correlated expression of GPNMB with survival of 39 GBM patients
using RNA expression and immunohistochemical data, establishing that
patients with relatively high mRNA GPNMB transcript levels (wt+sv and wt),
>3-fold over normal brain, as well as positive immunohistochemistry, have
a significantly higher risk of death (hazard ratios, 3.0, 2.2, and 2.8,
respectively). CONCLUSIONS: Increased mRNA and protein levels in GBM patient
biopsy samples correlated with higher survival risk; as a detectable surface
membrane protein in glioma cells, the data indicate that GPNMB is a
potentially useful tumor-associated antigen and prognostic predictor for
therapeutic approaches with malignant gliomas or any malignant tumor that
expresses GPNMB.
PMID: 16609006 [PubMed - in process]>>>
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Stereotactic radiosurgery for four or more intracranial
metastases.
Bhatnagar
AK, Flickinger
JC, Kondziolka
D, Lunsford
LD.
Department of Radiation Oncology, University of Pittsburgh School of
Medicine, Pittsburgh, PA 15213, USA.
PURPOSE: To evaluate the outcomes after a single stereotactic radiosurgery
procedure for the care of patients with 4 or more intracranial metastases.
METHODS AND MATERIALS: Two hundred five patients with primary malignancies,
including non-small-cell lung carcinoma (42%), breast carcinoma (23%),
melanoma (17%), renal cell carcinoma (6%), colon cancer (3%), and others
(10%) underwent gamma knife radiosurgery for 4 or more intracranial
metastases at one time. The median number of brain metastases was 5 (range,
4-18) with a median total treatment volume of 6.8 cc (range, 0.6-51.0 cc).
Radiosurgery was used as sole management (17% of patients), or in
combination with whole brain radiotherapy (46%) or after failure of whole
brain radiotherapy (38%). The median marginal radiosurgery dose was 16 Gy
(range, 12-20 Gy). The mean follow-up was 8 months. RESULTS: The median
overall survival after radiosurgery for all patients was 8 months. The
1-year local control rate was 71%, and the median time to progressive/new
brain metastases was 9 months. Using the Radiation Therapy Oncology Group
recursive partitioning analysis (RPA) classification system, the median
overall survivals for RPA classes I, II, and III were 18, 9, and 3 months,
respectively (p < 0.00001). Multivariate analysis revealed total
treatment volume, age, RPA classification, and marginal dose as significant
prognostic factors. The number of metastases was not statistically
significant (p = 0.333). CONCLUSION: Radiosurgery seems to provide survival
benefit for patients with 4 or more intracranial metastases. Because total
treatment volume was the most significant predictor of survival, the total
volume of brain metastases, rather than the number of metastases, should be
considered in identifying appropriate radiosurgery candidates.
Publication Types:
PMID: 16338097 [PubMed - indexed for MEDLINE]>>>
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Role of radiotherapy in supratentorial primitive
neuroectodermal tumor in young children: results of the German HIT-SKK87 and
HIT-SKK92 trials.
Timmermann
B, Kortmann
RD, Kuhl
J, Rutkowski
S, Meisner
C, Pietsch
T, Deinlein
F, Urban
C, Warmuth-Metz
M, Bamberg
M.
Department of Radiation Oncology and the Institute for Medical Information
Processing, University of Tubingen, Tubingen, Germany. beate.timmermann@psi.ch
PURPOSE: To assess the outcome of young children with supratentorial
primitive neuroectodermal tumor (stPNET) treated by intensive postoperative
chemotherapy alone compared with treatment with chemotherapy and delayed
radiotherapy (RT). PATIENTS AND METHODS: From 1987 to 1992, children younger
than 3 years of age with stPNET were enrolled in the HIT-SKK87 trial in
Germany and Austria. After surgery, low-risk patients received maintenance
chemotherapy before RT. In high-risk patients, intensive induction
chemotherapy was followed by maintenance chemotherapy until delayed RT was
initiated. In the following trial, HIT-SKK92 methotrexate-based chemotherapy
was applied. In children with complete remission after three cycles, therapy
was finished without irradiation. Otherwise, radiotherapy or salvage
chemotherapy was administered. RESULTS: Twenty-nine children were eligible
(age, 3.0 to 37.0 months). All children received chemotherapy. In 15
children, no RT was administered. Four children had tumor progression during
chemotherapy and underwent irradiation. In 10 patients, RT was given after
chemotherapy. Overall survival (OS) and progression-free survival (PFS)
rates after 3 years were 17.2% and 14.9%, respectively. Twenty-four children
relapsed (13 at the tumor site only, three at distant site, and eight at
both local and distant sites). Positive impact on survival was observed in
children with complete resection but without statistical significance.
Administration of RT was the only significant predictive factor for OS and
PFS. Only one child not having RT survived. CONCLUSION: Outcome of infants
and babies with stPNET is unsatisfactory. Omission of RT jeopardizes
survival, even if intensive chemotherapy is applied. We suggest to limit any
delay of RT to a maximum of 6 months even in young children.
