-
MR diffusion tensor imaging and fiber tracking in 5
spinal cord astrocytomas.
Ducreux
D, Lepeintre
JF, Fillard
P, Loureiro
C, Tadie
M, Lasjaunias
P.
Department of Neuroradiology, CHU de Bicetre, Paris XI University, Le
Kremlin-Bicetre, France.
Spinal cord astrocytomas are rare neoplasms that can result in alteration of
the spinal cord structural integrity, which can be assessed by using
diffusion tensor imaging methods. Our objective was to visualize the
deformation of the posterior spinal cord lemniscal and corticospinal tracts
in 5 patients with low-grade astrocytomas compared with 10 healthy
volunteers by using 3D fiber-tracking reconstructions.
PMID: 16418387 [PubMed - indexed for MEDLINE]
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Perfusion MR imaging of an intracranial collision tumor
confirmed by image-guided biopsy.
Jun
P, Garcia
J, Tihan
T, McDermott
MW, Cha
S.
Department of Radiology, University of California, San Francisco, CA 94143,
USA.
We present a patient with a new intracranial mass lesion that was initially
interpreted as a metastasis on conventional anatomic MR imaging. On dynamic,
contrast-enhanced, susceptibility-weighted perfusion MR imaging, however,
there were regional hemodynamic differences within the lesion. Image-guided
open biopsy targeting these regions uncovered a collision tumor between a
typical meningioma and a metastatic breast carcinoma. In cases where
conventional anatomic MR imaging is ambiguous, physiology-based neuroimaging
methods provide complementary physiologic information useful for
discriminating between histologically unique tissue types.
Publication Types:
PMID: 16418364 [PubMed - indexed for MEDLINE]
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Incidence and causes of nondegenerative nonvascular
dementia: a population-based study.
Knopman
DS, Petersen
RC, Cha
RH, Edland
SD, Rocca
WA.
Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minn
55905, USA. knopman@mayo.edu
BACKGROUND: Information on the incidence of nondegenerative and nonvascular
dementia is limited. DESIGN: We used the records-linkage system of the
Rochester Epidemiology Project to ascertain incident cases of dementia in
Rochester, Minn, from January 1, 1990, through December 31, 1994. To define
causes of dementia, we reviewed all diagnoses, imaging study results,
laboratory test results, and clinical courses, as recorded historically in
the patient dossier. RESULTS: We found 560 incident cases of dementia, and
60 of them (10.7%) had onset before the age of 70 years (younger-onset
group). Forty-three cases (7.7%) were due to nondegenerative nonvascular
causes and represented 30.0% of the total in the younger-onset group, but
only 5.0% of the total in the older-onset group (aged 70-99 years). The most
common nondegenerative nonvascular causes were cancer with or without brain
metastases (n = 13), chronic alcoholism (n = 7), and chronic mental illness
(n = 11). There were no cases of dementia due to normal-pressure
hydrocephalus, subdural hematoma, hypothyroidism, vitamin B12 deficiency, or
neurosyphilis. There were 2 individuals with acute confusion due to subdural
hematoma and 1 with hypothyroidism whose cognition normalized with therapy.
CONCLUSIONS: Nondegenerative nonvascular causes were more common than
expected in patients with a younger onset of dementia. None of the patients
with dementia reverted to normal with treatment of the putative reversible
cause.
PMID: 16476810 [PubMed - indexed for MEDLINE]
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Polymorphisms associated with asthma are inversely
related to glioblastoma multiforme.
Blakely
J, Schwartzbaum
J, Feychting
M, Ahlbom
A, Malmer
B, Doss
H, Debinski
W.
University of Nottingham, Queen's Medical Centre, Nottingham, United
Kingdom.
PMID: 16510612 [PubMed - in process]
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The Small Organic Compound HA14-1 Prevents Bcl-2
Interaction with Bax to Sensitize Malignant Glioma Cells to Induction of
Cell Death.
Manero
F, Gautier
F, Gallenne
T, Cauquil
N, Gree
D, Cartron
PF, Geneste
O, Gree
R, Vallette
FM, Juin
P.
Institut National de la Sante et de la Reserche Medicale U601, Departement
de Recherche en Cancerologie, Nantes, France.
A functional imbalance between proapoptotic Bax and antiapoptotic Bcl-2 is
likely to participate in the resistance of cancer cells to therapy. We show
here that ethyl
2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
(HA14-1), a small organic compound recently proposed to function as an
inhibitor of Bcl-2, increases the sensitivity of human glioblastoma cells to
radiotherapy and chemotherapy. This sensitizing effect is lost if Bcl-2
expression, but not Bcl-xL expression, is knocked down or if cells only
express a mutant of Bax that does not interact with Bcl-2. This points to a
specific Bcl-2 inhibitory function of HA14-1 and implies that it selectively
involves hindrance of Bcl-2 binding to Bax, which HA14-1 inhibits in
cell-free assays and in cells in receipt of an apoptotic stimulation.
Moreover, HA14-1, in combination with a cytotoxic treatment, slows down the
growth of glioblastoma in vivo. Thus, the inhibition of Bcl-2 achieved by
HA14-1 might improve treatment outcome. (Cancer Res 2006; 66(5): 2757-64).
