-
Treatment of glioblastoma multiforme: a new standard.
Henson
JW.
Stephen E. and Catherine Pappas Center for Neuro-Oncology, Neurology
Service, and Division of Neuroradiology, Department of Radiology,
Massachusetts General Hospital, Boston; Harvard Medical School, Boston,
Mass, USA. henson@helix.mgh.harvard.edu
PMID: 16533960 [PubMed - in process]*
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-
Increased regulatory T-cell fraction amidst a diminished
CD4 compartment explains cellular immune defects in patients with malignant
glioma.
Fecci
PE, Mitchell
DA, Whitesides
JF, Xie
W, Friedman
AH, Archer
GE, Herndon
JE 2nd, Bigner
DD, Dranoff
G, Sampson
JH.
Division of Neurosurgery, Departments of Surgery, Pathology, Medicine, and
Biostatistics and Bioinformatics, Duke University Medical Center, Durham,
North Carolina.
Immunosuppression is frequently associated with malignancy and is
particularly severe in patients with malignant glioma. Anergy and
counterproductive shifts toward T(H)2 cytokine production are
long-recognized T-cell defects in these patients whose etiology has remained
elusive for >30 years. We show here that absolute counts of both CD4(+) T
cells and CD4(+)CD25(+)FOXP3(+)CD45RO(+) T cells (T(regs)) are greatly
diminished in patients with malignant glioma, but T(regs) frequently
represent an increased fraction of the remaining CD4 compartment. This
increased T(reg) fraction, despite reduced counts, correlates with and is
sufficient to elicit the characteristic manifestations of impaired patient
T-cell responsiveness in vitro. Furthermore, T(reg) removal eradicates
T-cell proliferative defects and reverses T(H)2 cytokine shifts, allowing T
cells from patients with malignant glioma to function in vitro at levels
equivalent to those of normal, healthy controls. Such restored immune
function may give license to physiologic antiglioma activity, as in vivo,
T(reg) depletion proves permissive for spontaneous tumor rejection in a
murine model of established intracranial glioma. These findings dramatically
alter our understanding of depressed cellular immune function in patients
with malignant glioma and advance a role for T(regs) in facilitating tumor
immune evasion in the central nervous system. (Cancer Res 2006; 66(6):
3294-302).
PMID: 16540683 [PubMed - in process]
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-
Activation of Stat3 in Human Melanoma Promotes Brain
Metastasis.
Xie
TX, Huang
FJ, Aldape
KD, Kang
SH, Liu
M, Gershenwald
JE, Xie
K, Sawaya
R, Huang
S.
Departments of Neurosurgery, Pathology, Surgical Oncology, Gastrointestinal
Medical Oncology, and Cancer Biology, The University of Texas M.D. Anderson
Cancer Center and Program in Cancer Biology, The University of Texas
Graduate School of Biomedical Sciences at Houston, Houston, Texas.
Brain metastasis is a major cause of morbidity and mortality in patients
with melanoma. The molecular changes that lead to brain metastasis remain
poorly understood. In this study, we developed a model to study human
melanoma brain metastasis and found that Stat3 activity was increased in
human brain metastatic melanoma cells when compared with that in cutaneous
melanoma cells. The expression of activated Stat3 is also increased in human
brain metastasis specimens when compared with that in the primary melanoma
specimens. Increased Stat3 activation by transfection with a constitutively
activated Stat3 enhanced brain metastasis, whereas blockade of Stat3
activation by transfection with a dominant-negative Stat3 suppressed brain
metastasis of human melanoma cells in animal models. Furthermore, altered
Stat3 activity profoundly affected melanoma angiogenesis in vivo and
melanoma cell invasion in vitro and significantly affected the expression of
basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF),
and matrix metalloproteinase-2 (MMP-2) in vivo and in vitro. Finally, Stat3
activity transcriptionally regulated the promoter activity of bFGF in
addition to VEGF and MMP-2 in human melanoma cells. These results indicated
that Stat3 activation plays an important role in dysregulated expression of
bFGF, VEGF, and MMP-2 as well as angiogenesis and invasion of melanoma cells
and contributes to brain metastasis of melanoma. Therefore, Stat3 activation
might be a new potential target for therapy of human melanoma brain
metastases. (Cancer Res 2006; 66(6): 3188-96).
PMID: 16540670 [PubMed - as supplied by publisher]
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Elongation factor-2 kinase regulates autophagy in human
glioblastoma cells.
Wu
H, Yang
JM, Jin
S, Zhang
H, Hait
WN.
Departments of Pharmacology and Medicine and The Cancer Institute of New
Jersey, University of Medicine and Dentistry of New Jersey/Robert Wood
Johnson Medical School, New Brunswick, New Jersey.
Elongation factor-2 kinase (eEF-2 kinase), also known as Ca(2+)/calmodulin-dependent
kinase III, regulates protein synthesis by controlling the rate of peptide
chain elongation. The activity of eEF-2 kinase is increased in glioblastoma
and other malignancies, yet its role in neoplasia is uncertain. Recent
evidence suggests that autophagy plays an important role in oncogenesis and
that this can be regulated by mammalian target of rapamycin (mTOR). Because
eEF-2 kinase lies downstream of mTOR, we studied the role of eEF-2 kinase in
autophagy using human glioblastoma cell lines. Knockdown of eEF-2 kinase by
RNA interference inhibited autophagy in glioblastoma cell lines, as measured
by light chain 3 (LC3)-II formation, acidic vesicular organelle staining,
and electron microscopy. In contrast, overexpression of eEF-2 kinase
increased autophagy. Furthermore, inhibition of autophagy markedly decreased
the viability of glioblastoma cells grown under conditions of nutrient
depletion. Nutrient deprivation increased eEF-2 kinase activity and
decreased the activity of S6 kinase, suggesting an involvement of mTOR
pathway in the eEF-2 kinase regulation of autophagy. These results suggest
that eEF-2 kinase plays a regulatory role in the autophagic process in tumor
cells; and eEF-2 kinase is a downstream member of the mTOR signaling; eEF-2
kinase may promote cancer cell survival under conditions of nutrient
deprivation through regulating autophagy. Therefore, eEF-2 kinase may be a
part of a survival mechanism in glioblastoma and targeting this kinase may
represent a novel approach to cancer treatment. (Cancer Res 2006; 66(6):
3015-23).
PMID: 16540650 [PubMed - in process]
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-
Monitoring the growth effect of xenotransplanted human
medulloblastoma in an immunocompromised mouse model using in vitro and ex
vivo green fluorescent protein imaging.
Chiou
SH, Kao
CL, Lin
HT, Tseng
WS, Liu
RS, Chung
CF, Ku
HH, Lin
CP, Wong
TT.
Department of Education and Research, The Neurological Institute, Taiwan,
Republic of China.
INTRODUCTION: Medulloblastoma (MB) is one of the most common malignant brain
tumors in children. It is a radiosensitive tumor. At 5 years after radical
surgical excision and craniospinal axis irradiation, the tumor-free survival
rate is from 50 to 70% [Halperin EC, Constine LS, Tarbell NJ, Kun LE.