Publication Types:
PMID: 16575007 [PubMed - indexed for MEDLINE]
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Human telomere reverse transcriptase expression predicts
progression and survival in pediatric intracranial ependymoma.
Tabori
U, Ma
J, Carter
M, Zielenska
M, Rutka
J, Bouffet
E, Bartels
U, Malkin
D, Hawkins
C.
Division of Hematology/Oncology, The Hospital for Sick Children and the
University of Toronto, Toronto, Canada.
PURPOSE: Pediatric intracranial ependymomas are a heterogeneous group of
neoplasms with unpredictable clinical and biologic behavior. As part of
ongoing studies to identify potential biologic and therapeutic markers, we
analyzed the role of human telomere reverse transcriptase (hTERT; the
catalytic subunit of telomerase) expression as a prognostic marker for this
disease. PATIENTS AND METHODS: Primary intracranial ependymomas that were
resected at our institution between 1986 and 2004 were identified through
the pathology and oncology databases. A tissue array was constructed from
the patient samples and hTERT expression was evaluated by
immunohistochemistry. Twenty-one samples were also analyzed for telomerase
activity (telomerase repeat amplification protocol assay). RESULTS:
Eighty-seven tumors from 65 patients were analyzed. Five-year
progression-free survival was 57% (SEM, 12%) and 21% (SEM, 8%) for hTERT-negative
and hTERT-positive tumors, respectively (P = .002). Five-year overall
survival was 84% (SEM, 7%) and 41% (SEM, 7%) for hTERT-negative and hTERT-positive
tumors, respectively (P = .001). There was good correlation between
telomerase activity and hTERT expression (kappa = 0.637). Multivariate
analysis revealed hTERT expression to be the single most important predictor
of survival of all known pathologic, clinical, and treatment factors (hazard
ratio, 60.4; 95% CI, 6.4 to 561). All four patients with hTERT-negative
tumors at relapse are still alive, with median follow-up of 11.2 years.
CONCLUSION: In this study, hTERT expression was the strongest predictor of
outcome and was independent of other clinical and pathologic prognostic
markers. It represents a simple and reliable biologic prognostic factor for
intracranial ependymomas. These results should be confirmed in larger
prospective trials.
PMID: 16575002 [PubMed - indexed for MEDLINE]
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Incidence of infusion plan alterations after angiography
in patients undergoing intra-arterial chemotherapy for brain tumors.
Newton
HB, Figg
GM, Slone
HW, Bourekas
E.
Division of Neuro-Oncology and Dardinger Neuro-Oncology Center, Department
of Neurology, Ohio State University Medical Center and James Cancer Hospital
& Solove Research Institute, 465 Means Hall, 1654 Upham Drive, Columbus,
Ohio, USA, newton.12@osu.edu.
During intra-arterial (IA) chemotherapy of brain tumors, the initial vessels
chosen for infusion are based on the vascular distribution of the tumor as
revealed by CT or MR imaging. However, angiography may reveal details of
vascular anatomy that require an alteration of the vessel infusion plan. The
incidence of infusional alterations and the underlying vascular anatomy
involved remains unknown in patients with brain tumors undergoing IA
chemotherapy. To evaluate this question, we performed a chart, CT/MRI, and
angiography review of brain tumor patients receiving IA chemotherapy.
Seventy-eight patients were identified with primary (39) and metastatic (39)
brain tumors. The cohort consisted of 40 males and 38 females, with a mean
age of 47.8 years. During the course of IA treatment, angiographic review
identified 5 patients (6.4%) that required an alteration of the vessel
infusion plan. In three cases, angiography demonstrated more substantial
perfusion of the tumor from a different arterial supply. In two cases,
angiography revealed variations in normal anatomy associated with unexpected
tumor perfusion. Careful interpretation of angiography at the initiation of
each cycle of IA chemotherapy is very important to verify that the
appropriate vessels have been chosen for drug infusion, in order to maximize
regional dose intensity. In our series, the angiography results necessitated
an alteration of the infusion plan in 6.4% of the patient cohort.
PMID: 16614945 [PubMed - as supplied by publisher]
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Vinorelbine combined with a protracted course of
temozolomide for recurrent brain Metastases: a phase I trial.
Omuro
AM, Raizer
JJ, Demopoulos
A, Malkin
MG, Abrey
LE.
Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York
Avenue, New York, 10021, USA, abreyl@mskcc.org.