PMID: 16510597 [PubMed - in process]>>>
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N-myc Can Substitute for Insulin-Like Growth Factor
Signaling in a Mouse Model of Sonic Hedgehog-Induced Medulloblastoma.
Browd
SR, Kenney
AM, Gottfried
ON, Yoon
JW, Walterhouse
D, Pedone
CA, Fults
DW.
Department of Neurosurgery, University of Utah School of Medicine, Salt Lake
City, Utah.
Medulloblastoma is a malignant brain tumor that arises in the cerebellum in
children, presumably from granule neuron precursors (GNP). Advances in
patient treatment have been hindered by a paucity of animal models that
accurately reflect the molecular pathogenesis of human tumors. Aberrant
activation of the Sonic hedgehog (Shh) and insulin-like growth factor (IGF)
pathways is associated with human medulloblastomas. Both pathways are
essential regulators of GNP proliferation during cerebellar development. In
cultured GNPs, IGF signaling stabilizes the oncogenic transcription factor
N-myc by inhibiting glycogen synthase kinase 3beta-dependent phosphorylation
and consequent degradation of N-myc. However, determinants of Shh and IGF
tumorigenicity in vivo remain unknown. Here we report a high frequency of
medulloblastoma formation in mice following postnatal overexpression of Shh
in cooperation with N-myc. Overexpression of N-myc, alone or in combination
with IGF signaling mediators or with the Shh target Gli1, did not cause
tumors. Thus, Shh has transforming functions in addition to induction of N-myc
and Gli1. This tumor model will be useful for testing novel medulloblastoma
therapies and providing insight into mechanisms of hedgehog-mediated
transformation. (Cancer Res 2006; 66(5): 2666-72).
PMID: 16510586 [PubMed - in process]
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Interleukin-23-Expressing Bone Marrow-Derived Neural
Stem-Like Cells Exhibit Antitumor Activity against Intracranial Glioma.
Yuan
X, Hu
J, Belladonna
ML, Black
KL, Yu
JS.
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los
Angeles, California and Department of Experimental Medicine, University of
Perugia, Perugia, Italy.
Neural progenitor-like cells have been isolated from bone marrow and the
cells have the ability of tracking intracranial tumor. However, the capacity
of the cells to deliver molecules for activating immune response against
intracranial tumor and the identity of cellular and molecular factors that
are involved in such immune responses have yet to be elucidated. Here, we
isolated neural stem-like cells from the bone marrow of adult mice. The
isolated cells were capable of producing progenies of three lineages,
neurons, astrocytes, and oligodendrocytes, in vitro and tracking glioma in
vivo. By genetically manipulating bone marrow-derived neural stem-like cells
(BM-NSC) to express a recently discovered cytokine, interleukin (IL)-23, the
cells showed protective effects in intracranial tumor-bearing C57BL/6 mice.
Depletion of subpopulation lymphocytes showed that CD8(+) T cells were
critical for the antitumor immunity of IL-23-expressing BM-NSCs and that
CD4(+) T cells and natural killer (NK) cells participated in the activity.
Furthermore, the IL-23-expressing BM-NSC-treated survivors were resistant to
the same tumor rechallenge associated with enhanced IFN-gamma, but not
IL-17, expression in the brain tissue. Taken together, these data suggest
that IL-23-expressing BM-NSCs can effectively induce antitumor immunity
against intracranial gliomas. CD8(+) T cells are critical for such antitumor
activity; in addition, CD4(+) T cells and NK cells are also involved.
(Cancer Res 2006; 66(5): 2630-8).
PMID: 16510582 [PubMed - in process]
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Delta-24 increases the expression and activity of
topoisomerase I and enhances the antiglioma effect of irinotecan.
Gomez-Manzano
C, Alonso
MM, Yung
WK, McCormick
F, Curiel
DT, Lang
FF, Jiang
H, Bekele
BN, Zhou
X, Alemany
R, Fueyo
J.
Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer
Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
PURPOSE: In this study, we sought to determine whether Delta-24 could
sensitize glioma cells to the topoisomerase I inhibitor irinotecan (CPT-11)
and to identify the mechanisms underlying this enhanced anticancer effect.
EXPERIMENTAL DESIGN: We used human glioblastoma cell lines for the in vitro
studies. The expression of topoisomerase I was determined in Western blot
analyses, and topoisomerase I activity was determined by measuring the
relaxation of a supercoiled DNA. The cell cycle distribution of cells was
determined by flow cytometry analysis of the cellular DNA content. Cell
viability was quantified by a
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tissue
culture infection dose assays were used to quantitate adenovirus
replication. For the in vivo studies, athymic mice received intracranial/intratumoral
injections of Delta-24 in combination with CPT-11, after which animal
survival was monitored. RESULTS: Delta-24 infection caused human glioma
cells to accumulate in the S phase and induced the expression and activity
of topoisomerase I as shown by Western blot and in vitro enzymatic activity
assays. Further, we showed that the sequential administration of Delta-24
and CPT-11 to human glioma cell cultures potentiated the CPT-11-mediated
anticancer effect in vitro without modifying the replicative phenotype of
the oncolytic adenovirus. In vivo experiments showed that the single
intratumoral administration of Delta-24 to intracranially implanted human
glioma xenografts followed by the systemic administration of CPT-11 resulted
in significantly prolonged animal survival. CONCLUSIONS: The combination of
Delta-24 treatment with CPT-11 showed an enhanced anticancer effect, which
suggests that the interaction between adenoviral and human proteins can be
exploited in rational anticancer therapies comprising replication-competent
adenoviruses and conventional chemotherapeutic agents.