Pediatric radiation oncology (2005)]. CASE REPORT: In this study, we
established xenotransplanted human MB (hMB) cells - isochromosome 17q - in a
severe combined immunodeficiency (SCID) mouse model. We further transduced
green fluorescent protein (GFP) into hMB cells to evaluate these hMB cells
grafted in SCID mice. RESULTS: The result of an ex vivo GFP imaging system
showed that a small lesion of the third-week-hMB-transplanted graft
presented "green" signals with a clear tumor margin before any
tumor-related symptoms were noted. We also demonstrated that the tumor
progression could be monitored by GFP imaging for up to 12 weeks
post-transplantation. CONCLUSIONS: This novel approach of GFP imaging
assessment provides more accurate information of tumor status for
experimental brain tumor studies. Because MB is sensitive to radiation and
also response to chemotherapy, this SCID mouse model will be helpful for
preclinical studies in the future.
PMID: 16541296 [PubMed - as supplied by publisher]
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-
Phase I Trial of Intrathecal Spartaject Busulfan in
Children with Neoplastic Meningitis: a Pediatric Brain Tumor Consortium
Study (PBTC-004).
Gururangan
S, Petros
WP, Poussaint
TY, Hancock
ML, Phillips
PC, Friedman
HS, Bomgaars
L, Blaney
SM, Kun
LE, Boyett
JM.
Authors' Affiliations: The Preston Robert Tisch Brain Tumor Center at Duke,
Duke University Medical Center, Durham, North Carolina.
PURPOSE: A phase I trial of intrathecal Spartaject Busulfan (SuperGen, Inc.,
San Ramon, CA) was conducted in children with neoplastic meningitis
following recurrent primary brain tumors to describe toxicities, estimate
the maximum tolerated dose (MTD), and document evidence of responses to this
agent.EXPERIMENTAL DESIGN: The continuous reassessment method was used to
assign cohorts of patients to doses of intrathecal Spartaject Busulfan via
an Ommaya reservoir and/or lumbar puncture twice weekly for 2 weeks followed
by an assessment of toxicity and response. Patients with stable disease or
an objective response continued to receive intrathecal Spartaject Busulfan
plus systemic chemotherapy at regular intervals. Cerebrospinal fluid and
blood were obtained for pharmacokinetic studies in patients with Ommaya
reservoirs after the first dose of intrathecal Spartaject Busulfan. Seven
evaluable patients were assigned to the starting dose of 5 mg, two patients
to 7.5 mg, three patients to 10 mg, seven patients to 13 mg, and four
patients to 17 mg.RESULTS: Between September 2000 and May 2003, 28 patients
were enrolled in this study. Twenty-three patients (median age, 8.8 years;
range, 2.5-19.5 years) were evaluable for estimating the MTD, and
dose-limiting toxicities were observed in three and included grade 3
vomiting (n = 1 at 5 mg), grade 3 headache (n = 1 at 17 mg), and grade 3
arachnoiditis (n = 1 at 17 mg). Pharmacokinetic data showed that
post-infusion concentrations of busulfan ranged from 50 to 150 mug/mL and
declined to <1 mug/mL within 5 hours.CONCLUSIONS: Intrathecal Spartaject
Busulfan was well tolerated in children with neoplastic meningitis from
brain tumors, and the recommended dose for future phase II studies is 13 mg.
PMID: 16533779 [PubMed - in process]
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Distribution of nuclear size and internuclear distance
are important criteria for grading astrocytomas.
Nafe
R, Van
de Nes J, Yan
B, Schlote
W.
Department of Neuroradiology, Clinics of Johann Wolfgang Goethe University,
Frankfurt am Main, Germany. r.nafe@em.uni-frankfurt.de
AIM: The differentiation between low-grade astrocytomas and anaplastic
astrocytomas is susceptible to considerable inter-observer variability. In
order to contribute to a better standardization of astrocytoma-grading based
on quantitative data, the present study focuses on two important aspects not
being considered in previous morphometric studies: elaboration of a decision
flow chart for tumor grading based on morphometric parameters and
appropriate cut-off-values, easily performed using low-cost equipment such
as measuring oculars; investigation of the distribution (histograms) of
parameters describing nuclear size and internuclear distance, which had been
represented in previous studies by their mean and standard deviation only.
MATERIAL AND METHODS: At least 300 tumor cell nuclei per case were
investigated in paraffin sections from surgical specimen of 75 patients with
astrocytomas WHO grade II (n = 23) and anaplastic astrocytomas WHO grade III
(n = 52) by means of a digital image analysis system. RESULTS: The
morphometric data showed significant differences between both groups of
tumors. According to multivariate analysis, the best contribution to tumor
grading was achieved by means of parameters concerning the distribution of
values for nuclear diameters and internuclear distances. A decision tree was
constructed using a knowledge based algorithm, which provided astrocytoma
grading based on the distribution of values for nuclear diameter, as well as
the numerical nuclear density and proliferation index. Measurements using a
measuring ocular took an acceptable amount of time (1.5 hour per case) and
showed good reproducibility when compared with measurement by means of
digital image analysis. CONCLUSION: The study demonstrates that a
morphometric examination of tumor cell nuclei in paraffin sections supports
the clinically important differential diagnosis between low-grade and
high-grade astrocytomas. The method for classification and the data
published in the present study constitute a good basis for a standardized
and reproducible grading procedure for astrocytomas, which can be performed
in any histologic laboratory even without a digital image analysis system.
PMID: 16465775 [PubMed - indexed for MEDLINE]
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Extramedullary plasmacytoma extensively affecting the
sella turcica and paranasal sinuses.
Oishi
T, Kasai
H, Sakurai
Y, Kawamoto
K.
Department of Neurosurgery, Kansai Medical University, Osaka, Japan.
We report a 62-year-old Japanese male who complained of double vision and
showed clear boundary mass extending to the clivus, intrasella, suprasella,
ethmoidal sinus and sphenoid sinus on neuroimaging. The tumor mass was
partially resected via transsphenoidal approach and was diagnosed as the
extramedullary plasmacytoma by IgA immunostaining and electron microscopy.
Making diagnosis from the imaging findings was difficult in this rare case,
but immunohistological and electron microscopic examinations were useful for
pathological diagnosis.
Publication Types:
PMID: 16465774 [PubMed - indexed for MEDLINE]
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Malignant lymphoma of the central nervous system:
difficult histologic diagnosis after glucocorticoid therapy prior to biopsy.
Choi
YL, Suh
YL, Kim
D, Ko
YH, Sung
CO, Lee
JI.
Department of Pathology, Samsung Medical Centre, Sungkyunkwan University
School of Medicine, Seoul, Korea.
Four cases of central nervous system (CNS) lymphoma are reported which
presented obstacles in diagnosis due to steroid treatment prior to biopsy.
Reliable diagnoses were provided by molecular analysis. Malignant lymphoma
of the CNS may be indistinguishable from other conditions, even in view of
the gravity of the diagnosis. All patients had a previous history of
glucocorticoid injection, for 2-18 days prior to stereotactic brain biopsy.
