| 1: Brain.
2006 Jul;129(Pt 7):1884-91. Epub 2006 May 2. |
|
-
Histological growth patterns and genotype in
oligodendroglial tumours: correlation with MRI features.
Jenkinson
MD, du
Plessis DG, Smith
TS, Joyce
KA, Warnke
PC, Walker
C.
Departments of Neurosurgery, University of Liverpool Liverpool, UK.
michael.jenkinson@liv.ac.uk
Oligodendroglial neoplasms with the -1p/-19q genotype are more indolent with
longer survival and increased therapeutic responsiveness than those with
intact 1p/19q, but the biological basis for these clinical differences is
unclear. Recent research suggests that oligodendrogliomas with and without
the -1p/-19q genotype may be distinguished by their magnetic resonance
imaging (MRI) appearance, suggesting possible differences in growth
characteristics. This study examined the relationship between genotype and
histological growth patterns of oligodendroglial neoplasms in association
with MR imaging characteristics. Tumour imaging features assessed on MRI
included sharp-versus-indistinct border, smooth-versus-irregular contour,
homogeneous-versus-heterogeneous signal, contrast enhancement and
paramagnetic susceptibility effect. Growth patterns (solid : mixed :
infiltrative), tumour-margin transitions in cellularity and calcification
were determined histopathologically. Allelic imbalance in chromosomes 1p36
and 19q13 was determined. Thirty-three oligodendrogliomas (25 with 1p/19q
loss) and 53 oligoastrocytomas (18 with 1p/19q loss) were investigated.
Solid, mixed or infiltrative growth patterns were seen in grade II and grade
III tumours with or without 1p/19q loss, but infiltrative growth was more
common in tumours with intact 1p/19q (chi2: P = 0.029). Grade III tumours
were more likely to have a solid growth pattern (chi2: P = 0.046) associated
with contrast enhancement (chi2: P = 0.011). Transition in cellularity at
the radiological margin did not differ according to genotype. All cases with
T1 or T2 signal homogeneity had intact 1p/19q. Tumours with sharp/smooth
borders were more likely to have intact 1p/19q than those with
indistinct/irregular borders (chi2: P < 0.001), but this was not related
to histological growth characteristics. This study identified a group of
oligodendroglial tumours with intact 1p/19q displaying distinctive MR
imaging features that were unrelated to the histopathology characteristics.
PMID: 16670176 [PubMed - indexed for MEDLINE]3
-
| 2: Cancer.
2006 Jun 25;108(3):157-62. |
|
-
Detection of malignant hematopoietic cells in cerebral
spinal fluid previously diagnosed as atypical or suspicious.
Schinstine
M, Filie
AC, Wilson
W, Stetler-Stevenson
M, Abati
A.
Cytopathology Section, Laboratory of Pathology, National Cancer Institute,
National Institutes of Health, Bethesda, Maryland 20892-1500, USA.
BACKGROUND: Involvement of the cerebrospinal fluid (CSF) by hematopoietic
malignancies may be difficult to document by morphology alone. In cases with
low numbers of cells or ambiguous morphology, the diagnoses of
"atypical" or "suspicious" may be used. The significance
of these diagnostic terms in this scenario has not been well established.
METHODS: Between January 2000 and July 2004, 32 patients with known lymphoma
or leukemia and an initial diagnosis of "atypical" or
"suspicious" using morphologic criteria were identified.
Subsequent flow cytometry (FC) and cytologic data from these patients were
evaluated. RESULTS: Of the 32 patients with an initial diagnosis of
"atypical" or "suspicious," 40.6% (n = 13) had negative
first and subsequent FC and morphologic evaluation of their CSF samples with
follow-up up to 1 year. Nineteen patients (59.4%) had malignant
hematopoietic cells identified in subsequent CSF samples by cytology and/or
FC. CONCLUSIONS: In patients with a previous history of lymphoma or a
hematopoietic malignancy, a majority of the patients (59.4%) with an
"atypical" or "suspicious" diagnosis on CSF will
ultimately have malignant cells identified in the CSF by cytology and/or FC.
Many of these patients can be identified more expediently with the
concurrent utilization of flow cytometry.
PMID: 16649227 [PubMed - indexed for MEDLINE]
-
| 3: Cancer
Res. 2006 Aug 1;66(15):7490-501. |
|
Epigenomic profiling reveals novel and frequent targets
of aberrant DNA methylation-mediated silencing in malignant glioma.
Kim
TY, Zhong
S, Fields
CR, Kim
JH, Robertson
KD.
Department of Biochemistry and Molecular Biology and University of Florida
Shands Cancer Center Program in Cancer Genetics, Epigenetics, and Tumor
Virology, University of Florida College of Medicine, Gainesville, Florida.
Malignant glioma is the most common central nervous system tumor of adults
and is associated with a significant degree of morbidity and mortality.
Gliomas are highly invasive and respond poorly to conventional treatments.
Gliomas, like other tumor types, arise from a complex and poorly understood
sequence of genetic and epigenetic alterations. Epigenetic alterations
leading to gene silencing, in the form of aberrant CpG island promoter
hypermethylation and histone deacetylation, have not been thoroughly
investigated in brain tumors, and elucidating such changes is likely to
enhance our understanding of their etiology and provide new treatment
options. We used a combined approach of pharmacologic inhibition of DNA
methylation and histone deacetylation, coupled with expression microarrays,
to identify novel targets of epigenetic silencing in glioma cell lines. From
this analysis, we identified >160 genes up-regulated by
5-aza-2'-deoxycytidine and trichostatin A treatment. Further
characterization of 10 of these genes, including the putative metastasis
suppressor CST6, the apoptosis-inducer BIK, and TSPYL5, whose function is
unknown, revealed that they are frequent targets of epigenetic silencing in
glioma cell lines and primary tumors and suppress glioma cell growth in
culture. Furthermore, we show that other members of the TSPYL gene family
are epigenetically silenced in gliomas and dissect the contribution of
individual DNA methyltransferases to the aberrant promoter hypermethylation
events. These studies, therefore, lay the foundation for a comprehensive
understanding of the full extent of epigenetic changes in gliomas and how
they may be exploited for therapeutic purposes. (Cancer Res 2006; 66(15):
7490-501).
PMID: 16885346 [PubMed - in process]
-
| 4: Cancer
Res. 2006 Aug 1;66(15):7473-81. |
|
ROS Fusion Tyrosine Kinase Activates a SH2
Domain-Containing Phosphatase-2/Phosphatidylinositol 3-Kinase/Mammalian
Target of Rapamycin Signaling Axis to Form Glioblastoma in Mice.
Charest
A, Wilker
EW, McLaughlin
ME, Lane
K, Gowda
R, Coven
S, McMahon
K, Kovach
S, Feng
Y, Yaffe
MB, Jacks
T, Housman
D.
Department of Biology and Center for Cancer Research, Massachusetts
Institute of Technology, Cambridge, Massachusetts and Brigham and Women's
Hospital, Department of Pathology, Boston, Massachusetts.
Glioblastoma multiforme is the most common and lethal form of primary brain
cancer. Diagnosis of this advanced glioma has a poor prognosis due to the
ineffectiveness of current therapies. Aberrant expression of receptor
tyrosine kinases (RTK) in glioblastoma multiformes is suggestive of their
role in initiation and maintenance of these tumors of the central nervous
system. In fact, ectopic expression of the orphan RTK ROS is a frequent
event in human brain cancers, yet the pathologic significance of this
expression remains undetermined. Here, we show that a glioblastoma-associated,
ligand-independent rearrangement product of ROS (FIG-ROS) cooperates with
loss of the tumor suppressor gene locus Ink4a;Arf to produce glioblastomas
in the mouse. We show that this FIG-ROS-mediated tumor formation in vivo
parallels the activation of the tyrosine phosphatase SH2 domain-containing
phosphatase-2 (SHP-2) and a phosphatidylinositol 3-kinase/Akt/mammalian
target of rapamycin signaling axis in tumors and tumor-derived cell lines.
We have established a fully penetrant preclinical model for adult onset of
glioblastoma multiforme in keeping with major genetic events observed in the
human disease. These findings provide novel and important insights into the
role of ROS and SHP-2 function in solid tumor biology and set the stage for
preclinical testing of targeted therapeutic approaches. (Cancer Res 2006;
66(15): 7473-81).
PMID: 16885344 [PubMed - in process]
-
| 5: Cancer
Res. 2006 Aug 1;66(15):7445-52. |
|
Notch Pathway Inhibition Depletes Stem-like Cells and
Blocks Engraftment in Embryonal Brain Tumors.
Fan
X, Matsui
W, Khaki
L, Stearns
D, Chun
J, Li
YM, Eberhart
CG.
Departments of Pathology and Oncology, Johns Hopkins University School of
Medicine, Baltimore, Maryland and Molecular Pharmacology and Chemistry
Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
The Notch signaling pathway is required in both nonneoplastic neural stem
cells and embryonal brain tumors, such as medulloblastoma, which are derived
from such cells. We investigated the effects of Notch pathway inhibition on
medulloblastoma growth using pharmacologic inhibitors of gamma-secretase.
Notch blockade suppressed expression of the pathway target Hes1 and caused
cell cycle exit, apoptosis, and differentiation in medulloblastoma cell
lines. Interestingly, viable populations of better-differentiated cells
continued to grow when Notch activation was inhibited but were unable to
efficiently form soft-agar colonies or tumor xenografts, suggesting that a
cell fraction required for tumor propagation had been depleted. It has
recently been hypothesized that a small population of stem-like cells within
brain tumors is required for the long-term propagation of neoplastic growth
and that CD133 expression and Hoechst dye exclusion (side population) can be
used to prospectively identify such tumor-forming cells. We found that Notch
blockade reduced the CD133-positive cell fraction almost 5-fold and totally
abolished the side population, suggesting that the loss of tumor-forming
capacity could be due to the depletion of stem-like cells. Notch signaling
levels were higher in the stem-like cell fraction, providing a potential
mechanism for their increased sensitivity to inhibition of this pathway. We
also observed that apoptotic rates following Notch blockade were almost
10-fold higher in primitive nestin-positive cells as compared with nestin-negative
ones. Stem-like cells in brain tumors thus seem to be selectively vulnerable
to agents inhibiting the Notch pathway. (Cancer Res 2006; 66(15): 7445-52).