Temozolomide (TMZ) has shown modest efficacy in the treatment of recurrent
brain metastasis (BM). We designed a new regimen utilizing dose-intensified,
protracted course of TMZ in combination with vinorelbine, a lipophilic
large-spectrum agent, in an attempt to improve the efficacy of TMZ. This
phase I study was conducted to establish the maximum tolerated dose (MTD) of
vinorelbine for this combination. Patients with recurrent or progressive BM
were eligible. Chemotherapy consisted of 28-day cycles with TMZ (150
mg/m(2), days 1-7 and 15-21) and vinorelbine (days one and eight at
escalating doses). The starting dose was 15 mg/m(2), with increments of 5
mg/m(2) for each cohort of 3-6 patients, until MTD was reached (30 mg/m(2)).
A total of 21 patients were enrolled; the median age was 59 (41-77). The
primary tumor was lung cancer in 13 patients (NSCLC in 10, SCLC in 3),
breast in 6, renal in 1 and endometrial in 1. Vinorelbine dose was 15 mg/m(2
)in seven patients, 20 mg/m(2) in five, 25 mg/m(2) in four and 30 mg/m(2) in
six. Grades 3 and 4 neutropenia developed in six patients, lymphopenia in
nine, and thrombocytopenia in six; other toxicities were rare. No
dose-limiting toxicity was seen. Out of 18 evaluable patients 2 had a
radiographic response (one partial and one minor). Disease was stable in 6
of 18 patients and the median survival was 27 weeks. This regimen was well
tolerated and a phase II trial using a dose of 30 mg/m(2) of vinorelbine is
warranted.
PMID: 16614943 [PubMed - as supplied by publisher]>>>
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Increased concentrations of transforming growth factor
beta1 and beta2 in the plasma of patients with glioblastoma.
Schneider
T, Sailer
M, Ansorge
S, Firsching
R, Reinhold
D.
Department of Neurosurgery, Otto-von-Guericke University, Leipziger Strasse
44, D-39120, Magdeburg, Germany, thomas.schneider@medizin.uni-magdeburg.de.
Recently, several in vitro studies have demonstrated production of the
potent immunosuppressive cytokine transforming growth factor beta
(TGF-beta)2 in glioblastoma cell lines. Systematic studies of the
concentration of TGF-beta isoforms in the plasma of patients harboring
intracerebral tumors do not exist.In the present study, the concentrations
of TGF-beta1 and TGF-beta2 in platelet-poor plasma of 21 patients with
glioblastoma before and after extensive resection were measured by specific
ELISA systems and related to survival.The plasma concentrations of latent
TGF-beta1 of patients with glioblastoma prior to surgery were significantly
higher in comparison to healthy control probands, but not to patients with
multiple sclerosis (MS). Furthermore, latent TGF-beta2 was found to be
significantly increased in the plasma of patients with glioblastoma in
comparison to healthy control probands and patients with MS. After extensive
resection of the tumor, the value of latent TGF-beta2 evidently
decreased.Interestingly, the concentration of latent TGF-beta2 prior to
surgery was correlated with survival and a strong relationship was found
between the survival and the difference of latent TGF-beta2 levels prior to
surgery minus the TGF-beta2 concentrations 7 days after surgery. A higher
difference in these plasma concentrations >6 ng/ml vs. <6 ng/ml
clearly correlates with a longer survival time. In conclusion, this study
suggests that glioblastoma does secret TGF-beta2 in vivo and that TGF-beta2
may play an important role in glioblastoma patients.
PMID: 16614941 [PubMed - as supplied by publisher]>>>
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Inhibition of hypoxia inducible factor-1alpha
(HIF-1alpha) decreases vascular endothelial growth factor (VEGF) secretion
and tumor growth in malignant gliomas.
Jensen
RL, Ragel
BT, Whang
K, Gillespie
D.
Department of Neurosurgery, University of Utah, Salt Lake City, Utah, USA.
INTRODUCTION: Hypoxia inducible factor-1alpha (HIF-1alpha) regulates
vascular endothelial growth factor (VEGF), the presumed principal mediator
of angiogenesis in malignant gliomas, under normal physiologic conditions.
We examined the effect of HIF-1alpha on VEGF secretion, tumor growth, and
angiogenesis in malignant gliomas. METHODS: We examined 175 human gliomas
for expression of HIF-1alpha and its downstream-regulated proteins.
HIF-1alpha expression and VEGF secretion in glioma cell lines under normoxia
and hypoxia were examined using ELISA and Western blot. Malignant glioma
cell lines were transfected with dominant-negative HIF-1alpha
(DN-HIF-1alpha) expression vector or siRNA constructs against the HIF-1alpha
gene. Growth studies were conducted on cells with the highest VEGF/HIF-1alpha
inhibition isolated from stable transfected cell lines. MIB-1-labeling index
and microvascular density (MVD) measurements were performed on the in vivo
tumors. RESULTS: HIF-1 expression correlates with malignant glioma phenotype
and was not confined to perinecrotic, pseudopalisading cells. VEGF and HIF-1
expression was high in glioma cell lines even under normoxia, and increased
after exposure to hypoxia or growth factor stimulation. Cells transfected
with DN-HIF-1alpha or HIF-1alpha siRNA demonstrated decreased HIF-1alpha and
VEGF secretion. In vivo but not in vitro growth decreased in response to
VEGF and HIF-1 inhibition. HIF-1 siRNA studies showed decreased VEGF
secretion and in vitro and in vivo growth of glioma cell lines. MVD was
unchanged but MIB-1 proliferation index decreased for both types of HIF-1
inhibition. CONCLUSIONS: VEGF and HIF-1alpha are elevated in malignant
gliomas. HIF-1alpha inhibition results in VEGF secretion inhibition.