PMID: 16428500 [PubMed - indexed for MEDLINE]
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Phase I evaluation of oral and intravenous vinorelbine in
pediatric cancer patients: a report from the Children's Oncology Group.
Johansen
M, Kuttesch
J, Bleyer
WA, Krailo
M, Ames
M, Madden
T.
Division of Pharmacy, University of Texas M.D. Anderson Cancer Center, 1515
Holcombe Boulevard, Houston, TX 77030, USA.
PURPOSE: Vinorelbine (Navelbine) is an orally absorbable Vinca with broad
antitumor activity. It differs from other Vinca in that it is structurally
modified on the catharanthine nucleus and has differential actions on
tubulin that render it less neurotoxic than other compounds in this class.
We conducted a phase I study of vinorelbine given the activity of Vinca
alkaloids in many pediatric tumors. EXPERIMENTAL DESIGN: We evaluated the
safety and pharmacokinetics of oral and i.v. vinorelbine administered weekly
x 6 in children (age, 2-17 years) with different tumors. Patients with
disease involvement in the bone marrow were eligible but were stratified and
dose-escalated separately. Oral vinorelbine (week 1) was administered as
liquid-filled gelatin capsules at thrice the i.v. dose. Intravenous
vinorelbine doses of 24 to 37.5 mg/m(2) were administered on weeks 2 to 6.
RESULTS: The dose-limiting toxicity in patients without marrow involvement
was reversible neutropenia. Common nonhematologic toxicities included <
or = grade 2 nausea/vomiting and increased hepatic transaminases. A higher
mean i.v. Cl(TB) was observed (1.75 +/- 1.0 L/h/kg) compared with adult
reports, with a mean t(1/2B) of 16.5 +/- 9.7 hours. Mean oral
bioavailability was 28.5 +/- 22.5%. The apparent oral clearance (12.1 +/-
13.0 L/h/kg) and volume of distribution (69.4 +/- 30.6 L/kg) were
substantially higher than in adults given similar oral doses. CONCLUSIONS:
The maximum tolerated dose in children without bone marrow involvement was
30 mg/m(2), similar to that reported in adults, with myelosuppression being
the dose-limiting toxicity. Higher plasma clearance resulted in lower area
under the plasma concentration-time curves at a given dose compared with
that reported in adults.
Publication Types:
PMID: 16428494 [PubMed - indexed for MEDLINE]
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-
Expression of carbonic anhydrase IX in astrocytic tumors
predicts poor prognosis.
Haapasalo
JA, Nordfors
KM, Hilvo
M, Rantala
IJ, Soini
Y, Parkkila
AK, Pastorekova
S, Pastorek
J, Parkkila
SM, Haapasalo
HK.
Department of Pathology, Centre for Laboratory Medicine, Tampere University
Hospital, FIN-33521 Tampere, Finland.
PURPOSE: Carbonic anhydrase IX (CA IX) is a hypoxia-inducible enzyme, which
is associated with neoplastic growth. Ectopic CA IX expression has been
observed in several tumors, whose normal counterparts do not express this
enzyme. Normal human brain tissue shows only slight or no expression of CA
IX.EXPERIMENTAL DESIGN: We describe CA IX expression in human diffusely
infiltrating astrocytomas. The association of CA IX is evaluated with
clinicopathologic and molecular factors including cell proliferation and
apoptosis as well as the expression of p53 and epidermal growth factor
receptor.RESULTS: CA IX immunopositivity was observed in 284 cases of 362
(78%) tumors. The positive areas were often located in close proximity to
necrotic regions (P < 0.001). The CA IX immunoreactivity showed strong
association with tumor malignancy grades (P < 0.0001). CA IX showed no
association with p53 expression nor did it correlate with epidermal growth
factor receptor-amplification, apoptosis, or cell proliferation. CA IX
intensity had significant prognostic value in univariate (P=0.0011, log-rank
test) and multivariate survival analysis (P = 0.038, Cox
analysis).CONCLUSIONS: CA IX expression is common in diffusely infiltrating
high-grade astrocytomas. Our results suggest that CA IX is a useful
biomarker for predicting poor prognosis of astrocytic tumors. It may also be
a promising target molecule for the improvement of therapeutic interventions
in astrocytomas.
PMID: 16428489 [PubMed - indexed for MEDLINE]
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-
Quality of randomized controlled trials reporting in the
primary treatment of brain tumors.
Lai
R, Chu
R, Fraumeni
M, Thabane
L.