PMID: 16885340 [PubMed - in process]
-
| 6: Cancer
Res. 2006 Aug 1;66(15):7429-37. |
|
High-grade glioma formation results from postnatal pten
loss or mutant epidermal growth factor receptor expression in a transgenic
mouse glioma model.
Wei
Q, Clarke
L, Scheidenhelm
DK, Qian
B, Tong
A, Sabha
N, Karim
Z, Bock
NA, Reti
R, Swoboda
R, Purev
E, Lavoie
JF, Bajenaru
ML, Shannon
P, Herlyn
D, Kaplan
D, Henkelman
RM, Gutmann
DH, Guha
A.
Arthur & Sonia Labatt Brain Tumour Research Centre and Mouse Imaging
Centre, The Hospital for Sick Children.
High-grade gliomas are devastating brain tumors associated with a mean
survival of <50 weeks. Two of the most common genetic changes observed in
these tumors are overexpression/mutation of the epidermal growth factor
receptor (EGFR) vIII and loss of PTEN/MMAC1 expression. To determine whether
somatically acquired EGFRvIII expression or Pten loss accelerates high-grade
glioma development, we used a previously characterized RasB8 glioma-prone
mouse strain, in which these specific genetic changes were focally
introduced at 4 weeks of age. We show that both postnatal EGFRvIII
expression and Pten inactivation in RasB8 mice potentiate high-grade glioma
development. Moreover, we observe a concordant loss of Pten and EGFR
overexpression in nearly all high-grade gliomas induced by either EGFRvIII
introduction or Pten inactivation. This novel preclinical model of
high-grade glioma will be useful in evaluating brain tumor therapies
targeted to the pathways specifically dysregulated by EGFR expression or
Pten loss. (Cancer Res 2006; 66(15): 7429-37).
PMID: 16885338 [PubMed - in process]3
-
| 7: Eur
J Cancer. 2006 May;42(8):1120-8. Epub 2006 Apr 24. |
|
-
Analysis of patients with supratentorial primitive
neuro-ectodermal tumours entered into the SIOP/UKCCSG PNET 3 study.
Pizer
BL, Weston
CL, Robinson
KJ, Ellison
DW, Ironside
J, Saran
F, Lashford
LS, Tait
D, Lucraft
H, Walker
DA, Bailey
CC, Taylor
RE.
Alder Hey's Children's Hospital-Oncology Unit, Eaton Road, Liverpool L12
2AP, UK. bpizer@liv.ac.uk
The SIOP PNET 3 study was designed to determine whether 10 weeks of
moderately intensive chemotherapy given after surgery and before
radiotherapy (RT) would improve the outcome for patients with primitive
neuroectodermal tumours (PNETs) compared with RT alone. Patients with a
histological diagnosis of supratentorial PNET (StPNET) and no radiological
evidence of metastatic disease were initially eligible for randomisation to
either chemotherapy followed by craniospinal RT 35 Gy in 21 fractions with a
boost of 20 Gy in 12 fractions to the primary site, or RT alone. In respect
of the increasing recognition that StPNET were high-risk tumours,
randomisation for this group closed in November 1999. This analysis includes
both randomised and non-randomised patients with StPNET entered into the
study database. Sixty-eight patients aged 2.9-16.6 years (median 6.5 years)
were included in the analysis (chemotherapy+RT: 44, RT alone: 24).
Fifty-four patients (79%) had a non-pineal and 14 (21%) a pineal site. At a
median follow-up of 7.4 years, for all patients overall survival (OS) at 3
and 5 years was 54.4% and 48.3%, respectively. Event-free survival (EFS) at
3 and 5 years was 50.0% and 47.0%, respectively. There was no statistically
significant difference in OS or EFS according to treatment received. OS
(P=0.05) and EFS (P=0.03) were significantly better for patients with pineal
primary sites. EFS for pineal tumours were 92.9% at 3 years and 71.4% at 5
years and for non-pineal primaries 40.7% at 3 years and 40.7% at 5 years.
This study confirmed the relatively good survival for non-metastatic pineal
PNETs but poor survival of non-pineal StPNETs. There was no evidence that
pre-radiation chemotherapy improved outlook. Future treatment programs
should be directed at the particular natural history of these tumours, to
further define prognostic factors and to explore further biological
characteristics.
Publication Types:
- Randomized
Controlled Trial
PMID: 16632346 [PubMed - indexed for MEDLINE]3
-
| 8: Eur
J Cancer. 2006 May;42(8):1052-6. Epub 2006 Mar 31. |
|
-
Defining the appropriate radiotherapy regimen for
metastatic spinal cord compression in non-small cell lung cancer patients.
Rades
D, Stalpers
LJ, Schulte
R, Veninga
T, Basic
H, Engenhart-Cabilic
R, Schild
SE, Hoskin
PJ.
Department of Radiation Oncology, University Medical Center Hamburg
Eppendorf, University Hospital Hamburg, Martinistr. 52, D-20246 Hamburg,
Germany. Rades.Dirk@gmx.net
Many different schedules are used world wide for radiotherapy (RT) of
metastatic spinal cord compression (MSCC). Non-small cell lung cancer (NSCLC)
patients have an extraordinarily poor survival prognosis and would benefit
from a short overall treatment time. This retrospective study compares
short-course RT (1 x 8 Gy/1 day, 5 x 4 Gy/1 week) and long-course RT (10 x 3
Gy/2 weeks, 15 x 2.5 Gy/3 weeks, 20 x 2 Gy/4 weeks) for functional outcome
in 252 NSCLC patients developing MSCC. Improvement of motor function
occurred in 14% of patients, no change in 54%, and deterioration in 32%.
Functional outcome was affected by the time of developing motor deficits
before RT (>14 days better than 1-7 days and 8-14 days, P<0.001), not
by the radiation regimen (P=0.87). In the short-course RT group, functional
outcome was similar for 1 x 8 Gy and 5 x 4 Gy (P=0.94). Short-course and
long-course RT appear similarly effective for MSCC in NSCLC patients. As 1 x
8 Gy and 5 x 4 Gy showed comparable results, 1 x 8 Gy can be considered
appropriate.
PMID: 16580192 [PubMed - indexed for MEDLINE]3
-
| 9: Int
J Cancer. 2006 Aug 1;119(3):484-92. |
|
-
L-type amino acid transporter 1 as a potential molecular
target in human astrocytic tumors.
Nawashiro
H, Otani
N, Shinomiya
N, Fukui S, Ooigawa H, Shima K, Matsuo
H, Kanai
Y, Endou
H.
Department of Neurosurgery, National Defense Medical College, Tokorozawa,
Saitama, Japan. nawa1957@ndmc.ac.jp
L-type amino acid transporter 1 (LAT1) is a Na+-independent neutral amino
acid transport agency and essential for the transport of large neutral amino
acids. LAT1 has been identified as a light chain of the CD98 heterodimer
from C6 glioma cells. LAT1 also corresponds to TA1, an oncofetal antigen
that is expressed primarily in fetal tissues and cancer cells. We have
investigated for the first time, the expression of the transporter in the
human primary astrocytic tumor tissue from 60 patients. LAT1 is unique
because it requires an additional single membrane spanning protein, the
heavy chain of 4F2 cell surface antigen (4F2hc), for its functional
expression. 4F2hc expression was also determined by immunohistochemistry.
Kaplan-Meier analyses demonstrated that high LAT1 expression correlated with
poor survival for the study group as a whole (p<0.0001) and for those
with glioblastoma multiforme in particular (p=0.0001). Cox regression
analyses demonstrated that LAT1 expression was one of significant predictors
of outcome, independent of all other variables. On the basis of these
findings, we also investigated the effect of the specific inhibitor to LAT1,
2-aminobicyclo-2 (2,2,1)-heptane-2-carboxylic acid (BCH), on the survival of
C6 glioma cells in vitro and in vivo using a rat C6 glioma model. BCH
inhibited the growth of C6 glioma cells in vitro and in vivo in a
dose-dependent manner. Kaplan-Meier survival data of rats treated with BCH
were significant. These findings suggest that LAT1 could be one of the
molecular targets in glioma therapy. Copyright (c) 2006 Wiley-Liss, Inc.
PMID: 16496379 [PubMed - indexed for MEDLINE]
-
| 10: J
Clin Oncol. 2006 Aug 1;24(22):3651-6. |
|
-
Phase II trial of tipifarnib in patients with recurrent
malignant glioma either receiving or not receiving enzyme-inducing
antiepileptic drugs: a North American Brain Tumor Consortium Study.
Cloughesy
TF, Wen
PY, Robins
HI, Chang
SM, Groves
MD, Fink
KL, Junck
L, Schiff
D, Abrey
L, Gilbert
MR, Lieberman
F, Kuhn
J, DeAngelis
LM, Mehta
M, Raizer
JJ, Yung
WK, Aldape
K, Wright
J, Lamborn
KR, Prados
MD.