HIF-1alpha expression affects glioma tumor growth, suggesting clinical
applications for malignant glioma treatment.
PMID: 16612574 [PubMed - as supplied by publisher]>>>
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Rejection of RG-2 gliomas is mediated by microglia and T
lymphocytes.
Mariani
CL, Kouri
JG, Streit
WJ.
Department of Neuroscience, College of Medicine, University of Florida, P.O.
Box 100244, Gainesville, FL, 32611, USA, marianic@mail.vetmed.ufl.edu.
Immunotherapy holds great promise for the treatment of invasive brain
tumors, and we are interested specifically in evaluating immune stimulation
of microglial cells as one potential strategy. In order to better understand
the tumor fighting capabilities of microglial cells, we have compared the
responses of syngeneic (Fisher 344) and allogeneic (Wistar) rat strains
after intracranial implantation of RG-2 gliomas. Animals were evaluated by
clinical examination, magnetic resonance imaging (MRI) and
immunohistochemistry for microglial and other immune cell antigens. While
lethal RG-2 gliomas developed in all of the Fisher 344 rats, tumors grew
variably in the Wistar strain, sometimes reaching considerable sizes, but
eventually all of them regressed. Tumor regression was associated with
greater numbers of T cells and CD8 positive cells and increases in MHC I and
CD4 positive microglia. Our findings suggest that the combined mobilization
of peripheral and CNS endogenous immune cells is required for eradicating
large intracranial tumors.
PMID: 16612573 [PubMed - as supplied by publisher]
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Lactacystin Exhibits Potent Anti-tumor Activity in an
Animal Model of Malignant Glioma when Administered via Controlled-release
Polymers.
Legnani
FG, Pradilla
G, Thai
QA, Fiorindi
A, Recinos
PF, Tyler
BM, Gaini
SM, Dimeco
F, Brem
H, Olivi
A.
Department of Neurosurgery, School of Medicine, Johns Hopkins University,
Italy.
Lactacystin, a proteasome-inhibitor, has been shown to induce apoptosis of
experimental gliomas in vitro. However, its systemic toxicity prevents
further clinical use. To circumvent this problem, lactacystin can be
delivered intratumorally. We tested the efficacy of lactacystin incorporated
into controlled-release polymers for treating experimental gliomas.
9L-gliosarcoma and F98-glioma cell lines were treated with lactacystin
(10-100 mug/ml) for 72 h in vitro. Cell-viability was measured with MTT-assays.
Toxicity of lactacystin/polycarboxyphenoxypropane-sebacic-acid (pCPP : SA)
polymers was tested in vivo using Fischer-344 rats intracranially implanted
with lactacystin polymers loaded from 0.1 to 2% lactacystin by weight. The
efficacy of 1, 1.3, 1.5 and 1.7% lactacystin/pCPP : SA polymers was
determined in Fischer-344 rats intracranially challenged with 9L and treated
either simultaneously or 5 days after tumor implantation. Lactacystin was
cytotoxic in 9L cells, causing a 16 +/- 8% growth inhibition at 10-mug/ml
that increased to 78 +/- 4% at 100-mug/ml. Similarly, lactacystin inhibited
growth of F98 by 18 +/- 8% at 10-mug/ml and 74 +/- 2% at 100-mug/ml in
vitro. Polymers released lactacystin for 21 days and intracranial
implantation in rats neither generate local nor systemic toxicity at doses
lower than 2%. Treatment with lactacystin/pCPP : SA polymers with loading
concentrations of 1.0, 1.3, and 1.5% prolonged survival of animals
intracranially challenged with 9L when polymers where inserted in the day of
tumor implantation. In conclusion, lactacystin exhibits potent cytotoxic-activity
against 9L and F98 in vitro, it can be efficiently incorporated and
delivered using controlled-release polymers, and at the proposed
concentrations lactacystin polymers are safe for CNS delivery and prolong
survival in the 9L model.
PMID: 16609837 [PubMed - as supplied by publisher]
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New concepts in surgery of WHO grade II gliomas:
functional brain mapping, connectionism and plasticity - a review.
Duffau
H.
Department of Neurosurgery, UMR-S678 Inserm, Hopital Salpetriere, Paris,
France.