The pathologic examination revealed in all cases axonal destruction and
reactive gliosis with a variable infiltration of B- or T lymphocytes and
macrophages. Characteristically, scattered degenerating small round cells
with pyknotic or fragmented nuclei were also observed. However, the
molecular assessment of paraffin-embedded tissues revealed the monoclonal
IgH gene rearrangement, which allowed the confident diagnosis of B cell
lymphoma. The histopathological findings of the present cases suggest that
the tumor cells might be selectively destroyed by steroid treatment, which
may render diagnosis impossible. Thus, molecular genetic investigation
constitutes an important tool for establishing a diagnosis of CNS lymphoma
obscured by steroid administration. This is especially true in cases where a
paucity of tumor cells is observed or when monoclonality fails to be
demonstrated by immunohistochemical tests.
Publication Types:
PMID: 16465772 [PubMed - indexed for MEDLINE]
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Molecular analysis of chromosome 1, 10 and 19
abnormalities in human oligodendroglial tumors: relationship between
frequency of LOH grade, age and gender.
Gresner
SM, Rieske
P, Wozniak
K, Piaskowski
S, Jaskolski
DJ, Skowronski
W, Golanska
E, Sikorska
B, Liberski
PP.
Department of Molecular Pathology and Neuropathology, Medical University of
Lodz, Poland. sylwiagresner@yahoo.com
BACKGROUND: Loss of heterozygosity (LOH) on 1p and 19q is observed in most
oligodendroglial tumors. LOH on 10q appears to be less common in these
tumors as compared to other gliomas. PATIENTS AND METHODS: We reviewed 14
patients with oligodendroglial tumors (10 low-grade and 4 anaplastic
oligodendroglioma) to evaluate the frequency of LOH on 1p, 10q and 19q and
correlate it with tumor grade and patients' age and gender; 5 loci on 1p and
5 on 19q as well as 4 on 10q were analyzed for LOH using PCR techniques.
RESULTS: LOH on 1p together with 19q was detected in 6 tumors, 1 tumor
showed deletion of 19q accompanied with deletion on 10q. Deletion on 1p was
associated with deletion of 19q (p < 0.005) and mutual associations among
deletions at loci on 19q (p < 0.05) were found. Patients with LOH on 1p
were younger on average than patients with retained heterozygosity (p =
0.05). Grade II oligodendrogliomas predominated among younger patients (p
< 0.01) while grade III oligodendrogliomas predominated among women (p
< 0.005). No association between LOH on 1p nor 19q and tumor grade or
patients' gender was found. CONCLUSION: Our study provides several
clinically interesting findings and further supports the hypothesis of
chromosome 1p and 19q involvement in the oligodendroglial cancerogenesis.
PMID: 16465770 [PubMed - indexed for MEDLINE]*
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-
Role and relevance of neurocognitive assessment in
clinical trials of patients with CNS tumors.
Meyers
CA, Brown
PD.
Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer
Center, Houston, TX 77030, USA. cameyers@mdanderson.org
The inclusion of neurocognitive end points in clinical trials of patients
with CNS tumors is increasing. Neurocognitive end points are used to
understand what cognitive problems exist before treatment to establish a
baseline by which the effect of treatment is judged, and to determine
whether different treatment regimens improve neurocognitive function due to
better tumor control, slow expected neurocognitive deterioration due to the
tumor, or have more or less short- and long-term neurotoxicity. However, the
use of neurocognitive end points in clinical trials for patients with CNS
tumors is in its infancy, so that long-term outcomes are difficult to
predict and the ability to determine the effects of different agents and
treatment approaches is scant. Including this aspect of patient evaluation
in addition to survival and time to tumor progression will yield better
risk-versus-benefit assessments as well as provide a basis for improving
interventions.
Publication Types:
PMID: 16525186 [PubMed - indexed for MEDLINE]
-
-
Primary CNS lymphoma.
Batchelor
T, Loeffler
JS.
Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts
General Hospital, Boston, MA 02114, USA. tbatchelor@partners.org
Primary CNS lymphoma (PCNSL), an uncommon form of extranodal non-Hodgkin's
lymphoma (NHL), has increased in incidence during the last three decades and
occurs in both immunocompromised and immunocompetent hosts. PCNSL in
immunocompetent patients is associated with unique diagnostic, prognostic,
and therapeutic issues, and the management of this malignancy is different
from that of other forms of extranodal NHL. Characteristic imaging features
should be suggestive of the diagnosis, avoidance of corticosteroids, if
possible, and early neurosurgical consultation for stereotactic biopsy.
Because PCNSL may involve the brain, CSF, and eyes, diagnostic evaluation
should include assessment of all of these regions as well as screening for
possible occult systemic disease. Resection provides no therapeutic benefit
and should be reserved for the rare patient with neurologic deterioration
due to brain herniation. Whole-brain radiation therapy (WBRT) alone is
insufficient for durable tumor control and is associated with a high risk of
neurotoxicity in patients older than age 60. Neurotoxicity typically is
associated with significant cognitive, motor, and autonomic dysfunction, and
has a negative impact on quality of life. Chemotherapy and WBRT together
improve tumor response rates and survival compared with WBRT alone.
Methotrexate-based multiagent chemotherapy without WBRT is associated with
similar tumor response rates and survival compared with regimens that
include WBRT, although controlled trials have not been performed. The risk
of neurotoxicity is lower in patients treated with chemotherapy alone.
Publication Types:
PMID: 16525183 [PubMed - indexed for MEDLINE]
-
-
Diagnosis and treatment of recurrent high-grade
astrocytoma.
Butowski
NA, Sneed
PK, Chang
SM.
Department of Neurological Surgery, University of California, San Francisco,
San Francisco, CA 94143-0350, USA.
High-grade gliomas represent a significant source of cancer-related death,
and usually recur despite treatment. In this analysis of current brain tumor
medicine, we review diagnosis, standard treatment, and emerging therapies
for recurrent astrocytomas. Difficulties in interpreting radiographic
evidence, especially with regard to differentiating between tumor and
necrosis, present a formidable challenge. The most accurate diagnoses come
from tissue confirmation of recurrent tumor, but a combination of imaging
techniques, such as magnetic resonance spectroscopy imaging, may also be
relevant for diagnosis. Repeat resection can prolong life, but repeat
irradiation of the brain poses serious risks and results in necrosis of
healthy brain tissue; therefore, reirradiation is usually not offered to
patients with recurrent tumors. We describe the use of conventional
radiotherapy, intensity-modulated radiotherapy, brachytherapy, radiosurgery,
and photodynamic therapy for recurrent high-grade glioma. The use of
chemotherapy is limited by drug distribution and toxicity, but the
development of new drug-delivery techniques such as convection-enhanced
delivery, which delivers therapeutic molecules at an effective concentration
directly to the brain, may provide a way to reduce systemic exposure to
cytotoxic agents. We also discuss targeted therapies designed to inhibit
aberrant cell-signaling pathways, as well as new experimental therapies such
as immunotherapy. The treatment of this devastating disease has so far been
met with limited success, but emerging knowledge of neuroscience and the
development of novel therapeutic agents will likely give patients new
options and require the neuro-oncology community to redefine clinical trial
design and strategy continually.
Publication Types:
PMID: 16525182 [PubMed - indexed for MEDLINE]
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-
Recent advances in the treatment of malignant astrocytoma.
Reardon
DA, Rich
JN, Friedman
HS, Bigner
DD.