UCLA Neuro-Oncology Program, David Geffen School of Medicine at UCLA,
University of California, Los Angeles, Los Angeles, CA 90095, USA. tcloughe@ucla.edu
PURPOSE: A phase II study was undertaken in patients with recurrent
malignant glioma to determine the efficacy and safety of tipifarnib, a
farnesyltransferase inhibitor, dosed at the respective maximum-tolerated
dose (MTD) for patients receiving and not receiving enzyme-inducing
antiepileptic drugs (EIAEDs). Because tipifarnib undergoes extensive hepatic
metabolism, MTD is doubled in patients on EIAEDs. The population included 67
patients with glioblastoma multiforme (GBM) and an exploratory group of 22
patients with anaplastic glioma (AG). PATIENTS AND METHODS: Patients
received tipifarnib (300 and 600 mg bid for 21 days every 4 weeks in non-EIAED
and EIAED patients, respectively). All patients were assessable for efficacy
and safety. RESULTS: Two AG patients (9.1%) and eight GBM patients (11.9%)
had progression-free survival (PFS) more than 6 months. Among the latter
eight GBM patients, six of 36 patients (16.7%; 95% CI, 7% to 32%) were not
receiving EIAEDs and two of 31 patients (6.5%; 95% CI, 1% to 20%) were
receiving EIAEDs. Four patients had partial responses in group A GBM and one
patient had a partial response group B GBM. An exploratory comparison of PFS
between GBM groups A and B was statistically significant (P = .01). Patients
not receiving EIAEDs had a higher incidence and increased severity of
hematologic events. However, the incidence and severity of rash (the
previously determined dose-limiting toxicity in patients receiving EIAEDs)
seemed similar in EIAED and non-EIAED subgroups. CONCLUSION: Tipifarnib (300
mg bid for 21 days every 4 weeks) shows modest evidence of activity in
patients with recurrent GBM who are not receiving EIAEDs and is generally
well tolerated in this population.
PMID: 16877733 [PubMed - in process]
-
| 11: J
Clin Oncol. 2006 Aug 1;24(22):3644-50. |
|
-
Phase I single-dose study of intracavitary-administered
iodine-131-TM-601 in adults with recurrent high-grade glioma.
Mamelak
AN, Rosenfeld
S, Bucholz
R, Raubitschek
A, Nabors
LB, Fiveash
JB, Shen
S, Khazaeli
MB, Colcher
D, Liu
A, Osman
M, Guthrie
B, Schade-Bijur
S, Hablitz
DM, Alvarez
VL, Gonda
MA.
Maxine Dunitz Neurosurgical Institute, Cedars Sinai Medical Center, Los
Angeles, CA 90048, USA. Adam.Mamelak@cshs.org
PURPOSE: TM-601 binds to malignant brain tumor cells with high affinity and
does not seem to bind to normal brain tissue. Preclinical studies suggest
that iodine-131 (131I) -TM-601 may be an effective targeted therapy for the
treatment of glioma. We evaluated the safety, biodistribution, and dosimetry
of intracavitary-administered 131I-TM-601 in patients with recurrent glioma.
PATIENTS AND METHODS: Eighteen adult patients (17 with glioblastoma
multiforme and one with anaplastic astrocytoma) with histologically
documented recurrent glioma and a Karnofsky performance status of > or =
60% who were eligible for cytoreductive craniotomy were enrolled. An
intracavitary catheter with subcutaneous reservoir was placed in the tumor
cavity during surgery. Two weeks after surgery, patients received a single
dose of 131I-TM-601 from one of three dosing panels (0.25, 0.50, or 1.0 mg
of TM-601), each labeled with 10 mCi of 131I. RESULTS: Intracavitary
administration was well tolerated, with no dose-limiting toxicities
observed. 131I-TM-601 bound to the tumor periphery and demonstrated
long-term retention at the tumor with minimal uptake in any other organ
system. Nonbound peptide was eliminated from the body within 24 to 48 hours.
Only minor adverse events were reported during the 22 days after
administration. At day 180, four patients had radiographic stable disease,
and one had a partial response. Two of these patients further improved and
were without evidence of disease for more than 30 months. CONCLUSION: A
single dose of 10 mCi 131I-TM-601 was well tolerated for 0.25 to 1.0 mg
TM-601 and may have an antitumoral effect. Dosimetry and biodistribution
from this first trial suggest that phase II studies of 131I-TM-601 are
indicated.
PMID: 16877732 [PubMed - in process]3
-
| 12: J
Clin Oncol. 2006 Aug 1;24(22):3636-43. |
|
-
Health status measurements at diagnosis as predictors of
survival among adults with brain tumors.
McCarter
H, Furlong
W, Whitton
AC, Feeny
D, DePauw
S, Willan
AR, Barr
RD.
The Juravinski Cancer Centre, Hamilton, Ontario, Canada.
PURPOSE: The intent of this study was to determine whether baseline measures
of functional capacity and performance could be used to predict survival in
adults following the diagnosis of brain tumors. PATIENTS AND METHODS:
Comprehensive health status and health-related quality of life (HRQL) were
measured using the Health Utilities Index (HUI; McMaster University,
Hamilton, Canada) system by a self-assessment questionnaire in a survey of
100 consecutive patients. The Karnofsky Performance Score (KPS) and
Folstein's Mini-Mental State Examination (MMSE) scores were measured by a
physician blinded to the HUI results. The patients were observed for up to 5
years to recorded dates of death. RESULTS: An HUI questionnaire was
completed for 93% of the patients and 69% died within 5 years of assessment.
The HUI revealed a burden of morbidity and complexity of disability that far
exceeded that reported for the general population. KPS and MMSE correlated
strongly with each other (r = 0.52; P < .001). A decrease of 0.1 units in
HUI Mark 2 (HUI2) self-care single-attribute utility score was associated
with an increased hazard of death of 30% (P = .023) for patients with
low-grade tumors (n=25). For patients with high-grade tumors (n=56), a 10
unit decrease in the KPS, a 5 unit decrease in MMSE, and a 0.1 decrease in
HUI Mark 3 (HUI3) speech and dexterity single-attribute scores were
associated with an increased hazard of death of 20% (P = .022), 26% (P =
.015), 36% (P = .021), and 18% (P = .035), respectively. CONCLUSION: Scores
derived from the measurement of HRQL following diagnosis can predict
survival in adults with brain tumors.
PMID: 16877731 [PubMed - in process]
-
| 13: J Neurosurg. 2006 Jul;105(1):41-50. |
|
Cellular immunity of patients with malignant glioma:
prerequisites for dendritic cell vaccination immunotherapy.
Rapp
M, Ozcan
Z, Steiger
HJ, Wernet
P, Sabel
MC, Sorg
RV.
Department of Neurosurgery, Heinrich-Heine-University Medical Center,
Dusseldorf Germany.
OBJECT: Vaccination therapy that uses dendritic cells (DCs) is a promising
immunotherapeutic approach. However, it relies on intact cellular immunity
and efficient generation of mature DCs, both of which can be impaired in
patients with glioma. Therefore, the immune status and ex vivo generation of
DC in such patients were studied. METHODS: The frequencies of white blood
cell subsets and monocyte-derived, mature DCs in patients with high-grade
gliomas and healthy control volunteers were analyzed using flow cytometry.
In the patients, frequencies of lymphocytes, T cells, and B cells were
reduced in comparison with the volunteers in the control group, whereas
frequencies of neutrophils and monocytes were increased. There were no
differences between the two groups in terms of white blood cell counts or
the frequency of NK cells and the major T-cell subsets. The responsiveness
of T cells to lectin stimulation was normal. For monocytes, lower
frequencies of CD80+ and CD86+ cells but not of CD40+ and HLA-DR+ cells were
observed in patients. Ex vivo DC generation in a two-step culture protocol
in autologous plasma-supplemented medium or in serum-free medium showed only
minor differences in CD80 and HLA-DR expression between the patient and
control groups. Frequencies of CD83+, CD1a+, CD14-, CD40+, and CD86+ cells
were comparable. Overall, the serum-free medium was superior to the
plasma-supplemented medium and allowed efficient ex vivo generation of
CD83+, CD1a+, and CD14- mature DCs. CONCLUSIONS: Only minor defects in the
immune status of patients with glioma were observed, which probably would
not hamper immunotherapy. Mature DCs can be generated successfully in normal
numbers and with typical immunophenotypes from monocytes of patients with
glioma, particularly under serum-free conditions.
PMID: 16874889 [PubMed - in process]3
-
| 14: J Neurosurg. 2006 Jul;105(1):6-14. |
|
Comparison between neuroimaging classifications and
histopathological diagnoses using an international multicenter brain tumor
magnetic resonance imaging database.
Julia-Sape
M, Acosta
D, Majos
C, Moreno-Torres
A, Wesseling
P, Acebes
JJ, Griffiths
JR, Arus
C.
Department of Biochemistry and Molecular Biology, Science Faculty Unit,
Universitat Autbnoma de Barcelona, Cerdanyola del Valles, Spain.
OBJECT: The aim of this study was to estimate the accuracy of routine
magnetic resonance (MR) imaging studies in the classification of brain
tumors in terms of both cell type and grade of malignancy. METHODS: The
authors retrospectively assessed the correlation between neuroimaging
classifications and histopathological diagnoses by using multicenter
database records from 393 patients with brain tumors. An ontology was
devised to establish diagnostic agreement. Each tumor category was compared
with the corresponding histopathological diagnoses by dichotomization.
Sensitivity, specificity, positive and negative predictive values (PPVs and
NPVs, respectively), and the Wilson 95% confidence intervals (CI) for each
were calculated. In routine reporting of MR imaging examinations, tumor
types and grades were classified with a high specificity (85.2-100%);
sensitivity varied, depending on the tumor type and grade, alone or in
combination. The recognition of broad diagnostic categories (neuroepithelial
or meningeal lesions) was highly sensitive, whereas when both detailed type
and grade were considered, sensitivity diverged, being highest in low-grade
meningioma (sensitivity 100%, 95% CI 96.2-100.0%) and lowest in high-grade
meningioma (sensitivity 0.0%, 95% CI 0.0-65.8%) and low-grade
oligodendroglioma (sensitivity 15%, 95% CI 5.2-36.0%). In neuroepithelial
tumors, sensitivity was inversely related to the precision in reporting of
grade and cellular origin; "glioma" was a frequent neuroimaging
classification associated with higher sensitivity in the corresponding
category. The PPVs varied among categories, in general being greater than
their prevalence in this dataset. The NPV was high in all categories
(69.8-100%). CONCLUSIONS: The PPVs and NPVs provided in this study may be
used as estimates of posttest probabilities of diagnostic accuracy using MR
imaging. This study targets the need for noninvasively increasing
sensitivity in categorizing most brain tumor types while retaining high
specificity, especially in the differentiation of high- and low-grade glial
tumor classes.