Despite a recent literature supporting the impact of surgery on the natural
history of low-grade glioma (LGG), the indications of resection still remain
a matter of debate, especially because of the frequent location of these
tumors within eloquent brain areas - thus with a risk to induce a permanent
postoperative deficit. Therefore, since the antagonist nature of this
surgery is to perform the most extensive glioma removal possible, while
preserving the function and the quality of life, new concepts were recently
applied to LGG resection in order to optimize the benefit/risk ratio of the
surgery.First, due to the development of functional mapping methods, namely
perioperative neurofunctional imaging and intrasurgical direct electrical
stimulation, the study of cortical functional organization is currently
possible for each patient - in addition to an extensive neuropsychological
assessment. Such knowledge is essential because of the inter-individual
anatomo-functional variability, increased in tumors due to cerebral
plasticity phenomena. Thus, brain mapping enables to envision and perform a
resection according to individual functional boundaries.Second, since LGG
invades not only cortical but also subcortical structures, and shows an
infiltrative progression along the white matter tracts, new techniques of
anatomical tracking and functional mapping of the subcortical white matter
pathways were also used with the goal to study the individual effective
connectivity - which needs imperatively to be preserved during the
resection.Third, the better understanding of brain plasticity mechanisms,
induced both by the slow-growing LGG and by the surgery itself, were equally
studied in each patient and applied to the surgical strategy by
incorporating individual dynamic potential of reorganization into the
operative planning.The integration of these new concepts of individual
functional mapping, connectivity and plastic potential to the surgery of LGG
has allowed an extent of surgical indications, an optimization of the
quality of resection (neuro-oncological benefit), and a minimization of the
risk of sequelae (benefit on the quality of life). In addition, such a
strategy has also fundamental applications, since it represents a new door
to the connectionism and cerebral plasticity.
PMID: 16607477 [PubMed - as supplied by publisher]
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Iatrogenic cerebellar implantation of a vestibular
schwannoma. Case report.
Patrick
TA, Giannini
C, Ebersold
MJ, Link
MJ.
Department of Neurologic Surgery, Mayo Clinic and Mayo Foundation,
Rochester, Minnesota 55902, USA.
Metastatic seeding or iatrogenic implantation of numerous types of primary
central nervous system tumors, typically along cerebrospinal fluid pathways,
is a frequently described albeit rare phenomenon and has never been reported
in association with vestibular schwannoma (VS). The authors present a case
of inadvertent surgical implantation of VS into the cerebellar hemisphere
during resection of a recurrent VS in the cerebellopontine angle and
internal auditory canal. A 42-year-old man presented with a 2.5-cm right VS
that was removed without complication via a retrosigmoid approach. Routine
imaging performed 5 years later revealed a 1.5-cm recurrence of the VS that
was subsequently removed by reopening the retrosigmoid craniotomy. Five
years later--10 years after initial presentation--follow-up imaging revealed
a 1-cm recurrence of the VS and a separate 2.2-cm tumor in the inferior
cerebellar parenchyma with surrounding edema. Both tumors were removed
without complication by reopening the previous retrosigmoid craniotomy.
Histological evaluation of these tumors revealed features typical of VS and
similar to those of the tissue obtained from the two prior resections. Given
the similarities among these tumors in pathological appearance and mitotic
index, the presence of the intraparenchymal cerebellar schwannoma was
probably due to intraoperative iatrogenic implantation.
Publication Types:
PMID: 16572663 [PubMed - indexed for MEDLINE]
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Coexisting intracranial meningeal melanocytoma, dermoid
tumor, and Dandy-Walker cyst in a patient with neurocutaneous melanosis.
Case report.
Kang
SG, Yoo
do S, Cho
KS, Kim
DS, Chang
ED, Huh
PW, Kim
MC.
Department of Neurosurgery, Uijeongbu St. Mary's Hospital, The Catholic
University of Korea College of Medicine, Uijeongbu, Geoynggi, Republic of
Korea.
Neurocutaneous melanosis (NCM) associated with Dandy-Walker malformation is
a very rare congenital neurodysplasia with the same origin. Primary
intracranial melanocytic and dermoid tumors are also benign congenital
lesions that usually arise from the leptomeninges and are formed by the
inclusion of cutaneous ectoderm at the time of neural tube closure. The
authors describe a patient with coexisting intracranial meningeal
melanocytoma, NCM with Dandy-Walker malformation, and intraventricular
dermoid tumor.
Publication Types:
PMID: 16572661 [PubMed - indexed for MEDLINE]
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Primary myxoma of the parafalcine meninges. Case report.
Powers
CJ, Pizzi
CC, Cummings
TJ, Friedman
AH.
Division of Neurosurgery, Department of Surgery, Duke University Medical
Center, Durham, North Carolina 27710, USA.