Preston Robert Tisch Brain Tumor Center at Duke University, Duke University
Medical Center, Durham, NC 27710, USA. reard003@mc.duke.edu
Malignant gliomas, including the most common subtype, glioblastoma
multiforme (GBM), are among the most devastating of neoplasms. Their
aggressive infiltration in the CNS typically produces progressive and
profound disability--ultimately leading to death in nearly all cases.
Improvement in outcome has been elusive despite decades of intensive
clinical and laboratory research. Surgery and radiotherapy, the traditional
cornerstones of therapy, provide palliative benefit, while the value of
chemotherapy has been marginal and controversial. Limited delivery and tumor
heterogeneity are two fundamental factors that have critically hindered
therapeutic progress. A novel chemoradiotherapy approach, consisting of
temozolomide administered concurrently during radiotherapy followed by
adjuvant systemic temozolomide, has recently demonstrated a meaningful,
albeit modest, improvement in overall survival for newly diagnosed GBM
patients. As cell-signaling alterations linked to the development and
progression of gliomas are being increasingly elucidated, targeted therapies
have rapidly entered preclinical and clinical evaluation. Responses to
therapies that function via DNA damage have been associated with specific
mediators of resistance that may also be subject to targeted therapies.
Other approaches include novel locoregional delivery techniques to overcome
barriers of delivery. The simultaneous development of multiple advanced
therapies based on specific tumor biology may finally offer glioma patients
improved survival.
Publication Types:
PMID: 16525180 [PubMed - indexed for MEDLINE]
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-
Current strategies in treatment of oligodendroglioma:
evolution of molecular signatures of response.
Jaeckle
KA, Ballman
KV, Rao
RD, Jenkins
RB, Buckner
JC.
Mayo Clinic, Rochester, NY, USA. jaeckle.kurt@mayo.edu
Oligodendroglioma frequently (> or = 70%) responds to radiation and
chemotherapy, and is the first CNS neoplasm in which a genetic signature (1p
and 19q deletion) has been associated with outcome within the context of
large clinical trials. Current translational investigations focus on
deletions or mutations of potential tumor suppressor genes, epigenetic
alterations, amplification or mutation of growth factor and regulatory
genes, and characterization of signaling events and regulatory protein
expression. The most compelling data has involved 1p and 19q loss, which is
observed in over 50% of anaplastic oligodendrogliomas. In two randomized
phase III trials (Radiation Therapy Oncology Group 9402 and European
Organisation for Research and Treatment of Cancer 26951), the addition of
neoadjuvant or adjuvant procarbazine, lomustine, and vincristine (PCV;
respectively) to radiotherapy did not produce superior survival as compared
with radiotherapy alone. A modest increase in progression-free survival was
observed with the addition of PCV, but at the cost of increased toxicity.
Combined 1p and 19q loss identified a favorable prognostic group in both
studies, which appeared to be independent of treatment arms. However, it is
unclear whether these deletions represent surrogate markers of a favorable
biologic tumor behavior, or are predictive of outcome after specific
treatment. Currently, there is insufficient data to allow therapeutic
decisions to be made solely on the basis of 1p and 19q gene deletion status.
Future phase III trials are evaluating other chemotherapeutic and targeted
agents, including temozolomide, and include correlative investigations of
aberrant molecular events in these neoplasms, which may lead to future
therapeutic strategies that are based on specific molecular signatures.
Publication Types:
PMID: 16525179 [PubMed - indexed for MEDLINE]
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-
CASE 2. Meningeal metastases from ovarian carcinoma.
Mukhopadhyay
S, Mukhopadhyay
S, El-Zammar
O, Khurana
KK, Graziano
SL.
Department of Medicine, and the Division of Hematology-Oncology, State
University of New York Upstate Medical University, Syracuse, NY, USA.
Publication Types:
PMID: 16484706 [PubMed - indexed for MEDLINE]
-
-
White matter anisotropy in post-treatment childhood
cancer survivors: preliminary evidence of association with neurocognitive
function.
Khong
PL, Leung
LH, Fung
AS, Fong
DY, Qiu
D, Kwong
DL, Ooi
GC, McAlanon
G, Cao
G, Chan
GC.
Department of Diagnostic Radiology, Queen Mary Hospital, The University of
Hong Kong, Hong Kong, China. plkhong@hkucc.hku.hk
PURPOSE: We aim to determine if the loss of white matter fractional
anisotropy (FA), measured by diffusion tensor magnetic resonance imaging
(DTI), in post-treatment childhood medulloblastoma (MED) and acute
lymphoblastic leukemia (ALL) survivors correlate with intelligence quotient
(IQ) scores. MATERIALS AND METHODS: MED and ALL survivors (n = 30; 20 male,
10 female; age range, 6.0 to 22.1 years; mean, 13.1 years) were recruited
for DTI and IQ tests. In this cross-sectional study, age-matched normal
control (n = 55; 32 male, 23 female; age range, 6.0 to 23 years; mean, 12.1
years) DTI was obtained to compute percentage difference in white matter FA
(DeltaFA%) for each patient compared with the age-matched control group.
Multivariate regression analysis was performed to determine the
relationships between DeltaFA%, age at treatment, irradiation dose, time
interval from treatment, and full-scale IQ (FSIQ), verbal IQ (VIQ), and
performance IQ (PIQ). Receiver operating characteristics curves were used to
determine the best DeltaFA% cutoffs for predicting FSIQ, VIQ, and PIQ of
less than 85. RESULTS: DeltaFA% had a significant effect on FSIQ (adjusted
r2 = 0.439; P < .001), VIQ (adjusted r(2) = 0.237; P = .028), and PIQ
(adjusted r(2) = 0.491; P < .001) after adjusting for the effects of age
at treatment, irradiation dose, and time interval from treatment. The best
DeltaFA% value to predict less than 85 scores in FSIQ, VIQ, and PIQ was
-3.3% with specificities of 100% and sensitivities ranging from 77.8% to
87.5%. CONCLUSION: Our preliminary findings suggest that white matter FA may
be a clinically useful biomarker for the assessment of treatment-related
neurotoxicity in post-treatment childhood cancer survivors.
PMID: 16484697 [PubMed - indexed for MEDLINE]
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| 18: J
Neurol. 2006 Mar 20; [Epub ahead of print] |
|
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Glioblastoma multiforme presenting as bilateral internal
auditory canal tumors.
Lee
JW, Houtchens
M, Hochberg
F, Price
B, Md
ML, Cunnane
M, Pfannl
R, Maccollin
M.
Dept. of Neurology, Massachusetts General Hospital-East, Bldg 149, 13th St.,
Charlestown, MA 02129, USA, maccollin@helix.mgh.harvard.edu.
PMID: 16541215 [PubMed - as supplied by publisher]
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Retrospective analysis of the efficacy and tolerability
of levetiracetam in brain tumor patients.
Newton
HB, Goldlust
SA, Pearl
D.
Dardinger Neuro-Oncology Center and Division of Neuro-Oncology, Department
of Neurology, Ohio State University Medical Center, Columbus, Ohio, USA.