PMID: 16874886 [PubMed - in process]2
-
| 15: J Neurosurg. 2006 Jul;105(1):148-52. |
|
Decompression of cavernous sinus meningioma for
preservation and improvement of cranial nerve function. Technical note.
Couldwell
WT, Kan
P, Liu
JK, Apfelbaum
RI.
Department of Neurosurgery, University of Utah School of Medicine, Salt Lake
City, Utah 84132, USA. william.couldwell@hsc.utah.edu
Meningiomas are the most common tumors affecting the cavernous sinus (CS).
Despite advances in microsurgery and radiosurgery, treatment of CS
meningiomas remains difficult and controversial. As in cases of other
meningiomas, the goal of treatment for CS meningioma is long-term growth
control and preservation of neural function. Gross-total resection, the
ideal treatment for meningioma, is not always possible to obtain in patients
with CS meningiomas with an acceptable level of morbidity. Therefore,
microsurgery and radiosurgery have recently been advocated as a combined
therapy to achieve good control of tumor growth and favorable functional
outcome. The authors describe a technique in which tumor volume can be
reduced to a minimal residual amount, while preserving cranial nerve
function. This enables the smallest field to be treated radiosurgically. The
optic nerve is decompressed, and the tumor mass is reduced to provide at
least a 5-mm interpositional distance between the optic nerve and the
residual lesion. Direct decompression of the CS, with opening of the lateral
and superior sinus walls, and piecemeal removal of the tumor in
"safe" locations are performed to facilitate an improvement in
cranial nerve function. The authors describe the use of this technique in a
series of patients and demonstrate improvement of cranial nerve function in
a subset of these patients.
PMID: 16871891 [PubMed - in process]
-
| 16: J Neurosurg. 2006 Jul;105(1):132-5. |
|
Glioblastoma multiforme with diffusion-weighted magnetic
resonance imaging characteristics mimicking primary brain lymphoma. Case
report.
Toh
CH, Chen
YL, Hsieh
TC, Jung
SM, Wong
HF, Ng
SH.
First Department of Diagnostic Radiology, Chang Gung Memorial Hospital at
Linkou, Republic of China. eldomtoh@gmail.com
The authors report on the first case of corpus callosum glioblastoma
multiforme (GBM) with diffusion-weighted (DW) magnetic resonance (MR)
imaging findings that mimicked those for lymphoma but with MR spectroscopy
results absent of lymphoma characteristics. This 68-year-old man presented
with rapid, progressive impairment in short-term memory as well as slow
responses and a change in his personality within 3 weeks of admission.
Results of cranial computed tomography revealed a slightly hyperdense corpus
callosum tumor with bihemispheric involvement. Magnetic resonance images
showed a homogeneous mass with strong enhancement. The mass showed water
restriction on DW MR images and apparent diffusion coefficient (ADC) maps
but no markedly elevated lipid resonance on MR spectroscopy. The patient
underwent tumor resection. Results of pathological studies with
immunohistochemical analysis confirmed that the lesion was GBM.
Diffusion-weighted MR imaging together with ADC mapping and MR spectroscopy
was reported to be useful in differentiating GBM and primary brain lymphoma.
The lymphomas were hyperintense to gray matter on DW MR images and
isointense to hypointense on ADC maps because of water restriction. In
contrast, the GBMs were hyperintense to gray matter on both DW MR images and
ADC maps because of the T2 shine-through effect. On MR spectroscopy, lipid
resonance was markedly elevated in lymphoma but only slightly elevated in
GBM.
PMID: 16871888 [PubMed - in process]3
-
| 17: J Neurosurg. 2006 Jul;105(1):119-28. |
|
Participation of an abnormality in the transforming
growth factor-beta signaling pathway in resistance of malignant glioma cells
to growth inhibition induced by that factor.
Zhang
L, Sato
E, Amagasaki
K, Nakao
A, Naganuma
H.
Department of Neurosurgery, University of Yamanashi, Faculty of Medicine,
Yamanashi, Japan.
OBJECT: Malignant glioma cells secrete and activate transforming growth
factor-beta (TGFbeta) and are resistant to growth inhibition by that factor.
Nevertheless, the mechanism underlying this effect remains poorly
understood. In this study, the mechanism of the resistance to growth
inhibition induced by TGFbeta was investigated. METHODS: The authors
examined the expression of downstream components of the TGFbeta receptor,
including Smad2, Smad3, Smad4, and Smad7, and the effect of TGFbeta1
treatment on the phosphorylation of Smad2 and the nuclear translocation of
Smad2 and Smad3 by using 10 glioma cell lines and the A549 cell line, which
is sensitive to TGFbeta-mediated growth inhibition. The expression of two
transcriptional corepressor proteins, SnoN and Ski, and the effect of
TGFbeta1 treatment on the expression of the SnoN protein and the cell cycle
regulators p21, p15, cyclin-dependent kinase-4 (CDK4), and cyclin D1 were
also examined. Expression of the Smad2 and Smad3 proteins was lower in the
glioma cell lines than in the A549 cell line and in normal astrocytes. In
particular, Smad3 expression was low or very low in nine of the 10 malignant
glioma cell lines. Expression of Smad4 was low in four glioma cell lines,
and expression of the Smad7 protein was similar when compared with protein
expression in the A549 cell line and in normal astrocytes. The levels of
Smad2 phosphorylation after TGFbeta1 treatment were lower in glioma cell
lines than in the A549 cell line, except for one glioma cell line. Seven of
the 10 glioma cell lines exhibited lower levels of nuclear translocation of
Smad2 and Smad3, and two cell lines that expressed very low levels of Smad3
protein showed no nuclear translocation. All glioma cell lines expressed the
SnoN protein and its expression was unaltered by treatment with TGFbeta1.
Three glioma cell lines expressed high levels of the Ski protein. The
expression of the p21(cip1), p15(INK4B), CDK4, and cyclin D1 proteins was
not altered by TGFbeta1, treatment, except in one cell line that displayed a
slight increase in p21 protein. Overall, the expression of the Smad2 and
Smad3 proteins was low in the glioma cell lines, the phosphorylation and
nuclear translocation of Smad2 and Smad3 were impaired, and the TGFbeta
receptor signal did not affect the expression of the SnoN, p21, p15, cyclin
D1, and CDK4 proteins. CONCLUSIONS: These results suggest that the ability
to resist TGFbeta-mediated growth inhibition in malignant glioma cells is
due to abnormalities in the TGFbeta signaling pathway.
PMID: 16871886 [PubMed - in process]3
-
| 18: J Neurosurg. 2006 Jul;105(1):111-8. |
|
An accelerated senescence response to radiation in
wild-type p53 glioblastoma multiforme cells.
Quick
QA, Gewirtz
DA.
Department of Pharmacology and Toxicology and Massey Cancer Center, Virginia
Commonwealth University, Richmond, Virginia 23298, USA.
OBJECT: Radiotherapy is one of the few treatment options available for
glioblastoma multiforme (GBM); however, the basis for its overall
ineffectiveness in GBM is not fully understood. The present study was
designed to explore the nature of the response to ionizing radiation in GBM
cells to gain insight into the basis for the general failure of radiotherapy
in the treatment of this disease. METHODS: The response to fractionated
radiotherapy was examined in GBM cell lines with differing p53 status. A
viable cell number was determined during an 8-day period; accelerated
senescence was based on beta-galactosidase staining and cell morphology;
apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated
deoxyuridine triphosphate nick-end labeling assay and fluorescence-activated
cell-sorter analysis, whereas the expression of cell-cycle regulatory
proteins was monitored by Western blot analysis. Based on clonogenic
survival, the wild-type p53 U87 cells and mutant p53 T98 cells demonstrated
essentially identical sensitivity to fractionated radiotherapy; however,
neither cell line underwent apoptosis, and the primary response to
irradiation was growth arrest. The wild-type p53 GBM cells showed clear
evidence of accelerated senescence in response to irradiation. In contrast,
senescence was not evident in mutant p53 GBM cells or GBM cells in which p53
function was abrogated by the viral E6 protein. The T98 (mutant p53) cells
demonstrated a relatively robust proliferative recovery whereas both the
rate and extent of recovery were attenuated in the wild-type p53 U87 cells.
CONCLUSIONS: Both accelerated senescence and conventional growth arrest are
likely to represent alternative responses to apoptosis in irradiated GBM
cells.
PMID: 16871885 [PubMed - in process]3
-
| 19: J Neurosurg. 2006 Jul;105(1):88-95. |
|
Apoptosis in human glioblastoma cells produced using
embryonic stem cell-derived astrocytes expressing tumor necrosis
factor-related apoptosis-inducing ligand.
Germano
IM, Uzzaman
M, Benveniste
RJ, Zaurova
M, Keller
G.