Department of Clinical Epidemiology and Biostatistics, McMaster University,
Hamilton, Ontario, Canada. rlai@neuro.columbia.edu
PURPOSE: To assess the reporting quality of randomized controlled trials (RCTs)
in the primary treatment of brain tumors and to identify significant
predictors of quality. PATIENTS AND METHODS: Two investigators searched
MEDLINE, EMBASE, and bibliographies of retrieved articles for RCTs in the
primary treatment of brain tumors published between January 1990 and
December 2004. We assessed the quality of overall reporting and key
methodologic factors reporting (allocation concealment, blinding, and
intention to treat [ITT]). Two investigators also rated articles
independently using items from the revised Consolidated Standards of
Reporting Trials statement. A generalized estimated equation was used to
generate regression models that identified significant factors associated
with quality of reporting. RESULTS: We retrieved 74 relevant RCTs that
randomly assigned 14,498 brain tumor patients. The quality of overall
reporting has improved during the last 15 years, but eight of the 15
methodologic items were reported in less than 50% of trials. In the
appraisal of the reporting quality of key methodologies, allocation
concealment, blinding, and adherence to the ITT principle were reported in
less than 30% of articles. Multivariable regression models revealed that an
impact factor more than 1.66, publication after 1995, and sample size more
than 280 were significant factors associated with better overall reporting,
whereas complete industrial funding, impact factors more than 2.64, and
positive primary outcomes were predictors of higher ratings of the three
most important methodologic qualities. CONCLUSION: Despite improvement in
general reporting quality, key methodologies that safeguard against biases
may still benefit from better description. Significant factors associated
with better reporting may act as surrogates for other characteristics.
PMID: 16505433 [PubMed - in process]>>>
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Heteronymous inferior quadrantanopsia from a hypothalamic
metastasis.
Baehring
JM, de
Lotbiniere A, Bannykh
S.
Department of Neurosurgery, Yale University School of Medicine, New Haven,
CT, USA.
Publication Types:
PMID: 16314960 [PubMed - indexed for MEDLINE]
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Ependymoma: new therapeutic approaches including
radiation and chemotherapy.
Merchant
TE, Fouladi
M.
Division of Radiation Oncology, St. Jude Children's Research Hospital,
Memphis, TN 38105, USA. thomas.merchant@stjude.org
Recent advances in neuroimaging, neurosurgery and radiation therapy have
improved disease control and functional outcomes for children with
ependymoma, including children under the age of 3 years. The rate of
gross-total resection has been increased to 85% in some series and 3 year
progression-free survival after radiation therapy as high as 75% has been
reported along with significant reductions in neurologic, endocrine and
cognitive deficits. Based on these advances and renewed interest in
radiation therapy as a frontline treatment modality, attention has been
refocused on disease control instead of radiotherapy avoidance. Future
research in the treatment of this tumor, that afflicts fewer than 200
children in the US each year, will focus on molecular biology, clarifying
risk factors for tumor control and late effects, and testing novel agents.
Publication Types:
PMID: 16195801 [PubMed - indexed for MEDLINE]
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-
Atypical teratoid/rhabdoid tumors of the central nervous
system.
Reddy
AT.
University of Alabama at Birmingham, Birmingham, AL 35233, USA. Areddy@PEDS.uab.edu
Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central
nervous system neoplasm that usually affects very young children and is
typically deadly despite very aggressive treatment. Considered rare, the
tumor was not recognized as a distinct entity until the 80's, due to its
similar features with other primitive tumors. Although AT/RT has become
increasingly recognized, published data has been based on small series and
are retrospective. Based on these data, there are occasional long-term
survivors, most of whom received intensive multi-modal therapy. AT/RT is the
first pediatric brain tumor for which a candidate tumor suppressor gene has
been identified. A mutation or deletion in the INI1 gene occurs in the
majority of AT/RT tumors. The function of the gene is not yet understood.
Prospective clinical and biologic trials are greatly needed to understand
the efficacy of therapeutic interventions, as well as the role of the gene.
Publication Types:
PMID: 16195799 [PubMed - indexed for MEDLINE]
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Anti-angiogenic therapy in pediatric neuro-oncology.
Kieran
MW.
Harvard Medical School, USA. mark_kieran@dfci.harvard.edu
In order to grow, tissues require additional nutrients and oxygen as well as
removal of waste products. Tumors achieve this by up-regulating angiogenic
cytokines and/or down-regulating natural inhibitory proteins that allow
neovascularization to proceed. Brain tumors continue to account for
significant morbidity and mortality, in spite of significant advances in
neurosurgical and radiation techniques and new chemotherapy combinations. As
such, there is a real and immediate need for novel biologic therapies that
can target these tumors. A number of new drugs that target different aspects
of the angiogenic cascade have been identified and are now in clinical
trials in children with primary brain tumors. In many of these pre-clinical
and clinical studies, anti-angiogenic therapy has been well tolerated, has
lacked many of the traditional toxicities of radiation and chemotherapy,
does not require blood-brain barrier penetration, and targets a critical
pathway in central nervous system tumor development. This review will
discuss what angiogenesis is, how pediatric brain tumors regulate
angiogenesis to obtain a vascular supply, what types of inhibitors are
available, how different classes of inhibitors work, the types of resistance
possible, how rapidly these inhibitors may work, and what surrogate markers
of activity are available to follow response.