The authors report on an unusual case of a primary intracranial myxoma in a
39-year-old woman. The patient presented with headache and generalized
seizure. Magnetic resonance imaging revealed a large right frontal tumor
resembling a parasagittal meningioma. A gross-total resection was performed,
and histological review confirmed the lesion as a myxoma. Results of
additional workup revealed the absence of a primary myxoma elsewhere. This
case represents the third published report of a primary intracranial myxoma
and the second report of a supratentorial myxoma.
Publication Types:
PMID: 16572660 [PubMed - indexed for MEDLINE]
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Von Hippel-Lindau disease germline mutations in Mexican
patients with cerebellar hemangioblastoma.
Rasmussen
A, Nava-Salazar
S, Yescas
P, Alonso
E, Revuelta
R, Ortiz
I, Canizales-Quinteros
S, Tusie-Luna
MT, Lopez-Lopez
M.
Department of Neurogenetics and Molecular Biology, Instituto Nacional de
Neurologia y Neurocirugia Manuel Velasco Suarez, Mexico.
OBJECT: Central nervous system (CNS) hemangioblastomas are benign vascular
tumors arising either sporadically or as a manifestation of von
Hippel-Lindau (VHL) disease, a hereditary cancer syndrome. The authors
studied a series of patients with CNS hemangioblastomas and their families
to identify germline mutations in the VHL tumor suppressor gene and to
establish a predictive testing and screening protocol. METHODS: Patients
admitted between 2002 and 2004 to the Instituto Nacional de Neurologia y
Neurocirugia for hemangioblastoma were prospectively enrolled, together with
their at-risk family members. The authors performed the molecular analysis
of the VHL gene by using polymerase chain reaction and direct genetic
sequencing. All asymptomatic mutation carriers underwent genetic counseling
and tumor surveillance. Ninety-eight individuals were tested for VHL
mutations--23 symptomatic and 75 asymptomatic individuals belonging to 16
families. Seven of the families had definite clinical criteria of VHL
disease, five had sporadic hemangioblastoma, and four had CNS
hemangioblastoma combined with minor visceral signs. Molecular genetic
testing identified five germline mutations in six of the definite VHL
families (sensitivity 85%), but none in the possible VHL and sporadic
hemangioblastoma cases; four of these mutations had been previously
described and one is a novel mutation present in two unrelated families.
After patients carrying the mutation were identified, they underwent
clinical screening and asymptomatic VHL-related lesions were identified in
43%. CONCLUSIONS: Genetic testing for mutations in the VHL gene is crucial
in patients with CNS hemangioblastoma. The prompt identification of patients
carrying the genetic mutation allows for a multidisciplinary screening
protocol to decrease morbidity and mortality rates in these patients, while
avoiding costly and invasive procedures for noncarriers.
PMID: 16572651 [PubMed - indexed for MEDLINE]
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Effectiveness of neuronavigation in resecting solitary
intracerebral contrast-enhancing tumors: a randomized controlled trial.
Willems
PW, Taphoorn
MJ, Burger
H, Berkelbach
van der Sprenkel JW, Tulleken
CA.
Department of Neurosurgery, University Medical Center Utrecht, The
Netherlands. p.willems@neuro.azu.nl
OBJECT: The goal of this study was to assess the impact of neuronavigation
on the cytoreductive treatment of solitary contrast-enhancing intracerebral
tumors and outcomes of this treatment in cases in which neuronavigation was
preoperatively judged to be redundant. METHODS: The authors conducted a
prospective randomized study in which 45 patients, each harboring a solitary
contrast-enhancing intracerebral tumor, were randomized for surgery with or
without neuronavigation. Peri- and postoperative parameters under
investigation included the following: duration of the procedure; surgeon's
estimate of the usefulness of neuronavigation; quantification of the extent
of resection, determined using magnetic resonance imaging; and the
postoperative course, as evaluated by neurological examinations, the
patient's quality-of-life self-assessment, application of the Barthel index
and the Karnofsky Performance Scale score, and the patient's time of death.
The mean amount of residual tumor tissue was 28.9% for standard surgery (SS)
and 13.8% for surgery involving neuronavigation (SN). The corresponding mean
amounts of residual contrast-enhancing tumor tissue were 29.2 and 24.4%,
respectively. These differences were not significant. Gross-total removal (GTR)
was achieved in five patients who underwent SS and in three who underwent SN.
Median survival was significantly shorter in the SN group (5.6 months
compared with 9 months, unadjusted hazard ratio = 1.6); however, this
difference may be attributable to the coincidental early death of three
patients in the SN group. No discernible important effect on the patients'
3-month postoperative course was identified. CONCLUSIONS: There is no
rationale for the routine use of neuronavigation to improve the extent of
tumor resection and prognosis in patients harboring a solitary enhancing
intracerebral lesion when neuronavigation is not already deemed advantageous
because of the size or location of the lesion.
Publication Types:
PMID: 16572647 [PubMed - indexed for MEDLINE]
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Posterior spinal cord herniation into an extradural
thoracic arachnoid cyst: surgical treatment. Case report and review of the
literature.