Department of Neurosurgery, Mount Sinai School of Medicine, New York, New
York 10029, USA. isabelle.germano@mountsinai.org
OBJECT: Embryonic stem (ES) cell-derived astrocytes have several theoretical
and practical advantages as gene therapy vectors in the treatment of
malignant gliomas. The aim of this study was to test the proapoptotic
effects of ES cell-derived astrocytes expressing transgenic tumor necrosis
factor-related apoptosis-inducing ligand (TRAIL) in human malignant glioma
cells. METHODS: Mouse ES cells containing a doxycycline-inducible transgene
were engineered with human TRAIL (hTRAIL) and then directed to differentiate
into astrocytes. The ES cell-derived-TRAIL-expressing astrocytes were
cocultured with human malignant glioma cells. Reverse transcriptase
polymerase chain reaction, immunocytochemistry, terminal deoxynucleotidyl
transferase-mediated deoxyuridine triphosphate nick-end labeling, and flow
cytometry were used to quantify results. In vitro coculture of ES
cell-derived astrocytes expressing hTRAIL with A172 human malignant glioma
cells after doxycycline induction caused a significant decrease in cell
viability from 85 +/- 2% at baseline to 8 +/- 2% posttreatment (p <
0.001). Labeling with apoptotic markers showed that cell death occurred by
means of apoptosis. A significant increase in apoptotic rate (88 +/- 3%)
from baseline (4 +/- 2%) was found in A172 cells after doxycycline induction
(p < 0.005). This effect was superior to the apoptotic rate seen after
treatment with recombinant TRAIL (57 +/- 2%). A decrease in cell viability
and an increase in the apoptotic rate were not found in TRAIL-expressing-ES
cell-derived astrocytes after induction with doxycycline or in A172 cells
exposed to doxycycline alone. CONCLUSIONS: Engineering of transgenic hTRAIL
by using ES cell-derived astrocytes induced apoptosis in human malignant
glioma cells while sparing nontumor astrocytes. The apoptotic effects of
transgenic hTRAIL are greater than those of recombinant hTRAIL. Analysis of
these results suggests that hTRAIL-expressing-ES cell-derived astrocytes
should be considered in the development of new in vivo strategies to treat
malignant human gliomas.
PMID: 16871882 [PubMed - in process]3
-
| 20: J Neurosurg. 2006 Jul;105(1):60-4. |
|
Meningothelioma as the predominant histological subtype
of midline skull base and spinal meningioma.
Lee
JH, Sade
B, Choi
E, Golubic
M, Prayson
R.
Brain Tumor Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
44195, USA. leej@ccf.org
OBJECT: This study was undertaken to test a hypothesis that meningiomas of
the midline skull base and spine are predominantly of the meningothelial
histological subtype. METHODS: The cases of 794 consecutive patients who
underwent resection for meningioma at the Cleveland Clinic between January
1991 and March 2004 were reviewed retrospectively. The authors analyzed the
relationship between the tumors' histological subtypes and sites of origin
in the 731 patients from this group who harbored tumors that were determined
to be benign histologically (World Health Organization Grade I).
Meningothelial meningiomas (MMs) accounted for 63.5% (464/731) of the Grade
I tumors. The incidence of MM according to the site of origin was as
follows: 84.9% (186/219) in the midline skull base, 58.3% (35/60) in the
lateral skull base, 48.5% (183/377) in a non-skull base location, and 80%
(60/75) in spinal locations. The incidence of MM in the midline skull base
and spinal locations were significantly higher than in non-skull base or
lateral skull base locations. CONCLUSIONS: Meningiomas of the midline
neuraxis are predominantly meningotheliomas. Analysis of the increasingly
available data on genetic and topographic characteristics of MMs suggests
that they may represent a unique entity, contrary to the prevailing belief
that all benign meningiomas are identical tumors.
PMID: 16871881 [PubMed - in process]3
-
| 21: J Neurosurg. 2006 Jul;105(1):51-9. |
|
Dural involvement in primary extradural meningiomas of
the cranial vault.
Bassiouni
H, Asgari
S, Hubschen
U, Konig
HJ, Stolke
D.
Department of Neurosurgery, University Hospital Essen, Essen, Germany.
hibassiouni@yahoo.de
OBJECT: The authors retrospectively analyzed a consecutive series of
patients with cranial vault primary extradural meningioma (PEM), with
particular regard to the tumor's dural involvement. The pertinent literature
was reviewed. METHODS: Clinical data were retrospectively obtained in a
consecutive series of 16 patients treated for a PEM at two institutions
between 1992 and 2004. The authors created a classification system based on
dural involvement of the tumors. Nine women and six men (mean age 55 years)
presented with a painless, slowly progressive swelling. Preoperative
magnetic resonance (MR) imaging revealed dural enhancement at the site of
tumor in 11 patients. On surgical inspection, the tumor infiltrated the dura
in all but three patients. Histological examination of tissue samples
demonstrated tumor infiltration of the dura in all 14 patients in whom the
dura had been resected. Three recurrent tumors were observed on follow-up
examination during a mean period of 5.8 years (range 1.5-13 years) and
required extirpation. In addition to one patient in whom there was
histological evidence of malignancy, the other two cases involved two
patients in whom no apparent dural involvement was observed during the first
surgery. In a review of the literature, the authors found that histological
examination showed dural involvement in 22%; the dura was not histologically
evaluated in the remaining patients (78%). Postoperative follow-up data
exceeding 2 years were only provided in two of the reported cases.
CONCLUSIONS: Tumor infiltration of the dura should be assumed in PEMs of the
cranial vault, and resection of the dura at the site of craniotomy is
recommended to prevent tumor recurrence.
PMID: 16871880 [PubMed - in process]2
-
| 22: J Neurosurg. 2006 Jul;105(1
Suppl):76. |
|
Staged surgical treatment of a giant neonatal
craniopharyngioma. Case illustration.
Wellons
JC 3rd, Tubbs
RS.
Division of Pediatric Neurosurgery, Children's Hospital of Alabama,
Birmingham 35233, USA.
PMID: 16871876 [PubMed - in process]
-
| 23: J Neurosurg. 2006 Jul;105(1
Suppl):65-70. |
|
Immunogene therapy as a treatment for malignant brain
tumors in young mice.
Glick
RP, Lichtor
T, Lin
H, Tarlock
K, Cohen
EP.
Department of Neurosurgery, Cook County Hospital and Rush Medical College
Chicago, Illinois 60612, USA. rpglick@hotmail.com
OBJECT: New and innovative forms of effective treatments for malignant brain
tumors in children are urgently needed. The authors have previously shown
that intracerebral injection into the tumor bed of allogeneic fibroblasts
genetically engineered to secrete interleukin-2 (IL-2) results in
prolongation of survival and an antitumor immunocytotoxic response in adult
mice that harbor intracerebral gliomas. The first goal of this study was to
determine if malignant gliomas (GI261) could be treated in mice (C57BL/6) in
the pediatric age group (weanlings [2-3 weeks old] and adolescents [3-4
weeks old]). The second goal was to determine the effectiveness of using
IL-2-secreting allogeneic fibroblasts as a protective vaccine to prevent the
development of intracerebral gliomas in these young mice. METHODS: Using
GI261 glioma cells derived from a spontaneously arising glioma in C57BL/6
immunocompetent mice, animals 2 to 4 weeks of age received an intracranial
injection of 5 x 10(4) tumor cells into the right frontal lobe through a bur
hole. The treatment vaccine consisted of 10(6) allogeneic IL-2-secreting
fibroblasts, given at the time of tumor injection (treatment experiments) or
at three weekly intervals prior to tumor injection (protection experiments).
Control groups received either medium or nonsecreting allogeneic
fibroblasts. The effects of this treatment on survival and long-term
immunity were investigated. The results demonstrate a significant
prolongation of survival in animals harboring intracerebral gliomas that
were treated with intracerebral injections of IL-2-secreting allogeneic
fibroblasts (p < 0.05). Morbidity and mortality rates did not increase as
a result of intracerebral immunization. Compared with naive controls,
long-term survivors demonstrated immune memory, as evidenced by prolongation
of survival when they were rechallenged with tumor cells. The results of the
protection experiment demonstrate a significant delay (p < 0.005) in the
development of gliomas in the animals pretreated with either allogeneic
nonsecreting or allogeneic IL-2-secreting fibroblasts prior to the
introduction of tumor cells. In addition, in 78% of these animals a tumor
did not develop when rechallenged. CONCLUSIONS: These results demonstrate
the efficacy and safety of using intratumoral injection of IL-2-secreting
allogeneic fibroblasts as a treatment or protective vaccine in young mice.
It is hoped that these preclinical studies will lead to a clinical trial for
the treatment of malignant brain tumors in children.
PMID: 16871873 [PubMed - in process]2
-
| 24: Neurology.
2006 Aug 2; [Epub ahead of print] |
|
Polymorphism in Sp1 recognition site of the EGF receptor
gene promoter and risk of glioblastoma.
Carpentier
C, Laigle-Donadey
F, Marie
Y, Auger
N, Benouaich-Amiel
A, Lejeune
J, Kaloshi
G, Delattre
JY, Thillet
J, Sanson
M.
From INSERM U711 (C.C., Y.M., N.A., A.B.-A., J.-Y.D., J.T., M.S.), Biologie
des Interactions Neurones and Glie, Universite Pierre et Marie Curie,
Faculte de Medecine, and Groupe Hospitalier Pitie-Salpetriere, and Service
de Neurologie Mazarin (F.L.-D., A.B.-A., J.L., G.K., Y.-Y.D., M.S.), Hopital
de la Salpetriere, Paris, France.
Abstract-- We investigated two polymorphisms of the epidermal growth factor
receptor promoter as potential risk factors and prognostic markers for
glioblastoma. The -216T allele (which results in a 30% higher activity) was
more frequent in the patients compared with the control population (224/376
= 59.6% vs 165/352 = 46.8%; p = 0.0006) corresponding to an odd ratio of
1.67 (1.24; 2.25). A modest difference in median survival was also
associated with the TT genotype.
PMID: 16885506 [PubMed - as supplied by publisher]3
-
| 25: Neurosurgery.
2006 Aug;59(2):389-96; discussion 389-96. |
|
-
Francesco Durante: the history of intracranial
meningiomas and beyond.
Tomasello
F, Germano
A.
Neurosurgical Clinic, Department of Neurosciences, Psychiatry, and
Anesthesiology, University of Messina, School of Medicine, Messina, Italy.
FRANCESCO DURANTE FROM Letojanni, Sicily, was the first surgeon in the
history of neurosurgery to successfully remove a cranial base meningioma.