Publication Types:
PMID: 16195797 [PubMed - indexed for MEDLINE]>>>
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Cavernous angioma within an olfactory groove meningioma.
Case report.
Klein
O, Freppel
S, Auque
J, Civit
T.
Department of Neurosurgery, Hopital Central, Nancy, France. o.klein@chu-nancy.fr
The authors present the case of a 60-year-old woman who was admitted to
their institution after suffering a subarachnoid hemorrhage (SAH).
Neuroimaging data demonstrated an olfactory groove meningioma surrounded by
a slight edema, but there was no evidence of SAH, although results of the
lumbar puncture demonstrated xanthochromic cerebrospinal fluid. Angiography
confirmed the diagnosis of meningioma, but results of magnetic resonance
imaging led the authors to suspect a cavernoma within the meningioma. This
diagnosis was established by pathological examination of the resected
lesion. The patient did well and was discharged soon after surgery. This
very rare association and the propensity of each of these lesions to be
revealed by hemorrhage are discussed.
PMID: 16509509 [PubMed - in process]
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Reduced expression of the transporter associated with
antigen processing 1 molecule in malignant glioma cells, and its restoration
by interferon-gamma and -beta.
Satoh
E, Mabuchi
T, Satoh
H, Asahara
T, Nukui
H, Naganuma
H.
Department of Neurosurgery, University of Yamanashi, Faculty of Medicine,
Yamanashi, Japan. eijis@yamanashi.ac.jp
OBJECT: It remains unclear whether malignant glioma cells can deliver tumor
antigens efficiently to major histocompatibility complex (MHC) Class I
molecules. To elucidate the mechanism of antigen presentation in malignant
gliomas, the authors examined the expression of the transporter associated
with antigen processing 1 (TAP1), which transports antigens to MHC Class I
molecules, and low-molecular-mass polypeptide 2 (LMP2), which is a subunit
of a proteasome. They also analyzed the effects of interferon (IFN)-gamma
and IFN-beta on the expression of these molecules. METHODS: Five glioma
cells expressed undetectable or very low levels of TAP1 protein and did not
express TAP1 messenger (m)RNA. Normal brain tissue and glioma tissue
specimens also showed undetectable levels of TAP1 protein and the same
levels of LMP2 protein as lymphoblastoid B cells. Treatments of the tumor
cells with IFN-gamma, or -beta enhanced the expression of both TAP1 protein
and mRNA as well as the expression of MHC Class I molecules. The expression
of LMP2 protein was not altered by the IFN treatments. The authors analyzed
structural alterations in the TAP1 promoter region in eight malignant glioma
cell lines. Single nucleotide polymorphism was found in 446 bp up-stream of
the translation start site of the TAP1 gene, and a point mutation was found
in 34 bp upstream of the TAP1 gene. CONCLUSIONS: Malignant glioma cells may
be less immunogenic due to low levels of TAP1 expression. Upregulated
expression of TAP1 and MHC Class I molecules by IFN-gamma and -beta may
enhance antigen presentation in malignant glioma cells.
PMID: 16509500 [PubMed - in process]
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Integrated positron emission tomography and magnetic
resonance imaging-guided resection of brain tumors: a report of 103
consecutive procedures.
Pirotte
B, Goldman
S, Dewitte
O, Massager
N, Wikler
D, Lefranc
F, Ben
Taib NO, Rorive
S, David
P, Brotchi
J, Levivier
M.
Department of Neurosurgery, PET/Cyclotron Biomedical Unit, Hopital Erasme,
Universite Libre de Bruxelles, Brussels, Belgium. bpirotte@ulb.ac.be
OBJECT: The aim of this study was to evaluate the integration of positron
emission tomography (PET) scanning data into the image-guided resection of
brain tumors. METHODS: Positron emission tomography scans obtained using
fluorine-18 fluorodeoxyglucose (FDG) and L-[methyl-11C]methionine (MET) were
combined with magnetic resonance (MR) images in the navigational planning of
103 resections of brain tumors (63 low-grade gliomas [LGGs] and 40
high-grade gliomas [HGGs]). These procedures were performed in 91 patients
(57 males and 34 females) in whom tumor boundaries could not be accurately
identified on MR images for navigation-based resection. The level and
distribution of PET tracer uptake in the tumor were analyzed to define the
lesion contours, which in turn yielded a PET volume. The PET
scanning-demonstrated lesion volume was subsequently projected onto MR
images and compared with MR imaging data (MR volume) to define a final
target volume for navigation-based resection-the tumor contours were
displayed in the microscope's eyepiece. Maximal tumor resection was
accomplished in each case, with the intention of removing the entire area of
abnormal metabolic activity visualized during surgical planning. Early
postoperative MR imaging and PET scanning studies were performed to assess
the quality of tumor resection. Both pre- and postoperative analyses of MR
and PET images revealed whether integrating PET data into the navigational
planning contributed to improved tumor volume definition and tumor
resection. Metabolic information on tumor heterogeneity or extent was useful
in planning the surgery. In 83 (80%) of 103 procedures, PET studies
contributed to defining a final target volume different from that obtained
with MR imaging alone. Furthermore, FDG-PET scanning, which was performed in
a majority of HGG cases, showed that PET volume was less extended than the
MR volume in 16 of 21 cases and contributed to targeting the resection to
the hypermetabolic (anaplastic) area in 11 (69%) of 16 cases. Performed in
59 LGG cases and 23 HGG cases, MET-PET demonstrated that the PET volume did
not match the MR volume and improved the tumor volume definition in 52 (88%)
of 59 and 18 (78%) of 23, respectively. Total resection of the area of
increased PET tracer uptake was achieved in 54 (52%) of 103 procedures.