Nejat
F, Cigarchi
SZ, Kazmi
SS.
Department of Neurosurgery, Children's Hospital Medical Center, Tehran
University of Medical Sciences, Tehran, Iran. nejat@sina.tums.ac.ir
The authors describe the case of a 2-year-old boy who experienced
progressive spastic paraparesis for several months. Magnetic resonance
imaging revealed an extensive extradural arachnoid cyst at the T3-L1 levels
and posterior spinal cord herniation at T3-4. Surgical release of the neck
of the hernia and total resection of the arachnoid cyst were performed. The
patient had good clinical recovery several weeks after surgical
decompression. This case highlights an exceedingly rare type of spinal cord
herniation in a pediatric age group, and focuses on the abnormalities of the
dorsal dura mater, together with imaging and intraoperative findings.
Publication Types:
PMID: 16572642 [PubMed - indexed for MEDLINE]
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Factor X deficiency presenting as a pseudotumor. Case
report.
Thachil
JV, Caswell
M, Keenan
R, Hayhurst
C, Crooks
DA, May
PL, O'Brien
DF.
Department of Haematology, Royal Liverpool Children's Hospital NHS Trust,
Alder Hey, Liverpool, United Kingdom.
The authors report their experience in successfully treating a 15-week-old
child who became comatose following a spontaneous intracerebral hemorrhage.
It was initially believed that a tumor in the right frontal lobe caused the
hemorrhage. Coagulation studies revealed abnormal results on presentation,
and the problem was only partially corrected after an infusion of fresh
frozen plasma. The child underwent an emergency craniotomy in which the
hematoma was evacuated, and a biopsy specimen was obtained from a firm mass
at the base of the hematoma cavity. Postoperatively, the child recovered
completely, and an analysis of detailed coagulation studies revealed that
the child had a factor X deficiency. Histological analysis of the biopsy
specimen revealed normal brain tissue with hemorrhagic infiltration.
Subsequently, the child achieved normal developmental milestones. A
diagnosis of congenital bleeding disorder should be considered in children
with spontaneous intracerebral hemorrhage, even in those with no prior
episode of extracerebral spontaneous hemorrhage.
Publication Types:
PMID: 16572640 [PubMed - indexed for MEDLINE]
-
C-kit gene mutation: common and widely distributed in
intracranial germinomas.
Kamakura
Y, Hasegawa
M, Minamoto
T, Yamashita
J, Fujisawa
H.
Department of Neurosurgery, Kanazawa University Hospital, Japan.
OBJECT: Of the intracranial germ cell tumors (IGCTs), 10% of germinomas and
most nongerminomatous tumors remain refractory to multimodality therapy. The
authors investigated the mutation of c-kit and the expression of its product
KIT in IGCTs to identify tumors susceptible to imatinib mesylate, a
synthetic agent targeting KIT. METHODS: The authors investigated 26 IGCTs,
including 13 germinomas, five mixed germ cell tumors (MGCTs), four immature
teratomas (ITs), and two each of yolk sac tumors and choriocarcinomas. These
tumors were examined for the expression of KIT and CD34 by
immunohistochemical analysis, and for mutations in exons 2, 8 to 11, 13, and
17 of c-kit. Strong KIT expression was found in the cell membrane of
germinomas (100%) and germinomatous cells of MGCTs (80%), as well as in the
cytoplasm of epithelial and smooth-muscle cells of ITs. The membranous
expression of CD34 was found in the nongerminomatous tumor cells and the
chondrocytes of MGCTs (60%), ITs (100%), and a choriocarcinoma (50%), but
not in germinomas and germinomatous cells. A total of five missense
mutations distributed in exons 2, 11, 13, and 17 of c-kit were detected in
three (23%) of the 13 germinomas. The novel mutations E73K, T96M (both in
exon 2), and A636V (in exon 13) were detected in a single tumor. The
presence or type of c-kit mutation was not correlated with patient
prognosis. CONCLUSIONS: Immunohistochemical analysis of KIT expression is
useful for the diagnosis of germinoma. This study may help in clarifying the
pathogenesis of IGCTs and in identifying tumors susceptible to drugs
targeting KIT.
PMID: 16572634 [PubMed - indexed for MEDLINE]
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Pediatric intramedullary spinal cord tumors.
Auguste
KI, Gupta
N.
Department of Neurological Surgery, University of California, San Francisco,
CA 94143-0112, USA.
Publication Types:
PMID: 16448908 [PubMed - indexed for MEDLINE]
-
-
Intramedullary spinal cord metastasis: clinical
management and surgical considerations.
Chi
JH, Parsa
AT.
Department of Neurological Surgery, University of California, San Francisco,
CA 94143, USA. chijo@neurosurg.ucsf.edu
Publication Types:
PMID: 16448907 [PubMed - indexed for MEDLINE]
-
-
Spinal cord hemangioblastomas.