Durante was Chairman of Clinical Surgery at the Royal University of Rome
(now University "La Sapienza") for 45 years, participating in the
birth of the "Policlinic Umberto I," and was one of the most
famous surgeons in the country. He was also a Master in general surgery, a
Senator of the Kingdom of Italy, and a personal friend of the King of Italy
and the Emperor of Austria-Hungary. His contributions are still applicable
to medicine today, not only to the neurosurgical community, but also other
surgical disciplines, because he developed innovative practices in the
fields of oncology, general surgery, and orthopedics in addition to
designing special surgical instruments. In commemoration of his legacy, the
International Francesco Durante Award is bestowed upon world-renowned
surgeons.
PMID: 16883180 [PubMed - in process]2
-
| 26: Neurosurgery.
2006 Aug;59(2):238-43; discussion 238-43. |
|
-
Surgically treated tuberculum sellae and diaphragm sellae
meningiomas: the importance of short-term visual outcome.
Park
CK, Jung
HW, Yang
SY, Seol
HJ, Paek
SH, Kim
DG.
Department of Neurosurgery, Seoul National University College of Medicine,
Clinical Research Institute, Seoul National University Hospital, Seoul,
Korea.
OBJECTIVE: The visual outcome in patients with tuberculum and diaphragm
sellae meningiomas treated with microsurgery was evaluated. Prognostic and
diagnostic values of short- and long-term postoperative visual outcome and
etiology for postoperative visual deterioration are discussed with special
attention. METHODS: Clinical data for 30 surgically treated patients with
tuberculum and diaphragm sellae meningiomas were reviewed retrospectively.
The mean duration of the follow-up period was 75.9 months (range, 12-151
mo). Mean tumor diameter and volume was 25.9 mm (range, 16.3-63.3 mm) and
12.4 cm (range, 2.3-125.6 cm). A visual impairment score was used to assess
the short-term (< or =2 wk after surgery) and the long-term (>6 mo
after surgery) postoperative visual outcome. Various predictive factors for
visual outcome were tested statistically. RESULTS: Complete resection was
achieved in 23 out of 30 (76.7%) patients. Average preoperative, short- and
long-term visual impairment scores were 48.2, 43.4, and 40.9, respectively.
Favorable visual outcome was achieved in 80% of patients in the short term
and 70% in the long term. Short-term postoperative aggravation of visual
function was an ominous sign of further aggravation or at least of little
hope for recovery, whereas there was a tendency to improve in the long term
if short-term postoperative visual function showed favorable outcome.
Recurrence or regrowth of tumor fully was responsible for late deterioration
of visual function. No significant prognostic factor for visual outcome
could be found. CONCLUSION: Short-term postoperative visual outcome was a
strong indicator of permanent visual outcome after surgery for tuberculum
sellae and diaphragm sellae meningiomas.
PMID: 16883164 [PubMed - in process]2
-
| 27: Neurosurgery.
2006 Aug;59(2):E433-4; discussion E433-4. |
|
-
Surgifoam and mitoxantrone in the glioblastoma multiforme
postresection cavity: the first step of locoregional chemotherapy through an
ad hoc-placed catheter: technical note.
Ferroli
P, Broggi
M, Franzini
A, Maccagnano
E, Lamperti
M, Boiardi
A, Broggi
G.
Department of Neurosurgery, National Neurological Institute Carlo Besta,
Milan, Italy. ferrolipaolo@hotmail.com
OBJECTIVE: To investigate the safety and feasibility of a novel form of
treatment offered by the direct intraoperative application of a
Surgifoam-mitoxantrone mix into a glioblastoma multiforme postresection
cavity. A technique for the placement of an intracavity catheter connected
with a subcutaneous reservoir for further locoregional mitoxantrone
administration is also described. METHODS: Between January and December
2004, 22 consecutive recurrent glioblastoma multiforme patients (14 men, 8
women; age, 56-72 yr; average, 64 yr; median, 65 yr) were enrolled in this
study. All patients underwent image-assisted gross total resection of the
pathological tissue. A Surgifoam-mitoxantrone mix (1 g Surgifoam powder, 3
ml physiological solution, and 12 mg mitoxantrone in 6 ml) was used to fill
the surgical cavity. A ventricular catheter, connected to a Rickham
subcutaneous reservoir, was then positioned in the surgical cavity for
future mitoxantrone administration. RESULTS: Toxic effects caused by
mitoxantrone administration were not observed in any patients during the
first postoperative month. On postoperative Days 1, 7, and 30, computed
tomographic scans excluded surgical complications. In three patients,
residual tumor was disclosed. CONCLUSION: A mix of Surgifoam and
mitoxantrone could be safely applied intraoperatively into the post-glioblastoma
multiforme resection cavity without any observable side effects. This
technique may benefit both the surgeon and the patient by taking advantage
of the drug's hemostatic and cytostatic properties.
PMID: 16883158 [PubMed - in process]
-
| 28: Neurosurgery.
2006 Jul;59(1):193-200; discussion 193-200. |
|
-
A novel model of intramedullary spinal cord tumors in
rats: functional progression and histopathological characterization.
Caplan
J, Pradilla
G, Hdeib
A, Tyler
BM, Legnani
FG, Bagley
CA, Brem
H, Jallo
G.
Department of Neurosurgery, Johns Hopkins University, School of Medicine,
Baltimore, Maryland 21287, USA.
OBJECTIVE: Intramedullary spinal cord tumors are difficult lesions to treat
given their recurrence rate and limited treatment options. The absence of an
adequate animal model, however, has hindered the development of new
treatment paradigms. In this study, we describe the technique for
intramedullary injection of two experimental rodent gliomas (9L and F98) and
present the methodology for functional and histopathological analysis of
tumor progression. METHODS: F344 rats (n = 24) were randomized into three
groups. Group 1 (n = 8) received a 5 microl intramedullary injection of
Dulbecco's modified Eagle medium, Group 2 received a 5 microl intramedullary
injection of 9L gliosarcoma (100,000) cells, and Group 3 received a 5 microl
intramedullary injection of F98 glioma (100,000) cells. The animals were
anesthetized, a 2 cm incision was made in the dorsal mid-thoracic region,
and the spinous process of the T5 vertebrae was removed to expose the
intervertebral space. The ligamentum flavum was removed, and an
intramedullary injection was made into the spinal cord. The animals were
evaluated daily for signs of paralysis using the Basso, Beattie, and
Bresnahan scale and sacrificed after the onset of deficits for
histopathological analysis. RESULTS: Animals injected with 9L-gliosarcoma
had a median onset of hind limb paresis at 12 +/- 2.9 days. Animals injected
with F98 glioma had a median onset of hind limb paresis at 19 +/- 3 days.
Animals injected with Dulbecco's modified Eagle medium did not show
neurological deficits. Hematoxylin-eosin cross sections confirmed the
presence of intramedullary 9L and F98 tumor invading the spinal cord.
Control animals had no significant histopathological findings. CONCLUSION:
Animals injected with 9L or F98 consistently developed hind limb paresis in
a reliable and reproducible manner. The progression of neurological deficits
is similar to that seen in patients with intramedullary spinal cord tumors.
These findings suggest that this model mimics the behavior of intramedullary
spinal cord tumors in humans and may be used to examine the efficacy of new
treatment options for both low- and high-grade intramedullary tumors.
PMID: 16823316 [PubMed - indexed for MEDLINE]2
-
| 29: Neurosurgery.
2006 Jul;59(1):105-14; discussion 105-14. |
|
-
Intraoperative high-field magnetic resonance imaging in
transsphenoidal surgery of hormonally inactive pituitary macroadenomas.
Nimsky
C, von
Keller B, Ganslandt
O, Fahlbusch
R.
Department of Neurosurgery, University of Erlangen-Nurnberg, Erlangen,
Germany. nimsky@nch.imed.uni-erlangen.de
OBJECTIVE: The aim of the study was to evaluate the effect of intraoperative,
high-field (1.5 T) magnetic resonance imaging (MRI) on the results of
transsphenoidal surgery of hormonally inactive pituitary macroadenomas.
METHODS: One hundred six patients (tumor size, 29.9 +/- 10.1 mm; minimum,
11.3 mm; maximum, 57.2 mm) with hormonally inactive pituitary macroadenoma
were investigated by intraoperative high-field MRI during transsphenoidal
surgery. If intraoperative imaging depicted an accessible tumor remnant,
resection was continued. RESULTS: Among the 85 patients in whom complete
tumor removal was intended preoperatively, intraoperative imaging revealed
definite tumor remnants or suspicious findings in 36 (42%) patients. Imaging
led to an extended resection in 29 (34%) patients of this group. Among them,
resection could be completed in 21. This increased the rate of complete
tumor removal from 58% (49 out of 85) to 82% (70 out of 85). In the group of
patients with intended partial removal (n = 21), resection was extended in
38% (eight out of 21) because of intraoperative imaging. Comparison with
scanning 3 months after surgery did not reveal any false-negative findings
of intraoperative MRI; in six cases, intraoperative MRI was suspicious for
some minor remnant that could not be reproduced in the postoperative
control. CONCLUSION: The extent of resection in transsphenoidal surgery can
be reliably assessed using intraoperative high-field MRI. In addition to the
suprasellar compartment, intra- and parasellar structures are also
visualized in great detail. Intraoperative imaging acts as an immediate
intraoperative quality control, allowing one to not only increase the extent
of resection, but to also increase the percentage of complete removals.
Publication Types:
PMID: 16823306 [PubMed - indexed for MEDLINE]
-
| 30: Neurosurgery.
2006 Jul;59(1):98-104; discussion 98-104. |
|
-
Low morbidity associated with use of n-butyl
cyanoacrylate liquid adhesive for preoperative transarterial embolization of
central nervous system tumors.
Kim
LJ, Albuquerque
FC, Aziz-Sultan
A, Spetzler
RF, McDougall
CG.