Seizures are a common complication of primary (PBT) and metastatic (MBT)
brain tumors, affecting approximately 50% of all patients during the course
of their illness. Anti-convulsant therapy of these tumor-induced seizures is
often inadequate with conventional anti-epileptic drugs (AEDs), due to a
variety of factors, including activation of glutaminergic NMDA receptors,
immune-mediated neuronal damage, and anatomic alterations of neuronal input
pathways. Levetiracetam (LEV) is a new AED with a novel mechanism of action,
which includes reducing the Ca(++) current through neuron-specific, high
voltage activated Ca(++) channels (n-type). Because of this unique
mechanism, it has been postulated that LEV may be effective in controlling
tumor-induced seizures. A retrospective chart review was performed of all
patients who had received LEV for seizure control. Forty-one patients were
reviewed (22 female, 19 male), with a median age of 47.5 years (range
25-81). There were 34 patients with PBT and 7 with MBT. LEV was used as an
add-on AED in 33 patients and as monotherapy in eight patients, with a
median dose of 1500 mg/day (range 500-3500). The baseline median seizure
frequency for the cohort was 1 per week. After the addition of LEV and
follow-up for a minimum of 4 weeks, the median seizure frequency was reduced
to 0 per week (59% of patients noted complete seizure control). Overall, the
seizure frequency was reduced in 90% of patients (P<0.0001; Sign test).
The most common toxicity was somnolence, noted in 37% of patients. LEV was
very effective and well tolerated in brain tumor patients with seizures, and
should be considered for add-on therapy to current AEDs, or as a substitute
anti-convulsant for monotherapy.
PMID: 16541329 [PubMed - as supplied by publisher]
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Assessment of imaging studies used with radiosurgery: a
volumetric algorithm and an estimation of its error. Technical note.
Snell
JW, Sheehan
J, Stroila
M, Steiner
L.
Lars Leksell Gamma Knife Center, Department of Neurological Surgery,
University of Virginia Health System, Charlottesville, Virginia 22908, USA.
The Gamma Knife has played an increasingly important role in the
neurosurgical treatment of patients. Intracranial lesions are not removed by
radiosurgery. Rather, the goal of treatment is to induce tumor control.
During planning, the creation of dose-volume histograms requires an accurate
volumetric analysis of intracranial lesions selected for radiosurgery. In
addition, an accurate follow-up imaging analysis of tumor volume is
essential for assessing the results of radiosurgery. Nevertheless, sources
of volumetric error and their expected magnitudes must be properly
understood so that the operator may correctly interpret apparent changes in
tumor volume. In this paper, the authors examine the often-neglected
contributions of imaging geometry (principally image slice thickness and
separation) to overall volumetric error. One of the fundamental sources of
volumetric error is that resulting from the geometry of the acquisition
protocol. The authors consider the image sampling geometry of tomographic
modalities and its contribution to volumetric error through a simulation
framework in which a synthetic digital tumor is taken as the primary model.
Because the exact volume of the digital phantom can be computed, the volume
estimates derived from tomographic "slicing" can be directly
compared precisely and independently from other error sources. In addition
to providing empirical bounds on volumetric error, this approach provides a
tool for guiding the specification of imaging protocols when a specific
volumetric accuracy, or volume change sensitivity, for particular structures
is sought a priori. Using computational geometry techniques, the volumetric
error associated with image acquisition geometry was shown to be dependent
on the number of slices through the region of interest (ROI) and the lesion
volume. With a minimum of five slices through the ROI, the volume of a
compact lesion could be calculated accurately with less than 10% error,
which was the predetermined goal for the purposes of computing accurate
dose-volume histograms and determining follow-up changes in tumor volume.
Accurate dose-volume histograms can be generated and follow-up volumetric
assessments performed, assuming accurate lesion delineation, when the object
is visualized on at least five axial slices. Volumetric analysis based on
fewer than five slices yields unacceptably larger errors (that is, >
10%). These volumetric findings are particularly relevant for radiosurgical
treatment planning and follow-up analysis. Through the application of this
volumetric methodology and a greater understanding of the error associated
with it, neurosurgeons can better perform radiosurgery and assess its
outcome.
PMID: 16509161 [PubMed - indexed for MEDLINE]
-
Reorganization of the cortical control of movement due to
radiation necrosis. Case report.
Hou
BL, Holodny
AI, Cooperman
N, Gutin
PH.
Functional Magnetic Resonance Imaging Laboratory, and Department of
Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021,
USA.
The authors report a case of reorganization of the cortical control of
movement caused by radiation necrosis based on an analysis of functional
magnetic resonance (fMR) imaging data acquired during a finger-tapping
paradigm. Radiation necrosis in this patient extended from the parietal lobe
anteriorly to the primary motor cortex (PMC), and fMR imaging demonstrated
an increase in activation in the ipsilateral supplementary motor area. This
is similar to the consequences of invasion by glial tumors into the PMC.
Publication Types:
PMID: 16509159 [PubMed - indexed for MEDLINE]
-
Meningeal plasma cell granuloma with relapsing
polychondritis. Case report.
Sato
K, Kubota
T, Kitai
R, Miyamori
I.
Division of Neurosurgery, Department of Sensory and Locomotor Medicine,
Faculty of Medical Sciences, University of Fukui, Japan. ksato@fmsrsa.fukui-med.ac.jp
Relapsing polychondritis (RP) is a rare systemic disease characterized by
recurrent inflammation of the cartilaginous structures and connective
tissue. Central nervous system lesions in association with RP have
occasionally been reported, but intracranial mass lesions have not been
described. The authors report the first such case, in which a 51-year-old
man presented with parasagittal meningeal plasma cell granuloma with RP. The
mass was subtotally resected and adjuvant radiotherapy was administered. The
patient did not experience any recurrence of the lesion during an 8-year
follow-up period. In this case, the exact diagnosis of RP was made based on
symptoms of respiratory tract chondritis, which was successfully treated by
the placement of tracheobronchial stents.
Publication Types:
PMID: 16509158 [PubMed - indexed for MEDLINE]
-
Comment in:
Quantitative analysis of the working area and angle of
attack for the retrosigmoid, combined petrosal, and transcochlear approaches
to the petroclival region.
Siwanuwatn
R, Deshmukh
P, Figueiredo
EG, Crawford
NR, Spetzler
RF, Preul
MC.
Division of Neurological Surgery, Barrow Neurological Institute, St.
Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.
OBJECT: The authors quantitatively assessed the working areas and angles of
attack associated with retrosigmoid (RS), combined petrosal (CP), and
transcochlear (TC) craniotomies. METHODS: Four silicone-injected cadaveric
heads were bilaterally dissected using three approaches progressing from the
least to the most extensive. Working areas were determined using the
Optotrak 3020 system on the upper and middle thirds of the petroclivus and
brainstem. Angles of attack were studied using the Elekta SurgiScope at the
Dorello canal and the origin of the anterior inferior cerebellar artery
(AICA). The TC approach provided significantly greater (p < 0.001)
working areas at the petroclivus (755.6 +/- 130.1 mm2) and brainstem (399.3
+/- 68.2 mm2) than the CP (354.1 +/- 60.3 and 289.7 +/- 69.9 mm2) and RS
approaches (292.4 +/- 59.9, 177.2 +/- 54.2 mm2, respectively). The brainstem
working area associated with the CP approach was significantly larger (p
< 0.001) than that associated with the RS route. There was no difference
in the petroclival working area comparing the CP and RS approaches (p =
0.149). The horizontal and vertical angles of attack achieved using the TC
approach were wider than those of the CP and RS at the Dorello canal and the
origin of the AICA (p < 0.001). CONCLUSIONS: The CP approach offers a
more extensive working area than the RS for lesions involving the
anterolateral surface of the brainstem, but not for petroclival lesions. The
TC approach provides the widest corridor, improving the working area and
angle of attack to both areas, but hearing must be sacrificed and the facial
nerve is at risk.