Lonser
RR, Oldfield
EH.
Surgical Neurology Branch, National Institute of Neurological Disorders and
Stroke, National Institutes of Health, Bethesda, MD 20892-1414, USA. lonserr@ninds.nih.gov
Publication Types:
PMID: 16448906 [PubMed - indexed for MEDLINE]
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-
Spinal cord astrocytomas: presentation, management, and
outcome.
Roonprapunt
C, Houten
JK.
Department of Neurosurgery, North Shore University Hospital, 300 Community
Drive, Manhasset, NY 11030, USA.
Publication Types:
PMID: 16448905 [PubMed - indexed for MEDLINE]
-
-
Clinical management of intramedullary spinal ependymomas
in adults.
Lee
J, Parsa
AT, Ames
CP, McCormick
PC.
Department of Neurological Surgery, University of Utah, Salt Lake City, 30
N, 1900 E, RM 3B409, UT 84112, USA.
Publication Types:
PMID: 16448904 [PubMed - indexed for MEDLINE]
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-
Radiographic features of intramedullary spinal cord
tumors.
Waldron
JS, Cha
S.
Department of Neurological Surgery, M779, Box 0112, University of
California, San Francisco, CA 94143-0112, USA. waldronj@neurosurg.ucsf.edu
Publication Types:
PMID: 16448903 [PubMed - indexed for MEDLINE]
-
-
Pathologic and epidemiologic findings of intramedullary
spinal cord tumors.
Tihan
T, Chi
JH, McCormick
PC, Ames
CP, Parsa
AT.
Department of Pathology, University of California, San Francisco, CA 94143,
USA. tarik.tihan@ucsf.edu
Publication Types:
PMID: 16448902 [PubMed - indexed for MEDLINE]
-
-
Genetics and molecular biology of intramedullary spinal
cord tumors.
Chi
JH, Cachola
K, Parsa
AT.
Department of Neurological Surgery, University of California, San Francisco,
CA 94143, USA. chijo@neurosurg.ucsf.edu
Publication Types:
PMID: 16448901 [PubMed - indexed for MEDLINE]
-
Better image-guided surgery.
Roitberg
B.
Department of Neurosurgery, University of Illinois at Chicago, Chicago, Il.
60612
Publication Types:
PMID: 16583501 [PubMed - indexed for MEDLINE]
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-
Transsulcal microsurgical approach for subcortical small
brain lesions: technical note.
Jabre
A, Patel
A.
Department of Neurosurgery, Boston University Medical Center, Boston, MA
02118, USA. ajabre@bu.edu
We describe a transsulcal microsurgical approach for removal of small
subcortical brain lesions, guided by frameless stereotaxy. This technique of
simultaneous stereotactic localization of the subcortical lesion and its
adjacent sulcus, before surgical approach, results in optimal surgical
planning, leading to minimal brain tissue loss and excellent surgical
outcome.
Publication Types:
PMID: 16488262 [PubMed - indexed for MEDLINE]
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-
Lhermitte-Duclos disease: 11C-methionine positron
emission tomography data in 4 patients.
Van
Calenbergh F, Vantomme
N, Flamen
P, Demaerel
P, Sciot
R, Legius
E, Mortelmans
L, Plets
C.
Department of Neurosurgery, University hospital Gasthuisberg, B-3000 Leuven,
Belgium. frank.vancalenbergh@uz.kuleuven.ac.be
BACKGROUND: Lhermitte-Duclos disease is a cerebellar lesion, characterized
by an overgrowth of cerebellar ganglion cells, which replace granular cells
and Purkinje cells. Lhermitte-Duclos disease may be a manifestation of
Cowden syndrome (multiple hamartoma-neoplasia syndrome). The nature of LDD,
whether neoplastic, dysplastic, or hamartomatous, is still not exactly
understood. Metabolic imaging of the amino acid metabolism using PET could
be useful for noninvasive characterization of these lesions. METHODS: To
define the Meth-PET imaging characteristics of these lesions, we undertook a
Meth-PET study in 4 patients with LDD after obtaining informed consent. All
4 patients had clinical signs of Cowden syndrome. In 2, the diagnosis was
made with MRI; in 2, it was confirmed histologically. RESULTS: Using Meth-PET,
the cerebellar lesions had a high methionine uptake, except in the
subtotally resected lesion. The uptake of the lesions was markedly higher
than that of the contralateral normal regions. The mean L/C ratio was 2.07.
CONCLUSION: 11C-methionine positron emission tomography visualizes the
lesion of Lhermitte-Duclos disease as a high uptake area. This amino acid
hypermetabolism may be related to the slow growth of the lesions, and is an
argument to suggest that patients with LDD should be followed up carefully
to detect progression of the cerebellar lesion.
PMID: 16488255 [PubMed - indexed for MEDLINE]
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Volume 5, Number 16 - 18 April
2006