Division of Neurological Surgery, Barrow Neurological Institute, St.
Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.
OBJECTIVE: To determine the safety and efficacy of preoperative embolization
of central nervous system tumors with n-butyl cyanoacrylate (NBCA) liquid
adhesive. METHODS: Over a 6-year period, 35 consecutive patients (12 women,
23 men; mean age, 42 yr; range, 6 mo-75 yr) with a central nervous system
tumor underwent preoperative embolization with NBCA. Tumor type, location,
endovascular and surgical treatment, percent of tumor embolization,
estimated blood loss, and neurological deficits related to embolization were
evaluated retrospectively. RESULTS: One hundred feeding arteries were
embolized (mean, 3 vessels/patient). In only one (3%) case was a normal
artery inadvertently occluded by the embolization. During the follow-up
period, the resulting neurological deficit resolved completely. There were
no neurological deficits or inadvertent embolization events in the remaining
34 cases. The mean percent of tumor embolized was 68%, but this did not
significantly correlate with operative blood loss (Pearson's correlation
coefficient, r = 0.049). CONCLUSION: In experienced hands, central nervous
system tumors can be embolized with NBCA liquid adhesive with a high degree
of safety and efficacy. We think that adroit embolization technique with
NBCA and other embolisates should be part of the contemporary
neuroendovascular armamentarium.
PMID: 16823305 [PubMed - indexed for MEDLINE]
-
| 31: Neurosurgery.
2006 Jul;59(1):E208; discussion E208. |
|
-
Intradural cervical lipoma with parenchymal marginal
fibrous tissue: case report.
Iwatsuki
K.
Department of Neurosurgery, Osaka University Medical School, Suita, Osaka
565-0871, Japan. kiwatsuki@nsurg.med.osaka-u.ac.jp
OBJECTIVE: The author reports an intradural cervical subpial lipoma with
parenchymal marginal fibrous tissue causing neurological deterioration.
METHODS: Computed tomographic and magnetic resonance imaging scans revealed
the lesion. Magnetic resonance imaging fat suppression was an especially
useful tool for diagnosis. RESULTS: The gross appearance and microscopic
findings implied that this tumor had a progressive character. A subtotal
resection was carried out and pathological studies confirmed the diagnosis.
CONCLUSION: Postoperatively, the patient made an excellent recovery.
Publication Types:
PMID: 16823291 [PubMed - indexed for MEDLINE]2
-
| 32: Neurosurgery.
2006 Jul;59(1):E206; discussion E206. |
|
-
Primary melanocytic tumor of the cerebellopontine angle
mimicking a vestibular schwannoma: case report.
Piedra
MP, Scheithauer
BW, Driscoll
CL, Link
MJ.
Department of Neurological Surgery, Mayo Clinic College of Medicine,
Rochester, Minnesota 55901, USA.
OBJECTIVE: The majority of tumors of the cerebellopontine angle (CPA) are
benign. We report the case of a primary malignant melanoma of the CPA that
mimicked a vestibular schwannoma (acoustic neuroma). We discuss the
differential diagnosis and prognosis of melanotic lesions at this location.
CLINICAL PRESENTATION: A 49-year-old man presented with a 7-year history of
unilateral deafness and a several month history of imbalance, intractable
nausea and vomiting, as well as weight loss. A neurological work-up revealed
a large tumor in the left CPA radiographically diagnosed as a vestibular
schwannoma. INTERVENTION: A translabyrinthine approach revealed a pigmented,
vascular neoplasm encasing vessels and cranial nerves of the left CPA. The
tumor was subtotally resected, and a histopathological diagnosis of melanoma
was made. The patient had no history of cutaneous melanoma and no other site
of disease was ever discovered. CONCLUSION: This case most likely represents
primary melanoma of the central nervous system that mimicked a vestibular
schwannoma. The differential diagnosis of melanotic lesions of the CPA is
discussed as are the prognostic implications of each diagnosis.
Publication Types:
PMID: 16823290 [PubMed - indexed for MEDLINE]2
-
| 33: Oncogene.
2006 Jul 31; [Epub ahead of print] |
|
-
Alternative splicing of the ErbB-4 cytoplasmic domain and
its regulation by hedgehog signaling identify distinct medulloblastoma
subsets.
Ferretti
E, Di
Marcotullio L, Gessi
M, Mattei
T, Greco
A, Po
A, De
Smaele E, Giangaspero
F, Riccardi
R, Di
Rocco C, Pazzaglia
S, Maroder
M, Alimandi
M, Screpanti
I, Gulino
A.
1Department of Experimental Medicine and Pathology, University La Sapienza,
Roma, Italy.
Medulloblastoma (MB) results from aberrant development of cerebellar neurons
in which altered hedgehog (Hh) signalling plays a major role. We
investigated the possible influence of Hh signalling on ErbB-receptor
expression in MB, in particular that of the ErbB-4 CYT-1 and CYT-2 isoforms
generated by alternative splicing of the cytoplasmic domain. ErbB-4
expression was downregulated in Hh-induced MBs from Patched-1(+/-) mice. Hh
signalling (reflected by enhanced expression of the Gli1 transcription
factor) inhibited ErbB-4 expression in mouse cerebellar granule progenitors
and human MB cells. Analysis of 26 human primary MBs revealed a subset of 11
tumors characterized by low Gli1 levels, upregulated ErbB-4 expression and
increased CYT-1:CYT-2 ratios. Interestingly, CYT-1 and Gli1 levels were
inversely correlated. ErbB-4 CYT-1 and CYT-2 had different phenotypic
effects in cultured MB cells: in response to neuregulin treatment, CYT-2
overexpression inhibited proliferation whereas CYT-1, which includes a
phosphatidylinositol 3-kinase (PI3K)-binding site that is missing in CYT-2,
enhanced resistance to starvation- and etoposide-induced apoptosis by
activating PI3K/Akt signalling. CYT-1:CYT-2 ratios displayed correlation
with tumor histotype and ErbB-2 levels, which are established prognostic
indices for MB. These findings demonstrate that low-level Hh signalling in
human MB is associated with the selective maintenance of high ErbB-4 CYT-1
expression, an alteration that exerts tumor-promoting effects.Oncogene
advance online publication, 31 July 2006; doi:10.1038/sj.onc.1209716.
PMID: 16878160 [PubMed - as supplied by publisher]
-
| 34: Oncogene.
2006 Jun 15;25(25):3501-8. Epub 2006 Jan 30. |
|
-
Inhibition of tumor growth and metastasis in vitro and in
vivo by targeting macrophage migration inhibitory factor in human
neuroblastoma.
Ren
Y, Chan
HM, Fan
J, Xie
Y, Chen
YX, Li
W, Jiang
GP, Liu
Q, Meinhardt
A, Tam
PK.
Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China.
reny@ccf.org
Macrophage migration inhibitory factor (MIF) has been defined as a novel
oncogene. Our previous results have shown that MIF may contribute to the
progression of neuroblastoma by (a) inducing N-Myc expression and (b)
upregulating the expression of angiogenic factors. The aim of this study was
to test whether tumor growth could be inhibited by reduction of endogenous
MIF expression in neuroblastoma and clarify the molecular mechanisms
underlying MIF reduction on the control of neuroblastoma growth. We
established human neuroblastoma cell lines stably expressing antisense MIF
(AS-MIF) cDNA. These stable transfectants were characterized by cell
proliferation, gene expression profile, tumorigenicity and metastasis in
vitro and in vivo. Decreased MIF expression was observed after transfection
with AS-MIF in neuroblastoma cells and downregulation of MIF expression
significantly correlated with decreased expression of N-Myc, Ras, c-Met and
TrkB at protein level. Affymetrix microarray analysis revealed that
expression of IL-8 and c-met was inhibited and neuroblastoma-favorable genes
such as EPHB6 and BLU were upregulated in MIF reduced cells. Neuroblastoma
cell growth exhibited a nearly 80% reduction in AS-MIF transfectants in
vitro. Furthermore, mice in which tumors formed after subcutaneous injection
of AS-MIF transfectants showed a 90% reduction in tumor growth compared to
control. Metastasis in mice was also suppressed dramatically. Our data
demonstrate that targeting MIF expression is a promising therapeutic
strategy in human neuroblastoma therapy, and also identifies the MIF target
genes for further study.
PMID: 16449971 [PubMed - indexed for MEDLINE]3
-
| 35: Rev Neurol. 2006 Aug 16-31;43(4):213-7. |
|
[The medulloblastoma.]
[Article in Spanish]
Figols-Ladron
de Guevara J, Lafuente-Sanchez
JV.
Hospital Universitario Marques de Valdecilla, 39008 Santander, Espana.
INTRODUCTION AND DEVELOPMENT. Medulloblastoma is a cerebellar small cell
tumor, whose ancestor cell has not been yet identified in the human normal
embriology: its exact origin is, in fact, still unknown. Nevertheless, one
of the most acceptable possibilities facing the origin of the tumor is the
remaining rests of cerebellar outer granular sheet. It is a predominantly
infantile tumor, less frequent in young adults, and World Health
Organization (WHO) classification has assignated grade IV of malignancy. In
this publication of the WHO, medulloblastomas have been subclassified into:
classic, desmoplastic, medulloblastomas with extensive nodularity and
advanced neuronal differentiation and large cell medulloblastomas. Real
differences dealing with survival and prognosis amidst these subvarieties
have been noted in extensive series. CONCLUSION. The most frequently genetic
alteration is the presence of isochromosome 17q in most of 50% of the cases.
PMID: 16883510 [PubMed - in process]4
-
| 36: Surg Neurol. 2006 Aug;66(2):160-5. |
|
-
The selection of the optimal therapeutic strategy for
petroclival meningiomas.
Park
CK, Jung
HW, Kim
JE, Paek
SH, Kim
DG.
Department of Neurosurgery, Seoul National University College of Medicine,
Clinical Research Institute, Seoul National University Hospital, Seoul
110-744, South Korea.