PMID: 16509157 [PubMed - indexed for MEDLINE]
-
Antitumor efficacy improved by local delivery of
species-specific endostatin.
Huszthy
PC, Brekken
C, Pedersen
TB, Thorsen
F, Sakariassen
PO, Skaftnesmo
KO, Haraldseth
O, Lonning
PE, Bjerkvig
R, Enger
PO.
Gene Therapy Program, Department of Oncology and Medical Physics, Haukeland
University Hospital, Bergen, Norway. Peter.Hsuzthy@helse-bergen.no
OBJECT: Conflicting results have been reported concerning the antitumor
efficacy of the angiogenesis inhibitor endostatin. This may be due to
differences in the biological distribution of endostatin between studies or
to the varying biological efficacies of the different protein forms that
were examined. To address this issue, the authors used a local delivery
approach in which each tumor cell secreted endostatin, providing uniform
endostatin levels throughout the tumors. This allowed a direct assessment of
the biological efficacy of soluble endostatin in vivo. METHODS: The authors
genetically engineered BT4C gliosarcoma cells so that they would stably
express and secrete either the human or murine form of endostatin.
Endostatin-producing cells or mock-infected cells were implanted
intracerebrally in syngeneic BD-IX rats. The antitumor efficacy of
endostatin was evaluated on the basis of survival data and tumor volume
comparisons. In addition, microvascular parameters were assessed. The
authors confirmed the continuous release of endostatin by the BT4C cells. A
magnetic resonance imaging-assisted comparison of tumor volumes revealed
that local production of murine endostatin significantly inhibited tumor
growth. Notably, 40% of the animals in this treatment group experienced
long-term survival without histologically verifiable tumors 7 months after
cell implantation. After local treatment with murine endostatin, tumor blood
plasma volumes were reduced by 71%, microvessel density counts by 84%, and
vascular area fractions by 75%. In contrast, human endostatin did not
inhibit tumor growth significantly in this model. Centrally located regions
of necrosis were present in tumors secreting both the human and the murine
species-specific form of endostatin. CONCLUSIONS: The results suggest that
endostatin inhibits tumor angiogenesis in vivo in a species-specific manner.
PMID: 16509155 [PubMed - indexed for MEDLINE]***
-
Intraoperative corticomuscular motor evoked potentials
for evaluation of motor function: a comparison with corticospinal D and I
waves.
Fujiki
M, Furukawa
Y, Kamida
T, Anan
M, Inoue
R, Abe
T, Kobayashi
H.
Department of Neurosurgery, School of Medicine, Oita University, Oita,
Japan. fujiki@med.oita-u.ac.jp
OBJECT: The goal of this study was to compare motor evoked potentials
recorded from muscles (muscle MEPs or corticomuscular MEPs) with
corticospinal MEPs recorded from the cervical epidural space (spinal MEPs or
corticospinal MEPs) to assess their efficacy in the intraoperative
monitoring of motor function. METHODS: Muscle and spinal MEPs were
simultaneously recorded during surgery in 80 patients harboring brain
tumors. Each case was assigned to one of four groups according to final
changes in the MEPs: (1) Group A, in which there was an increased amplitude
in the muscle MEP with an increased 13 wave amplitude (12 cases); (2) Group
B, in which there was no significant change in the MEP (43 cases); (3) Group
C, in which there was a decreased muscle MEP amplitude (< 35% of the
control) with a decreased I wave amplitude but an unchanged D wave (15
cases); or (4) Group D, in which there was an absent muscle MEP with a
decreased D wave amplitude (10 cases). In patients in Group A, the increase
in the amplitude of the muscle MEP (range of increase 128-280%, mean
increase 188.75 +/- 48.79%) was well correlated with the increase in the 13
wave in corticospinal MEPs. Most of these patterns were observed in patients
harboring meningiomas (10 [83.3%] of 12 cases). Patients in Group B
displayed no changes in muscle and corticospinal MEPs and no signs of
postoperative neurological deterioration. Patients in Group C showed a
substantial decrease in the amplitude of the muscle MEP (range of decrease
5.3-34.8% based on the control waveform, mean change 21.81 +/- 10.93%)
without deterioration in the corticospinal D wave, and exhibited severe
immediate postoperative motor dysfunction. This indicates dysfunction of the
cortical gray matter, including the motor cortices, which are supposed to
generate I waves. Patients in Group D exhibited decreases in the
corticospinal D wave (range of decrease 21.5-55%, mean decrease 39.75 +/-
11.45%) and an immediate cessation of the muscle MEP as well as severe
permanent motor paresis. CONCLUSIONS: These results indicate that, during
surgery, monitoring of corticomuscular MEPs (which are related to I waves)
is a much more sensitive method for the detection of immediate motor
cortical damage than monitoring of corticospinal MEPs (D wave).
Publication Types:
PMID: 16509151 [PubMed - indexed for MEDLINE]
-
Bromocriptine treatment of invasive giant prolactinomas
involving the cavernous sinus: results of a long-term follow up.
Wu
ZB, Yu
CJ, Su
ZP, Zhuge
QC, Wu
JS, Zheng
WM.
Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical
College, Wenzhou, People's Republic of China. zhebaowu@yahoo.com.cn
OBJECT: The aim of this study was to observe long-term clinical outcomes in
a group of patients treated with bromocriptine for invasive giant
prolactinomas involving the cavernous sinus. METHODS: Data from 20 patients
with invasive giant prolactinomas at the authors' institutions between July
1997 and June 2004 were retrospectively reviewed. The criteria to qualify
for study participation included: (1) tumor diameter greater than 4 cm,
invading the cavernous sinus to an extent corresponding to Grade III or IV
in the classification scheme of Knosp and colleagues; (2) serum prolactin (PRL)
level greater than 200 ng/ml; and (3) clinical signs of hyperprolactinemia
and mass effect. Among the 20 patients who met the criteria, six had
undergone unsuccessful transcranial or transsphenoidal microsurgery prior to
bromocriptine treatment and 14 patients received bromocriptine as the
primary treatment. Eleven of the 20 patients underwent adjuvant
radiotherapy. After a mean follow-up period of 37.3 months, the clinical
symptoms in all patients improved by different degrees. Tumor volume on
magnetic resonance images was decreased by a mean of 93.3%. In 11 patients,
the tumor had almost completely disappeared; in the other nine patients,
residual tumor invaded the cavernous sinus. Visual symptoms improved in 13
of the patients who had presented with visual loss. Eight patients had
normal PRL levels. The postoperative PRL level was more than 200 ng/ml in
seven patients. During the course of drug administration, cerebrospinal
fluid leakage occurred in one patient, who subsequently underwent
transsphenoidal surgery. No case of apoplexy occurred during bromocriptine
treatment. CONCLUSIONS: Dopamine agonist medications are effective as a
first-line therapy for invasive giant prolactinomas, because they can
significantly shrink tumor volume and control the PRL level. Tumor mass
vanishes in some patients after bromocriptine treatment; in other patients
with localized residual tumor, stereotactic radiosurgery is a viable option
so that unnecessary surgery can be avoided. The application of radiotherapy
does not reliably shrink tumor volume.