CONCLUSIONS: Imaging guidance with PET scanning provided independent and
complementary information that helped to assess tumor extent and plan tumor
resection better than with MR imaging guidance alone. The PET scanning
guidance could help increase the amount of tumor removed and target
image-guided resection to tumor portions that represent the highest evolving
potential.
PMID: 16509498 [PubMed - in process]
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Management of meningiomas en plaque of the sphenoid wing.
Schick
U, Bleyen
J, Bani
A, Hassler
W.
Clinic of Neurological Surgery, Wedau Kliniken, Duisburg, Germany.
Uta_Schick@web.de
OBJECT: The authors present their findings on growth patterns in a large
series of surgically treated meningiomas en plaque of the sphenoid wing.
METHODS: A retrospective case analysis was performed in 67 patients (53 of
whom were female) harboring meningiomas en plaque originating from the
sphenoid wing, who underwent surgery between 1991 and 2002. The standard
surgical approach consisted of pterional craniotomy and extradural resection
of any infiltrated bone. The intracranial tumor was removed, and the dura
mater and bone were reconstructed. The follow-up period ranged from 6 to 118
months (mean 45.7 months). Total macroscopic resection was achieved in 40
patients. Forty-eight meningiomas extended to the orbital roof and/ or the
lateral orbital wall, 34 involved the extraconal space, and eight the
intraconal space. Fifty-four tumors involved the superior orbital fissure,
46 the optic canal, and 21 the inferior orbital fissure. Twelve tumors
infiltrated the cavernous sinus and 27 involved the anterior clinoid
process. There were no deaths in this group of patients; the rate of minor
morbidity was 11.9% and the rate of major morbidity was 3%. Subtotal
resections were performed in 27 patients because there was intraorbital
tumor (eight patients), tumor in the cavernous sinus (nine patients), tumor
beyond the tentorial notch (three patients), tumor invading the superior
orbital fissure (four patients), and tumor of the skull base (three
patients). Five patients underwent postoperative three-dimensional conformal
radiotherapy, which resulted in stable tumor volume at follow up. Tumor
recurrence was identified in seven patients (10.4%) postoperatively (range
of follow up 13-47 months). CONCLUSIONS: The goal of surgery is complete
tumor removal without morbidity. An exact analysis of tumor growth and its
involvement of different structures is mandatory before performing surgery.
PMID: 16509494 [PubMed - in process]
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Recombinant activated factor VII in the treatment of
near-fatal bleeding during pediatric brain tumor surgery. Report of two
cases and review of the literature.
Hartmann
M, Sucker
C, Messing
M.
Department of Anesthesiology, and Institute for Hemostasis and Transfusion
Medicine, University Hospital Dusseldorf, Germany. matthias.hartmann@uni-duesseldorf.de
Recombinant activated factor VII (rFVIIa) was successfully used in two
pediatric cases to control microvascular bleeding during brain tumor
surgery. The agent demonstrated a marked effect on the intraoperative blood
coagulation after failure of conventional therapy with fresh-frozen plasma,
platelet concentrates, and inhibition of the fibrinolytic system.
Remarkably, rFVIIa was effective in the present cases in which assessment of
hemostasis yielded normal results. The use of rFVIIa should be considered in
otherwise untreatable microvascular bleeding in pediatric neurosurgery.
PMID: 16509483 [PubMed - in process]
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A granulomatous reaction to Avitene mimicking recurrence
of a medulloblastoma. Case report.
O'Shaughnessy
BA, Schafernak
KT, DiPatri
AJ Jr, Goldman
S, Tomita
T.
Division of Pediatric Neurosurgery, Department of Pathology, and Division of
Pediatric Hematology/Oncology, Children's Memorial Hospital, Feinberg School
of Medicine, Northwestern University, Chicago, Illinois 60614, USA.
Microfibrillar collagen hemostat (MCH), also known by its trade name Avitene,
is commonly used to control hemorrhage during neurosurgery. Among the
documented complications associated with this agent, a granulomatous foreign
body reaction is rare, having been described in the central nervous system
in only one previous clinical report. In the present study, the authors
report the case of a 3-year-old boy who presented with a lesion which
appeared to be the recurrence of a tumor 2 months after he had undergone
gross-total resection for a medulloblastoma. The patient underwent resection
of the presumed recurrent tumor, but histopathological analysis of the
specimen revealed a granulomatous foreign body reaction to MCH and no tumor
recurrence. In addition to describing the case, the authors review the
surgical literature on foreign body reactions to MCH.