BACKGROUND: Broad experience with the management of petroclival meningiomas
was analyzed to optimize therapeutic strategy. METHODS: The records of 75
patients with petroclival meningioma were reviewed. The population was
divided into a microsurgery group (n = 49), a radiosurgery group (n = 12), a
radiation therapy group (n = 5), and an observation group (n = 9) according
to the modality of primary treatment. In the microsurgery group, the tumor
was completely resected in 10 patients. Eleven of the 39 patients with
incomplete resections sequentially underwent adjuvant radiation therapy or
radiosurgery. The median follow-up period was 86 months (range, 48-210
months). The median follow-up period of the radiosurgery, the radiation
therapy, and the observation group was 52 months (range, 48-71 months), 56
months (range, 51-72 months), and 63 months (range, 53-68 months),
respectively. Management outcomes were evaluated with respect to tumor
control rate, neurological deficit, and functional status assessed by the
Karnofsky Performance Score. RESULTS: In the microsurgery group, 11 (22.4%)
patients eventually showed tumor progression. However, there was only one
recurrence if adjuvant therapy was used after incomplete removal. The
incidence of favorable outcomes for cranial neuropathies was better in the
incomplete resection group (69.2%) than for patients in the complete
resection group (20%, P = .032). Moreover, a favorable functional outcome
predominated in the incomplete resection group (76.9%) compared with the
complete resection group (30%, P = .049). The disease was stable in both the
radiation therapy and the radiosurgery groups during the follow-up period,
with functional status and cranial nerve function perfectly preserved in
these patients. No predictive factor other than short symptom duration was
found to be significant. CONCLUSIONS: Because the growth rate of petroclival
meningioma is low and good functional status can be guaranteed, intended
incomplete resection should be considered as an acceptable treatment option.
Adjuvant treatment after surgery is useful in the control of residual
tumors. Radiosurgery may be appropriate as the primary treatment in
asymptomatic patients with small tumor; however, more aggressive treatment
is needed in young patients or patients with short symptom durations.
PMID: 16876612 [PubMed - in process]2
| 37: Neurosci
Res. 2006 Jun 27; [Epub ahead of print] |
|
-
Glial cell-derived neurotrophic factor (GDNF) promotes
low-grade Hs683 glioma cell migration through JNK, ERK-1/2 and p38 MAPK
signaling pathways.
Song
H, Moon
A.
College of Pharmacy, Duksung Women's University, 419 Ssangmun-Dong,
Dobong-Gu, Seoul 132-714, Republic of Korea.
Invasion of tumor cells is the primary cause of therapeutic failure in the
treatment of malignant gliomas. In an attempt to investigate the properties
of the malignant progression of glioma cells, we examined the correlation
between cell migration and glial cell-derived neurotrophic factor (GDNF)
secretion of two glioma cell lines which differ in their invasive
phenotypes. Here, we show that the high-grade C6 cells are more migrative
and secrete more GDNF than the low-grade Hs683 cells. GDNF signaling is more
highly activated in C6 cells than in Hs683 cells. Treatment of the Hs683
cells with GDNF significantly increased migration comparable to the C6
cells, revealing the autocrine and/or paracrine effect of GDNF on promotion
of the glioma cell migration. We then examined the involvement of mitogen-activated
protein kinases (MAPKs) including c-Jun N-terminal protein kinase (JNK),
extracellular signal-regulated kinases (ERKs) and p38 MAPK in Hs683 cell
migration induced by GDNF. A prominent activation of JNK, ERKs and p38 MAPK
was observed in the GDNF-treated cells. Functional studies showed that the
activation of these MAPKs was critical for Hs683 cell migration induced by
GDNF. Our findings revealing molecular mechanisms for the promoting effect
of GDNF on glioma cell migration may provide an insight into a better
understanding to the malignant progression of human gliomas.
PMID: 16814421 [PubMed - as supplied by publisher]3
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| 38: J Neurooncol. 2006 Jun;78(2):179-85. Epub 2006 Apr 21. |
|
-
Extension of paralimbic low grade gliomas: toward an
anatomical classification based on white matter invasion patterns.
Mandonnet
E, Capelle
L, Duffau
H.
Department of Neurosurgery, Inserm U678, Hopital de la Salpetriere, 47-83 Bd
de l'hopital, 75651, Cedex, 13, Paris, France.
OBJECT: Low grade gliomas are both proliferative and diffusive tumors, as
recently modelized. When proliferation is predominant, the tumor is rather
bulky and its main locations are the supplementary motor area and the
paralimbic system. Diffusion occurs preferentially along white matter
tracts. Recent anatomo-functional studies, performed both in vitro and in
vivo, have described the fiber tracts centered around the insula. We thus
propose to analyze the extension of paralimbic low grade gliomas in terms of
invaded subcortical pathways. METHODS: We retrospectively reviewed the MRIs
of patients followed for a WHO grade II glioma at the Salpetriere Hospital
between 1991 and 2003. We selected patients with tumors centered on the
insula and extending in temporal and frontal lobes (Type 2b-2c-3 of
Yasargil's classification). We then analyzed on FLAIR sequences the
extension (tracked on successive examinations before any treatment) along
two main fasciculi in that area: the uncinate and arcuate fasciculi.
RESULTS: A total of 40 patients fulfilled the inclusion criteria. The
uncinate fasiculus was invaded in 28 cases, the arcuate fasciculus in 9
cases, and both fasciculi in 3 cases. Longitudinal follow-up was available
in 16 cases, and confirmed the preferential extension along these fasciculi.
CONCLUSION: This kinetic analysis of extension of paralimbic low grade
gliomas confirms that these tumors spread along distinct subcortical
fasciculi. Due to the functional role of these pathways, this classification
could be useful to elaborate therapeutic strategy (prognosis index, pre- and
intra-operative neuropsychological testing, functional outcome).
PMID: 16739029 [PubMed - in process]3
-
| 39: Neurosurgery.
2006 Jun;58(6):E1210; discussion E1210. |
|
-
Cerebellar tumor extension as a late event of
long-standing, supratentorial low-grade gliomas: case report.
Roth
J, Nass
D, Ram
Z.
Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv,
Israel.
OBJECTIVE AND IMPORTANCE: Nonpilocytic low-grade glial tumors in adults
occur mostly in the supratentorial compartment. However, a few cases of
infratentorial low-grade gliomas (LGG) have been described. The occurrence
of LGG in the cerebellum in the setting of a previously existing
supratentorial glioma is rare. CLINICAL PRESENTATION: We present three young
patients with a histologically confirmed diagnosis of long-standing
supratentorial LGG. All three patients presented years after their initial
diagnosis with a second, nonenhancing lesion in the cerebellum, compatible
with the radiological appearance of LGG. Two patients subsequently became
symptomatic from these lesions and underwent surgical resection of the
cerebellar lesions that were found to have similar pathological features to
the original supratentorial tumors. This was confirmed by histology (both
patients) and genetic markers (one patient). INTERVENTION: Magnetic
resonance imaging did not demonstrate tumor continuity between the
supratentorial and infratentorial lesions in any of the patients. The third
patient has shown no cerebellar symptoms to date and is only followed with
periodic magnetic resonance imaging. CONCLUSION: The anatomic/pathological
basis of these rare cases may include a primary, multicentric tumor
formation, or a secondary tumor infiltration of the cerebrocerebellar
pathways, leading to the formation of the cerebellar tumor.
Publication Types:
PMID: 16723871 [PubMed - indexed for MEDLINE]3
-
| 40: Am
J Surg Pathol. 2006 May;30(5):657-64. |
|
-
Assessment and prognostic significance of mitotic index
using the mitosis marker phospho-histone H3 in low and intermediate-grade
infiltrating astrocytomas.
Colman
H, Giannini
C, Huang
L, Gonzalez
J, Hess
K, Bruner
J, Fuller
G, Langford
L, Pelloski
C, Aaron
J, Burger
P, Aldape
K.
Department of Neuro-Oncology, MD Anderson Cancer Center, 1515 Holcombe
Boulevard, Houston, TX 77030, USA. hcolman@mdanderson.org
Distinguishing between grade II and grade III diffuse astrocytomas is
important both for prognosis and for treatment decision-making. However,
current methods for distinguishing between grades based on proliferative
potential are suboptimal, making identification of clear cutoffs difficult.
In this study, we compared the results from immunohistochemical staining for
phospho-histone H3 (pHH3), a specific marker of cells undergoing mitosis,
with standard mitotic counts (number of mitoses/10 high-power fields) and
MIB-1 labeling index values for assessing proliferative activity. We tested
the relationship between pHH3 staining and tumor grade and prognosis in a
retrospective series of grade II and III infiltrating astrocytomas from a
single institution. The pHH3 index (per 1000 cells), MIB-1 index (per 1000
cells), and number of mitoses per 10 high-power fields were determined for
each of 103 cases of grade II and III diffuse astrocytomas from patients
with clinical follow-up. pHH3 staining was found to be a simple and reliable
method for identifying mitotic figures, allowing a true mitotic index to be
determined. The pHH3 mitotic index was significantly associated both with
the standard mitotic count and with the MIB-1 index. Univariate analyses
revealed that all 3 measurements of proliferation were significantly
associated with survival. However, the pHH3 mitotic index accounted for a
larger proportion of variability in survival than standard mitotic count or
MIB-1/Ki-67 labeling index. After adjusting for age, extent of resection,
and performance score, the pHH3 mitotic index remained an independent
predictor of survival. Thus, pHH3 staining provides a simple and reliable
method for quantifying proliferative potential and for the stratification of
patients with diffuse astrocytomas into typical grade II and III groups.
These results also suggest that pHH3 staining may be a useful method in
other neoplasms in which accurate determination of proliferation potential
is relevant to tumor grading or clinical treatment decision-making.
PMID: 16699322 [PubMed - indexed for MEDLINE]3
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|
Volume 5, Number 32 - 7 August 2006