Publication Types:
PMID: 16509147 [PubMed - indexed for MEDLINE]
-
Custom-tailored transdural anterior transpetrosal
approach to ventral pons and retroclival regions.
Steiger
HJ, Hanggi
D, Stummer
W, Winkler
PA.
Department of Neurosurgery, Heinrich-Heine-University Medical School,
Dusseldorf, Germany. Steiger@uni-duesseldorf.de
OBJECT: The extradural anterior petrosectomy approach to the pons and
midbasilar artery (mid-BA) has the main disadvantage that the extent of
resection of the petrous apex cannot be as minimal as desired given that the
surgical target field is not visible during bone removal. Unnecessary or
excessive drilling poses the risk of injury to the internal carotid artery,
vestibulocochlear organ, and seventh and eighth cranial nerves. The use of a
custom-tailored transdural anterior transpetrosal approach can potentially
avoid these pitfalls. METHODS: A technique for a transdural anterior
petrosectomy was developed in the operating theater and anatomy laboratory.
Following a subtemporal craniotomy and basal opening of the dura mater, the
vein of Labbe is first identified and protected. Cerebrospinal fluid ([CSF]
50-100 ml) is drained via a spinal catheter. The tent is incised behind the
entrance of the trochlear nerve toward the superior petrosal sinus (SPS),
which is coagulated and divided. The dura is stripped from the petrous
pyramid. Drilling starts at the petrous ridge and proceeds laterally and
ventrally. The trigeminal nerve is unroofed. The internal acoustic meatus is
identified and drilling is continued laterally as needed. The bone of the
Kawase triangle toward the clivus can be removed down to the inferior
petrosal sinus if necessary. Anterior exposure can be extended to the
carotid artery if required. It is only exceptionally necessary to follow the
greater superior petrosal nerve toward the geniculate ganglion and to expose
the length of the internal acoustic canal. The modified transdural anterior
petrosectomy exposure has been used in nine patients-two with a mid-BA
aneurysm, two with a dural arteriovenous fistula, one with a pontine glioma,
three with a pontine cavernoma, and one with a pontine abscess. In one
patient with a mid-BA aneurysm, subcutaneous CSF collection occurred during
the postoperative period. No CSF fistula or approach-related cranial nerve
deficit developed in any of these patients. There was no retraction injury
or venous congestion of the temporal lobe nor any venous congestion due to
the obliteration of the SPS or the petrosal vein. CONCLUSIONS: The
custom-made transdural anterior petrosectomy appears to be a feasible
alternative to the formal extradural approach.
PMID: 16509145 [PubMed - indexed for MEDLINE]
-
Category-specific cortical mapping: color-naming areas.
Roux
FE, Lubrano
V, Lauwers-Cances
V, Mascott
CR, Demonet
JF.
Institut National de la Sante et de la Recherche Medicale, Unite 455,
Toulouse, France. rouxfran@compuserve.com
OBJECT: It has been hypothesized that a certain degree of specialization
exists within language areas, depending on some specific lexical repertories
or categories. To spare hypothetical category-specific cortical areas and to
gain a better understanding of their organization, the authors studied
patients who had undergone electrical stimulation mapping for brain tumors
and they compared an object-naming task with a category-specific task (color
naming). METHODS: Thirty-six patients with no significant preoperative
language deficit were prospectively studied during a 2-year period. Along
with a reading task, both object- and color-naming tasks were used in brain
mapping. During color naming, patients were asked to identify 11 visually
presented basic colors. The modality specificity of the color-naming sites
found was subsequently tested by asking patients to retrieve the color
attributes of objects. High individual variability was observed in language
organization among patients and in the tasks performed. Significant
interferences in color naming were found in traditional language
regions-that is, Broca (p < 0.003) and Wernicke centers (p =
0.05)--although some color-naming areas were occasionally situated outside
of these regions. Color-naming interferences were exclusively localized in
small cortical areas (< 1 cm2). Anatomical segregation of the different
naming categories was apparent in 10 patients; in all, 13 color-specific
naming areas (that is, sites evoking no object-naming interference) were
detected in the dominant-hemisphere F3 and the supramarginal, angular, and
posterior parts of the temporal gyri. Nevertheless, no specific brain region
was found to be consistently involved in color naming (p > 0.05). At five
sites, although visually presented color-naming tasks were impaired by
stimulation, auditory color naming (for example, "What color is
grass?") was performed with no difficulty, showing that
modality-specific areas can be found during naming. CONCLUSIONS: Within
language areas, a relative specialization of cortical language areas for
color naming can be found during electrical stimulation mapping.
PMID: 16509144 [PubMed - indexed for MEDLINE]
-
Comment in:
Development of a histological pseudocapsule and its use
as a surgical capsule in the excision of pituitary tumors.
Oldfield
EH, Vortmeyer
AO.
Surgical Neurology Branch, National Institute of Neurological Diseases and
Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
oldfielde@ninds.nih.gov
OBJECT: The presence of a histological pseudocapsule around pituitary tumors
was noted in the early 1900s. Since that time there has been no emphasis on
the sequence of the stages of its development or on the relationship between
these stages and the capacity to identify very small pituitary tumors at
surgery in patients in whom preoperative imaging has been nondiagnostic. In
addition, limited emphasis has been given to the pseudocapsule's use for
selective and complete resection of pituitary adenomas. METHODS: The
development of the pseudocapsule was examined by performing histological
analysis of portions of pituitary glands removed during 805 operations for
Cushing disease. Twenty-five adenomas, each measuring between 0.25 and 4 mm
in maximum diameter, were detected in the excised specimens; 17 were
adenocorticotropic hormone-positive adenomas and eight were incidental
tumors (four prolactin-secreting and four nonsecreting lesions). In 16
tumors the size of the adenoma could be established. The distribution of
tumor size in relation to the presence of a histological pseudocapsule
indicates a transition from the absence of a reticulin capsule (tumor
diameter < or =1 mm) through the initial compression of surrounding
tissue (tumor diameter 1-2 mm) to the presence of a multilayered reticulin
capsule observed when adenomas become larger (tumor diameter 2-3 mm).
CONCLUSIONS: The absence of a reticulin capsule in cases of very small
tumors may contribute to limited localization of these lesions during
surgical exploration of the pituitary gland. In this article the authors
describe surgical techniques in which the histological pseudocapsule is used
as a surgical capsule during pituitary surgery. In their experience,
recognition of this surgical capsule and its use at surgery has contributed
to the identification of microadenomas buried in the pituitary gland, aided
the recognition of subtle invasion of the pituitary capsule and contiguous
dura mater, and enhanced the consistency of complete tumor excision with
small and large tumors.
PMID: 16509142 [PubMed - indexed for MEDLINE]
-
Germinoma: unusual imaging and pathological
characteristics. Report of two cases.