PMID: 16509478 [PubMed - in process]
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Influence of light fluence rate on the effects of
photodynamic therapy in an orthotopic rat glioma model.
Angell-Petersen
E, Spetalen
S, Madsen
SJ, Sun
CH, Peng
Q, Carper
SW, Sioud
M, Hirschberg
H.
Department of Surgical Oncology, The Norwegian Radium Hospital, Oslo,
Norway. evenag@labmed.uio.no
OBJECT: Failure of treatment for high-grade gliomas is usually due to local
recurrence at the site of resection, indicating that a more aggressive local
therapy could be beneficial. Photodynamic therapy (PDT) is a local treatment
involving the administration of a tumor-localizing photosensitizing drug, in
this case aminolevulinic acid (ALA). The effect depends on the total light
energy delivered to the target tissue, but may also be influenced by the
rate of light delivery. METHODS: In vitro experiments showed that the
sensitivity to ALA PDT of BT4C multicellular tumor spheroids depended on the
rate of light delivery (fluence rate). The BT4C tumors were established
intracranially in BD-IX rats. Microfluorometry of frozen tissue sections
showed that photosensitization is produced with better than 200:1
tumor/normal tissue selectivity after ALA injection. Four hours after
intraperitoneal ALA injection (125 mg/kg), 26 J of 632 nm light was
delivered interstitially over 15 (high fluence rate) or 90 (low fluence
rate) minutes. Histological examination of animals treated 14 days after
tumor induction demonstrated extensive tumor necrosis after low-fluence-rate
PDT, but hardly any necrosis after high-fluence-rate treatment. Neutrophil
infiltration in tumor tissue was increased by PDT, but was similar for both
treatment regimens. Low-fluence-rate PDT administered 9 days after tumor
induction resulted in statistically significant prolongation of survival for
treated rats compared with nontreated control animals. CONCLUSIONS:
Treatment with ALA PDT induced pronounced necrosis in tumors only if the
light was delivered at a low rate. The treatment prolonged the survival for
tumor-bearing animals.
PMID: 16509154 [PubMed - in process]
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Falcotentorial meningioma: surgical outcome in 14
patients.
Goto
T, Ohata
K, Morino
M, Takami
T, Tsuyuguchi
N, Nishio
A, Hara
M.
Department of Neurosurgery, Osaka City University Graduate School of
Medicine, Osaka, Japan.
OBJECT: The authors evaluated their surgical experience over 20 years with
14 treated falcotentorial meningiomas. METHODS: In the past 20 years, 14
patients with falcotentorial junction meningiomas were surgically treated.
There were seven men and seven women, whose ages ranged from 34 to 79 years.
On the basis of neuroimaging studies, the authors analyzed the influence of
the anatomical relationship of the tumor to the vein of Galen, patency of
the vein of Galen, tumor size, and the signal intensities on the magnetic
resonance images to determine possible difficulties that might be
encountered during surgery and to prognosticate the outcome of surgery.
Depending on the relationship with the vein of Galen, tumors were labeled as
either a superior or an inferior type. All tumors were resected via an
occipital transtentorial approach. The surgical outcome in eight patients
was excellent; in the remaining six patients, it was fair. Of the prognostic
factors, tumor location especially seemed to be the most important (p <
0.01, Fisher exact test). The outcome associated with the inferior type of
tumor was significantly less optimal probably due to the relationship to the
deep veins and the brainstem. In this series, the occlusion of deep veins
did not significantly influence outcome. CONCLUSIONS:. Classification of the
tumor location by preoperative neuroimaging studies can be helpful in
estimating the surgical difficulty that might be encountered in treating the
falcotentorial junction meningioma.
PMID: 16509146 [PubMed - in process]
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Cumulative incidence of radiation-induced cavernomas in
long-term survivors of medulloblastoma.
Lew
SM, Morgan
JN, Psaty
E, Lefton
DR, Allen
JC, Abbott
R.
Department of Neurosurgery, Medical College of Wisconsin/Children's Hospital
of Wisconsin, Milwaukee, Wisconsin 53226, USA. slew@neuroscience.mcw.edu
OBJECT: The goal of this study was to determine the incidence of
radiation-induced cavernomas in children treated for medulloblastoma.
METHODS: A retrospective chart and film review was performed for all
patients treated for medulloblastoma at the Insitute for Neurology and
Neurosurgery/Beth Israel Medical Center between August 1996 and the present.
The clinical and radiographic histories of pediatric patients (ages 3-21
years at diagnosis) with a histologically confirmed diagnosis of
medulloblastoma who received craniospinal radiation therapy were reviewed.