Rushing
EJ, Sandberg
GD, Judkins
AR, Vezina
G, Kadom
N, Myseros
JS, Packer
RJ, Santi
M.
Department of Neuropathology and Ophthalmic Pathology, Armed Forces
Institute of Pathology, Washington, DC 20306-6000, USA. rushinge@afip.osd.mil
Primary germ cell neoplasms of the central nervous system typically develop
as midline mass lesions during the first three decades of life. The authors
present two cases with atypical clinicopathological features that stimulate
discussion on the diagnosis and management of these tumors. The first
patient was an 11-year-old boy of Japanese-American heritage who presented
with a 6-month-long history of cognitive decline, difficulty swallowing,
unsteady gait, and intermittent right-sided posturing. The initial magnetic
resonance (MR) image of the brain displayed a mildly increased T2 signal in
the cerebral peduncles, putamen, and globus pallidus bilaterally. Follow-up
MR images showed an increase in the T2 signal abnormality in the left basal
ganglia. The second patient was a 10-year-old Caucasian boy who presented
with diabetes insipidus and subsequently displayed progressive fatigue,
involuntary eye and mouth movements, and obsessive-compulsive behavior. An
MR image demonstrated signs of mineral deposition and foci of increased T2
signal in both basal ganglia. Follow-up MR images demonstrated a progressive
increase in the T2 signal (which was then located within the mesial temporal
lobe). A biopsy performed on the left thalamic lesion in the first patient
revealed a germinoma. The patient was treated with chemotherapy and died 2
years later. The second patient underwent a lumbar puncture, which
demonstrated an elevated level of beta-human chorionic gonadotropin. Despite
the lack of a mass on MR images in this child, the need for a tissue
diagnosis prompted the authors to perform an anterior temporal lobectomy.
The diagnosis of diffuse germinoma was confirmed, and the patient was
treated with adjunctive chemotherapy. Although uncommon, germ cell tumors
can present outside the midline and exhibit a multifocal growth pattern.
Publication Types:
PMID: 16506503 [PubMed - indexed for MEDLINE]
-
Brainstem stereotactic biopsy sampling in children.
Pincus
DW, Richter
EO, Yachnis
AT, Bennett
J, Bhatti
MT, Smith
A.
Department of Neurosurgery, University of Florida, Gainesville, Florida
32610, USA. pincus@neurosurgery.ufl.edu
OBJECT: Although it is widely accepted that biopsy sampling is not indicated
for the diagnosis and empiric treatment of diffuse pontine glioma, it is
common to encounter patients with brainstem lesions that cannot be diagnosed
on the basis of imaging studies alone. In cases not amenable to resection, a
tissue diagnosis may still be necessary to make appropriate treatment
recommendations. The authors retrospectively reviewed their institutional
experience with stereotactic biopsy procedures in pediatric patients during
a 4-year period. METHODS: A three-dimensional graphics workstation was used
for trajectory planning to obtain biopsy samples of brainstem lesions in 10
patients. One patient experienced mild diplopia postoperatively. No other
morbidity was noted; no patient died as a result of the procedure. The
biopsy procedure yielded a pathological diagnosis in all cases. A later
resection in one patient resulted in a change in diagnosis. Overall, the
pathological findings were varied, and in some cases the tissue diagnosis
altered the treatment recommendations. CONCLUSIONS: The findings in this
small series suggest that brainstem stereotactic biopsy sampling in children
is a safe procedure with a high diagnostic yield. In patients in whom
radiographic findings are not consistent with diffuse pontine glioma and
resection is not appropriate, stereotactic biopsy sampling should be
considered.
Publication Types:
PMID: 16506498 [PubMed - indexed for MEDLINE]
-
-
Cellular telephones and risk for brain tumors: a
population-based, incident case-control study.
Gale
BD, Juran
D.
Publication Types:
PMID: 16534134 [PubMed - in process]
-
-
An MRI view of a ruptured dermoid cyst.
Ernemann
U, Rieger
J, Tatagiba
M, Weller
M.
Department of Neuroradiology, University of Tubingen Medical School, Hoppe-Seyler-Strasse
3, 72076 Tubingen, Germany. ulrike.ernemann@med.uni-tuebingen.de
Publication Types:
PMID: 16434673 [PubMed - indexed for MEDLINE]
-
-
Oligodendroglial tumor chemotherapy using
"decreased-dose-intensity" PCV: a Singapore experience.
Ty
AU, See
SJ, Rao
JP, Khoo
JB, Wong
MC.
Department of Neurology, National Neuroscience Institute, Singapore General
Hospital Campus, Singapore.
The authors propose "decreased-dose-intensity" PCV (procarbazine,
lomustine [CCNU], and vincristine) chemotherapy for Asian patients with
oligodendroglial tumors. In this study, all seven patients with
oligodendroglioma (OD) and eight with anaplastic oligodendroglioma (AO) had
objective responses or stable disease. Median progression-free survival was
greater than 29 months (OD) and 36.5 months or greater (AO); 86% of patients
with OD and 63% with AO remain progression-free. Twenty-four Common Toxicity
Criteria Grade 3/4 adverse events were noted.
Publication Types:
PMID: 16434664 [PubMed - indexed for MEDLINE]
-
-
Interleukin-8 CSF levels predict survival in patients
with leptomeningeal metastases.
Brandsma
D, Taphoorn
MJ, de
Jager W, Bonfrer
H, Algra
A, Reijneveld
JC, Boogerd
W, Korse
T, Verbeek
MM, Rijkers
GT, Voest
EE.
Department of Neurology, University Medical Center Utrecht, Utrecht, The
Netherlands. d.brandsma@umcutrecht.nl
Median survival of patients with leptomeningeal metastases (LM) is 4 to 6
months, with a few long-term survivors. Current prognostic factors for
survival have limited value. The authors measured the CSF levels of nine
inflammatory proteins in 57 patients with LM and determined their prognostic
value. High interleukin (IL)-8 CSF levels predicted short-term survival
independently. The data indicate that IL-8 CSF levels may serve as a
prognosticator in patients with LM, but prospective validation is needed.
PMID: 16434663 [PubMed - indexed for MEDLINE]
-
-
Sperm protein 17 is expressed in human nervous system
tumours.
Grizzi
F, Gaetani
P, Franceschini
B, Di
Ieva A, Colombo
P, Ceva-Grimaldi
G, Bollati
A, Frezza
EE, Cobos
E, Rodriguez
y Baena R, Dioguardi
N, Chiriva-Internati
M.
Istituto Clinico Humanitas, IRCCS, 20089 Rozzano, Milan, Italy. fabio.grizzi@humanitas.it
BACKGROUND: Human sperm protein 17 (Sp17) is a highly conserved protein that
was originally isolated from a rabbit epididymal sperm membrane and testis
membrane pellet. It has recently been included in the cancer/testis (CT)
antigen family, and shown to be expressed in multiple myeloma and ovarian
cancer. We investigated its immunolocalisation in specimens of nervous
system (NS) malignancies, in order to establish its usefulness as a target
for tumour-vaccine strategies. METHODS: The expression of Sp17 was assessed
by means of a standardised immunohistochemical procedure [(mAb/antigen)
MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS
malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas,
16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25
meningeal tumours, and five periphe |
Volume 5, Number 12 - 20 March
2006