Fifty-nine patients were identified, with a mean age at radiation treatment
of 7.7 years and a mean follow-up time of 7.2 years. The dose to the
craniospinal axis was 24 Gy (31 patients) or 36 Gy (28 patients). The
radiation energy in the craniospinal axis was provided by photons in 55
patients and protons in four. All patients received a posterior fossa boost
of 54 Gy (46 patients) or 72 Gy (13 patients). Twenty-six lesions developed
in 18 patients (31%) during the observation period. The cumulative incidence
of lesion development was 5.6, 14, and 43%, at 3, 5, and 10 years,
respectively. The sites of occurrence were cerebral (20 cases) and
cerebellar (six cases). There was no significant correlation between age at
diagnosis, sex, craniospinal radiation dose or energy source, and lesion
development. Only one patient required surgical intervention for a
symptomatic hemorrhagic lesion in the frontal lobe. Histological analysis in
this case was consistent with cavernoma. CONCLUSIONS: Cavernomas are common
after cranial irradiation in children, and their incidence increases over
time. Most of these lesions follow a benign course and do not require
intervention.
PMID: 16506497 [PubMed - in process]
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Phase II trial of conformal radiation therapy for
pediatric patients with craniopharyngioma and correlation of surgical
factors and radiation dosimetry with change in cognitive function.
Merchant
TE, Kiehna
EN, Kun
LE, Mulhern
RK, Li
C, Xiong
X, Boop
FA, Sanford
RA.
Division of Radiation Oncology, Department of Biostatistics, St. Jude
Children's Research Hospital, and Semmes-Murphey Neurologic and Spine
Institute, Memphis, Tennessee 38105-2794, USA. thomas.merchant@stjude.org
OBJECT: A Phase II trial of conformal radiation therapy (CRT) for
craniopharyngioma was conducted to determine whether the irradiated volume
could be safely reduced to decrease effects on cognitive function. METHODS:
Between July 1997 and January 2003, 28 pediatric patients (median age 7.3
+/- 4.12 years) received CRT in whom doses (54-55.8 Gy) were administered to
the gross tumor volume (solid and cystic components) surrounded by a 1-cm
clinical target volume margin. Patients were evaluated serially with
neuropsychometric testing. Statistical analyses were performed to determine
the effect of clinical factors and radiation dosimetry on intelligence
quotient (IQ). The median follow-up period was 36.6 months (range 24.4-80
months). The estimated 3-year progression-free survival rate was 90.3 +/-
7.3%. Three patients experienced local disease progression. Cognitive
outcome for patients was adversely affected by the following factors: age
younger than 7.4 years (p = 0.001), an interval between symptoms and
diagnosis of more than 73 days (p = 0.06), more extensive surgery (p =
0.014), multiple surgical procedures (p = 0.002), diabetes insipidus (p =
0.02), hydrocephalus at diagnosis (p = 0.009), a cerebrospinal fluid shunt
(p = 0.005), shunt revisions (p = 0.01), Ommaya reservoir laterality (p =
0.005), and cyst aspirations (p = 0.02). The percentage of total brain,
supratentorial brain, or left temporal lobe volumes receiving a dose in
excess of 45 Gy had a significant impact on longitudinal IQ. CONCLUSIONS:
The use of CRT with a 1-cm margin for clinical target volume results in
tumor control equivalent to that achieved using conventionally planned
radiation therapy. Surgical morbidity and a volume-receiving dose more than
45 Gy are factors affecting longitudinal IQ after CRT in patients treated
for craniopharyngioma.
PMID: 16506496 [PubMed - in process]
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PCV chemotherapy for recurrent glioblastoma.
Schmidt
F, Fischer
J, Herrlinger
U, Dietz
K, Dichgans
J, Weller
M.
Department of General Neurology, Hertie Institute for Clinical Brain
Research, University of Tuebingen, Medical School, Tuebingen, Germany.
friederike.schmidt@uni-tuebingen.de
The authors administered procarbazine,
1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU, lomustine), and
vincristine (PCV) to 86 patients with recurrent glioblastoma. There were
three partial responses, but no complete responses. Median progression-free
survival was 17.1 weeks and progression-free survival at 6 months was 38.4%.
World Health Organization grade III/IV hematologic toxicity was common
(25.6%), but nonhematologic toxicity was mild.
PMID: 16505319 [PubMed - in process]>>>
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Notch3 signaling initiates choroid plexus tumor
formation.
Dang
L, Fan
X, Chaudhry
A, Wang
M, Gaiano
N, Eberhart
CG.
Institute for Cell Engineering, Johns Hopkins University School of Medicine,
Baltimore, MD 21205, USA.
Notch3 has been studied in the context of brain development, but whether it
plays a role in the formation of brain tumors is unclear. We demonstrate
that the introduction of constitutively active Notch3 into periventricular
cells of embryonic day 9.5 mice causes the formation of choroid plexus
tumors (CPTs). Tumors arose in the fourth ventricles in 83% of animals and
were associated with hydrocephalus. They were microscopically highly similar
to choroid plexus papillomas in humans, with an ongoing proliferation rate
of 4-6%. Signs of Notch pathway activity were also present in human choroid
plexus lesions, and receptor mRNA levels in papillomas were elevated over
those in non-neoplastic choroid plexus. Notch2 was overexpressed
approximately 500-fold in one case, suggesting that the role of this pathway
in CPTs may not be specific to Notch3. Our findings indicate that activated
Notch3 can function as an oncogene in the developing brain, and link the
Notch pathway to human CPT pathogenesis.
PMID: 16186803 [PubMed - indexed for MEDLINE]
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Volume 5, Number 10 - 7 March
2006